Miracle-dz/UniFAR-FTUs huggingface dataset:
FNR activates and represses transcription in vitro

FNR is an iron-binding transcriptional regulator for anaerobic gene expression in Escherichia coli. Footprinting studies with the purified protein have confirmed that it is a site-specific DNA-binding protein. Transcription tests with the positively-regulated FFmelR promoter and the negatively-regulated ndh promoter likewise demonstrated that FNR can activate or repress transcription in vitro. Reducing conditions were not required but activity was abolished by substituting an essential cysteine residue with alanine (C122A) and the affinity for DNA was reduced by iron-depletion. The start point(s) for transcription of the FNR-repressed NADH dehydrogenase II gene (ndh) were identified by transcript mapping and the corresponding promoter (‒35 and ‒10 sequences) was located immediately downstream of the FNR-binding site.
Adaptor Protein‐2 Interaction with Arrestin Regulates GPCR Recycling and Apoptosis

G protein‐coupled receptors (GPCRs) are integral to cellular function in nearly all physiologic and many pathologic processes. GPCR signaling represents an intricate balance between receptor activation, inactivation (desensitization, internalization and degradation) and resensitization (recycling and de novo synthesis). Complex formation between phosphorylated GPCRs, arrestins and an ever‐increasing number of effector molecules is known to regulate cellular function. Previous studies have demonstrated that, although N‐formyl peptide receptor (FPR) internalization occurs in the absence of arrestins, FPR recycling is arrestin‐dependent. Furthermore, FPR stimulation in the absence of arrestins leads to receptor accumulation in perinuclear endosomes and apoptosis. In this study, we show that the interaction of GPCR‐bound arrestin with adaptor protein‐2 (AP‐2) is a critical anti‐apoptotic event. In addition, AP‐2 associates with the receptor‐arrestin complex in perinuclear endosomes and is required for proper post‐endocytic GPCR trafficking. Finally, we observed that depletion of endogenous AP‐2 results in the initiation of apoptosis upon stimulation of multiple GPCRs, including P2Y purinergic receptors and CXCR2, but not CXCR4. We propose a model in which the abnormal accumulation of internalized GPCR‐arrestin complexes in recycling endosomes, resulting from defective arrestin‐AP‐2 interactions, leads to the specific initiation of aberrant signaling pathways and apoptosis.
Log-Likelihood Metrics Based on Two-Symbol-Interval Observations for LDPC Codes with BDPSK Transmission

Iterative decoding of low-density parity-check codes transmitted over noncoherent channels using binary differential phase-shift keying modulation is examined. Using the joint estimation approach and the averaged likelihood function approach, the log-likelihood ratios of the two values of each bit, based on two contiguous received signal samples that convey the bit, are derived. In addition, a simplified approximate metric is introduced and shown to yield similar performance to the two metrics. Simulation results also show that these metrics derived here outperform the existing Gaussian metric. The performances of these metrics in the presence of phase noise and signal-to-noise ratio estimation error are also studied.
Synthetic Lethality Exploitation by an Anti–Trop-2-SN-38 Antibody–Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2–wild-type Triple-Negative Breast Cancer

Purpose: Both PARP inhibitors (PARPi) and sacituzumab govitecan (IMMU-132) are currently under clinical evaluation in triple-negative breast cancer (TNBC). We sought to investigate the combined DNA-damaging effects of the topoisomerase I (Topo I)–inhibitory activity of IMMU-132 with PARPi disruption of DNA repair in TNBC. Experimental Design: In vitro, human TNBC cell lines were incubated with IMMU-132 and various PARPi (olaparib, rucaparib, or talazoparib) to determine the effect on growth, double-stranded DNA (dsDNA) breaks, and cell-cycle arrest. Mice bearing BRCA1/2-mutated or –wild-type human TNBC tumor xenografts were treated with the combination of IMMU-132 and PARPi (olaparib or talazoparib). Study survival endpoint was tumor progression to >1.0 cm3 and tolerability assessed by hematologic changes. Results: Combining IMMU-132 in TNBC with all three different PARPi results in synergistic growth inhibition, increased dsDNA breaks, and accumulation of cells in the S-phase of the cell cycle, regardless of BRCA1/2 status. A combination of IMMU-132 plus olaparib or talazoparib produces significantly improved antitumor effects and delay in time-to-tumor progression compared with monotherapy in mice bearing BRCA1/2-mutated HCC1806 TNBC tumors. Furthermore, in mice bearing BRCA1/2–wild-type tumors (MDA-MB-468 or MDA-MB-231), the combination of IMMU-132 plus olaparib imparts a significant antitumor effect and survival benefit above that achieved with monotherapy. Most importantly, this combination was well tolerated, with no substantial changes in hematologic parameters. Conclusions: These data demonstrate the added benefit of combining Topo I inhibition mediated by IMMU-132 with synthetic lethality provided by PARPi in TNBC, regardless of BRCA1/2 status, thus supporting the rationale for such a combination clinically. Clin Cancer Res; 23(13); 3405–15. ©2017 AACR.
Perception of Risk and Curb Standing at Street Corners by Older Pedestrians

The distances stood from passing traffic of 696 pedestrians waiting to cross signal-controlled intersections were observed. Previous research on elderly pedestrians suggested that the elderly are less perceptive of dangers in the traffic environment because of diminished cognitive abilities. In fact, observations established that older pedestrians were the safest age group, standing the farthest away from traffic. This was especially the case for the most at-risk group, older women. In addition, older pedestrians were the most able to discern greater risks of accidental injury under nighttime crossing conditions and to take appropriate safety precautions.
*Conflict of Interest Statement Click here to download Conflict of Interest Statement: Conflict of Interest Statement.docx Highlights: Placental Viability and RNA Quality Placental explant size and duration of culture affect explant RNA quality. Placental micro explants (≤50mg) in long-term cultured

We evaluated the impact of placental explant size (micro ≤50mg; macro ~200mg), oxygen concentration, culture method and duration on RNA quality. Our findings show that micro explants cultured at 8% oxygen have the best RNA quality and tissue structure after 6 days culture. Explants from early cultures produced poor quality RNA and should be avoided. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. *Conflict of Interest Statement Click here to download Conflict of Interest Statement: Conflict of Interest Statement.docx
Utility of conventional transbronchial needle aspiration with rapid on-site evaluation (c-TBNA-ROSE) at a tertiary care center with endobronchial ultrasound (EBUS) facility

Background: Conventional transbronchial needle aspiration (c-TBNA) is an underutilized bronchoscopic modality. Endobronchial ultrasound (EBUS) guided-TBNA though efficacious is an expensive modality, facilities of which are available at only limited centers. c-TBNA is cost-effective and has potential for wide utilization especially in resource-limited settings. Rapid on-site evaluation (ROSE) improves the yield of c-TBNA. Materials and Methods: A retrospective review of the bronchoscopy records (May 2012 to July 2014) was performed. The patients who underwent c-TBNA with ROSE were included in the study and their clinical details were extracted. Convex probe EBUS-TBNA was being regularly performed during the study period by the operators performing c-TBNA. Results: c-TBNA with ROSE was performed in 41 patients with mean age of 42.4 (16.2) years. The most frequently sampled node stations (>90% patients) were the subcarinal and lower right paratracheal. Representative samples could be obtained in 33 out of the 41 patients (80.4%). c-TBNA was diagnostic in 32 [tuberculosis (TB)-8, sarcoidosis-9, and malignancy-15] patients out of the 41 patients. The overall diagnostic yield (sensitivity) of c-TBNA with ROSE was 78%. Mean procedure duration was 18.4 (3.1) min and there were no procedural complications. Conclusion: c-TBNA with ROSE is a safe, efficacious, and cost-effective bronchoscopic modality. When it was performed by operators routinely performing EBUS-TBNA, diagnostic yields similar to that of EBUS-TBNA can be obtained. Even at the centers where EBUS facilities are available, c-TBNA should be routinely performed.
Ross River Virus Envelope Glycans Contribute to Type I Interferon Production in Myeloid Dendritic Cells

ABSTRACT Alphaviruses are mosquito-transmitted viruses that cause significant human disease, and understanding how these pathogens successfully transition from the mosquito vector to the vertebrate host is an important area of research. Previous studies demonstrated that mosquito and mammalian-cell-derived alphaviruses differentially induce type I interferons (alpha/beta interferon [IFN-α/β]) in myeloid dendritic cells (mDCs), where the mosquito cell-derived virus is a poor inducer of IFN-α/β compared to the mammalian-cell-derived virus. Furthermore, the reduced IFN-α/β induction by the mosquito cell-derived virus is attributed to differential N-linked glycosylation (29). To further evaluate the role of viral envelope glycans in regulating the IFN-α/β response, studies were performed to assess whether the mosquito cell-derived virus actively inhibits IFN-α/β induction or is simply a poor inducer of IFN-α/β. Coinfection studies using mammalian- and mosquito cell-derived Ross River virus (mam-RRV and mos-RRV, respectively) indicated that mos-RRV was unable to suppress IFN-α/β induction by mam-RRV in mDC cultures. Additionally, a panel of mutant viruses lacking either individual or multiple N-linked glycosylation sites was used to demonstrate that N-linked glycans were essential for high-level IFN-α/β induction by the mammalian-cell-derived virus. These results suggest that the failure of the mosquito cell-derived virus to induce IFN-α/β is due to a lack of complex carbohydrates on the virion rather than the active suppression of the DC antiviral response.
Resistance of Cultivated Tomato to Cell Content-Feeding Herbivores Is Regulated by the Octadecanoid-Signaling Pathway1

The octadecanoid signaling pathway has been shown to play an important role in plant defense against various chewing insects and some pathogenic fungi. Here, we examined the interaction of a cell-content feeding arachnid herbivore, the two-spotted spider mite (Tetranychus urticae Koch), with cultivated tomato (Lycopersicon esculentum) and an isogenic mutant line (defenseless-1 [def-1]) that is deficient in the biosynthesis of the octadecanoid pathway-derived signal, jasmonic acid (JA). Spider mite feeding and fecundity ondef-1 plants was significantly greater than on wild-type plants. Decreased resistance of def-1 plants was correlated with reduced JA accumulation and expression of defensive proteinase inhibitor (PI) genes, which were induced in mite-damaged wild-type leaves. Treatment of def-1 plants with methyl-JA restored resistance to spider mite feeding and reduced the fecundity of female mites. Plants expressing a35S::prosystemin transgene that constitutively activates the octadecanoid pathway in a Def-1-dependent manner were highly resistant to attack by spider mites and western flower thrips (Frankliniella occidentalis), another cell-content feeder of economic importance. These findings indicate that activation of the octadecanoid signaling pathway promotes resistance of tomato to a broad spectrum of herbivores. The techniques of amplified fragment length polymorphism (AFLP) and bulk segregant analysis were used to map the Def-1 gene to a region on the long arm of chromosome 3 that is genetically separable from the map position of known JA biosynthetic genes. Tight linkage ofDef-1 to a T-DNA insertion harboring the maize (Zea mays) Dissociation transposable element suggests a strategy for directed transposon tagging of the gene.
Do clinical clerks suffer ethical erosion? Students' perceptions of their ethical environment and personal development

BACKGROUND. Little is known about the ethical dilemmas that medical students believe they encounter while working in hospitals or how students feel these dilemmas affect them. The authors examine how clinical students perceive their ethical environment, their feelings about their dilemmas, and whether these dilemmas erode students' ethical principles. METHOD. An anonymous mail survey was sent in 1992–93 to the 1,853 third- and fourth-year medical students enrolled at six Pennsylvania medical schools. The survey addressed whether students had encountered situations they felt were ethically problematic, their attitudes toward these situations, and their perceptions of their personal ethical development. Data were analyzed with logistic regression; respondents' comments were analyzed qualitatively. RESULTS. Of the 665 students (36%) who responded, 58% reported having done something they believed was unethical, and 52% reported having misled a patient; 80% reported at least one of these two behaviors. In addition, 98% had heard physicians refer derogatorily to patients; 61% had witnessed what they believed to be unethical behavior by other medical team members, and of these students, 54% felt like accomplices. Many students reported dissatisfaction with their actions and ethical development: 67% had felt bad or guilty about something they had done as clinical clerks; 62% believed that at least some of their ethical principles had been eroded or lost. Controlling for other factors, students who had witnessed an episode of unethical behavior were more likely to have acted improperly themselves for fear of poor evaluation [odds ratio, OR, 1.37 (95% CI, 1.18–1.60)] or to fit in with the team [OR 1.45 (1.25–1.69)]. Moreover, students were twice as likely to report erosion of their ethical principles if they had behaved unethically for fear of poor evaluation [OR 2.25 (1.47–3.45)] or to fit in with the team [OR 1.78 (1.18–2.71)]. CONCLUSION. The ethical dilemmas that medical students perceive as affecting them while serving as clinical clerks are apparently common and often detrimental, and warrant the attention of physicians, educators, and ethicists.
Unemployment Duration: Competing and Defective Risks

This paper examines the determinants of unemployment duration in a competing risks framework with two destination states, namely, inactivity and employment. The major innovation is our recognition of defective risks. We first use a polynomial hazard function to test for the presence of two-sources of defective risks: search involving a random process of unlucky draws that yields a non-proper duration distribution; and a split-population model in which the decision by some individuals not to consider certain destination states produces a defective distribution. Having established the primacy of the latter model, we refine it using a more flexible piecewise-constant baseline hazard function. This specification broadly confirms our earlier findings but offers a more convincing explanation for positive and zero transition rates out of unemployment. Although we do not reject the null of proportionality, abandoning the proportionality assumption does not materially alter our conclusions.
10: Oxygen Transport During Exercise at Altitude and the Lactate Paradox Lessons from Operation Everest II and Pikes Peak

It seems unlikely that oxygen-limited metabolism explains the increased lactate concentrations in blood or muscle during exercise at high altitude compared with sea level values because: 1. Even marked hypoxia equivalent to that at the summit of Mt. Everest may not be sufficiently severe to impair function or to impair muscle oxidative metabolism markedly during exercise; 2. At this very high altitude, muscle hypoxemia is probably not the limiting factor for exercise performance; other systems, i.e., the cerebral cortex [24, 33], probably fail before hypoxemia impairs muscle metabolism; 3. The traditional view of oxygen-limited aerobic metabolism during exercise at high altitude does not explain a long-standing dilemma in altitude physiology, the lactate paradox (in which blood lactate accumulation during exercise is increased on arrival at high altitude but falls with acclimatization), because the lactate fall is independent of muscle oxygenation; 4. Net lactate release by the leg during exercise is independent of oxygenation; 5. Kinetic studies show that lactate appearance and disappearance are closely linked and both increase with acute altitude exposure and decrease with acclimatization; 6. Lactate appearance rate is strongly correlated with, and may be influenced by, the extent of beta-adrenergic stimulation; 7. The beta-adrenergic stimulation may be, in part, determined by the degree of arterial oxygenation.
Clinico-radiological aspects of neurocysticercosis in pediatric population in a tertiary hospital.

INTRODUCTION Neurocysticercosisis common in developing countries including Nepal. Clinicalpresentations vary depending on the CT scan findings of head. Adequate information of neurocysticercosis in children from Western Nepal is lacking. This study was conducted with an objective of evaluating the most common clinical and radiological picture in children suffering from NCC at a tertiary care teaching hospital in Western Nepal. METHODS Hospital records of all pediatric inpatients, admitted from 16th June 2010 to 15th December 2012, consistent with the diagnosis of Neurocysticercosis were reviewed. RESULTS Forty nine cases of neurocysticercosis were enrolled. Their age varied 2.6 years to 14 years with the mean age of 10.6 years and the peak age was at 12 years with slight male predominance, ratio being male:female 1.2:1. The commonest presentation was seizures (n=38; 77.5 %); partial seizures being most common. Most of the lesions were single (n=44; 89.8%), predominantly in the parietal region (n=20; 40.8%) and most were in transitional stage (61.22%) in Computed tomography (CT). However, number of lesions from CT scan of head showed no significance in association with seizure types (p=0.84). In addition, perilesional edema and scolex within the lesion were noted in 67.34% and 18.36% of the cases respectively. CONCLUSIONS Any child presenting with acute onset of afebrile seizure should be screened for neurocysticercosis provided other common infective and metabolic causes are ruled out. CT scan is the valuable diagnostic tool to support our diagnosis.
Weekly digestibilities of diets supplemented with corn oil, lard or tallow by weanling swine.

Two experiments were conducted to evaluate supplementation of diets with 8% corn oil, lard or tallow. In Exp. 1, 36 barrows weaned at 21 d of age were used to evaluate the effects of these three diets on digestibilities of fat and dry matter and subsequent N retentions from wk 1 to 4 postweaning. In Exp. 2, 147 weanling pigs in six replicates were used to evaluate weekly growth and feed performance measurements when fed these same diets for a 4-wk postweaning period. A large quantity of fat was absorbed (P less than .01) during wk 1 postweaning by pigs fed the corn oil diet, with the quantity absorbed similar for the three sources of fat from wk 2 to 4. Diets with corn oil had a higher apparent fat digestibility than diets supplemented with lard or tallow during each week postweaning (P less than .05). Apparent digestibility of fat increased (P less than .01) for each fat source each week postweaning but appeared to reach a plateau by wk 3 postweaning. Differences in apparent digestibility of fat between fat sources narrowed from wk 1 to wk 4, with digestibility of corn oil increasing from 79 to 89% and of animal fat sources increasing from 67 to 84%. Apparent digestibility of dry matter tended (P less than .10) to be highest when corn oil was provided during the initial 2-wk postweaning period. Although N retention was highest during wk 1 postweaning when the corn oil was fed, this response was attributed to the higher feed intakes of pigs fed this diet. (ABSTRACT TRUNCATED AT 250 WORDS)
Human resource management, strategic involvement and e-HRM technology

Associated with the emergence of internet-based human resource management technology is rhetoric predicting that such technological advances (electronic human resource management technology or e-HRM) will make HRM in organizations more strategic. Yet such a prediction is contested in the literature on the role of technology in organizations. Using a large survey data-set consisting of 5665 companies that are located in 32 different countries, we use non-recursive simultaneous equation models with instrumental variables to empirically evaluate competing theoretical perspectives in this literature. We find and show that strategic HR involvement and greater e-HRM capability are both directly and reciprocally related supporting both theoretical perspectives but also showing each is not mutually exclusive. We discuss the implication of these results for human resource management theory, practice and future research.
Fiber Bragg Grating Inscription in a Thin-Core Fiber for Displacement Measurement

A compact power-referenced fiber displacement sensor is proposed and experimentally demonstrated. It comprises a simple structure in which a section of a photosensitive thin-core fiber (TCF) containing a fiber Bragg grating (FBG) is spliced into another single-mode fiber. Both the core mode and cladding mode of TCF are coupled at the core-mismatch junction and appear as two well-defined resonance bands in reflection spectrum from the downstream FBG. The cladding modes exhibit strong bending dependence due to bending-induced loss in the recoupling from the cladding modes to the core mode. The cladding modes in reflection are collected to measure the bending of fiber. Meanwhile, the intensity of the core mode is virtually unaffected by the bending of fiber and, thus, can be used as a power reference to cancel out any light source fluctuations. In addition, temperature change just makes the reflection spectrum shift and does not change its intensity, making it a good candidate for measuring displacement and temperature simultaneously.