Miracle-dz/UniFAR-FTUs huggingface dataset:
Inefficient Translocation of Preproinsulin Contributes to Pancreatic β Cell Failure and Late-onset Diabetes*

Background: Preproinsulin signal peptide mutations have been linked to human diabetes. Results: Preproinsulin mutants fail to be fully translocated across the endoplasmic reticulum membrane, accumulate in the cytosol, and lead to β cell death. Conclusion: Cytosolic preproinsulin accumulation contributes to β cell failure. Significance: This reveals a novel pathogenesis of diabetes associated with inefficient preproinsulin translocation and cytosolic accumulation. Among the defects in the early events of insulin biosynthesis, proinsulin misfolding and endoplasmic reticulum (ER) stress have drawn increasing attention as causes of β cell failure. However, no studies have yet addressed potential defects at the cytosolic entry point of preproinsulin into the secretory pathway. Here, we provide the first evidence that inefficient translocation of preproinsulin (caused by loss of a positive charge in the n region of its signal sequence) contributes to β cell failure and diabetes. Specifically, we find that, after targeting to the ER membrane, preproinsulin signal peptide (SP) mutants associated with autosomal dominant late-onset diabetes fail to be fully translocated across the ER membrane. The newly synthesized, untranslocated preproinsulin remains strongly associated with the ER membrane, exposing its proinsulin moiety to the cytosol. Rather than accumulating in the ER and inducing ER stress, untranslocated preproinsulin accumulates in a juxtanuclear compartment distinct from the Golgi complex, induces the expression of heat shock protein 70 (HSP70), and promotes β cell death. Restoring an N-terminal positive charge to the mutant preproinsulin SP significantly improves the translocation defect. These findings not only reveal a novel molecular pathogenesis of β cell failure and diabetes but also provide the first evidence of the physiological and pathological significance of the SP n region positive charge of secretory proteins.
An experimental framework for evaluation of facial feature extraction methods

Facial feature extraction is one of the hottest research topics in pattern recognition. Scholars have proposed numerous facial feature extraction methods based on various discriminant criteria, models, and algorithms. Each method has its own advantages and shortcomings. Unfortunately, till now there is no sound theoretical framework to evaluate their total performance. People have to resort to their experimental results. Since recognition accuracies and computational times of a particular facial feature extraction method in a certain simulation experiment are heavily depend on many factors such as, face image database, number of training samples per class, type of cross-validation, classifier, and parameter of the classifier used in the experiment. Thus, experimental design pays a key role in evaluation of their performance. In this paper we propose an experimental framework which can be used as a platform for a relatively fair comparison among facial feature extraction methods.
Space-Time Assumptions Behind NP-Hardness of Propositional Satisfiability

For some problems, we know feasible algorithms for solving them. Other computational problems (such as propositional satisfiability) are known to be NP-hard, which means that, unless P=NP (which most computer scientists believe to be impossible), no feasible algorithm is possible for solving all possible instances of the corresponding problem. Most usual proofs of NP-hardness, however, use Turing machine – a very simplified version of a computer – as a computation model. While Turing machine has been convincingly shown to be adequate to describe what can be computed in principle, it is much less intuitive that these oversimplified machine are adequate for describing what can be computed effectively; while the corresponding adequacy results are known, they are not easy to prove and are, thus, not usually included in the textbooks. To make the NP-hardness result more intuitive and more convincing, we provide a new proof in which, instead of a Turing machine, we use a generic computational device. This proof explicitly shows the assumptions about spacetime physics that underlie NP-hardness: that all velocities are bounded by the speed of light, and that the volume of a sphere grows no more than polynomially with radius. If one of these assumptions is violated, the proof no longer applies; moreover, in such space-times we can potentially solve the satisfiability problem in polynomial time. 1 Formulation of the Problem General problem. Which problems can be solved in feasible time and which cannot? To answer this question, it is necessary to formally describe which algorithms are feasible, what is a problem, and how can we know that a problem cannot be solved by a feasible algorithm. Let us recall how this is done in theory of computation; for details, see, e.g., [2, 4, 7]. Feasibility: a brief reminder. Many algorithms are feasible; for example, most algorithms whose computation time is bounded by a square or a cube of
Noncommutative Geometry and Matrix Theory: Compactification on Tori

We study toroidal compactification of Matrix theory, using ideas and results of noncommutative geometry. We generalize this to compactification on the noncommutative torus, explain the classification of these backgrounds, and argue that they correspond in supergravity to tori with constant background three-form tensor field. The paper includes an introduction for mathematicians to the IKKT formulation of Matrix theory and its relation to the BFSS Matrix theory.
Differential expression of αB-crystallin causes maturationdependent susceptibility of oligodendrocytes to oxidative stress

Oligodendrocyte precursor cells (OPCs) are most susceptible to oxidative stress in the brain. However, the cause of differences in susceptibility to oxidative stress between OPCs and mature oligodendrocytes (mOLs) remains unclear. Recently, we identified in vivo that αB-crystallin (aBC) is expressed in mOLs but not in OPCs. Therefore, we examined in the present study whether aBC expression could affect cell survival under oxidative stress induced by hydrogen peroxide using primary cultures of OPCs and mOLs from neonatal rat brains. Expression of aBC was greater in mOLs than in OPCs, and the survival rate of mOLs was significantly higher than that of OPCs under oxidative stress. Suppression of aBC by siRNA transfection resulted in a decrease in the survival rate of mOLs under oxidative stress. These data suggest that higher susceptibility of OPCs than mOLs to oxidative stress is due, at least in part, to low levels of aBC expression. [BMB Reports 2013; 46(10): 501-506]
Voice over application-level multicast

In this paper, we present a thorough and realistic analysis of voice (i.e. audio conferencing) over application-level multicast (ALM). Through flexibility and ease-of-deployment, ALM is a compelling alternative group-communication technique to IP multicast-which has yet to see wide-scale deployment in the Internet. However, proposed ALM techniques suffer from inherent latency inefficiencies, which we show, through realistic simulation and exploration of perceived quality in multi-party conversation, to be greatly problematic for the realisation of truly-scalable audio-conferencing systems over ALM. By incorporating talkspurt data from a large and detailed corpus of multi-party conversation, and through using network-simulation techniques based on actual Internet latency measurements, we develop our previous work on the application-level network audio-conferencing (ALNAC) routing protocol into a thorough analysis of the problem, leading to a novel model for assessing the perceptual quality of multi-party conversation and to novel techniques for speaker prediction. We show that through adaptation to conversational patterns, the ALNAC protocol can achieve perceptual quality for large-scale audio conferencing that, with little cost to each end-system node, is comparable to IP multicast
Direct tunneling gate leakage current in transistors with ultrathin silicon nitride gate dielectric

We present a study on the characterization and modeling of direct tunneling gate leakage current in both N- and P-type MOSFETs with ultrathin silicon nitride (Si/sub 3/N/sub 4/) gate dielectric formed by the jet-vapor deposition (JVD) technique. The tunneling mechanisms in the N- and PMOSFETs were clarified. The electron and hole tunneling masses and barrier potentials for the different tunneling mechanisms mere extracted from measured data using a new semi-empirical model. This model was used to project the scaling limits of the JVD Si/sub 3/N/sub 4/ gate dielectric based on the supply voltages for the various technology nodes and the maximum tolerable direct tunneling gate current for high-performance and low-power applications.
Greater than 2-bits/cell MLC storage for ultra high density phase change memory using a novel sensing scheme

Multi-level-cell (MLC) is a critical technology to achieve low bit cost for phase change memory. However, resistance drift is an intrinsic material property that kills memory window and imposes formidable challenges for MLC. In this work, we report a radically different sensing concept that exploits the non-linear R-V characteristics of PCM that can easily accommodate 8 resistance levels in three independent 10X sensing windows (100KΩ~1MΩ × 3) all on same read speed. Each sensing window only needs to store 2~3 resistance levels instead of 8 levels needed in conventional MLC method, thus can tolerate resistance drift without closing the memory windows. A maximum of 16 levels of MLC is demonstrated on a 256Mb chip that is suitable for 4-bits/cell application.
Coordinated Versus Decentralized Exploration In Multi-Agent Multi-Armed Bandits

In this paper, we introduce a multi-agent multiarmed bandit-based model for ad hoc teamwork with expensive communication. The goal of the team is to maximize the total reward gained from pulling arms of a bandit over a number of epochs. In each epoch, each agent decides whether to pull an arm, or to broadcast the reward it obtained in the previous epoch to the team and forgo pulling an arm. These decisions must be made only on the basis of the agent’s private information and the public information broadcast prior to that epoch. We first benchmark the achievable utility by analyzing an idealized version of this problem where a central authority has complete knowledge of rewards acquired from all arms in all epochs and uses a multiplicative weights update algorithm for allocating arms to agents. We then introduce an algorithm for the decentralized setting that uses a value-ofinformation based communication strategy and an exploration-exploitation strategy based on the centralized algorithm, and show experimentally that it converges rapidly to the performance of the centralized method.
Review Paper: What Evidence Supports the Use of Computerized Alerts and Prompts to Improve Clinicians' Prescribing Behavior?

Alerts and prompts represent promising types of decision support in electronic prescribing to tackle inadequacies in prescribing. A systematic review was conducted to evaluate the efficacy of computerized drug alerts and prompts searching EMBASE, CINHAL, MEDLINE, and PsychINFO up to May 2007. Studies assessing the impact of electronic alerts and prompts on clinicians' prescribing behavior were selected and categorized by decision support type. Most alerts and prompts (23 out of 27) demonstrated benefit in improving prescribing behavior and/or reducing error rates. The impact appeared to vary based on the type of decision support. Some of these alerts (n = 5) reported a positive impact on clinical and health service management outcomes. For many categories of reminders, the number of studies was very small and few data were available from the outpatient setting. None of the studies evaluated features that might make alerts and prompts more effective. Details of an updated search run in Jan 2009 are included in the supplement section of this review.
Planning and Dealing: Piecemeal Land Controls as a Problem of Local Legitimacy

PAGE I. PLAN JURISPRUDENCE AS REFORM . 848 A. The Assertion of Judicial Control over Piecemeal Changes . 848 L Traditional Planning Law and Plan Jurisprudence. 848 2. The Fasano Case . 851 B. The Federalist No. 10 and Local Land Decisions . 853 C. A Historical Excursion into Plan Jurisprudence: Of Variances and Referenda . 857 L Variances and the Quasi-Judicialization of Land Use Decisions . 857 2. Referenda and the Problem of Controlling Majoritarian Rule . 863
Visualization of information processing in the human brain : recent advances in MEG and functional MRI

Hardbound. This book is the first to present in-depth evaluation of MEG andfMRI and their integration in basic and clinical brainresearch.With 44 chapters written by well-known experts intheir respective fields, this volume is divided into 6 sectionsto thematically highlight the topics that have been most activelystudied in recent years.Opening with the potential of the twomethods, the chapters proceed to discuss sensory, cognitive andmovement-related processings, to pathophysiological processing, and finally to discuss instrumentation, modeling and dataanalysis in MEG.The book will be useful to a variety ofinterdisciplinary professionals, such as neurobiological andbiomedical scientists, neurologists, psychiatrists, neurosurgeons, psychologists, physicists and engineer
The Human Vaginal Bacterial Biota and Bacterial Vaginosis

The bacterial biota of the human vagina can have a profound impact on the health of women and their neonates. Changes in the vaginal microbiota have been associated with several adverse health outcomes including premature birth, pelvic inflammatory disease, and acquisition of HIV infection. Cultivation-independent molecular methods have provided new insights regarding bacterial diversity in this important niche, particularly in women with the common condition bacterial vaginosis (BV). PCR methods have shown that women with BV have complex communities of vaginal bacteria that include many fastidious species, particularly from the phyla Bacteroidetes and Actinobacteria. Healthy women are mostly colonized with lactobacilli such as Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners, though a variety of other bacteria may be present. The microbiology of BV is heterogeneous. The presence of Gardnerella vaginalis and Atopobium vaginae coating the vaginal epithelium in some subjects with BV suggests that biofilms may contribute to this condition.
Intelligent provisioning using ontology for ubiquitous computing

Ubiquitous computing environment, as a new paradigm of the digital information era, has been introduced to respond to rapid changes in society and culture. Home and abroad studies in recent years have made rapid progress in the ubiquitous environment, and it had influence on various fields such as intelligent context aware systems. Today, technology research around the world competes for the preoccupancy of the core technology as well as the development of technology for providing context aware system more intelligent, more sophisticated. Research in recent is underway the implementation of intelligent provisioning system using the ontology. Provisioning means to prepare in advance by resources needed at the request to be able to use fast and reliable service according to user's request. Erstwhile provisioning system did not providing a personalized service that provides the service after context aware. Accordingly, there is a need for studies of intelligent context aware provisioning technique considering environments and context necessary to user. In this paper, in order to provide a service that is optimized for the needs of the user, propose an ontology-based intelligent provisioning service method taking into account the usage patterns and the context of the user. The proposed system is recognized the status of the user and demonstrated a process of reasoning techniques for fit service. And it is possible to the expansion of intelligence.
Echinocandins: a new class of antifungal.

The echinocandins represent the first new antifungal drug class introduced for more than 15 years. They inhibit the synthesis of β - D -glucan in fungal cell walls. Their strengths include low toxicity, rapid fungicidal activity against most isolates of Candida spp. and predictable favourable kinetics allowing once a day dosing. In addition to Candida spp. , their inhibitory spectrum includes Aspergillus spp. and Pneumocystis carinii , but not Cryptococcus neoformans . The first licensed echinocandin product is caspofungin
Japanese plums (Prunus salicina Lindl.) and phytochemicals--breeding, horticultural practice, postharvest storage, processing and bioactivity.

Previous reviews of plum phytochemical content and health benefits have concentrated on the European plum, Prunus domestica L. However, the potential bioactivity of red- and dark red-fleshed Japanese plums, Prunus salicina Lindl. , so-called blood plums, appears to warrant a significant increase in exposure, as indicated in a recent review of the whole Prunus genus. Furthermore, Japanese plums are the predominant plum produced on an international basis. In this review the nutrient and phytochemical content, breeding, horticultural practice, postharvest treatment and processing as well as bioactivity (emphasising in vivo studies) of Japanese plum are considered, with a focus on the anthocyanin content that distinguishes the blood plums.
Toward a Unified Theory of Depression among Urban African American Youth: Integrating Socioecologic, Cognitive, Family Stress, and Biopsychosocial Perspectives

With the recent increase in empirical studies investigating depression among urban African American youth comes the need to refine and integrate theoretical perspectives that address culture-specific etiologic mechanisms and developmental trajectories. The purpose of this article is to review four theories of depression relevant to the study of African American adolescents and to offer suggestions for the integration of theories to enhance the culturally relevant design of empirical investigations. It is argued that all four theories—socioecologic, cognitive, family stress, and biopsychosocial—center on the role of oppression in the development of urban Black youth and that an integrated theory would assume this underlying construct as its core focus. A macrotheoretical model synthesizing the four theories is presented, with oppression identified as the key catalyst in the chain of factors that might ultimately lead to adolescent depression. Implications for further theory development and empirical research on adolescent depression are discussed.
Phonological Awareness: From Research to Practice

Phonological Awareness Defined. Theoretical Background. Phonological Awareness Development. A Phonological Deficit Hypothesis for Dyslexia. Children with Spoken Language Impairment. Phonological Awareness Assessment. Phonological Awareness Intervention: Guiding Principles. Phonological Awareness Intervention: Instructional Frameworks. Gillon Clendon, Cupples, Flynn, Lacono, Schmidtke, Yoder, Young, Phonological Awareness Development in Children with Physical, Sensory, or Intellectual Impairment. Concluding Remarks. Appendix: English Phonemes.
Entry of B Cell Receptor into Signaling Domains Is Inhibited in Tolerant B Cells

Signal transduction through the B cell antigen receptor (BCR) is altered in B cells that express a receptor that recognizes self-antigen. To understand the molecular basis for the change in signaling in autoreactive B cells, a transgenic model was used to isolate a homogeneous population of tolerant B lymphocytes. These cells were compared with a similar population of naive B lymphocytes. We show that the BCR from naive B cells enters a detergent-insoluble domain of the cell within 6 s after antigen binding, before a detectable increase in BCR phosphorylation. This fraction appears to be important for signaling because it is enriched for lyn kinase but lacks CD45 tyrosine phosphatase and because the BCR that moves into this domain becomes more highly phosphorylated. Partitioning of the BCR into this fraction is unaffected by src family kinase inhibition. Tolerant B cells do not efficiently partition the BCR into the detergent-insoluble domain, providing an explanation for their reduced tyrosine kinase activation and calcium flux in response to antigen. These results identify an early, regulated step in antigen receptor signaling and self-tolerance.
A novel hybrid rendering approach to soft tissue cutting in surgical simulation

As a feasible alternative approach, computer-based surgical simulators have been developed over the past few decades to enhance traditional surgical training. But most surgery simulators still suffer from stability and efficiency problems when simulating complex surgical procedures like cutting with respect to the graphical rendering. For naturalistic rendering, the response of soft tissue during the cutting operation should be cautiously verified, analyzed and simulated. In this paper, a novel hybrid rendering approach to tracheotomy simulation combining traditional mesh-based rendering with emerging point-based rendering is proposed, where mesh-based rendering algorithm is applied on the non-surgical area while point-based rendering algorithm is applied on the surgical area. Central to our method is different appropriate rendering methods applied to the two regions respectively, resulting in a contribution to the speed up of the calculation. The approach has been integrated into our virtual tracheotomy surgery training prototype system. The details and results of experiments indicate that our hybrid rendering approach is suitable in the design of surgical simulators. It can keep the visual reality while significantly increasing the efficiency and stability for simulation of soft-tissue's cutting.