Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-dimensional retinal organoids from mouse pluripotent stem cells mimic in vivo development with enhanced stratification and rod photoreceptor differentiation

Purpose The generation of three-dimensional (3D) organoids with optic cup–like structures from pluripotent stem cells has created opportunities for investigating mammalian retinal development in vitro. However, retinal organoids in culture do not completely reflect the developmental state and in vivo architecture of the rod-dominant mouse retina. The goals of this study were to develop an efficient protocol for generating retinal organoids from stem cells and examine the morphogenesis of rods in vitro. Methods To assess rod photoreceptor differentiation in retinal organoids, we took advantage of Nrl-green fluorescent protein (GFP) mice that show rod-specific expression of GFP directed by the promoter of leucine zipper transcription factor NRL. Using embryonic and induced pluripotent stem cells (ESCs and iPSCs, respectively) derived from the Nrl-GFP mouse, we were successful in establishing long-term retinal organoid cultures using modified culture conditions (called High Efficiency Hypoxia Induced Generation of Photoreceptors in Retinal Organoids, or HIPRO). Results We demonstrated efficient differentiation of pluripotent stem cells to retinal structures. More than 70% of embryoid bodies formed optic vesicles at day (D) 7, >50% produced optic cups by D10, and most of them survived until at least D35. The HIPRO organoids included distinct inner retina neurons in a somewhat stratified architecture and mature Müller glia spanning the entire retina. Almost 70% of the cells in the retinal organoids were rod photoreceptors that exhibited elongated cilia. Transcriptome profiles of GFP+ rod photoreceptors, purified from organoids at D25–35, demonstrated a high correlation with the gene profiles of purified rods from the mouse retina at P2 to P6, indicating their early state of differentiation. Conclusions The 3D retinal organoids, generated by HIPRO method, closely mimic in vivo retinogenesis and provide an efficient in vitro model to investigate photoreceptor development and modeling disease pathology.
Aspirin prescription and outcomes in hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS).

BACKGROUND We investigated aspirin-prescribing patterns and potential benefits on cardiovascular morbidity and mortality in hemodialysis patients. STUDY DESIGN Cohort study. SETTING & PARTICIPANTS Data included 28,320 randomly selected hemodialysis patients from the Dialysis Outcomes and Practice Patterns Study I and II. PREDICTOR Aspirin prescription at study baseline. OUTCOMES & MEASUREMENTS Prescription was investigated by means of logistic regression. All-cause mortality, all-cause hospitalization, cardiac event, myocardial infarction, cerebrovascular (CVA), gastrointestinal bleed, transient ischemic attack, and subdural hematoma were examined. Cox regression examined the risk of mortality and hospitalization. All models accounted for facility clustering and demographics and comorbid conditions. RESULTS Wide variation was found in aspirin prescription, from 8% in Japan to 41% in Australia and New Zealand. Characteristics significantly associated with increased odds of prescription included coronary artery disease, cerebrovascular disease, diabetes, male sex, nonblack race, peripheral vascular disease, age, hypertension, and absence of gastrointestinal bleeding. Aspirin was associated with decreased risk of stroke in all patients (relative risk [RR], 0.82; P < 0.01) and increased risk of myocardial infarction (RR, 1.21; P = 0.01) and cardiac event (RR, 1.08; P < 0.01) in all patients, with similar results for patients with coronary artery disease. There was no increase in gastrointestinal bleeding. LIMITATIONS Observational studies are not protected from biases, despite adjustments. There is potential for aspirin use to be underreported because of its availability without prescription. CONCLUSIONS The hypothesis that prescribing aspirin to hemodialysis patients decreases cardiovascular disease risk is not supported. Aspirin might decrease CVA and appears not to increase hemorrhagic risk. This should be an incentive for randomized controlled trials.
Synergy between Face Alignment and Tracking via Discriminative Global Consensus Optimization

An open question in facial landmark localization in video is whether one should perform tracking or tracking-by-detection (i.e. face alignment). Tracking produces fittings of high accuracy but is prone to drifting. Tracking-by-detection is drift-free but results in low accuracy fittings. To provide a solution to this problem, we describe the very first, to the best of our knowledge, synergistic approach between detection (face alignment) and tracking which completely eliminates drifting from face tracking, and does not merely perform tracking-by-detection. Our first main contribution is to show that one can achieve this synergy between detection and tracking using a principled optimization framework based on the theory of Global Variable Consensus Optimization using ADMM; Our second contribution is to show how the proposed analytic framework can be integrated within state-of-the-art discriminative methods for face alignment and tracking based on cascaded regression and deeply learned features. Overall, we call our method Discriminative Global Consensus Model (DGCM). Our third contribution is to show that DGCM achieves large performance improvement over the currently best performing face tracking methods on the most challenging category of the 300-VW dataset.
Efficacy of sustained topical dorzolamide therapy for cystic macular lesions in patients with retinitis pigmentosa and usher syndrome.

OBJECTIVE To determine the efficacy of sustained topical therapy with dorzolamide hydrochloride, 2%, on visual acuity and cystic macular lesions in patients with retinitis pigmentosa and Usher syndrome. METHODS In a retrospective case series at a university hospital, 64 eyes of 32 patients with retinitis pigmentosa or Usher syndrome receiving treatment with the topical dorzolamide formulation for 6 to 58 months were enrolled. Changes in visual acuity on the Early Treatment Diabetic Retinopathy Study chart and central foveal zone thickness on optical coherence tomography were measured during follow-up for the duration of treatment. RESULTS Among the study cohort, 20 of 32 patients (63%) showed a positive response to treatment in at least 1 eye and 13 patients (41%) showed a positive response in both eyes. Four patients (20%) showed an initial response and a subsequent rebound of macular cysts. In 8 patients (25%), there was no response to treatment and the macular cysts worsened when compared with the pretreatment level. Ten patients (31%) had improvement in visual acuity by 7 or more letters in at least 1 eye at the most recent follow-up visit. Sixteen patients (67%) showed a reduction of more than 11% in the central foveal zone thickness in at least 1 eye when compared with the pretreatment level. CONCLUSIONS Patients with either retinitis pigmentosa or Usher syndrome who received treatment of cystoid macular edema with topical dorzolamide followed by an optical coherence tomography-guided strategy showed a decrease in central foveal zone thickness in most cases. Visual acuity improved in almost one-third of the cases, suggesting a potential corresponding visual benefit.
Decreased Proportion of Cytomegalovirus Specific CD8 T-Cells but No Signs of General Immunosenescence in Alzheimer’s Disease

Cytomegalovirus (CMV) has been suggested as a contributing force behind the impaired immune responsiveness in the elderly, with decreased numbers of naïve T-cells and an increased proportion of effector T-cells. Immunological impairment is also implicated as a part of the pathogenesis in Alzheimer’s disease (AD). The aim of this study was to investigate whether AD patients present with a different CMV-specific CD8 immune profile compared to non-demented controls. Blood samples from 50 AD patients and 50 age-matched controls were analysed for HLA-type, CMV serostatus and systemic inflammatory biomarkers. Using multi-colour flow cytometry, lymphocytes from peripheral blood mononuclear cells were analysed for CMV-specific CD8 immunity with MHC-I tetramers A01, A02, A24, B07, B08 and B35 and further classified using CD27, CD28, CD45RA and CCR7 antibodies. Among CMV seropositive subjects, patients with AD had significantly lower proportions of CMV-specific CD8 T-cells compared to controls, 1.16 % vs. 4.13 % (p=0.0057). Regardless of dementia status, CMV seropositive subjects presented with a lower proportion of naïve CD8 cells and a higher proportion of effector CD8 cells compared to seronegative subjects. Interestingly, patients with AD showed a decreased proportion of CMV-specific CD8 cells but no difference in general CD8 differentiation.
Mechanisms involved in enhancement of matrix metalloproteinase‐9 expression in macrophages by interleukin‐33

Endothelial transmigration of macrophages is accomplished by matrix metalloproteinase (MMP)‐induced degradation of the basement membrane and extracellular matrix components. Macrophages upregulate MMP‐9 expression and secretion upon immunological challenges and require its activity for migration during inflammatory responses. Interleukin (IL)‐33 is a recently discovered pro‐inflammatory cytokine that belongs to the IL‐1 family. The aim of this study was to elucidate the mechanisms underlying IL‐33‐induced MMP‐9 expression in the mouse monocyte/macrophage line RAW264.7. IL‐33 increased MMP‐9 mRNA and protein expression in RAW264.7 cells. Blockage of IL‐33‐IL‐33 receptor (ST2L) binding suppressed IL‐33‐mediated induction of MMP‐9. IL‐33 induced phosphorylation and nuclear translocation of extracellular signal‐regulated kinase 1/2 (ERK1/2) and nuclear factor‐kappa B (NF‐κB). Chromatin immunoprecipitation indicated that IL‐33 increased c‐fos recruitment to the MMP‐9 promoter. Reporter assay findings also revealed that IL‐33 stimulated the transcriptional activity of activator protein 1 (AP‐1). Pre‐treatment of the cells with a specific inhibitor of ERK1/2 and NF‐κB attenuated the IL‐33‐induced activation of AP‐1 subunits, transcriptional activity of AP‐1, and expression of MMP‐9. We also demonstrated that ERK‐dependent activation of cAMP response element binding protein (CREB) is a key step for AP‐1 activation by IL‐33. These results indicate an essential role of ERK/CREB and NF‐κB cascades in the induction of MMP‐9 in monocytes/macrophages through AP‐1 activation.
Muslims in Britain: making social and political space

The management of social, religious and ethnic diversity is a key social policy concern in Britain, and Muslims in particular have become a focus of attention in recent years. This timely and topical volume examines the position of Muslims in Britain and how they are changing and making social, political and religious space. With contributions from world renowned scholars on British Muslims and from policy makers writing on issues of concern to Muslims and others alike, the book explores how British Muslims are changing social and religious spaces such as mosques and the role of women, engaging in politics, creating media and other resources, and thus developing new perspectives on Islam and transforming Muslim society from within. Chapters cover issues of religion and politics, Britishness, governance, parallel lives, gender issues, religion in civic space, ethnicity, and inter ethnic and religious relations, as well as the role of intellectuals, chaplains and activists in reforming Islam and renovating the British political landscape. Providing a broad and comprehensive examination of the key issues surrounding Muslims in the UK, this book will be a valuable resource for students, lecturers and researchers in sociology, social policy, geography, politics, Islamic studies and other related disciplines.
BED1, a gene encoding a galactosyltransferase homologue, is required for polarized growth and efficient bud emergence in Saccharomyces cerevisiae

The ellipsoidal shape of the yeast Saccharomyces cerevisiae is the result of successive isotropic/apical growth switches that are regulated in a cell cycle-dependent manner. It is thought that growth polarity is governed by the remodeling of the actin cytoskeleton that is itself under the control of the cell cycle machinery. The cell cycle and the morphogenesis cycle are tightly coupled and it has been recently suggested that a morphogenesis/polarity checkpoint control monitors bud emergence in order to maintain the coupling of these two events (Lew, D. J., and S. I. Reed. 1995. J. Cell Biol. 129:739-749). During a screen based on the inability of cells impaired in the budding process to survive when the morphogenesis checkpoint control is abolished, we identified and characterized BED1, a new gene that is required for efficient budding. Cells carrying a disrupted allele of BED1 no longer have the wild-type ellipsoidal shape characteristic of S. cerevisiae, are larger than wild-type cells, are deficient in bud emergence, and depend upon an intact morphogenesis checkpoint control to survive. These cells show defects in polarized growth despite the fact that the actin cytoskeleton appears normal. Our results suggest that Bed1 is a type II membrane protein localized in the endoplasmic reticulum. BED1 is significantly homologous to gma12+, a S. pombe gene coding for an alpha-1,2,-galactosyltransferase, suggesting that glycosylation of specific proteins or lipids could be important for signaling in the switch to polarized growth and in bud emergence.
Early Prediction of Tumor Response: A Future Strategy for Optimizing Cancer Treatment

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is successfully capable of imaging glucose metabolism of the tumor cells. Tumor glucose metabolism using FDG-PET has a potential to distinguish viable cancer cells from those in suspension or necrotic components because the degree of tumor FDG uptake is closely associated with its prolifera‐ tion activity. There is cumulative evidence showing that reduction in FDG uptake value on the early phase after the initiation of chemotherapy more reliably predicts a favorable outcome of patients with breast cancer. Therefore, FDG-PET could help to individualize treatment and to avoid potentially ineffective chemotherapies. In this article, we discuss and illustrate the role and limitations of FDG-PET in the management of neoadjuvant chemotherapy in breast cancer.
Architecture-Aware Technique for Mapping Area-Time Efficient Custom Instructions onto FPGAs

Area-time efficient custom instructions are desirable for maximizing the performance of reconfigurable processors. Existing data path merging techniques based on resource sharing can be deployed to improve area efficiency of custom instructions. However, these techniques lead to large increase in the critical path delay. In this paper, we propose a novel strategy that takes into account the architectural constraints of the FPGA device in order to realize custom instructions with low-area delay product. The proposed strategy is based on partitioning the custom instruction data paths into a set of basic clusters such that they can be combined using a heuristic-based cluster merging process to maximize the utilization of FPGA logic blocks. Unlike the resource sharing method, the proposed cluster merging process does not maximize sharing of common resources and this leads to lesser reliance on multiplexers for implementing custom instructions. Resource sharing is only applied sparingly at the final stage to increase utilization of logic blocks. We show that the proposed technique leads to more than 34 percent, 34 percent, and 42 percent average reduction in area costs for Spartan-3, Virtex-4, and Virtex-5 architectures, respectively, when compared to optimizations achieved through commercial synthesis tool. We have also shown that the proposed technique leads to more than 18 percent, 17 percent, and 13 percent average reduction in area costs for Spartan-3, Virtex-4, and Virtex-5, respectively, when compared to results obtained using one of the most efficient resource sharing-based method reported in the literature. In addition, the proposed technique outperforms the resource sharing-based method in terms of area-delay product, with average reductions of more than 27 percent, 34 percent, and 19 percent for Spartan-3, Virtex-4, and Virtex-5, respectively.
A Knockout of the Tsg101 Gene Leads to Decreased Expression of ErbB Receptor Tyrosine Kinases and Induction of Autophagy Prior to Cell Death

The Tumor Susceptibility Gene 101 (Tsg101) encodes a multi-domain protein that mediates a variety of molecular and biological processes including the trafficking and lysosomal degradation of cell surface receptors. Conventional and conditional knockout models have demonstrated an essential requirement of this gene for cell cycle progression and cell viability, but the consequences of a complete ablation of Tsg101 on intracellular processes have not been examined to date. In this study, we employed mouse embryonic fibroblasts that carry two Tsg101 conditional knockout alleles to investigate the expression of ErbB receptor tyrosine kinases as well as stress-induced intracellular processes that are known to be associated with a defect in growth and cell survival. The conditional deletion of the Tsg101 gene in this well-controlled experimental model resulted in a significant reduction in the steady-state levels of the EGFR and ErbB2 but a stress-induced elevation in the phosphorylation of mitogen activated protein (MAP) kinases independent of growth factor stimulation. As part of an integrated stress response, Tsg101-deficient cells exhibited extensive remodeling of actin filaments and greatly enlarged lysosomes that were enriched with the autophagy-related protein LC3. The increase in the transcriptional activation and expression of LC3 and its association with Lamp1-positive lysosomes in a PI3K-dependent manner suggest that Tsg101 knockout cells utilize autophagy as a survival mechanism prior to their ultimate death. Collectively, this study shows that a knockout of the Tsg101 gene causes complex intracellular changes associated with stress response and cell death. These multifaceted alterations need to be recognized as they have an impact on defining particular functions for Tsg101 in processes such as signal transduction and lysosomal/endosomal trafficking.
ATTITUDES OF GREEK PHYSICAL EDUCATION TEACHERS TOWARD INCLUSION OF STUDENTS WITH DISABILITIES

The purpose of this study was to examine the attitudes of Greek physical education teachers toward the inclusion of students with disabilities in regular education settings and to compare the results with the findings of similar studies. The sample consisted of 93 participants, all physical education teachers working at different schools of Athens. Each subject completed the Teacher Integration Attitudes Questionnaire (Sideridis and Chandler, 1997), which assesses scores for four factors: skills, benefits, acceptance and support. The results of the study showed that the attitudes of physical education teachers toward the inclusion of students with disabilities in their regular classes are related to the level of knowledge that the teachers believe they have for the special needs conditions; in addition, they doubt that inclusion could be workable, due to the lack of appropriate support services. In the light of the findings, the concept of inclusion was further analysed.
The positive false discovery rate: a Bayesian interpretation and the q-value

Multiple hypothesis testing is concerned with controlling the rate of false positives when testing several hypotheses simultaneously. One multiple hypothesis testing error measure is the false discovery rate (FDR), which is loosely defined to be the expected proportion of false positives among all significant hypotheses. The FDR is especially appropriate for exploratory analyses in which one is interested in finding several significant results among many tests. In this work, we introduce a modified version of the FDR called the “positive false discovery rate” (pFDR). We discuss the advantages and disadvantages of the pFDR and investigate its statistical properties. When assuming the test statistics follow a mixture distribution, we show that the pFDR can be written as a Bayesian posterior probability and can be connected to classification theory. These properties remain asymptotically true under fairly general conditions, even under certain forms of dependence. Also, a new quantity called the “q-value” is introduced and investigated, which is a natural “Bayesian posterior p-value,” or rather the pFDR analogue of the p-value. 1. Introduction. When testing a single hypothesis, one is usually concerned with controlling the false positive rate while maximizing the probability of detecting an effect when one really exists. In statistical terms, we maximize the power conditional on the Type I error rate being at or below some level. The field of multiple hypothesis testing tries to extend this basic paradigm to the situation where several hypotheses are tested simultaneously. One must define an appropriate compound error measure according to the rate of false positives one is willing to encounter. Then a procedure is developed that allows one to control the error rate at a desired level, while maintaining the power of each test as much as possible. The most commonly controlled quantity when testing multiple hypotheses is the family wise error rate (FWER), which is the probability of yielding one or more false positives out of all hypotheses tested. The most familiar example of this is the Bonferroni method. If there are m hypothesis tests, each test is controlled so that the probability of a false positive is less than or equal to α/m for some chosen value of α. It then follows that the overall FWER is less than or equal to α . M any
Thespis: Actor-Based Causal Consistency

Thespis is a middleware that innovatively leverages the Actor model to implement causal consistency over an industry-standard database, whilst abstracting complexities for application developers behind a REST open-protocol interface. Our evaluation considers correctness, performance and scalability aspects. We also run empirical experiments using YCSB to show the efficacy of the approach for a variety of workloads.