Miracle-dz/UniFAR-FTUs huggingface dataset:
Incremental conductance levels of GABAA receptors in dopaminergic neurones of the rat substantia nigra pars compacta

1 Molecular and biophysical properties of GABAA receptors of dopaminergic (DA) neurones of the pars compacta of the rat substantia nigra were studied in slices and after acute dissociation. 2 Single‐cell reverse transcriptase‐multiplex polymerase chain reaction confirmed that DA neurones contained mRNAs encoding for the α3 subunit of the GABAA receptor, but further showed the presence of α4 subunit mRNAs. α2, β1 and γ1 subunit mRNAs were never detected. Overall, DA neurones present a pattern of expression of GABAA receptor subunit mRNAs containing mainly α3/4β2/3γ3. 3 Outside‐out patches were excised from DA neurones and GABAA single‐channel patch‐clamp currents were recorded under low doses (1‐5 μM) of GABA or isoguvacine, a selective GABAA agonist. Recordings presented several conductance levels which appeared to be integer multiples of an elementary conductance of 4‐5 pS. This property was shared by GABAA receptors of cerebellar Purkinje neurones recorded in slices (however, with an elementary conductance of 3 pS). Only the 5‐6 lowest levels were analysed. 4 A progressive change in the distribution of occupancy of these levels was observed when increasing the isoguvacine concentration (up to 10 μM) as well as when adding zolpidem (20‐200 nM), a drug acting at the benzodiazepine binding site: both treatments enlarged the occupancy of the highest conductance levels, while decreasing that of the smallest ones. Conversely, Zn2+ (10 μM), a negative allosteric modulator of GABAA receptor channels, decreased the occupancy of the highest levels in favour of the lowest ones. 5 These properties of α3/4β2/3γ3‐containing GABAA receptors would support the hypothesis of either single GABAA receptor channels with multiple open states or that of a synchronous recruitment of GABAA receptor channels that could involve their clustering in the membranes of DA neurones.
The evolution of coastal tourism destinations: a path plasticity perspective on tourism urbanisation

ABSTRACT Evolutionary and relational approaches to economic development are gaining ground in geography as a discipline, although in the subfield of tourism geography, their potential is only just becoming recognised. This article focuses on the evolution of mature tourism destinations, taking the path dependency concept forward from the notion of path creation into the new domain of path plasticity. Drawing on the notion of cultural political economy, we examine how tourism destinations can break with path dependency routines incrementally and move steadily towards different future paths, which may recast tourism in a different light in the overall “urban” context of the destination. Using a case study of a Mediterranean coastal destination on Catalonia's Costa Daurada, we explore the inter-tangled tourism and urban development processes in relation to the socio-spatial dimensions of urban change. The article argues for a wider range of social and cultural criteria in the analysis of tourism evolution – advocating the use of path plasticity and a cultural political economy approach – to offer an alternative perspective on shifting tourism situations, reflecting the inherently “urbanising” nature of tourism development in the traditional coastal resort context. It adds to the growing literature on governance and strategy-making in sustainable tourism.
Assessment Literacy for Teacher Candidates: A Focused Approach.

The assessment of student learning has always been an integral element of the craft of teaching; however, contemporary demands for demonstrable student growth and teacher accountability have heightened the importance of this domain of professional responsibility. Additionally, there is evidence that many novice and experienced teachers tend to be relatively weaker in this domain as compared to other areas of professional practice, such as instructional planning, instructional delivery, and classroom management. This article describes an approach to developing the assessment literacy of teacher candidates in a nationally accredited, public university. A definition of assessment literacy and a conceptual framework for the foundational knowledge and skills of assessment literacy are presented and explained within the context of a focused, one-credit course for pre-service general education teachers. Evidence of impact is provided, as are limitations and cautions. The article concludes with grounded insights into the need to develop the assessment literacy of teacher candidates.
The small GTPase ADP-Ribosylation Factor 1 mediates the sensitivity of triple negative breast cancer cells to EGFR tyrosine kinase inhibitors

The clinical use of EGFR-targeted therapy, in triple negative breast cancer patients, has been limited by the development of resistance to these drugs. Although activated signaling molecules contribute to this process, the molecular mechanisms remain relatively unknown. We have previously reported that the small GTPase ADP-Ribosylation Factor 1 (ARF1) is highly expressed in invasive breast cancer cells and acts as a molecular switch to activate EGF-mediated responses. In this study, we aimed at defining whether the high expression of ARF1 limits sensitivity of these tumor cells to EGFR inhibitors, such as gefitinib. Here, we show that the knock down of ARF1 expression or activity decreased the dose and latency time required by tyrosine kinase inhibitors to induce cell death. This may be explained by the observation that the depletion of ARF1 suppressed gefitinib-mediated activation of key mediators of survival such as ERK1/2, AKT and Src, while enhancing cascades leading to apoptosis such as the p38MAPK and JNK pathways, modifying the Bax/Bcl2 ratio and cytochrome c release. In addition, inhibiting ARF1 expression and activation also results in an increase in gefitinib-mediated EGFR internalization and degradation further limiting the ability of this receptor to promote its effects. Interestingly, we observed that gefitinib treatment resulted in the enhanced activation of ARF1 by promoting its recruitment to the receptor AXL, an important mediator of EGFR inhibition suggesting that ARF1 may promote its pro-survival effects by coupling to alternative mitogenic receptors in conditions where the EGFR is inhibited. Together our results uncover a new role for ARF1 in mediating the sensitivity to EGFR inhibition and thus suggest that limiting the activation of this GTPase could improve the therapeutic efficacy of EGFR inhibitors.
Impact of Pharmacogenetic Markers of CYP2B6, Clinical Factors, and Drug-Drug Interaction on Efavirenz Concentrations in HIV/Tuberculosis-Coinfected Patients

ABSTRACT Comprehensive information on the effects of cytochrome P450 2B6 (CYP2B6) polymorphisms, clinical factors, and drug-drug interactions on efavirenz concentrations in HIV/tuberculosis-coinfected (HIV/TB) patients is unavailable. A total of 139 HIV/TB adults, 101 of whom received a rifampin-containing anti-TB regimen, were prospectively enrolled to receive efavirenz (600 mg)/tenofovir/lamivudine. Nine single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped. Plasma efavirenz concentrations were measured at 12 weeks. The median (interquartile range [IQR]) efavirenz concentration was 2.3 (1.4 to 3.9) mg/liter. The SNPs (frequencies of heterozygous and homozygous mutants) were 64C>T (10% and 1%), 499C>G (0% and 0%), 516G>T (47% and 8%), 785A>G (54% and 10%), 1375A>G (0% and 0%), 1459C>T (3% and 0%), 3003C>T (44% and 27%), 18492T>C (39% and 6%), and 21563C>T (57% and 5%). The four most frequent CYP2B6 haplotypes identified were *1/*6 (41%), *1/*1 (35%), *1/*2 (7%), and *6/*6 (7%). The heterozygous/homozygous mutation associated with low efavirenz concentrations was 18492T>C (P < 0.001), and those associated with high efavirenz concentrations were 516G>T, 785A>G, and 21563C>T (all P < 0.05). Haplotype *1/*1 was associated with low efavirenz concentrations, and *6/*6, *1/*6, and *5/6 were associated with high efavirenz concentrations. As shown by multivariate analysis, low efavirenz concentrations were significantly associated with the *1/*1 haplotype (beta = −1.084, P = 0.027) and high body weight (beta = −0.076, P = 0.002). In conclusion, pharmacogenetic markers of CYP2B6 have the greatest impact with respect to inducing low plasma efavirenz concentrations in HIV/TB Thai patients.
Recombinant human growth hormone improves the fat redistribution syndrome (lipodystrophy) in patients with HIV.

OBJECTIVE To determine the efficacy of recombinant human growth hormone (rhGH) in the treatment of the fat redistribution syndrome (FRS) in patients with HIV. DESIGN A prospective, open-label study. SETTING An urban, university-affiliated Infectious Disease Clinic. PATIENTS Ten HIV-infected patients (seven men, three women) with FRS. INTERVENTIONS Treatment with 6 mg of rhGH a day, subcutaneously for 12 weeks. MAIN OUTCOME MEASURES Body mass index (BMI), body composition by bioelectrical impedance analysis (BIA), body composition by anthropometrics (including waist/hip ratio), buffalo hump. RESULTS The mean age was 41.7 years, the CD4 cell count was 247, and the HIV RNA was 95 735 copies/ml; 50% had undetectable viral RNA. The BMI was significantly increased from baseline to the end of treatment with growth hormone (25.3-26.9 kg/m2; P < 0.04); the waist/hip ratio significantly decreased from baseline levels, after treatment with growth hormone (1.03-0.9; P < 0.04); mid-thigh circumference increased significantly when baseline was compared with measures after treatment (49.1-51.8 cm; P < 0.03). One patient had to discontinue therapy because of hyperglycemia. CONCLUSION Short-term treatment with rhGH improved the alterations in body shape that occur with FRS in HIV-infected patients. Waist/hip ratios and mid-thigh circumference are useful measures to follow alterations in body shape in FRS.
Extraction of an overlapped second harmonic chirp component using the fractional fourier transform

In ultrasound harmonic imaging with chirp coded excitation, the axial resolution can be improved by increasing the excitation signal bandwidth. However, increasing the bandwidth will cause overlapping between the received nonlinear second harmonic chirp component (SHCC) and the fundamental component. For the spectrally overlapping harmonics, signal decoding using the second harmonic matched filter (SHMF) typically produces higher range sidelobes level (RSLL), which reduces the image contrast. A multi-pulse detection scheme such as pulse inversion can be used to extract the overlapped SHCC; however it is susceptible to motion artifacts and reduced system frame-rate. In this study, the fractional Fourier transform (FrFT) is proposed with chirp coded excitation for the extraction of the overlapped SHCC. The experimental results indicate at least a 13 dB improvement in the RSLL of the FrFT filtered compressed SHCC when compared with the unfiltered compressed SHCC.
Susceptibility of Equine Chorionic Girdle Cells to Lymphokine‐Activated Killer Cell Activity

PROBLEM: Equine chorionic girdle cells are a subpopulation of highly invasive trophoblast cells that attach and invade the uterine epithelium on Day 35 (Day 0 = day of ovulation). These invading chorionic girdle cells form endometrial cups that are associated with a marked local maternal leukocytic response that may result in the demise of the cups at Day 120 of pregnancy. Once endometrial cups become established in the uterine wall they do not express MHC antigens, and therefore may only be susceptible to non‐MHC restricted cytotoxic cells. The susceptibility of cultured chorionic girdle cells to LAK cell cytotoxicity was tested in order to evaluate the role of this type of cytotoxicity in the life‐cycle of endometrial cup tissue.
Chicken suprachiasmatic nuclei: I. Efferent and afferent connections

The avian circadian system is composed of multiple inputs, oscillators, and outputs. Among its oscillators are the pineal gland, retinae, and a hypothalamic structure assumed to be homologous to the mammalian suprachiasmatic nucleus (SCN). Two structures have been suggested as this homolog—the medial SCN (mSCN) and the visual SCN (vSCN). The present study employed biotin dextran amine (BDA) and cholera toxin B subunit (CTB) as anterograde and retrograde tracers to investigate the connectivity of the mSCN and vSCN in order to address this issue. Intravitreal injections of CTB were used to determine whether one or both of these structures receives afferent input from retinal ganglion cells. Both the vSCN and mSCN receive terminal retinal input, with the strongest input terminating in the vSCN. Precise iontophoretic injections of BDA and CTB in the mSCN and vSCN were used to identify efferents and afferents. The avian mSCN and vSCN collectively express more efferents and afferents than does the mammalian SCN. A subset of these connections matches the connections that have been established in rodent species. Individually, both the mSCN and vSCN are similar to the mammalian SCN in terms of their connections. Based on these data and other studies, we present a working model of the avian SCN that includes both the mSCN and vSCN as hypothalamic oscillators. We contend that both structures are involved in a suprachiasmatic complex that, as a functional group, may be homologous to the mammalian SCN. J. Comp. Neurol. 496:97–120, 2006. © 2006 Wiley‐Liss, Inc.
Self-adaptive ontology-based focused crawling: A literature survey

Web crawlers are known to us since the birth of the internet since 1990, as the web pages are interconnected among themselves and form a unique path along which the crawler travels to fetch the information requested by the user/author. But the traditional crawlers are not able to distinguish between the relevant and the partially relevant web pages. Due to this the crawler had to fetch a huge amount of data from the web even if the web was not fully relevant to the user. This resulted in formation of the crawlers that were committed to the single topic given by the user. These crawlers were known as focused crawlers. These focused crawlers do not crawl the whole web as opposed to the traditional crawlers, as they only crawl the specific part of the web that is related to the given topic. This paper summarizes different qualities of various focused crawlers at present. Basically it divides the focused crawler into two different classes namely Semantic and Social Semantic. Semantic Focused Crawlers uses the ontology to its advantage and to obtain the topics that are contextually related to the given topic. Social Semantic Focused Crawlers takes the advantages of the social networking sites to obtain the web pages that are contextually related to the given topic, and usually the pages are shared by the people that have some interest in some topic related to the queried topic.
Transformation by simian virus 40 induces virus-specific, related antigens in the surface membrane and nuclear envelope.

Nucleus- and mitochondrion-free membranes from hamster lymphocytes transformed by simian virus 40 (SV40), GD248 cells, cause guinea pigs to produce immune sera that reveal the presence in GD248 plasma membranes and mitochondria of two types of glycoprotein that are not detected in membranes of normal lymphocytes [Schmidt-Ullrich, R. , Thompson, W. S. & Wallach, D. F. H. (1977) Proc. Natl. Acad. Sci. USA 74, 643-647]. Indirect immune fluorescence of living, SV40-transformed T19 hamster reticulum cells, Balb/c 3T3 mouse fibroblasts, and W18 VA2 human fibroblasts, using the antisera against GD248 membrane, at 4 degrees produced a distinct cell surface fluorescence; however, above 20 degrees , staining at the nuclear perimeter, the SV40 U-antigen reaction, becomes equally prominent. In SV40-transformed cells that had been fixed in cold acetone, as well as in purified GD248 nuclei, thermostable U-antigen staining is dramatic, but there is no reaction for nuclear T-antigen. Rabbit antisera against T19 cells gave immunofluorescence reactions equivalent to those obtained with the antisera against GD248 cells. Normal guinea pig or rabbit sera and cells that had not been transformed by SV40 gave no reaction. Our sera from tumor-bearing hamsters gave only nuclear T-antigen fluorescence. The results indicate the presence of related, SV40-specific antigens in the surface membranes, nuclear envelope, and possibly other intracellular organelles of SV40-transformed cells.
Antiepileptic drugs for neuropathic pain and fibromyalgia.

CLINICAL QUESTION Are antiepileptic drugs associated with reduced pain intensity in patients with neuropathic pain or fibromyalgia? BOTTOM LINE In treating diabetic neuropathy and postherpetic neuralgia compared with placebo, gabapentin and pregabalin are associated with a modest increase in the number of patients experiencing meaningful pain reduction. In treating fibromyalgia, compared with placebo, pregabalin alone is associated with a small increase in the number of patients experiencing meaningful pain reduction. There is insufficient evidence for other antiepileptics.
How successful organizations drive innovation

Purpose The authors analyze IBM research and outline how the most successful established organizations approach innovation and prescribe specific strategies that can help all organizations innovate like an outperformer. Design/methodology/approach In a 2014 survey of more than 1,000 C-suite executives and their direct reports, we found that the most successful organizations approach innovation differently. Findings The top six percent of organizations in both operating efficiency and revenue growth pursue distinct strategies in innovation organization, culture and process. Practical Implications For today’s business leaders, innovation blends the art and science of anticipating the future. It requires understanding what the full potential of new technologies will be, of knowing what customers need and want, even before they know it themselves. And it requires building organizational and ecosystem-wide capabilities to execute and deliver. Successful organizations align innovation activities with business objectives, and they are not afraid to experiment. Originality/value Outlines the best practices of the most successful innovators. For example, these, organizations align innovation activities directly with business objectives, pursue “open” innovation structures and create specialized innovation teams. They also source new ideas from diverse locations, often leveraging big data and analytics; innovation is funded separately and measured rigorously.
Food intake, growth rate, food conversion and food choice in broilers fed on diets high in rapeseed meal and pea meal, with observations on sensory evaluation of the resulting poultry meat

1. Experiments were done to measure the effects of 100 and 200 g/kg of either pea meal or low glucosinolate, low erucic acid rapeseed meal on food intake and growth, food choice and meat organoleptic quality in broiler chickens. 2. The test diets were formulated to be iso-energetic and iso-nitrogenous with a soy–wheat control diet. In all diets, lysine was fixed at 11·0 g/kg and all other indispensable amino acids were present in excess of requirements. 3. Food intake was little affected by the inclusion of 100 g/kg of pea meal in the diet but 200 g/kg of peas caused a decrease. Rapeseed produced a decrease in food intake at both dietary concentrations. 4. Weight gain was similarly affected, but food conversion from d 0 to d 42 was little affected by the inclusion of either peas or rapeseed. 5. Absolute breast muscle weight was affected by diet but there was no significant difference in breast weight as a proportion of total body weight. 6. From d 7 onwards, selection against the pea-containing diet approached statistical significance. Between d 7 and d 14, birds ate almost twice as much of the control as of the pea-containing diet. Birds offered a rapeseed meal diet ate similar amounts of that and the control diet. 7. The breast meat from birds given 200 g rapeseed/kg was the only meat identified as different but no strong aversion was expressed by the tasting panel.
What Difference Do New Factor Models Make in Portfolio Allocation?

This paper examines the economic implications of new factor models and shows that the Hou, Xue, and Zhang (HXZ, 2015a) four-factor model outperforms the Fama and French (FF5, 2015a) five-factor model for investing in anomalies in- and out-of-sample. The difference in certainty-equivalent returns between the two models can be more than 6% per year under modest model uncertainty and margin requirements. The outperformance of the HXZ model appears to come from its better ability to describe the mean rather than the covariance matrix of asset returns.
Differences in Rates of Cancer Screening by Usual Source of Medical Care: Data from the 1987 National Health Interview Survey

Data from the Cancer Control Supplement of the 1987 Health Interview Survey (NHIS), a nationally representative sample of the United States population, was used to examine rates of six screening tests for cancer. The rates of screening were compared for people who receive their usual source of medical care in an HMO or prepaid group practice versus those who receive it in the fee-for-service sector. The purpose of this article is to determine whether HMOs remain more likely to offer cancer screening examinations than the fee-for-service sector. Results indicate that for five of six screening tests examined (Pap smear, mammography, breast physical examination, digital rectal examination, and blood stool test), members of HMOs are significantly more likely to have received the test within the last 3-year period. These results hold in a multivariate analysis when many factors correlated with selection into HMOs, health status, and use of medical services are controlled for, although results are only generalizable to whites. Future research should focus on why the rates for five of the six cancer screening tests examined are higher in HMO settings, and how we can use the HMO experience to improve consensus as to the usefulness of the tests in the non-HMO physician pool, and ultimately increase rates of screening tests in the non-HMO population.
Essays in Strategic Experimentation and Bargaining

This dissertation consists of Four Chapters: Chapter 1 analyses a situation where competing agents involved in making the same discovery have alternative research avenues to pursue. Agents are uncertain about the quality of the available research methods. They learn about a particular method in light of their search experiences. One can relate this to R&D activities in the pharmaceutical industry, electronics industry etc. This scenario is modeled as a Two-armed Bandit problem. We consider two alternative settings. One has two risky arms which are perfectly negatively correlated and the other one has one safe arm and one risky arm. I show that with a winner-takes all structure and heterogeneity among agents with respect to their innate abilities, there is always an excessive amount of experimentation along one of the lines of research. This phenomenon is called Duplication which implies that there is too much specialisation along a line of research when efficiency would require more diversification. Chapter 2 explores the scenario where competing agents trying to make the same discovery have alternate methods of research to choose from and agents may be privately informed about the quality of a method. The model is an extension of the second setting with symmetric firms, where each firm may experience private arrival of information along the good risky avenue. I show that there is a symmetric non-cooperative equilibrium in which there is excessive amount of experimentation along the risky avenue if the prior is