Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular signal-regulated kinase is involved in tumor necrosis factor-α-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells

Objectives—Mucus secretion and inflammatory cytokines are increased in cases of chronic sinusitis with polyp. In this study we initially investigated the localization of MUC5AC protein in human nasal polyps. We then examined whether tumor necrosis factor-α (TNF-α) induces MUC5AC gene expression and whether extracellular signal-regulated kinase (ERK) plays a role in TNF-α-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells. Finally, we investigated whether MUC5AC and activated ERK are co-expressed in goblet cells. Material and Methods—Human nasal polyp epithelial cells were isolated and subcultured. Passage-2 polyp epithelial cells were treated with 10 ng/ml TNF-α. ERK involvement was determined by Western blotting and MUC5AC gene expression by reverse transcriptase polymerase chain reaction. An ERK kinase assay and an inhibitor study using PD98059 were also performed. Immunohistochemical staining using polyclonal MUC5AC antibody and a phospho-specific ERK antibody was done in nasal polyps. Results—MUC5AC was found to be expressed in the majority of goblet cells in human nasal polyp epithelium. TNF-α induced MUC5AC gene expression, and ERK activation was found to be essential for TNF-α-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells. In addition, both MUC5AC and activated ERK were co-expressed in goblet cells of human nasal polyp epithelium. Conclusions—TNF-α induces MUC5AC gene expression via ERK in cultured human nasal polyp epithelial cells.
Distributional analyses in the picture–word interference paradigm: Exploring the semantic interference and the distractor frequency effects

The present study explores the distributional features of two important effects within the picture–word interference paradigm: the semantic interference and the distractor frequency effects. These two effects display different and specific distributional profiles. Semantic interference appears greatly reduced in faster response times, while it reaches its full magnitude only in slower responses. This can be interpreted as a sign of fluctuant attentional efficiency in resolving response conflict. In contrast, the distractor frequency effect is mediated mainly by a distributional shift, with low-frequency distractors uniformly shifting reaction time distribution towards a slower range of latencies. This finding fits with the idea that distractor frequency exerts its effect by modulating the point in time in which operations required to discard the distractor can start. Taken together, these results are congruent with current theoretical accounts of both the semantic interference and distractor frequency effects. Critically, distributional analyses highlight and further describe the different cognitive dynamics underlying these two effects, suggesting that this analytical tool is able to offer important insights about lexical access during speech production.
Time and Effort Required by Persons with Spinal Cord Injury to Learn to Use a Powered Exoskeleton for Assisted Walking.

BACKGROUND Powered exoskeletons have been demonstrated as being safe for persons with spinal cord injury (SCI), but little is known about how users learn to manage these devices. OBJECTIVE To quantify the time and effort required by persons with SCI to learn to use an exoskeleton for assisted walking. METHODS A convenience sample was enrolled to learn to use the first-generation Ekso powered exoskeleton to walk. Participants were given up to 24 weekly sessions of instruction. Data were collected on assistance level, walking distance and speed, heart rate, perceived exertion, and adverse events. Time and effort was quantified by the number of sessions required for participants to stand up, walk for 30 minutes, and sit down, initially with minimal and subsequently with contact guard assistance. RESULTS Of 22 enrolled participants, 9 screen-failed, and 7 had complete data. All of these 7 were men; 2 had tetraplegia and 5 had motor-complete injuries. Of these, 5 participants could stand, walk, and sit with contact guard or close supervision assistance, and 2 required minimal to moderate assistance. Walk times ranged from 28 to 94 minutes with average speeds ranging from 0.11 to 0.21 m/s. For all participants, heart rate changes and reported perceived exertion were consistent with light to moderate exercise. CONCLUSIONS This study provides preliminary evidence that persons with neurological weakness due to SCI can learn to walk with little or no assistance and light to somewhat hard perceived exertion using a powered exoskeleton. Persons with different severities of injury, including those with motor complete C7 tetraplegia and motor incomplete C4 tetraplegia, may be able to learn to use this device.
Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders.

OBJECTIVE Bipolar disorders are prevalent major illnesses with high rates of morbidity, comorbidity, disability, and mortality. A growing number of psychotropic drugs are used to treat bipolar disorder, often off-label and in untested, complex combinations. METHODS To quantify utilization rates for psychotropic drug classes, this study used the 2002-2003 U.S. national MarketScan research databases to identify 7,760 persons with ICD-9 bipolar disorder subtypes. Survival analysis was used to estimate times until initial monotherapies were augmented, changed, or discontinued. RESULTS The most commonly prescribed first drug class was antidepressants (50% of patients), followed by mood stabilizers (25%: anticonvulsants, 17%, and lithium, 8%), sedatives (15%), and antipsychotics (11%). At study midpoint only 44% of patients were receiving monotherapy. Those receiving monotherapy were ranked by initial drug prescribed and percentage of patients (bipolar I and bipolar II): antidepressants (55% and 65%), lithium (51% and 41%), antipsychotics (32% and 31%), anticonvulsants (28% and 29%), and sedatives (28%, 25%). Median time to adding another psychotropic was 2.5-times less than median time to changing the initial treatment (16.4 compared with 40.9 weeks), and stopping was rare. Median weeks until therapy was changed in any way for 25% of patients was as follows: lithium, 29 weeks; antidepressants, 13; anticonvulsants, 13; antipsychotics, 13; and sedatives, 9. CONCLUSIONS Antidepressants were the first-choice agent twice as often as mood stabilizers. Lithium was sustained longer than monotherapy with other mood stabilizers. Time to augmentation was much shorter than time to change or discontinuation.
Simple Genetic Selection Protocol for Isolation of Overexpressed Genes That Enhance Accumulation of Membrane-Integrated Human G Protein-Coupled Receptors in Escherichia coli

ABSTRACT The efficient production of membrane proteins in bacteria remains a major challenge. In this work, we sought to identify overexpressed genes that enhance the yields of recombinant membrane proteins in Escherichia coli. We developed a genetic selection system for bacterial membrane protein production, consisting of membrane protein fusions with the enzyme β-lactamase and facile selection of high-production strains on ampicillin-containing media. This system was used to screen the ASKA library, an ordered library of plasmids encoding all the known E. coli open reading frames (ORFs), and several clones with the ability to accumulate enhanced amounts of recombinant membrane proteins were selected. Notably, coexpression of ybaB, a gene encoding a putative DNA-binding protein of unknown function, was found to enhance the accumulation of a variety of membrane-integrated human G protein-coupled receptors and other integral membrane proteins in E. coli by up to 10-fold. The results of this study highlight the power of genetic approaches for identifying factors that impact membrane protein biogenesis and for generating engineered microbial hosts for membrane protein production.
On the time course of exogenous cueing effects in bilinguals: Higher proficiency in a second language is associated with more rapid endogenous disengagement

Previous investigations have demonstrated a bilingual advantage on various aspects of executive control. It remains unclear how the language proficiency of bilinguals might relate to the mechanisms involved in attentional disengagement. In the present investigation, we tested the hypothesis that high bilingual proficiency would lead to a more rapid endogenous disengagement of attention from task-irrelevant peripheral cues. We predicted that more rapid attentional disengagement would result in an earlier appearance of inhibition of return (IOR). In this study Hindi–English bilinguals who differed in their L2 (English) proficiency participated in a target detection task. Visual targets were preceded by uninformative peripheral cues at various stimulus onset asynchronies (SOAs) allowing for us to visualize the time course of cue-related facilitation and inhibition. High-proficient Hindi–English bilinguals showed an earlier appearance of IOR than did low-proficient bilinguals, suggesting increased efficiency in disengagement of attention from task-irrelevant inputs. Furthermore, consistent with the “global” advantage that characterizes bilinguals in many tasks, the high-proficient group outperformed low-proficient bilinguals in overall reaction time.
Two major Smad pathways in TGF‐β superfamily signalling

Members of the transforming growth factor‐β (TGF‐β) superfamily bind to two different serine/threonine kinase receptors, i.e. type I and type II receptors. Upon ligand binding, type I receptors specifically activate intracellular Smad proteins. R‐Smads are direct substrates of type I receptors; Smads 2 and 3 are specifically activated by activin/nodal and TGF‐β type I receptors, whereas Smads 1, 5 and 8 are activated by BMP type I receptors. Nearly 30 proteins have been identified as members of the TGF‐β superfamily in mammals, and can be classified based on whether they activate activin/TGF‐β‐specific R‐Smads (AR‐Smads) or BMP‐specific R‐Smads (BR‐Smads). R‐Smads form complexes with Co‐Smads and translocate into the nucleus, where they regulate the transcription of target genes. AR‐Smads bind to various proteins, including transcription factors and transcriptional co‐activators or co‐repressors, whereas BR‐Smads interact with other proteins less efficiently than AR‐Smads. Id proteins are induced by BR‐Smads, and play important roles in exhibiting some biological effects of BMPs. Understanding the mechanisms of TGF‐β superfamily signalling is thus important for the development of new ways to treat various clinical diseases in which TGF‐β superfamily signalling is involved.
Shanxi Province cervical cancer screening study II: Self‐sampling for high‐risk human papillomavirus compared to direct sampling for human papillomavirus and liquid based cervical cytology

The objective of this study was to compare the sensitivity and specificity of a new method for self-sampling for high risk human papillomavirus (HPV) with direct sampling and liquid based cervical cytology. In Shanxi Province, China, 8,497 women (ages 27–56) underwent a self-sample for HPV using a conical-shaped brush placed into the upper vagina and rotated. Three to sixteen months later the women were screened with liquid-based cytology and direct HPV tests. Subjects with any abnormal test underwent colposcopy and multiple biopsies. Mean age was 40.9 years. 4.4 percent of subjects had ≥CIN II, 26% a positive self-sample and 24% a positive direct test for HPV. The sensitivity for detection of ≥CIN II was 87.5% for self-sampling, and 96.8% for the direct test (P < 0.001). The specificity was 77.2% for the self-sample and 79.7% for the direct test. With an abnormal Pap defined as ASCUS or greater the sensitivity of the Pap for the detection of ≥ CIN II was 88.3% and the specificity was 81.2%. We conclude that self-sampling for HPV is less sensitive for ≥ CIN II than the direct test, but similar to liquid based cytology.
Tracking skeletal fusion feature for one shot learning gesture recognition

Accessibility of RGB-D sensors have facilitated the research in gesture recognition. During sundry approaches, it is found that skeleton information is significant especially for one shot learning by virtue of the minimum requirement of data. We made a review on state-of-the-art approaches for gesture recognition in one shot learning. Based on bag of visual model (BOVW), this paper presents a study on skeletal tracking from RGB-D and puts forward a novel skeletal fusion feature extracted from these data, namely skeletal filtered features around key points (SFFK). The proposed SFFK feature is efficient, precise and robust. Efforts were made to optimize the gesture segmentation algorithm based on dynamic time warping (DTW). We propose different ways to gain the motion matrix, during which we find one performs best. That is taking OR operation on two difference images obtained from three adjacent frames. Finally, we evaluated our approach on the ChaLearn gesture dataset (CGD). The results show that our approach is remarkably superior to those existed approaches on CGD.
Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice

Early microglial accumulation in Alzheimer's disease (AD) delays disease progression by promoting clearance of β-amyloid (Aβ) before formation of senile plaques. However, persistent Aβ accumulation despite increasing microglial numbers suggests that the ability of microglia to clear Aβ may decrease with age and progression of AD pathology. To determine the effects of aging and Aβ deposition on microglial ability to clear Aβ, we used quantitative PCR to analyze gene expression in freshly isolated adult microglia from 1.5-, 3-, 8-, and 14-month-old transgenic PS1-APP mice, an established mouse model of AD, and from their nontransgenic littermates. We found that microglia from old PS1-APP mice, but not from younger mice, have a twofold to fivefold decrease in expression of the Aβ-binding scavenger receptors scavenger receptor A (SRA), CD36, and RAGE (receptor for advanced-glycosylation endproducts), and the Aβ-degrading enzymes insulysin, neprilysin, and MMP9, compared with their littermate controls. In contrast, PS1-APP microglia had a 2.5-fold increase in the proinflammatory cytokines IL-1β (interleukin-1β) and tumor necrosis factor α (TNFα), suggesting that there is an inverse correlation between cytokine production and Aβ clearance. In support of this possibility, we found that incubation of cultured N9 mouse microglia with TNFα decreased the expression of SRA and CD36 and reduced Aβ uptake. Our data indicate that, although early microglial recruitment promotes Aβ clearance and is neuroprotective in AD, as disease progresses, proinflammatory cytokines produced in response to Aβ deposition downregulate genes involved in Aβ clearance and promote Aβ accumulation, therefore contributing to neurodegeneration. Antiinflammatory therapy for AD should take this dichotomous microglial role into consideration.
Longitudinal study on the relationship between serum albumin and periodontal disease.

AIM The purpose of this study was to evaluate the relationship between periodontal disease and the general health status in community-dwelling elderly using the serum albumin concentration as a criterion index of the severity of underlying disease and nutrition. MATERIAL AND METHODS Six hundred subjects aged 70 years underwent a baseline examination. Dental examinations were carried out at baseline and once a year for 4 years. Periodontal conditions were estimated for subjects with at least one remaining tooth. Clinical attachment levels at six sites of all teeth present were measured. A change in loss of attachment of 3 mm or greater in 1 year at each site was defined as periodontal disease progression. Data were analysed in subjects for whom data were available for 4 years. RESULTS Serum albumin concentration at baseline ranged from 3.4 to 5.0 g/dl with a mean of 4.3+/-0.2. When the analysis was stratified by smoking status, we found that serum albumin concentration had a significant effect on periodontal disease progression among non-smokers (standardized regression coefficient=-0.16; p=0.017), using multiple regression analysis. CONCLUSIONS The findings of the present study suggest that serum albumin concentration is a significant risk predictor of periodontal disease progression among elderly non-smokers.
Wages, Productivity, and Worker Characteristics: Evidence from Plant‐Level Production Functions and Wage Equations

We use a unique new data set that combines data on individual workers and their employers to estimate marginal productivity differentials among different types of workers. We then compare these to estimated relative wages, leading to new evidence on productivity‐based and nonproductivity‐based explanations of the determination of wages. Among our findings are (1) the higher pay of prime‐aged workers (aged 35–54) and older workers (aged 55+) is reflected in higher point estimates of their relative marginal products, and (2) for the most part, the lower relative earnings of women are not reflected in lower relative marginal products.
Behavioural effects of acute tryptophan depletion in healthy male volunteers

Acute tryptophan depletion (ATD) studies have been used to assess the role of the serotonergic system in various aspects of human behaviour. Changes in mood have already been described in selected groups of individuals submitted to ATD. The present study was a randomized, double-blind, cross-over trial designed to evaluate the effects of ATD on mood, memory, attention and induced anxiety in normal male volunteers. Twelve healthy male volunteers were submitted to two separate sessions of ATD, 1 week apart. Drinks containing either a balanced mixture of amino acids (B) or a similar mixture devoid of tryptophan (T–) were administered in each session. Mood was assessed using self-rating scales. Attention and memory were assessed using a battery of psychological tests. Anxiety induction was carried out using a simulation of public speaking. Blood levels of tryptophan were assessed before and after the B and T– drinks. Results showed that ATD markedly decreased plasma tryptophan (p< 0.0001). Mood ratings, memory and attention were not changed by the T– drink. There was no difference among the anxiety levels measured under T– or B mixtures. These data supports the notion that ATD does not change mood and cognitive function in healthy subjects.
Pension Deficits and the Design of Private Debt Contracts

We find a positive relation between the amount of pension deficits and the cost of bank loans. The effect of pension deficits on the cost of bank loans is driven by financial constraints, information-asymmetry problems, and higher pension-investment risk. Banks tighten lending terms for firms with larger pension deficits by requiring collateral, increasing the number of loan covenants, and shortening loan maturity. Borrowers with larger pension deficits are also more likely to violate covenants in the future. Collectively, these findings indicate that pension deficits represent an additional source of risk priced by banks.
Three‐dimensional surface imaging for clinical trials: Improved precision and reproducibility in circumference measurements of thighs and abdomens

Numerous body contouring and laser‐assisted liposuction devices have recently obtained or are seeking FDA clearance, and assessment of efficacy of these devices is largely based upon qualitative comparisons of before and after photographs and measurable changes in patient circumference. The current standard for measuring body circumference in clinical trials involves the use of a standard measuring tape. These manual measurements introduce human error and may incorrectly support or refute a device or procedure's efficacy. A promising alternative to manual measurements is three‐dimensional (3D) photography. This technology allows circumference measurements to be performed on 3D digital models. Our objective is to compare the precision and reproducibility of manual versus 3D photographic measurement of body circumference.
Emergence of a Highly Pathogenic Avian Influenza Virus from a Low-Pathogenic Progenitor

ABSTRACT Avian influenza (AI) viruses of the H7 subtype have the potential to evolve into highly pathogenic (HP) viruses that represent a major economic problem for the poultry industry and a threat to global health. However, the emergence of HPAI viruses from low-pathogenic (LPAI) progenitor viruses currently is poorly understood. To investigate the origin and evolution of one of the most important avian influenza epidemics described in Europe, we investigated the evolutionary and spatial dynamics of the entire genome of 109 H7N1 (46 LPAI and 63 HPAI) viruses collected during Italian H7N1 outbreaks between March 1999 and February 2001. Phylogenetic analysis revealed that the LPAI and HPAI epidemics shared a single ancestor, that the HPAI strains evolved from the LPAI viruses in the absence of reassortment, and that there was a parallel emergence of mutations among HPAI and later LPAI lineages. Notably, an ultradeep-sequencing analysis demonstrated that some of the amino acid changes characterizing the HPAI virus cluster were already present with low frequency within several individual viral populations from the beginning of the LPAI H7N1 epidemic. A Bayesian phylogeographic analysis revealed stronger spatial structure during the LPAI outbreak, reflecting the more rapid spread of the virus following the emergence of HPAI. The data generated in this study provide the most complete evolutionary and phylogeographic analysis of epidemiologically intertwined high- and low-pathogenicity viruses undertaken to date and highlight the importance of implementing prompt eradication measures against LPAI to prevent the appearance of viruses with fitness advantages and unpredictable pathogenic properties. IMPORTANCE The Italian H7 AI epidemic of 1999 to 2001 was one of the most important AI outbreaks described in Europe. H7 viruses have the ability to evolve into HP forms from LP precursors, although the mechanisms underlying this evolutionary transition are only poorly understood. We combined epidemiological information, whole-genome sequence data, and ultradeep sequencing approaches to provide the most complete characterization of the evolution of HPAI from LPAI viruses undertaken to date. Our analysis revealed that the LPAI viruses were the direct ancestors of the HPAI strains and identified low-frequency minority variants with HPAI mutations that were present in the LPAI samples. Spatial analysis provided key information for the design of effective control strategies for AI at both local and global scales. Overall, this work highlights the importance of implementing rapid eradication measures to prevent the emergence of novel influenza viruses with severe pathogenic properties.