Miracle-dz/UniFAR-FTUs huggingface dataset:
The differences in neural network activity between methamphetamine abusers and healthy subjects performing an emotion‐matching task: functional MRI study

Methamphetamine (MA) abusers commonly exhibit socially problematic behaviors, such as diminished empathy, decreased emotional regulation and interpersonal violence, which may be attributable to alterations in emotional experience. However, few studies have used functional MRI to examine directly the emotional experience of threatening or fearful non‐face images in MA abusers. In this study, we investigated possible differences in neural correlates of negative emotional experiences between abstinent MA abusers and healthy subjects using complex visual scenes depicting fear or threat derived from the International Affective Picture System. In within‐group analyses, healthy subjects and MA abusers activated a similarly distributed cortical network, prominently including the amygdala, fusiform gyrus, parahippocampal gyrus, ventrolateral prefrontal cortex and inferior frontal cortex. In between‐group analyses, however, MA abusers showed a reduced activation in the bilateral dorsolateral prefrontal cortex and insula, and increased activation in the fusiform gyrus, hippocampus, parahippocampal gyrus and posterior cingulate cortex, relative to healthy subjects. Hypoactivation of the insula in MA abusers relative to healthy subjects suggests that the ability to have an emotional response to threatening scenes and empathy for another's pain could be compromised in MA abusers. Hyperactivity in the fusiform gyrus, parahippocampal gyrus and posterior cingulate cortex in MA abusers relative to healthy subjects indicates that threatening and fearful images from the International Affective Picture System may remind MA abusers of episodic memory related to similar experiences. Therefore, functional impairment of these neural networks in MA abusers may contribute to altered emotional experience in social interactions, which could lead to increased negative mood and stress in interpersonal communication. Copyright © 2011 John Wiley & Sons, Ltd.
Organizational Transparency: Conceptualizations, Conditions, and Consequences

Transparency is an increasingly prominent area of research that offers valuable insights for organizational studies. However, conceptualizations of transparency are rarely subject to critical scrutiny and thus their relevance remains unclear. In most accounts, transparency is associated with the sharing of information and the perceived quality of the information shared. This narrow focus on information and quality, however, overlooks the dynamics of organizational transparency. To provide a more structured conceptualization of organizational transparency, this article unpacks the assumptions that shape the extant literature, with a focus on three dimensions: conceptualizations, conditions, and consequences. The contribution of the study is twofold: (a) On a conceptual level, we provide a framework that articulates two paradigmatic positions underpinning discussions of transparency, verifiability approaches and performativity approaches; (b) on an analytical level, we suggest a novel future research agenda for studying organizational transparency that pays attention to its dynamics, paradoxes, and performative characteristics.
Calcium influx selects the fast mode of endocytosis in the synaptic terminal of retinal bipolar cells

To investigate the regulation of endocytosis by Ca2+, we have made capacitance measurements in the synaptic terminal of depolarizing bipolar cells from the retina of goldfish. After a brief depolarization, all of the excess membrane was retrieved rapidly (τ ≈1 s). But when the rise in free [Ca2+] was reduced by the introduction of Ca2+ buffers [1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate (BAPTA) or EGTA], a large fraction of the membrane was retrieved by a second, slower mechanism (τ ≥ 10 s). The block of fast endocytosis by EGTA could be overcome by increasing the amplitude of the Ca2+ current, demonstrating that Ca2+ influx was the trigger for fast endocytosis. These manipulations of the Ca2+ signal altered the relative proportions of fast and slow endocytosis but did not modulate the rate constants of these processes. A brief stimulus that triggered fast endocytosis did not generate a significant rise in the spatially averaged [Ca2+], indicating that Ca2+ regulated endocytosis through an action close to the active zone. The slow mode of retrieval occurred at the resting [Ca2+]. These results demonstrate that Ca2+ influx couples fast endocytosis and exocytosis at this synapse.
Calculating core‐level excitations and x‐ray absorption spectra of medium‐sized closed‐shell molecules with the algebraic‐diagrammatic construction scheme for the polarization propagator

Core‐level excitations are generated by absorption of high‐energy radiation such as X‐rays. To describe these energetically high‐lying excited states theoretically, we have implemented a variant of the algebraic‐diagrammatic construction scheme of second‐order ADC(2) by applying the core‐valence separation (CVS) approximation to the ADC(2) working equations. Besides excitation energies, the CVS‐ADC(2) method also provides access to properties of core‐excited states, thereby allowing for the calculation of X‐ray absorption spectra. To demonstrate the potential of our implementation of CVS‐ADC(2), we have chosen medium‐sized molecules as examples that have either biological importance or find application in organic electronics. The calculated results of CVS‐ADC(2) are compared with standard TD‐DFT/B3LYP values and experimental data. In particular, the extended variant, CVS‐ADC(2)‐x, provides the most accurate results, and the agreement between the calculated values and experiment is remarkable. © 2014 Wiley Periodicals, Inc.
Aromatic Hydrocarbon Receptor Interaction with the Retinoblastoma Protein Potentiates Repression of E2F-dependent Transcription and Cell Cycle Arrest*

Polyhalogenated aromatic hydrocarbons, of which 2,3,7,8-tetrachloro-p-dioxin (TCDD) is the prototype compound, elicit a variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans. In cultured cells, TCDD shows marked effects on the regulation of cell cycle progression, including thymocyte apoptosis, induction of keratinocyte proliferation and terminal differentiation, and inhibition of estrogen-dependent proliferation in breast cancer cells. The presence of an LXCXE domain in the dioxin aromatic hydrocarbon receptor (AHR), suggested that the effects of TCDD on cell cycle regulation might be mediated by protein-protein interactions between AHR and the retinoblastoma protein (RB). Using the yeast two-hybrid system, AHR and RB were in fact shown to bind to each other. In vitro pull-down experiments with truncated AHR peptides indicated that at least two separate AHR domains form independent complexes with hypophosphorylated RB. Coimmunoprecipitation of whole cell lysates from human breast carcinoma MCF-7 cells, which express both proteins endogenously, revealed that AHR associates with RB in vivo only after receptor transformation and nuclear translocation. However, the AHR nuclear translocator and transcriptional heterodimerization partner, is not required for (nor is it a part of) the AHR·RB complexes detected in vitro. Ectopic expression of AHR and RB in human osteosarcoma SAOS-2 cells, which lack endogenous expression of both proteins, showed that AHR synergizes with RB to repress E2F-dependent transcription and to induce cell cycle arrest. Furthermore, AHR partly blocked T-antigen-mediated reversal of RB-dependent transcriptional repression. These results uncover a potential function for the AHR in cell cycle regulation and suggest that this function may be that of serving as an environmental sensor that signals cell cycle arrest when cells are exposed to certain environmental toxicants.
The hFbpABC Transporter from Haemophilus influenzae Functions as a Binding-Protein-Dependent ABC Transporter with High Specificity and Affinity for Ferric Iron

ABSTRACT Pathogenic Haemophilus influenzae, Neisseria spp. (Neisseria gonorrhoeae and N. meningitidis), Serratia marcescens, and other gram-negative bacteria utilize a periplasm-to-cytosol FbpABC iron transporter. In this study, we investigated the H. influenzae FbpABC transporter in a siderophore-deficient Escherichia coli background to assess biochemical aspects of FbpABC transporter function. Using a radiolabeled Fe3+ transport assay, we established an apparent Km = 0.9 μM and Vmax = 1.8 pmol/107cells/min for FbpABC-mediated transport. Complementation experiments showed that hFbpABC is dependent on the FbpA binding protein for transport. The ATPase inhibitor sodium orthovanadate demonstrated dose-dependent inhibition of FbpABC transport, while the protonmotive-force-inhibitor carbonyl cyanide m-chlorophenyl hydrazone had no effect. Metal competition experiments demonstrated that the transporter has high specificity for Fe3+ and selectivity for trivalent metals, including Ga3+ and Al3+, over divalent metals. Metal sensitivity experiments showed that several divalent metals, including copper, nickel, and zinc, exhibited general toxicity towards E. coli. Significantly, gallium-induced toxicity was specific only to E. coli expressing FbpABC. A single-amino-acid mutation in the gene encoding the periplasmic binding protein, FbpA(Y196I), resulted in a greatly diminished iron binding affinity Kd = 5.2 × 10−4 M−1, ∼14 orders of magnitude weaker than that of the wild-type protein. Surprisingly, the mutant transporter [FbpA(Y196I)BC] exhibited substantial transport activity, ∼35% of wild-type transport, with Km = 1.2 μM and Vmax = 0.5 pmol/107cells/min. We conclude that the FbpABC complexes possess basic characteristics representative of the family of bacterial binding protein-dependent ABC transporters. However, the specificity and high-affinity binding characteristics suggest that the FbpABC transporters function as specialized transporters satisfying the strict chemical requirements of ferric iron (Fe3+) binding and membrane transport.
Identification of Infection- and Defense-Related Genes via a Dynamic Host-Pathogen Interaction Network Using a Candida Albicans-Zebrafish Infection Model

Candida albicans infections and candidiasis are difficult to treat and create very serious therapeutic challenges. In this study, based on interactive time profile microarray data of C. albicans and zebrafish during infection, the infection-related protein-protein interaction (PPI) networks of the two species and the intercellular PPI network between host and pathogen were simultaneously constructed by a dynamic interaction model, modeled as an integrated network consisting of intercellular invasion and cellular defense processes during infection. The signal transduction pathways in regulating morphogenesis and hyphal growth of C. albicans were further investigated based on significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins from which we can gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. The hyphal growth PPI network, zebrafish PPI network and host-pathogen intercellular PPI network were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host, and may help improve medical therapies and facilitate the development of new antifungal drugs.
Suicide and attempted suicide in Huntington disease: implications for preclinical testing of persons at risk.

Suicide behavior in Huntington disease (HD) was assessed by examining the proportion of deaths attributed to suicide among 452 deceased individuals with HD and the number and pattern of attempted suicides among a total population of 831 HD patients from the National Huntington Disease Research Roster. It was found that 5.7% of deaths among affected persons resulted from suicide and 27.6% of patients attempted suicide at least once. Comparison of this group with the general population indicated that the proportion of deaths due to suicide among persons with HD is almost four times greater than the corresponding proportion for the U.S. Caucasian population. Age at onset of HD was not significantly different between HD suicide and non-suicide patients, although suicide occurred more frequently in the early to middle stages of the illness. The "success" rate among HD suicide attempters did not differ from the general population rates in several western European countries. The relatively high suicide and attempted suicide rates in HD indicate that thorough psychological testing of at-risk persons and extensive patient support systems must be integral components of a program to identify HD gene carriers using a genetic marker.
High endogenous estradiol is associated with increased venous distensibility and clinical evidence of varicose veins in menopausal women.

OBJECTIVE The purpose of this study was to determine if there is an association between elevated sex hormones (ie, serum estradiol, sex hormone binding globulin [SHBG], testosterone) and increased venous distension and clinical evidence of varicose veins in menopausal women. METHODS Participants were 104 healthy volunteer menopausal women, aged 48 to 65 years, who were not undergoing hormonal treatment. Of these 104, 14 were excluded from analyses because their estradiol levels were compatible with a premenopausal condition (4), because they had missing values for insulin concentration (5), and because they did not show up at venous vessel examination (5). Patients underwent a physical examination to determine the presence of varicose veins; a venous strain-gauge plethysmographic examination to compute instrumental measures of venous distensibility; and laboratory analyses of blood so serum testosterone, estradiol, SHBG, glucose, and insulin could be measured. There were also prevalence ratios and odds ratios used to test the presence of an association between biochemical and instrumental variables. RESULTS Serum levels of estradiol in the upper tertile of the frequency distribution were significantly associated with clinical evidence of varicose veins (prevalence odds ratios 3.6; 95% CI 1.1-11.6) and with increased lower limb venous distensibility (prevalence odds ratios 4.4; 95% CI 1.2-15.5). No association was found for SHBG and testosterone. CONCLUSIONS Our finding that high serum levels of estradiol are associated with clinical evidence of varicose veins and instrumental measurements indicating increased venous distensibility in menopausal women suggests that endogenous estrogens may play a role in the development of this very common venous vessel abnormalities.
Law Enforcement in a Federal System: On the Strategic Choice of Sanction Levels

This paper explores law enforcement in a federal system to address the reality that the level of deterrence often results from decision making at different levels of the system. In this setting, the presence of interregional externalities in the form of crime diversion induces socially excessive law enforcement incentives at the local level. We show that the adverse repercussions of uncoordinated enforcement decisions at the local level may be ameliorated by the strategic choice of the sanction at the central level. A nonmaximal sanction may be optimal, even though a maximal sanction would be optimal when the central level chooses all law enforcement variables. This conclusion shows that optimal law enforcement in a federal system must take account of the strategic interdependencies of relevant actors. We also discuss whether other arrangements of decision-making powers may be associated with higher levels of welfare.
Selective induction heating for wafer level bonding and packaging

Selective induction heating for wafer level bonding is presented. The purpose of this paper is to investigate the relationships between the geometry of solder loop and temperature distribution in induction heating. Using finite element method (FEM) and IR thermal imager, temperature distribution and variation are explored, which shows that the temperature on the solder loops is a function of the area and edge width in the induction heating. The temperature difference between the solder loop and its center on PCB is about 180°, which shows an obvious selective heating effect. Thermal images of circle and square solder array indicate uniform temperature distribution on the PCB in the induction heating. Good agreement between measured and simulated temperature variation have been achieved.
p38 MAPK, but not ERK1/2, is critically involved in the cytotoxicity of the novel vascular disrupting agent combretastatin A4

Combretastatin A4 (CA4) is a novel vascular disrupting agent that has promising clinical efficacy because of its ability to inhibit microtubule assembly and subsequently disrupt tumor blood flow. In this study, we demonstrate that mitogen‐activated protein kinases (MAPKs) are critically involved in the cytotoxicity of CA4. CA4 stimulates both extracellular signal‐regulated kinases (ERK1/2) and p38 MAPK in the BEL‐7402 hepatocellular carcinoma cell line in a time‐ and dose‐dependent manner. This stimulation is a result of CA4‐induced microtubule disassembly, which is a reversible process. Reversibility of microtubule disassembly is evidenced by the ability of disassembled microtubules to reassemble just a few hours after CA4 treatment. p38 MAPK, but not ERK1/2, contributes to this microtubule reassembly following CA4 exposure, and only inhibition of p38 MAPK, but not ERK1/2, synergistically enhances CA4‐induced G2/M cell cycle arrest. Consistent with this, p38 MAPK inhibitors such as SB203580 and SB202190 also synergistically enhance the cytotoxicity of CA4 in cells where p38 MAPK is activated by CA4. This enhancement appears to be specific for CA4 because the cytotoxicity of other microtubule‐targeted agents such as paclitaxel, vinorelbine and colchicine was not affected by p38 MAPK inhibitors. These data indicate that p38 MAPK is a potential anticancer target and that the combination of CA4 with p38 MAPK inhibitors may be a novel and promising strategy for cancer therapy. © 2007 Wiley‐Liss, Inc.
Targeting EGF-receptor(s) - STAT1 axis attenuates tumor growth and metastasis through downregulation of MUC4 mucin in human pancreatic cancer

Transmembrane proteins MUC4, EGFR and HER2 are shown to be critical in invasion and metastasis of pancreatic cancer. Besides, we and others have demonstrated de novo expression of MUC4 in ~70-90% of pancreatic cancer patients and its stabilizing effects on HER2 downstream signaling in pancreatic cancer. Here, we found that use of canertinib or afatinib resulted in reduction of MUC4 and abrogation of in vitro and in vivo oncogenic functions of MUC4 in pancreatic cancer cells. Notably, silencing of EGFR family member in pancreatic cancer cells decreased MUC4 expression through reduced phospho-STAT1. Furthermore, canertinib and afatinib treatment also inhibited proliferation, migration and survival of pancreatic cancer cells by attenuation of signaling events including pERK1/2 (T202/Y204), cyclin D1, cyclin A, pFAK (Y925) and pAKT (Ser473). Using in vivo bioluminescent imaging, we demonstrated that canertinib treatment significantly reduced tumor burden (P=0.0164) and metastasis to various organs. Further, reduced expression of MUC4 and EGFR family members were confirmed in xenografts. Our results for the first time demonstrated the targeting of EGFR family members along with MUC4 by using pan-EGFR inhibitors. In conclusion, our studies will enhance the translational acquaintance of pan-EGFR inhibitors for combinational therapies to combat against lethal pancreatic cancer.
The immunogenomics of minor histocompatibility antigens

Summary: Minor histocompatibility (H) antigens are a diverse assemblage of major histocompatibility complex (MHC)‐bound peptides with the unifying property of acting as alloantigens that induce allogeneic tissue rejection. They are a consequence of any form of accumulated genetic variation that translates to differential MHC‐presented peptide epitopes, the most common form of which is simple sequence polymorphisms. The universe of potential minor H antigens is large when transplantation is performed between genetically unrelated, MHC‐matched individuals, especially considering the remarkable discriminative sensitivity of T cells. However, the phenomenon of immunodominance greatly simplifies immune responses that ensue. One mouse minor H antigen, H60, stands out in that the preponderance of the CD8 T cell response elicited in a complex alloantigenic setting is directed against this single minor H antigen epitope. Its immunodominance is because mice lacking H60 develop an unusually robust T cell repertoire dedicated to this single minor H antigen. The now well‐characterized mouse minor H antigen system should provide a vehicle to assess the degree to which immunodominant alloantigens contribute to transplant rejection.
Urine Proteomics Biomarkers in Renal Transplantation: An Overview

A major goal of clinical proteomics was to identify biomarkers that can aid in the diagnosis and prognosis of different conditions. These biomarkers will not only assist the clinician in the diagnosis of a disease but they will also give directions as to which therapy may be more appropriate for each patient, thus contributing to the development of personalized medicine. This review discusses the current concepts in urine proteomics aimed at identifying predictive biomarkers that could detect the presence of acute rejection or chronic allograft dysfunction early on and for instance be used to personalize immunosuppressive therapies for kidney transplant patients.
Experimental evaluation of the usefulness of microsatellite DNA for detecting demographic bottlenecks

Evolutionary and conservation biologists often use molecular markers to evaluate whether populations have experienced demographic bottlenecks that resulted in a loss of genetic variation. We evaluated the utility of microsatellites for detection of recent, severe bottlenecks and compared the amounts of genetic diversity lost in bottlenecks of different sizes. In experimental mesocosms, we established replicate populations by releasing 1, 2, 4 or 8 pairs of the western mosquitofish, Gambusia affinis (Poeciliidae). Using eight polymorphic microsatellite loci, we quantified seven indices of genetic diversity or change that have been used to assess the effects of demographic bottlenecks on populations. We compared indices for the experimentally bottlenecked populations to those for the source population and examined differences between populations established with different numbers of founders. Direct count heterozygosity and the proportion of polymorphic loci were not very sensitive to genetic changes that resulted from the experimental bottlenecks. Heterozygosity excess and expected heterozygosity were useful to varying degrees in the detection of bottlenecks. Allelic diversity and temporal variance in allele frequencies were most sensitive to genetic changes that resulted from the bottlenecks, and the temporal variance method was slightly more correlated with bottleneck size than was allelic diversity. Based on comparisons to a previous study with allozymes, heterozygosity, temporal variance in allele frequencies and allelic diversity, but not proportion of polymorphic loci, appear to be more sensitive to demographic bottlenecks when quantified using microsatellites. We found that analysis of eight highly polymorphic loci was sufficient to detect a recent demographic bottleneck and to obtain an estimate of the magnitude of bottleneck severity.