Academic literature 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.

The most important moment of whole project is the change of the status. Creation of unique sarcophagus for an object of mass-production - one of many globally manufactured objects become a part of a unique, authentic object and authorship. Transformation of one of the mass-product to the skeleton of author's object. Mass-product gives dimensions to the original object - it is directing process of creation. By creating its own unique case the object of mass-production is finally closer to human scale: one piece of furniture vs. one carpenter.

Onboard hydrogen storage is an enabling factor in the development of fuel cell powered passenger cars. Ammonia borane (AB) hydrolysis is one of the potential technologies for onboard hydrogen storage. In this study, kinetics of catalyzed ammonia borane hydrolysis using ruthenium-supported-on-carbon has been measured. For reacting flows, chemical kinetics determines the rates of heat generation and species production or consumption in the overall energy and mass balances respectively. Kinetic measurements under isothermal conditions provide critical data for the design of hydrolysis reactors. It is, however, not always possible to eliminate the effects of internal diffusion in a heterogeneous chemical reaction. In such cases, the reaction efficiency (η), which depends on the effective liquid phase diffusivity (Deff) in the catalyst medium, should be determined. Determination of intrinsic kinetic parameters using apparent kinetics data is, thus, a challenge. In this study, the change in AB concentration (CAB) with reaction time (t) has been directly measured. It was observed that the AB hydrolysis reaction had orders between zero and one in a temperature range of 26°C to 55°C. A unified Langmuir-Hinshelwood (LH) model has been adopted to describe the reaction kinetics. The intrinsic kinetic parameters (A, Ea, ΔHads, K0) as well as Deff need to be estimated by inverse analysis of the measured CAB vs t data. Conventionally, kinetic parameters are determined using linear fitting. Sometimes, however, it is impossible to converge to a unique value by using the linear fitting approach as there are several values providing regression coefficients greater than 0.99. In this study, the multiple-variable inverse problem has been solved using a nonlinear fitting algorithm based on Powell’s conjugate-gradient error minimization. This algorithm minimizes errors without using derivatives. As a result, the uncertainties in the kinetic parameter estimation have been significantly reduced by the new approach.