Miracle-dz/UniFAR-FTUs huggingface dataset:
Cdk5 activity in the brain – multiple paths of regulation

ABSTRACT Cyclin dependent kinase-5 (Cdk5), a family member of the cyclin-dependent kinases, plays a pivotal role in the central nervous system. During embryogenesis, Cdk5 is indispensable for brain development and, in the adult brain, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation. However, Cdk5 activity becomes deregulated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, which leads to neurotoxicity. Therefore, precise control over Cdk5 activity is essential for its physiological functions. This Commentary covers the various mechanisms of Cdk5 regulation, including several recently identified protein activators and inhibitors of Cdk5 that control its activity in normal and diseased brains. We also discuss the autoregulatory activity of Cdk5 and its regulation at the transcriptional, post-transcriptional and post-translational levels. We finally highlight physiological and pathological roles of Cdk5 in the brain. Specific modulation of these protein regulators is expected to provide alternative strategies for the development of effective therapeutic interventions that are triggered by deregulation of Cdk5.
Cyclosporine A for neuroprotection: establishing dosing guidelines for safe and effective use

Numerous neuroprotective compounds have been investigated to ameliorate secondary changes and the progression of injury after the primary insult in traumatic brain injury (TBI). This cascade of events is complex and difficult to abate once initiated following the primary injury. The clinical consequences of this secondary injury are unpredictable and often permanently incapacitating. Cyclosporine A (CsA) interrupts the endogenous mediators of secondary insult through inhibition of the mitochondrial permeability transition pore and prevention of subsequent mitochondrial dysfunction. This drug may have a role in neuroprotection but has several pharmacologic effects that must be considered when using it in the TBI population. This review discusses the physiologic responses following TBI that may affect CsA efficacy and safety when used for neuroprotective indications. So far, CsA seems to be safe in the TBI population. The role of CsA after acute TBI will be better defined after the completion of upcoming planned clinical trials.
Tonotopic multi-layered perceptron: a neural network for learning long-term temporal features for speech recognition

We have been reducing word error rates (WER) on conversational telephone speech (CTS) tasks by capturing long-term (/spl sim/500ms) temporal information using multilayered perceptrons (MLP). In this paper we experiment with an MLP architecture called tonotopic MLP (TMLP), incorporating two hidden layers. The first of these is tonotopically organized: for each critical band, there is a disjoint set of hidden units that use the long-term energy trajectory as the input. Thus, each of these subsets of hidden units learns to discriminate single band energy trajectory patterns. The rest of the layers are fully connected to their inputs. When used in combination with an intermediate-term (/spl sim/100ms) MLP system to augment standard PLP features, the TMLP reduces the WER on the 2001 Nist Hub-5 CTS evaluation set (Eval2001) by 8.87% relative. We show some practical advantages over our previous methods. We also report results from a series of experiments to determine the best ranges of hidden layer sizes and total parameters with respect to the number of training patterns for this task and architecture.
Implicitness as a Guiding Principle in Machine Translation

There is an extcnlal fitctor with vcry substantial conscquenec,,; lot the internal design o1" machine translation systems: exteno aibility. When a machine mmslation system has to allow lbr adding m'bitrary soumc m~d target languages without each time adaptint; the atmady existing pa~ts of the system, tim Reed arises for at careftflly defiv.ed interface ~;tr,ctm'e to which modules R)r addithmal lauguagcs may bc linked. The design that besl lneets these requirements is the pivot or inter l ingual appmac, h, since it~ such a system them is only a single interface whi,:b gives access it) all tim languages already included in {itc system.
Role of nitric oxide and peroxynitrite in apoptosis - relation to endonuclease activity

Apoptosis is a form of cell death utilized physiologically to maintain tissue homeostasis, as well as in response to various toxic and inflammatory stimuli or anticancer drugs. Since the process of apoptosis is followed by phagocytosis, the cleavage of DNA to low molecular weight material may serve as a protective function limiting the probability of gene transfer to the nuclei of viable neighbor cells. Many different endonucleases have been proposed as candidates responsible for the internucleosomal cleavage of the genomic DNA observed during apoptosis. The main effect was attributed to the alkaline DNase I (Mg 2+ and caspase-dependent) and acid-DNase II. It was also documented that both of them contain a potential protease (caspase) cleavage site, but they can be also activated upon the influence of other "fragmentation factors", including nitric oxide (NO). The complexity of biological effects induced by NO may be the result of the cell redox state changes, due to its potential interaction with superoxide. The apoptotic effect of both, nitric oxide (NO) and peroxynitrite (ONOO) are dose-dependent and cell-specific may point out the existence of possible "inducible" form of endonuclease.
Covert Channels Parameters Evaluation Using the Information Theory Statements

This paper describes a packet length network covert channel and violators possibilities to build such a channel. Then the technique to estimate and limit the capacity of such channel is presented. The calculation is based on the information theory statements and helps to diminish the negative effects of covert channels in information systems, e.g. data leakage.
The impact of modifying attentional bias on vulnerability to pain

The preferential deployment of attention to noxious versus benign information in the internal and external environment - “attentional bias” - is thought to confer vulnerability to pain. The current thesis tested this putative mechanism by modifying the bias using the visual-probe task (attentional bias modification; ABM) and examining effects of this experimental manipulation on attentional bias and critical pain outcomes. Drawing on recent evidence that the impact of pain on attentional bias varies across its temporal components, this thesis additionally tested the component stages of attentional bias implicated in pain experience by manipulating the duration for which visual-probe stimuli were presented. Study 1 confirmed that both rapid and slower attentional orienting was biased in individuals with persistent musculoskeletal pain. Results from Studies 2 and 3 indicated that acute experimentally-induced pain modified the faster bias and that participants whose fast bias was modified had reduced vulnerability to cold pressor pain, in comparison with control participants. This suggested that mechanisms of initial orienting were more active in the acute pain experience. Studies 4 and 5 revealed that concurrently retraining fast and slower bias was optimal for persistent musculoskeletal pain. Results of a systematic review and meta-analysis indicated a small overall statistical effect of ABM on pain severity. Critically, however, whereas ABM had been effective at reducing acute pain severity, this was not the case for persistent pain. Overall, these findings suggest that the faster bias influenced vulnerability to acute pain, indicating a potential therapeutic target for future research. However, retraining the earlier stage of attention alone did not influence persistent pain outcomes, where there appeared to be greater involvement of the slower bias. It was concluded that not only could attentional bias influence critical pain outcomes, but that the optimal timings may vary across temporal pain classifications.
A study of topic similarity measures

In this poster we describe an investigation of topic similarity measures. We elicit assessments on the similarity of 10 pairs of topic from 76 subjects and use these as a benchmark to assess how well each measure performs. The measures have the potential to form the basis of a predictive technique, for adaptive search systems. The results of our evaluation show that measures based on the level of correlation between topics concords most with general subject perceptions of search topic similarity.
Application-level isolation to cope with malicious database users

System protection mechanisms such as access controls can be fooled by authorized but malicious users, masqueraders, and misfeasors. Intrusion detection techniques are therefore used to supplement them. The capacity of these techniques, however is limited: innocent users may be mistaken for malicious ones while malicious users stay at large. Isolation is a method that has been applied to protect systems from damage while investigating further. This paper proposes the use of isolation at an application level to gain its benefits while minimizing loss of resources and productive work in the case of incidents later deemed innocent. We describe our scheme in the database context. It isolates the database transparently from further damage by users suspected to be malicious, while still maintaining continued availability for their transactions. Isolation is complicated by the inconsistencies that may develop between isolated database versions. We present both static and dynamic approaches to identify and resolve conflicts. Finally, we give several examples of applications in which the isolation scheme should be worthwhile and be able to achieve good performance.
Evaluation of hypermedia application development and management systems

In this paper we propose and study a framework for evaluating Hypermedia Application Development and Management Systems (HADMS) in relation to specific application requirements. We address the need for HADMS capable to efficiently support the main users involved in the life cycle of hypermedia applications, namely designers, programmers/implementers, authors/administrators and end-users. A HADMS consists of a hypermedia application development and management methodology and the respective environment. In this work, we propose and classify a set of evaluation criteria. These are mainly imposed by real life development and the need to support forthcoming, or next generation, features for hypermedia applications. We also introduce a simple framework for a comparative evaluation of HADMS. Furthermore, we demonstrate the use of the criteria and the framework proposed, for the case of three real-life applications. A representative set of seven HADMS is selected and the evaluation of these systems is carried out, leading to some useful conclusions and suggestions for future work.
Overconfidence and Occupational Choice

A statistical theory of overconfidence is proposed and applied to the issue of occupational choice. Individuals who can choose whether to engage in an activity or not must estimate their performance. The estimates have error and that error has positive expectation among those who engage in the activity. As a result, an unbiased ex ante estimate of performance in an occupatoin results in an ex post biased estimate of ability among those enter. The statistical theory of overconfidence provides a number of testable implications, most significant of which is that overconfidence should be more prevalent in occupations where estimates of ability are noisier. This and other implications are tested and found to hold using the Current Population Survey and Panel Study of Income Dynamics data.
Draft Genome Sequence of a Thermophilic Member of the Bacillaceae, Anoxybacillus flavithermus Strain Kn10, Isolated from the Kan-nawa Hot Spring in Japan

ABSTRACT Here, we report the draft genome sequence of the Anoxybacillus flavithermus Kn10 strain (NBRC 109594), isolated from a water drain of the Kan-nawa Hot Spring in Japan. The draft genome sequence is composed of 90 contigs for 2,772,624 bp with 41.6% G+C content and contains 2,883 protein-coding genes and 80 tRNA genes.
Adapt, move or die – how will tropical coral reef fishes cope with ocean warming?

Previous studies hailed thermal tolerance and the capacity for organisms to acclimate and adapt as the primary pathways for species survival under climate change. Here we challenge this theory. Over the past decade, more than 365 tropical stenothermal fish species have been documented moving poleward, away from ocean warming hotspots where temperatures 2–3 °C above long‐term annual means can compromise critical physiological processes. We examined the capacity of a model species – a thermally sensitive coral reef fish, Chromis viridis (Pomacentridae) – to use preference behaviour to regulate its body temperature. Movement could potentially circumvent the physiological stress response associated with elevated temperatures and may be a strategy relied upon before genetic adaptation can be effectuated. Individuals were maintained at one of six temperatures (23, 25, 27, 29, 31 and 33 °C) for at least 6 weeks. We compared the relative importance of acclimation temperature to changes in upper critical thermal limits, aerobic metabolic scope and thermal preference. While acclimation temperature positively affected the upper critical thermal limit, neither aerobic metabolic scope nor thermal preference exhibited such plasticity. Importantly, when given the choice to stay in a habitat reflecting their acclimation temperatures or relocate, fish acclimated to end‐of‐century predicted temperatures (i.e. 31 or 33 °C) preferentially sought out cooler temperatures, those equivalent to long‐term summer averages in their natural habitats (~29 °C). This was also the temperature providing the greatest aerobic metabolic scope and body condition across all treatments. Consequently, acclimation can confer plasticity in some performance traits, but may be an unreliable indicator of the ultimate survival and distribution of mobile stenothermal species under global warming. Conversely, thermal preference can arise long before, and remain long after, the harmful effects of elevated ocean temperatures take hold and may be the primary driver of the escalating poleward migration of species.
Spatiotemporal analysis of the cortical sources of the steady‐state visual evoked potential

This study aimed to characterize the neural generators of the steady‐state visual evoked potential (SSVEP) to repetitive, 6 Hz pattern‐reversal stimulation. Multichannel scalp recordings of SSVEPs and dipole modeling techniques were combined with functional magnetic resonance imaging (fMRI) and retinotopic mapping in order to estimate the locations of the cortical sources giving rise to the SSVEP elicited by pattern reversal. The time‐varying SSVEP scalp topography indicated contributions from two major cortical sources, which were localized in the medial occipital and mid‐temporal regions of the contralateral hemisphere. Colocalization of dipole locations with fMRI activation sites indicated that these two major sources of the SSVEP were located in primary visual cortex (V1) and in the motion sensitive (MT/V5) areas, respectively. Minor contributions from mid‐occipital (V3A) and ventral occipital (V4/V8) areas were also considered. Comparison of SSVEP phase information with timing information collected in a previous transient VEP study (Di Russo et al. [ 2005 ] Neuroimage 24:874–886) suggested that the sequence of cortical activation is similar for steady‐state and transient stimulation. These results provide a detailed spatiotemporal profile of the cortical origins of the SSVEP, which should enhance its use as an efficient clinical tool for evaluating visual‐cortical dysfunction as well as an investigative probe of the cortical mechanisms of visual‐perceptual processing. Hum. Brain Mapp, 2007. © 2006 Wiley‐Liss, Inc.
Exploring standardisation and knowledge networking processes in transnational human resource management.

Purpose – It is argued that a key step in becoming a “transnational” company is to implement transnational HRM (THRM). However, what is meant by THRM and how can it be assessed? The purpose of this paper is to develop the characteristics of THRM along two dimensions: standardisation and knowledge networking, in contrast to many existing studies which focus on IHRM strategies and structures. Standardisation and knowledge networking are to be examined at both the meta and operational levels.Design/methodology/approach – The paper is based on two case studies of major German MNCs, both with significant operations in Spain and the UK. Data were collected by means of semi‐structured interviews with senior managers, HR managers and labour representatives.Findings – The findings show that THRM can be operationalised using knowledge networking and standardisation on a meta level, in terms of principles, and at an operational level in terms of practices. The two firms show differences in the process and intensity .
Multiple myeloma cancer stem cells

Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contributes to disease relapse, but the mechanisms of drug resistance have not been fully understood. The major signaling pathways involved in the regulation of self-renewal and differentiation of MMSCs include Hedgehog (Hh), Wingless (Wnt), Notch and PI3K/Akt/mTOR. However, the precise role of these signaling pathways needs to be clarified. It has been reported that the microRNA profile of MMSCs is remarkably different than that of non-MMSCs. Therefore, the search for targeting MMSCs has also been focused on microRNAs. Complex and mutual interactions between the MMSC and the surrounding bone marrow (BM) microenvironment sustain self-renewal and survival of MMSC. However, the required molecules for the interaction of the MMSC and the surrounding BM microenvironment need to be further identified. In this review, we summarize the current state of knowledge of MMSCs regarding their phenotype, mechanisms of drug resistance, signaling pathways that regulate MMSCs self-renewal and differentiation, abnormal microRNAs expression, and their interactions with the BM microenvironment.
A study measuring the effect of high serum triglyceride and cholesterol on glucose elevation in human serum.

OBJECTIVES The purpose of this study is to further confirm the results documented in previous studies and to test the hypothesis of the presence of any correlation and if found, the regression nature of such correlation between triglyceride and glucose levels in one hand and cholesterol and glucose levels in the other hand. METHODS Samples were collected between March and August 2009 from 438 of both males and females from two patient groups; a) non-diabetic patients, b) non-insulin dependent type II diabetic patients. The patients' serum glucose; cholesterol and triglyceride were simultaneously determined. A comparison study was conducted on the effect of the elevated level of each of the parameters (Cholesterol and Triglyceride) on glucose elevation. RESULTS The results showed that there was a significant difference in the number of cases with high glucose values >110 mg/dl among the three different study groups. There was a significant difference in the number of cases with glucose values >110 mg/dl between the two different study groups; 1) triglyceride <151 mg/dl and cholesterol >201 mg/dl, 2) triglyceride >151 mg/dl and cholesterol>201 mg/dl. CONCLUSION The elevation in triglyceride but not cholesterol has the same effect of both triglyceride and cholesterol elevation together on the association with increasing levels of high glucose in blood.
Development of Usability Criteria for E-Learning Content Development Software.

Revolutionary advancements have been observed in e-learning technologies though an amalgamated evaluation methodology for new generation e-learning content development tools is not available. The evaluation of educational software for online use must consider its usability and as well as its pedagogic effectiveness. This study is a first step towards the definition of criteria for evaluating e-learning tools. A preliminary user study involving a group of pre-service instructional designers, observed during their interaction with e-learning tools, is reported. Throughout the study, specific usability attributes of these e-learning tools were identified. Participants were assigned to rate the importance of functional and pedagogical competences proposed during the criteria development phase. The findings of the study revealed 31 evaluation criteria under the headings of technical, media, and assessment competences. Among the groups of benchmarks proposed and rated by the users, assessment was considered as the most important one while technical and media features were even.The following step was actual implemention of the usability criteria into evaluation of fifteen leading software used in e-learning across the world. Mostly, tools were observed as having limitations in terms of capabilities. Comparing to the other software, Captivate, Softchalk, and Lectora were regarded as outstanding tools by the participants. Following the discussion on the limitations of the study, some implications for further research were proposed.
Surface Zn-proteinase as a molecule for defense of Leishmania mexicana amazonensis promastigotes against cytolysis inside macrophage phagolysosomes

The role of the surface membrane Zn-proteinase in protecting the cellular integrity of the macrophage parasite Leishmania mexicana amazonensis from intraphagolysosomal cytolysis was studied. These cells lose their infectivity to host macrophages after prolonged cultivation in axenic growth medium. The virulent and attenuated variants of the parasite cells were cloned. Failure of these attenuated parasite cells to survive inside macrophage phagolysosomes is associated with 20- to 50-fold reduction in the expression of surface gp63 protein. In situ inhibition of gp63 proteinase activity inside Leishmania-infected macrophage phagolysosomes with targeted delivery of an inhibitor of gp63 proteinase activity, 1,10-phenanthroline, selectively eliminated intracellular Leishmania amastigotes, further suggesting the importance of this proteinase in phagolysosomal survival of the parasite. An upstream sequence (US) of the gp63 gene was cloned in front of the bacterial chloramphenicol acetyltransferase (CAT) gene in plasmid pCATbasic. Transfection of L. mexicana amazonensis cells with this recombinant plasmid showed that expression of the CAT gene from this US is 15- to 20-fold higher in virulent clones than in avirulent clones of the parasite. Band shift analysis with the cloned US also showed that binding of protein(s) was 15- to 20-fold higher in virulent cell extract than in avirulent cell extract. Coating of attenuated cells or liposomes with proteolytically active gp63 protects them from degradation inside macrophage phagolysosomes. These results suggest a novel mechanism of survival of this phagolysosomal parasite with the help of its surface Zn-proteinase.