Miracle-dz/UniFAR-FTUs huggingface dataset:
Reversible Association between the V1and V0 Domains of Yeast Vacuolar H+-ATPase Is an Unconventional Glucose-Induced Effect

ABSTRACT The yeast vacuolar H+-ATPase (V-ATPase) is a multisubunit complex responsible for organelle acidification. The enzyme is structurally organized into two major domains: a peripheral domain (V1), containing the ATP binding sites, and an integral membrane domain (V0), forming the proton pore. Dissociation of the V1 and V0 domains inhibits ATP-driven proton pumping, and extracellular glucose concentrations regulate V-ATPase activity in vivo by regulating the extent of association between the V1 and V0 domains. To examine the mechanism of this response, we quantitated the extent of V-ATPase assembly in a variety of mutants with known effects on other glucose-responsive processes. Glucose effects on V-ATPase assembly did not involve the Ras-cyclic AMP pathway, Snf1p, protein kinase C, or the general stress response protein Rts1p. Accumulation of glucose 6-phosphate was insufficient to maintain or induce assembly of the V-ATPase, suggesting that further glucose metabolism is required. A transient decrease in ATP concentration with glucose deprivation occurs quickly enough to help trigger disassembly of the V-ATPase, but increases in cellular ATP concentrations with glucose readdition cannot account for reassembly. Disassembly was inhibited in two mutant enzymes lacking ATPase and proton pumping activities or in the presence of the specific V-ATPase inhibitor, concanamycin A. We propose that glucose effects on V-ATPase assembly occur by a novel mechanism that requires glucose metabolism beyond formation of glucose 6-phosphate and generates a signal that can be sensed efficiently only by a catalytically competent V-ATPase.
Modified nucleotides of tRNAPro restrict interactions in the binary primer/template complex of M-MuLV.

In all retroviruses, reverse transcription is primed by a cellular tRNA, which is base-paired through its 3'-terminal 18 nucleotides to a complementary sequence on the viral RNA genome termed the primer binding site (PBS). Evidence for specific primer-template interactions in addition to this standard interaction has recently been demonstrated for several retroviruses. Here, we used chemical and enzymatic probing to investigate the interactions between Moloney murine leukemia virus (M-MuLV) RNA and its natural primer tRNAPro. The existence of extended interactions was further tested by comparing the viral RNA/tRNAPro complex with simplified complexes in which viral RNA or tRNA were reduced to the 18 nt of the PBS or to the complementary tRNA sequence. These data, combined with computer modeling provide important clues on the secondary structure and three-dimensional folding of the M-MuLV RNA/tRNAPro complex. In contrast with other retroviruses, we found that the interaction between tRNAPro and the M-MuLV RNA template is restricted to the standard PBS interaction. In this binary complex, the viral RNA is highly constrained and the rest of tRNAPro is rearranged, with the exception of the anticodon arm, leading to a very compact structure. Unexpectedly, when a synthetic tRNAPro lacking the post-transcriptional modifications is substituted for the natural tRNAPro primer, the interactions between the primer and the viral RNA are extended. Hence, our data suggest that the post-transcriptional modifications of natural tRNAPro prevent additional contacts between tRNAPro and the U5 region of M-MuLV RNA.
An examination of the cross-sectional relationship of beta and return in international stock returns: evidence from emerging and developed markets

This paper will follow Pettengill et al.’s (1995) approach to examine the unconditional and conditional relationship between beta and returns from January 1995 to May 2017 in a well globally diversified sample of 22 emerging markets and 23 developed markets. Additionally, Pettengill et al.’s (1995) methodology is adjusted to take into account 1-year time-varying beta values to supplement and check the robustness of the initial results. The empirical results for the full sample as well as both sub-samples indicate that there is no significant unconditional relationship between beta and returns, however, when differentiating between upand downmarkets a significant conditional relationship is found. This paper adds to the existing literature by examining and comparing a large sample of both developed and emerging markets, as well as, confirming the results according to Pettengill et al.’s methodology with time-varying betas. Risk-return relationship, unconditional, conditional, time-varying betas
The Relationship of the Infrapatellar Branches of the Saphenous Nerve to Arthroscopy Portals and Incisions for Anterior Cruciate Ligament Surgery: An Anatomic Study *

The purposes of this study were 1) to carefully define the anatomic distribution of the infrapatellar branches of the saphenous nerve, 2) to provide the surgeon with reliable parameters for where the nerve is most commonly encountered, and 3) to provide specific surgical recommendations to minimize the risk of nerve injury. To accomplish these goals, we dissected 20 cadaveric, fresh-frozen, matched-pair knees. Calipers were used to measure the distance from the nerve to three clinically relevant and easily reproducible landmarks: the inferior pole of the patella, the medial border of the patella at its midpoint, and a point 2 cm medial to the patellar ligament at the level of the joint line. Distances were recorded with the knees in extension and in 90° of flexion to examine the effect of dynamic knee motion on nerve position. We consistently found two main trunks of the nerve that traverse the knee primarily in a medial to lateral but somewhat proximal to distal direction. Because of this, we recommend that incisions for arthroscopy portals be made in a horizontal fashion to decrease the likelihood of nerve injury. Measured from both the inferior pole of the patella and the medial border of the patella, the nerve moved distally with knee flexion. We therefore recommend that incisions across the anterior aspect of the knee be made with the knee in flexion. In 8 of our 20 specimens, the nerve was actually found at the landmark located 2 cm medial to the patellar ligament. This is an extremely high-risk area and should be avoided if possible.
Intraspecific Variation and Phylogenetic Relationships in the Genus Entamoeba as Revealed by Riboprinting

ABSTRACT. Eighty‐seven isolates of amebae assigned to the genus Entamoeba have been studied by riboprinting (restriction enzyme polymorphism analysis of polymerase chain reaction amplified small subunit ribosomal RNA genes). Twenty‐four distinct patterns were obtained, most of which corresponded to previously described species. In three species (Entamoeba coli, Entamoeba gingivalis and Entamoeba moshkovskii) intraspecific variation was detected that led to the grouping of isolates into ‘ribodemes’ (populations of amebae that share the same riboprint pattern). The riboprint data were used to estimate genetic distances among and within species for the construction of phylogenetic trees based on parsimony and distance analyses. The trees obtained with the two methods are largely congruent. In some cases the estimated distances between species were greater than the upper limit recommended for the fragment comigration method of analysis indicating unusually deep branches within this genus. However, it appears that those species producing cysts with eight nuclei, those producing cysts with one nucleus, and those producing cysts with four nuclei form morphologically based groups that are supported by the riboprint data. The oral parasite Entamoeba gingivalis, which does not encyst, clusters with the third group indicating secondary loss of this ability.
HPA-1, 3, 5 GENOTYPING TO ESTABLISH A TYPED PLATELET DONOR PANEL

Summary Platelet antigen typing of blood donors is not routinely performed. Usually, ABO-matched platelets are transfused. In situations where the recipient has a human platelet-associated (HPA) antibody resulting in refractoriness to platelet transfusions, post-transfusion purpura or neonatal alloimmune thrombocytopenia, HPA-typed platelets may be required. Having a panel of HPA-typed donors would be helpful. This study utilised PCR-RFLP and PCR-SSP methods to determine the HPA-1, 3, 5 genotypes of 1,000 blood donors to establish a panel of HPA homozygous donors who could donate platelets for patients with anti-HPA-antibodies. The study demonstrates the HPA genotype frequencies in a Western Australian blood donor population and has identified donors who are homozygous for the "aa" and "bb" genotypes for HPA-1, 3 and 5. The Australian Red Cross Blood Service-NW Region can now use these data to develop a panel of HPA-1, 3 and 5 "aa" and "bb" homozygous platelet donors, which can be accessed for patients with HPA antibodies requiring platelet transfusion.
Neoplastic pericardial effusion. Efficacy and safety of intrapericardial treatment with cisplatin.

AIMS To evaluate the clinical efficacy, safety, and long-term effect of intrapericardial treatment with cisplatin in large neoplastic pericardial effusions. METHODS AND RESULTS Out of the registry of 260 patients undergoing pericardiocentesis, 42 patients with neoplastic pericardial effusion (69% males, mean age 58.8+/-13.2 years) were selected for treatment with cisplatin (single instillation of 30 mg.m(-2) x 24h(-1)) in addition to the tumour-specific systemic chemotherapy. All patients underwent clinical examination, echocardiography, pericardiocentesis, pericardioscopy, and epicardial biopsy. Pericardial effusion and biopsy analyses included biochemistry, cytology, serology, microbiology, histology, immunohistology, and PCR. The following malignancies were established: lung cancer, 52.4%; breast cancer, 19.0%; Hodgkin's disease, 4.8%; oesophageal cancer, 2.4%; mesothelioma, 2.4%; colon cancer, 4.8%; and undifferentiated cancer of unknown origin, 14.2%. Cisplatin appeared to prevent recurrence of pericardial effusion during the first 3 months of the follow-up in 92.8%, and after 6 months in 83.3% of the patients. Lung cancer patients had fewer effusion relapses at the 6 months follow-up (4.5%) than breast cancer patients (37.5%)(P<0.05). Myocardial ischemia occurred after 1/42 cisplatin instillations, but there were no other complications. CONCLUSION Intrapericardial treatment with cisplatin appeared to successfully prevent recurrences of neoplastic pericardial effusion. The treatment was more successful in lung than in breast cancer patients.
Option-Implied Tail Risk, Timing by Hedge Funds, and Performance

This paper focuses on an unexplored dimension of fund managers’ timing ability: market-wide tail risk implied by information in options markets. We investigate whether hedge fund managers can strategically time market tail risk implied by options through adjusting their portfolios’ market exposure to changes in market tail risk. Using an extensive sample of 6,147 equity-oriented hedge funds over the period 1996 to 2012, we find strong evidence of tail risk timing ability of hedge fund managers. We conduct bootstrap analysis and confirm that our tail risk timing ability is not attributed to pure luck. Furthermore, tail risk timing ability brings significant economic value to investors. Specifically, in out-of-sample tests, top-ranked hedge funds outperform bottom-ranked funds by 5–7% annually after adjusting for common risk factors. Also, we find that managers’ tail risk timing skill persists over time, suggesting that hedge fund managers’ tail risk timing ability reflects true managerial skill. Our overall results are robust to various hedge fund characteristics, subsample or sub-period analysis, the use of alternative timing abilities, and other hedge funds’ managerial skills. Our empirical examination emphasizes the role of market-wide option-implied tail risk in hedge fund managers’ skill and their performance.
Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis.

OBJECTIVES To evaluate the role of piperine as an inhibitor of Rv1258c of Mycobacterium tuberculosis. METHODS Rifampicin, in combination with piperine, was tested against M. tuberculosis H37Rv and rifampicin-resistant (rif(r)) M. tuberculosis. A laboratory-generated rifampicin-resistant mutant (rif(r)) of M. tuberculosis was tested for drug susceptibility and the expression level of the putative efflux protein (Rv1258c) by real-time PCR. The three-dimensional (3D) structure of Rv1258c was also predicted using an in silico approach. RESULTS In the present study, rifampicin in combination with piperine, a trans-trans isomer of 1-piperoyl-piperidine, reduced the MIC and mutation prevention concentration (MPC) of rifampicin for M. tuberculosis H37Rv, including multidrug-resistant (MDR) M. tuberculosis and clinical isolates. Moreover, piperine effectively enhanced the bactericidal activity of rifampicin in time-kill studies and also significantly extended its post-antibiotic effect (PAE). In the presence of rifampicin, M. tuberculosis rif(r) showed a 3.6-fold overexpression of Rv1258c. The 3D structure of Rv1258c, using in silico modelling, was analysed to elucidate the binding of piperine to the active site. CONCLUSIONS The results of this study are suggestive of piperine's involvement in the inhibition of clinically overexpressed mycobacterial putative efflux protein (Rv1258c). Piperine may be useful in augmenting the antimycobacterial activity of rifampicin in a clinical setting.
Pre-surgery disability compensation predicts long-term disability among workers with carpal tunnel syndrome.

BACKGROUND We sought to identify early risk factors for work disability compensation prior to and after carpal tunnel syndrome (CTS) surgery, and to determine whether pre-surgery disability compensation is associated with long-term disability. METHODS Washington State workers' compensation administrative data and data from interviews with workers 18 days (median) after submitting new workers' compensation claims for CTS were examined. Baseline risk factors for pre-surgery disability compensation and for long-term disability (>365 days of work disability compensation prior to 2 years after claim filing) were evaluated for workers who underwent CTS surgery and had at least 1 day of disability compensation (N = 670). RESULTS After adjustment for baseline long-term disability risk factors, workers with pre-surgery disability compensation had over five times the odds of long-term disability. Baseline factors in multiple domains, including job, psychosocial, clinical, and worker pain and function, were associated with both pre-surgery disability compensation and long-term disability. CONCLUSIONS Risk factors for work disability prior to and after CTS surgery are similar, and early work disability is a risk factor for long-term CTS-related disability. An integrated approach to CTS-related disability prevention could include identifying and addressing combined risk factors soon after claim filing, more efficient use of conservative treatments and appropriate work modifications to minimize early work loss, and, when indicated, timely surgical intervention.
Parental Beliefs about Returns to Different Types of Investments in School Children

ABSTRACT Using a representative sample of 1,962 parents in England, we study how parents perceive the returns to parental time investments, material investments, and school quality. Parents perceive the returns to three hours of weekly time investments or £30 of weekly material investments to matter more than moving a child to a better school. Material investments are perceived as more productive if children attend higher-quality schools. Perceived returns do not differ with the child’s initial human capital or gender, and they are highly correlated with actual investment decisions.
A Cohort Model of Visual Word Recognition

A model of word recognition is proposed which assumes that when a word is encountered, the first available orthographic code activates all lexical entries that are positionally consistent with that information (i.e., the word's cohort). As subsequently encoded orthographic information becomes available, activation is withdrawn from lexical entries with which it is inconsistent, and the cohort is resolved when only a single candidate remains. The model is intended to characterize: (1) The initial encoding of the graphic information; (2) the recording of that information into an abstract orthographic form; (3) the manner in which the appropriate lexical entries are then activated; (4) the process whereby subsequent orthographic encoding resolves those activated entries to a single candidate; and finally (5) the way in which subjects use information for making decisions as it emerges during this processing. The model includes two critical points. The first is that letter identity information is encoded in the form of a complex orthographic unit termed a wickelgraph. A wickelgraph includes an encoding of the target letter's identity information as its core, plus, as a context, the identity of its two immediately adjacent letters. The set of possible wickelgraphs is assumed to instantiate the rules of orthography. The second point is that once a cohort is established, the perceiver can sample its status at any point during resolution and base a decision on the outcome of that sample. Some tasks (e.g., naming) may allow for a decision based on the initial status of the cohort, while others (e.g., lexical decision) can require its complete resolution. Six experiments are reported that illustrate some of these cohort effects in lexical access.
MiR-195 Suppresses Cervical Cancer Migration and Invasion Through Targeting Smad3

Objective MicroRNAs (miRNAs) play crucial roles in cervical cancer development and progression. The purposes of this study were to investigate the role of miR-195 in cervical cancer and clarify the regulation of Smad3 by miR-195. Methods Quantitative real-time polymerase chain reaction was used to examine miR-195 expression in cervical cancer tissues and cell lines. The clinicopathological significance of miR-195 down-regulation was further analyzed. Transwell migration and invasion assays were performed. A luciferase reporter assay was conducted to confirm the target gene of miR-195, and the results were validated in cervical cancer tissues and cell lines. Results MiR-195 was significantly decreased in clinical tissues and cervical cancer cell lines. The low miR-195 level was significantly correlated with higher International Federation of Gynecology and Obstetrics stage, node metastasis, and deep stromal invasion. Up-regulation of miR-195 suppressed cell migration and invasion in vitro. Smad3 was verified as a direct target of miR-195, which was further confirmed by the inverse expression of miR-195 and Smad3 in patients’ specimens. Conclusions The newly identified miR-195/Smad3 pathway provides an insight into cervical cancer metastasis and may represent a novel therapeutic target.
Comparing Advanced Practice Providers and Physicians as Providers of e-Visits.

BACKGROUND Although electronic delivery (electronic visits [e-visits]) of healthcare services by advanced practice providers (APPs) is growing, literature defining the roles of different providers and comparing outcomes is lacking. We analyzed two e-visit models at the University of Pittsburgh Medical Center (UPMC) to compare their providers (physicians and APPs) and associated outcomes. MATERIALS AND METHODS We identified all e-visits for the UPMC AnywhereCare Continuity (physician providers for existing patients) and Convenience (physician and APP providers for Pennsylvania residents) services (n=2,184) using Epic Systems (Verona, WI) MyChart data (November 2013-August 2014). We compared e-visits by service and provider type for patient characteristics, volume, response time, primary diagnoses, and number of prescriptions. We used statistical tests to determine differences in patient characteristics and an ordinary least square linear regression, controlling for patient characteristics, to determine differences in prescribing. RESULTS Of the completed e-visits (n=1,791), 72.5% were with APPs, and 27.5% were with physicians. APP patients were younger, higher income, and more likely to be unmarried. Sinusitis patients were more likely to use the Continuity service, whereas those with urinary tract or upper respiratory infections were more likely to use the Convenience service. Finally, provider type was significantly associated with prescribing, with APPs prescribing more. CONCLUSIONS Some demographic variation exists between users of APP versus physician e-visits. Provider response time seems more driven by service policy than provider type. Finally, variation exists between provider types in quantities of prescriptions written. As health systems and policymakers develop protocols and reimbursement strategies for e-visits, these model considerations will be important.
The Influence of Hypomania Symptoms on Income in Self-Employment

Despite the assumption that symptoms of hypomania are detrimental, they may prove beneficial within self-employment contexts. Drawing on person-environment (P/E) fit theory and using the first National Epidemiologic Survey on Alcohol Related Conditions (NESARC 1), our conservative inferences are that for self-employed individuals, hypomania has a positive association with income, self-employed individuals with higher education have higher levels of income with increasing hypomania score, and older self-employed individuals with a higher hypomania score have a higher income. These findings have implications for the literature on hypomania symptoms and self-employment related labor market outcomes.