Miracle-dz/UniFAR-FTUs huggingface dataset:
Sunitinib Treatment Exacerbates Intratumoral Heterogeneity in Metastatic Renal Cancer

Purpose: The aim of this study was to investigate the effect of VEGF-targeted therapy (sunitinib) on molecular intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mccRCC). Experimental Design: Multiple tumor samples (n = 187 samples) were taken from the primary renal tumors of patients with mccRCC who were sunitinib treated (n = 23, SuMR clinical trial) or untreated (n = 23, SCOTRRCC study). ITH of pathologic grade, DNA (aCGH), mRNA (Illumina Beadarray) and candidate proteins (reverse phase protein array) were evaluated using unsupervised and supervised analyses (driver mutations, hypoxia, and stromal-related genes). ITH was analyzed using intratumoral protein variance distributions and distribution of individual patient aCGH and gene-expression clustering. Results: Tumor grade heterogeneity was greater in treated compared with untreated tumors (P = 0.002). In unsupervised analysis, sunitinib therapy was not associated with increased ITH in DNA or mRNA. However, there was an increase in ITH for the driver mutation gene signature (DNA and mRNA) as well as increasing variability of protein expression with treatment (P < 0.05). Despite this variability, significant chromosomal and transcript changes to key targets of sunitinib, such as VHL, PBRM1, and CAIX, occurred in the treated samples. Conclusions: These findings suggest that sunitinib treatment has significant effects on the expression and ITH of key tumor and treatment specific genes/proteins in mccRCC. The results, based on primary tumor analysis, do not support the hypothesis that resistant clones are selected and predominate following targeted therapy. Clin Cancer Res; 21(18); 4212–23. ©2015 AACR.
A Comprehensive Map of Insulator Elements for the Drosophila Genome

Insulators are DNA sequences that control the interactions among genomic regulatory elements and act as chromatin boundaries. A thorough understanding of their location and function is necessary to address the complexities of metazoan gene regulation. We studied by ChIP–chip the genome-wide binding sites of 6 insulator-associated proteins—dCTCF, CP190, BEAF-32, Su(Hw), Mod(mdg4), and GAF—to obtain the first comprehensive map of insulator elements in Drosophila embryos. We identify over 14,000 putative insulators, including all classically defined insulators. We find two major classes of insulators defined by dCTCF/CP190/BEAF-32 and Su(Hw), respectively. Distributional analyses of insulators revealed that particular sub-classes of insulator elements are excluded between cis-regulatory elements and their target promoters; divide differentially expressed, alternative, and divergent promoters; act as chromatin boundaries; are associated with chromosomal breakpoints among species; and are embedded within active chromatin domains. Together, these results provide a map demarcating the boundaries of gene regulatory units and a framework for understanding insulator function during the development and evolution of Drosophila.
Input Admittance Characteristics of Permanent Magnet Brushless AC Motor Drive Systems

This paper analyzes the input admittance/impedance characteristics of a permanent-magnet brushless AC motor drive system, taking account of the influence of both current and speed control loops as well as the motor and inverter losses. It is shown that, if voltage feedforward compensation is not employed, the input admittance of the drive system differs significantly from that of an ideal constant power load, and is influenced by the speed and current control loop bandwidths. It is also shown that, when the drive is connected to a DC supply via an LRC filter, the magnitude of the input admittance at the filter resonant frequency has a crucial effect on system stability margin.
The Use of Multizone Models to Estimate an Airborne Chemical Contaminant Generation and Decay Profile: Occupational Exposures of Hairdressers to Vinyl Chloride in Hairspray During the 1960s and 1970s

Vinyl chloride (VC) was used as a propellant in a limited percentage of aerosol hairspray products in the United States from approximately 1967 to 1973. The question has arisen whether occupational exposures of hairdressers to VC‐containing hairsprays in hair salons were sufficient to increase the risk for developing hepatic angiosarcoma (HAS). Transient two‐zone and steady‐state three‐zone models were used to estimate the historical airborne concentration of VC for individual hairdressers using hairspray as well as estimated contributions from other hairdressers in the same salon. Concentrations of VC were modeled for small, medium, and large salons, as well as a representative home salon. Model inputs were determined using published literature, and variability in these inputs was also considered using Monte Carlo techniques. The 95th percentile for the daily time‐weighted average exposure for small, medium, and large salons, assuming a market‐share fraction of VC‐containing hairspray use from the Monte Carlo analysis, was about 0.3 ppm, and for the home salon scenario was 0.1 ppm. The 95th percentile value for the cumulative lifetime exposure of the hairdressers was 2.8 ppm‐years for the home salon scenario and 2.0 ppm‐years for the small, medium, and large salon scenarios. If using the assumption that all hairsprays used in a salon contained VC, the 95th percentile of the theoretical lifetime cumulative dose was estimated to be 52–79 ppm‐years. Estimated lifetime doses were all below the threshold dose for HAS of about 300 to 500 ppm‐years reported in the published epidemiology literature.
Executive functioning, cortisol reactivity, and symptoms of psychopathology in girls with premature adrenarche

Abstract The study examined the interaction between early maturational timing (measured by premature adrenarche [PA]) and executive functioning and cortisol reactivity on symptoms of psychopathology. The study included 76 girls aged 6 through 8 years (mean = 7.50, SD = 0.85) with PA (n = 40) and on-time adrenarche (n = 36). Girls completed a battery of psychological and neuropsychological tests and blood sampling for cortisol. Parents completed the Child Behavior Checklist. The results demonstrated that girls with PA with lower levels of executive functioning had higher externalizing and anxious symptoms compared to other girls. In addition, girls with PA who demonstrated increases in serum cortisol had higher externalizing symptoms than those with stable patterns. Finally, girls with PA who demonstrated decreases in cortisol reported higher depressive symptoms. The findings from this study provide important information concerning the impact of cognitive functioning and stress reactivity on adjustment to early maturation in girls with PA. The results of this research may inform screening and intervention efforts for girls who may be at greatest risk for emotional and behavioral problems as a result of early maturation.
Species delimitation and genetic diversity analysis in Salvia with the use of ISSR molecular markers

Abstract Thirty-nine plant specimens of six Salvia species were collected from different localities of the Alborz mountain region in Iran and studied for morphological and genetic variability and species relationship. Inter simple sequence repeats (ISSR) molecular markers showed a high degree of within-species and interspecific genetic variability in Salvia. Analysis of molecular variance and Hickory tests showed significant molecular difference among the studied populations. A principal coordinate analysis plot of morphological characters grouped the species into two distinct groups, supporting their taxonomic treatment. This was partly supported by ISSR networking. The Mantel test did not show a correlation between genetic distance and the geographical distance of the studied populations. STRUCTURE and reticulation analyses revealed some degree of gene fl ow among the species. The present study showed that ISSR molecular markers could be used in Salvia species delimitation along with morphological study.
Age-Related Differences in Motor Imagery: Working Memory as a Mediator

Background/Study Context: Although motor imagery is a well-established phenomenon in healthy younger adults, it seems necessary to determine if older adults are still able to accurately perform imagery tasks before investigating the application of motor imagery in rehabilitation. Therefore, the purpose of this study was to determine if there is a progressive decline in motor imagery performance with age. Furthermore, we wanted to verify whether the effects of age on motor imagery were due to (or mediated by) deficits of working memory. Methods: This study examined the key characteristics of the motor imagery ability in three groups of healthy older men and women (60–69, 70–79, and ≥80 years; mean age M = 73.8, SD = 8.3) and 40 younger subjects aged 20 to 30 years (M = 28.87, SD = 2.5). Imagery ability was measured using the Movement Imagery Questionnaire (MIQ), the Controllability of Motor Imagery (CMI) test, and two different chronometry tests. To estimate the mediational effect of working memory on age differences in the imagery measures, we employed latent variable structural equation modeling (SEM). Results: The main findings indicated that motor imagery ability (generation, visual and kinesthetic imagery ability, controllability, and temporal organization) were better in young adults compared with older adults 70 years and older, but not in older adults 60 to 69 years of age. The analysis of the mediational effect of working memory on age differences in the motor imagery measures showed that the inclusion of working memory increased the amount of explained variance in the MIQ (ΔR 2 = .03), in the CMI test (ΔR 2 = .15), as well as in the mental chronometry tests (ΔR 2 = .16) Conclusion: Our findings suggest that there is potential for motor imagery to be compromised in the older age ranges, which may limit motor imagery as a rehabilitative strategy in older and in cognitively impaired individuals.
Model Specification and Risk Premia: Evidence from Futures Options

This paper examines model specification issues and estimates diffusive and jump risk premia using S&P futures option prices from 1987 to 2003. We first develop a time series test to detect the presence of jumps in volatility, and find strong evidence in support of their presence. Next, using the cross section of option prices, we find strong evidence for jumps in prices and modest evidence for jumps in volatility based on model fit. The evidence points toward economically and statistically significant jump risk premia, which are important for understanding option returns.
The N-Terminal Domain of the Drosophila Retinoblastoma Protein Rbf1 Interacts with ORC and Associates with Chromatin in an E2F Independent Manner

Background The retinoblastoma (Rb) tumor suppressor protein can function as a DNA replication inhibitor as well as a transcription factor. Regulation of DNA replication may occur through interaction of Rb with the origin recognition complex (ORC). Principal Findings We characterized the interaction of Drosophila Rb, Rbf1, with ORC. Using expression of proteins in Drosophila S2 cells, we found that an N-terminal Rbf1 fragment (amino acids 1–345) is sufficient for Rbf1 association with ORC but does not bind to dE2F1. We also found that the C-terminal half of Rbf1 (amino acids 345–845) interacts with ORC. We observed that the amino-terminal domain of Rbf1 localizes to chromatin in vivo and associates with chromosomal regions implicated in replication initiation, including colocalization with Orc2 and acetylated histone H4. Conclusions/Significance Our results suggest that Rbf1 can associate with ORC and chromatin through domains independent of the E2F binding site. We infer that Rbf1 may play a role in regulating replication directly through its association with ORC and/or chromatin factors other than E2F. Our data suggest an important role for retinoblastoma family proteins in cell proliferation and tumor suppression through interaction with the replication initiation machinery.
Mechanism of toughening for polypropylene blended with ethylene–propylene–diene rubber following selective crosslinking

Toughening mechanism of polypropylene (PP) blended with ethylene-propylene-diene rubber (EPDM) following selective crosslinking was examined in comparison with that of blends of PP before crosslinking. The yield stress, strength of craze, and density of void which are dominant factors for enhancing toughness in PP blends were evaluated and the deformation and fracture mechanism was discussed. It was concluded that toughness of PP blended with EPDM is improved by selective crosslinking, since the improvement of the craze strength is greater than the drop in the release of the constraint of strain.
The effect of nest ectoparasites on parental provisioning in a north‐African population of the Blue Tit Parus caeruleus

Bird nests are often heavily infested with several haematophagous ectoparasite species that drain energy and other essential resources needed for the development of the rapidly growing chicks. The nutritional requirements of altricial chicks can only be satisfied by the parents frequently bringing prey to the nest. In a 3-year study, we tested experimentally whether a parasite-induced change in the nutritional budgets of the chicks in an Algerian population of the Blue Tit, could be compensated by a response in parental food provisioning behaviour. We found that nestling body mass and size did not differ between heat-treated ‘parasitefree’ nests and heavily infested control nests. However, after controlling for potential confounding variables (laydate, clutch size, chick age, year), we found that broods of heavily infested control nests were more frequently visited and fed than broods that received antiparasite treatment. The results are discussed in the framework of theory related to behavioural responses of hosts to parasites.
Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice

Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright’s F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance.
Effects of Tailored Risk Communications for Skin Cancer Prevention and Detection: The PennSCAPE Randomized Trial

Background: Prevention and early detection measures for melanoma, such as sun avoidance and skin examinations, are important, but are practiced inconsistently. In this replication of the Project SCAPE trial, we sought to determine whether tailored print materials were more effective at improving adherence than generic print materials for patients at increased risk of skin cancer. Methods: Participants were randomized to receive personalized mailed communications about their skin cancer risk and recommended sun protection, or generic mailings. Participants were Caucasian adults, at moderate or high risk for skin cancer, recruited in outpatient primary care. The main outcomes were overall sun protection behaviors and specific protective behaviors including use of sunscreen, shirt, hat, sunglasses, shade, and sun avoidance; recent sunburns; and skin self-examination and provider skin examination. Results: One hundred ninety-two (93.2%) subjects completed the study. Six outcome variables showed significant intervention condition effects in mixed effects models: overall sun protection behavior (P = 0.025); sunscreen use (P = 0.026); use of sunglasses (P = 0.011); sunburns in the past three months (P = 0.033); recency of last skin self-exam (P = 0.017); and frequency of skin exams by health care provider (P = 0.016). Conclusions: Relative to generic communications, tailored risk communications resulted in improved adherence to six skin cancer protective behaviors, including a composite sun protection behavior measure, sunburns, and health care provider skin examinations. Impact: Tailored interventions can be more effective in improving patient prevention behaviors than nontailored, generic information for patients at moderate to high risk of skin cancer. Cancer Epidemiol Biomarkers Prev; 24(2); 415–21. ©2014 AACR.
The geography of coordination: dealing with distance in R&D work

Geographically distributed development creates new questions about how to coordinate multi-site work. In this paper, we present four methods product development organizations used to coordinate their work: functional areas of expertise, product structure, process steps, and customization. We describe the benefits and difficulties with each model. Finally, we discuss two difficulties that occur irrespective of the model used: consequences of unequal distribution of project mass, and finding expertise.
Congenital Limb Reduction Defects in Infants: A Look at Possible Associations with Maternal Smoking and Hypertension

Abstract : Case control studies suggest an association between prenatal smoking and infant limb defects possibly due to vascular disruption in the embryo. It has also been suggested that maternal hypertension may be associated with the occurrence of congenital limb defects, either due to the effects of the disease or possibly medications such as the calcium channel blockers used to treat this condition. This project examined these associations. Between 1987 and 1995, 1544 singleton infants with limb defects and reduction defects were identified. These cases were frequency matched by year of birth to 6176 children without congenital limb defects. Prenatal smoking was found not to be associated with an increased risk of limb defects in general, nor were the presence of either gestational hypertension or chronic hypertension, as indicated on the birth certificate, associated with increased risk of giving birth to children with limb defects. However, examination of specific types of malformation revealed that maternal smoking was associated with a greater than two-fold increased risk of transverse reduction limb defects. Chronic or gestational hypertension were not associated with increased risks of any specific defect. This finding related to smoking is consistent with previous studies, and emphasizes the continued need for public health interventions designed to reduce prenatal smoking. Studies including a larger number of hypertensive women, preferably including data on the use of specific anti-hypertensive medications prenatally, are needed before any conclusions can be drawn between possible associations of maternal hypertension (or its treatment) and the occurrence of congenital limb defects.
Association between receptor density, cellular activation, and transformation of adhesive behavior of flowing lymphocytes binding to VCAM‐1

We investigated the ability of purified vascular cell adhesion molecule‐1 (VCAM‐1), adsorbed on plastic, to capture and immobilize flowing lymphocytes, and the dependence of adhesive behavior on activation of the counter‐receptor, α4β1 integrin. This integrin/immunoglobulin interaction bound lymphocytes at a wall shear stress at which the β2‐integrin family has previously been found ineffective (> 0.1 Pa), and whereas lymphocytes rolled on lower concentrations of VCAM‐1 (10 μg/ml), they were stationary at high concentrations (100 μg/ml). Activation of α4β1 integrin by Mn2+ or by antibody 12G10 or treatment of lymphocytes with phorbol ester caused transformation to stationary adhesion, and increased binding significantly only at the lower concentrations of VCAM‐1. We thus hypothesized that formation of a high density of ligand between VCAM‐1 and α4β1 integrin actively transformed lymphocyte behavior. This concept was supported by the finding that the proportion of lymphocytes rolling on the higher concentrations of VCAM‐1 increased if cells were pretreated with azide to block energy‐dependent responses, or if intracellular Ca2+ was chelated. However, not all activation responses were equivalent: only phorbol ester induced marked spreading of immobilized cells, and if pretreatment was prolonged, this agent even reduced the efficiency of initial attachment of flowing lymphocytes. Azide treatment had no effect on transformation to stationary adhesion caused by Mn2+ or activating antibody. Thus, different forms of lymphocyte activation were identifiable: external modification of integrin converted rolling to stationary attachment, did not require ATP, and was reversible; high‐density ligand binding induced an energy‐dependent signal for conversion from rolling to stationary attachment, but not spreading; and protein kinase C activation promoted stationary attachment and spreading, but not necessarily capture. VCAM‐1 is thus a versatile adhesion receptor capable of supporting all stages of leukocyte attachment, i.e. rolling, stationary, and spreading, and of ligand‐induced transformation of adhesion, although an additional signal appears necessary to promote lymphocyte spreading and migration.
Intratympanic Steroid Therapy for Sudden Hearing Loss: A Review of the Literature

Objective: Administration of steroids systematically is considered to be the most commonly accepted treatment for idiopathic sudden sensorineural hearing loss (ISSNHL). In recent years there has been increasing scientific interest in treating ISSNHL by means of local steroid delivery. Usually, intratympanic steroids are used in three main protocols, as initial treatment, as adjunctive treatment given concomitantly with systemic steroids and as salvage treatment after failure of standard therapy. The purpose of this review is to examine the published literature regarding the therapeutic value of each method of treatment and to seek answers about the best delivery technique and the optimal administration schedule. Data Sources: Literature review from 1996 to 2009, PubMed and Medline. Study Selection: We searched for trials concerning clinical evaluation of intratympanic steroids in ISSNHL patients, as a salvage treatment, as a first line therapy and in combination with the conventional therapy. Randomized and non-randomized case control studies and case series studies were the types of trials available for review. Data Extraction: All the articles described in the study selection were used for this review. Data Synthesis: Statistical techniques were not used. Conclusion: On the basis of the available literature, it seems that topical steroids can be a valuable solution for ISSNHL patients who either cannot tolerate systemic steroid therapy or are refractory to it. Concerning the combined therapy, due to the controversial results of the existing studies, it cannot be determined yet whether this treatment protocol could yield superior results as a first line therapy. The need for establishment of standard criteria of hearing recovery should be underlined.