Journal articles on the topic 'Mass-production vs unique'

To signal cell responses, Ca2+ is released from storage through intracellular Ca2+ channels. Unlike most plasmalemmal channels, these are clustered in quasi-crystalline arrays, which should endow them with unique properties. Two distinct patterns of local activation of Ca2+ release were revealed in images of Ca2+ sparks in permeabilized cells of amphibian muscle. In the presence of sulfate, an anion that enters the SR and precipitates Ca2+, sparks became wider than in the conventional, glutamate-based solution. Some of these were “protoplatykurtic” (had a flat top from early on), suggesting an extensive array of channels that activate simultaneously. Under these conditions the rate of production of signal mass was roughly constant during the rise time of the spark and could be as high as 5 μm3 ms−1, consistent with a release current >50 pA since the beginning of the event. This pattern, called “concerted activation,” was observed also in rat muscle fibers. When sulfate was combined with a reduced cytosolic [Ca2+] (50 nM) these sparks coexisted (and interfered) with a sequential progression of channel opening, probably mediated by Ca2+-induced Ca2+ release (CICR). Sequential propagation, observed only in frogs, may require parajunctional channels, of RyR isoform β, which are absent in the rat. Concerted opening instead appears to be a property of RyR α in the amphibian and the homologous isoform 1 in the mammal.

Under the assumption that the abundance of 7Li in Population II stars represents the primordial Li abundance (with perhaps a small contribution from GCR spallation) and that GCR spallation/fusion processes cannot contribute to more than ≃ 10 − 20% of the Li abundance observed in Pop. I stars and in the solar system, one must conclude that most of Li in Pop. I stars has a stellar origin.Possible stellar Li producers are discussed: low mass AGB stars (2−5M⊙) (C-stars), high mass AGB stars (5 - 8M⊙), supernovae of type II (M > 10M⊙) and novae. The various problems connected with all of these sources are indicated: in particular, we discuss the Li production in AGB stars when evolutionary effects due to the metallicity are taken into account, and the fact that novae do not seem to be good candidate for Li production, as suggested by a recent nucleosynthesis study. We then calculate the yields from these stellar sources and predict the behavior of log N(Li) vs. [Fe/H] by means of a galactic chemical evolution model.We conclude that, although a unique model cannot be found, due to the uncertainties still existing in the stellar nucleosynthesis, the most likely scenario is that Li is partly produced in type II supernovae (v-induced nucleosynthesis) and partly in massive AGB stars.

An electrochemical amperometric ethylene sensor with solid polymer electrolyte (SPE) and semi-planar three electrode topology involving a working, pseudoreference, and counter electrode is presented. The polymer electrolyte is based on the ionic liquid 1-butyl 3-methylimidazolium bis(trifluoromethylsulfonyl)imide [BMIM][NTf2] immobilized in a poly(vinylidene fluoride) matrix. An innovative aerosol-jet printing technique was used to deposit the gold working electrode (WE) on the solid polymer electrolyte layer to make a unique electrochemical active SPE/WE interface. The analyte, gaseous ethylene, was detected by oxidation at 800 mV vs. the platinum pseudoreference electrode. The sensor parameters such as sensitivity, response/recovery time, repeatability, hysteresis, and limits of detection and quantification were determined and their relation to the morphology and microstructure of the SPE/WE interface examined. The use of additive printing techniques for sensor preparation demonstrates the potential of polymer electrolytes with respect to the mass production of printed electrochemical gas sensors.

Extracorporeal circulation provides critical life support in the face of cardiopulmonary or renal failure, but it also introduces a host of unique morbidities characterized by edema formation, cardiac insufficiency, autonomic dysfunction, and altered vasomotor function. We tested the hypothesis that cyclohexanone (CHX), a solvent used in production of extracorporeal circuits and intravenous (IV) bags, leaches into the contained fluids and can replicate these clinical morbidities. Crystalloid fluid samples from circuits and IV bags were analyzed by gas chromatography-mass spectrometry to provide a range of clinical CHX exposure levels, revealing CHX contamination of sampled fluids (9.63–3,694 μg/l). In vivo rat studies were conducted ( n = 49) to investigate the effects of a bolus IV infusion of CHX vs. saline alone on cardiovascular function, baroreflex responsiveness, and edema formation. Cardiovascular function was evaluated by cardiac output, heart rate, stroke volume, vascular resistance, arterial pressure, and ventricular contractility. Baroreflex function was assessed by mean femoral arterial pressure responses to bilateral carotid occlusion. Edema formation was assessed by the ratio of wet to dry organ weights for lungs, liver, kidneys, and skin. CHX infusion led to systemic hypotension; pulmonary hypertension; depressed contractility, heart rate, stroke volume, and cardiac output; and elevated vascular resistance ( P < 0.05). Mean arterial pressure responsiveness to carotid occlusion was dampened after CHX infusion (from +17.25 ± 1.8 to +5.61 ± 3.2 mmHg; P < 0.05). CHX infusion led to significantly higher wet-to-dry weight ratios vs. saline only (3.8 ± 0.06 vs. 3.5 ± 0.05; P < 0.05). CHX can reproduce clinical cardiovascular, neurological, and edema morbidities associated with extracorporeal circulatory treatment.

The chemical composition of milk can be significantly affected by different factors across the dairy supply chain, including primary production practices. Among the latter, the feeding system could drive the nutritional value and technological properties of milk and dairy products. Therefore, in this work, a combined foodomics approach based on both untargeted metabolomics and metagenomics was used to shed light onto the impact of feeding systems (i.e., hay vs. a mixed ration based on hay and fresh forage) on the chemical profile of raw milk for the production of hard cheese. In particular, ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) was used to investigate the chemical profile of raw milk (n = 46) collected from dairy herds located in the Po River Valley (Italy) and considering different feeding systems. Overall, a total of 3320 molecular features were putatively annotated across samples, corresponding to 734 unique compound structures, with significant differences (p < 0.05) between the two feeding regimens under investigation. Additionally, supervised multivariate statistics following metabolomics-based analysis allowed us to clearly discriminate raw milk samples according to the feeding systems, also extrapolating the most discriminant metabolites. Interestingly, 10 compounds were able to strongly explain the differences as imposed by the addition of forage in the cows’ diet, being mainly glycerophospholipids (i.e., lysophosphatidylethanolamines, lysophosphatidylcholines, and phosphatidylcholines), followed by 5-(3′,4′-Dihydroxyphenyl)-gamma-valerolactone-4′-O-glucuronide, 5a-androstan-3a,17b-diol disulfuric acid, and N-stearoyl glycine. The markers identified included both feed-derived (such as phenolic metabolites) and animal-derived compounds (such as lipids and derivatives). Finally, although characterized by a lower prediction ability, the metagenomic profile was found to be significantly correlated to some milk metabolites, with Staphylococcaceae, Pseudomonadaceae, and Dermabacteraceae establishing a higher number of significant correlations with the discriminant metabolites. Therefore, taken together, our preliminary results provide a comprehensive foodomic picture of raw milk samples from different feeding regimens, thus supporting further ad hoc studies investigating the metabolomic and metagenomic changes of milk in all processing conditions.

This study combines data on changes in cardiovascular variables with body mass (Mb) and with exercise intensity to model the oxygen supply available to birds during flight. Its main purpose is to provide a framework for identifying the factors involved in limiting aerobic power input to birds during flight and to suggest which cardiovascular variables are the most likely to have been influenced by natural selection when considering both allometric and adaptive variation. It is argued that natural selection has acted on heart rate (fh) and cardiac stroke volume (Vs), so that the difference in the arteriovenous oxygen content (CaO2-Cv¯O2) in birds, both at rest and during flight, is independent of Mb. Therefore, the Mb exponent for oxygen consumption (V(dot)O2) during flight can be estimated from measurements of heart rate and stroke volume. Stroke volume is likely to be directly proportional to heart mass (Mh) and, using empirical data, values for the Mb coefficients and exponents of various cardiovascular variables are estimated. It is concluded that, as found for mammals, fh is the main adaptive variable when considering allometric variation, although Mh also shows a slight scaling effect. Relative Mh is likely to be the most important when considering adaptive specialisations. The Fick equation may be represented as: (V(dot)O2)Mbz = (fh)Mbw x (Vs)Mbx x (CaO2 - Cv¯O2)Mby , where w, x, y, z are the body mass exponents for each variable and the terms in parentheses represent the Mb coefficients. Utilising this formula and data from the literature, the scaling of minimum V(dot)O2 during flight for bird species with a 'high aerobic capacity' (excluding hummingbirds) is calculated to be: 166Mb0.77&plusmn;0.09 = 574Mb-0.19&plusmn;0.02 x 3.48Mb0.96&plusmn;0.02 x 0.083Mb0.00&plusmn;0.05 , and for hummingbirds (considered separately owing to their unique wing kinematics) it is: 314Mb0.90&plusmn;0.22 = 617Mb-0.10&plusmn;0.06 x 6.13Mb1.00&plusmn;0.11 x 0.083Mb0.00&plusmn;0.05 . These results are largely dependent on the cardiovascular values obtained from pigeons flying near to the minimum power speed of 10 m s-1, but would appear to provide realistic values. Both the measured and the estimated V(dot)O2 for hummingbirds appear to scale with a larger Mb exponent than that for all other birds, and it is suggested that this is as a result of the larger Mb exponent for flight muscle mass as the larger species of hummingbirds try to maintain hovering performance. It is proposed that estimated V(dot)O2 for birds during flight, which is based on Mh in combination with estimates of fh and CaO2-Cv¯O2, gives an indirect measure of relative aerobic power input and, when corrected for the estimated scaling influences of the mechano-chemical conversion efficiency and lift generation with respect to Mb, may be a useful indicator of the relative capacity of the muscle to sustain power output and lift production during flight.

Abstract Introduction: Mutations in IDH1 and IDH2 are recurrent in AML and several other cancers, resulting in the aberrant production of the onco-metabolite, R-2-hydroxyglutarate (2-HG), as well as an inability of mutant IDH1 to convert cytoplasmic alpha-ketoglutarate to isocitrate via reductive carboxylation. Currently, inhibitors of the neomorphic enzymes that abrogate the production of 2-HG, such as AG-120, are FDA-approved, but are not curative. Using a novel computational method (MiSL), we identified acetyl CoA carboxylase (ACACA) as a potential druggable target specifically in IDH1-mutated AML. ACACA regulates the de novo synthesis of lipid precursors by converting acetyl CoA to malonyl CoA building blocks. We hypothesize that IDH1 mutant AML exhibits a defect in reductive carboxylation and de novo fatty acid synthesis conferring preferential susceptibility to ACACA inhibition. Here, we investigate this hypothesis by comprehensively quantifying the metabolic landscape, including non-polar lipid metabolites, conferred by IDH1 R132H mutation compared to IDH2 mutation in isogenic cell lines and primary samples. Moreover, we investigate the in vitro and in vivo effects of targeting de novo lipid synthesis on IDH1 and IDH2 mutant AML. Methods: Comprehensive metabolomic profiling of primary FACS-purified AML blasts was performed using an in-house protocol optimised for extraction of non-polar lipid metabolites from less than 1 million primary cells. CD33+CD45+ leukemic blasts were profiled from 17 patient samples with IDH1 mutation (n=6), IDH2 mutation (n=5), or IDH1/2 wildtype (n=6) after culturing in serum-free media. 6 independent cord-blood CD34+ cells were profiled as a negative control. For validation of IDH1-specific effects, isogenic THP-1 cells transduced with doxycycline-inducible wildtype and R132H mutant IDH1 or R140Q mutant and wildtype IDH2 were profiled. Molecules were identified according to their molecular weight and retention time using Mass Hunter software (Agilent) and the Human Metabolome Database. For in vivo studies, primary AML samples were engrafted in NSG mice that were subjected to dietary modification with low lipid diet and/or treatment with selective inhibitors of ACACA and mutant IDH1. Results: Principle component analysis of metabolite abundance of 1400 unique compounds revealed striking differences between IDH1 and IDH2 mutant AML. Both IDH1 and IDH2 mutant samples produced high levels of 2-HG compared to wildtype AML and CD34+ cells (50 fold increase, P=4.5E-05). A major perturbation in multiple phospholipid fatty acid species was conferred by IDH1 R132H, but not by IDH2 mutation. The same pattern was observed in cell lines with 49 lipid species decreased in the presence of mutant IDH1 compared to only 2 perturbed with mutant IDH2. Direct comparison of IDH1 vs IDH2 mutant primary samples revealed 54 lipid metabolites significantly down-regulated in IDH1 mutant blasts (adjusted P value <0.05). To investigate the effects of targeting de novo lipid synthesis on IDH1 mutant AML in vivo, we engrafted primary IDH1 mutant AML and tested growth with lipid-free compared to normal diet. At 12 weeks, IDH1 mutant AML showed reduced growth in the bone marrow of mice on lipid-free diet (SU389 11% vs 40%, n=10 mice, P=0.03 and SU372 21% vs 34%, n=10, P=0.02 Mann-Whitney U). IDH1 mutant AML was susceptible to ACACA inhibition with shRNA, CRISPR targeting, or selective nanomolar inhibitors. Knockdown of ACACA with independent shRNAs caused a defect in cell growth in the presence of IDH1 R132H, but not in its absence or with scrambled shRNA (p=0.009, shRNA #1 vs. scrambled; p=0.01, shRNA #2 vs. scrambled) in vitro and in xenografts. Primary IDH1 R132 mutated AML blasts were selectively sensitive to ACACA inhibitor treatment compared to IDH1 wildtype normal karyotype blasts (IC50 0.6 uM vs 6 uM, p=0.009). Notably, IDH1-mutant AML blasts pre-treated with 10mM AG-120 remained susceptible to ACACA inhibition, identifying a 2-HG independent vulnerability. Similar findings were observed in a solid tumor IDH1 mutant sarcoma model in vivo. Conclusion : These results support our hypothesis that IDH1 mutant AML exhibits a defect in de novo fatty acid synthesis conferring preferential susceptibility to ACACA inhibition, and suggests that pharmacologic inhibitors of ACACA may complement IDH1 mutation-specific inhibitors in the clinic. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 3265 Introduction: The clinically significant forms of thalassemia are associated with transfusional and non-transfusional iron overload (IO). IO contributes to cirrhosis, cardiac failure and endocrinopathies, amongst other complications. Despite advances in iron load monitoring and chelation therapy, patients still continue to be at risk of iron-associated complications. Free iron leads to production of reactive oxygen species and oxidative damage of lipids, proteins, and DNA, resulting in apoptosis and organ damage. Tools that allow for early detection of iron associated changes and toxicities may allow for earlier clinical intervention. Thalassemia major (TM) patients have increased levels of the lipid peroxidation marker malondialdehyde (MDA), which decreases with chelation therapy. The DNA oxidative damage marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG) has not been studied in thalassemia patients. Iron associated oxidative damage has been shown to affect cell and organelle membranes, affect glucose and lipid homeostasis, and contribute to inflammation, fibrosis and organ damage. We hypothesized that metabolomics technologies that assess changes in global metabolite profiles (metabolism of sugars, lipids, amino acids etc) may have a role to play as biomarkers of iron load, organ damage, or therapeutic response. Aims: 1) To use metabolomics technologies to determine if we can identify metabolite profile differences between thalassemia patients and control individuals, 2) To examine 8-OHdG levels as a marker of DNA oxidative damage in thalassemia, 3) To use metabolomics technologies to investigate for correlations between metabolite profiles and markers of iron load and oxidative damage. Methods: 24 subjects were enrolled with a mean age of 34 years (7 TM, 2 thalassemia intermedia (TI), 2 hemoglobin H disease (HbH) and 1 pure red cell aplasia, and 12 age and sex matched controls). Iron load was assessed with serum ferritin, non-transferrin bound iron (NTBI), LIC by magnetic resonance imaging (MRI), and cardiac MRI T2*. Serum and urine samples were collected at baseline, as well as 6 and 12 months. Serum MDA and urinary 8-OHdG were measured and correlated with iron load markers. Mass spectrometry metabolomics data of serum samples were analyzed using supervised multivariate regression techniques to identify relations to markers of iron load, oxidative damage and disease. Results: Serum ferritin and NTBI were significantly higher in the IO group compared to controls (p < 0.05). The mean LIC was 8.42 +/− 6.17 mg iron/gm dry weight and mean cardiac T2* was 31 +/− 17.03 ms in the study group. Serum MDA (0.021 +/− 0.01 vs 0.012 +/− 0.003 mmol/g protein, p < 0.001) and urinary 8-OHdG (17.26 +/− 8.61 vs 2.49 +/− 1.13 ng/mg Cr, p < 0.001) were significantly increased in iron-overloaded patients. Metabolite profiling of baseline serum revealed a significant difference in the IO group compared to controls (p = 0.006, R2 = 0.929). Significantly distinct metabolite profiles reflected the 3 distinct types of thalassemias (TM, TI, HbH) and different chelation therapy regimens. There was a significant relationship between serum metabolite profiles and markers of iron load including serum ferritin, LIC, and cardiac T2* (p < 0.05). A significant relationship was seen between serum metabolite profiles and, i) MDA (p = 0.007) and ii) urinary 8-OHdG (p = 0.01). Predictive models identified a profile of 19 different features that were predictive of serum MDA levels, and a profile of 52 unique features that were predictive of serum 8OHdG levels. The relationship of metabolite profiles to oxidative damage markers was more robust when reanalyzed based on chelator status (deferasirox vs non-deferasirox). Conclusion: Markers of oxidative damage are increased in iron overloaded thalassemia patients, with the first report of elevated 8-OHdG in this population. Metabolomics identifies different metabolite profiles between iron overloaded thalassemia patients and controls. Unique serum metabolite profiles show relationships with iron load, markers of lipid and DNA oxidative damage, type of thalassemia, and chelation therapy. These metabolite profiles may have the potential to serve as biomarkers for diagnosis, prognosis, organ damage, and therapeutic response in iron loaded thalassemia patients. Disclosures: No relevant conflicts of interest to declare.

Abstract One outstanding issue in allogeneic hematopoietic transplantation is impaired immune reconstitution. As the primary site of T cell development, the thymus plays a key role in the generation of a strong yet self-tolerant adaptive immune response, essential in the face of the potential threat from pathogens or neoplasia. Allogeneic hematopoietic transplantation may acutely damage the thymus through the chemo or radiotherapy, antibody therapy of the conditioning regime, infections acquired by the immunosuppressed patient, and thymic graft versus host disease. To date, attempts to improve thymic reconstitution have been disappointing. Pre-clinical experiments and pilot clinical trials tried to assess the role of a variety of therapeutic approaches, such as transfer of lymphoid progenitor cells, thymic grafts, or enhancement of thymopoiesis by administration of hormonal or cytokine/growth factor-based therapies, such as sex-steroid blockade, and IL-7, IL-22, KGF, or Flt-3 ligand administration (reviewed in Chaudhry et al., Immunol Rev. 2016). In mouse MHC mismatched transplantation models (F1 H-2d/b→parent H-2b), we previously found that infusion of donor versus recipient alloreactive NK cells eradicated recipient-type lympho-hematopoietic lineage cells, thereby enhancing engraftment, protecting from GvHD and eradicating leukemia (Ruggeri et al., Science 2002). Here, in the same models we show that infusion of alloreactive NK cells greatly accelerates the post-hematopoietic transplant recovery of donor-type immune cells, i.e., dendritic cells (DCs) (p<0.001), B lineage cells (p<0.001) and thymocytes (p<0.001) and maturation to B (p<0.001) and T cells (p<0.001). By the use of recipient chimeric mice displaying different tissue (i.e., hematopoietic vs non-hematopoietic) susceptibility to donor alloreactive NK cell killing, we show that a specific interaction between donor alloreactive NK cells and recipient DCs is responsible for the accelerated immune rebuilding. We find that donor-versus-recipient alloreactive NK cells trigger recipient DCs to synthesize a protein factor in a DNA translation-depended fashion (i.e., blocking DNA transcription in DCs abrogated the DC ability to produce the factor), and release it. Infusion of NK/DC co-culture supernatants containing this factor induced bone marrow and thymic stromal cells to produce IL-7 (p<0.001) and c-Kit ligand (p<0.001) and, thereby, the extraordinarily accelerated maturation of donor DCs, B- and T-cell precursors. Interestingly, in vitro experiments with human thymic stromal cells that support human thymocyte proliferation and differentiation demonstrated the exact same mechanisms. Supernatants from human alloreactive NK cell clones and human (HLA-class I KIR ligand mismatched) allogeneic DCs induced IL-7 production by human thymic stromal cells which in turn supported accelerated proliferation and maturation of human thymocytes (p<0.001). The murine and the human "immune rebuilding" factors displayed biochemical similarities as they both are highly hydrophobic 12KDa molecular weight proteins. Mass spectrometry analysis by stable isotope labeling with amino acids in cell culture (SILAC) identified Beta-2 Microglobulin (B2M) as the newly synthesized protein sharing the above biochemical features and present both in murine and human samples. B2M-KO mice used as recipients of MHC mismatched bone marrow transplant and given donor versus recipient alloreactive NK cells were unable to undergo accelerated immune rebuilding. However, their defect was repaired and accelerated rebuilding of donor-type DCs (p<0.001), B lineage cells (p<0.001) and thymocytes (p<0.001) was restored by the administration of culture supernatants obtained from alloreactive NK cells and wild-type (non-KO) MHC mismatched DCs. Finally, RNA interference experiments that silenced the B2M gene in human DCs resulted in loss of biological activity of supernatants obtained from alloreactive NK cells and B2M-silenced DCs. B2M plays a key role in the immune system as it is known to be part of MHC class I molecules. However, its role in signaling for immune precursor cell development has never been recognized. Here we report the discovery of a novel cellular and molecular pathway initiated by alloreactive NK cells and mediated by B2M that leads to greatly accelerated rebuilding of B and T cells after hematopoietic transplantation. Disclosures No relevant conflicts of interest to declare.

Introduction Early diagnosis, effective therapy and precise monitoring are central for improving clinical outcomes in systemic light chain (AL) amyloidosis. Diagnosis and disease response assessment is primarily based on the presence of monoclonal immunoglobulins and free light chains (FLC). The ideal goal of therapy associated with best outcomes is a complete responses (CR), defined by the absence of serological clonal markers. In both instances, detection of the monoclonal component (M-component) is based on serum FLC assessment together with traditional serum and urine electrophoretic approaches, which present inherent limitations and lack sensitivity particularly in AL where the levels are typically low. Novel mass spectrometry methods provide sensitive, accurate identification of the M-component and may prove instrumental in the timely management of patients with low-level amyloidogenic light chain production. Here we assess the performance of quantitative immunoprecipitation FLC mass spectrometry (QIP-FLC-MS) at diagnosis and during monitoring of AL amyloidosis patients treated with bortezomib-based regimens. Methods We included 46 serial patients with systemic AL amyloidosis diagnosed and treated at the UK National Amyloidosis Centre (UK-NAC). All patients had detailed baseline assessments of organ function and serum FLC measurements. Baseline, +6- and +12-month serum samples were retrospectively analysed by QIP-FLC-MS. Briefly, magnetic microparticles were covalently coated with modified polyclonal sheep antibodies monospecific for free kappa light chains (anti-free κ) and free lambda light chains (anti-free λ). The microparticles were incubated with patient sera, washed and treated with acetic acid (5% v/v) containing TCEP (20 mM) in order to elute FLC in monomeric form. Mass spectra were acquired on a MALDI-TOF-MS system (Bruker, GmbH). Results were compared to serum FLC measurements (Freelite®, The Binding Site Group Ltd), as well as electrophoretic assessment of serum and urine proteins (SPE, sIFE, UPE and uIFE). Results Cardiac (37(80%) patients) and renal (31(67%) patients) involvement were most common; 25(54%) patients presented with both. Other organs involved included liver (n=12), soft tissue (n=4), gastrointestinal tract (n=3) and peripheral nervous system (n=2). Baseline Freelite, SPE, sIFE and uIFE measurements identified a monoclonal protein in 42(91%), 22(48%), 34(74%) and 21(46%) patients, respectively. A panel consisting of Freelite + sIFE identified the M-component in 100% of the samples. QIP-FLC-MS alone also identified an M-component in 100% of the samples and was 100% concordant with Freelite for typing the monoclonal FLC (8 kappa, 34 lambda). In 4 patients, QIP-FLC-MS identified an additional M-protein that was not detected by the other techniques. In addition, 4/8(50%) kappa and 4/38(11%) lambda patients showed a glycosylation pattern of monoclonal FLCs at baseline by mass spectrometry. Interestingly, the frequency of renal involvement was significantly lower for patients with non-glycosylated forms (25% vs 76%, p=0.01), while no similar relationship was found for any other organs. During the 1-year follow-up period, 17 patients achieved a CR; QIP-FLC-MS identified serum residual disease in 13(76%) of these patients. Conclusion In our series, QIP-FLC-MS was concordant with current serum methods for identifying the amyloidogenic light chain type and provided, against all other individual tests, improved sensitivity for the detection of the monoclonal protein at diagnosis and during monitoring. The ability to measure the unique molecular mass of each monoclonal protein offers clone-specific tracking over time. Glycosylation of free light chains is over-represented in AL patients which may allow earlier diagnosis and better risk-assessment of organ involvement. Persistence of QIP-FLC-MS positive M component in patients otherwise in CR may allow targeted therapy. Overall, QIP-FLC-MS demonstrates potential to be exploited as a single serum test for precise serial assessment of monoclonal proteins in patients with AL amyloidosis. Disclosures Wechalekar: GSK: Honoraria; Janssen-Cilag: Honoraria; Amgen: Research Funding; Takeda: Honoraria; Celgene: Honoraria.

Summary Investigating the properties of live heavy oil, as pressure declines from the original reservoir pressure to ambient pressure, can aid in interpreting and simulating the response of heavy-oil reservoirs undergoing primary production. Foamy oil has a distinctly different and more complex behavior compared to conventional oil as the reservoir pressure depletes and the gas leaves solution from the oil. Solution gas separates very slowly from the oil; thus, conventional pressure/volume/temperature (PVT) measurements are not trivial to perform. In this paper, we present novel experiments that utilize X-ray computerized assisted technology (CT) scanning and low field nuclear magnetic resonance (NMR) techniques. These nondestructive tomographic methods are capable of providing unique in-situ measurements of how oil properties change as pressure depletes in a PVT cell. Specifically, this paper details measurements of oil density, oil and gas formation volume factor, solution gas/oil ratio, (GOR), and oil viscosity as a function of pressure. Experiments were initially performed at a slow rate, as in conventional PVT tests, allowing equilibrium to be reached at each pressure step. These results are compared to non-equilibrium tests, whereby pressure declines linearly with time, as in coreflood experiments. The incremental benefit of the proposed techniques is that they provide more detailed information about the oil, which improves our understanding of foamy-oil properties. Introduction Understanding fluid behavior of heavy oils is important for reservoir simulation and production response predictions. In heavy-oil reservoirs, the oil viscosity and density are commonly reported, but there is little experimental data in the literature reporting how oil properties change with pressure. This information would be especially useful for production companies seeking to understand and improve their primary (cold production) response. It is already widely known that foamy-oil behavior is a major cause for increased production in cold heavy-oil reservoirs along with sand production. Therefore, it would be valuable to first study the bulk fluid properties of live heavy oil prior to sandpack-depletion experiments. If the response of these properties to incremental pressure reduction can be established, this can be compared with fluid expansion during pressure depletion in a sandpack. CT scanning is useful in studying high-pressure PVT relationships. Images of a pressure vessel filled with live oil can be taken as the volume of the vessel is expanded and used to calculate bulk densities and free gas saturation. Also, CT images allow us to visually see where free gas is formed in the vessel. For example, CT scanning can be used to provide an indication of whether or not small bubbles nucleate within the oil and then slowly coalesce into a gas cap, or if free gas forms straight away. CT scanning provides much more information than conventional PVT cells. Uncertainties about where gas is forming in the oil, its effect on oil properties, and transient behavior cannot be reconciled in conventional PVT cells. Also, from CT images, the formation of microbubbles could be inferred based on the density of the oil with the dissolved gas. If the oil density decreases below the bubblepoint pressure, then it is likely that gas has come out of solution but remains within the oil; therefore, the resulting mixture is less dense than the original live oil. However, if oil density increases as the gas evolves, then the oil does not contain small gas bubbles, and gas has separated from the oil. Also, the free gas saturation growth with time, and comparison of images at equilibrium vs. immediately after the expansion of the vessel, can provide mass transfer information about gas bubble growth, supersaturation, and gravity separation. When characterizing heavy oil and bitumen fluid properties, oil viscosity is one of the most important pieces of information that has to be obtained. The high viscosities of heavy oil and bitumen present a significant obstacle to the technical and economic success of a given enhanced oil recovery option. As a result, in-situ oil viscosity measurement techniques would be of considerable benefit to the industry. In heavy-oil reservoirs that are undergoing primary production, this problem is further complicated by the presence of the gas leaving solution with the oil. Above the bubblepoint, the gas is fully dissolved into the oil; thus, the live oil exists as a single-phase fluid. Once the pressure drops below the bubblepoint and gas begins to leave solution, the oil viscosity behavior is no longer well understood. In addition to our CT analysis, this work also presents the use of low field NMR as a tool for making in-situ viscosity estimates of live and foamy oil. NMR spectra change significantly as pressure drops and gas leaves solution, and these changes can be correlated to physical changes in the oil viscosity.

Despite its major role in cellular biology, metabolism has only recently acquired a principal role in the research of the most profound cellular cycle disturbance, cancerous transformation. Myelodysplastic syndromes (MDS), a massively heterogeneous group of Hematopoietic Stem/ Progenitor Cell (HSC/HPC) disorders lie at the interface of normal differentiation and malignant transformation and have thus drew great attention due to their polymorphic presentation and elusive pathophysiology. Failure to establish a direct etiopathogenic relationship with specific genetic aberrations, along with the novel finding of a highly deregulated HIF1 activity by several unrelated research groups worldwide, including ours, urged us to investigate the metabolomic status of human bone marrow derived differentiating myeloid lineage in comparison with one another as well as with control samples. BM aspiration samples collected from 14 previously untreated MDS patients (10 patients with &lt;5% (1 SLD, 8MLD, 1del5q, group 1- G1) and 4 with &gt;5% BM blasts (2 EB1, 2 EB2group 2 - G2)) and 5 age matched controls. Myeloid lineage cells were isolated through ficoll bilayer protocol. All samples contained homogenous myeloid lineage subpopulations, assessedthrough optical microscopy. Two different metabolite extraction protocols were applied. The one with the best metabolites yield (50% MeOH, 30% ACN, 20% H2O) was chosen. LC-MS/MS analysis was performed using UPLC 1290 system (Agilent Technologies) coupled to a TripleTOF 5600+ mass spectrometer (SCIEX) equipped with SWATH acquisition, SelexION technology and an electrospray ionization source (ESI). A threshold of a minimum of three samples expressing a given metabolite was set against data sparsity. Data tables were scaled by data centering and setting unit variance. Log2 Foldcalculation and PLS analysis were performed for the two datasets (positive and negative ion-modes). R2 and Q2 for positive ion-mode and negative-ion mode analyses were determined. Both datasets were merged in a unique data table by taking into account maximum absolute log2 foldvalues, when a metabolite was found in both datasets. Warburg effect was evidently present in both the G1 and G2 vs control comparisons, yet the role of this stem like aerobic glycolysis seems markedly different in the two groups. While in the G2 group it serves to rescue glucose from complete burn in the mitochondrion and thus shuts it towards nucleotide synthesis (Pentose Phosphate Pathway found upregulated) with the added benefit of increased reduced Glutathione synthesis and improved redox state, in the G1 group proves detrimental. This greatly variable effect of the same phenomenon in the cellular fate lies upon the quality and functionality of the cellular mitochondrial content. G2 precursors presented functional mitochondrial (decreased NAD/NADH and FAD/FADH2) contrary to the G1 ones (Table). Failing TCA cycle, with increased NAD/NADH and FAD/FADH2 ratios and markedly increased ADP/ATP levels leads to FAs accumulation due to failure of effective adequate β oxidation. The uncontrolled increase in the NAD/NADH ratio stimulates upper glycolysis into a turbo mode further increasing the ADP/ATP, depleting cellular energy contents, engaging it to a never-ending deadly metabolism. The enormous abundance of upper glycolytic intermediates is relieved through phospholipid and ceramide synthesis, all found massively upregulated in both the MDS vs control yet also in the G1 vs G2 comparisons. FAs, mostly phospholipid and ceramide accumulation, interrupt the mitochondrial membrane lipidome further incapacitating metabolic integrity and inducing their autophagic degradation which further stimulates the Warburg effect. This type of metabolic reprogramming is eventually targeted to epigenetic modifier production, increased S-adenosyl-methionine, the major methyl group donor, 2-HydroxyGlutarate, a potent epigenetic modifier and notorious oncometabolite, Acetyl-Lysine, the major acetyl- group donor, even glutathione. We therefore present a model of an uncontrolled Warburg effect which in the G1 group confers premature death of the hematopoietic precursors, the ineffective hematopoiesis of MDS. Yet, under the pressure of the vastly upregulated epigenetic modifiers cellular fate changes, the G1 precursors adapt and transform to the G2 ones yet eventually to Acute Myeloid Leukemia blasts. Table Disclosures Vassilopoulos: Genesis pharma SA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

The outcomes of lymphoma patients treated with PD1 inhibitors (PD1i) vary significantly across different histologies with objective responses rates that are around 70% in classical Hodgkin lymphoma, but significantly lower, around 10%, in indolent non-Hodgkin lymphomas (iNHL). This may be due in part to the inability of PD1i to restore the function of exhausted T-cells (Tex) in the tumor microenvironment (TME). PD1 is expressed on various T-cell subsets, including effector cells and Tex. In this study we sought to identify markers of exhaustion beyond PD1 that define T-cell subsets with high reactivation potential in marginal zone lymphoma (MZL). To define different stages of exhaustion in MZL, we developed and validated a mass cytometry (CyTOF) panel which integrates T-cell markers of lineage, differentiation, activation, suppression, cytokine production and transcription factors associated with exhaustion. We analyzed 35 MZL spleens obtained at diagnosis and 6 reactive spleens. We identified a population of CD8 cells in MZL that express TIM3 without PD1, compose 1.5% (range 0.14-4.88%) of total CD8 cells and expand with activation through the TCR (6.2% of CD8, range 0.6-14.2%). Prolonged cytokine exposure has been shown to induce exhaustion in healthy T-cells, and so to determine whether PD1-TIM3+ cells are Tex, we treated healthy donor T-cells with activating beads and IL12 and analyzed them by flow cytometry. We showed that PD1-TIM3+ cells expand with repetitive activation and IL12 treatment suggesting that they are Tex. Since Tex have been shown to have a distinct transcription profile compared to functional effector T-cells, we analyzed the expression of several transcription factors (TFs) that are upregulated in Tex by CyTOF and compared them to other subsets of T-cells. PD1-TIM3+ cells expressed higher levels of Eomes, Tbet, TOX and Helios compared to activated effector cells, confirming that they are Tex, but lower levels levels of the same TFs compared to PD1+TIM3+ cells, consistent with a less severely exhausted phenotype. To characterize the function of PD1-TIM3+ cells, we manually gated on subsets of CD8+ non-naïve cells that were stained with the CyTOF panel and compared the different subsets. We showed that PD1-TIM3+ cells arise from effector cells, maintain their polyfunctionality by producing cytokines and chemokines and have a unique cytokine production profile, including perforin, granzyme B and proinflammatory cytokines, such as IL17A. Importantly, PD1-TIM3+ cells produced higher levels of most cytokines compared to more severely Tex expressing both PD1 and TIM3 (Fig 1). We then performed tSNE analysis where similar objects are modeled by nearby points. We determined that PD1-TIM3+ cells cluster together, suggesting that they are phenotypically homogeneous cells in terms of function and expression of activation markers and are significantly different from PD1+TIM3+ cells (Fig 2). We finally blocked PD1 or TIM3 and analyzed the effect of each antibody blockade on function. We showed that TIM3 blockade was able to restore the production of most cytokines to higher degrees than PD1 blockade. In addition, TIM3 blockade led to upregulation of CD28, which is critical for the rescue of Tex through costimulation, while PD1 blockade did not. We then analyzed the clinical outcomes of all 34 MZL patients. The frequency of PD1-TIM3+ cells was lower among observed patients who failed to achieve an event-free survival (EFS) of 12 months (EFS12) (0.8% vs 1.7%, p=0.02) and among treated patients that failed an EFS of 24 months (EFS24) (0.9 vs 1.7%, p=0.03), when compared to patients that reached these endpoints. Higher levels of PD1-TIM3+ cells were also associated with a trend towards improved overall survival (OS). Five-year OS was 88% vs. 69% in patients with PD1-TIM3+ levels >2% and <2% of total CD8 cells respectively (p=0.1) (Fig 3). Our study provides insights into the mechanisms of failure of PD1i in MZL and identifies a novel population of Tex with high reactivation potential which is clinically relevant and could serve as a target for future immunotherapies in iNHL. Disclosures Anagnostou: American Society of Hematology, Mayo Clinic/Iowa Lymphoma SPORE, Mayo Clinic Immune Monitoring Core, Mayo Clinic Hematology Small Grant: Research Funding. Novak:Celgene Coorperation: Research Funding. Ansell:Mayo Clinic Rochester: Employment; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding.

AbstractTailoring the nanostructure/morphology and chemical composition is important to regulate the electronic configuration of electrocatalysts and thus enhance their performance for water and urea electrolysis. Herein, the nitrogen-doped carbon-decorated tricomponent metal phosphides of FeP4 nanotube@Ni-Co-P nanocage (NC-FNCP) with unique nested hollow architectures are fabricated by a self-sacrifice template strategy. Benefiting from the multi-component synergy, the modification of nitrogen-doped carbon, and the modulation of nested porous hollow morphology, NC-FNCP facilitates rapid electron/mass transport in water and urea electrolysis. NC-FNCP-based anode shows low potentials of 248 mV and 1.37 V (vs. reversible hydrogen electrode) to attain 10 mA/cm2 for oxygen evolution reaction (OER) and urea oxidation reaction (UOR), respectively. In addition, the overall urea electrolysis drives 10 mA/cm2 at a comparatively low voltage of 1.52 V (vs. RHE) that is 110 mV lower than that of overall water electrolysis, as well as exhibits excellent stability over 20 h. This work strategizes a multi-shell-structured electrocatalyst with multi-compositions and explores its applications in a sustainable combination of hydrogen production and sewage remediation.

SARS-CoV-2, the virus responsible for COVID19, binds to ACE2, via its spike protein S1 subunit, leading to viral infection and respiratory disease. COVID-19 is associated with cardiovascular disease and systemic inflammation. Since ACE2 is expressed in vascular cells we questioned whether SARS-CoV-2 induces vascular inflammation and whether this is related to viral infection. Human microvascular endothelial cells (EC) were exposed to recombinant S1p (rS1p) 0.66 μg/mL for 10 min, 5h and 24h. Gene expression was assessed by RT-PCR and levels of IL6 and MCP1, as well as ACE2 activity, were assessed by ELISA. Expression of ICAM1 and PAI1 was assessed by immunoblotting. ACE2 activity was blocked by MLN4760 (ACE2 inhibitor) and siRNA. Viral infection was assessed by exposing Vero E6 (kidney epithelial cells; pos ctl) and EC to 10 5 pfu of SARS-CoV-2 where virus titre was measured by plaque assay. Co-IP coupled mass spectrometry protein identification and label free proteomics were used to investigate ACE2-mediated signalling. rS1p increased IL6 mRNA (14.2±2.1 vs. C:0.61±0.03 2^-ddCT) and levels (1221.2±18.3 vs. C:22.77±3.2 pg/mL); MCP1 mRNA (5.55±0.62 vs. C:0.65±0.04 2^-ddCT) and levels (1110±13.33 vs. C:876.9±33.4 pg/mL); ICAM1 (17.7±3.1 vs. C:3.9±0.4 AU) and PAI1 (5.6±0.7 vs. C: 2.9±0.2), p<0.05. MLN4760, but not rS1p, decreased ACE2 activity (367.4±18 vs. C: 1011±268 RFU, p<0.05) and blocked rS1p effects on ICAM1 and PAI1. ACE2 siRNA blocked rS1p-induced IL6 release, ICAM1, and PAI1 responses as well as rS1p-induced NFκB activation. Proteomics analysis of the global effect of rS1, identified biological process enrichment of proteins from virus transcription and NFκB signalling. ACE2 Co-IP identified 216 interacting proteins (filtered with ≥1 unique peptide, 1% FDR), linked to cytokine production and inflammation. EC were not susceptible to SARS-CoV-2 infection, while the virus replicated well in Vero E6. In conclusion, we demonstrate that rS1p induces an inflammatory response through ACE2 in endothelial cells. These effects seem to be independent of viral infection. Our findings suggest that vascular inflammation in COVID-19 involves activation of ACE2-mediated pro-inflammatory signalling that may be unrelated to viral replication.

This article is a comparison of two remarkably different takes on a single subject, namely the shifting meaning of the word ‘publishing’ brought about by the changes in literacy habits related to Web 2.0. One the one hand, we have Andrew Keen’s much lambasted 2007 book The Cult of the Amateur, which is essentially an attempt to defend traditional gatekeeper models of cultural production by denigrating online, user-generated content. The second is Spin journalist Andy Greenwald’s Nothing Feels Good, focusing on the Emo subculture of the early 2000s and its reliance on Web 2.0 as an integral medium for communication and the accumulation of subcultural capital. What I want to suggest in this article is that these two books, with their contrasting readings of Web 2.0, both tell us something specific about what the word “publishing” means and how it is currently undergoing a significant change brought about by a radical adaptation of literacy practices. What I think both books also do is give us an insight into how those changes are being interpreted, to be rejected on the one hand and applauded on the other. Both books have their faults. Keen’s work can fairly easily be passed off as a sort of cantankerous reminiscence for the legitimacy of an earlier era of publishing, and Greenwald’s Emos have, like all teen subcultures, changed somewhat. Yet what both books portray is an attempt to digest how Web 2.0 has altered perceptions of what constitutes legitimate speaking positions and how that is reflected in the literacy practices that shape the relationships among authors, readers, and the channels through which they interact. Their primary difference is a disparity in the value they place on Web 2.0’s amplification of the Internet’s use as a social and communicative medium. Greenwald embraces it as the facilitator of an open-access dialogue, whereas Keen sees it as a direct threat to other, more traditional, gatekeeper genres. Accordingly, Keen begins his book with a lament that Web 2.0’s “democratization” of media is “undermining truth, souring civic discourse and belittling expertise, experience, and talent … it is threatening the very future of our cultural institutions” (15). He continues, Today’s editors, technicians, and cultural gatekeepers—the experts across an array of fields—are necessary to help us to sift through what’s important and what’s not, what is credible from what is unreliable, what is worth spending our time on as opposed to the white noise that can be safely ignored. (45) As examples of the “white noise,” he lists some of the core features of Web 2.0—blogs, MySpace, YouTube and Facebook. The notable similarity between all of these is that their content is user generated and, accordingly, comes from the position of the personal, rather than from a gatekeeper. In terms of their readership, this presents a fundamental shift in an understanding of authenticated speaking positions, one which Keen suggests underwrites reliability by removing the presence of certifiable expertise. He looks at Web 2.0 and sees a mass of low grade, personal content overwhelming traditional benchmarks of quality and accountability. His definition of “publishing” is essentially one in which a few, carefully groomed producers express work seen as relevant to the wider community. The relationship between reader and writer is primarily one sided, mediated by a gatekeeper and rests on the assumption by all involved that the producer has the legitimacy to speak to a large, and largely silent, readership. Greenwald, by contrast, looks at the same genres and comes to a remarkably different and far more positive conclusion. He focuses heavily on the lively message boards of the social networking site Makeoutclub, the shift to a long tail marketing style by key Emo record labels such as Vagrant and Drive-Thru Records and, in particular, the widespread use of LiveJournal (www.livejournal.com) by suburban, Emo fixated teenagers. Of this he writes: The language is inflated, coded as ‘adult’ and ‘poetic’, which often translates into affected, stilted and forced. But if one can accept that, there’s a sweet vulnerability to it. The world of LiveJournal is an enclosed circuit where everyone has agreed to check their cynicism at the sign on screen; it’s a pulsing, swoony realm of inflated emotions, expectations and dialogue. (287) He specifically notes that one cannot read mediums like LiveJournal in the same style as their more traditional counterparts. There is a necessity to adopt a reading style conducive to a dialogue devoid of conventional quality controls. It is also, he notes, a heavily interconnected, inherently social medium: LiveJournals represent the truest and easiest realization of the essential teenage (and artistic) tenet of the importance of a ‘room of one’s own’, and yet the framework of the website is enough to make each individual room interconnected into a mosaic of richly felt lives. (288) Where Keen sees Web 2.0 as a shift way from established cultural forums, Greenwald sees it as an interconnected conversation. His definition of publishing is more fluid, founded on a belief not in the authenticity of a single, validated voice but on the legitimacy of interaction and communication entirely devoid of any gatekeepers. Central to understanding the difference between Greenwald and Keen is the issue or whether or not we accept the legitimacy of personal voices and how we evaluate the kind of reading practices involved in interpreting them. In this respect, Greenwald’s reference to “a room of one’s own” is telling. When Virginia Woolf wrote A Room of One’s Own in 1929, Web 2.0 wasn’t even a consideration, but her work dealt with a similar subject matter, detailing the key role the novel genre played in legitimising women’s voices precisely because it was “young enough to be soft in [their] hands” (74). What would eventually emerge from Woolf’s work was the field of feminist literary criticism, which hit its stride in the mid-eighties. In terms of its understanding of the power relations inherent to cultural production, particularly as they relate to gatekeeping, it’s a rich academic tradition notably lacking in the writing on Web 2.0. For example, Celia Lury’s essay “Reading the Self,” written more than ten years before the popularisation of the internet, looks specifically at the way in which authoritative speaking positions gain their legitimacy not just through the words on the page but through the entire relationships among author, genre, channels of distribution, and readership. She argues that, “to write is to enter into a relationship with a community of readers, and various forms of writing are seen to involve and imply, at any particular time, various forms of relationship” (102). She continues, so far as text is clearly written/read within a particular genre, it can be seen to rest upon a more or less specific set of social relations. It also means that ‘textual relations’—that is, formal techniques, reading strategies and so on—are not held separate from ‘non-textual relations’—such as methods of cultural production and modes of distribution—and that the latter can be seen to help construct ‘literary value.’ (102) The implication is that an appropriation of legitimised speaking positions isn’t done purely by overthrowing or contesting an established system of ‘quality’ but by developing a unique relationship between author, genre, and readership. Textual and non-textual practices blur together to create literary environments and cultural space. The term “publishing” is at the heart of these relationships, describing the literacies required to interpret particular voices and forms of communication. Yet, as Lury writes, literacy habits can vary. Participation in dialogue-driven, user-generated mediums is utterly different from conventional, gatekeeper-driven ones, yet the two can easily co-exist. For instance, reading last year’s Man Booker prize-winner doesn’t stop one from reading, or even writing, blogs. One can enact numerous literacy practices, move between discourses and inhabit varied relationships between genre, reader, and writer. However, with the rise of Web 2.0 a whole range of literacies that used to be defined as “private sphere” or “everyday literacies,” everything from personal conversations and correspondence to book clubs and fanzines, have become far, far more public. In the past these dialogue-based channels of communication have never been in a position where they could be defined as “publishing.” Web 2.0 changes that, moving previously private sphere communication into online public space in a very obvious way. Keen dismisses this shift as a wall of white noise, but Greenwald does something equally interesting. To a large extent, his positive treatment of Web 2.0’s “affected, stilted and forced” user-generated content is validated by his focus on a “Youth” subculture, namely Emo. Indeed, he heavily links the impact of youthful subcultural practices with the internet, writing that Teenage life has always been about self-creation, and its inflated emotions and high stakes have always existed in a grossly accelerated bubble of hypertime. The internet is the most teenage of media because it too exists in this hypertime of limitless limited moments and constant reinvention. If emo is the soundtrack to hypertime, then the web is its greatest vehicle, the secret tunnel out of the locked bedroom and dead-eyed judgmental scenes of youth. (277) In this light, we accept the voices of his Emo subjects because, underneath their low-quality writing, they produce a “sweet vulnerability” and a “dialogue,” which provides them with a “secret tunnel” out of the loneliness of their bedrooms or unsupportive geographical communities. It’s a theme that hints at the degree to which discussions of Web 2.0 are often heavily connected to arguments about generationalism, framed by the field of youth studies and accordingly end up being mined for what Tara Brabazon calls “spectacular youth subcultures” (23). We see some core examples of this in some of the quasi-academic writing on the subject of “Youth.” For example, in his 2005 book XYZ: The New Rules of Generational Warfare, Michael Grose declares Generation Y as “post-literate”: Like their baby boomer parents and generation X before them, generation Ys get their information from a range of sources that include the written and spoken word. Magazines and books are in, but visual communication is more important for this cohort than their parents. They live in a globalised, visual world where images rather than words are universal communication media. The Internet has heightened the use of symbols as a direct communicator. (95) Given the Internet is overwhelmingly a textual medium, it’s hard to tell exactly what Grose’s point is other than to express his confusion over new literacy practices. In a similar vein and in a similar style, Rebecca Huntley writes in her book The World According to Y, In the Y world, a mobile phone is not merely a phone. It is, as described by demographer Bernard Salt, “a personal accessory, a personal communications device and a personal entertainment centre.” It’s a device for work and play, flirtation and sex, friendship and family. For Yers, their phone symbolizes freedom and flexibility. More than that, your mobile phone symbolizes you. (16) Like Keen, Grose and Huntley are trying to understand a shift in publishing and media that has produced new literacy practices. Unlike Keen, Grose and Huntley pin the change on young people and, like Greenwald, they turn a series of new literacy practices into something akin to what Dick Hebdige called “conspicuous consumption” (103). It’s a term he linked to his definition of bricolage as the production of “implicitly coherent, though explicitly bewildering, systems of connection between things which perfectly equip their users to ‘think’ their own world” (103). Thus, young people are differentiated from the rest of the population by their supposedly unique consumption of “symbols” and mobile phones, into which they read their own cryptic meanings and develop their own generational language. Greenwald shows this methodology in action, with the Emo use of things like LiveJournal, Makeoutclub and other bastions of Web 2.0 joining their record collections, ubiquitous sweeping fringes and penchant for accessorised outfits as part of the conspicuous consumption inherent to understandings of youth subculture. The same theme is reflected in Michel de Certeau’s term “tactics” or, more common amongst those studying Web 2.0, Henry Jenkins’s notion of “poaching”. The idea is that people, specifically young people, appropriate particular forms of cultural literacy to redefine themselves and add a sense of value to their voices. De Certeau’s definition of tactics, as a method of resistance “which cannot count on a ‘proper’ (a spatial or institutional localization), nor thus on a borderline distinguishing the other as a visible totality” (489), is a prime example of how Web 2.0 is being understood. Young people, Emo or not, engage in a consumption of the Internet, poaching the tools of production to redefine the value of their voices in a style completely acceptable to the neo-Marxist, Birmingham school understanding of youth and subculture as a combination producing a sense of resistance. It’s a narrative highly compatible within the fields of cultural and media studies, which, despite major shifts brought about by people like Ken Gelder, Sarah Thornton, Keith Kahn-Harris and the aforementioned Tara Brabazon, still look heavily for patterns of politicised consumption. The problem, as I think Keen inadvertently suggests, is that the Internet isn’t just about young people and their habits as consumers. It’s about what the word “publishing” actually means and how we think about the interaction among writers, readers, and the avenues through which they interact. The idea that we can pass off the redefinition of literacy practices brought about by Web 2.0 as a subcultural youth phenomena is an easy way of bypassing wider cultural shifts onto a token demographic. It presents Web 2.0 as an issue of “Youth” resisting the hegemony of traditional gatekeepers, which is effectively what Greenwald does. Yet such an approach has a very short shelf life. It’s a little like claiming the telephone or the television set were “youth genres.” The uptake of new technologies will inadvertently impact differently on those who grew up with them as compared to those who grew up without them. Yet ultimately changes in literacy habits are much larger than a generationalist framework can really express, particularly given the first generation of “digital natives” are now in their thirties. There’s a lot of things wrong with Andrew Keen’s book but one thing he does do well is ground the debate about Web 2.0 back to issues of legitimate speaking positions and publishing. That said, he also significantly simplifies those issues when he claims the problem is purely about the decline of traditional gatekeeper models. Responding to Keen’s criticism of him, Creative Commons founder Lawrence Lessig writes, I think it is a great thing when amateurs create, even if the thing they create is not as great as what the professional creates. I want my kids to write. But that doesn’t mean that I’ll stop reading Hemingway and read only what they write. What Keen misses is the value to a culture that comes from developing the capacity to create—independent of the quality created. That doesn’t mean we should not criticize works created badly (such as, for example, Keen’s book…). But it does mean you’re missing the point if you simply compare the average blog to the NY times (Lessig). What Lessig expresses here is the different, but not mutually exclusive, literacy practices involved in the word “publishing.” Publishing a blog is very different to publishing a newspaper and the way readers react to both will change as they move in and out the differing discursive spaces each occupies. In a recent collaborative paper by Sue Thomas, Chris Joseph, Jess Laccetti, Bruce Mason, Simon Mills, Simon Perril, and Kate Pullinger, they describe this capacity to move across different reading and writing styles as “transliteracy.” They define the term as “the ability to read, write and interact across a range of platforms, tools and media from signing and orality through handwriting, print, TV, radio and film, to digital social networks” (Thomas et al.). It’s a term that perfectly describes the capacity to move fluidly across discursive environments. Here we return to Greenwald’s use of a framework of youth and subculture. While I have criticised the Birminghamesque fixation on a homogeneous “Youth” demographic enacting resistance through conspicuous consumption, there is good reason to use existing subculture studies methodology as a means of understanding how transliteracies play out in everyday life. David Chaney remarks, the idea of subculture is redundant because the type of investment that the notion of subculture labelled is becoming more general, and therefore the varieties of modes of symbolization and involvement are more common in everyday life. (37) I think the increasing commonality of subcultural practices in everyday life actually makes the idea more relevant, not less. It does, however, make it much harder to pin things on “spectacular youth subcultures.” Yet the focus on “everyday life” is important here, shifting our understanding of “subculture” to the types of literacies played out within localised, personal networks and experiences. As de Certeau has argued, the practice of everyday life is an issue of “a way of thinking invested in a way of acting, an art of combination which cannot be dissociated from an art of using” (Certeau 486). This is as true for our literacy practices as anything else. Whether we choose to label those practices subcultural or not, our ability to interpret, take part in and react to different communicative forums is clearly fundamental to our understanding of the world around us, regardless of our age. Sarah Thornton suggests a useful alternate definition of subculture when she talks about subcultural capital: Subcultural capital is the linchpin of an alternative hierarchy in which the aces of age, gender, sexuality and race are all employed in order to keep the determinations of class, income and occupation at bay (105). This is an understanding that avoids easy narratives of young people and their consumption of Web 2.0 by recognising the complexity with which people’s literacy habits, in the cultural sense, connect to their active participation in the production of meaning. Subcultural capital implies that the framework through which individuals read, interpret, and shift between discursive environments, personalising and building links across the strata of cultural production, is acted out at the local and personal level, rather than purely through the relationship between a producing gatekeeper and a passive, consuming readership. If we recognise the ability for readers to connect multiple mediums, to shift between reading and writing practices, and to seamlessly interpret and digest markedly different assumptions about legitimate speaking voices across genres, our understanding of what it means to “publish” ceases to be an issue of generationalism or conventional mediums being washed away by the digital era. The issue we see in both Keen and Greenwald is an attempt to digest the way Web 2.0 has forced the concept of “publishing” to take on a multiplicity of meanings, played out by individual readers, and imbued with their own unique and interwoven textual and cultural literacy habits. It’s not only Emos who publish livejournals, and it’s incredibly naive to assume gatekeepers have ever really held a monopoly on all aspects of cultural production. What the rise of Web 2.0 has done is simply to bring everyday, private sphere dialogue driven literacies into the public sphere in a very obvious way. The kind of discourses once passed off as resistant youth subcultures are now being shown as common place. Keen is right to suggest that this will continue to impact, sometimes negatively, on traditional gatekeepers. Yet the change is inevitable. As our reading and writing practices alter around new genres, our understandings of what constitutes legitimate fields of publishing will also change. References Brabazon, Tara. From Revolution to Revelation. Aldershot: Ashgate, 2005. de Certeau, Michel. “Practice of Every Day Life.” Cultural Theory and Popular Culture. Ed. John Story. London: Prentice Hall, 1998. 483–94. Chaney, David. “Fragmented Culture and Subcultures.” After Subculture. Ed. Andy Bennett and Keith Kahn-Harris. Houndsmill: Palgrave McMillian, 2004. 36–48. Greenwald, Andy. Nothing Feels Good: Punk Rock, Teenagers and Emo. New York: St Martin’s Griffin, 2003. Grose, Michael. XYZ: The New Rules of Generational Warfare. Sydney: Random House, 2005. Hebdige, Dick. Subculture: The Meaning of Style. London: Methuen and Co Ltd, 1979. Huntley, Rebecca. The World According to Y. Crows Nest: Allen and Unwin, 2006. Keen, Andrew. The Cult of the Amateur. London: Nicholas Brealey Publishing, 2007. Lessig, Lawrence. “Keen’s ‘The Cult of the Amateur’: BRILLIANT!” Lessig May 31, 2007. Aug. 19 2008 ‹http://www.lessig.org/blog/2007/05/keens_the_cult_of_the_amateur.html>. Lury, Celia. “Reading the Self: Autobiography, Gender and the Institution of the Literary.” Off-Centre: Feminism and Cultural Studies. Ed. Sarah. Franklin, Celia Lury, and Jackie Stacey. Hammersmith: HarperCollinsAcademic, 1991. 97–108. Thomas, Sue, Chris Joseph, Jess Laccetti, Bruce Mason, Simon Mills, Simon Perril, and Kate Pullinger. “Transliteracy: Crossing Divides.” First Monday 12.12. (2007). Apr. 1 2008 ‹http://www.uic.edu/htbin/cgiwrap/bin/ojs/index.php/fm/article/view/2060/1908>. Thornton, Sarah. Club Cultures: Music, Media and Subcultural Capital. Oxford: Polity Press, 1995. Woolf, Virginia. A Room of One’s Own. Frogmore: Triad/Panther Press, 1977.

This issue of M/C Journal is devoted to all things cute – Internet animals and stuffed toys, cartoon characters and branded bears. In what follows our nine contributors scrutinise a diverse range of media objects, discussing everything from the economics of Grumpy Cat and the aesthetics of Furbys to Reddit’s intellectual property dramas and the ethics of kitten memes. The articles range across diverse sites, from China to Canada, and equally diverse disciplines, including cultural studies, evolutionary economics, media anthropology, film studies and socio-legal studies. But they share a common aim of tracing out the connections between degraded media forms and wider questions of culture, identity, economy and power. Our contributors tell riveting stories about these connections, inviting us to see the most familiar visual culture in a new way. We are not the first to take cute media seriously as a site of cultural politics, and as an industry in its own right. Cultural theory has a long, antagonistic relationship with the kitsch and the disposable. From the Frankfurt School’s withering critique of cultural commodification to revisionist feminist accounts that emphasise the importance of the everyday, critics have been conducting sporadic incursions into this space for the better part of a century. The rise of cultural studies, a discipline committed to analysing “the scrap of ordinary or banal existence” (Morris and Frow xviii), has naturally provided a convincing intellectual rationale for such research, and has inspired an impressive array of studies on such things as Victorian-era postcards (Milne), Disney films (Forgacs), Hallmark cards (West, Jaffe) and stock photography (Frosh). A parallel strand of literary theory considers the diverse registers of aesthetic experience that characterize cute content (Brown, Harris). Sianne Ngai has written elegantly on this topic, noting that “while the avant-garde is conventionally imagined as sharp and pointy, as hard- or cutting-edge, cute objects have no edge to speak of, usually being soft, round, and deeply associated with the infantile and the feminine” (814). Other scholars trace the historical evolution of cute aesthetics and commodities. Cultural historians have documented the emergence of consumer markets for children and how these have shaped what we think of as cute (Cross). Others have considered the history of domestic animal imagery and its symptomatic relationship with social anxieties around Darwinism, animal rights, and pet keeping (Morse and Danahay, Ritvo). And of course, Japanese popular culture – with its distinctive mobilization of cute aesthetics – has attracted its own rich literature in anthropology and area studies (Allison, Kinsella). The current issue of M/C Journal extends these lines of research while also pushing the conversation in some new directions. Specifically, we are interested in the collision between cute aesthetics, understood as a persistent strand of mass culture, and contemporary digital media. What might the existing tradition of “cute theory” mean in an Internet economy where user-generated content sites and social media have massively expanded the semiotic space of “cute” – and the commercial possibilities this entails? As the heir to a specific mode of degraded populism, the Internet cat video may be to the present what the sitcom, the paperback novel, or the Madonna video was to an earlier moment of cultural analysis. Millions of people worldwide start their days with kittens on Roombas. Global animal brands, such as Maru and Grumpy Cat, are appearing, along with new talent agencies for celebrity pets. Online portal I Can Haz Cheezburger has received millions of dollars in venture capital funding, becoming a diversified media business (and then a dotcom bubble). YouTube channels, Twitter hashtags and blog rolls form an infrastructure across which a vast amount of cute-themed user-generated content, as well as an increasing amount of commercially produced and branded material, now circulates. All this reminds us of the oft-quoted truism that the Internet is “made of kittens”, and that it’s “kittens all the way down”. Digitization of cute culture leads to some unusual tweaks in the taste hierarchies explored in the aforementioned scholarship. Cute content now functions variously as an affective transaction, a form of fandom, and as a subcultural discourse. In some corners of the Internet it is also being re-imagined as something contemporary, self-reflexive and flecked with irony. The example of 4Chan and LOLcats, a jocular, masculinist remix of the feminized genre of pet photography, is particularly striking here. How might the topic of cute look if we moving away from the old dialectics of mass culture critique vs. defense and instead foreground some of these more counter-intuitive aspects, taking seriously the enormous scale and vibrancy of the various “cute” content production systems – from children’s television to greeting cards to CuteOverload.com – and their structural integration into current media, marketing and lifestyle industries? Several articles in this issue adopt this approach, investigating the undergirding economic and regulatory structures of cute culture. Jason Potts provides a novel economic explanation for why there are so many animals on the Internet, using a little-known economic theory (the Alchian-Allen theorem) to explain the abundance of cat videos on YouTube. James Meese explores the complex copyright politics of pet images on Reddit, showing how this online community – which is the original source of much of the Internet’s animal gifs, jpegs and videos – has developed its own procedures for regulating animal image “piracy”. These articles imaginatively connect the soft stuff of cute content with the hard stuff of intellectual property and supply-and-demand dynamics. Another line of questioning investigates the political and bio-political work involved in everyday investments in cute culture. Seen from this perspective, cute is an affect that connects ground-level consumer subjectivity with various economic and political projects. Carolyn Stevens’ essay offers an absorbing analysis of the Japanese cute character Rilakkuma (“Relaxed Bear”), a wildly popular cartoon bear that is typically depicted lying on the couch and eating sweets. She explores what this representation means in the context of a stagnant Japanese economy, when the idea of idleness is taking on a new shade of meaning due to rising under-employment and precarity. Sharalyn Sanders considers a fascinating recent case of cute-powered activism in Canada, when animal rights activists used a multimedia stunt – a cat, Tuxedo Stan, running for mayor of Halifax, Canada – to highlight the unfortunate situation of stray and feral felines in the municipality. Sanders offers a rich analysis of this unusual political campaign and the moral questions it provokes. Elaine Laforteza considers another fascinating collision of the cute and the political: the case of Lil’ Bub, an American cat with a rare genetic condition that results in a perpetually kitten-like facial expression. During 2011 Lil’ Bub became an online phenomenon of the first order. Laforteza uses this event, and the controversies that brewed around it, as an entry point for a fascinating discussion of the “cute-ification” of disability. These case studies remind us once more of the political stakes of representation and viral communication, topics taken up by other contributors in their articles. Radha O’Meara’s “Do Cats Know They Rule YouTube? How Cat Videos Disguise Surveillance as Unselfconscious Play” provides a wide-ranging textual analysis of pet videos, focusing on the subtle narrative structures and viewer positioning that are so central to the pleasures of this genre. O’Meara explains how the “cute” experience is linked to the frisson of surveillance, and escape from surveillance. She also explains the aesthetic differences that distinguish online dog videos from cat videos, showing how particular ideas about animals are hardwired into the apparently spontaneous form of amateur content production. Gabriele de Seta investigates the linguistics of cute in his nuanced examination of how a new word – meng – entered popular discourse amongst Mandarin Chinese Internet users. de Seta draws our attention to the specificities of cute as a concept, and how the very notion of cuteness undergoes a series of translations and reconfigurations as it travels across cultures and contexts. As the term meng supplants existing Mandarin terms for cute such as ke’ai, debates around how the new word should be used are common. De Seta shows us how deploying these specific linguistic terms for cuteness involve a range of linguistic and aesthetic judgments. In short, what exactly is cute and in what context? Other contributors offer much-needed cultural analyses of the relationship between cute aesthetics, celebrity and user-generated culture. Catherine Caudwell looks at the once-popular Furby toy brand its treatment in online fan fiction. She notes that these forms of online creative practice offer a range of “imaginative and speculative” critiques of cuteness. Caudwell – like de Seta – reminds us that “cuteness is an unstable aesthetic that is culturally contingent and very much tied to behaviour”, an affect that can encompass friendliness, helplessness, monstrosity and strangeness. Jonathon Hutchinson’s article explores “petworking”, the phenomenon of social media-enabled celebrity pets (and pet owners). Using the famous example of Boo, a “highly networked” celebrity Pomeranian, Hutchinson offers a careful account of how cute is constructed, with intermediaries (owners and, in some cases, agents) negotiating a series of careful interactions between pet fans and the pet itself. Hutchinson argues if we wish to understand the popularity of cute content, the “strategic efforts” of these intermediaries must be taken into account. Each of our contributors has a unique story to tell about the aesthetics of commodity culture. The objects they analyse may be cute and furry, but the critical arguments offered here have very sharp teeth. We hope you enjoy the issue.Acknowledgments Thanks to Axel Bruns at M/C Journal for his support, to our hard-working peer reviewers for their insightful and valuable comments, and to the Swinburne Institute for Social Research for the small grant that made this issue possible. ReferencesAllison, Anne. “Cuteness as Japan’s Millenial Product.” Pikachu’s Global Adventure: The Rise and Fall of Pokemon. Ed. Joseph Tobin. Durham: Duke University Press, 2004. 34-48. Brown, Laura. Homeless Dogs and Melancholy Apes: Humans and Other Animals in the Modern Literary Imagination. Ithaca: Cornell University Press, 2010. Cross, Gary. The Cute and the Cool: Wondrous Innocence and Modern American Children's Culture. Oxford: Oxford University Press, 2004. Forgacs, David. "Disney Animation and the Business of Childhood." Screen 33.4 (1992): 361-374. Frosh, Paul. "Inside the Image Factory: Stock Photography and Cultural Production." Media, Culture & Society 23.5 (2001): 625-646. Harris, Daniel. Cute, Quaint, Hungry and Romantic: The Aesthetics of Consumerism. New York: Basic Books, 2000. Jaffe, Alexandra. "Packaged Sentiments: The Social Meanings of Greeting Cards." Journal of Material Culture 4.2 (1999): 115-141. Kinsella, Sharon. “Cuties in Japan” Women, Media and Consumption in Japan. Ed. Lise Skov and Brian Moeran. Honolulu: University of Hawaii Press, 1995. 220 - 54. Frow, John, and Meaghan Morris, eds. Australian Cultural Studies: A Reader. Chicago: University of Illinois Press, 1993. Milne, Esther. Letters, Postcards, Email: Technologies of Presence. New York: Routledge, 2012. Morse, Deborah and Martin Danahay, eds. Victorian Animal Dreams: Representations of Animals in Victorian Literature and Culture. Aldershot: Ashgate Publishing. 2007. Ngai, Sianne. "The Cuteness of the Avant‐Garde." Critical Inquiry 31.4 (2005): 811-847. Ritvo, Harriet. The Animal Estate: The English and Other Creatures in the Victorian Age. Cambridge: Harvard University Press, 1987. West, Emily. "When You Care Enough to Defend the Very Best: How the Greeting Card Industry Manages Cultural Criticism." Media, Culture & Society 29.2 (2007): 241-261.

For the past twenty years, academics and other social commentators have, by and large, shared the view that the phase of modernity through which we are currently passing is defined by two interrelated catalysts of change: the physical movement of people and the virtual movement of information around the globe. As we enter the second decade of the new millennium, it is certainly a timely moment to reflect upon the ways in which the prognoses of the scholars and scientists writing in the late twentieth century have come to pass, especially since—during the time this special issue has been in press—the revolutions that are gathering pace in the Arab world appear to be realising the theoretical prediction that the ever-increasing “flows” of people and information would ultimately bring about the end of the nation-state and herald an era of transnationalism (Appadurai, Urry). For writers like Arjun Appadurai, moreover, the concept of diaspora was key to grasping how this new world order would take shape, and how it would operate: Diasporic public spheres, diverse amongst themselves, are the crucibles of a postnational political order. The engines of their discourse are mass media (both interactive and expressive) and the movement of refugees, activists, students, laborers. It may be that the emergent postnational order proves not to be a system of homogeneous units (as with the current system of nation-states) but a system based on relations between heterogeneous units (some social movements, some interest groups, some professional bodies, some non-governmental organizations, some armed constabularies, some judicial bodies) ... In the short run, as we can see already, it is likely to be a world of increased incivility and violence. In the longer run, free from the constraints of the nation form, we may find that cultural freedom and sustainable justice in the world do not presuppose the uniform and general existence of the nation-state. This unsettling possibility could be the most exciting dividend of living in modernity at large. (23) In this editorial, we would like to return to the “here and now” of the late 1990s in which theorists like Arjun Appaduri, Ulrich Beck, John Urry, Zygmunt Bauman, Robert Robertson and others were “imagining” the consequences of both globalisation and glocalisation for the twenty-first century in order that we may better assess what is, indeed, coming to pass. While most of their prognoses for this “second modernity” have proven remarkably accurate, it is their—self-confessed—inability to forecast either the nature or the extent of the digital revolution that most vividly captures the distance between the mid-1990s and now; and it is precisely the consequences of this extraordinary technological revolution on the twin concepts of “glocality” and “diaspora” that the research featured in this special issue seeks to capture. Glocal Imaginaries Appadurai’s endeavours to show how globalisation was rapidly making itself felt as a “structure of feeling” (Williams in Appadurai 189) as well as a material “fact” was also implicit in our conceptualisation of the conference, “Glocal Imaginaries: Writing/Migration/Place,” which gave rise to this special issue. This conference, which was the culmination of the AHRC-funded project “Moving Manchester: Literature/Migration/Place (2006-10)”, constituted a unique opportunity to gain an international, cross-disciplinary perspective on urgent and topical debates concerning mobility and migration in the early twenty-first century and the strand “Networked Diasporas” was one of the best represented on the program. Attracting papers on broadcast media as well as the new digital technologies, the strand was strikingly international in terms of the speakers’ countries of origin, as is this special issue which brings together research from six European countries, Australia and the Indian subcontinent. The “case-studies” represented in these articles may therefore be seen to constitute something of a “state-of-the-art” snapshot of how Appadurai’s “glocal imaginary” is being lived out across the globe in the early years of the twenty-first century. In this respect, the collection proves that his hunch with regards to the signal importance of the “mass-media” in redefining our spatial and temporal coordinates of being and belonging was correct: The third and final factor to be addressed here is the role of the mass-media, especially in its electronic forms, in creating new sorts of disjuncture between spatial and virtual neighborhoods. This disjuncture has both utopian and dystopian potentials, and there is no easy way to tell how these may play themselves out in the future of the production of locality. (194) The articles collected here certainly do serve as testament to the “bewildering plethora of changes in ... media environments” (195) that Appadurai envisaged, and yet it can clearly also be argued that this agent of glocalisation has not yet brought about the demise of the nation-state in the way (or at the speed) that many commentators predicted. Digital Diasporas in a Transnational World Reviewing the work of the leading social science theorists working in the field during the late 1990s, it quickly becomes evident that: (a) the belief that globalisation presented a threat to the nation-state was widely held; and (b) that the “jury” was undecided as to whether this would prove a good or bad thing in the years to come. While the commentators concerned did their best to complexify both their analysis of the present and their view of the future, it is interesting to observe, in retrospect, how the rhetoric of both utopia and dystopia invaded their discourse in almost equal measure. We have already seen how Appadurai, in his 1996 publication, Modernity at Large, looks beyond the “increased incivility and violence” of the “short term” to a world “free from the constraints of the nation form,” while Roger Bromley, following Agamben and Deleuze as well as Appadurai, typifies a generation of literary and cultural critics who have paid tribute to the way in which the arts (and, in particular, storytelling) have enabled subjects to break free from their national (af)filiations (Pearce, Devolving 17) and discover new “de-territorialised” (Deleuze and Guattari) modes of being and belonging. Alongside this “hope,” however, the forces and agents of globalisation were also regarded with a good deal of suspicion and fear, as is evidenced in Ulrich Beck’s What is Globalization? In his overview of the theorists who were then perceived to be leading the debate, Beck draws distinctions between what was perceived to be the “engine” of globalisation (31), but is clearly most exercised by the manner in which the transformation has taken shape: Without a revolution, without even any change in laws or constitutions, an attack has been launched “in the normal course of business”, as it were, upon the material lifelines of modern national societies. First, the transnational corporations are to export jobs to parts of the world where labour costs and workplace obligations are lowest. Second, the computer-generation of worldwide proximity enables them to break down and disperse goods and services, and produce them through a division of labour in different parts of the world, so that national and corporate labels inevitably become illusory. (3; italics in the original) Beck’s concern is clearly that all these changes have taken place without the nation-states of the world being directly involved in any way: transnational corporations began to take advantage of the new “mobility” available to them without having to secure the agreement of any government (“Companies can produce in one country, pay taxes in another and demand state infrastructural spending in yet another”; 4-5); the export of the labour market through the use of digital communications (stereotypically, call centres in India) was similarly unregulated; and the world economy, as a consequence, was in the process of becoming detached from the processes of either production or consumption (“capitalism without labour”; 5-7). Vis-à-vis the dystopian endgame of this effective “bypassing” of the nation-state, Beck is especially troubled about the fate of the human rights legislation that nation-states around the world have developed, with immense effort and over time (e.g. employment law, trade unions, universal welfare provision) and cites Zygmunt Bauman’s caution that globalisation will, at worst, result in widespread “global wealth” and “local poverty” (31). Further, he ends his book with a fully apocalyptic vision, “the Brazilianization of Europe” (161-3), which unapologetically calls upon the conventions of science fiction to imagine a worst-case scenario for a Europe without nations. While fourteen or fifteen years is evidently not enough time to put Beck’s prognosis to the test, most readers would probably agree that we are still some way away from such a Europe. Although the material wealth and presence of the transnational corporations strikes a chord, especially if we include the world banks and finance organisations in their number, the financial crisis that has rocked the world for the past three years, along with the wars in Iraq and Afghanistan, and the ascendancy of Al-Qaida (all things yet to happen when Beck was writing in 1997), has arguably resulted in the nations of Europe reinforcing their (respective and collective) legal, fiscal, and political might through rigorous new policing of their physical borders and regulation of their citizens through “austerity measures” of an order not seen since World War Two. In other words, while the processes of globalisation have clearly been instrumental in creating the financial crisis that Europe is presently grappling with and does, indeed, expose the extent to which the world economy now operates outside the control of the nation-state, the nation-state still exists very palpably for all its citizens (whether permanent or migrant) as an agent of control, welfare, and social justice. This may, indeed, cause us to conclude that Bauman’s vision of a world in which globalisation would make itself felt very differently for some groups than others came closest to what is taking shape: true, the transnationals have seized significant political and economic power from the nation-state, but this has not meant the end of the nation-state; rather, the change is being experienced as a re-trenching of whatever power the nation-state still has (and this, of course, is considerable) over its citizens in their “local”, everyday lives (Bauman 55). If we now turn to the portrait of Europe painted by the articles that constitute this special issue, we see further evidence of transglobal processes and practices operating in a realm oblivious to local (including national) concerns. While our authors are generally more concerned with the flows of information and “identity” than business or finance (Appaduri’s “ethnoscapes,” “technoscapes,” and “ideoscapes”: 33-7), there is the same impression that this “circulation” (Latour) is effectively bypassing the state at one level (the virtual), whilst remaining very materially bound by it at another. In other words, and following Bauman, we would suggest that it is quite possible for contemporary subjects to be both the agents and subjects of globalisation: a paradox that, as we shall go on to demonstrate, is given particularly vivid expression in the case of diasporic and/or migrant peoples who may be able to bypass the state in the manufacture of their “virtual” identities/communities) but who (Cohen) remain very much its subjects (or, indeed, “non-subjects”) when attempting movement in the material realm. Two of the articles in the collection (Leurs & Ponzanesi and Marcheva) deal directly with the exponential growth of “digital diasporas” (sometimes referred to as “e-diasporas”) since the inception of Facebook in 2004, and both provide specific illustrations of the way in which the nation-state both has, and has not, been transcended. First, it quickly becomes clear that for the (largely) “youthful” (Leurs & Ponzanesi) participants of nationally inscribed networking sites (e.g. “discovernikkei” (Japan), “Hyves” (Netherlands), “Bulgarians in the UK” (Bulgaria)), shared national identity is a means and not an end. In other words, although the participants of these sites might share in and actively produce a fond and nostalgic image of their “homeland” (Marcheva), they are rarely concerned with it as a material or political entity and an expression of their national identities is rapidly supplemented by the sharing of other (global) identity markers. Leurs & Ponzanesi invoke Deleuze and Guattari’s concept of the “rhizome” to describe the way in which social networkers “weave” a “rhizomatic path” to identity, gradually accumulating a hybrid set of affiliations. Indeed, the extent to which the “nation” disappears on such sites can be remarkable as was also observed in our investigation of the digital storytelling site, “Capture Wales” (BBC) (Pearce, "Writing"). Although this BBC site was set up to capture the voices of the Welsh nation in the early twenty-first century through a collection of (largely) autobiographical stories, very few of the participants mention either Wales or their “Welshness” in the stories that they tell. Further, where the “home” nation is (re)imagined, it is generally in an idealised, or highly personalised, form (e.g. stories about one’s own family) or through a sharing of (perceived and actual) cultural idiosyncrasies (Marcheva on “You know you’re a Bulgarian when …”) rather than an engagement with the nation-state per se. As Leurs & Ponzanesi observe: “We can see how the importance of the nation-state gets obscured as diasporic youth, through cultural hybridisation of youth culture and ethnic ties initiate subcultures and offer resistance to mainstream cultural forms.” Both the articles just discussed also note the shading of the “national” into the “transnational” on the social networking sites they discuss, and “transnationalism”—in the sense of many different nations and their diasporas being united through a common interest or cause—is also a focus of Pikner’s article on “collective actions” in Europe (notably, “EuroMayDay” and “My Estonia”) and Harb’s highly topical account of the role of both broadcast media (principally, Al-Jazeera) and social media in the revolutions and uprisings currently sweeping through the Arab world (spring 2011). On this point, it should be noted that Harb identifies this as the moment when Facebook’s erstwhile predominantly social function was displaced by a manifestly political one. From this we must conclude that both transnationalism and social media sites can be put to very different ends: while young people in relatively privileged democratic countries might embrace transnationalism as an expression of their desire to “rise above” national politics, the youth of the Arab world have engaged it as a means of generating solidarity for nationalist insurgency and liberation. Another instance of “g/local” digital solidarity exceeding national borders is to be found in Johanna Sumiala’s article on the circulatory power of the Internet in the Kauhajoki school shooting which took place Finland in 2008. As well as using the Internet to “stage manage” his rampage, the Kauhajoki shooter (whose name the author chose to withhold for ethical reasons) was subsequently found to have been a member of numerous Web-based “hate groups”, many of them originating in the United States and, as a consequence, may be understood to have committed his crime on behalf of a transnational community: what Sumiala has defined as a “networked community of destruction.” It must also be noted, however, that the school shootings were experienced as a very local tragedy in Finland itself and, although the shooter may have been psychically located in a transnational hyper-reality when he undertook the killings, it is his nation-state that has had to deal with the trauma and shame in the long term. Woodward and Brown & Rutherford, meanwhile, show that it remains the tendency of public broadcast media to uphold the raison d’être of the nation-state at the same time as embracing change. Woodward’s feature article (which reports on the AHRC-sponsored “Tuning In” project which has researched the BBC World Service) shows how the representation of national and diasporic “voices” from around the world, either in opposition to or in dialogue with the BBC’s own reporting, is key to the way in which the Commission has changed and modernised in recent times; however, she is also clear that many of the objectives that defined the service in its early days—such as its commitment to a distinctly “English” brand of education—still remain. Similarly, Brown & Rutherford’s article on the innovative Australian ABC children’s television series, My Place (which has combined traditional broadcasting with online, interactive websites) may be seen to be positively promoting the Australian nation by making visible its commitment to multiculturalism. Both articles nevertheless reveal the extent to which these public service broadcasters have recognised the need to respond to their nations’ changing demographics and, in particular, the fact that “diaspora” is a concept that refers not only to their English and Australian audiences abroad but also to their now manifestly multicultural audiences at home. When it comes to commercial satellite television, however, the relationship between broadcasting and national and global politics is rather harder to pin down. Subramanian exposes a complex interplay of national and global interests through her analysis of the Malayalee “reality television” series, Idea Star Singer. Exported globally to the Indian diaspora, the show is shamelessly exploitative in the way in which it combines residual and emergent ideologies (i.e. nostalgia for a traditional Keralayan way of life vs aspirational “western lifestyles”) in pursuit of its (massive) audience ratings. Further, while the ISS series is ostensibly a g/local phenomenon (the export of Kerala to the rest of the world rather than “India” per se), Subramanian passionately laments all the progressive national initiatives (most notably, the campaign for “women’s rights”) that the show is happy to ignore: an illustration of one of the negative consequences of globalisation predicted by Beck (31) noted at the start of this editorial. Harb, meanwhile, reflects upon a rather different set of political concerns with regards to commercial satellite broadcasting in her account of the role of Al-Jazeera and Al Arabiya in the recent (2011) Arab revolutions. Despite Al-Jazeera’s reputation for “two-sided” news coverage, recent events have exposed its complicity with the Qatari government; further, the uprisings have revealed the speed with which social media—in particular Facebook and Twitter—are replacing broadcast media. It is now possible for “the people” to bypass both governments and news corporations (public and private) in relaying the news. Taken together, then, what our articles would seem to indicate is that, while the power of the nation-state has notionally been transcended via a range of new networking practices, this has yet to undermine its material power in any guaranteed way (witness recent counter-insurgencies in Libya, Bahrain, and Syria).True, the Internet may be used to facilitate transnational “actions” against the nation-state (individual or collective) through a variety of non-violent or violent actions, but nation-states around the world, and especially in Western Europe, are currently wielding immense power over their subjects through aggressive “austerity measures” which have the capacity to severely compromise the freedom and agency of the citizens concerned through widespread unemployment and cuts in social welfare provision. This said, several of our articles provide evidence that Appadurai’s more utopian prognoses are also taking shape. Alongside the troubling possibility that globalisation, and the technologies that support it, is effectively eroding “difference” (be this national or individual), there are the ever-increasing (and widely reported) instances of how digital technology is actively supporting local communities and actions around the world in ways that bypass the state. These range from the relatively modest collective action, “My Estonia”, featured in Pikner’s article, to the ways in which the Libyan diaspora in Manchester have made use of social media to publicise and support public protests in Tripoli (Harb). In other words, there is compelling material evidence that the heterogeneity that Appadurai predicted and hoped for has come to pass through the people’s active participation in (and partial ownership of) media practices. Citizens are now able to “interfere” in the representation of their lives as never before and, through the digital revolution, communicate with one another in ways that circumvent state-controlled broadcasting. We are therefore pleased to present the articles that follow as a lively, interdisciplinary and international “state-of-the-art” commentary on how the ongoing revolution in media and communication is responding to, and bringing into being, the processes and practices of globalisation predicted by Appadurai, Beck, Bauman, and others in the 1990s. The articles also speak to the changing nature of the world’s “diasporas” during this fifteen year time frame (1996-2011) and, we trust, will activate further debate (following Cohen) on the conceptual tensions that now manifestly exist between “virtual” and “material” diasporas and also between the “transnational” diasporas whose objective is to transcend the nation-state altogether and those that deploy social media for specifically local or national/ist ends. Acknowledgements With thanks to the Arts and Humanities Research Council (UK) for their generous funding of the “Moving Manchester” project (2006-10). Special thanks to Dr Kate Horsley (Lancaster University) for her invaluable assistance as ‘Web Editor’ in the production of this special issue (we could not have managed without you!) and also to Gail Ferguson (our copy-editor) for her expertise in the preparation of the final typescript. References Appadurai, Arjun. Modernity at Large: Cultural Dimensions of Globalisation. Minneapolis: U of Minnesota P, 1996. Bauman, Zygmunt. Globalization. Cambridge: Polity, 1998. Beck, Ulrich. What is Globalization? Trans. Patrick Camiller. Cambridge: Polity, 2000 (1997). Bromley, Roger. Narratives for a New Belonging: Diasporic Cultural Fictions. Edinburgh: Edinburgh UP, 2000. Cohen, Robin. Global Diasporas. 2nd ed. London and New York: Routledge, 2008. Deleuze, Gilles, and Felix Guattari. A Thousand Plateaus: Capitalism and Schizophrenia. Trans. Brian Massumi. Minneapolis: U of Minnesota P, 1987. Latour, Bruno. Reassembling the Social: An Introduction to Actor-Network Theory. Oxford: Oxford UP, 1995. Pearce, Lynne, ed. Devolving Identities: Feminist Readings in Home and Belonging. London: Ashgate, 2000. Pearce, Lynne. “‘Writing’ and ‘Region’ in the Twenty-First Century: Epistemological Reflections on Regionally Located Art and Literature in the Wake of the Digital Revolution.” European Journal of Cultural Studies 13.1 (2010): 27-41. Robertson, Robert. Globalization: Social Theory and Global Culture. London: Sage, 1992. Urry, John. Sociology beyond Societies. London: Routledge, 1999. Williams, Raymond. Dream Worlds: Mass Consumption in Late Nineteenth-Century France. Berkeley: U of California P, 1982.

I first came across etoy in Linz, Austria in 1995. They turned up at Ars Electronica with their shaved heads, in their matching orange bomber jackets. They were not invited. The next year they would not have to crash the party. In 1996 they were awarded Arts Electronica’s prestigious Golden Nica for web art, and were on their way to fame and bitterness – the just rewards for their art of self-regard. As founding member Agent.ZAI says: “All of us were extremely greedy – for excitement, for drugs, for success.” (Wishart & Boschler: 16) The etoy story starts on the fringes of the squatters’ movement in Zurich. Disenchanted with the hard left rhetorics that permeate the movement in the 1980s, a small group look for another way of existing within a commodified world, without the fantasy of an ‘outside’ from which to critique it. What Antonio Negri and friends call the ‘real subsumption’ of life under the rule of commodification is something etoy grasps intuitively. The group would draw on a number of sources: David Bowie, the Sex Pistols, the Manchester rave scene, European Amiga art, rumors of the historic avant gardes from Dada to Fluxus. They came together in 1994, at a meeting in the Swiss resort town of Weggis on Lake Lucerne. While the staging of the founding meeting looks like a rerun of the origins of the Situationist International, the wording of the invitation might suggest the founding of a pop music boy band: “fun, money and the new world?” One of the – many – stories about the origins of the name Dada has it being chosen at random from a bilingual dictionary. The name etoy, in an update on that procedure, was spat out by a computer program designed to make four letter words at random. Ironically, both Dada and etoy, so casually chosen, would inspire furious struggles over the ownership of these chancey 4-bit words. The group decided to make money by servicing the growing rave scene. Being based in Vienna and Zurich, the group needed a way to communicate, and chose to use the internet. This was a far from obvious thing to do in 1994. Connections were slow and unreliable. Sometimes it was easier to tape a hard drive full of clubland graphics to the underside of a seat on the express train from Zurich to Vienna and simply email instructions to meet the train and retrieve it. The web was a primitive instrument in 1995 when etoy built its first website. They launched it with a party called etoy.FASTLANE, an optimistic title when the web was anything but. Coco, a transsexual model and tabloid sensation, sang a Japanese song while suspended in the air. She brought media interest, and was anointed etoy’s lifestyle angel. As Wishart and Bochsler write, “it was as if the Seven Dwarfs had discovered their Snow White.” (Wishart & Boschler: 33) The launch didn’t lead to much in the way of a music deal or television exposure. The old media were not so keen to validate the etoy dream of lifting themselves into fame and fortune by their bootstraps. And so etoy decided to be stars of the new media. The slogan was suitably revised: “etoy: the pop star is the pilot is the coder is the designer is the architect is the manager is the system is etoy.” (Wishart & Boschler: 34) The etoy boys were more than net.artists, they were artists of the brand. The brand was achieving a new prominence in the mid-90s. (Klein: 35) This was a time when capitalism was hollowing itself out in the overdeveloped world, shedding parts of its manufacturing base. Control of the circuits of commodification would rest less on the ownership of the means of production and more on maintaining a monopoly on the flows of information. The leading edge of the ruling class was becoming self-consciously vectoral. It controlled the flow of information about what to produce – the details of design, the underlying patents. It controlled the flows of information about what is produced – the brands and logos, the slogans and images. The capitalist class is supplanted by a vectoral class, controlling the commodity circuit through the vectors of information. (Wark) The genius of etoy was to grasp the aesthetic dimension of this new stage of commodification. The etoy boys styled themselves not so much as a parody of corporate branding and management groupthink, but as logical extension of it. They adopted matching uniforms and called themselves agents. In the dada-punk-hiphop tradition, they launched themselves on the world as brand new, self-created, self-named subjects: Agents Zai, Brainhard, Gramazio, Kubli, Esposto, Udatny and Goldstein. The etoy.com website was registered in 1995 with Network Solutions for a $100 fee. The homepage for this etoy.TANKSYSTEM was designed like a flow chart. As Gramazio says: “We wanted to create an environment with surreal content, to build a parallel world and put the content of this world into tanks.” (Wishart & Boschler: 51) One tank was a cybermotel, with Coco the first guest. Another tank showed you your IP number, with a big-brother eye looking on. A supermarket tank offered sunglasses and laughing gas for sale, but which may or may not be delivered. The underground tank included hardcore photos of a sensationalist kind. A picture of the Federal Building in Oklamoma City after the bombing was captioned in deadpan post-situ style “such work needs a lot of training.” (Wishart & Boschler: 52) The etoy agents were by now thoroughly invested in the etoy brand and the constellation of images they had built around it, on their website. Their slogan became “etoy: leaving reality behind.” (Wishart & Boschler: 53) They were not the first artists fascinated by commodification. It was Warhol who said “good art is good business.”(Warhol ) But etoy reversed the equation: good business is good art. And good business, in this vectoral age, is in its most desirable form an essentially conceptual matter of creating a brand at the center of a constellation of signifiers. Late in 1995, etoy held another group meeting, at the Zurich youth center Dynamo. The problem was that while they had build a hardcore website, nobody was visiting it. Agents Gooldstein and Udatny thought that there might be a way of using the new search engines to steer visitors to the site. Zai and Brainhard helped secure a place at the Vienna Academy of Applied Arts where Udatny could use the computer lab to implement this idea. Udatny’s first step was to create a program that would go out and gather email addresses from the web. These addresses would form the lists for the early examples of art-spam that etoy would perpetrate. Udatny’s second idea was a bit more interesting. He worked out how to get the etoy.TANKSYSTEM page listed in search engines. Most search engines ranked pages by the frequency of the search term in the pages it had indexed, so etoy.TANKSYSTEM would contain pages of selected keywords. Porn sites were also discovering this method of creating free publicity. The difference was that etoy chose a very carefully curated list of 350 search terms, including: art, bondage, cyberspace, Doom, Elvis, Fidel, genx, heroin, internet, jungle and Kant. Users of search engines who searched for these terms would find dummy pages listed prominently in their search results that directed them, unsuspectingly, to etoy.com. They called this project Digital Hijack. To give the project a slightly political aura, the pages the user was directed to contained an appeal for the release of convicted hacker Kevin Mitnick. This was the project that won them a Golden Nica statuette at Ars Electronica in 1996, which Gramazio allegedly lost the same night playing roulette. It would also, briefly, require that they explain themselves to the police. Digital Hijack also led to the first splits in the group, under the intense pressure of organizing it on a notionally collective basis, but with the zealous Agent Zai acting as de facto leader. When Udatny was expelled, Zai and Brainhard even repossessed his Toshiba laptop, bought with etoy funds. As Udatny recalls, “It was the lowest point in my life ever. There was nothing left; I could not rely on etoy any more. I did not even have clothes, apart from the etoy uniform.” (Wishart & Boschler: 104) Here the etoy story repeats a common theme from the history of the avant gardes as forms of collective subjectivity. After Digital Hijack, etoy went into a bit of a slump. It’s something of a problem for a group so dependent on recognition from the other of the media, that without a buzz around them, etoy would tend to collapse in on itself like a fading supernova. Zai spend the early part of 1997 working up a series of management documents, in which he appeared as the group’s managing director. Zai employed the current management theory rhetoric of employee ‘empowerment’ while centralizing control. Like any other corporate-Trotskyite, his line was that “We have to get used to reworking the company structure constantly.” (Wishart & Boschler: 132) The plan was for each member of etoy to register the etoy trademark in a different territory, linking identity to information via ownership. As Zai wrote “If another company uses our name in a grand way, I’ll probably shoot myself. And that would not be cool.” (Wishart & Boschler:: 132) As it turned out, another company was interested – the company that would become eToys.com. Zai received an email offering “a reasonable sum” for the etoy.com domain name. Zai was not amused. “Damned Americans, they think they can take our hunting grounds for a handful of glass pearls….”. (Wishart & Boschler: 133) On an invitation from Suzy Meszoly of C3, the etoy boys traveled to Budapest to work on “protected by etoy”, a work exploring internet security. They spent most of their time – and C3’s grant money – producing a glossy corporate brochure. The folder sported a blurb from Bjork: “etoy: immature priests from another world” – which was of course completely fabricated. When Artothek, the official art collection of the Austrian Chancellor, approached etoy wanting to buy work, the group had to confront the problem of how to actually turn their brand into a product. The idea was always that the brand was the product, but this doesn’t quite resolve the question of how to produce the kind of unique artifacts that the art world requires. Certainly the old Conceptual Art strategy of selling ‘documentation’ would not do. The solution was as brilliant as it was simple – to sell etoy shares. The ‘works’ would be ‘share certificates’ – unique objects, whose only value, on the face of it, would be that they referred back to the value of the brand. The inspiration, according to Wishart & Boschsler, was David Bowie, ‘the man who sold the world’, who had announced the first rock and roll bond on the London financial markets, backed by future earnings of his back catalogue and publishing rights. Gramazio would end up presenting Chancellor Viktor Klima with the first ‘shares’ at a press conference. “It was a great start for the project”, he said, “A real hack.” (Wishart & Boschler: 142) For this vectoral age, etoy would create the perfect vectoral art. Zai and Brainhard took off next for Pasadena, where they got the idea of reverse-engineering the online etoy.TANKSYSTEM by building an actual tank in an orange shipping container, which would become etoy.TANK 17. This premiered at the San Francisco gallery Blasthaus in June 1998. Instant stars in the small world of San Francisco art, the group began once again to disintegrate. Brainhard and Esposito resigned. Back in Europe in late 1998, Zai was preparing to graduate from the Vienna Academy of Applied Arts. His final project would recapitulate the life and death of etoy. It would exist from here on only as an online archive, a digital mausoleum. As Kubli says “there was no possibility to earn our living with etoy.” (Wishart & Boschler: 192) Zai emailed eToys.com and asked them if them if they would like to place a banner ad on etoy.com, to redirect any errant web traffic. Lawyers for eToys.com offered etoy $30,000 for the etoy.com domain name, which the remaining members of etoy – Zai, Gramazio, Kubli – refused. The offer went up to $100,000, which they also refused. Through their lawyer Peter Wild they demanded $750,000. In September 1999, while etoy were making a business presentation as their contribution to Ars Electronica, eToys.com lodged a complaint against etoy in the Los Angeles Superior Court. The company hired Bruce Wessel, of the heavyweight LA law firm Irell & Manella, who specialized in trademark, copyright and other intellectual property litigation. The complaint Wessel drafted alleged that etoy had infringed and diluted the eToys trademark, were practicing unfair competition and had committed “intentional interference with prospective economic damage.” (Wishart & Boschler: 199) Wessel demanded an injunction that would oblige etoy to cease using its trademark and take down its etoy.com website. The complaint also sought to prevent etoy from selling shares, and demanded punitive damages. Displaying the aggressive lawyering for which he was so handsomely paid, Wessel invoked the California Unfair Competition Act, which was meant to protect citizens from fraudulent business scams. Meant as a piece of consumer protection legislation, its sweeping scope made it available for inventive suits such as Wessel’s against etoy. Wessel was able to use pretty much everything from the archive etoy built against it. As Wishart and Bochsler write, “The court papers were like a delicately curated catalogue of its practices.” (Wishart & Boschler: 199) And indeed, legal documents in copyright and trademark cases may be the most perfect literature of the vectoral age. The Unfair Competition claim was probably aimed at getting the suit heard in a Californian rather than a Federal court in which intellectual property issues were less frequently litigated. The central aim of the eToys suit was the trademark infringement, but on that head their claims were not all that strong. According to the 1946 Lanham Act, similar trademarks do not infringe upon each other if there they are for different kinds of business or in different geographical areas. The Act also says that the right to own a trademark depends on its use. So while etoy had not registered their trademark and eToys had, etoy were actually up and running before eToys, and could base their trademark claim on this fact. The eToys case rested on a somewhat selective reading of the facts. Wessel claimed that etoy was not using its trademark in the US when eToys was registered in 1997. Wessel did not dispute the fact that etoy existed in Europe prior to that time. He asserted that owning the etoy.com domain name was not sufficient to establish a right to the trademark. If the intention of the suit was to bully etoy into giving in, it had quite the opposite effect. It pissed them off. “They felt again like the teenage punks they had once been”, as Wishart & Bochsler put it. Their art imploded in on itself for lack of attention, but called upon by another, it flourished. Wessel and eToys.com unintentionally triggered a dialectic that worked in quite the opposite way to what they intended. The more pressure they put on etoy, the more valued – and valuable – they felt etoy to be. Conceptual business, like conceptual art, is about nothing but the management of signs within the constraints of given institutional forms of market. That this conflict was about nothing made it a conflict about everything. It was a perfectly vectoral struggle. Zai and Gramazio flew to the US to fire up enthusiasm for their cause. They asked Wolfgang Staehle of The Thing to register the domain toywar.com, as a space for anti-eToys activities at some remove from etoy.com, and as a safe haven should eToys prevail with their injunction in having etoy.com taken down. The etoy defense was handled by Marcia Ballard in New York and Robert Freimuth in Los Angeles. In their defense, they argued that etoy had existed since 1994, had registered its globally accessible domain in 1995, and won an international art prize in 1996. To counter a claim by eToys that they had a prior trademark claim because they had bought a trademark from another company that went back to 1990, Ballard and Freimuth argued that this particular trademark only applied to the importation of toys from the previous owner’s New York base and thus had no relevance. They capped their argument by charging that eToys had not shown that its customers were really confused by the existence of etoy. With Christmas looming, eToys wanted a quick settlement, so they offered Zurich-based etoy lawyer Peter Wild $160,000 in shares and cash for the etoy domain. Kubli was prepared to negotiate, but Zai and Gramazio wanted to gamble – and raise the stakes. As Zai recalls: “We did not want to be just the victims; that would have been cheap. We wanted to be giants too.” (Wishart & Boschler: 207) They refused the offer. The case was heard in November 1999 before Judge Rafeedie in the Federal Court. Freimuth, for etoy, argued that federal Court was the right place for what was essentially a trademark matter. Robert Kleiger, for eToys, countered that it should stay where it was because of the claims under the California Unfair Competition act. Judge Rafeedie took little time in agreeing with the eToys lawyer. Wessel’s strategy paid off and eToys won the first skirmish. The first round of a quite different kind of conflict opened when etoy sent out their first ‘toywar’ mass mailing, drawing the attention of the net.art, activism and theory crowd to these events. This drew a report from Felix Stalder in Telepolis: “Fences are going up everywhere, molding what once seemed infinite space into an overcrowded and tightly controlled strip mall.” (Stalder ) The positive feedback from the net only emboldened etoy. For the Los Angeles court, lawyers for etoy filed papers arguing that the sale of ‘shares’ in etoy was not really a stock offering. “The etoy.com website is not about commerce per se, it is about artist and social protest”, they argued. (Wishart & Boschler: 209) They were obliged, in other words, to assert a difference that the art itself had intended to blur in order to escape eToy’s claims under the Unfair Competition Act. Moreover, etoy argued that there was no evidence of a victim. Nobody was claiming to have been fooled by etoy into buying something under false pretences. Ironically enough, art would turn out in hindsight to be a more straightforward transaction here, involving less simulation or dissimulation, than investing in a dot.com. Perhaps we have reached the age when art makes more, not less, claim than business to the rhetorical figure of ‘reality’. Having defended what appeared to be the vulnerable point under the Unfair Competition law, etoy went on the attack. It was the failure of eToys to do a proper search for other trademarks that created the problem in the first place. Meanwhile, in Federal Court, lawyers for etoy launched a counter-suit that reversed the claims against them made by eToys on the trademark question. While the suits and counter suits flew, eToys.com upped their offer to settle to a package of cash and shares worth $400,000. This rather puzzled the etoy lawyers. Those choosing to sue don’t usually try at the same time to settle. Lawyer Peter Wild advised his clients to take the money, but the parallel tactics of eToys.com only encouraged them to dig in their heels. “We felt that this was a tremendous final project for etoy”, says Gramazio. As Zai says, “eToys was our ideal enemy – we were its worst enemy.” (Wishart & Boschler: 210) Zai reported the offer to the net in another mass mail. Most people advised them to take the money, including Doug Rushkoff and Heath Bunting. Paul Garrin counseled fighting on. The etoy agents offered to settle for $750,000. The case came to court in late November 1999 before Judge Shook. The Judge accepted the plausibility of the eToys version of the facts on the trademark issue, which included the purchase of a registered trademark from another company that went back to 1990. He issued an injunction on their behalf, and added in his statement that he was worried about “the great danger of children being exposed to profane and hardcore pornographic issues on the computer.” (Wishart & Boschler: 222) The injunction was all eToys needed to get Network Solutions to shut down the etoy.com domain. Zai sent out a press release in early December, which percolated through Slashdot, rhizome, nettime (Staehle) and many other networks, and catalyzed the net community into action. A debate of sorts started on investor websites such as fool.com. The eToys stock price started to slide, and etoy ‘warriors’ felt free to take the credit for it. The story made the New York Times on 9th December, Washington Post on the 10th, Wired News on the 11th. Network Solutions finally removed the etoy.com domain on the 10th December. Zai responded with a press release: “this is robbery of digital territory, American imperialism, corporate destruction and bulldozing in the way of the 19th century.” (Wishart & Boschler: 237) RTMark set up a campaign fund for toywar, managed by Survival Research Laboratories’ Mark Pauline. The RTMark press release promised a “new internet ‘game’ designed to destroy eToys.com.” (Wishart & Boschler: 239) The RTMark press release grabbed the attention of the Associated Press newswire. The eToys.com share price actually rose on December 13th. Goldman Sachs’ e-commerce analyst Anthony Noto argued that the previous declines in the Etoys share price made it a good buy. Goldman Sachs was the lead underwriter of the eToys IPO. Noto’s writings may have been nothing more than the usual ‘IPOetry’ of the time, but the crash of the internet bubble was some months away yet. The RTMark campaign was called ‘The Twelve Days of Christmas’. It used the Floodnet technique that Ricardo Dominguez used in support of the Zapatistas. As Dominguez said, “this hysterical power-play perfectly demonstrates the intensions of the new net elite; to turn the World Wide Web into their own private home-shopping network.” (Wishart & Boschler: 242) The Floodnet attack may have slowed the eToys.com server down a bit, but it was robust and didn’t crash. Ironically, it ran on open source software. Dominguez claims that the ‘Twelve Days’ campaign, which relied on individuals manually launching Floodnet from their own computers, was not designed to destroy the eToys site, but to make a protest felt. “We had a single-bullet script that could have taken down eToys – a tactical nuke, if you will. But we felt this script did not represent the presence of a global group of people gathered to bear witness to a wrong.” (Wishart & Boschler: 245) While the eToys engineers did what they could to keep the site going, eToys also approached universities and businesses whose systems were being used to host Floodnet attacks. The Thing, which hosted Dominguez’s eToys Floodnet site was taken offline by The Thing’s ISP, Verio. After taking down the Floodnet scripts, The Thing was back up, restoring service to the 200 odd websites that The Thing hosted besides the offending Floodnet site. About 200 people gathered on December 20th at a demonstration against eToys outside the Museum of Modern Art. Among the crowd were Santas bearing signs that said ‘Coal for eToys’. The rally, inside the Museum, was led by the Reverend Billy of the Church of Stop Shopping: “We are drowning in a sea of identical details”, he said. (Wishart & Boschler: 249-250) Meanwhile etoy worked on the Toywar Platform, an online agitpop theater spectacle, in which participants could act as soldiers in the toywar. This would take some time to complete – ironically the dispute threatened to end before this last etoy artwork was ready, giving etoy further incentives to keep the dispute alive. The etoy agents had a new lawyer, Chris Truax, who was attracted to the case by the publicity it was generating. Through Truax, etoy offered to sell the etoy domain and trademark for $3.7 million. This may sound like an insane sum, but to put it in perspective, the business.com site changed hands for $7.5 million around this time. On December 29th, Wessel signaled that eToys was prepared to compromise. The problem was, the Toywar Platform was not quite ready, so etoy did what it could to drag out the negotiations. The site went live just before the scheduled court hearings, January 10th 2000. “TOYWAR.com is a place where all servers and all involved people melt and build a living system. In our eyes it is the best way to express and document what’s going on at the moment: people start to about new ways to fight for their ideas, their lifestyle, contemporary culture and power relations.” (Wishart & Boschler: 263) Meanwhile, in a California courtroom, Truax demanded that Network Solutions restore the etoy domain, that eToys pay the etoy legal expenses, and that the case be dropped without prejudice. No settlement was reached. Negotiations dragged on for another two weeks, with the etoy agents’ attention somewhat divided between two horizons – art and law. The dispute was settled on 25th January. Both parties dismissed their complaints without prejudice. The eToys company would pay the etoy artists $40,000 for legal costs, and contact Network Solutions to reinstate the etoy domain. “It was a pleasure doing business with one of the biggest e-commerce giants in the world” ran the etoy press release. (Wishart & Boschler: 265) That would make a charming end to the story. But what goes around comes around. Brainhard, still pissed off with Zai after leaving the group in San Francisco, filed for the etoy trademark in Austria. After that the internal etoy wranglings just gets boring. But it was fun while it lasted. What etoy grasped intuitively was the nexus between the internet as a cultural space and the transformation of the commodity economy in a yet-more abstract direction – its becoming-vectoral. They zeroed in on the heart of the new era of conceptual business – the brand. As Wittgenstein says of language, what gives words meaning is other words, so too for brands. What gives brands meaning is other brands. There is a syntax for brands as there is for words. What etoy discovered is how to insert a new brand into that syntax. The place of eToys as a brand depended on their business competition with other brands – with Toys ‘R’ Us, for example. For etoy, the syntax they discovered for relating their brand to another one was a legal opposition. What made etoy interesting was their lack of moral posturing. Their abandonment of leftist rhetorics opened them up to exploring the territory where media and business meet, but it also made them vulnerable to being consumed by the very dialectic that created the possibility of staging etoy in the first place. By abandoning obsolete political strategies, they discovered a media tactic, which collapsed for want of a new strategy, for the new vectoral terrain on which we find ourselves. Works Cited Negri, Antonio. Time for Revolution. Continuum, London, 2003. Warhol, Andy. From A to B and Back Again. Picador, New York, 1984. Stalder, Felix. ‘Fences in Cyberspace: Recent events in the battle over domain names’. 19 Jun 2003. <http://felix.openflows.org/html/fences.php>. Wark, McKenzie. ‘A Hacker Manifesto [version 4.0]’ 19 Jun 2003. http://subsol.c3.hu/subsol_2/contributors0/warktext.html. Klein, Naomi. No Logo. Harper Collins, London, 2000. Wishart, Adam & Regula Bochsler. Leaving Reality Behind: etoy vs eToys.com & Other Battles to Control Cyberspace Ecco Books, 2003. Staehle, Wolfgang. ‘<nettime> etoy.com shut down by US court.’ 19 Jun 2003. http://amsterdam.nettime.org/Lists-Archives/nettime-l-9912/msg00005.html Links http://amsterdam.nettime.org/Lists-Archives/nettime-l-9912/msg00005.htm http://felix.openflows.org/html/fences.html http://subsol.c3.hu/subsol_2/contributors0/warktext.html Citation reference for this article Substitute your date of access for Dn Month Year etc... MLA Style Wark, McKenzie. "Toywars" M/C: A Journal of Media and Culture< http://www.media-culture.org.au/0306/02-toywars.php>. APA Style Wark, M. (2003, Jun 19). Toywars. M/C: A Journal of Media and Culture, 6,< http://www.media-culture.org.au/0306/02-toywars.php>