Miracle-dz/UniFAR-FTUs huggingface dataset:
Organizational learning with forgetting: Reconsidering the exploration–exploitation tradeoff

Prior exploration–exploitation models of organizational learning generally neglect forgetting. This study models organizational learning with forgetting and derives some novel implications. Most noteworthy, our findings point out limits to the contention that promoting rapid learning undermines long-run knowledge. Slower learning is not always better. When agents are subject to forgetting, raising the rate of interpersonal learning often enhances the diversity of beliefs within an organization, as well as the number and range of aspects of the environment that organizational members come to know. The rate of learning that maximizes organizational knowledge or diversity varies with the rate of forgetting. Organizations need not sacrifice diversity as they gain knowledge. Analyses of our model indicate that knowledge and diversity are positively correlated across organizations. Implications of forgetting redirect theorists, empirical researchers, and managers toward alternatives to some conclusions from prior exploration–exploitation modeling studies.
Detection of Large pK a Perturbations of an Inhibitor and a Catalytic Group at an Enzyme Active Site, a Mechanistic Basis for Catalytic Power of Many Enzymes*

Δ5-3-Ketosteroid isomerase catalyzes cleavage and formation of a C–H bond at a diffusion-controlled limit. By determining the crystal structures of the enzyme in complex with each of three different inhibitors and by nuclear magnetic resonance (NMR) spectroscopic investigation, we evidenced the ionization of a hydroxyl group (pK a ∼16.5) of an inhibitor, which forms a low barrier hydrogen bond (LBHB) with a catalytic residue Tyr14(pK a ∼11.5), and the protonation of the catalytic residue Asp38 with pK a of ∼4.5 at pH 6.7 in the interaction with a carboxylate group of an inhibitor. The perturbation of the pK a values in both cases arises from the formation of favorable interactions between inhibitors and catalytic residues. The results indicate that the pK a difference between catalytic residue and substrate can be significantly reduced in the active site environment as a result of the formation of energetically favorable interactions during the course of enzyme reactions. The reduction in the pK a difference should facilitate the abstraction of a proton and thereby eliminate a large fraction of activation energy in general acid/base enzyme reactions. The pK a perturbation provides a mechanistic ground for the fast reactivity of many enzymes and for the understanding of how some enzymes are able to extract a proton from a C–H group with a pK a value as high as ∼30.
Benefits of distraction

A considerable amount of research has been carried out with the aim of understanding the relationship between arousal and performance, but so far this topic has rarely been examined in the context of personality. In this study, we used a 2-group design ( N = 76) to investigate the effects of arousal, induced by cognitive activation, on introverts and extroverts in the context of follow-up tasks. Arousal was induced by an irrelevant auditory stimulus that implemented a high cognitive load while participants were attempting to remember the content of the text of an article. Extroverts showed a greater improvement in performance than did introverts in a consecutive task, a d2-Test of Attention, leading to the conclusion that extroverts benefit more from cognitive activation through external stimuli than do introverts. Theoretical implications are discussed in the framework of the Yerkes–Dodson law.
The Association of Serum Bisphenol A with Thyroid Autoimmunity

Introduction: Data on the association of bisphenol A (BPA) exposure and autoimmunity in humans is unclear. Objective: To elucidate the influence of BPA on thyroid autoimmunity, in the present study we assessed the association between serum BPA and thyroid autoantibodies. Methods: Serum samples from 2361 subjects, aged ≥15 years, from the Thai 4th National Health Examination Survey were measured for BPA, antithyroglobulin (TgAb), antithyroperoxidase (TPOAb) and antithyrotrophin receptor (TRAb) antibodies. Results: The proportion of subjects positive for TgAb, TPOAb and TRAb were 11.1%, 14.9% and 1.9%, respectively. With regard to BPA, 51.9% had serum BPA levels exceeding the detection limit of the assay (0.3). There was a significant increasing trend for subjects with TgAb (p < 0.05) and TPOAb (p < 0.001) positivity as BPA quartiles increased, particularly in the highest quartile. In contrast, no relationship between BPA quartiles and TRAb was found. Logistic regression analysis showed that age, gender and BPA quartiles were determinants of TPOAb or TgAb positivity, independent of BMI. However, only the association between BPA and TPOAb positivity was consistent in both men and women. Conclusions: BPA was independently associated with TPOAb positivity. However, its mechanism related to TPOAb positivity, subsequently leading to autoimmune thyroid disease, needs further investigation.
The ReNAissanCe of mRNA-based cancer therapy

About 25 years ago, mRNA became a tool of interest in anticancer vaccination approaches. However, due to its rapid degradation in situ, direct application of mRNA was confronted with considerable skepticism during its early use. Consequently, mRNA was for a long time mainly used for the ex vivo transfection of dendritic cells, professional antigen-presenting cells known to stimulate immunity. The interest in direct application of mRNA experienced a revival, as researchers became aware of the many advantages mRNA offers. Today, mRNA is considered to be an ideal vehicle for the induction of strong immune responses against cancer. The growing numbers of preclinical trials and as a consequence the increasing clinical application of mRNA as an off-the-shelf anticancer vaccine signifies a renaissance for transcript-based antitumor therapy. In this review, we highlight this renaissance using a timeline providing all milestones in the application of mRNA for anticancer vaccination.
The Iterated Lasso for High-Dimensional Logistic Regression By

We consider an iterated Lasso approach for variable selection and estimation in sparse, high-dimensional logistic regression models. In this approach, we use the Lasso (Tibshirani 1996) to obtain an initial estimator and reduce the dimension of the model. We then use the Lasso as the initial estimator in the adaptive Lasso (Zou 2006) to obtain the final selection and estimation results. We provide conditions under which this two-step approach possesses asymptotic oracle selection and estimation properties. One important aspect of our results is that the total number of covariates can be larger than the sample size. Simulation studies indicate that the iterated Lasso has superior performance in variable selection relative to the standard Lasso. A data example is used to illustrate the proposed approach.
Molecular and Phenotypic Heterogeneity in Mitochondrial Trifunctional Protein Deficiency Due To b-Subunit Mutations

Ute Spiekerkoetter, Bin Sun, Zaza Khuchua, Michael J. Bennett, and Arnold W. Strauss Department of Pediatrics and Vanderbilt Children’s Hospital, Vanderbilt University School of Medicine, Nashville, Tennessee; Heinrich Heine University Hospital, Department of General Pediatrics, Duesseldorf, Germany; Departments of Pathology and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
The Affective-Instinctual Level and Age

Are there differences in “life force”? Apart from the direction that this hypothetical “psychic energy” takes (e.g., possibly expressed as “will to live” or “will to die”), are the aged characterized by greater “instinctuality ,” or d o they possess less “drive” than the young? After Freud postulated an energetic “force” that sustained psychic activity, such questions found their way into the theoretical and empirical literature. However, operational indexing of the phenomenon has proven vexing. As they were unable to observe or test this “force” itself, psychologists have attempted to examine it indirectly through its effects on various personality components. It is not clear just what aspects or dimensions of personality should be examined to measure the influence of this “force. ” Investigators have fixed upon various dimensions for study (to date, moods, interests, projective test creations, traits, and segments of reported life style have been tapped) with varying outcomes and conclusions. Since we still do not know which aspect or aspects of personality (e.g., traits-in-general, or a trait; interests-in-general, or an interest) is or are the best or among the best reflectants of this force, in the present study samples of the age groups’ interests, moods, intensity of affect, along with nature and content of cognitions, were simultaneously examined for indications of this “force” and its possible differential expression as a function of age.
Hypermethylation of E‐cadherin is an independent predictor of improved survival in head and neck squamous cell carcinoma

The loss of E‐cadherin (ECAD) protein expression has been linked to aggressive head and neck squamous cell carcinoma (HNSCC). Promoter hypermethylation of the cadherin 1, type 1 (CDH1) gene (encoding ECAD) is 1 mechanism by which this protein can be inactivated, although this epigenetic alteration of the gene has not been linked conclusively to poorer patient outcome and, in fact, may be associated with better patient prognosis.
The philosophical, cultural, and historical aspects of complementary, alternative, unconventional, and integrative medicine in the Old World.

BACKGROUND Complementary, alternative, unconventional, and integrative medicine are types of natural medicine that have been known and practiced ever since the recording of history, and in particular in the Old World. This has been rediscovered in many countries, including the New World and especially in the United States. In this review, the philosophical, cultural, and historical aspects are discussed, and the many types of alternative medical practices are mentioned. OBSERVATIONS The study of complementary medicine shows that evidence required the medical establishment to take unconventional therapies more seriously, and realize that their use alongside traditional medicine, is rapidly increasing. CONCLUSIONS Complementary medicine is a formal method of health care in most countries of the Old World and is expected to become integrated in the modern medical system and to be part of the medical curriculum and the teaching programs of medical institutions as well. Issues of efficacy and safety of complementary medicine have become increasingly important and supervision of the techniques and procedures used is required. More research studies are needed to understand and use this type of medicine.
Platelet-Activating Factor Induces Nitric Oxide Synthesis in Trypanosoma cruzi-Infected Macrophages and Mediates Resistance to Parasite Infection in Mice

ABSTRACT Trypanosoma cruzi replicates in nucleated cells and is susceptible to being killed by gamma interferon-activated macrophages through a mechanism dependent upon NO biosynthesis. In the present study, the role of platelet-activating factor (PAF) in the induction of NO synthesis and in the activation of the trypanocidal activity of macrophages was investigated. In vitro, PAF induced NO secretion byT. cruzi-infected macrophages and the secreted NO inhibited intracellular parasite growth. The addition of a PAF antagonist, WEB 2170, inhibited both NO biosynthesis and trypanocidal activity. The inducible NO synthase/l-arginine pathway mediated trypanocidal activity, since it was inhibited by treatment withl-N-monomethyl arginine (l-NMMA), an l-arginine analog. PAF-mediated NO production in infected macrophages appears to be dependent on tumor necrosis alpha (TNF-α) production, since the addition of a neutralizing anti-TNF-α monoclonal antibody mAb inhibited NO synthesis. To test the role of PAF in mediating resistance or susceptibility to T. cruziinfection, infected mice were treated with WEB 2170, a PAF antagonist. These animals had higher parasitemia and earlier mortality than did vehicle-treated mice. Taken together, our results suggest that PAF belongs to a group of mediators that coordinate the mechanisms of resistance to infections with intracellular parasites.
Somatostatin sst(2) receptor-mediated inhibition of mesenteric afferent nerves of the jejunum in the anesthetized rat.

BACKGROUND & AIMS Octreotide inhibits visceral sensations in clinical studies, but the site of action and the receptor type(s) involved are unknown. Our aim was to investigate the effects of octreotide, the selective sst(2) receptor agonist (BIM 23027), and the sst(2) antagonist (Cyanamid154806) on the activity of mesenteric afferent fibers innervating the rat jejunum. Their effects were investigated on baseline discharge, mechanosensitivity, and responses to algesic chemicals. METHODS Extracellular multiunit recordings of jejunal afferent nerve firing were made in pentobarbitone-anesthetized (60 mg/kg intraperitoneally) male Wistar rats. RESULTS Octreotide and BIM23027 (0.001-100 microg/kg intravenously) each evoked a long-lasting inhibition of baseline discharge, which was blocked by cyanamid 154806 (3 mg/kg) and absent in chronically vagotomized animals. Afferent responses to bradykinin were also inhibited by an sst(2) receptor-mediated mechanism but were unaffected by vagotomy. Ramp distentions of the jejunum evoked a biphasic activation of afferent nerve discharge, the low threshold component of which was attenuated in vagotomized animals. Sst(2) receptor agonists significantly inhibited the mechanosensitivity of spinal, but not vagal, afferents. CONCLUSIONS These data suggest that activation of somatostatin sst(2) receptors inhibit populations of mesenteric afferents likely to be involved in nociceptive transmission.
Tidal modulation and triggering of low‐frequency earthquakes in northern Cascadia

We analyze the influence of Earth and ocean tides on the triggering of low‐frequency earthquakes (LFEs) in northern Cascadia using three LFE catalogs for southern Vancouver Island and Washington state from episodic tremor and slip events between 2003 and 2013. Sensitivities of LFE families to tidally induced fault normal stress, updip shear stress (UDSS), and corresponding time derivatives are computed and their geographic variability is mapped. We find localized areas showing higher sensitivity to UDSS than their surroundings, suggesting that tidal sensitivity depends on laterally heterogeneous physical properties such as variable pore fluid pressures and frictional properties along the plate interface. We observe that sensitivity of LFEs to UDSS rises dramatically from near zero on the first day of strong activity to a maximum ∼4 days later. In addition, the peak LFE rate transitions from a correlation with peak tidal shear stress rate to a correlation with peak tidal shear stress through large slow slip events. We identify 64 Rapid‐Tremor‐Reversals (RTRs) that start a few days after the main slip front. The RTRs have an average stress drop of ∼0.8 kPa and a majority (72%) occurs during periods of large positive UDSS. The combined observations imply that RTRs play an important role in slow slip processes and that modulation of creep rate due to tidal stress and tidal triggering of secondary events are jointly responsible for the observed tidal sensitivity.
Efficiency with Non‐Convexities: Extending the “Scandinavian Consensus” Approaches

There are two distinct 'Scandinavian consensus' approaches to public good supply, both based on agents' willingness to pay. A Wicksell-Foley public competitive equilibrium arises from a negative consensus in which no change of public environment, together with associated taxes and subsidies which finance it, will be unanimously approved. Alternatively, in a Lindahl or valuation equilibrium, charges for the public environment induce a positive consensus. To allow general nonconvexities to be regarded as aspects of the public environment, the authors extend recent generalizations of these equilibrium notions and prove counterparts to both the usual fundamental efficiency theorems of welfare economics. Copyright 1998 by The editors of the Scandinavian Journal of Economics.
Secondhand smoke exposure and quality of life in patients with heart failure.

BACKGROUND Secondhand smoke (SHS) exposure is associated with an increased risk of atherosclerotic heart disease and cardiac events. We sought to assess the effect of SHS on health-related quality of life (HRQOL) in patients with heart failure. METHODS Current nonsmokers with heart failure (N = 205) were enrolled in a cohort study. Exposure to SHS was assessed with a validated exposure questionnaire and a high-sensitivity assay for urinary cotinine level. Multidimensional HRQOL was evaluated with the RAND 36-Item Short Form Health Survey, which assesses 8 domains on a scale of 0 (worst) to 100 (best): physical functioning, bodily pain, role limitations due to physical health problems (role physical), role limitations due to emotional/personal problems (role emotional), emotional well-being, social functioning, energy/fatigue, and general health perceptions. A subset of patients (n = 75) agreed to assessment of functional status with a 6-minute walk test. RESULTS Self-reported exposure to SHS was associated with generally lower HRQOL scores in univariate analysis, with statistically and clinically significant reductions in 3 subscale scores: role physical (22.2 points), emotional well-being (11.0 points), and role emotional (16.2 points). Even after adjustment for clinical factors, such as age, sex, New York Heart Association class of heart failure, comorbidities, and medications, exposure to SHS remained an independent predictor of HRQOL scores in these domains. When increasing quartiles of urinary cotinine level were used as the exposure measure, qualitatively similar results were obtained. CONCLUSIONS Even low levels of SHS are associated with lower scores in several aspects of HRQOL. Physicians should advise patients with heart failure and their families to avoid SHS exposure.
Integrity of the occluding barrier in high-resistant thyroid follicular epithelium in culture. I. Dependence of extracellular Ca2+ is polarized.

The dependence of the thyroid occluding barrier on extracellular Ca2+ (Ca2+e) was studied in porcine thyrocyte monolayers resting on the collagen-coated porous filter of bicameral culture chambers. Ca2+ in the apical and basal media was selectively removed by ethylene glycol-bis(beta-amino-ethyl ether)N,N,N',N'-tetraacetic acid (EGTA), and the effect on occluding junction integrity was estimated by measuring the transepithelial electrical resistance (RTE) and the transepithelial flux (FTE) of 125I-, [3H]inulin and 125I-thyroglobulin. Experiments were also carried out to monitor the recovery of the occluding barrier after restitution of Ca2+e as well as to examine the effect of a second Ca2+ depletion period. Obtained data were correlated to changes in thyrocyte ultrastructure and distribution of filamentous actin as visualized by fluorescein isothiocyanate (FITC)-phalloidin. The thyrocyte monolayer developed RTE greater than 6000 ohms.cm2 after 6 to 8 days of culture. Total depletion of Ca2+e caused a rapid fall in RTE to about 50 ohms.cm2 after 10 min. Selective removal of Ca2+ in the basal medium induced a similar decline in RTE, which, however, was significantly retarded. Removal of apical Ca2+e alone was without effect on RTE. Corresponding responses were found in FTE experiments: the apicobasal transfer of radiotracers was unaltered after apical depletion, intermediary increased after basal depletion and maximally increased after total depletion of Ca2+e. Morphologically, monolayers lacking apical Ca2+e appeared normal except for shortening of microvilli at the apical plasma membrane. Removal of basal Ca2+e caused a focal dissociation of the adherens junction, which was most pronounced at the three-cell corners, leaving a slight dilation of the apical-most portion of the intercellular cleft. The adherent junction-associated actin bundle was partly retracted into the apical cytoplasm. The former occluding junction was distended and of reduced height at the sites of dissociated adherens junction. After total Ca2+ depletion, more severe alterations were found, i.e., contraction of cells and marked dilation of intercellular clefts. Readdition of Ca2+ to cultures depleted of basal Ca2+e for 10 min normalized RTE, FTE, and junctional morphology within 30 to 60 min. When a second period of basal depletion was introduced after recovery was obtained, the decrease in RTE and the retraction of the actin bundle occurred much more rapidly than during the first depletion. It is concluded that the thyroid occluding barrier depends on extracellular Ca2+ present only at the basal side of the occluding junction. Furthermore, this Ca2+ dependence seems to be spatially segregated along the lateral plasma membrane as well as along the circumference of the thyrocyte. (ABSTRACT TRUNCATED AT 400 WORDS)
Determining Exact Point Correspondences in 3D Measurement Systems Using Fringe Projection – Concepts, Algorithms and Accuracy Determination

Fringe projection systems for contactless surface measurements are increasingly used in applications of industrial inspection, quality control, rapid prototyping, archaeology, and in medical applications. Such systems provide increasing accuracy together with shorter measurement time and increasing data volume. The demands of increasing data volume, accuracy, and measurement speed can be satisfied using a more powerful calculation technique and better algorithms.
N2N Learning: Network to Network Compression via Policy Gradient Reinforcement Learning

While bigger and deeper neural network architectures continue to advance the state-of-the-art for many computer vision tasks, real-world adoption of these networks is impeded by hardware and speed constraints. Conventional model compression methods attempt to address this problem by modifying the architecture manually or using pre-defined heuristics. Since the space of all reduced architectures is very large, modifying the architecture of a deep neural network in this way is a difficult task. In this paper, we tackle this issue by introducing a principled method for learning reduced network architectures in a data-driven way using reinforcement learning. Our approach takes a larger `teacher' network as input and outputs a compressed `student' network derived from the `teacher' network. In the first stage of our method, a recurrent policy network aggressively removes layers from the large `teacher' model. In the second stage, another recurrent policy network carefully reduces the size of each remaining layer. The resulting network is then evaluated to obtain a reward -- a score based on the accuracy and compression of the network. Our approach uses this reward signal with policy gradients to train the policies to find a locally optimal student network. Our experiments show that we can achieve compression rates of more than 10x for models such as ResNet-34 while maintaining similar performance to the input `teacher' network. We also present a valuable transfer learning result which shows that policies which are pre-trained on smaller `teacher' networks can be used to rapidly speed up training on larger `teacher' networks.