Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and impact of HIV-1 protease mutation L76V on lopinavir resistance

Besides I47A, mutation L76V at the HIV protease gene has recently been proposed to cause lopinavir resistance. This change was present in 37 (2.7%) out of 1376 patients failing protease inhibitor containing regimens. Although 26 (70%) were on lopinavir, most had previously failed other protease inhibitors and carried multiple protease inhibitor resistance mutations. Therefore, L76V does not appear to be a primary lopinavir resistance change when the drug is used in combination therapy.
Regional FDI distribution in Bulgaria

ABSTRACT: This study seeks to understand why certain administrative regions in Bulgaria attract more FDI than others. For the purpose it plots data from the national statistics institute of Bulgaria on NUTS 3 level against data from FDI Markets database using a negative binomial model. The analysis shows that only major city regions in Bulgaria attract the most FDI with the rest significantly trailing behind.
The simian virus 40 large tumor antigen activates cSrc and requires cSrc for full neoplastic transformation.

AIM To investigate the role of the cellular protooncogene product, cSrc, in neoplastic transformation by the large tumor antigen of simian virus 40 (TAg), the ability of TAg to increase cSrc activity was examined. MATERIALS AND METHODS cSrc activity was measured in cells expressing wild-type or mutant TAg and compared to the parental line. RESULTS The results indicated that TAg expression in mouse 3T3 fibroblasts causes a dramatic increase in cSrc activity, a finding which establishes TAg as a cSrc activator. This ability depended upon a TAg, intact retinoblastoma-susceptibility gene product (Rb) family-binding site. In addition, genetic ablation of pRb in mouse fibroblasts increased cSrc activity, suggesting that pRb inactivation by TAg might be responsible for the observed cSrc activation. Furthermore, down-regulation or genetic ablation of cSrc alone, or together with the Src family members, Yes and Fyn, caused a dramatic reduction in the ability of TAg to transform mouse fibroblasts. CONCLUSION Taken together, these findings suggest for the first time that cSrc is part of an important pathway emanating from TAg and leading to neoplastic conversion.
Mutation of the Protein Kinase C Phosphorylation Site on Rat α1 Na+,K+-ATPase Alters Regulation of Intracellular Na+ and pH and Influences Cell Shape and Adhesiveness*

The enzyme Na+,K+-ATPase creates the transmembrane Na+ gradient that is of vital importance for functioning of all eukaryotic cells. Na+,K+-ATPase can be phosphorylated by protein kinase A (PKA) and protein kinase C (PKC), and these sites of phosphorylation have been identified. In the present study, we have examined the physiological significance of PKC phosphorylation of rat Na+,K+-ATPase. In COS cells transfected with wild type rat Na+,K+-ATPase α1, intracellular Na+ was higher and pH was lower than in cells transfected with rat Na+,K+-ATPase α1 in which the PKC phosphorylation site, Ser-23, had been mutated into alanine. Phorbol dibutyrate inhibited Na+,K+-ATPase-dependent ATP hydrolysis and Rb+ uptake in cells expressing wild type Na+,K+-ATPase but not in cells expressing S23A Na+,K+-ATPase. Cells expressing the S23A mutant had a more rounded appearance and attached less well to fibronectin than did untransfected cells or cells transfected with wild type rat Na+,K+-ATPase α1. These results indicate a functional role for PKC-mediated phosphorylation of rat Na+,K+-ATPase α1 and suggest a connection between this enzyme and cell adhesion.
Predictive values of component‐specific IgE for the outcome of peanut and hazelnut food challenges in children

Oral challenges are the gold standard in food allergy diagnostic, but time‐consuming. Aim of the study was to investigate the role of peanut‐ and hazelnut‐component‐specific IgE in the diagnostics of peanut and hazelnut allergy and to identify cutoff levels to make some challenges superfluous.
Frequency doubling by active in vivo motility of mechanosensory neurons in the mosquito ear

Across vertebrate and invertebrate species, nonlinear active mechanisms are employed to increase the sensitivity and acuity of hearing. In mosquitoes, the antennal hearing organs are known to use active force feedback to enhance auditory acuity to female generated sounds. This sophisticated form of signal processing involves active nonlinear events that are proposed to rely on the motile properties of mechanoreceptor neurons. The fundamental physical mechanism for active auditory mechanics is theorized to rely on a synchronization of motile neurons, with a characteristic frequency doubling of the force generated by an ensemble of motile mechanoreceptors. There is however no direct biomechanical evidence at the mechanoreceptor level, hindering further understanding of the fundamental mechanisms of sensitive hearing. Here, using in situ and in vivo atomic force microscopy, we measure and characterize the mechanical response of mechanosensory neuron units during forced oscillations of the hearing organ. Mechanoreceptor responses exhibit the hallmark of nonlinear feedback for force generation, with movements at twice the stimulus frequency, associated with auditory amplification. Simultaneous electrophysiological recordings exhibit similar response features, notably a frequency doubling of the firing rate. This evidence points to the nature of the mechanism, whereby active hearing in mosquitoes emerges from the double-frequency response of the auditory neurons. These results open up the opportunity to directly investigate active cellular mechanics in auditory systems, and they also reveal a pathway to study the nanoscale biomechanics and its dynamics of cells beyond the sense of hearing.
Effective Ethics Education for Graduate Social Work Students

The study explored the relationships between curriculum, field practice, and individual moral reasoning and a critically reasoned belief system for graduate social work students. Effective competency-based education enables individuals to develop the cognitive skills necessary to behave according to professional standards. Field practice enables individuals to transfer learning from classroom theory into practice, and dialogues with faculty, field supervisors, peers and veteran social workers inform individuals’ moral reasoning skills. Students from seven graduate schools of social work were invited to participate in an online survey consisting of three subscales, the POS-9, Field Placement, and the Pike Moral Reasoning Scale as well as several demographic questions. The POS-9 had a Cronbach’s alpha of . 987. The Field Placement Scale had a Cronbach’s alpha of . 982. Pike (1996) reports a Cronbach’s alpha of . 78 on the Moral Reasoning Scale. A multiple regression analysis (n = 94) revealed that gender and scores on the POS-9 significantly predicts critically-reasoned beliefs. The overall effect size on responses to the three subscales was 8.262507: For the POS only, the effect size is 3.5851525, for the Field Placement, it is 10.57968, and for the Moral Reasoning scale it is 1.872507. Levels of moral reasoning were found to be more rule-based than reason-
Day-night pattern of sudden death in obstructive sleep apnea.

BACKGROUND The risk of sudden death from cardiac causes in the general population peaks from 6 a.m. to noon and has a nadir from midnight to 6 a.m. Obstructive sleep apnea is highly prevalent and associated with neurohormonal and electrophysiological abnormalities that may increase the risk of sudden death from cardiac causes, especially during sleep. METHODS We reviewed polysomnograms and the death certificates of 112 Minnesota residents who had undergone polysomnography and had died suddenly from cardiac causes between July 1987 and July 2003. For four intervals of the day, we compared the rates of sudden death from cardiac causes among people with obstructive sleep apnea and the following: the rates among people without obstructive sleep apnea, the rates in the general population, and the expectations according to chance. For each interval, we assessed the median apnea-hypopnea index and the relative risk of sudden death from cardiac causes. We similarly analyzed sudden death from cardiac causes during three time intervals that correlate with usual sleep-wake cycles. RESULTS From midnight to 6 a.m., sudden death from cardiac causes occurred in 46 percent of people with obstructive sleep apnea, as compared with 21 percent of people without obstructive sleep apnea (P=0.01), 16 percent of the general population (P<0.001), and the 25 percent expected by chance (P<0.001). People with sudden death from cardiac causes from midnight to 6 a.m. had a significantly higher apnea-hypopnea index than those with sudden death from cardiac causes during other intervals, and the apnea-hypopnea index correlated directly with the relative risk of sudden death from cardiac causes from midnight to 6 a.m. For people with obstructive sleep apnea, the relative risk of sudden death from cardiac causes from midnight to 6 a.m. was 2.57 (95 percent confidence interval, 1.87 to 3.52). The analysis of usual sleep-wake cycles showed similar results. CONCLUSIONS People with obstructive sleep apnea have a peak in sudden death from cardiac causes during the sleeping hours, which contrasts strikingly with the nadir of sudden death from cardiac causes during this period in people without obstructive sleep apnea and in the general population.
Efficient denoising algorithms for large experimental datasets and their applications in Fourier transform ion cyclotron resonance mass spectrometry

Significance Every measurement is corrupted due to random fluctuations in the sample and the apparatus. Current efficient denoising algorithms require large matrix analysis, and become untractable even for moderately large datasets. Any series can be considered as an operator that modifies any input vector. By applying this operator on a series of random vectors and thus reducing the dimension of the data, it is possible, using simple algebra, to reduce noise in a robust manner. Furthermore, the structure of the underlying matrices allows a very fast and memory-efficient implementation. Counterintuitively, randomness is used here to reduce noise. This procedure, called urQRd (uncoiled random QR denoising), allows denoising to be applied to data of virtually unlimited size. Modern scientific research produces datasets of increasing size and complexity that require dedicated numerical methods to be processed. In many cases, the analysis of spectroscopic data involves the denoising of raw data before any further processing. Current efficient denoising algorithms require the singular value decomposition of a matrix with a size that scales up as the square of the data length, preventing their use on very large datasets. Taking advantage of recent progress on random projection and probabilistic algorithms, we developed a simple and efficient method for the denoising of very large datasets. Based on the QR decomposition of a matrix randomly sampled from the data, this approach allows a gain of nearly three orders of magnitude in processing time compared with classical singular value decomposition denoising. This procedure, called urQRd (uncoiled random QR denoising), strongly reduces the computer memory footprint and allows the denoising algorithm to be applied to virtually unlimited data size. The efficiency of these numerical tools is demonstrated on experimental data from high-resolution broadband Fourier transform ion cyclotron resonance mass spectrometry, which has applications in proteomics and metabolomics. We show that robust denoising is achieved in 2D spectra whose interpretation is severely impaired by scintillation noise. These denoising procedures can be adapted to many other data analysis domains where the size and/or the processing time are crucial.
Improved quality of life and cognitive stimulation therapy in dementia

Quality of life (QoL) is now seen as a key outcome in many aspects of dementia care. In a recent randomized controlled trial of Cognitive Stimulation Therapy (CST) groups, significant improvements in self-reported QoL were identified as well as changes in cognitive function. This further analysis of results from the trial examines whether the changes in these two domains occurred independently, perhaps for different reasons, or whether the effect of treatment on QoL was mediated by the changes in cognition. In all, 201 people with dementia living in residential homes or attending day centres were assessed using the Quality of Life-Alzheimer's Disease (QOL-AD) scale and a range of measures of cognition, dementia level, mood, dependency and communication. Participants were randomized to receive an intervention programme of CST or to receive treatment as usual. The QoL-AD and other measures were repeated eight weeks later. At baseline, higher QoL in dementia was significantly correlated with lower levels of dependency and depression, but not with cognitive function or dementia severity. Improvement in quality of life was associated with being female, low quality of life at baseline, reduced depression and increased cognitive function. Changes in cognitive function mediated the effects of treatment in improving QoL. These results suggest that whilst QoL in dementia appears to be independent of level of cognitive function, interventions aimed at improving cognitive function can, nonetheless, have a direct effect on QoL.
Substantial risk of “Accidental MCI” in healthy older adults: Base rates of low memory scores in neuropsychological assessment

When assessing older adults for mild cognitive impairment (MCI) or dementia, it is important to understand how often low memory scores are obtained in healthy people in order to minimize false positive diagnoses. This study examines the base rates of low memory scores in older adults across a battery of memory tests. Participants included older adults (55–79 years; N = 742) from the Neuropsychological Assessment Battery (NAB; Stern & White, 2003a) standardization sample. The NAB Memory Module consists of four co-normed memory tests (i.e., List Learning, Shape Learning, Story Learning, and Daily Living Memory) yielding 10 demographically corrected T-scores. When all 10 T-scores were examined simultaneously, 55.5% of older adults had one or more scores one standard deviation (SD) below the mean. At <1.5 SDs, 30.8% of healthy older adults obtained one or more low memory scores. Obtaining low memory scores occurs more often with lesser intellectual abilities. For example, 56.5% of older adults with low average intellectual abilities obtained one or more low memory scores (<1.5 SDs) compared to 21.1% with high average intellectual abilities. Understanding the base rates of low scores can reduce over-interpretation of isolated low memory scores and minimize false positive diagnoses of MCI. (JINS, 2007, 13, 490–500.)The data in Tables 3, 4, 5, 6, and 7 are original data produced by special permission of the Publisher, Psychological Assessment Resources, Inc., 16204 North Florida Avenue, Lutz, Florida 33549, from the standardization data presented in the Neuropsychological Assessment Battery Psychometric and Technical Manual by Travis White, Ph.D. and Robert A. Stern, Ph.D. Copyright 2001, 2003 by PAR, Inc. Further reproduction is prohibited without permission from PAR, Inc.
Advertisement selection for online videos

The significant increase of the audience of video-sharing websites has attracted large investments on contextual advertising. In this paper we investigate alternative techniques for selecting ads to be placed in videos during their exhibitions. In order to improve the effectiveness of these ads avoiding the high cost of image processing, we explore textual metadata created by the users and stored in the page that hosts the video. Our proposal consists in assigning weights to the metadata attributes, according to their relative importance. To estimate such an importance, we apply a block importance model. Our experimental results show that the metadata attributes which perform better in the task of selecting ads are the ones that provide the best descriptions of the video content. We also observed that the application of weights according to the studied block importance model obtained gains of about 7\% over the selection method without weights. Such a gain is relevant due to the possibility of increasing the profitability of ad selection systems and avoiding the negative impact on advertiser brand and credibility of placing non-relevant ads.
Inhibition of the spindle assembly checkpoint kinase TTK enhances the efficacy of docetaxel in a triple-negative breast cancer model.

BACKGROUND Triple-negative breast cancers (TNBC) are considered the most aggressive type of breast cancer, for which no targeted therapy exists at the moment. These tumors are characterized by having a high degree of chromosome instability and often overexpress the spindle assembly checkpoint kinase TTK. To explore the potential of TTK inhibition as a targeted therapy in TNBC, we developed a highly potent and selective small molecule inhibitor of TTK, NTRC 0066-0. RESULTS AND CONCLUSIONS The compound is characterized by long residence time on the target and inhibits the proliferation of a wide variety of human cancer cell lines with potency in the same range as marketed cytotoxic agents. In cell lines and in mice, NTRC 0066-0 inhibits the phosphorylation of a TTK substrate and induces chromosome missegregation. NTRC 0066-0 inhibits tumor growth in MDA-MB-231 xenografts as a single agent after oral application. To address the effect of the inhibitor in breast cancer, we used a well-defined mouse model that spontaneously develops breast tumors that share key morphologic and molecular features with human TNBC. Our studies show that combination of NTRC 0066-0 with a therapeutic dose of docetaxel resulted in doubling of mouse survival and extended tumor remission, without toxicity. Furthermore, we observed that treatment efficacy is only achieved upon co-administration of the two compounds, which suggests a synergistic in vivo effect. Therefore, we propose TTK inhibition as a novel therapeutic target for neoadjuvant therapy in TNBC.
Campus Environmental Factors Influencing Student Leadership Development and Civic Engagement

Campus Environmental Factors Influencing Student Leadership Development and Civic Engagement. (December 2011) Laura Dawn Boren, B.B.A.; M.S., Texas A&M University Chair of Advisory Committee: Dr. Bryan Cole Higher education institutions are continuously called upon by society to prepare students to be engaged citizens. The purpose of this study was to identify campus environmental factors perceived to influence student leadership development and civic engagement that resulted in students‘ perceived capacity to create positive social change. The study was conducted at a public four-year comprehensive higher education institution regionally located in the south central region of the United States. This qualitative study examined undergraduate students‘ perceptions of personal leadership, influences on personal leadership development, and experiences with leadership and civic engagement. Following a naturalistic qualitative research method, interviews were conducted with ten undergraduate participants. Organization social system model and social change model of leadership development were used as conceptual frameworks for the study. The researcher determined from participant responses that peer and mentor relationships, community identity, personal identity, and democratic experiences were key environmental factors influencing student leadership development and civic engagement. Collegiate relationships with peers and faculty/staff mentors were a
Silicon-based radar and imaging sensors operating above 120 GHz

This paper reviews the design considerations, integration issues, packaging and experimental performance of two, recently developed D-Band transceivers with on-die or above-IC antennas fabricated in a production SiGe BiCMOS technology. Potential solutions for future high-efficiency D- and G-Band radio and sensor transceivers are also investigated.
Mutations in Cartilage Oligomeric Matrix Protein Causing Pseudoachondroplasia and Multiple Epiphyseal Dysplasia Affect Binding of Calcium and Collagen I, II, and IX*

Mutations in type 3 repeats of cartilage oligomeric matrix protein (COMP) cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). We expressed recombinant wild-type COMP that showed structural and functional properties identical to COMP isolated from cartilage. A fragment encompassing the eight type 3 repeats binds 14 calcium ions with moderate affinity and high cooperativity and presumably forms one large disulfide-bonded folding unit. A recombinant PSACH mutant COMP in which Asp-469 was deleted (D469Δ) and a MED mutant COMP in which Asp-361 was substituted by Tyr (D361Y) were both secreted into the cell culture medium of human cells. Circular dichroism spectroscopy revealed only small changes in the secondary structures of D469Δ and D361Y, demonstrating that the mutations do not dramatically affect the folding and stability of COMP. However, the local conformations of the type 3 repeats were disturbed, and the number of bound calcium ions was reduced to 10 and 8, respectively. In addition to collagen I and II, collagen IX also binds to COMP with high affinity. The PSACH and MED mutations reduce the binding to collagens I, II, and IX and result in an altered zinc dependence. These interactions may contribute to the development of the patient phenotypes and may explain why MED can also be caused by mutations in collagen IX genes.
Structural Features of an OR37 Glomerulus: A Comparative Study

In the olfactory bulb (OB) a sophisticated neuronal network mediates the primary processing of sensory information and extensive investigations over the past decades have greatly improved our understanding of the morphology and neuronal organization of the OB. However, efforts have mostly been focused on the different radial layers, typical for the OB and little attention has been paid to individual odorant receptor specific glomeruli, the first relay station of sensory information. It has been assumed that glomeruli processing odorant information out of different contextual fields might require accordingly specialized neuronal networks. In this study, we have analyzed and compared the structural features as well as cell types in the periglomerular (PG) region of three odorant receptor specific glomeruli. The investigations were focused on glomeruli of the receptor type OR37A, a member of the unique OR37 subsystem, in comparison to glomeruli of OR18-2, a class I odorant receptor and OR256-17, a class II receptor. Each of the odorant receptor types is known to be activated by distinct odorants and their glomeruli are located in different regions of the bulb. We found significant differences in the size of the glomeruli as well as in the variability of the glomerulus size in individual mice, whereby the OR37A glomeruli featured a remarkably stable size. The number of cells surrounding a given glomerulus correlated strongly with its size which allowed comparative analyses of the surrounding cell types for individual glomeruli. The proportion of PG cells labeled by NeuN as well as putative GABAergic neurons labeled by GAD65 was quite similar for the different glomerulus types. However, the number of cells expressing distinct calcium-binding proteins, namely parvalbumin (PV), calbindin (CB) or calretinin (CR) varied significantly among the three glomerulus types. These data suggest that each odorant receptor specific glomerulus type may be surrounded by a unique network of PG cells.