Miracle-dz/UniFAR-FTUs huggingface dataset:
PBK/TOPK enhances aggressive phenotype in prostate cancer via β-catenin-TCF/LEF-mediated matrix metalloproteinases production and invasion

A Current challenge in prostate cancer treatment is how to differentiate aggressive disease from indolent prostate cancer. There is an urgent need to identify markers that would accurately distinguish indolent prostate cancer from aggressive disease. The aim of this study was to evaluate the role of PDZ Domain-binding kinase (PBK) in prostate cancer and to determine if PBK expression enhances aggressiveness in prostate cancer. Using archival tissue samples, gain-of-function and loss-of-function studies, we show that PBK expression is up-regulated in prostate cancer, and its expression level is commensurate with invasiveness. Modulation of PBK expression and function causally regulates the invasive ability of prostate cancer cells. Production of matrix metalloproteinases-2 and -9, which are key players in metastatic invasion, is up-regulated, and the promoters of these genes are transcriptionally activated by PBK via increased β-catenin-TCF/LEF signaling. Prostate cancer tissue specimens show that PBK's expression correlates with aggressive disease and distant metastasis in bone, lymph node and abdomen. Our in vitro and in situ data are in agreement that PBK could be a prognostic biomarker for prostate cancer that would discriminate aggressive prostate cancer from indolent disease, and is a potential target for the therapeutic intervention of aggressive prostate cancer in men.
Bistatically equivalent monostatic approximation for bistatic ISAR

Bistatic Inverse Synthetic Aperture Radar has recently gained interest as bistatic and multistatic radar systems are becoming increasingly popular. A theoretical foundation has been laid that introduces the concept of Bistatically Equivalent Monostatic (BEM) configuration, which allows approximating a bistatic geometry with a monostatic one. This greatly simplifies not only the geometrical understanding but also allows using monostatic ISAR processors to form bistatic ISAR images. In this paper further considerations are discussed, such as the analytical calculation of the effective rotation vector and the bistatic ISAR image plane when considering a BEM configuration. Simulated and real data analysis is also provided that prove the theoretical results.
Assessing Factors Related to Waist Circumference and Obesity: Application of a Latent Variable Model

Background. Because the use of BMI (Body Mass Index) alone as a measure of adiposity has been criticized, in the present study our aim was to fit a latent variable model to simultaneously examine the factors that affect waist circumference (continuous outcome) and obesity (binary outcome) among Iranian adults. Methods. Data included 18,990 Iranian individuals aged 20–65 years that are derived from the third National Survey of Noncommunicable Diseases Risk Factors in Iran. Using latent variable model, we estimated the relation of two correlated responses (waist circumference and obesity) with independent variables including age, gender, PR (Place of Residence), PA (physical activity), smoking status, SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure), CHOL (cholesterol), FBG (Fasting Blood Glucose), diabetes, and FHD (family history of diabetes). Results. All variables were related to both obesity and waist circumference (WC). Older age, female sex, being an urban resident, physical inactivity, nonsmoking, hypertension, hypercholesterolemia, hyperglycemia, diabetes, and having family history of diabetes were significant risk factors that increased WC and obesity. Conclusions. Findings from this study of Iranian adult settings offer more insights into factors associated with high WC and high prevalence of obesity in this population.
Unisex sports: challenging the binary

ABSTRACT This paper addresses some problems arising with respect to the male/female binary division that has traditionally been central to most sports. One strategy for dealing with this problem is to remove the binary and allow athletes of different sexes to compete together. Firstly, since there are different ways of ‘mixing’ athletes together, a distinction between two major kinds will be introduced: ‘mixed sports’ (sports with an allocated position for a number of males and females in a team, which retains the binary) and ‘unisex sports’ (sport participation of all athletes together based on merit, with no need to distinguish between sexes). Secondly, I shall offer a strategy for the modification of existing sports and the creation of new sports that would accommodate athletes of different sexes in ‘unisex sports’. This means paying attention to how sports are constructed and which abilities/skills they test. For unisex sports, two kinds of logic are suggested: ‘balance of abilities/skills logic’ proposes that we should seek a balance of what we presently understand as female and male (together with sex-neutral) abilities/skills to be included in the sporting challenge; whereas ‘complexity logic’ proposes the creation or modification of sports so as to test for a wider spectrum of abilities/skills.
An exploratory study of the effects of strenuous exercise on markers of coagulation activation, circulating microparticles, and inflammation in sickle cell trait

This exploratory study evaluated the effect of intense exercise on biomarkers of inflammation and coagulation activation in subjects with and without sickle cell trait (SCT). Fifteen healthy African American men (18‐35 years, 5 SCT, 10 control) completed a strenuous exercise protocol. Microparticle‐associated prothrombinase and tissue factor activities, as well as soluble VCAM, total white cell and monocyte count increased transiently in all subjects following exercise. In the SCT group, exercise resulted in increased d‐dimer, erythrocyte phosphatidylserine exposure, as well as increased circulating erythrocyte‐ and endothelial‐derived microparticle numbers. These alterations could contribute to exercise‐related complications in people with SCT.
Economic Freedom, Human Rights, and the Returns to Human Capital: An Evaluation of the Schultz Hypothesis

In 1975 Theodore W. Schultz suggested that the returns to human capital are highest in economic environments experiencing unexpected price, productivity, and technology shocks that create “disequilibria. ” In such environments, the ability of firms and individuals to adapt their resource allocations to shocks becomes most valuable. In the case of negative shocks, government policies that mitigate the impact of the shock will also limit the returns to the skills of managing risk or adapting resources to changing market forces. In the case of positive shocks, government policies may restrict access to credit, labor, or financial markets in ways that limit reallocation of resources toward newly emerging profitable sectors. This article tests the hypothesis that the returns to skills are highest in countries that allow individuals to respond to shocks. Using estimated returns to schooling and work experience from 122 household surveys in 86 developing countries, the article demonstrates a strong positive correlation between the returns to human capital and economic freedom, an effect that is observed throughout the wage distribution. Economic freedom benefits those workers who have attained the most schooling as well as those who have accumulated the most work experience.
Therapeutics , Targets , and Chemical Biology Function-Blocking ERBB 3 Antibody Inhibits the Adaptive Response to RAF Inhibitor

ERBB3/HER3 expression and signaling are upregulated in mutant BRAFmelanoma as an adaptive, prosurvival response to FDA-approved RAF inhibitors. Because compensatory ERBB3 signaling counteracts the effects of RAF inhibitors, cotargeting ERBB3 may increase the efficacy of RAF inhibitors in mutant BRAF models of melanoma. Here, we corroborate this concept by showing that the ERBB3 function-blocking monoclonal antibody huHER3-8 can inhibit neuregulin-1 activation of ERBB3 and downstream signaling in RAF-inhibited melanoma cells. Targeting mutant BRAF in combination with huHER3-8 decreased cell proliferation and increased cell death in vitro, and decreased tumor burden in vivo, compared with targeting either mutant BRAF or ERBB3 alone. Furthermore, the likelihood of a durable tumor response in vivo was increased when huHER3-8 was combined with RAF inhibitor PLX4720. Together, these results offer a preclinical proof of concept for the application of ERBB3-neutralizing antibodies to enhance the efficacy of RAF inhibitors in melanoma to delay or prevent tumor regrowth. As ERBB3 is often upregulated in response to other kinase-targeted therapeutics, these findings may have implications for other cancers as well. Cancer Res; 74(15); 4122–32. 2014 AACR.
Some Developmental Trends in Children's Information-Processing Strategies

The problem-solving strategies of 120 children from two age levels were compared by means of exploratory factor analyses. Essentially, these results replicated the factor structures of earlier studies based on the Das-Luria model. Disparities in factor loadings on some tasks were interpreted as suggestive of developmental differences in children's coding strategies which are compatible with Bruner's description of the course of cognitive growth.
Safety and Efficacy of RT002, an Injectable Botulinum Toxin Type A, for Treating Glabellar Lines: Results of a Phase 1/2, Open-Label, Sequential Dose-Escalation Study

BACKGROUND RT002 is a new injectable BoNTA product. This formulation limits the spread of BoNTA, potentially permitting safe administration of larger doses and possibly extending its duration of action. OBJECTIVE This phase 1/2 clinical study was designed to establish the safety of RT002 for the treatment of moderate-to-severe glabellar lines. MATERIALS AND METHODS Subjects were randomized into four groups (N=12/group). Cohorts 1-3 received escalating doses of RT002 ranging from half the equivalent dose of approved toxins up to twice the current dose levels. The safety of each dose was confirmed prior to administering the next dose. Subjects in Cohort 4 were treated with the highest dose and observed for 36 weeks or until GLSS returned to baseline. RESULTS All doses of RT002 were well-tolerated. Common AEs were headache and mild injection site reactions. At Week 4, all doses of RT002 were highly effective at maximum frown. Cohort 4 achieved 7 month median duration. At 6 months, 80% of subjects maintained a ≥1-point improvement in Investigator GLSS and 60% maintained WSS of None or Mild. Study limitations include an open-label design and modest number of subjects. CONCLUSION RT002 is a safe and effective BoNTA product with an extended duration of action.
Stratospheric variability and trends in models used for the IPCC AR4

Atmosphere and ocean general circulation model (AOGCM) experiments for the Intergovernmental Panel on Climate Change Fourth Assessment Report (AR4) are ana- lyzed to better understand model variability and assess the importance of various forcing mechanisms on stratospheric trends during the 20th century. While models represent the climatology of the stratosphere reasonably well in compar- ison with NCEP reanalysis, there are biases and large vari- ability among models. In general, AOGCMs are cooler than NCEP throughout the stratosphere, with the largest differ- ences in the tropics. Around half the AOGCMs have a top level beneath 2 hPa and show a significant cold bias in their upper levels ( 10 hPa) compared to NCEP, suggesting that these models may have compromised simulations near 10 hPa due to a low model top or insufficient stratospheric levels. In the lower stratosphere (50 hPa), the temperature variability associated with large volcanic eruptions is absent in about half of the models, and in the models that do include volcanic aerosols, half of those significantly overestimate the observed warming. There is general agreement on the verti- cal structure of temperature trends over the last few decades, differences between models are explained by the inclusion of different forcing mechanisms, such as stratospheric ozone depletion and volcanic aerosols. However, even when hu- man and natural forcing agents are included in the simu- lations, significant differences remain between observations and model trends, particularly in the upper tropical tropo- sphere (200 hPa-100 hPa), where, since 1979, models show a warming trend and the observations a cooling trend.
Use of HIV Resistance Testing After Prolonged Treatment Interruption

Background:HIV-1 genotypic resistance testing is not routinely recommended for patients who have been off antiretroviral therapy (ART) for longer than 4 weeks. We assessed the results and use of resistance testing in patients off ART. Methods:All HIV resistance genotypes from November 2003 through April 2008 were reviewed from one large teaching hospital and two private HIV practices. Inclusion criterion was having a genotypic resistance test after an ART interruption of at least 2 months. Medical records were reviewed using a standardized data collection sheet. Results:Sixty-two of 304 treatment-experienced patients with HIV genotypes met the inclusion criteria. Prior cumulative ART class exposure included nucleoside reverse transcriptase inhibitors in 54 patients, nonnucleoside reverse transcriptase inhibitors in 32 patients, and protease inhibitors in 30 patients. Resistance testing was performed at a mean of 12 months (range, 2.5-48 months) after ART interruption. The mean time between ART interruption and resistance testing did not differ for patients with mutations and those without mutations detected. Seventeen of 62 (27.4%) patients were found to have resistance mutations. Eleven patients were found to have mutations to nonnucleoside reverse transcriptase inhibitors, four patients had mutations to nucleoside reverse transcriptase inhibitors, and two patients had protease inhibitor-associated mutations. No patient had multiclass resistance. Among the 17 patients with mutations after treatment interruption, 15 had mutations that were either not present on a prior genotype (n = 2) or did not have a prior genotype (n = 13). Conclusions:HIV genotypic resistance assays may identify mutations even when performed after a prolonged treatment interruption and may offer clinically significant information. Current guidelines that discourage resistance testing after treatment interruptions of longer than 4 weeks should be re-evaluated.
Behavioral Finance and Retirement Plan Contributions: How Participants Behave, and Prescriptive Solutions

Behavioral research has made important, relevant contributions to retirement saving and investing. This work has cast a new light on participant behavior and its underpinnings: By and large, individuals are inert--with good intentions, poor follow-through, and bounded rationality. Loss aversion and decision-making biases often lead to unfortunate outcomes, including a poorly funded retirement. Further, behavioral economists have demonstrated that education and communication programs alone may not be effective in changing behavior. Instead, with their behavioral insights, they have offered new retirement plan design alternatives and empirically tested their efficacy in overcoming identified suboptimal behavior. These efforts are helping to pave a path of least resistance that should lead to greater retirement security. The Pension Protection Act of 2006 appears to support these alternatives by providing incentives to plan sponsors that implement automatic features such as automatic enrollment and deferral rate escalation. It also allows plan sponsors to choose more aggressive investment defaults. Perhaps implicit in this support is some advice to sponsors to accept participant behavior and to think more about changing their own by embracing automatic plan features.
Clinical Microbiology Reviews: Genesis of a Journal

SUMMARY In 1986 planning for a new ASM review journal, Clinical Microbiology Reviews (CMR), began. CMR would publish articles primarily of interest to persons concerned with pathogenesis, laboratory diagnosis, epidemiology, and control of human and veterinary pathogens. The first issue was published in January 1988, with quarterly publication since then. The journal quickly became successful in terms of subscribers and impact on the field, earning a strong national and international reputation. The achievements of CMR are owed to many persons, including the editorial board, the production team, and especially the contributing authors.
Does adding an appended oncology module to the Global Trigger Tool increase its value?

OBJECTIVE To determine any additional value in the evaluation of safety levels by adding an appended oncology module to the Institute for Healthcare Improvement's Global Trigger Tool (GTT). DESIGN Comparison of two independent retrospective chart reviews: one review team using the general GTT method and one using the general GTT method plus the appended oncology module on the same inpatient charts. SETTING The Department of Clinical Oncology at a Danish University Hospital (1000 beds). PARTICIPANTS All inpatients admitted to the hospital in 2010, n = 3692, biweekly sample of 10 admission charts resulting in a double review of 240 charts. MAIN OUTCOME MEASURES Total number of identified adverse events (AEs), distribution of identified AEs in the harm categories of the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP), AEs per 100 admissions and AEs per 1000 admission days. RESULTS No significant (95% confidence interval) difference was found between review teams using the general GTT versus the general GTT plus the appended oncology module on the total number of identified AEs, AEs per 100 admissions, AEs per 1000 admission days or in the overall distribution of identified AEs in the five NCC MERP harm categories. CONCLUSIONS The study showed that adding the appended oncology module to the GTT did not increase its value regarding the evaluation of safety levels. This finding could be due to the measurement error of the GTT. Further studies evaluating the measurement properties and the specific additional modules to the general GTT are needed.
Hormonal control of glycogen in the heart and other tissues in rats.

THE glycogen of the heart, unlike that of other tissues, has often been found to be greater in amount in the fasting animal than in the fully fed subject (Macleod and Prendergest, 1921; Evans, 1934; Bong, Junkersdorf and Steinborn, 1934; Lackey, Bunde, and Harris, 1946). Illingworth and Russell (1951) observed further that the cardiac glycogen of fasting hypophysectomized rats was lower than that of normal animals similarly fasted and that this difference could be overcome to a considerable degree by treatment with purified growth hormone during the fasting period. Also the cardiac glycogen of intact fasting rats was increased after the acute administration of growth hormone. These observations suggested that the activity of one or more pituitary hormones might be concerned with the increase in cardiac glycogen which is induced by fasting, and the experiments below were undertaken primarily as a further investigation of this point. In the same animals, glycogen was determined also in the gastrocnemius mus.
Left Main Coronary Ostial Stenosis after Aortic Valve Replacement: A Case Report

Coronary ostial stenosis is a rare but potentially life-threatening complication of aortic valve replacement (AVR). It can present potential complications such as acute coronary syndrome, left ventricular failure, ventricular arrhythmias, or sudden death. Exact pathogenetic mechanism is not known, but a few hypotheses have been proposed. We present a case of left main coronary stenosis 11 months after AV R was done for symptomatic critical aortic stenosis. High index of clinical suspicion and timely coronary angiography helped to determine the exact etiology. A percutaneous coronary intervention was done emergently. The patient has done very well so far.
Time-of-Flight Measurements on Schottky CdTe Detectors

The internal electric field distribution of Schottky barrier CdTe detectors was evaluated by using time-of-flight (TOF) measurements combined with Monte Carlo (MC) simulation. The evolution of the current waveforms from less than 1 s up to about 1300 s of DC bias duration was measured at room temperature. The observed temporal behavior of the current waveforms was well reproduced by MC simulation with simple linear variation of the electric field strength distribution with position x from the anode electrode. These observations indicate accumulation of negative space charges, which screens the applied electric field progressively from the cathode side toward the bulk. Based on the evolution of the current waveforms we can successfully extract the temporal evolution of electric field distribution characterized by triple exponential function.
Toward synthetic biology with engineered T cells: a long journey just begun.

It is an honor to provide retrospective comments as we enter a remarkable era of gene transfer therapy that will ultimately provide cures for a number of presently incurable diseases. As in nearly all fields, the present advances have been made by extending the advances of our predecessors. Friedmann has chronicled the origins of the field for those new to this discipline (Friedmann and Roblin, 1972; Friedmann, 1992). From my own experiences, I suspect that there are three qualities in common with all of the investigators who have had a role in bringing gene transfer to the threshold of success. First, each investigator must possess a remarkable degree of stubbornness to persist in the face of repeated experimental failures; further, investigators in this field had to persist when the field was held in generally low regard by other fields of biomedical research. Second, all of the senior investigators in gene transfer technologies share the attribute of having an extraordinarily long attention span, which in most cases spans several decades of sustained effort. Finally, I suspect that all gene therapy pioneers have multidisciplinary interests, and are comfortable with multitasking, a quality that is necessary to translate basic science advances in this multidisciplinary field. Below are some of the experiences that my team has faced and lessons from the challenges that we have encountered.
Visual Spatial Aftereffect from Prolonged Head-Tilt

Subjects with head upright were required to adjust a lighted bar in a dark room until the bar appeared vertical; the task was performed before and after 2 and 3 minutes of lateral head-tilt with their eyes closed. A visual spatial aftereffect was observed which varied as a function of the angle of head-tilt and which was opposite in direction to head-tilt.