Miracle-dz/UniFAR-FTUs huggingface dataset:
The transmembrane glycoprotein of human immunodeficiency virus type 1 induces syncytium formation in the absence of the receptor binding glycoprotein

To study the intracellular transport and biological properties of the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein (TM; gp41), we constructed a truncated envelope gene in which the majority of the coding sequences for the surface glycoprotein (SU; gp120) were deleted. Transient expression of this truncated env gene in primate cells resulted in the biosynthesis of two proteins with M(r)s of 52,000 and 41,000, respectively. Immunofluorescence studies with antibodies to the HIV-1 TM protein indicated that the intracellular and surface localization of these proteins were indistinguishable from those of the native HIV-1 gp120-gp41 complex. These results indicate that the oligosaccharide processing and cell surface transport of the HIV-1 TM protein were not dependent on the presence of the receptor binding subunit, gp120. Syncytium formation was readily detected upon expression of the deleted HIV-1 env gene into COS and CD4+ HeLa cell lines, suggesting that in the absence of gp120, the TM protein retained biological activity. This observation was confirmed by infection of primate and mouse cell lines with a recombinant vaccinia virus (vvgp41) expressing the truncated HIV-1 env gene. These results strongly suggest that (i) the two biological activities of the HIV-1 envelope glycoprotein can occur independently and (ii) the association of the two glycoprotein subunits may restrict the fusion activity of the transmembrane component to CD4+ cells.
Excessive consumption of alcohol in men as a biological influence factor in clinical laboratory investigations.

It is known that excessive alcohol consumption leads to changes in clinical chemical and haematological parameters that are reversed to a greater or lesser degree after alcohol consumption ceases. Such factors that lead to changes in vivo in the parameters studied are termed biological influence factors. In the study reported here the biological influence factor "excessive alcohol consumption" was assessed in its most severe form, namely alcoholism. To this end 24 clinical chemical parameters and 8 haematological parameters were studied in 82 male alcoholics. The diagnoses of alcohol abuse and alcoholism were made on the basis of the Munich Alcoholism Test (MALT) and the information obtained in the following standardized interviews and examinations: past history, an alcohol questionnaire, general physical examination and neurological examination. All forms were filled in completely. All steps in the clinical laboratory investigations were standardized, and all were subject to ongoing reliability control. In the comparison of the analytical results for the alcoholics with reference intervals for healthy persons (normal ranges) the following alterations were found, the percentage of the alcoholics being given in parentheses. (Table: see text) Furthermore, the result was below the location parameter of the reference sample group for: Urea (80%) Thus excessive alcohol consumption is clearly a biological influence factor that must be taken into consideration in the medical assessment of analytical results for numerous clinical chemical and haematological parameters. In determining reference values and reference intervals for the transverse assessment of analytical results for these parameters it is therefore absolutely essential that subjects with excessive alcohol consumption be excluded from the reference sample group. According to the present data, alcoholism can be neither detected nor excluded by evaluating a single parameter, i.e. on the basis of only one clinical chemical finding.
Pituitary pro-opiomelanocortin gene expression requires synergistic interactions of several regulatory elements

The pro-opiomelanocortin (POMC) gene is expressed very early during pituitary development, before expression of the other pituitary hormone genes, growth hormone and prolactin, and before expression of the Pit-1/GHF-1 transcription factor which activates those genes. Thus, analysis of the POMC promoter should provide markers of the early stages of pituitary development at the time when cells are being committed to expression of one or the other pituitary hormone. We have previously localized the rat POMC promoter to a 543-bp 5'-flanking DNA fragment of the gene using transfection and transgenic mice experiments. We have now used mutagenesis and in vitro protein-DNA binding studies to define three domains of the promoter which have distinct and complementary activities. Within these domains which require each other for full activity, at least nine regulatory elements were defined by in vitro footprinting and replacement mutagenesis. Each element appeared equally important for promoter activity, as mutagenesis of any element had similar effect on promoter activity. Most of the elements bound different AtT-20 nuclear proteins in gel mobility shift experiments. Whereas only two elements appeared to be binding sites for the known transcription factors AP-1 and chicken ovalbumin upstream promoter, the seven other elements appeared to bind nuclear proteins with novel properties. Thus, in contrast to the predominant role of Pit-1/GHF-1 in transcription of the growth hormone and prolactin genes, the control of an early pituitary gene, POMC, appears to depend on the synergistic interaction of several regulatory elements which bind different nuclear proteins.
Neuroprotective effect of curcumin against oxidative damage in BV-2 microglia and high intraocular pressure animal model.

PURPOSE The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. In this study, we aim to evaluate the antioxidant effects of curcumin in BV-2 microglia oxidative damage and assess its neuroprotective effects in a chronic high IOP rat model. METHODS BV-2 microglia cell line was used in an in vitro study and Wistar rats were used in an in vivo study. Cultured BV-2 microglia cells were pretreated with 10, 1, or 0.1 μM curcumin for 1 h, and sustained oxidative stress was induced by subjecting BV-2 microglia to 200 μM hydrogen peroxide (H2O2) for 24 h. MTT assay was used to determine cell viability. Changes of intracellular reactive oxygen species (ROS) and apoptosis were analyzed by flow cytometry. Three episcleral veins were cauterized to induce high IOP in Wistar rats and measured by Tonopen. After 6 weeks of treatment with curcumin (10 mg/kg/day) by intragastric administration, surviving of retinal ganglion cells was quantified. Activation of caspase 3, cytochrome c, BAX, and BCL2 was quantified by Western blotting both in BV-2 microglia and in animal model. Data were analyzed with the GraphPad Prism 5.0 software, and P<0.05 was considered to be statistically significant. RESULTS The in vitro study showed that when BV-2 microglia was pretreated with curcumin, the cell viability increased and the intracellular ROS and apoptosis significantly decreased. In the in vivo study, chronic mild IOP elevation was induced for 4 weeks. In the curcumin-treated group, curcumin protected rat BV-2 microglia from death significantly. In both H2O2-treated BV-2 microglia and glaucoma models, caspase 3, cytochrome c, and BAX were downregulated and BCL2 was upregulated in the curcumin-treated group. CONCLUSIONS Curcumin affords neuroprotective effects by inhibiting oxidative damage and could be a new or adjunctive treatment for glaucoma.
Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions

Transcription factor AP-1 transduces environmental signals to the transcriptional machinery. To ensure a quick response yet maintain tight control over AP-1 target genes, AP-1 activity is likely to be negatively regulated in nonstimulated cells. To identify proteins that interact with the Jun subunits of AP-1 and repress its activity, we developed a novel screen for detecting protein-protein interactions that is not based on a transcriptional readout. In this system, the mammalian guanyl nucleotide exchange factor (GEF) Sos is recruited to the Saccharomyces cerevisiae plasma membrane harboring a temperature-sensitive Ras GEF, Cdc25-2, allowing growth at the nonpermissive temperature. Using the Sos recruitment system, we identified new c-Jun-interacting proteins. One of these, JDP2, heterodimerizes with c-Jun in nonstimulated cells and represses AP-1-mediated activation.
Value Investing and Size Effect in the South Korean Stock Market

There are indications that value investing strategies have been able to outperform the overall market in several countries across the globe. In this article, the specific case of South Korea is analyzed. It would appear that from a rigorous statistical point of view there are no strong evidence supporting the outperformance of value stocks versus growth stocks in South Korea, particularly when measured on a yearly basis. These results were consistent using both MSCI value and growth indexes as well as constructing portfolios using the P/E, P/B, cash flow per share and average 5-year sales growth. The statistical tests performed failed to reject for the majority of the years that the monthly returns come from distributions with different medians. The test yielding rather consistent results on a yearly basis but for large periods of time (decades) the results were more mixed, pointing in some cases to value investing outperforming over that very long time frame. It should be noted that the final value of the portfolios was rather different when using criteria, such as low P/E, typically associated with value stocks. The tests also failed to reject the hypothesis of different means for the monthly returns of small, medium and large companies.
Performance of a frequency compensated EER-PA with memoryless DPD

The Envelope Elimination and Restoration (EER) technique has attracted significant attention recently because of its high efficiency under back-off operation. Memoryless Digital Predistortor (DPD) is indispensable for an EER power amplifier (PA) because of the EER PA's strong nonlinearity due to the dynamic power supply voltage. However, performance of the memoryless DPD is significantly degraded by the frequency response of the envelope amplifier in EER-PA. We have proposed a simple and useful EER-PA model to analyze the performance degradation of the memoryless DPD. Successful compensation of the third-order intermodulation distortion of two-tone signals has been demonstrated using the memoryless DPD and frequency response compensation based on this model. In this paper, we show that the proposed model is applicable not only to two-tone signals but also to OFDM test signals. An EER-PA with a split-band envelope amplifier has been developed for experimental verification. Measured adjacent channel leakage power ratio (ACPR) of the developed EER-PA was improved from −22.5 dBc to −42.5 dBc for a 1.4 MHz bandwidth OFDM test signal using the frequency response compensation and memoryless DPD.
Production of alkenes and novel secondary products by P450 OleTJE using novel H2O2‐generating fusion protein systems

Jeotgalicoccus sp. 8456 OleTJE (CYP152L1) is a fatty acid decarboxylase cytochrome P450 that uses hydrogen peroxide (H2O2) to catalyse production of terminal alkenes, which are industrially important chemicals with biofuel applications. We report enzyme fusion systems in which Streptomyces coelicolor alditol oxidase (AldO) is linked to OleTJE. AldO oxidizes polyols (including glycerol), generating H2O2 as a coproduct and facilitating its use for efficient OleTJE‐dependent fatty acid decarboxylation. AldO activity is regulatable by polyol substrate titration, enabling control over H2O2 supply to minimize oxidative inactivation of OleTJE and prolong activity for increased alkene production. We also use these fusion systems to generate novel products from secondary turnover of 2‐OH and 3‐OH myristic acid primary products, expanding the catalytic repertoire of OleTJE.
Psychosocial work environment and prediction of quality of care indicators in one Canadian health center.

BACKGROUND Few studies link organizational variables and outcomes to quality indicators. This approach would expose operant mechanisms by which work environment characteristics and organizational outcomes affect clinical effectiveness, safety, and quality indicators. QUESTION What are the predominant psychosocial variables in the explanation of organizational outcomes and quality indicators (in this case, medication errors and length of stay)? The primary objective of this study was to link the fields of evidence-based practice to the field of decision making, by providing an effective model of intervention to improve safety and quality. METHODS The study involved healthcare workers (n = 243) from 13 different care units of a university affiliated health center in Canada. Data regarding the psychosocial work environment (10 work climate scales, effort/reward imbalance, and social support) was linked to organizational outcomes (absenteeism, turnover, overtime), to the nurse/patient ratio and quality indicators (medication errors and length of stay) using path analyses. RESULTS The models produced in this study revealed a contribution of some psychosocial factors to quality indicators, through an indirect effect of personnel- or human resources-related variables, more precisely: turnover, absenteeism, overtime, and nurse/patient ratio. Four perceptions of work environment appear to play an important part in the indirect effect on both medication errors and length of stay: apparent social support from supervisors, appreciation of the workload demands, pride in being part of one's work team, and effort/reward balance. CONCLUSIONS This study reveals the importance of employee perceptions of the work environment as an indirect predictor of quality of care. Working to improve these perceptions is a good investment for loyalty and attendance. In general, better personnel conditions lead to fewer medication errors and shorter length of stay.
Dimensional Growth of the Rabbit Eye

The rabbit eye has been used experimentally in research in vision and ophthalmology. However, there is little information about postnatal growth. The purpose of this study was to determine growth patterns of the rabbit globe from birth to young adult status focusing in particular on the fibrous outer tunic of the globe, the sclera. Eyes of both sexes of New Zealand White rabbits were examined on postnatal days 1, 7, 14, 28, 42 and 56. Axial length, equatorial diameter and corneal diameter were measured using a digital caliper. Plastic-embedded tissue was used to quantify scleral thickness and cellular density at anterior, equatorial and posterior sites. Axial length increased 230% between postnatal days 1 and 56. The rate of growth was not linear and revealed two peaks. The first peak occurred between postnatal days 1–7, and the second between days 14–28. Eye opening occurred on days 9–11. Sex differences were seen, with the male eye being larger (p = 0.00001). Surface area measurements of sclera and cornea revealed that the sclera occupies approximately 5/6 of the outer surface of the globe and the cornea 1/6. Scleral thickness increased from day 1 to day 42 (70–155 µm at the equator) while fibroblast density was found to decrease (0.32 to 0.05 cells/µm2). The results suggested that eye opening precedes a unique increase in the rate of eye growth and visual processes may be playing a role in modulating the growth pattern between days 14 and 28.
Early diagnosis for colorectal cancer in China.

AIM To review the present studies on early diagnosis of colorectal cancer. METHODS The detective rate for early cancer is 1.7%-26.1% based on various statistical data, with much higher detective rate in endoscopy. Since early cancer means invasion involved in the mucosa or submucosa, the diagnosis can only be made when the invasive depth is identified. Pathological tissue materials from both surgical operation or endoscopic resection are suitable for early cancer evaluation. RESULTS Incidence of polyp malignancy is 1.4%-20.4%. The various constitutive proportion of polyps may explain the different rates. Malignant incidence is higher in adenomatous polyps, that for villous polyps can reach 21.3%-58.3%. Type II early stage of colorectal carcinoma is rarely reported in China. It is shown that majority of them were not malignant, most of type IIa being adenoma or hyperplasia, and IIb being inflammatory and IIc might be the isolated ulcers. The occurrence of malignancy of type II is far lower than that of polypoid lesion. In China, the qualitative diagnosis and classification of neoplasm generally adopted the WHO standard, including surgical excision or biopsies. There is impersonal evaluation between colorectal pre-malignancy and cancer. The former emphasizes the dysplasia of nuclei and gland, while the latter is marked with cancer invasion. Diagnosis of early stage colorectal cancer in endoscopy is made with too much caution which made the detective rate much lower. Mass screening for asymptomatic subjects and follow-up for high risk population are mainly used to find the early stage colorectal cancer in China. Fecal occult blood test is also widely made as primary screening test, galactose oxygenase test of rectal mucus (T antigen), fecal occult albumin test are also used. The detective rate of colorectal cancer is 24-36.5 per 105 mass population. CONCLUSION Although carcinoma associated antigen in blood or stool, microsatellite DNA instability for high risk familial history, molecular biology technology for stool oncogene or antioncogene, telomerase activity and exfoliative cytological examination for tumor marker, are utilized, none of them is used in mass screening by now.
Overconfidence, Sentiment and Beta Herding: A Behavioral Explanation of the Low-Beta Anomaly

We investigate asset returns using the concept of beta herding, which measures cross-sectional variations in betas induced by investors whose beliefs about the market are biased due to changes in confidence or sentiment. Overconfidence or optimistic sentiment causes beta herding (compression of individual assets’ betas towards the market beta), while under-confidence or pessimistic sentiment leads to adverse beta herding (dispersion of betas away from the market beta). We find that beta herding is related to the low-beta anomaly, as high beta stocks underperform low beta stocks on a risk-adjusted basis exclusively following periods of adverse beta herding. As an explanation of the low-beta anomaly, we propose the persistence of bias in betas (i.e., a large difference in betas) that lasts for more than one year as market uncertainty continues.
Mast Cell-Independent Mechanisms of Immediate Hypersensitivity: A Role for Platelets1

Mast cells have been implicated as the central effectors in allergic responses, yet a fatal anaphylactic response can be induced in mast cell-deficient mice. In this study, we examined the immediate hypersensitivity response in wild-type (WT) and mast cell-deficient mice (W/Wv) in two different tissues (skin and skeletal muscle). Vascular permeability and leukocyte recruitment were studied after immediate challenge or 4 h postchallenge in OVA-sensitized mice. In skin, immediate challenge induced a significant increase in vascular permeability (75%) within 30 min and was accompanied by increased leukocyte adhesion 4 h postchallenge. In the absence of mast cells, no changes in vascular permeability or leukocyte recruitment were observed in skin. In WT skeletal muscle, immediate challenge induced a rapid increase (80%) in vascular permeability within 5 min and significant leukocyte recruitment after 4 h. Surprisingly, in W/Wv, a gradual increase in vascular permeability was observed, reaching a maximum (50%) within 30 min. Despite the absence of mast cells, subsequent leukocyte emigration was similar to that observed in WT mice. Pretreatment with anti-platelet serum in W/Wv returned Ag-induced vascular permeability and leukocyte recruitment to baseline. Platelets were shown to interact with endothelium in skeletal muscle, but not dermal microvasculature. These data illustrate that mast cells play a prominent role in vascular permeability and leukocyte recruitment in skin in response to Ag, however, in skeletal muscle; these changes can occur in the absence of mast cells, and are mediated, in part, by the presence of platelets.
Who Fills Institutional Voids? Entrepreneurs’ Utilization of Political and Family Ties in Emerging Markets

How do entrepreneurs fill institutional voids that prevail in emerging markets? By incorporating insights from both the political and family embeddedness perspectives, we argue that both political ties and family ties can compensate for gaps in the institutional infrastructure of emerging markets. Specifically, we propose and examine the partial substitutability of family ties for political ties as a means of filling institutional voids. Our empirical work based on Chinese private enterprises strongly supports this argument. We also find that the effective utilization of family ties is contingent on both family members’ motivation (willingness to use resources for the firm) and entrepreneurs’ mobilization (authority in the family to mobilize family members). This study bridges the literature on political ties and family ties to understand their respective costs and benefits and therefore advances our understanding of entrepreneurs’ networking strategies in emerging markets.
Testing Lorentz invariance using an asymetric optical resonator

Recent experiments utilizing resonant cavities have produced remarkable results that limit the level of any possible violation of Lorentz Invariance. However, within the framework of the Standard Model Extension (SME) one parameter кtr remains significantly under-constrained compared to the other parameters. It has been shown an asymmetric optical resonator will be sensitive to violations of LI and specifically much more sensitive to кtr than conventional resonators. In this experiment such an asymmetric resonator is compared to a linear sapphire cavity with the measurement system is based on a 1064 nm YAG laser locked to the resonances of both cavities.
hnRNPM guides an alternative splicing program in response to inhibition of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells

Abstract Ewing sarcomas (ES) are biologically aggressive tumors of bone and soft tissues for which no cure is currently available. Most ES patients do not respond to chemotherapeutic treatments or acquire resistance. Since the PI3K/AKT/mTOR axis is often deregulated in ES, its inhibition offers therapeutic perspective for these aggressive tumors. Herein, by using splicing sensitive arrays, we have uncovered an extensive splicing program activated upon inhibition of the PI3K/AKT/mTOR signaling pathway by BEZ235. Bioinformatics analyses identified hnRNPM as a key factor in this response. HnRNPM motifs were significantly enriched in introns flanking the regulated exons and proximity of binding represented a key determinant for hnRNPM-dependent splicing regulation. Knockdown of hnRNPM expression abolished a subset of BEZ235-induced splicing changes that contained hnRNPM binding sites, enhanced BEZ235 cytotoxicity and limited the clonogenicity of ES cells. Importantly, hnRNPM up-regulation correlates with poor outcome in sarcoma patients. These findings uncover an hnRNPM-dependent alternative splicing program set in motion by inhibition of the mTOR/AKT/PI3K pathway in ES cells that limits therapeutic efficacy of pharmacologic inhibitors, suggesting that combined inhibition of the PI3K/AKT/mTOR pathway and hnRNPM activity may represent a novel approach for ES treatment.