Miracle-dz/UniFAR-FTUs huggingface dataset:
HMG-CoA reductase inhibitors activate the unfolded protein response and induce cytoprotective GRP78 expression.

AIMS Since apoptosis of macrophages induced by stress to the endoplasmic reticulum (ER) contributes to advanced atherosclerotic lesions, we sought to understand the effects of statins on the unfolded protein response (UPR). METHODS AND RESULTS We used pharmacological, biochemical, and siRNA (small interfering ribonucleic acid) approaches to determine the signalling cascades of statin-induced 78 kDa glucose-regulated protein (GRP78) gene transcription and its role in cytoprotection. Exposure of RAW264.7 macrophages to statins increased the expression of GRP78, activating transcription factor 6, X box protein-1, and phosphorylated eukaryotic translation initiation factor 2alpha, while it had no effect on CCAAT/enhancer binding protein-homologous protein. GRP78 induction was abolished by co-treatment with mevalonate and 1,2-bis(o-aminophenoxy)ethane-N, N, N',N'-tetraacetic acid, indicating the involvement of both 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase-dependent and -independent mechanisms. Studies on promoter activity measurements indicated that phosphoinositide turnover, cellular homologue of v-src (c-Src), protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and p38 are involved in upregulating GRP78 gene transcription. We also observed that elevation of intracellular Ca(2+) and interruption of small G proteins are two bifurcated but cooperative signalling pathways for c-Src activation, leading to downstream activation of phospholipase C, PKC, ERK, and p38. Functionally we demonstrated that fluvastatin could protect macrophages from hypoxia-induced cell death through GRP78 induction. CONCLUSION We demonstrate a novel action of statins of inducing a cytoprotective UPR, providing new insights into the clinical potential of statins for ameliorating ER stress-related diseases.
The New Synthesis in Moral Psychology

People are selfish, yet morally motivated. Morality is universal, yet culturally variable. Such apparent contradictions are dissolving as research from many disciplines converges on a few shared principles, including the importance of moral intuitions, the socially functional (rather than truth-seeking) nature of moral thinking, and the coevolution of moral minds with cultural practices and institutions that create diverse moral communities. I propose a fourth principle to guide future research: Morality is about more than harm and fairness. More research is needed on the collective and religious parts of the moral domain, such as loyalty, authority, and spiritual purity.
Effect of pre-processors on solution quality of University Course Timetabling Problem

This paper describes the effects of pre-processors on the solution quality of the university course timetabling problem. The University Course Timetabling Problem (UCTP) is regarded as both an NP-hard and NP-complete combinatorial optimization problem and is a difficult task since many constraints are needed to be satisfied in order to obtain a feasible solution. The constraints, in this case, are related to the characteristics and regulations of the particular institution. This paper describes the effects of pre-processors which consist of four matrices on the solution quality of the university course timetabling problem as they play a critical role and have significant impact on the solution. In order to evaluate the effects of the pre-processor matrices, the fitness score which is obtained without the pre-processor matrices are tabulated and compared against the fitness score that is obtained with the pre-processor matrices. Seven neighborhood structures are implemented and the experiment is conducted using the datasets obtained from Track 3 of the ITC-2007. The result indicates that there is a significant difference in terms of the fitness score between the solutions obtained without the pre-processors and with the pre-processors, with the latter showing promising results.
A Temporal Perspective of Merger and Acquisition and Strategic Alliance Initiatives

The incorporation of a temporal perspective in merger and acquisition (M&A) and alliance research has gained increasing popularity. Since a temporal perspective focuses on the management of time and its consequences, it contributes a unique value proposition to the M&A and alliance stream of research. Over the past 30 years researchers have explored a wide variety of topics and methodological approaches. As a result, research evidence has progressed in a somewhat fragmented manner where its cumulative impact is difficult to discern. The purpose of this review is to systematically assess the underlying logic and contributions of a temporal lens for the M&A and alliance literature as well as identify core temporal constructs, mechanisms, relationships, and promising research directions. The authors’ review of 144 published articles not only catalogs the state of the art and accumulated knowledge but also identifies critical hurdles that need to be addressed to chart future research directions.
An approach to assess and compare quality of security models

System security is an important artefact. However security is typically considered only at implementation stage nowadays in industry. This makes it difficult to communicate security solutions to the stakeholders earlier and raises the system development cost, especially if security implementation errors are detected. On the one hand practitioners might not be aware of the approaches that help represent security concerns at the early system development stages. On the other hand a part of the problem might be that there exists only limited support to compare different security development languages and especially their resulting security models. In this paper we propose a systematic approach to assess quality of the security models. To illustrate validity of our proposal we investigate three security models, which present a solution to an industrial problem. One model is created using PL/SQL, a procedural extension language for SQL; another two models are prepared with SecureUML and UMLsec, both characterized as approaches for model-driven security. The study results in a higher quality for the later security models. These contain higher semantic completeness and correctness, they are easier to modify, understand, and facilitate a better communication of security solutions to the system stakeholders than the PL/SQL model. We conclude our paper with a discussion on the requirements needed to adapt the model-driven security approaches to the industrial security analysis.
Inhibition of low density lipoprotein receptor expression by long‐term exposure to phorbol ester via p38 mitogen‐activated protein kinase pathway

The proximal region −234 to (+58 bp) of low‐density lipoprotein receptor (LDLR) is responsible for its up‐regulation by sterol regulatory element binding protein (SREBP). However, the mechanism of sterol‐independent repression of LDLR has not been determined yet. In this study, we observed that there was an early induction and a later repression of LDLR by phorbol ester (PMA) in SK‐Hep1 hepatocarcinoma cells and investigated the mechanisms through which PMA repressed LDLR transcription. SK‐Hep1 cells were exposed to PMA and LDLR mRNA was evaluated by RT‐PCR and Northern blot analysis. The effect of phorbol ester on LDLR transcriptional activity was studied using transient transfection of LDLR promoter‐luciferase constructs. Overexpression of N‐SREBP‐2, a dominant positive SREBP2, did not reverse the PMA‐repressed LDLR promoter activity. Serial deletion of LDLR promoter revealed that the region between −1,563 and −1,326 was responsible for the repression. The pretreatment with SB202190, an inhibitor for p38 mitogen‐activated protein kinase pathway (p38‐MAPK), but not other signaling inhibitors, reversed the PMA‐induced repression. The 24 h‐treatment with PMA efficiently arrested the SK‐Hep1 cell cycle at G0/G1 as demonstrated by FACS analysis and decreased the 3H‐thymidine incorporation. The PMA‐induced repression of LDLR transcription may be exerted by the factor(s), not SREBP2, induced or modified by p38‐MAPK‐mediated signaling pathway and associated with cell cycle blockage. © 2005 Wiley‐Liss, Inc.
Functional Analysis of the Yeast 40 kDa Cyclophilin Cyp40 and Its Role for Viability and Steroid Receptor Regulation

We have identified and characterized a homolog of the 40 kDa cyclophilins in the budding yeast Saccharomyces cerevisiae. At the amino acid level, this novel yeast cyclophilin, termed Cyp40, is 47% identical to human cyclophilin-40. Recombinant Cyp40 produced in bacteria has a peptidyl-prolyl cis-trans isomerase activity with a catalytic efficiency (k[cat]/K[m]) of 0.5 x 10(6)M(-1)s(-1), which can be inhibited by cyclosporin A with an IC50 value of 60nM. Using a polyclonal antibody against Cyp40 we have found that Cyp40 is predominantly cytoplasmic, and that its expression is induced 3-4-fold by heat shock. Moreover, Cyp40 can be coprecipitated from yeast extracts with the cytosolic molecular chaperone Hsp90. Surprisingly, a Cyp40-deficient yeast strain is fully viable at normal and elevated temperatures. Cyp40 is also dispensable for normal regulation of vertebrate steroid receptors in yeast. While other immunophilins could conceivably compensate a Cyp40 defect, our results are compatible with the notion that immunophilins may be fortuitous partners in the biochemically established steroid receptor-Hsp90 complex.
The Value of Experience-Centred Design Approaches in Dementia Research Contexts

Experience-Centred Design (ECD) has been applied in numerous HCI projects to call attention to the particular and dialogical nature of people's experiences with technology. In this paper, we report on ECD within the context of publicly-funded, long-stay residential dementia care, where the approach helped to highlight aspects of participants' felt experience, and informed sensitive and meaningful design responses. This study contributes an extended understanding of the quality of experience and the means of making sense in dementia, as well as unpicking the potential of ECD to support enriched experience and contextual meaning-making for people with dementia. Finally, we delineate what it is about Experience-Centred Design that differentiates the approach from other often-used approaches in designing in dementia contexts: 1) explorative thinking, 2) working within 'cuttings-out of time and space', 3) careful yet expressive methodology and documentation, and 4) working together to imagine futures. We end with considerations of how the contributions of this research may extend to other experience-centred projects in challenging settings.
Un estudio experimental del razonamiento cotidiano en tareas de syllogisms una aproximación pragmática

The purpose of thLr paper is to explore pragmatic reasoning in quasi-deductive tasks. Two experiments were performed with non-standard categozical syllogisms, involving probabikrtic quantzfiers (mostknost, many/few; not few/several) or standard ones (no/sonze; some/no). The subjects received the syllogisms either in a non-contextual mode (experiment I) or in the context of a narrative text (experiment 2), and they ought to choose among alternative responses, rating their confidence and explaining their choice. The content fformal vs. thematic) was manipulated in the first experiment. The second experinzent nzanipulated the congruence between the logical and the factual conclusions of the text, as well as the availability of the categorical terms of the prenzises. The results suggest that: a) the subjects accept the probabilistic quantifiers and they feel confidence with their responses; b) expezience based explanations are much more frequent than formal explanations; c) an atnzosphere effect for probabilzIrtic quantzfiers was obtained; d) self-confidence increases when congruent and available texts are provided, although the logical performance remains low. The resuts are conszitent with the notion of mental scenario in human reasonzng, and do not support the cwrent competence models.
ITERATIVE TECHNIQUES FOR BLIND SOURCE SEPARATION USING ONLY FOURTH-ORDER CUMULANTS

"Blind source separation" is an array processing problem without a priori information (no array manifold). This model can be identified resorting to 4th-order cumulants only via the concept of 4th-order signal subspace (FOSS) which is defined as a matrix space. This idea leads to a "Blind MUSIC" approach where identification is achieved by looking for the (approximate) intersections between the FOSS and the manifold of 1D projection matrices. Pratical implementations of these ideas are discussed and illustrated with computer simulations.
Behavioral / Systems / Cognitive Activity-Dependent Regulation of Retinogeniculate Signaling by Metabotropic Glutamate Receptors

Thalamocortical neurons in dorsal lateral geniculate nucleus (dLGN) dynamically convey visual information from retina to the neocortex. Activation of metabotropic glutamate receptors (mGluRs) exerts multiple effects on neural integration in dLGN; however, their direct influence on the primary sensory input, namely retinogeniculate afferents, is unknown. In the present study, we found that pharmacological or synaptic activation of type 1 mGluRs (mGluR1s) significantly depresses glutamatergic retinogeniculate excitation in rat thalamocortical neurons. Pharmacological activation of mGluR1s attenuates excitatory synaptic responses in thalamocortical neurons at a magnitude sufficient to decrease suprathreshold output of these neurons. The reduction in both NMDA and AMPA receptor-dependent synaptic responses results from a presynaptic reduction in glutamate release from retinogeniculate terminals. The suppression of retinogeniculate synaptic transmission and dampening of thalamocortical output was mimicked by tetanic activation of retinogeniculate afferent in a frequency-dependent manner that activated mGluR1s. Retinogeniculate excitatory synaptic transmission was also suppressed by the glutamate transport blocker TBOA (DL-threo-benzyloxyaspartic acid), suggesting that mGluR1s were activated by glutamate spillover. The data indicate that presynaptic mGluR1 contributes to an activity-dependent mechanism that regulates retinogeniculate excitation and therefore plays a significant role in the thalamic gating of visual information.
A Field Guide to Constructivism in the College Science Classroom: Four Essential Criteria and a Guide to Their Usage.

This field guide provides four essential criteria for constructivism as well as a guide for using these criteria to identify and assess the level of constructivism being used in an educational experience. The criteria include: 1) prior knowledge, 2) cognitive dissonance, 3) application with feedback, and 4) metacognition. This guide provides timely, valuable information and “best practices” for science educators, especially faculty in higher
Medical Outcome of Patients With Dementia in a Free-Standing Psychiatric Hospital

Background: The hospital outcome of patients with dementia is significantly worse than that of cognitively intact persons of the same age admitted to medical or surgical units but has not been investigated in psychiatric settings. Aim of study: To determine the medical outcome of patients with dementia admitted for behavioral disturbance to a free-standing psychiatric hospital. Methods: Emergency transfers from the psychiatric setting to a general hospital were used as proxies for medical deteriorations occurring among the 71 patients with dementia (age 78.4 ± 10.4 years; 40.1% males) and 71 age- and gender-matched nondementia control patients. The patients were identified in a cohort of 1000 patients consecutively admitted to a free-standing mental health institution. Logistic regression was used to determine the clinical and laboratory variables independently associated with medical deteriorations. Results: A total of 30 patients with dementia and 25 nondementia patients were transferred to a general hospital after an acute medical deterioration (42.3% vs 35.2%, P = .38). Febrile illnesses and falls with head trauma were the most common reasons for transfers in the dementia group, in which they constituted more than half of medical deteriorations, a proportion significantly higher than in the control group (P = .011). Admission hemoglobin levels were the only independent predictor of medical deterioration in this geriatric sample. Conclusions: Although nearly 50% of patients with dementia admitted for behavioral disturbance to a free-standing psychiatric institution required transfer to a general hospital, their rate of medical deteriorations was similar to age-matched nondementia control patients.
Modulating effects of the menstrual cycle on cardiorespiratory responses to exercise under acute hypobaric hypoxia.

The purpose of this study was to examine the hypothesis that the menstrual cycle-induced modulation of the cardiorespiratory response to exercise might be altered by acute exposure to altitude. During both the luteal and follicular phases, 9 moderately trained female subjects with normal menstrual cycles performed incremental exercise to maximal effort on a cycle ergometer at sea level (SL) and under hypobaric hypoxia (HH) at the equivalent of 3,000 m altitude. Both at rest and during exercise, minute ventilation (.VE) and oxygen uptake (.VO(2)) did not differ between the luteal and follicular phases (either at SL or HH). However, the ratio of . VE to . VO(2) (.VE /.VO(2)), both at rest and during peak exercise, was greater in the luteal phase than in the follicular phase under HH conditions. Furthermore, the partial pressure of end-tidal carbon dioxide (PETCO(2)) during exercise was lower in the luteal phase than in the follicular phase in HH. These results suggest that the menstrual cycle-induced modulation of the ventilatory response to exercise may be altered under acute hypobaric-hypoxic conditions.
The origin of short-term momentum effects’ profits

In the field of financial literature, many scholars have tried to solve the riddle of origin of momentum profits. But results are so far mixed and not ultimate. The purpose of this paper is to find the origin of short term momentum effect. For this purpose, a new set of variables has been chosen that comes under the classification of "Business Proxies. " Fourteen stock markets from around the globe have been chosen to find the origin. These markets are Argentina, Austria, Brazil, China, Chile, Greece, India, Italy, Ireland, Mexico, New Zealand, Pakistan, Turkey and the USA. It is found that, out of 4 independent variables, a variable SB (Starting a Business) has proved to be significant to explain the source of momentum whereas all other variables might or might not have influence over momentum profits.
Social gene — A new method to find rising stars

Finding rising star in social networks becomes a popular research topic in recent years. Rising star means he or she may be not so charming at the initial time but turns out to be an outstanding star over time. In academic network, rising star means the scholar who just starts his research career with not so many papers published. While in the future, the sum of citations and papers will increase and the scholar will be more outstanding. There are some works of scholarly assessment, however, few works are about finding rising stars. Most of the algorithms of finding rising star are based on random walk on a heterogeneous network constructed by bibliography. These methods need entire information of networks and fit for a long time. In this paper, we propose a method based on “Social Genes”, which are defined as the inside factors of scholars' activities characteristics. We use factor analysis to find the inside factors, calculate the weights by neural network, and make assessments via AHP method. The experiment results on APS dataset show our method is able to find more authors with high rank.
Tracking interacting people

A computer vision system for tracking multiple people in relatively unconstrained environments is described. Tracking is performed at three levels of abstraction: regions, people and groups. A novel, adaptive background subtraction method that combines colour and gradient information is used to cope with shadows and unreliable colour cues. People are tracked through mutual occlusions as they form groups and part from one another. Strong use is made of colour information to disambiguate occlusions and to provide qualitative estimates of depth ordering and position during occlusion. Some simple interactions with objects can also be detected. The system is tested using indoor and outdoor sequences. It is robust and should provide a useful mechanism for bootstrapping and reinitialisation of tracking using more-specific but less-robust human models.
HLA antigens in the Landry‐Guillain‐Barré syndrome and chronic relapsing polyneuritis

Forty‐four patients with inflammatory demyelinating polyneuritis (22 with Landry‐Guillain‐Barré syndrome, 6 with subacute polyneuritis, and 16 with chronic relapsing polyneuritis) were typed for genetic markers in and around the HLA region of chromosome 6. Patients with chronic relapsing polyneuritis showed a definite association with HLA‐AW30 and AW31 and probable associations with HLA‐B8, HLA‐DW3, and glyoxalase I. No significant associations were demonstrated with the Landry‐Guillain‐Barré syndrome although an increase in glyoxalase I was significant if combined with the results of typing in chronic relapsing polyneuritis. The total patient group showed significant increases in HLA‐AW30, HLA‐AW31, and HLA‐DW3. The results support the view that HLA‐linked genetic factors influence susceptibility to chronic relapsing polyneuritis and may contribute to the differences in clinical patterns observed in inflammatory demyelination of the peripheral nervous system.
Permafrost degradation and methane: low risk of biogeochemical climate-warming feedback

Climate change and permafrost thaw have been suggested to increase high latitude methane emissions that could potentially represent a strong feedback to the climate system. Using an integrated earth-system model framework, we examine the degradation of near-surface permafrost, temporal dynamics of inundation (lakes and wetlands) induced by hydro-climatic change, subsequent methane emission, and potential climate feedback. We find that increases in atmospheric CH4 and its radiative forcing, which result from the thawed, inundated emission sources, are small, particularly when weighed against human emissions. The additional warming, across the range of climate policy and uncertainties in the climate-system response, would be no greater than 0.1 ° C by 2100. Further, for this temperature feedback to be doubled (to approximately 0.2 ° C) by 2100, at least a 25-fold increase in the methane emission that results from the estimated permafrost degradation would be required. Overall, this biogeochemical global climate-warming feedback is relatively small whether or not humans choose to constrain global emissions.