Miracle-dz/UniFAR-FTUs huggingface dataset:
Individually Monitoring Ligand-Induced Changes in the Structure of the GABAA Receptor at Benzodiazepine Binding Site and Non-Binding-Site Interfaces

The mechanisms by which the GABA and benzodiazepine (BZD) binding sites of the GABA-A receptor are allosterically coupled remain elusive. In this study, we separately monitored ligand-induced structural changes in the BZD binding site (α/γ interface) and at aligned positions in the α/β interface. α1His101 and surrounding residues were individually mutated to cysteine and expressed with wild-type β2 and γ2 subunits in Xenopus laevis oocytes. The accessibilities of introduced cysteines to modification by methanethiosulfonate ethylammonium (MTSEA)-Biotin were measured in the presence and absence of GABA-site agonists, antagonists, BZDs, and pentobarbital. The presence of flurazepam or the BZD-site antagonist flumazenil (Ro15-1788) decreased the rate of modification of α1H101C at the BZD binding site. GABA and muscimol each increased MTSEA-Biotin modification of α1H101C located at the BZD-site, gabazine (SR-95531, a GABA binding site antagonist) decreased the rate, whereas pentobarbital had no effect. Modification of α1H101C at the α/β interface was significantly slower than modification of α1H101C at the BZD site, and the presence of GABA or flurazepam had no effect on its accessibility, indicating the physicochemical environments of the α/γ and α/β interfaces are different. The data are consistent with the idea that GABA-binding site occupation by agonists causes a GABA binding cavity closure that is directly coupled to BZD binding cavity opening, and GABA-site antagonist binding causes a movement linked to BZD binding cavity closure. Pentobarbital binding/gating resulted in no observable movements in the BZD binding site near α1H101C, indicating that structural mechanisms underlying allosteric coupling between the GABA and BZD binding sites are distinct.
Breakthrough to Awareness: a Neural Network Model of Conscious and Unconscious Perception

A neural network model is constructed to mimic the processing involved in semantic and working memory when subliminal effects are involved. These effects involve modifications of reaction time to later inputs, according as to whether or not there has been conscious or unconscious processing of the earlier input. The model is constructed of two separate modules, one (a semantic memory module) allowing for processing at a semantic, but unconscious, level, and the other (a working memory module) for conscious experience. The latter module, although a replica of the earlier one, has different lateral connectivity and output function than the former. The model is shown to give a good fit to the data on the processing of polysemous words obtained by Marcel(1980). Further tests are suggested for the model, and a possible cortical implementation suggested. The relevance of the model to recent approaches to consciousness is also explored.
Self-reported health behaviour change in adults: analysis of the Canadian Community Health Survey 4.1.

INTRODUCTION Knowledge of Canadians' experiences in making health behaviour changes (HBCs) in general, and among those at risk due to body mass index (BMI), would help inform health promotion / disease prevention programs. Selected self reported HBCs in the past 12 months by BMI category were examined in this secondary analysis of the Canadian Community Health Survey 4.1. These HBCs included increased sports/exercise, weight loss and improved eating habits. Barriers to HBC were also examined. METHODS Descriptive analyses and forward stepwise logistic regression were completed on data from respondents 18 years and older. Self-reported BMI was corrected by the method of Connor Gorber et al. (2008). RESULTS Our final sample was n = 111 449. Overall, 58% of respondents had made an HBC, with increased sports/exercise as the most important HBC in 29% of the sample, followed by improved eating habits (10%) and weight loss (7%). Half (51%) experienced barriers to HBC; lack of will power was most commonly cited, followed by work and family responsibilities. Obese respondents reported HBC more frequently than normal-weight respondents (60% vs. 55%), but the prevalence of increased sports/ exercise and improved eating habits was similar across BMI categories. Regression models accounted for only 6%-10% of the total variance. CONCLUSION That a majority of respondents had made at least one HBC bodes well for positively shifting population health. Additional work to further characterize the population, and to improve on population indicators, is needed to assess the impact of health promotion/disease prevention efforts. These findings provide important first population benchmarks for future work.
L'identification de facteurs communs de la liquidité sur le marché parisien des actions

This article proposes a new approach to liquidity on financial markets : do not considers liquidity individually, or stock by stock, but takes a common or systematic approach. Common factors in liquidity do exist, and they can cause the liquidity of each stock to vary simultaneously. This point was discussed in a previous article. The aim of the present article is to identify these common factors: which variables have a common impact on every stock in the market simultaneously? The common components of liquidity can have a macro-economic origin (interest or inflation or unemployment rates, etc) or a structural origin (profitability, volumes, etc). The identification of these common liquidity factors is researched through an empirical study on the Parisian and Euronext stock markets. The methodology used is a multiple linear regression of four market liquidity indicators (spread, depth, volume and number of transactions) on the Parisian and Euronext markets by different explanatory variables chosen after the study of pricing models with intuitive reasoning.
Pragmatics in Analogical Mapping

Theories of analogical reasoning differ in the roles they ascribe to pragmatic factors as a source of constraints on analogical mappings. The multiconstraint theory as instantiated in the ACME model (Holyoak & Thagard, 1989a) claims that pragmatic constraints interact with structural and semantic constraints within the mapping stage itself, in addition to influencing pre-mapping and post-mapping stages. Participants in three experiments were asked to generate mappings between non-isomorphic analogs for which mappings for some elements were ambiguous on structural grounds. In all experiments, manipulations of participants' processing goals influenced their preferred mappings. At the same time, goal-irrelevant information contributed to many-to-one mappings (Experiments 1 and 2) and to the resolution of mappings that were ambiguous on the basis of goal-relevant information alone (Experiment 3). The qualitative pattern of results was successfully simulated using the ACME model, implementing the impact of processing goals as an inhibitory process of selective attention.
Reasoning with Simplifying Assumptions: A Methodology and Example

Simplifying assumptions are a powerful technique for dealing with complexity, which is used in all branches of science and engineering. This work develops a formal account of this technique in the context of heuristic search and automated reasoning. We also present a methodology for choosing appropriate simplifying assumptions in specific domains, and demonstrate the use of this methodology with an example of reasoning about typed partial functions in an automated programming assistant.
An improved STI method for evaluating Mandarin speech intelligibility

Speech Transmission Index (STI) is a physical metric predicting the speech intelligibility. It shows a good correlation with the subjective intelligibility when used for English, but it has not been reported to be applicable to such tonal language as Mandarin. In this study, the traditional STI method is improved by adopting an accumulative normal distribution assumption between the signal-to-noise ratios and intelligibility, in which some characteristics of Mandarin speech are taken into considered. Results from psychoacoustic perceptual experiments show that the improved method is more suitable for objective evaluation of Mandarin speech intelligibility in noisy and reverberant listening conditions compared with the traditional method. The correlation coefficient between the subjective intelligibility and the objective STI is improved from 0.97 to 0.98; and the standard error decreased from 15.67% to 6.58%. This method is also expected to be applicable to other languages.
Aldose Reductase Inhibition Prevents Allergic Airway Remodeling through PI3K/AKT/GSK3β Pathway in Mice

Background Long-term and unresolved airway inflammation and airway remodeling, characteristic features of chronic asthma, if not treated could lead to permanent structural changes in the airways. Aldose reductase (AR), an aldo-sugar and lipid aldehyde metabolizing enzyme, mediates allergen-induced airway inflammation in mice, but its role in the airway remodeling is not known. In the present study, we have examined the role of AR on airway remodeling using ovalbumin (OVA)-induced chronic asthma mouse model and cultured human primary airway epithelial cells (SAECs) and mouse lung fibroblasts (mLFs). Methods Airway remodeling in chronic asthma model was established in mice sensitized and challenged twice a week with OVA for 6 weeks. AR inhibitor, fidarestat, was administered orally in drinking water after first challenge. Inflammatory cells infiltration in the lungs and goblet cell metaplasia, airway thickening, collagen deposition and airway hyper-responsiveness (AHR) in response to increasing doses of methacholine were assessed. The TGFβ1-induced epithelial-mesenchymal transition (EMT) in SAECs and changes in mLFs were examined to investigate AR-mediated molecular mechanism(s) of airway remodeling. Results In the OVA-exposed mice for 6 wks inflammatory cells infiltration, levels of inflammatory cytokines and chemokines, goblet cell metaplasia, collagen deposition and AHR were significantly decreased by treatment with AR inhibitor, fidarestat. Further, inhibition of AR prevented TGFβ1-induced altered expression of E-cadherin, Vimentin, Occludin, and MMP-2 in SAECs, and alpha-smooth muscle actin and fibronectin in mLFs. Further, in SAECs, AR inhibition prevented TGFβ1- induced activation of PI3K/AKT/GSK3β pathway but not the phosphorylation of Smad2/3. Conclusion Our results demonstrate that allergen-induced airway remodeling is mediated by AR and its inhibition blocks the progression of remodeling via inhibiting TGFβ1-induced Smad-independent and PI3K/AKT/GSK3β-dependent pathway.
FPGA implementation of BCH decoder for memory systems

BCH (Bose-Chaudhuri-Hocquenghem) coding is very useful to detect and correct the errors in communication system and also on-chip (computer) memory systems. This paper presents a High-speed BCH decoder that corrects double-adjacent and single-bit errors in parallel and serially corrects multiple-bit errors instead of double-adjacent errors. Its operation is based on extending an existing decoder that corrects only single-bit errors in parallel and serially corrects double-adjacent errors at low speed. The proposed constructed decoder design is suitable for nanoscale memory systems, in which double-adjacent and single-bit errors occur at a higher probability compared to the multiple-bit errors. This paper also shows that the area and delay overheads incurred by the proposed scheme are significantly lower than traditional BCH decoders capable of correcting any double-bit errors in parallel.
Surgical Management of Lumbar Degenerative Spondylolisthesis

Lumbar degenerative spondylolisthesis (DS) is a common cause of low back pain, radiculopathy, and/or neurogenic claudication. Treatment begins with a trial of nonsurgical methods, including physical therapy, NSAIDs, and epidural corticosteroid injections. Surgical treatment with decompression and fusion is recommended for patients who do not respond to this initial regimen. Although much has been published in the past two decades on the surgical management of DS, the optimal method remains controversial. Interbody fusion may improve arthrodesis rates and can be performed via numerous surgical approaches. Minimally invasive techniques continue to be developed. Particular attention to surgical management of DS in the elderly is warranted given the increasing numbers of elderly persons. Healthcare utilization in the future must take into account evidence-based medicine that establishes clinically effective practices while simultaneously being cost effective.
Breaking Through: The Making of Minority Executives in Corporate America

In one of the first in-depth studies to focus on minorities who have made it to the top, Breaking Through examines the crucial connection between corporate culture and the advancement of people of color. American companies may tout their equal opportunity initiatives, but with 95% of all executive-level positions in the United States held by white males, most of these programs clearly fall far short of their goals when it comes to diversifying upper management. Yet, even in the face of such overwhelming odds, some minority executives do break through to the highest leadership ranks. What can we learn from these success stories? The often surprising conclusions drawn by authors Thomas and Gabarro represent important milestones both for the study of organizational practice and for minorities planning their own course of professional achievement. Here are the determining factors--both individual and organizational--that correspond to the advancement of minority executives to the highest levels.
Cytokine production in a murine model of recurrent herpetic stromal keratitis.

PURPOSE To determine the pattern of cytokine production in the cornea and its relationship with viral antigens, in our murine model of recurrent ocular herpes simplex virus (HSV)-1 infection. METHODS Six weeks after corneal inoculation with HSV-1, the eyes of latently infected and control mice were UV irradiated and examined for signs of disease and viral reactivation. The eyes of five mice with recurrent stromal disease and two controls were processed for immunohistochemistry on days 4, 7, 10, and 14 after irradiation. Sections were double stained for viral antigens and one of the following cytokines: interleukin (IL)-1ss, IL-2, IL-4, IL-6, IL-10, IL-12, and interferon (IFN)-gamma. RESULTS Fifty percent of mice showed signs of recurrent stromal disease, the severity of which peaked on day 10 after UV irradiation. There was a large cellular infiltrate in the stroma of all the corneas with recurrent disease and the predominant cytokines were IL-1ss, IL-6, IL-10, IL-12, and IFN-gamma, all present in large numbers of cells on the days studied. There were very few cells producing IL-2 and IL-4. Control eyes had no significant cytokine-producing cells in the stroma. CONCLUSIONS These observations suggest that recurrent herpetic stromal keratitis (HSK) may not be characterized by a classic T-helper (Th)1 or Th2 response. However, the large number of IFN-gamma(+) and IL-12(+) cells and the relative absence of IL-4 favors a Th1 response, and despite the numerous IL-10(+) cells, the overall balance of cytokine production appears to be proinflammatory.
A Preliminary Study on Clustering Student Learning Data

Clustering techniques have been used on educational data to find groups of students who demonstrate similar learning patterns. Many educational data are relatively small in the sense that they contain less than a thousand student records. At the same time, each student may participate in dozens of activities, and this means that these datasets are high dimensional. Finding meaningful clusters from these datasets challenges traditional clustering algorithms. In this paper, we show a variety of ways to cluster student grade sheets using various clustering and subspace clustering algorithms. Our preliminary results suggest that each algorithm has its own strength and weakness, and can be used to find clusters of different properties. We also show that subspace clustering is well suited to identify meaningful patterns embedded in such data sets.
Structure Preserving Manipulation and Interpolation for Multi‐element 2D Shapes

This paper presents a method that generates natural and intuitive deformations via direct manipulation and smooth interpolation for multi‐element 2D shapes. Observing that the structural relationships between different parts of a multi‐element 2D shape are important for capturing its feature semantics, we introduce a simple structure called a feature frame to represent such relationships. A constrained optimization is solved for shape manipulation to find optimal deformed shapes under user‐specified handle constraints. Based on the feature frame, local feature preservation and structural relationship maintenance are directly encoded into the objective function. Beyond deforming a given multi‐element 2D shape into a new one at each key frame, our method can automatically generate a sequence of natural intermediate deformations by interpolating the shapes between the key frames. The method is computationally efficient, allowing real‐time manipulation and interpolation, as well as generating natural and visually plausible results.
GROWTH CONTROL OF DIFFERENTIATED FETAL RAT HEPATOCYTES IN PRIMARY MONOLAYER CULTURE

Dialyzed fetal bovine serum contains two distinct growth-controlling macromolecular fractions: one stimulates and the other inhibits proliferation of primary cultured differentiated fetal rat hepatocytes. Both fractions are precipitated by ammonium sulfate (50% saturation, pH 7.4, 4°C). Serum fraction I (SFI, mol wt ≥ 120,000 daltons estimated by gel filtration with Bio-gel P200) appears to contain at least two factors which function, respectively, to initiate DNA synthesis (activity pH 4–10 stable) and to increase the rate at which initiated cells traverse the cell cycle (activity pH 4 and pH 10 labile). Intraperitoneal injections of SFI into adult rats have produced detectable stimulation of hepatic but not renal DNA synthesis. Serum fraction II (SFII, mol wt 40,000–80,000 daltons) suppresses in vitro incorporation of CH3-[3H]thymidine into DNA under conditions which diminish neither cell viability nor cell attachment. Mixing experiments indicate that SFI and SFII mutually antagonize each other with respect to DNA synthesis and cell multiplication. Thus, both the relative and absolute serum levels of multiple factors control in vitro fetal hepatocyte proliferation.
Hypoxia and Acidification Have Additive and Synergistic Negative Effects on the Growth, Survival, and Metamorphosis of Early Life Stage Bivalves

Low oxygen zones in coastal and open ocean ecosystems have expanded in recent decades, a trend that will accelerate with climatic warming. There is growing recognition that low oxygen regions of the ocean are also acidified, a condition that will intensify with rising levels of atmospheric CO2. Presently, however, the concurrent effects of low oxygen and acidification on marine organisms are largely unknown, as most prior studies of marine hypoxia have not considered pH levels. We experimentally assessed the consequences of hypoxic and acidified water for early life stage bivalves (bay scallops, Argopecten irradians, and hard clams, Mercenaria mercenaria), marine organisms of significant economic and ecological value and sensitive to climate change. In larval scallops, experimental and naturally-occurring acidification (pH, total scale = 7.4–7.6) reduced survivorship (by >50%), low oxygen (30–50 µM) inhibited growth and metamorphosis (by >50%), and the two stressors combined produced additively negative outcomes. In early life stage clams, however, hypoxic waters led to 30% higher mortality, while acidified waters significantly reduced growth (by 60%). Later stage clams were resistant to hypoxia or acidification separately but experienced significantly (40%) reduced growth rates when exposed to both conditions simultaneously. Collectively, these findings demonstrate that the consequences of low oxygen and acidification for early life stage bivalves, and likely other marine organisms, are more severe than would be predicted by either individual stressor and thus must be considered together when assessing how ocean animals respond to these conditions both today and under future climate change scenarios.
Nonclausal deduction in first-order temporal logic

This paper presents a proof system for first-order temporal logic. The system extends the nonclausal resolution method for ordinary first-order logic with equality, to handle quantifiers and temporal operators. Soundness and completeness issues are considered. The use of the system for verifying concurrent programs is discussed and variants of the system for other modal logics are also described.
Incremental Feature Selection and l1 Regularization for Relaxed Maximum-Entropy Modeling

We present an approach to bounded constraintrelaxation for entropy maximization that corresponds to using a double-exponential prior or `1 regularizer in likelihood maximization for log-linear models. We show that a combined incremental feature selection and regularization method can be established for maximum entropy modeling by a natural incorporation of the regularizer into gradientbased feature selection, following Perkins et al. (2003). This provides an efficient alternative to standard `1 regularization on the full feature set, and a mathematical justification for thresholding techniques used in likelihood-based feature selection. Also, we motivate an extension to n-best feature selection for linguistic features sets with moderate redundancy, and present experimental results showing its advantage over `0, 1-best `1, `2 regularization and over standard incremental feature selection for the task of maximum-entropy parsing.1
Background Digital Calibration of Comparator Offsets in Pipeline ADCs

This brief presents a low-cost digital technique for background calibration of comparator offsets in pipeline analog-to-digital converters (ADCs). Thanks to calibration, comparator offset errors above half the stage least-significant bit margin in a unitary redundancy scheme are admissible, thus relaxing comparator design requirements and allowing their optimization for low-power high-speed applications and low input capacitance. The technique also makes it possible to relax design requirements of stage amplifiers within the pipeline queue, since output swing and driving capability are significantly lower. In this brief, the proposal is validated using realistic hardware-behavioral models.
IMPLEMENTATION OF A BAYESIAN FILTER IN A PHOTORECEPTOR CELL

In this study we consider how probability distributions calculated in probabilistic cognitive models can be represented and processed in the brain. More exactly we show that a photoreceptor cell can compute a simple Bayesian inference in a binary Hidden Markov Model (HMM), based on the underlying biochemical interactions of this single cell. We derive, under steady-state conditions, a formal equivalence between the probablistic model and the molecular mechanisms, and show that the equivalence can be extended to the dynamic case. From the photoreceptor example we see that biochemical interactions can represent probability distributions and implement basic probabilistic reasoning.
Compensation of Some Time Dependent Deformations in Tomography

This work concerns 2D+t dynamic tomography. We show that a much larger class of deformations than the affine transforms can be compensated analytically within filtered back projection algorithms in 2D parallel beam and fan beam dynamic tomography. We present numerical experiments on the Shepp and Logan phantom showing that nonaffine deformations can be compensated. A generalization to 3D cone beam tomography is proposed