Miracle-dz/UniFAR-FTUs huggingface dataset:
Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation

In a yeast two-hybrid screen using the full-length Akt as bait, we found that prohibitin 2 (PHB2) specifically interacts with Akt. The C terminus of Akt (amino acids 413-480) and a central region of PHB2 (amino acids 120-232) are responsible for their mutual interaction. PHB2 acts as a transcriptional repressor in cells. PHB2 interacts with both MyoD and MEF2, and represses both MyoD- and MEF2-dependent gene transcription. Furthermore, binding of PHB2 to both MyoD and MEF2 significantly decreases upon myogenic differentiation. When stably expressed in C2C12 myogenic cells, PHB2 inhibits myogenin induction and phenotypic muscle differentiation. PHB2 was found to specifically recruit histone deacetylase 1, which is probably responsible for its repressive activity. Co-expression of Akt can partially reduce PHB2 binding to MyoD and relieve the repressive effect of PHB2 on myogenic reporters, which could be one of the mechanisms underlying Akt-mediated MyoD activation and accelerated muscle differentiation.
Deep Brain Stimulation Reveals Emotional Impact Processing in Ventromedial Prefrontal Cortex

We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact of emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated and the change of blood flow associated with the DBS. In subjects with a low emotional impact, activity measured as blood flow rose when the electrode was turned on, while in subjects of high impact, the activity at this site in the ventromedial prefrontal cortex declined when the electrode was turned on. We conclude that changes of neurotransmission in the ventromedial prefrontal cortex had an effect on the tissue that depends on changes of monoamine concentration interacting with specific combinations of inhibitory and excitatory monoamine receptors.
Leisure time physical activity and strenuousness of work as predictors of physical functioning: a 28 year follow up of a cohort of industrial employees

Aims: To examine associations of leisure time physical activity and physical strenuousness of work with physical functioning 28 years later. Methods: A cohort (n = 902) of metal industry employees was studied for exercise and housework activity in 1973 and 1978, and for BMI, current smoking, strenuousness of work, grip strength, and chronic diseases in 1973. Of the 670 survivors in 2000, 529 (79%) responded to all studied items in a follow up questionnaire including the SF-36 Physical Functioning (PF) scale. Belonging to the lower quartile of the PF scale denoted poor functioning. Results: Vigorous exercise and housework activity were inversely associated with poor PF 28 years later in both white-collar and blue-collar workers. Engaging in activities of any intensity was similarly associated among the blue-collar workers. In a multiple logistic regression model including as independent variables age, sex, occupational class, the number of chronic diseases, vigorous leisure time physical activity, BMI, physical work strenuousness, and smoking (all measured at baseline), the risk of poor PF at follow up was decreased by vigorous leisure time physical activity and increased by high physical strenuousness of work, high BMI, and smoking. The effect of work strenuousness was mainly due to that among the blue-collar group. Allowing for baseline grip strength did not materially alter the results. Conclusion: Vigorous leisure time physical activity decreased the risk of poor physical functioning as perceived considerably later in life, while high work strenuousness, smoking, and overweight increased it. Among blue-collar workers a beneficial association was observed with all leisure time activity, including that of lower intensity.
Control of Lysis of T4-infected Escherichia coli

The lysis of Escherichia coli B/5 infected with T4Dr48 could be delayed by addition of 9-aminoacridine (9AA). Infected cells showed an early period of maximal response followed by a decline in sensitivity. The ultimate rate of lysis was also affected by the dye. Deoxyribonucleic acid (DNA), protein, and lysozyme synthesis began at the normal time in complexes inhibited by 9AA addition. The rates of synthesis of these macromolecules were lower in the presence of the dye, with DNA and lysozyme synthesis being more strongly affected than total protein synthesis. Penicillin-sensitive cell wall synthesis stopped at about 10 min after infection. Inhibition of oxidative metabolism by early potassium cyanide addition prevented lysis in the presence of intracellular lysozyme. The cyanide-sensitive event occurred at about 20 min in normal infections, and between 30 and 40 min in 9AA-inhibited infections. 9AA could alter both the time at which the cyanide-sensitive event occurred and the time of lysis. Addition of chloramphenicol did not prevent lysis once intracellular lysozyme was present. Lysis from without of infected cells consisted of three phases: an initial sensitivity, followed by a short period of resistance, and then a return to sensitivity in normal infections. The demonstration of the late return to sensitivity depended on the presence of intracellular lysozyme, and could be delayed by 9AA addition.
Enhanced 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity in human colorectal cancer not expressing low density lipoprotein receptor.

BACKGROUND We have previously shown that 63.3% of colorectal cancer neoplastic specimens did not express the Low Density Lipoprotein Receptor (LDLR) protein and that the absence of LDLR predicted shorter survival. We now report the findings of a preliminary study on HMG-CoA reductase (HMG-CoAR) activity in neoplastic tissue specimens of human colorectal cancers (CRC) expressing or not expressing LDLR. MATERIALS AND METHODS The tissue specimens were obtained from 16 patients (10 males and 6 females) undergoing surgical resection for CRC, and previously characterized for LDLR (7 not expressing LDLR and 9 expressing LDLR). HMG-CoAR activity was measured by radiochemical assay using 14C-HMG-CoA as substrate. RESULTS HMG-CoAR activity was significantly higher in specimens not expressing LDLR than in those expressing LDLR [8.3 pmol/min/mg prot (2.4-16) vs 3.9 pmol/min/mg prot (1.2-7.8), data expressed as median value and the range, p = 0.02, Wilcoxon Rank sum test)]. CONCLUSIONS The cholesterol requirement in CRC not expressing LDLR may be met by increasing endogenous synthesis. For this reason, the use of HMG-CoA R inhibitors for the treatment of CRC expressing high HMG-CoAR activity-dependence for growth may be clinically important.
Standard promotion practices versus up-or-out contracts

In most firms a worker in any period is either promoted, left in the same job, or fired (demotions are typically rare), and there is no specific date by which a promotion needs to occur. In other employment situations, however, up-or-out contracts are common, i.e., if a worker is not promoted by a certain date the worker must leave the firm. This paper develops a theory that explains why and when each of these practices is employed. Our theory is based on asymmetric learning in labor markets and incentives associated with the prospect of future promotion. Our main result is that firms employ up-orout contracts when firm-specific human capital is low while they employ standard promotion practices when it is high. We also find that, if firms can commit to a wage floor for promoted workers and effort provision is important, then up-or-out contracts are employed when low-level and high-level jobs are similar. We believe these results are of interest because they are consistent with many of the settings in which up-or-out is typically observed such as law firms and academic institutions.
Modulation of synaptic transmission and long-term potentiation: effects on paired pulse facilitation and EPSC variance in the CA1 region of the hippocampus.

1. Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) were made from guinea pig hippocampal CA1 pyramidal cells. The sensitivity of paired pulse facilitation (PPF) and EPSC variance to changes in synaptic transmission was investigated and the results were compared with the changes in these parameters evoked by long-term potentiation (LTP). 2. Presynaptic manipulations, such as activation of presynaptic gamma-aminobutyric acid-B receptors by baclofen, blockade of presynaptic adenosine receptors by theophylline, blockade of presynaptic potassium channels by cesium, and increasing the Ca(2+)-Mg2+ ratio in the external recording solution, each reliably changed PPF in a fashion reciprocal to the change in the EPSC amplitude. However, recruitment of additional synaptic release sites by increasing stimulus strength and antagonism of non-N-methyl-D-aspartate (NMDA) glutamate receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) failed to alter PPF. 3. Presynaptic manipulations including increased stimulus strength gave the predicted changes in the value of mean 2/variance (M2/sigma 2). Moreover, postsynaptic manipulations that altered EPSC amplitude, including blockade of non-NMDA receptors by CNQX, or changing the holding potential of the postsynaptic cell, gave little change in M2/sigma 2, as would be predicted for manipulations resulting in a uniform postsynaptic change. 4. LTP caused no change in PPF, whereas the presynaptic manipulations, which caused a similar amount of potentiation to that induced by LTP, significantly decreased PPF. On the other hand, LTP did increase M2/sigma 2, although the increase was less than that predicted for a purely presynaptic mechanism. (ABSTRACT TRUNCATED AT 250 WORDS)
SARS-CoV Antibody Prevalence in All Hong Kong Patient Contacts

A total of 1,068 asymptomatic close contacts of patients with severe acute respiratory (SARS) from the 2003 epidemic in Hong Kong were serologically tested, and 2 (0.19%) were positive for SARS coronavirus immunoglobulin G antibody. SARS rarely manifests as a subclinical infection, and at present, wild animal species are the only important natural reservoirs of the virus.
Localization of the Bannayan-Riley-Ruvalcaba syndrome gene to chromosome 10q23.

BACKGROUND & AIMS Bannayan-Riley-Ruvalcaba syndrome is a congenital syndrome with characteristic features of macrocephaly, cognitive and motor dysfunction, subcutaneous and visceral lipomas and hemangiomas, and intestinal juvenile polyposis. It has been suggested that Bannayan-Riley-Ruvalcaba syndrome may be a variant of juvenile polyposis coli because of the shared features of intestinal juvenile polyps. The aim of this study was to precisely map loss of DNA from 2 patients with intestinal juvenile polyposis and karyotypic abnormalities involving chromosome 10q. METHODS DNA was extracted from peripheral leukocytes drawn from each patient and each patient's biological parents. The DNA was amplified by polymerase chain reaction using primers specific for microsatellites located on chromosome 10q. RESULTS Precise mapping localized a maximal distance of 1.0 cM that was commonly deleted from each patient's genome, between D10S541 and D10S1735. This area overlaps the region for Cowden disease, a distinct hamartomatous intestinal polyposis syndrome with increased risk of breast and thyroid carcinoma. CONCLUSIONS The three hamartomatous polyposis syndromes, Bannayan-Riley-Ruvalcaba syndrome, juvenile polyposis coli, and Cowden disease, may share the same genetic defect because of their common map localization to chromosome 10q23.
How Successful State Education Improvement Programs Work.

S UDDENLY, I understood what it meant to be a principal, to be a leader in my school. That workshop made all the differ ence. " So spoke a 50-year-old principal whose low-scoring school had been re quired to participate in a state-spon sored school improvement program. This principal had begun to grasp the underlying dimensions of school im provement, dimensions that could pro vide a principal or other school leader with the strategies necessary to start up and carry out an improvement effort, to make it successful, and to install it as an ongoing Lf-renewing activity. States nave created two general types of educational improvement programs, each of which can provide a conceptual framework for school leaders to guide the multi-textured process of improving education locally. The first type of pro gram is school based and engages local
Using Experimental Evolution to Study the Physiological Mechanisms of Desiccation Resistance in Drosophila melanogaster

Data from populations undergoing experimental evolution can be used to make comparisons between physiologically differentiated populations and to determine evolutionary trajectories. Comparisons of long‐established laboratory populations of Drosophila melanogaster that are strongly differentiated with respect to desiccation resistance are used to test alternative hypotheses concerning the mechanisms that fruit flies use to survive bouts of extreme desiccation. This comparative study supports the hypothesis that, in at least one case, D. melanogaster can evolve increased resistance to desiccation by decreasing water loss rates and by increasing bulk water content but not by increasing metabolic water content or dehydration tolerance. While glycogen was involved in water storage, its primary role was in water binding, not the production of metabolic water. Measurement of the trajectories of these component mechanisms during selection for desiccation resistance is used to demonstrate that water loss rate quickly plateaus in response to selection, while water content continues to improve. This disparity reveals the value of studying evolutionary trajectories and the need for longer‐term selection studies in evolutionary physiology.
A Greedy Approach for Budgeted Maximum Inner Product Search

Maximum Inner Product Search (MIPS) is an important task in many machine learning applications such as the prediction phase of a low-rank matrix factorization model for a recommender system. There have been some works on how to perform MIPS in sub-linear time recently. However, most of them do not have the flexibility to control the trade-off between search efficient and search quality. In this paper, we study the MIPS problem with a computational budget. By carefully studying the problem structure of MIPS, we develop a novel Greedy-MIPS algorithm, which can handle budgeted MIPS by design. While simple and intuitive, Greedy-MIPS yields surprisingly superior performance compared to state-of-the-art approaches. As a specific example, on a candidate set containing half a million vectors of dimension 200, Greedy-MIPS runs 200x faster than the naive approach while yielding search results with the top-5 precision greater than 75\%.
Intracellular free zinc during cardiac excitation-contraction cycle: calcium and redox dependencies.

AIMS Zinc exists in biological systems as bound and histochemically reactive free Zn(2+). It is an essential structural constituent of many proteins, including enzymes from cellular signalling pathways, in which it functions as a signalling molecule. In cardiomyocytes at rest, Zn(2+) concentration is in the nanomolar range. Very little is known about precise mechanisms controlling the intracellular distribution of Zn(2+) and its variations during cardiac function. METHODS AND RESULTS Live-cell detection of intracellular Zn(2+) has become feasible through the recent development of Zn(2+)-sensitive and -selective fluorophores able to distinguish Zn(2+) from Ca(2+). Here, in freshly isolated rat cardiomyocytes, we investigated the rapid changes in Zn(2+) homeostasis using the Zn(2+)-specific fluorescent dye, FluoZin-3, in comparison to Ca(2+)-dependent fluo-3 fluorescence. Zn(2+) sparks and Zn(2+) transients, in quiescent and electrically stimulated cardiomyocytes, respectively, were visualized in a similar manner to known rapid Ca(2+) changes. Both Zn(2+) sparks and Zn(2+) transients required Ca(2+) entry. Inhibiting the sarcoplasmic reticulum Ca(2+) release or increasing the Ca(2+) load in a low-Na(+) solution suppressed or increased Zn(2+) movements, respectively. Mitochondrial inhibitors slightly reduced both Zn(2+) sparks and Zn(2+) transients. Oxidation by H₂O₂ facilitated and acidic pH inhibited the Ca(2+)-dependent Zn(2+) release. CONCLUSION It is proposed that Zn(2+) release during the cardiac cycle results mostly from intracellular free Ca(2+) increase, triggering production of reactive oxygen species that induce changes in metal-binding properties of metallothioneins and other redox-active proteins, aside from ionic exchange on these proteins.
Debt Maturity and the International Financial Architecture

This paper presents a theory of the maturity of international sovereign debt and derives its implications for the reform of the international financial architecture. It presents a general equilibrium model in which the need to roll over external debt disciplines the policies of debtor countries but makes them vulnerable to unwarranted debt crises owing to bad shocks. The paper presents a welfare analysis of several measures that have been discussed in recent debates, such as the adoption of renegotiation-friendly clauses in debt contracts and the establishment of an international bankruptcy regime for sovereigns.
The relationship between self-efficacy, collective efficacy and sport performance in men's and women's ice hockey goaltender teams

Past research has shown a positive relationship between efficacy and performance (Feltz & Lirgg, 1998). Feltz and Lirgg (1998) found a positive relationship between efficacy and sport performance in hockey players, however they excluded goaltenders due to their unique position. The present study replicated Feltz and Lirgg (1998) with only goaltenders. Data was collected from 12 goaltenders from three Ontario hockey leagues. Efficacy was measured through an online questionnaire and official game statistics provided the performance measures. Data was collected for 70 games to total of 112 responses. Results of this study revealed non-significant relationships between both selfand collective efficacy and all performance indicators. Results of the present study are not consistent with Feltz and Lirgg’s (1998), however other published research has found a non-significant relationship between efficacy and sport performance (Sitzmann & Yeo, 2013). Therefore, it is possible that goaltender efficacy is not the most influential psychological construct.
Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin, stem cell factor, and interleukin-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro.

Thrombopoietin (Tpo), the ligand for the c-mpl receptor, is a major regulator of platelet production in vivo. Treatment of mice with purified recombinant Tpo increases platelet count fourfold and expands colony-forming unit-megakaryocyte (CFU-Meg) numbers. Other cytokines including interleukin-3 (IL-3), IL-6, IL-11, erythropoietin (Epo), and stem cell factor (SCF) can stimulate megakaryopoiesis. Therefore, we examined the effects of recombinant murine Tpo in combination with these cytokines on megakaryopoiesis in vitro. Murine marrow cells were cultured in agar in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% horse serum and beta-mercaptoethanol in the presence of recombinant growth factors, and CFU-Meg colonies were counted on day 5. Megakaryocyte ploidy was analyzed using murine marrow cells cultured for 5 days in IMDM supplemented with 1% nutridoma-SP and recombinant growth factors. Megakaryocytes were identified by labeling with the 4A5 antibody and ploidy was analyzed by flow cytometry. Tpo supported the growth of CFU-Meg in a dose-dependent manner. Although the addition of SCF (50 ng/mL), Epo (2 U/mL), or IL-11 (50 ng/mL) alone exerted only a modest effect on CFU-Meg growth, the combination of SCF plus Tpo, Epo plus Tpo, or IL-11 plus Tpo resulted in a synergistic enhancement of the number of CFU-Meg colonies. IL-3 alone supported CFU-Meg colony growth, and the effects of IL-3 plus Tpo or IL-6 plus Tpo on colony growth appeared to be approximately additive. Fifty percent of megakaryocytes generated in cultures containing IL-3 or Epo displayed < or = 16 N ploidy. In contrast, cultures containing Tpo uniquely generated large numbers (30% to 35% of the total) of megakaryocytes with > or = 64N ploidy. These results show that Tpo stimulates both proliferation of committed megakaryocytic progenitor cells and maturation of megakaryocytes, and that two multipotent cytokines, SCF and IL-11, as well as a late-acting erythroid cytokine, Epo, can synergize with Tpo to stimulate proliferation of CFU-Meg.
The Reliability and Validity of the Computerized Double Inclinometer in Measuring Lumbar Mobility

Study Design : Repeated measures reliability/validity study. Objectives : To determine the concurrent validity, test-retest, inter-rater and intra-rater reliability of lumbar flexion and extension measurements using the Tracker M.E. computerized dual inclinometer (CDI) in comparison to the modified-modified Schober (MMS) Summary of Background : Numerous studies have evaluated the reliability and validity of the various methods of measuring spinal motion, but the results are inconsistent. Differences in equipment and techniques make it difficult to correlate results. Methods : Twenty subjects with back pain and twenty without back pain were selected through convenience sampling. Two examiners measured sagittal plane lumbar range of motion for each subject. Two separate tests with the CDI and one test with the MMS were conducted. Each test consisted of three trials. Instrument and examiner order was randomly assigned. Intra-class correlations (ICCs 2, 2 and 2, 2) and Pearson correlation coefficients (r) were used to calculate reliability and concurrent validity respectively. Results : Intra-trial reliability was high to very high for both the CDI (ICCs 0.85 - 0.96) and MMS (ICCs 0.84 - 0.98). However, the reliability was poor to moderate, when the CDI unit had to be repositioned either by the same rate (ICCs 0.16 - 0.59) or a different rater (ICCs 0.45 - 0.52). Inter-rater reliability for the MMS was moderate to high (ICCs 0.75 - 0.82) which bettered the moderate correlation obtained for the CDI (ICCs 0.45 - 0.52). Correlations between the CDI and MMS were poor for flexion (0.32; p<0.05) and poor to moderate (-0.42 - -0.51; p<0.05) for extension measurements. Conclusion : When using the CDI, an average of subsequent tests is required to obtain moderate reliability. The MMS was highly reliable than the CDI. The MMS and the CDI measure lumbar movement on a different metric that are not highly related to each other.