Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of cross-linked profilin:beta/gamma-actin on the dynamics of the microfilament system in cultured cells.

There is evidence that the profilin:actin complex is the immediate precursor in the formation of actin filaments in cells. This paper describes the cell morphology and microfilament distribution after microinjection of covalently cross-linked profilin:beta/gamma-actin (PxA) in two different cell lines. Injected cells were either kept unstimulated or stimulated with platelet-derived growth factor (PDGF) before fixation and visualization of filamentous actin. After injection of low doses of PxA, the cells displayed an actin organization characterized by a clearance of diffuse fluorescence from a region immediately interior of ruffling edges and the appearance of small dots of fluorescence in the same region. At higher concentrations, PxA effectively inhibited outgrowth of lamellae and microspikes, and there was a drastic reduction of actin staining in the zone behind the advancing edge. This effect is reminiscent of the effect of cytochalasin B on fibroblasts and the growth cone of neuronal cells. As in these cases, there remained a rim of actin-dependent fluorescence on the very edge of the membrane lamella, particularly in the PxA-treated fibroblasts. The interference of PxA with the formation of surface structures was pronounced after PDGF stimulation. Here, PxA effectively eliminated the enhancement of the ruffling activity in the cell edges and on the dorsal surface of the cells. In contrast to PxA, injection of non-cross-linked profilin:beta/gamma-actin had no apparent effect on cell morphology and microfilament distribution except for an increased concentration of filamentous actin in one of the cell lines.
The Role of Long-Term Memory in Digit–Symbol Test Performance in Young and Older Adults

ABSTRACT The psychological functions assessed by substitution tests, and the age-related performance decline, are not well understood. Here several aspects of long-term memory were manipulated across younger and older adults. A 45-page Digit–Symbol test was employed. Each page contained a 9-item digit symbol code-table and 9 response items. There were 9 study conditions with each condition deployed across 5 pages, or trials, of the test. The conditions were formed by crossing two within-subjects factors, each with 3 levels. The first factor, Digit Order, pertained to having the code table digits in numerical order vs. a pseudo-random order fixed across trials vs. a pseudo-random order that varied across trials. The second factor, Symbol Pairing, pertained to having a fixed digit–symbol pairing across trials vs. having a varying digit–symbol pairing across trials vs. having a novel set of 9 symbols introduced on each of the 5 trials. Including the additional factor, Age, resulted in a 2 × 3 × 3 mixed randomised block design. The older group was slowed, F(1, 22) = 17.267, p < . 001, and overall-performance was poorer when the digits were arranged non-numerically, F(1,44) = 55.403, p < . 001. An Age by Symbol–Order interaction indicated that use of novel symbols disadvantaged only the older participants, F(1, 44) = 6.577, p = . 014. While there was no evidence that incidental paired-associate learning or spatial memory affect digit–symbol performance, symbol familiarity may be important to digit symbol test completion in older adults. The benefit of ordinally arranged digits in the coding table highlights a fundamental process difference between Digit–Symbol and Symbol–Digit test formats.
Very mild cases of Rett syndrome with skewed X inactivation

Background: Rett syndrome, a common cause of mental retardation in females, is caused by mutations in the MECP2 gene. Most females with MECP2 mutations fulfil the established clinical criteria for Rett syndrome, but single cases of asymptomatic carriers have been described. It is therefore likely that there are individuals falling between these two extreme phenotypes. Objective: To describe three patients showing only minor symptoms of Rett syndrome. Findings: The patient with the best intellectual ability had predominantly psychiatric problems with episodes of uncontrolled aggression that have not been described previously in individuals with MECP2 mutations. All three patients had normal hand function, communicated well, and showed short spells of hyperventilation only under stress. Diagnosis in such individuals requires the identification of subtle signs of Rett syndrome in girls with a mild mental handicap. Analysis of the MECP2 gene revealed mutations that are often found in classical Rett syndrome. Skewed X inactivation was present in all three cases, which may explain the mild phenotype. Conclusions: Because of skewed X inactivation, the phenotype of Rett patients may be very mild and hardly recognisable.
Meningiomas and obesity reconsidered

Recognition of the preponderance of female patients with meningiomas and the demonstration of estrogen receptors in four of six meningiomas by Donnell et al {3} suggested an important role for estrogen as a cause or promoter of this tumor. Well known is the fact that obese women, who have increased peripheral conversion of androstenedione to estrone, have more available estrogens. Bellur et al {23 conducted a case-control study of 176 meningioma patients matched with an equal number of patients with other neurological diseases. They suggested that a significant association existed between meningiomas and obesity in women but not in men. Tilzer et al { 5 ] found that all of his 6 reported patients with meningiomas lacked estrogen receptors but most contained large amounts of progesterone receptor. We conducted a retrospective study of 203 adult intracranial meningioma patients seen at the University of Kansas between 1747 and 1984 for whom heights and weights were recorded within a year of diagnosis. As suggested by the Health and Nutrition Examination Survey (HANES) 19711774, obesity was defined as moderate when 10 to 17% above the desirable weight or marked when more than 17% above the desirable weight fl]. Comparison was then made to the prevalence of obesity in the general population, as defined by the HANES study. These benchmark data were as close to the time midpoint of the study as we could achieve. We found over twice as many women (137) as men (66) in our series of 203 adult patients, as would be expected. The Table shows the distribution of the HANES population and our meningioma patients separately for males and females in three categories: obese (marked), obese (moderate), and not obese. By contingency table analysis, the meningioma patients were not more likely to be obese than were those in the HANES population. When markedly obese patients were compared to a combined group of those who were not obese or were moderately obese, significant differences were not found (males: x2 = 0.2, p > 0.6; females: x2 = 0.1, p > 0.7). Similarly, when markedly obese patients were compared only to those who were not obese, significant differences were not found (males: x2 = 1.5,p > 0.1; females: x2 = 1.8, p > 0.1). Comparison of all three groups showed a significant trend toward ideal weight and not obesity (males: x 2 = 1 2 . 1 , ~ > 0.05; females: x 2 = 17.1, p > 0.01). This was further confirmed by specific analysis of x L for linear trend (males: x2 = 6.18, p < 0.025; females: x2 = 4.2, p < 0.05). This is explained by the fact that just about Prevalence of Obesity among Meningioma Patients and in HANES Survey
Clozapine-associated elevation in serum triglycerides.

OBJECTIVE This study was conducted to determine serum lipid level changes in patients who received clozapine or haloperidol. METHOD Medical records of 222 inpatients treated with clozapine or haloperidol were reviewed. Age, weight, gender, daily antipsychotic dose, total cholesterol level, serum triglyceride level, and concurrent medications were recorded. RESULTS Clozapine-treated men had significantly higher follow-up serum triglyceride concentrations over baseline than did haloperidol-treated men. Female patients experienced serum triglyceride level elevations regardless of antipsychotic treatment. Changes in total cholesterol levels were not significantly different between treatment groups. CONCLUSIONS An increase in serum triglyceride levels occurred in clozapine-treated patients; screening for serum triglyceride elevations may be warranted before treatment with clozapine.
Analysis of the human sex ratio by using overdispersion models

For study of the human sex ratio, one of the most important data sets was collected in Saxony in the 19th century by Geissler. The data contain the sizes of families, with the sex of all children, at the time of registration of the birth of a child. These data are reanalysed to determine how the probability for each sex changes with family size. Three models for overdispersion are fitted: the beta–binomial model of Skellam, the ‘multiplicative’ binomial model of Altham and the double‐binomial model of Efron. For each distribution, both the probability and the dispersion parameters are allowed to vary simultaneously with family size according to two separate regression equations. A finite mixture model is also fitted. The models are fitted using non‐linear Poisson regression. They are compared using direct likelihood methods based on the Akaike information criterion. The multiplicative and beta–binomial models provide similar fits, substantially better than that of the double‐binomial model. All models show that both the probability that the child is a boy and the dispersion are greater in larger families. There is also some indication that a point probability mass is needed for families containing children uniquely of one sex.
Participation for Empowerment and Sustainability: How Development Support Communication Makes a Difference

AbstractDevelopment Support Communication (DSC) is a term first used by the United Nations Development Programme to refer to the development project support reaching specific groups of people with new ideas, information, and technologies to get rural communities to participate in development programmes to act as the implementors. This article describes how DSC was successfully employed by the Philippines government in a three-year experimental project to transfer selected agricultural technology to small farmers, fishermen, women, and youth at five pilotbarangay sites. It is hoped that the project will help increase the participation of small agricultural producers in identifying technologies for research and quality of life, in line with the targets of Philippines 2000. This project shows that when DSC is integrated into development work, it facilitates the attainment of the project objectives for community development.
The Characteristics that Provide Independent Information about Average U.S. Monthly Stock Returns

We take up Cochrane’s (2011) challenge to identify the firm characteristics that provide independent information about average U.S. monthly stock returns by simultaneously including 94 characteristics in Fama-MacBeth regressions that avoid overweighting microcaps and adjust for data snooping bias. We find that while 12 characteristics are reliably independent determinants in non-microcap stocks during 1980-2014 as a whole, return predictability fell sharply in 2003 such that just two characteristics have been independent determinants since then. Outside of microcaps, the hedge returns to exploiting characteristics-based predictability have also been insignificantly different from zero since 2003.
The Role of PIWIL4, an Argonaute Family Protein, in Breast Cancer*

P-element-induced wimpy testis (PIWI) proteins bind to PIWI-interacting RNAs and play key roles in the biogenesis and functions of PIWI-interacting RNAs. It has been reported that PIWI proteins are essential for stem cell self-renewal and germline development in diverse organisms and that they are ectopically expressed in multiple forms of cancer. However, the role of PIWI in cancer remains elusive. Here we report that one of the four PIWI proteins in humans, PIWIL4, is highly expressed in both breast cancer tissues and the cytoplasm of MDA-MB-231 cells derived from breast cancer. Reducing PIWIL4 expression drastically impairs the migration ability of MDA-MB-231 cells, significantly increases their apoptosis, and mildly affects their proliferation. Our transcriptome and proteome analysis reveal that these functions are at least partially achieved via the PIWIL4 regulation of TGF-β and FGF signaling pathways and MHC class II proteins. These findings suggest that PIWIL4 may serve as a potential therapeutic target for breast cancer.
P10-1 open-label, multicenter study of sipuleucel-T in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) previously treated with sipuleucel-T: Evaluation of antigen-presenting cell (APC) activation.

147 Background: Sipuleucel-T is an autologous cellular immunotherapy that has demonstrated an improvement in survival among men with asymptomatic or minimally symptomatic mCRPC. P10-1 (NCT01338012) is an open-label, multicenter study of sipuleucel-T in men with mCRPC previously treated with sipuleucel-T in the androgen-dependent setting on the PROTECT trial (a prospective, randomized, controlled Phase III study of sipuleucel-T in men with prostate-specific antigen recurrence following radical prostatectomy; NCT00779402). This preliminary analysis of P10-1 evaluates the pattern of APC activation in pts re-treated with sipuleucel-T after progression to mCRPC. METHODS Eligible pts include those previously treated with at least one infusion of sipuleucel-T on PROTECT and who progressed to the mCRPC state. Pts receive up to three additional infusions of sipuleucel-T. APC activation is assessed by CD54 upregulation expressed as the ratio of the average number of CD54 molecules on post-culture vs. pre-culture cells. RESULTS As of September 14, 2012, 7 pts have been enrolled and have received an infusion of sipuleucel-T. The median interval between the last infusion in PROTECT and the first infusion in P10-1 was 8.6 years. The Table shows a higher fold change in CD54 expression in the first P10-1 treatment compared with the initial infusion in PROTECT. CONCLUSIONS This is the first report of pts re-treated with sipuleucel-T after prior treatment in an earlier disease setting. These preliminary data are consistent with the presence of an immunological memory response to the immunizing antigen several years following initial treatment. CLINICAL TRIAL INFORMATION NCT01338012. [Table: see text].
Anti-interleukin-6 antibody treatment improves survival during gut-derived sepsis in a time-dependent manner by enhancing host defense.

OBJECTIVE To determine the in vivo neutralizing activities of anti-interleukin-6 (IL-6) antibody on survival rate and host defense in a clinically relevant model of infection. DESIGN Prospective, randomized, experimental animal study. SETTING University and Shriners Burns Institute research laboratories. SUBJECTS Two hundred seventy-six adult, female Balb/c mice. INTERVENTIONS Balb/c mice were treated with 10 micrograms of antimurine IL-6 antibody, nonspecific murine immunoglobulin G (IgG), or placebo at 2, 4, or 8 hrs after they underwent bacterial challenge by gavage of 10(10) Escherichia coli and thermal injury. The survival rate was determined. The number of viable translocated bacteria, the total amount of translocation, and the percentage of bacteria that survived were also studied in different tissues. MEASUREMENTS AND MAIN RESULTS Survival rate after burn and gavage was significantly improved in animals treated with antimurine IL-6 antibody at 2 and 4 hrs but not at 8 hrs after injury compared with control animals treated with nonspecific IgG or saline. The IL-6 serum concentration was significantly lower after burn and gavage in the animals treated 2 and 4 hrs after injury compared with nontreated animals. Better killing of translocated bacteria was observed in the tissues of animals treated with antimurine IL-6 antibody 2 hrs after injury. CONCLUSIONS Treatment with antimurine IL-6 antibody at 2 and 4 hrs after injury, but not at 8 hrs after injury, positively affects outcome during gut-derived sepsis. Moreover, the beneficial effect of treatment after 2 hrs was related to an enhanced clearance of translocated bacteria.
Predictors of poor response during asthma therapy differ with definition of outcome.

AIMS To evaluate phenotypic and genetic variables associated with a poor long-term response to inhaled corticosteroid therapy for asthma, based independently on lung function changes or asthma exacerbations. MATERIALS & METHODS We tested 17 phenotypic variables and polymorphisms in FCER2 and CRHR1 in 311 children (aged 5-12 years) randomized to a 4-year course of inhaled corticosteroid during the Childhood Asthma Management Program (CAMP). RESULTS Predictors of recurrent asthma exacerbations are distinct from predictors of poor lung function response. A history of prior asthma exacerbations, younger age and a higher IgE level (p < 0.05) are associated with recurrent exacerbations. By contrast, lower bronchodilator response to albuterol and the minor alleles of RS242941 in CRHR1 and T2206C in FCER2 (p < 0.05) are associated with poor lung function response. Poor lung function response does not increase the risk of exacerbations and vice versa (p = 0.72). CONCLUSION Genetic and phenotypic predictors of a poor long-term response to inhaled corticosteroids differ markedly depending on definition of outcome (based on exacerbations vs lung function). These findings are important in comparing outcomes of clinical trials and in designing future pharmacogenetic studies.
Apraxias in Neurodegenerative Dementias

Background: Apraxia is a state of inability to carry out a learned motor act in the absence of motor, sensory or cerebellar defect on command processed through the Praxis circuit. Breakdown in default networking is one of the early dysfunction in cortical dementias and result in perplexity, awkwardness, omission, substitution errors, toying behavior and unrecognizable gestures in response to command with voluntary reflex dissociation where, when unobserved patient will carry out reflex movements normally. Awareness into the organicity of these phenomenas will help in early diagnosis, which will help in initiating appropriate treatment and slowing down the progression of the disease. Aims and Objectives: The aim was to look for the various kinds of apraxias in patients with dementia using appropriate simple tests. Patients and Methods: Three hundred patients satisfying Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for dementia were evaluated in detail with mandatory investigations for dementia followed by testing for ideational, ideomotor, limb-kinetic, buccopharyngeal, dressing apraxia, constructional apraxia and gait apraxias in addition to recording of rare apraxias when present. Results: Alzheimer's disease showed maximum association with apraxias in all the phases of the disease ideational, ideomotor, dressing and constructional apraxias early and buccopharyngeal and gait apraxia late. Frontotemporal lobe dementia showed buccopharyngeal and gait apraxias late into the disease. Cortical basal ganglionic degeneration showed limb apraxias and diffuse Lewy body disease showed more agnosias and less apraxias common apraxias seen was Ideational and Ideomotor. Conclusion: Recognition of the apraxias help in establishing organicity, categorization, caregiver education, early strategies for treatment, avoiding anti-psychotics and introducing disease modifying pharmacotherapeutic agents and also prognosticating.
Backhaul for Low-Altitude UAVs in Urban Environments

Unmanned Aerial Vehicles (UAVs) acting as access points in cellular networks require wireless backhauls to the core network. In this paper we employ stochastic geometry to carry out an analysis of the UAV backhaul performance that can be achieved with a network of dedicated ground stations. We provide analytical expressions for the probability of successfully establishing a backhaul and the expected data rate over the backhaul link, given either an LTE or a millimeter-wave backhaul. We demonstrate that increasing the density of the ground station network gives diminishing returns on the performance of the UAV backhaul, and that for an LTE backhaul the ground stations can benefit from being co-located with an existing base station network.
Somatic TP53 mutation mosaicism in a patient with Li–Fraumeni syndrome

We present a girl who developed adrenocortical adenoma at the age of 1 year and osteosarcoma at the age of 5 years. There was no history of cancer in her parents and their relatives. However, both tumors were typical for the Li–Fraumeni syndrome (LFS), and the patient met criteria for germline TP53 mutation testing. A mutation in codon 282 (Arg282Trp) was identified in her blood lymphocyte genomic DNA. The substitution was found in neither of her parents, which indicated a possibility of a de novo mutation. Unexpectedly, sequencing of the DNA of the patient repeatedly showed allelic imbalance in favor of the normal allele. This observation prompted us to investigate the putative somatic mosaicism in the patient consisting of normal cells and cells heterozygous for the mutation. The imbalance was also examined in two other non‐invasively sampled tissues, buccal cells, and cells from the urine sediment, and sequencing was confirmed with two other independent methods. While the findings in blood and the urine sediment were similar, in buccal cells both alleles were present in equal amounts. The allele ratio in lymphocytes was consistent with a mosaic where about 2/3 of cells carried two normal alleles and only 1/3 was heterozygous for the mutation. Despite the mosaicism the girl developed two early childhood tumors of mesodermal origin, and her phenotype was thus not milder than that of other germline TP53 mutation carriers. To our knowledge this is the first description of somatic mosaicism for a de novo TP53 mutation in LFS. © 2008 Wiley‐Liss, Inc.
Risk Factors Associated with Methicillin Resistance among Staphylococcus aureus Infections in Veterans

Background. Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging concern in infectious disease practice. Although MRSA infections occur in a wide variety of anatomic sites, the majority of studies considering the risk factors for methicillin resistance among S. aureus infections have focused on MRSA bacteremia. Objective. To describe risk factors associated with methicillin resistance among S. aureus infections at different anatomic sites. Methods. We collected information on the demographic and clinical characteristics of patients examined at the Atlanta Veterans Affairs Medical Center with S. aureus infections during the period from June 2007 through May 2008. We used multivariate logistic regression to describe factors significantly associated with methicillin resistance. Results. There were 568 cases of S. aureus infection among 528 patients. We identified 352 cases (62%) of MRSA infection and 216 cases (38%) of methicillin-sensitive S. aureus infection. The adjusted odds of methicillin resistance were higher among infections that occurred among patients who had a prior history of MRSA infection (odds ratio [OR], 3.9 [95% confidence interval {CI}, 2.3–6.4]) or resided in a long-term care facility during the past 12 months (OR, 2.0 [95% CI, 1.0-4.0]) but were lower for infections that occurred among patients who had undergone a biopsy procedure during the past 12 months (OR, 0.7 [95% CI, 0.6-0.9]). Most cases of infection were community-onset infections (523 [92%] of 568 cases), and about one-half (278 [49%]) were not healthcare associated. Conclusions. Compared with previous studies of methicillin resistance among patients with S. aureus bacteremia, we found similar factors to be associated with methicillin resistance among S. aureus isolates recovered from more diverse anatomic sites of infection. Of note, nearly one-half of our cases of MRSA infection were not healthcare associated.