Dissertations / Theses on the topic 'Pod anatomy'

The human race has always faced environmental challenges. What differs at present, however, are the scale and entrenched social structures (e.g., capitalism, man/nature duality, a dominant social paradigm) that are contributing to these problems and our own irrationality when it comes to possible solutions. Implicit testing methodologies, borrowed from experimental psychology, may be able to bypass some of these issues and provide a means to identify simple 'point of decision' interventions to effect change in behavior on an individual level. The approach adopted in the current thesis was to explore the extent to which movement dynamics (measured using MouseTracker) can inform the decisional anatomy of an important pro-environmental activity — recycling. MouseTracker is a useful methodology as it assesses the real-time conflict that people experience when confronted with the decision to recycle a particular item or not. There were three stages to the progression of this research: (1) using focus groups to gain knowledge of undergraduates' beliefs and opinions towards recycling (Study 1); (2) assessing the utility of MouseTracker as an implicit tool to explore recycling decisions (Expts. 1 & 2); and (3) establishing the extent to which personal (i.e, Social Value Orientation) and situational factors (i.e., environmental primes) influence the anatomy of recycling decisions (Expts. 3-6). Results from the focus groups confirmed that university undergraduates hold widely held societal beliefs about recycling, thereby justifying their inclusion in the current investigation. Experiments 1 and 2 confirmed the utility of MouseTracker as a methodology to explore recycling decisions. Overall, participants displayed a stronger attraction to putting recyclable items in the rubbish bin than garbage in the recycle bin, a tendency that was reduced with increasing levels of environmental concern. Results in the subsequent experiments were mixed. An important individual difference variable (i.e., Social Value Orientation) failed to show an influence on recycling behavior (Expt. 3), and subtle environmental primes produced a collection of modest effects (Expts. 4 & 5). Most notably, a messy environment improved recycling performance (Expt. 5). Compelling results were observed, however, when self-directed attention was manipulated (Expt. 6). In particular, recycling performance was enhanced in the presence of a mirror, thereby confirming the relation between self-focus and normative behavior (the efficient disposal of waste). Discussion centers on the theoretical and practical implications of the current findings, limitations with the methodology employed, and consideration is given to future research on this important societal topic.

The endocannabinoid system (ECS) is known to be involved in key aspects of cell maintenance within the human colon, as well as being dysregulated in pathophysiological conditions, including colon inflammation and cancer. However, the contribution of the ECS within each of these conditions has not been fully elucidated. This indicates that the current identification of key targets within the ECS that are involved in gut pathology could be used as potential novel therapeutics. Two experimental approaches were designed and optimised to give an insight into ECS signal regulation within the human colon and to screen ECS therapeutics, tetrahydrocannabinol (THC) and cannabidiol (CBD); a human colon ex vivo explant culture model and an innovative multiplexed quantitative gene expression technology, the GenomeLab GeXP system (Beckman Coulter). Gene targets were identified that are known markers of regulation and function in cells of healthy tissue. An assay, the hCellMarkerPlex was designed that incorporated twenty-three of these gene targets, epithelial (EZR, KRT18, SLC9A2), proliferation (PCNA, CCND1, MS4A12), differentiation (B4GANLT2, CDX1, CDX2), apoptotic (CASP3, NOX1, NTN1), fibroblast (FSP1, COL1A1), structural (ACTG2, CNN1, DES), gene transcription (HDAC1), stem cell (LGR5), endothelial (VWF) and mucin production (MUC2). The hCellMarkerPlex identified gene signatures which distinguished between normal, adenoma and carcinoma tissue, identifying cellular processes showing abnormal activity associated with pathological status. The resulting biomarker profiles were used to establish a human colon explant culture system. The human colon explant culture presents a novel model to study modulation of the ECS and screen ECS therapeutics. Combined with the GenomeLab GeXP System multiple components of the ECS were assessed at the gene regulatory level. A custom designed GeXP assay, the hECSplex, was developed. hECSplex gene expression signatures of EC receptors (CNR1, CNR2, GPR55 and TRPV1), ECS enzymes (NAPE-PLD, GDE1, DAGLA, DAGLB, FAAH, FAAH2 and PTGS2), inflammatory (IL1B, IL10, IL6, LEP, TNF and SOCS3), signalling pathway (ID1, BCL2, CFL1, BIRC5, TP53, MYC and KRAS), lipid production (SREBF1, ACACA), and plasma-membrane (OCLN) markers revealed altered expression of ECS components in carcinogenesis compared to normal tissue. Abstract vi . The hECSplex gene expression signature of colon explants showed that ECS was not altered during culture, emphasising the explant models capability as a pharmaceutical tool to test current and novel therapeutics. Applications of both THC and CBD to normal colon explants at different concentrations do not lead to any significant changes. Indicating the current pharmacological use of phytocannabinoids is causing no adverse effects in surrounding healthy colon tissue. The GenomeLab System presents new opportunities to interrogate multiple components of the endocannabinoid signalling system in small colon explant tissue samples, and in response to ECS therapeutics.

Introduction: Endovascular aneurysm repair(EVAR) has become the main treatment for abdominal aortic aneurysm(AAA). Anatomical features of the AAA are pivotal in EVAR success. The aim of this study was to evaluate known anatomical features as risk factors for the freedom from reintervention(FFR) taking into account the new-generation endografts. Materials and Methods: This study was a retrospective monocentric study including consecutive patients treated by EVAR from 2012 to 2018 in elective setting. All currently reported anatomic factors including aortic neck and iliac arteries proprieties were examined using the pre-operative AngioCT-imaging. The primary endpoint was to define the anatomical risk factors affecting the FFR. Results: A total of 653 patients treated by standard EVAR were included. The mean age was 75.6±8 years. The mean follow-up was 34±11 months. FFR was 98.4%,97.4%,96% and 87.3% at 6,12,24 and 48 months, respectively. Larger aortic neck diameter was significant risk factor for FFR(P=0.001). Aortic neck severe angulation >60° was correlated to the need for reintervention(P=0.001). Larger aneurysm diameter was associated with higher incidence of reinterventions(P<0.001). Infrarenal aortic length(IRAL) measured as distance between renal artery and aortic bifurcation level, was associated with lower FFR(P=0.002). Similarly, the mean aorto-iliac length(MAIL) measured as the sum of distance between the most distal renal artery and iliac bifurcation in both sides divided by two, resulted a negative factor for FFR (P=0.002). At the multivariate analysis of anatomical features, aortic neck diameter (HR1.18;CI:1.02-1.37,P=0.03) and MAIL (HR1.02;CI:1.01-1.04,P=0.01) were confirmed as significant risk factors for FFR. Conclusion: This 7-years real-world study focused on the analysis of anatomic risk factors predisposing for graft-related reinterventions at mid-term. Patient survival and FFR are satisfactory and compatible with other studies results. Aortic neck diameter and MAIL resulted the main risk factors for FFR. IRAL and MAIL resulting significant factors are not described before and need further investigations.

Spinal Muscular Atrophy (SMA), traditionally described as a predominantly childhood form of motor neuron disease, is a leading genetic cause of infant mortality. Although motor neurons are undoubtedly the primary affected cell type, SMA is now widely recognised as a multisystem disorder, where a variety of organs and systems in the body are also affected. Vascular perfusion abnormalities have previously been reported in both patients and mouse models of SMA, however it remains unclear whether these defects are secondary to the motor neuron pathology for which this disease is known. Through analysis of the 'Taiwanese' murine model of severe SMA (Smn-/-;SMN2tg/0, Smn-/+) we report significant vascular defects in the retinas of SMA mice, a tissue devoid of motor neurons, thus providing strong evidence that these vascular defects are independent of motor neuron pathologies. We show that restoration of Smn levels by antisense oligonucleotide treatment at birth significantly ameliorates retinal vascular defects. Next, we report defects in the neural retina, with a significant decrease in key neural cells in SMA mice. A similar vascular pathology was expected in the spleen of SMA mice given that the spleen is small and pale in appearance; however, the density of the intrinsic vasculature remained unchanged. We report that the spleen is disproportionately small in SMA mice, correlated to low levels of cell proliferation, increased cell death, and multiple lacunae. The SMA spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganized fibrotic architecture. Histologically distinct white pulp fails to form and this is reflected in an almost complete absence of B lymphocytes necessary for normal immune function. Taken together, these results highlight both the vascular and immune systems as key targets of SMA pathology that should be considered during treatment of this disease.

Folates are water-soluble B vitamins, which maintain DNA stability by regulating nucleotide synthesis and DNA methylation. Folates influence CRC risk and their ability to prevent or promote carcinogenesis may be dependent on several variables here investigated. No in vitro study has yet modelled the physiological folate status that human colon cells are exposed to in vivo. This study evaluates the ability of different forms and concentrations of folate to maintain DNA stability and normal cell function in folate-sufficient and stable human colonocytes and to modify DNA instability and the acquisition of abnormal characteristics in folate-deficient and genomically-unstable colonocytes. Non-malignant human NCM460 colonocytes cultured at physiologically-relevant concentrations of 5-methyl-THF or FA, representing the average deficient (2.5 ng/mL), sufficient (10 ng/mL) or highest post-supplementation (100 ng/mL) folate levels found in human plasma were used in this study as a model of colon-folate interaction. This work established that FA is taken up and/or retained to a lesser extent than 5-methylTHF and is less efficient at maintaining DNA stability and normal cellular characteristics in folate-sufficient and genomically-stable colonocytes at baseline, particularly at deficient and sufficient concentrations in the medium to longer term (14-21 days). During repletion of folate-deficient and genomically-unstable cells, sufficient concentrations of FA do not increase intracellular folate status and worsen the unstable phenotype, by perpetuating DNA instability and enabling the acquisition of a more pro-malignant protein expression. On the contrary, employing 5-methyl-THF sufficiency for repletion positively modifies the abnormal protein profile and morphological features of folate-deficient cells, mitigating potential progression to malignant transformation. When high post-supplementation concentrations are employed, both folate forms increase intracellular folate status, but drive a more promalignant and stress-induced proteome profile and, in the case of 5-methyl-THF, promote abnormal cell morphologies. In conclusion, the folate type, concentration employed, baseline folate status and timing of exposure to folate supplementation are important variables that should be taken into account by future studies evaluating the potential impact of mandatory FA fortification on CRC.

Colorectal neoplasia (CRN) continues to be a leading cause of morbidity and mortality in the developed world and with westernisation, similar trends are now emerging in the developing world. Although secondary prevention through screening programmes has reduced mortality, uptake remains poor due to the invasive nature of colonoscopy, which also exerts increased costs to the health care system. Primary prevention remains the ultimate aim to reduce the morbidity and mortality associated with CRN. In this regard, chemoprevention strategies through regular use of aspirin and other NSAIDS have showed great promise but the associated significant side-effects of these drugs has prevented their routine clinical application for this purpose. Hence there is an urgent need for the identification of safer alternatives for primary prevention of CRN. In parallel to this search, better understanding of the molecular pathogenesis of CRN to identify biomarkers that aid in stratification of at risk individuals would also help. In this regard, the role of chronic inflammation and the influence of host genetics in the pathogenesis of CRN has been the focus of extensive research in recent years. However there is a lack of studies which have investigated these associations in an exclusively screened population, which confers some advantages for this type of investigation. Firstly, most of the screened subjects are relatively healthy, asymptomatic and with no significant co-morbidities, the factors which could otherwise influence the levels of inflammatory markers. Secondly, the screened population is in the 50 to74 year age group which represents the group with a high prevalence of CRN and hence increasing the possibility of finding associations which would be more relevant and generalisable. Thirdly, the selected controls match the cases in all important respects, apart from having CRN, thus increasing the validity of the findings in this population. The Grampian region was one of the first in the UK to participate in the National Colorectal Cancer Screening Programme and this resource gave the ideal opportunity to conduct research involving an exclusively screened population. Utilising this cohort, the current thesis addressed three important aspects of the association between inflammation and CRN. Firstly the investigation of the association of inflammatory genotype, inflammatory phenotype and CRN risk. Secondly the impact of environmental factors, specifically dietary antiinflammatory salicylic acid intakes on CRN risk. And finally assessing if inflammation, and hence in the long term risk of CRN, could be attenuated through a comprehensive anti-inflammatory dietary supplementation in the form of a randomised dietary intervention clinical trial. The study of the association of polymorphisms in key inflammatory genes (IL1B- 31, IL8-251, IL6-174, TNFα-308, IL10-1082, IL10-592, PTGS2-765, and IL1RN VNTR) and CRN risk showed some significant findings. A novel finding was that the homozygous IL1B-31C*C genotype was associated with statistically significant increased risk of CRN, OR 1.63 (95% CI 1.06-2.50) whilst the IL8-251 A*A genotype increased the propensity of having high risk lesions by two-fold (OR 2.04; 95% CI 1.02-4.07). The study of circulating inflammatory marker levels in subjects in whom the CRN was in-situ showed that increased CRP levels were associated with increased risk of CRN, OR 1.55 (95% CI 1.00-2.39). Increased levels of IL8 were associated with increased risk of having a high risk lesion, OR 2.57 (95% CI 1.03-6.44). In a sub group of subjects, it was observed that levels IL8 and CRP decreased following polypectomy (mean IL8 20.3 pg/ml to 14.9 pg/ml, p=0.05 and mean CRP 5.99 mg/l to 3.82 mg/l, p=0.07) raising an important question regarding the sequence of the inflammation-neoplasia cascade, “Is inflammation the cause or the effect of neoplasia?” The study of the association of dietary salicylic acid (SA) and CRN using the newly constructed SA database showed that high levels of total SA (aspirin and dietary SA) intakes were associated with a 75% and moderate levels with a 67% decreased risk of CRN. But dietary SA on its own showed no significant effect on CRN risk probably because of low intake levels in the current cohort. Applying the SA database to populations with higher dietary SA intake would help to further explore its association with CRN risk. The randomised clinical trial examining the effect of a combined antiinflammatory dietary supplement (curcumin, omega-3 PUFA and polyphenols rich fruit smoothie) on markers of inflammation in subjects who had adenomatous colorectal polyps removed showed that the inflammatory marker levels in the control group who just continued their habitual diet remained stable without any statistically significant changes at 6 weeks compared to the baseline. Whereas following 6 weeks of dietary intervention, there was marginally significant increase in IL8 and IL1B levels. One of the possible mechanisms for increase in pro-inflammatory marker levels in the intervention group was the weight gain seen in the intervention group. In the intervention group, the post-intervention mean weight (86.80kgs) was significantly higher than the pre-intervention mean weight (85.38 kgs). In summary, the findings from these investigations suggest that a proinflammatory genotype (IL1B-31C*C and IL8-251 A*A) and elevated circulating inflammatory marker levels (CRP and IL8) are associated with increased risk of CRN. And along with the findings that regular NSAID use and total dietary SA are associated with decreased risk of CRN, our data point to inflammation as an underlying pathogenetic mechanism in CRN. The pilot clinical trial has demonstrated that a clinical trial with combined dietary supplementation is feasible, but challenging. The anti-inflammatory dietary intervention strategy employed to reduce the inflammatory markers did not achieve the desired effect and hence more research is required to establish the ideal delivery strategy of the anti-inflammatory dietary agents. Once this is established, dietary chemoprevention of CRN as a safe alternative should be a realistic achievable goal in the future.

Slits and their Roundabout (Robo) receptors were identified based on their role in regulating axon guidance, but are known to play multiple roles in development, including regulating heart development and myoblast migration. There are 3 vertebrate Slits (Slit1 – 3) and 4 Robos (Robo1 – 4), and previous work has demonstrated expression of Slit and Robo family members in and around developing joints where their function is unclear. Mutations in human Robo3 have been linked to degenerative joint disorders, such as scoliosis and rheumatoid arthritis. Misregulation of other members of the Slit/Robo signalling pathway is also reported in cells from arthritic joints. This suggests that Slit/Robo signalling is required for normal joint development and/or maintenance, though our understanding of their roles in these processes is rudimentary. The central question of my thesis is to determine the role/s of Slit/Robo signalling in limb and joint development. In situ hybridisation confirmed strong expression of Slits and Robos throughout mouse limb and joint development, though no expression of Slit1 or Robo3 was detected. Analysis of Slit1/2, Slit3 and Robo1 mutant (loss-of-function) mice revealed normal limb development, however misexpression of dominant-negative Robo2 during chicken limb development caused shortening of cartilage elements. To begin to identify molecular changes that may compensate for the loss of Slit/Robo signalling I demonstrated members of the Sema3/PlexinA/Nrp axon guidance family are expressed in patterns comparable to those of Robo1, Robo2 and Slit3. I discovered that PlexinA1 is downregulated in Slit3 mutant mouse limbs. My results suggest the role for Silt/Robo signalling may be more complex than previously thought and do not define a clear role for signalling during limb development. My results suggest the role for Silt/Robo signalling may be more complex than previously thought and do not define a clear role for signalling during limb development. Previous work has linked Slit/Robo signalling to development of degenerative joint disorders, and I propose some hypotheses as to how Slit/Robo signalling could cause bone and joint defects.

The ability of essential oils (EO) to manipulate the intestinal microbiota may potentiate their application in food as nutraceutical and as prophylactic agents for colonic disease. Little is known about the influence of EO on gut bacteria, the mechanism of their antibacterial action and genotoxicity to the host. Here, the antibacterial activities of EO in pure and in a mixed faecal culture were investigated. These antibacterial activities were further studied to compare the selective nature of EO and their effects on membrane integrity. The growth of gut pathogens and commensals was inhibited in a dose-dependent manner in pure culture, with most of the pathogens, Escherichia coli O157:H7, Clostridium difficile, C. perfringens and Salmonella typhimurium are sensitive to nerolidol, thymol, eugenol and geraniol at a half maximal inhibitory concentration (IC50) of 50-500 ppm. These concentrations of EO and mainly nerolidol were also inhibitory to some gut commensals, in particular affecting Faecalibacterium prausnitzii adversely in pure culture. In contrast, in the mixed culture system beneficial groups of bacteria, including F. prausnitzii, as determined by qPCR of 16S rRNA genes were not affected. Thymol and geraniol at 500 ppm suppressed the growth of total bacteria, resulting in minimal fermentation. A lower dose of 100 ppm of EO compounds was effective in suppressing the pathogen, C. difficile with no concern for commensal bacteria or their fermentation products, acetate, propionate and butyrate. This study also discovered that the proteome of commensal, Faecalibacterium prausnitzii and pathogenic gut bacteria, Escherichia coli, in response to EO compounds are affected differently. Thymol and eugenol down-regulated virulence factors in E. coli. The tested EO compounds were not genotoxic in the comet assay at non-toxic doses. Differential effects of EO compounds on gut pathogens and commensals and their non-toxicity but geno-protective properties could be applicable in improving gut health in man.

Our hypothesis is that the polyamine biosynthetic pathway, a pathway essential in many cellular functions, is modulated by NSAIDs and that this is, at least in part, how NSAID chemoprevention is mediated. An <i>in vitro </i>model of colorectal cancer was used: two cell lines one of which is COX positive and one COX negative to determine the effects of a range of selective and non-selective NSAIDs on various reactions within the polyamine pathway.  NSAIDs are cytotoxic to colorectal cancer cells regardless of their COX expression.  NSAID-mediated inhibition of cell growth is accompanied by inhibition of ODC activity, partial depletion of polyamine concentrations and up-regulation of polyamine catabolism. In order to investigate the importance of polyamine metabolism, a specific polyamine inhibitor α-difluoromethylornithine (DFMO) was used in combination with the NSAIDs.  DFMO <i>per se </i>is not toxic to cells and it does not enhance NSAID mediated toxicity.  DFMO in combination with the NSAIDs did cause increased catabolic activity and more sustained polyamine depletion than either alone, however no additional decrease in ODC activity was observed.  This suggests that NSAID toxicity is not enhanced by DFMO in this <i>in vitro </i>model. Analysis of the mode of death indicated that the NSAIDs caused apoptotic cell death, confirmed through biochemical and morphological studies and that the NSAIDs affected gene expression of key enzymes in the polyamine biosynthetic pathway. Our findings suggest that modulation of the polyamine pathway by NSAIDs is at least part of the mechanism of action involved in cancer chemoprevention. Therefore modulation of the polyamine pathway may be useful for design of new chemopreventative drugs.

Purpose: Hypoxia in colorectal cancer (CRC) and gastroesophageal cancer (GEC) decreases tumour responsiveness to radio and chemotherapy leading to cancer progression and poor prognosis. This is the first study to utilise [18F]FAZA hypoxia radiotracer in patients with CRC and GEC. Methods: Six patients (mean age 68±8 years, 2 males and 4 females) with CRC and 4 patients diagnosed with GEC (mean age 65 years, 3 males and 1 female) were included in the study. [18F]FAZA was synthesised at the John Mallard Scottish PET Centre. After injection with 370 MBq of [18F]FAZA, PET/CT images with 60 min dynamic scan were acquired. In addition, 15 min static scans 2 hr post injection were performed. 3D PET images were reconstructed iteratively using an ordered subset expectation maximization (OSEM) method and fused to the corresponding low-dose CT images. [18F]FAZA uptake parameters including maximum standard uptake value (SUVmax), tumour-to-muscle ratio (T/M), tumour-to-bowel ratio (T/B) and volume of interest (VOI) were measured. Results: 4 out 6 patients with CRC (66%) showed clear uptake of [18F]FAZA in the primary tumour. The mean tumour SUVmax was 2.2±0.91 (range 1.12 - 3.71). The tumour SUVmax was significantly higher compared with muscle and bowel (t(5) =3.11, P=0.03), (t(5) =3.08, P=0.03), respectively. However, tumour SUVmean didn't differ significantly compared with muscle and bowel (t(5) =2.41 , P=0.06), (t(5) =2.46 , P=0.06) respectively. The mean tumour to muscle ratio (T/M) ratio was 1.89±0.64 (range 1.10 - 2.87), while the mean tumour to normal bowel (T/B) was 1.92±0.64 (range 1.08 - 2.74). However, [18F]FAZA did not accumulate in any of the tumours found in patients with GEC. Conclusions: [18F]FAZA PET/CT imaging is suitable and feasible for detecting CRC hypoxic tumour regions with image quality that can be used in clinical practice.

The aim of this thesis is to evaluate the short and long term effectiveness of foot orthoses in the treatment of plantar fasciitis.Three studies were undertaken, the first two informing the third. The aim of the first study was to establish prescription habits of Australian and New Zealand podiatrists in order to ascertain the most commonly prescribed foot orthoses. The second study was conducted to establish the most appropriate outcome measure to assess the effectiveness of foot orthoses in the treatment of plantar faciitis. The main study, a pragmatic single-blind randomised control trial, was conducted to evaluate the effectiveness of three types of foot orthoses in the treatment of plantar fasciitis. The research concluded that provision of appropriate foot orthoses produces small short-term benefits in function for people with plantar fasciitis, but no effect is apparent at twelve months.

The available strategies for the treatment of complex bone defects are limited and do not effectively promote bone tissue regeneration. Smart biomaterials have been investigated and designed as a suitable tool for application in degenerative diseases. In particular, magnetic materials are a class of smart biomaterials that showed promising results in bone tissue regeneration or as a diagnostic use. Therefore, the development of biomaterials with magnetic properties is an emerging field of research. The present work describes the application of biomineralisation process, to develop novel biocompatible and bioactive hybrid biomaterials with superparamagnetic properties. Collagen type I-like peptide matrix (RCP) was mineralised with Fe+2/Fe3+-doped hydroxyapatite and engineered into hybrid microspheres (RCPFeHA) by using an appositely developed and optimized emulsification process. Thorough investigation of physicochemical, morphological, thermal, magnetic and biologic properties of the new hybrid microspheres, as induced by the presence of the inorganic nanophase and controlled iron substitution into hydroxyapatite lattice, revealed bone-like composition, designed shape and size, tailored magnetization, good cytocompatibility and significant activity in inducing osteogenic differentiation and expression of genes relevant for bone tissue formation. Microspheres were stable in physiological and inflammatory-mimicking conditions and delivered calcium and iron ions, which could be related to the osteogenic differentiation of murine pre-osteoblasts cells and human mesenchymal stem cells. On the other hand, the effect of microspheres composition on the release of important growth factor in bone tissue regeneration (i.e. rhBMP-2) was studied under static and pulsed electromagnetic field, and bioactive and slow release over the time was obtained. The unique features exhibited by the new hybrid magnetic microspheres are interesting and promising for application as new biomaterials with ability of remote activation and control by using external magnetic fields, that might be addressed to smart and personalized applications in medicine, particularly in bone tissue regeneration or smart drug delivery systems.

El Diagnòstic Genètic Preimplantacional (o DGP) és un conjunt de metodologies, que s'apliquen en el transcurs d'un cicle de reproducció assistida, i que permeten la selecció d'embrions sans en parelles afectes de malalties genètiques hereditàries com la fibrosi quística o l'hemofília, entre moltes altres.<br/>A més, també s'utilitza per realitzar un cribatge d'alteracions cromosòmiques (o aneuploïdies) que puguin afectar l'embrió, ja que s'ha evidenciat que aquestes són molt abundants en avortaments. S'ha postulat que una selecció positiva dels embrions lliures de aneuploïdies (és a dir, euploides) hauria d'augmentar la taxa d'embaràs dels embrions transferits al pacient. Publicacions recents, però, han demostrat que encara que es seleccionin els embrions euploides, la taxa d'embaràs no millora significativament, essent al voltant del 13%, mentre que en pacients als quals no s'aplica el DGP és del 30%. <br/>Un dels motius per aquest reduït èxit bé pot ser la tècnica utilitzada per realitzar el cribatge de aneuploïdies, la FISH, que limita l'estudi a només nou dels 23 cromosomes de l'embrió, quedant doncs més de la meitat sense diagnosticar. Per tant, els embrions que es transfereixen com euploides utilitzant la FISH poden contenir aneuploïdies per a qualsevol dels cromosomes restants no analitzats, fet que implica que l'embrió no implanti o que no generi un embaràs viable. <br/>Alternativament a la FISH, existeix la CGH que permet la detecció de tots els 23 cromosomes de l'embrió. La CGH s'ha aplicat prèviament en el DGP, però té l'inconvenient del temps necessari per realitzar la metodologia, que és de tres dies i que implica que no hi ha prou temps per diagnosticar els embrions abans de transferir-los a la pacient. Així doncs, els embrions s'han de congelar a l'espera d'obtenir els resultats de la CGH, per a ser transferits els que siguin euploides en un altre cicle de reproducció assistida. Aquest procés té apart de la desavantatge de les molèsties que implica la necessitat d'aplicar dos cicles de reproducció assistida contigus a la pacient, el fet que entre el 20-40% dels embrions no sobreviuen al procés de congelació / descongelació. Això pot suposar que encara que un embrió hagi estat diagnosticat com euploide per a tots els cromosomes mitjançant CGH, no es pugui arribar a transferir degut a no sobreviure a la congelació / descongelació. <br/>Per tal de solucionar aquestes desavantatges, una proposta metodològica alternativa és analitzar indirectament el ovòcit mitjançant estudi del corresponent 1er corpuscle polar (1CP). Amb aquesta alternativa, consistent en biopsiar el 1CP a després de la fecundació (o Dia 0), es disposa de fins a 4 dies per obtenir el resultat de la CGH. Això possibilita poder transferir en el mateix cicle de reproducció assistida els embrions derivats d'oòcits potencialment euploides, sense necessitat de congelar i descongelar. Aquesta proposta té el desavantatge, de quedar fora d'anàlisi les anomalies cromosòmiques d'origen masculí o les produïdes en el propi embrió durant les primeres divisions. Malgrat aquesta limitació, i atès que el 80% de les aneuploïdies l'embrió s'originen en l'ovòcit, l'anàlisi amb CGH de l'ovòcit permet detectar la majoria d'embrions aneuploides. Per això aquesta aproximació metodològica és molt adequada per al DGP. <br/>En aquesta tesi doctoral, s'ha aplicat un protocol de DGP per evitar malalties genètiques conjuntament amb un cribatge de aneuploïdies d'origen femení mitjançant la CGH aplicada al 1CP. Aquest doble diagnòstic genètic s'ha definit com diagnòstic genètic preimplantacional de doble factor (o DF-PGD) i ha estat aplicat, durant aquesta tesi doctoral per primera vegada en tot el món. <br/>Concretament, el DF-PGD s'ha aplicat a embrions de deu famílies afectes de Fibrosi Quística, la Síndrome d'Angelman o bé de Von Hippel-Lindau, aconseguint incrementar la taxa d'embaràs fins al 33%, respecte del 12,5% que és la que s'obté quan no es realitza aquest doble anàlisi. S'ha produït el naixement de quatre nadons sans per les respectives malalties familiars. Tot i admetent que aquests resultats són preliminars, apunten que el procediment del DF-PGD és útil per diagnosticar les malalties genètiques hereditàries i a la vegada, permet un augment considerable de la taxa d'embaràs en aquest grup de pacients. <br/>Amb l'objectiu de constatar si el DF-PGD indicat no només a dones d'edat avançada, sinó també en dones joves, aquesta tesi inclou un estudi citogenètic complet d'ovòcits de dones joves, analitzant mitjançant la CGH ambdues cèl·lules constituent del ovòcit madur: el 1CP i la corresponent MII. S'han inclòs en l'estudi dels 84 oòcits de dones joves (de 24 a 26 anys) que participen en programes de donació d'ovòcits en centres de reproducció assistida. S'ha evidenciat que un 40% dels ovòcits contenen aneuploïdies. Així doncs, el DF-PGD pot ser una bona opció per millorar l'actual taxa d'embaràs en pacients amb malalties genètiques hereditàries, independentment de l'edat de la pacient. <br/>En conclusió, en aquesta tesi doctoral s'ha evidenciat que el DF-PGD és una variant de DGP que no només és molt recomanada per a parelles en les quals la dona té una edat reproductiva avançada (més de 35 anys) sinó també per a parelles joves, i que pot resultar molt útil per incrementar les actuals taxa d'embaràs.<br>Preimplantation genetic diagnosis (or PGD) is a set of methodologies that is applied during a cycle of assisted reproduction, allowing the selection of healthy embryos in couples suffering from inherited genetic diseases as cystic fibrosis, haemophilia and many others. <br/>It also is used to perform a screening for chromosomal abnormalities (or aneuploidy) that may affect the embryo, as it has become clear that these are very abundant in abortions. It has been postulated that a positive selection of embryos free of aneuploidy (i.e. euploid embryos) should increase the pregnancy rate of embryos transferred to the patient. Recent publications, however, have shown that although the selection of euploid embryos, the pregnancy rate does not improve significantly, with about 13%, whereas patients who did not apply the DGP are 30%. <br/>One reason for this limited success may well be the technique used for screening for aneuploidy, the FISH, which limits the study to only nine of the 23 chromosomes of the embryo, thus leaving more than half undiagnosed. Therefore, the embryos are transferred as euploid using FISH may contain aneuploidy of the other chromosomes not analyzed, which implies that either a failure of the embryo implantation.<br/>Alternatively to the FISH, the CGH technique allows the detection of all 23 chromosomes of the embryo. The CGH has been applied previously in the PGD, but has the disadvantage of the time required for the methodology, which is three days and that means that there is not enough time to diagnose embryos before transferring them to the patient. Thus, embryos must be frozen to await the results of the CGH to be transferred. This process has the disadvantage of being apart from the discomfort that implies the need to implement two cycles of assisted reproduction to the patient, the fact that between 20-40% of embryos do not survive the process of freezing / thawing. This may mean that while an embryo has been diagnosed as euploide for all chromosomes by CGH, can not be transferred due to not surviving the freezing / thawing process.<br/>To overcome these disadvantages, an alternative methodology is to analyze indirectly through study of the corresponding oocyte corpuscle 1st Polar (1PB). With this alternative, consisting of the biopsy in 1PB after fertilization (or Day 0), it is up to 4 days for the result of the CGH. This enables transfer in the same cycle of assisted reproduction embryos derived from oocytes euploides potentially without the need to freeze and thaw. This proposal has the disadvantage of being left out of the analysis of chromosomal abnormalities or male origins were produced in the embryo during the first division. Despite this limitation, given that 80% of embryo aneuploidy originates in the oocyte, the CGH analysis of oocytes can detect the majority of aneuploid embryos. Therefore the methodological approach is very suitable for the DGP. <br/>In this thesis, we have implemented a protocol for PGD to avoid disease with a genetic screening for aneuploidy in female origin by CGH applied to 1PB. This dual genetic diagnosis has been defined as preimplantation genetic diagnosis of double-factor (or DF-PGD) and has been applied during this thesis for the first time around the world. <br/>Specifically, the DF-PGD has been applied to embryos of ten families affected by cystic fibrosis, Angelman syndrome or von Hippel-Lindau, achieving pregnancy rate increased to 33% on the 12.5% which is obtained when the DF-PGD is not analysis. There was the birth of four healthy babies by their illness relatives. Even accepting that these results are preliminary, it suggests that the proceedings of the DF-PGD is useful for diagnosing hereditary genetic diseases and also allows an increase in pregnancy rate in this group of patients. <br/>Aiming to establish whether the DF-PGD indicated not only older women but also young women, this thesis includes a comprehensive cytogenetic study of oocytes from young women looking through CGH both constituent cells of mature oocyte, the 1CP and the corresponding MII. We performed a study of young women 84 oocytes (24 to 26 years) involved in egg donation programs in assisted reproduction centres. After its analysis, we concluded that 40% of the oocytes contain aneuploidy. Thus, the DF-PGD may be a good option to improve the current pregnancy rate in patients with inherited genetic diseases, regardless of the age of the patient.<br/>In conclusion, this thesis has shown that the DF-PGD is a variant of PGD is not only highly recommended for couples where the woman has an advanced age (over 35 years) but also for young couples and that can be useful to increase the current rate of pregnancy.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico<br>A esquistossomose acomete pelo menos 230 milhÃes de pessoas e està associada com pelo menos 200.000 mortes anualmente no mundo. A detecÃÃo dos antÃgenos circulantes de Schistosoma està se tornando uma ferramenta promissora para o diagnÃstico de infecÃÃes ativas. Os nÃveis sÃricos desses antÃgenos estÃo relacionados com a carga parasitÃria e a intensidade de infecÃÃo e diminuem rapidamente apÃs o tratamento medicamentoso, demonstrando ser uma abordagem Ãtil tambÃm na avaliaÃÃo da resposta terapÃutica. Foi avaliada a prevalÃncia da infecÃÃo ativa pelo S. mansoni atravÃs do ensaio Up- Converting Phosphor Lateral Flow (UCP-LF) para determinaÃÃo do AntÃgeno AnÃdico Circulante (CAA) na urina e comparada com a da tÃcnica de Kato-Katz para a detecÃÃo de ovos nas fezes e com a do teste Point-of-Care â CCA (POC-CCA), que detecta o AntÃgeno CatÃdico Circulante (CCA) na urina. AlÃm disso, a resposta terapÃutica foi avaliada pelos mÃtodos que detectam os antÃgenos circulantes seis semanas apÃs o tratamento. O estudo foi realizado na localidade de Bananeiras, Capistrano, uma Ãrea endÃmica no Estado do CearÃ. De 297 habitantes da localidade, 285 aceitaram participar do estudo, dos quais 159 receberam o tratamento. Destes, 128 entregaram as amostras de urina e fezes requisitadas antes e apÃs o tratamento e foram avaliados pelos trÃs mÃtodos. O ensaio UCP-LF CAA detectou 44 positivos (34,4%). A tÃcnica de Kato-Katz revelou apenas duas amostras de fezes positivas (1,6%) e o POC-CCA detectou 8 positivos (6,2%). As sensibilidades dos diferentes ensaios foram determinadas contra um padrÃo ("ouro") de positividade de infecÃÃo combinado, mostrando-se maior para o ensaio UCP-LF CAA (92%), seguido pelo POC-CCA (17%), enquanto o Kato-Katz (trÃs lÃminas) teve uma sensibilidade muito baixa (4%). A maior taxa de prevalÃncia de infecÃÃes ativas encontrada foi em pessoas com idades de 30 a 39 anos. As concentraÃÃes de CAA antes do tratamento variaram de 0,16 a 61,12 pg CAA / ml de urina, havendo um decrÃscimo significativo dos nÃveis de CAA apÃs seis semanas do tratamento (Wilcoxon, P = 0,003). Dessa maneira, tendo em conta essas observaÃÃes promissoras, o UCP-LF CAA mostrou um valor potencial para a determinaÃÃo da prevalÃncia de esquistossomose mansoni em Ãreas de baixa endemicidade; contudo, outros estudos mais amplos sÃo necessÃrios.

This thesis is focused on the key role of extracellular matrix in skin tissue engineering. Firstly, I presented three dimensional structures derived through the physiological secretion of extracellular matrix (ECM), that may be a bioinspired scaffold. I performed a biological characterization of cell-assembled ECMs from three different sub-populations of skin fibroblasts; papillary fibroblasts (Pfi), reticular fibroblasts (Rfi), and dermal papilla fibroblasts (DPfi). Fibroblast sub-populations were cultured with ascorbic acid to promote cell-assembled matrix production for 10 days. Cells were removed and the remaining matrices were characterized. I found that the ECM assembled by Pfi exhibited randomly oriented fibers, associated with highest interfibrillar space, reflecting ECM characteristics which are physiologically present within the papillary dermis. Mass spectrometry followed by immunofluorescence analysis showed that Thrombospondin is preferentially expressed within the DPfi ECM. In another experiment, keratinocytes were seeded on the top of cell depleted ECMs to generate epidermal skin constructs. I found that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, while Rfi matrices were unable to support membrane formation. Thus, inspiration should be taken from these different ECMs, to design therapeutic biomaterials in skin engineering applications. In the second part, I focused on human decellularized matrix for soft tissue repair and I investigated the biological interaction post-implant of this scaffold. The aims of this second part were to show the clinical results after the application of human decellularized matrix in patients suffering from abdominal hernia and to evaluate the response one year post implant, through morphological analysis of biopsy specimens. Clinical results showed that all the patients revealed a well tolerability of human decellularized matrix. Post-implant morphological results showed cellular repopulation, neo-angiogenesis, minimal inflammatory response and a well-organized collagen matrix in all biopsies. This scaffold can be considered a safe product to treat large abdominal defects.

Thesis (Ph. D.)--University of California, Riverside, 2009.<br>Includes abstract. Includes bibliographical references (leaves 293-348). Issued in print and online. Available via ProQuest Digital Dissertations.

The phosphatidylinositol-3-kinase/AKT (Protein Kinase B)/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway, downstream of tyrosine kinase receptors, is upregulated in human cancers including breast and colon cancers. Glycogen synthase kinase 3 (GSK 3) is a serine/threonine protein kinase plays important role in various cellular processes including glycogen synthesis mediated by insulin signalling pathway. Moreover, 5' adenosine monophosphate activated protein kinase (AMPK), a crucial cellular energy sensor, has regulatory role in cell growth and proliferation through mTOR pathway. Phosphatidylcholine (PtdCho) is the major phospholipid in the mammalian cell membranes and is mainly synthesized by the CDP-choline pathway. Malignant transformation has been reported to be associated with altered choline metabolism. Hyperactivation of the PI3K/AKT signalling pathway upregulates the key enzymes of phospholipid metabolism. The first line antidiabetic drug, metformin, modulates glucose and concomitant lipid metabolism through AMPK activation. Studies suggest phosphatidylcholine biosynthesis and breakdown through CDP-choline pathway are modulated by glucose metabolism and de novo fatty acid synthesis. Cancer cell growth inhibitory effect of PI3K/AKT/mTOR/GSK3 pathway inhibitors and metformin were investigated by cytotoxic assay, western blot and cell cycle analysis in breast and colon cancer cells. IC50 values of anticancer drugs and combination indices between drug combinations were determined. 31P-NMR was carried out on cell extracts after drug treatments. [14C (U)] glucose and [3H] choline incorporation into lipids were also determined. All inhibitors targeting PI3K/AKT/mTOR signaling pathway, GSK3 and metformin have cancer cell growth inhibition. By 31P-NMR, PI3K/AKT/mTOR pathway inhibition induced agent-specific changes in PCho intensity. Increased UDP-sugars observed in breast and colon cancer cell extracts treated with LY294002 and AZD8055, an effect abrogated by inclusion of a GSK3 inhibitor. A link between glycolytic intermediates and phosphatidylcholine biosynthesis was investigated by metformin and GSK3 inhibitor in breast and colon cancer cells.

Questo lavoro di ricerca nasce dal desiderio di indagare il potenziale riflessivo, euristico e trasformativo della dimensione embodied nei processi di insegnamento/apprendimento. Per farlo ha interrogato un gruppo di insegnanti della scuola primaria, coinvolgendole in una ricerca partecipativa sulle proprie pratiche di insegnamento e sul loro modo unico di incarnarle (embodied teaching), a partire da un’attivazione corporea specifica (Anatomia Esperienziale). La mia domanda di ricerca si è orientata in due direzioni. Ad un livello metodologico potrebbe essere formulata nel seguente modo: come interrogare l’embodied teaching (Bresler, 2014) di professionisti della scuola, cioè il modo incarnato di interpretare il processo di insegnamento/apprendimento? Ad un livello tematico, invece, l’interrogativo di fondo potrebbe essere così posto: cosa emerge quando si va ad attivare un processo di riflessione sulla pratica professionale di un gruppo di insegnanti della scuola primaria a partire da un’interrogazione che passa dalla percezione e dall’attivazione corporea? Collocandomi nell’area di ricerca della Pedagogia del corpo (Gamelli, 2011), il macro-paradigma dell’embodiment ha rappresentato un riferimento epistemologico importante per il lavoro. In esso ho trovato un fertile incontro di studi, ricerche e pratiche provenienti da ambiti molto distanti, tra cui le scienze cognitive (l’enactive embodiment di Varela, Thompson, Rosch, 1991), l’ambito performativo (Farnell, 1995; Sheets-Johnstone, 1999; Bresler, 2014) e quello più legato all’educazione (Gamelli, 2011; Rossi, 2017). È precisamente all’incontro di queste tre aree che si colloca la prospettiva di ricerca del presente lavoro. La parte empirica della ricerca si è svolta con un gruppo di sette insegnanti di una scuola primaria milanese, su adesione volontaria, in sei incontri di tre ore circa ciascuno. Il setting di ricerca è stato strutturato in modo che ci fosse una stratificazione dell’esperienza corporea proposta affinchè ognuna delle partecipanti potesse contattare il proprio embodied teaching nel rispetto del proprio stile personale e corporeo di insegnamento. La metodologia della “co-operative-inquiry” (Heron, Reason, 1997) e la successiva interpretazione di Formenti nella “spirale della conoscenza” (Formenti, 2009), oltre che fornirmi un riferimento epistemologico in termini di dimensione partecipata della conoscenza, mi hanno fornito riferimenti importanti per disegnare la struttura interna degli incontri in modo coerente con i miei presupposti teorici. L’anatomia esperienziale del Body-Mind Centering è stata la pratica somatica che ho utilizzato per la ricerca empirica. Tutti gli incontri sono stati audioregistrati e trascritti. Dopo una prima analisi tematica attraverso NVivo, è maturata la decisione di andare verso una svolta più performativa della mia ricerca. Questo cambio di prospettiva ha richiesto l’ideazione e la costruzione di un dettagliato – e inedito – metodo di ricerca embodied. Si tratta di uno dei passaggi più originali della mia ricerca di dottorato, che ha visto l’inizio di un lavoro di analisi corporea e performativa dei dati attraverso segmenti audio e testuali che ho selezionato dalle trascrizioni e dai materiali audio degli incontri con le insegnanti. Questa analisi performativa, documentata in 160 riprese video, si è poi direzionata verso la creazione di una video-performance utilizzata come restituzione alle insegnanti rilanciandolo e aprendo nuovi interrogativi e così possibili sviluppi per ricerche future legate alla dimensione corporea della professione insegnante.<br>This thesis is deeply connected with the will of investigating the reflective, heuristic and transformative potential of the embodied dimension in teaching and learning processes. For this purpose, I engaged a group of Primary School teachers in a participatory research focused on their personal way of embodying teaching practices (embodied teaching) starting from a specific body activation (Experiential Anatomy). My research question was twofold. At a methodological level I was interested in interrogating the embodied teaching (Bresler 2014) of school professionals, namely their own way of performing the teaching/learning processes. At a thematic level the question was: what does it happen when a researcher activate a reflective process on professional practices of a group of primary school teachers through body activations? My main theoretical frame is represented by Embodied Pedagogy (Gamelli, 2011) and my fundamental epistemological reference is the so-called “embodiment paradigm”. This paradigm is a generative common ground for studies and practices connected to heterogeneous fields as cognitive sciences (Varela, Thompson and Rosch, 1991), performative disciplines (Farnell, 1995; Sheets-Johnstone, 1999; Bresler, 2014) and education (Gamelli, 2011; Rossi, 2017). My research perspective lies exactly at the crossroads of these three main areas. The empirical part of my research took place in a Primary School of Milan. I addressed a group of teachers with a research proposal structured on six meetings of three hours each. The research setting was designed in a way that allowed a multi-layered experience of the body activations in order to let each participant explore her own embodied teaching, namely her own personal way of performing teaching. The “co-operative inquiry” theorized by Heron and Reason (1997) and Formenti’s “Spyral of knowledge” (2009) were the two main epistemological pivots in reflecting on the research objectives, as they both advance the idea of research as a co-construction of participatory knowledge. They were also fundamental in order to design the internal structure of each meeting consistently with my theoretical assumptions. Experiental Anatomy of Body-Mind Centering was the somatic practice that I used for the empirical part. Each meeting was audio-recorded and transcribed. After a first thematic analysis with Nvivo I decided to turn my research in a performative direction. This change of perspective required the creation of a detailed embodied research method. This is the most original part of my thesis that consisted in a performative analysis of a selection of collected data (originated in the six meetings with the participants) in the form of textual and audio excerpts. This performative analysis, documented by 160 video shootings, ended in the creation of a video-performance that was used as a starting point of the final meeting with research participants. The use of this aestethic and performative object in the research setting revealed itself as a powerful tool in order to trigger an high level of participation in the group. The final meeting, in fact, was a fundamental moment as the participants’ reflections transformed “my” performative composition in a shared knowledge connected with all the research process. The results were very interesting both in terms of new questions raised by the teachers and of future research possibilities in the direction of embodied teaching.

Abstract Background: Epithelioid hemangioma (EH) of bone is a vascular neoplasm with a ubiquitous distribution, including bone and soft tissue. The clinical behavior of EH is complicated because of its multifocal presentation and rare lymph node involvement. To date, up to 25% EH of bone presents synchronous bone lesions and specific gene alterations. Recently, a novel and recurrent FOS gene rearrangement was present in nearly one third of EH across a variety of locations. Before the discovery of gene rearrangements specific to this rare entity, EH was often misdiagnosed as epithelioid hemangioendothelioma (EHE) or angiosarcoma. Acute Myeloid Leukemia (AML) is characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation, frequently resulting in impaired hematopoietic differentiation that results in granulocytopenia, thrombocytopenia or anemia, with or without leukocytosis. Currently, Azacitidine is the first-line clinical drug for both MDS and AML, whereas Venetoclax is mainly used for chronic lymphocytic leukemia (CLL) patients with or without 17p deletion. The combination of Venetoclax with Azacitidine is being tested with positive clinical results in AML therapy. However, the molecular mechanisms underlying the effect of this combination therapy are still unclear. Therefore, in this study we analyzed the molecular effects of Azacitidine and Venetoclax combination on the nuclear inositide-dependent pathways, mainly focus on PLC-β1. Aim: This study aimed at describing for the first time a metachronous multifocal lesions case of EH with fatal outcome and analyze the role of inositide pathways in AML.<br>Results: Here we reported the first case of EH with multifocal metachronous bone lesions. This case shows the possible existence of multifocal metachronous EH without producing a fatal outcome. FOS gene rearrangement is critical to assistant the diagnosis of EH. On the other hand, we studied inositide signalling in AML, confirming the IC50 of MOLM-13, HL-60, THP-1 and U-937 hematopoietic cell lines when exposed to Azacitidine and Venetoclax. Moreover, Azacitidine and Venetoclax treatment could induce an increase of the Sub-G0/G1 phase, as well as a G0/G1 arrest in MOLM-13 cells and HL-60 cells. At the same time, it seems to prolong the S phase in U-937 cells. Furthermore, the combination therapy was also able to specifically induce myelopoiesis, as MOLM-13 and THP-1 cells showed an increased expression of CD14. Finally, the combined treatment triggers a higher expression of PLC-β1, which activates the signaling pathway to degrade PKCα.

The present Master thesis focuses on evalution of CO2 concentration and irradiance on selected leaf anatomical parameters of European Beech (Common Beech) Fagus sylvatica L.. The process of photosynthesis is remarkably determined by numerous extrenal factors, among them by atmoshperic CO2 concentration and irradiance and is closely correlated with leaf anatomical parameters. One of these most important anatomical parameters affecting the net assimilation rate is an internal leaf surface, which corresponds to mesophyll area avialable for gas exhcange. Experimental material of the study was sampled from the leaves of juvenile trees of F. sylvatica planted in 2005 and growing under ambient (390 ppm, AC) and elevated (700 ppm, EC) CO2 concentrations on the experimental site of the Global Change Research Center AS CR at Bílý Kříž in the Beskydy Mountains. Sun and shade leaves were sampled from trees of both CO2 treatments in two seasons 3 years apart (2009 and 2012). To determine leaf anatomical parameters, the stereological methods were applied, which yield unbiased estimation of measured parameters, particularly the Fakir method for internal leaf surface determination. The EC effect was observed on the leaves sampled in 2009 only in the decrease of proportion of intercellular spaces in mesophyll. In...

On the basis of the contradictory opinions of Bulgarian critics, the objective of this study was to compare the short story cycle Under the monastery vine by Elin Pelin and The We/l of Saint Clare by Anatole France and to determine their relation. Detailed analyse of the books revealed the significant difference. Elin Pelin in the legendary stories presents his model of the ideal world (the world of the fantasy of the common faith of Bulgarian people). Bulgarian writer demonstrates the truth he is convinced of to the reader by basing the narrative on the plot. The We/l af Saint Clare is not a homogeneous book, it can be devided into two parts, where the first part deals with the impressive themes that are remarked by the parnasist beginnings of Anatole France (his pure aesthetical attitude towards writing is at variance with the attitude of Elin Pelin). The stories of the second part are full of philosophical meditations and monologues, in which a french writer takes the engaged position, characteristic for his supreme works. He is not only against the fanatic and dog matic manifestations of the religion like Elin Pelin, but he is also against the faith as such. However Anatole France does not directly instruct the reader, he only demonstrates that any "truth" could be challenged and questioned and any...

Thesis (M.S.)--State University of New York at Buffalo, 2008.<br>Title from PDF title page (viewed on Jan. 14, 2009) Available through UMI ProQuest Digital Dissertations. Thesis adviser: Kesavadas, Thenkurrisi Includes bibliographical references.

Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 2007.<br>Source: Dissertation Abstracts International, Volume: 68-10, Section: B, page: 6618. Adviser: Marsha L. Frazier. Includes bibliographical references.

Thèse (M.Sc.) -- Université Laval, 1997.<br>Les chapitres 2 et 3 ont été rédigés par l'auteur et collab. en anglais, avec résumés en français, et publiés ou soumis dans différents titres de périodiques. Bibliogr. Publ. aussi en version électronique.