Miracle-dz/UniFAR-FTUs huggingface dataset:
Propagating Waves Can Explain Irregular Neural Dynamics

Cortical neurons in vivo fire quite irregularly. Previous studies about the origin of such irregular neural dynamics have given rise to two major models: a balanced excitation and inhibition model, and a model of highly synchronized synaptic inputs. To elucidate the network mechanisms underlying synchronized synaptic inputs and account for irregular neural dynamics, we investigate a spatially extended, conductance-based spiking neural network model. We show that propagating wave patterns with complex dynamics emerge from the network model. These waves sweep past neurons, to which they provide highly synchronized synaptic inputs. On the other hand, these patterns only emerge from the network with balanced excitation and inhibition; our model therefore reconciles the two major models of irregular neural dynamics. We further demonstrate that the collective dynamics of propagating wave patterns provides a mechanistic explanation for a range of irregular neural dynamics, including the variability of spike timing, slow firing rate fluctuations, and correlated membrane potential fluctuations. In addition, in our model, the distributions of synaptic conductance and membrane potential are non-Gaussian, consistent with recent experimental data obtained using whole-cell recordings. Our work therefore relates the propagating waves that have been widely observed in the brain to irregular neural dynamics. These results demonstrate that neural firing activity, although appearing highly disordered at the single-neuron level, can form dynamical coherent structures, such as propagating waves at the population level.
Class I defective herpes simplex virus DNA as a molecular cloning vehicle in eucaryotic cells

Defective herpes simplex virus type 1 genomes are composed of head-to-tail tandem repeats of small regions of the nondefective genome. Monomeric repeat units of class I defective herpes simplex virus genomes were cloned into bacterial plasmids. The repeat units functioned as replicons since both viral and convalently linked bacterial plasmid DNA replicated (with the help of DNA from nondefective virus) when transfected into rabbit skin cells. Recombinant plasmids were packaged into virions and were propagated from culture to culture by infection with progeny virus. Replication was evidently by a rolling circle mechanism since plasmid DNA was present in a high-molecular-weight form in transfected cells. Circular recombinant plasmid DNA replicated with a high degree of fidelity. In contrast, linear plasmid DNA underwent extensive deletions of both viral and bacterial sequences when transfected into rabbit skin cells. Derivative plasmids, a fraction of the size of the parental plasmid, were rescued by transforming Escherichia coli with DNA from the transfected rabbit skin cells. These plasmids functioned as shuttle vectors since they replicated faithfully in both eucaryotic and procaryotic cells.
Configuration of the thermal landscape determines thermoregulatory performance of ectotherms

Significance Environmental temperatures drive major ecological processes, largely because the physiology of any organism depends on its temperature. For this reason, many animals behave in ways that prevent their body temperatures from fluctuating, even as climate changes dramatically. Using a combination of computer simulations and controlled experiments, we show that thermoregulation depends not only on the mean and variance of operative environmental temperatures but also on the spatial arrangement of these temperatures. Our results have further implications for ecological models that rely on estimates of activity to predict the responses to climatic change. Although most organisms thermoregulate behaviorally, biologists still cannot easily predict whether mobile animals will thermoregulate in natural environments. Current models fail because they ignore how the spatial distribution of thermal resources constrains thermoregulatory performance over space and time. To overcome this limitation, we modeled the spatially explicit movements of animals constrained by access to thermal resources. Our models predict that ectotherms thermoregulate more accurately when thermal resources are dispersed throughout space than when these resources are clumped. This prediction was supported by thermoregulatory behaviors of lizards in outdoor arenas with known distributions of environmental temperatures. Further, simulations showed how the spatial structure of the landscape qualitatively affects responses of animals to climate. Biologists will need spatially explicit models to predict impacts of climate change on local scales.
A comparison of urinary nuclear matrix protein‐22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer:the prognostic value of false‐positive results

Objectives To evaluate the diagnostic and prognostic value of the nuclear matrix protein‐22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false‐positive test results in patients followed up for bladder cancer.
Household whole and low-fat milk consumption in Poland: a censored system approach

Milk products are a preeminent food category in Poland, providing both employment and dietary benefit. This thesis investigates factors affecting household milk consumption in Poland, paying attention to the effect of outmigration, an issue in Poland. We apply both the bivariate two-part model (B2P) and multivariate sample-selection model (MSSM) to the milk consumption data in Poland and choose the bivariate two-part model based on theoretical, practical, and statistical grounds. We estimate actual milk expenditure and explain the dependence of whole and low-fat milk consumption decisions using the B2P model.
Regulatory indicators in the European Union and the Organization for Economic Cooperation and Development: Performance assessment, organizational processes, and learning

The Organization for Economic Cooperation and Development (OECD) has produced four waves of regulatory management indicators. By contrast, the European Union has never adopted a common system of indicators, although it is much more integrated and less heterogeneous than the OECD. This cannot be explained by the different propensity for performance measurement: the European Union has agreed on policy metrics in economic and social policy areas, and regulation is a fundamental tool for this organization. Although structural variables matter, to answer questions about adoption (Yes/No), timing (when) and content of indicators (what type of indicators) we need the additional aid of policy learning and empirical observations on organizational processes. We find that the OECD process was one of self-directed learning fuelled by high socialization, internal validation of knowledge, favorable attitudes and posture of the secretariat, and mutually constitutive roles of delegates and staff. For the European Union we find the reverse. These findings contribute to the literature on policy learning, regulation, and global performance measurement.
Direct Field-Circuit Coupled Analysis and Corresponding Experiments of Electromagnetic Resonant Coupling System

Based on electromagnetic (EM) field resonantly coupling technology, a novel contactless power transfer system is analyzed in this paper. A detailed field-circuit coupling model is proposed taking into account the influences of near field strength and circuit constraints simultaneously. Therefore, the distribution of magnetic field strength under different angular frequencies and spacing distances are calculated through direct field-circuit coupled method. In the experimental aspect, a resonantly coupling system contains planar disc resonators is designed. It is shown by measurement results that property of system is basically consistent with the results derived in article. Moreover, the solution accuracy is improved through this technology to recharge electrical devices or transfer power.
Effect of sodium butyrate on induction of cellular and viral DNA syntheses in polyoma virus-infected mouse kidney cells

Sodium butyrate inhibited initiation of viral and cellular DNA replication in polyoma virus-infected mouse kidney cells. Ongoing viral or cellular DNA replication, however, was not affected by the presence of the substance. Butyrate had no effect on T-antigen synthesis and on the stimulation of transcription, one of the earliest reactions of the infected cells to the appearance of T-antigen, nor did it inhibit expression of late viral genes (synthesis of viral capsid proteins). In addition to blocking the onset of DNA synthesis, butyrate also inhibited stimulation of the activities of enzymes involved in DNA synthesis. When butyrate was removed, viral and cellular DNA syntheses were induced in parallel after a lag period of approximately 4 h. At the same time, the activities of enzymes involved in DNA synthesis increase. If protein synthesis was inhibited during part of the lag period, the initiation of DNA synthesis was retarded for the same time interval, suggesting that the proteins involved in the initiation of DNA replication had to be made. We have developed an in vitro system for measuring DNA synthesis in crude nuclear preparations which mimics the status of DNA replication in intact cells and may help in future experiments to study the requirements for initiation of cellular and viral DNA synthesis and the possible involvement of T-antigens in this reaction.
A systemic analysis on pemetrexed in treating patients with breast cancer.

BACKGROUND This systemic analysis was conducted to evaluate the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic breast cancer as first or second line chemotherapy. METHODS Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with breast cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. RESULTS In first line pemetrexed based regimens, 10 clinical studies which including 513 patients with advanced breast cancer were considered eligible for inclusion. For second line pemetrexed based chemotherapy, 5 clinical studies which including 281 patients with advanced breast cancer were considered eligible. Systemic analysis suggested that, in all patients, pooled RR was 32.6% (167/513) in pemetrexed based first line regimens, and 13.9 % (39/281) in pemetrexed based second line regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia in pemetrexed based first line treatment; and lymphopenia, neutropenia, leukopenia, as well as anemia in second line chemotherapy. One treatment related death occurred with pemetrexed based second line treatment. CONCLUSION This systemic analysis suggests that pemetrexed based first line regimens are associated with a reasonable response rate and acceptable toxicity, however with low response rate for treating patients with metastatic breast cancer when is used in the second line.
Transcription Factor 7-Like 2 Regulates β-Cell Survival and Function in Human Pancreatic Islets

OBJECTIVE—Type 2 diabetes is characterized by impaired insulin secretion in response to increased metabolic demand. This defect in β-cell compensation seems to result from the interplay between environmental factors and genetic predisposition. Genome-wide association studies reveal that common variants in transcription factor 7-like 2 (TCF7L2) are associated with increased risk of type 2 diabetes. The aim of the present study was to establish whether TCF7L2 plays a role in β-cell function and/or survival. RESEARCH DESIGN AND METHODS—To investigate the effects of TCFL7L2 depletion, isolated islets were exposed to TCF7L2 small interfering RNA (siRNA) versus scrambled siRNA, and β-cell survival and function were examined. For TCF7L2 overexpression, islets were cultured in glucose concentrations of 5.5–33.3 mmol/l and the cytokine mix interleukin-1β/γ-interferon with or without overexpression of TCF7L2. Subsequently, glucose-stimulated insulin secretion (GSIS), β-cell apoptosis [by transferase-mediated dUTP nick-end labeling assay and Western blotting for poly(ADP-ribose) polymerase and Caspase-3 cleavage], and β-cell proliferation (by Ki67 immunostaining) were analyzed. RESULTS—Depleting TCF7L2 by siRNA resulted in a 5.1-fold increase in β-cell apoptosis, 2.2-fold decrease in β-cell proliferation (P < 0.001), and 2.6-fold decrease in GSIS (P < 0.01) in human islets. Similarly, loss of TCF7L2 resulted in impaired β-cell function in mouse islets. In contrast, overexpression of TCF7L2 protected islets from glucose and cytokine-induced apoptosis and impaired function. CONCLUSIONS—TCF7L2 is required for maintaining GSIS and β-cell survival. Changes in the level of active TCF7L2 in β-cells from carriers of at-risk allele may be the reason for defective insulin secretion and progression of type 2 diabetes.
Association between oxidative stress and macromolecular damage in elderly patients with age-related macular degeneration

Background and aims: The aim of the present study was to determine whether age and gender affect the imbalance between oxidant production and antioxidant levels in age-related macular degeneration (ARMD) patients. Methods: Total superoxide dismutase (T-SOD), total glutathione peroxidase (T-GSHPx), and catalase (CAT) activities, as well as malondialdehyde (MDA), protein carbonyl (PC), 8-Hydroxy-29-deoxyguanosine (8-OHdG) and total oxidation status (TOS) levels, were measured in the following groups subdivided by age and gender: 156 early-ARMD patients; 80 wet-late ARMD patients; 72 dry-late ARMD patients; and 207 healthy controls. Results: Among all study participants, women aged 50–54 had higher T-SOD and T-GSHPx activities and lower MDA, PC, TOS and 8-OHdG levels than age-matched men (p<0.05), whereas older women were not significantly different from age-matched older men. Significantly increased oxidative damage was associated with ARMD patients >60 years of age in both sexes compared with controls (p<0.01 for 60–64 and 65–69-year-old ARMD subgroups; p<0.001 for 70–74 and 75–80-year-old ARMD subgroups). Multiple regression analysis demonstrates that age significantly affects antioxidant status and oxidative damage in ARMD patients compared with controls (controls, p<0.05; ARMD patients, p<0.001). A direct correlation with antioxidant enzyme activities and an inverse correlation with oxidative DNA, protein and lipid damage were also observed in premenopausal women (controls, p<0.05; ARMD patients, p<0.001). Conclusions: Aging and postmenopausal status may be aggravating factors contributing to redox imbalance and oxidative damage in ARMD patients.
Norovirus diversity in children with gastroenteritis in South Africa from 2009 to 2013: GII.4 variants and recombinant strains predominate

SUMMARY From 2009 to 2013 the diversity of noroviruses (NoVs) in children (⩽5 years) hospitalized with gastroenteritis in South Africa was investigated. NoVs were genotyped based on nucleotide sequence analyses of partial RNA-dependent RNA polymerase (RdRp) and capsid genes. Seventeen RdRp genotypes (GI.P2, GI.P3, GI.P6, GI.P7, GI.P not assigned (NA), GI.Pb, GI.Pf, GII.P2, GII.P4, GII.P7, GII.P13, GII.P16, GII.P21, GII.Pc, GII.Pe, GII.Pg, GII.PNA) and 20 capsid genotypes (GI.1, GI.2, GI.3, GI.5, GI.6, GI.7, GI.NA, GII.1, GII.2, GII.3, GII.4, GII.6, GII.7, GII.10, GII.12, GII.13, GII.14, GII.16, GII.17, GII.21) were identified. The combined RdRp/capsid genotype was determined for 275 GII strains. Fifteen confirmed recombinant NoV strains circulated during the study period. NoV GII.P4/GII.4 (47%) and GII.Pe/GII.4 (18%) predominated, followed by GII.PNA/GII.3 (10%) and GII.P21/GII.3 (7%). Other prevalent strains included GII.Pg/GII.12 (6%) and GII.Pg/GII.1 (3%). Two novel recombinants, GII.Pg/GII.2 and GII.Pg/GII.10 were identified. In 2013 the replacement of GII.4 New Orleans 2009 and GII.P21/GII.3, which predominated during the early part of the study, with GII.4 Sydney 2012 and GII.PNA/GII.3 was observed. This study presents the most comprehensive recent data on NoV diversity in Africa.
A Genome-Wide Association Study to Identify Potential Germline Copy Number Variants for Sporadic Breast Cancer Susceptibility

Breast cancer (BC) predisposition in populations arises from both genetic and nongenetic risk factors. Structural variations such as copy number variations (CNVs) are heritable determinants for disease susceptibility. The primary objectives of this study are (1) to identify CNVs associated with sporadic BC using a genome-wide association study (GWAS) design; (2) to utilize 2 distinct CNV calling algorithms to identify concordant CNVs as a strategy to reduce false positive associations in the hypothesis-generating GWAS discovery phase, and (3) to identify potential candidate CNVs for follow-up replication studies. We used Affymetrix SNP Array 6.0 data profiled on Caucasian subjects (422 cases/348 controls) to call CNVs using algorithms implemented in Nexus Copy Number and Partek Genomics Suite software. Nexus algorithm identified CNVs associated with BC (731 autosomal CNVs with >5% frequency in the total sample and Q < 0.05). Thirteen CNVs were identified when Partek algorithm-called CNVs were overlapped with Nexus-identified CNVs; these CNVs showed concordances for frequency, effect size, and direction. Coding genes present within BC-associated CNVs were known to play a role in disease etiology and prognosis. Long noncoding RNAs identified within CNVs showed tissue-specific expression, indicating potential functional relevance of the findings. The identified candidate CNVs warrant independent replication.
The estimated prevalence of chronic obstructive pulmonary disease in a general practice population.

OBJECTIVE To estimate the prevalence of chronic obstructive pulmonary disease (COPD) in a general practice population in the UK. METHOD Four postal respiratory questionnaire surveys were carried out between 1993 and 2001. Subjects from the 2001 study were invited for spirometry if they were aged 30 years or more, had indicated that they were 'ever smokers' in any of the surveys, and/or had been considered to have likely obstructive airways disease on the basis of their replies to the 2001 questionnaire. RESULTS 2646 subjects were invited for spirometry of whom 871 (32.9%) attended. Results were available for 825 participants. 163 of these subjects were categorised as having COPD. The estimated prevalence in the whole population was 4.1% with the highest prevalence (14.7%) in those aged 60-69 years. In those aged over 40 years it was 9.6%. CONCLUSION This study suggests that the prevalence of COPD is much higher than the previous estimates of between 1 and 2%.
Candida albicans Cell Wall Glycosylation May Be Indirectly Required for Activation of Epithelial Cell Proinflammatory Responses

ABSTRACT Oral epithelial cells discriminate between the yeast and hyphal forms of Candida albicans via the mitogen-activated protein kinase (MAPK) signaling pathway. This occurs through phosphorylation of the MAPK phosphatase MKP1 and activation of the c-Fos transcription factor by the hyphal form. Given that fungal cell wall polysaccharides are critical in host recognition and immune activation in myeloid cells, we sought to determine whether β-glucan and N- or O-glycosylation was important in activating the MAPK/MKP1/c-Fos hypha-mediated response mechanism and proinflammatory cytokines in oral epithelial cells. Using a series of β-glucan and N- and O-mannan mutants, we found that N-mannosylation (via Δoch1 and Δpmr1 mutants) and O-mannosylation (via Δpmt1 and Δmnt1 Δmnt2 mutants), but not phosphomannan (via a Δmnn4 mutant) or β-1,2 mannosylation (via Δbmt1 to Δbmt6 mutants), were required for MKP1/c-Fos activation, proinflammatory cytokine production, and cell damage induction. However, the N- and O-mannan mutants showed reduced adhesion or lack of initial hypha formation at 2 h, resulting in little MKP1/c-Fos activation, or restricted hypha formation/pseudohyphal formation at 24 h, resulting in minimal proinflammatory cytokine production and cell damage. Further, the α-1,6-mannose backbone of the N-linked outer chain (corresponding to a Δmnn9 mutant) may be required for epithelial adhesion, while the α-1,2-mannose component of phospholipomannan (corresponding to a Δmit1 mutant) may contribute to epithelial cell damage. β-Glucan appeared to play no role in adhesion, epithelial activation, or cell damage. In summary, N- and O-mannosylation defects affect the ability of C. albicans to induce proinflammatory cytokines and damage in oral epithelial cells, but this may be due to indirect effects on fungal pathogenicity rather than mannose residues being direct activators of the MAPK/MKP1/c-Fos hypha-mediated immune response.
Effects of the acetabular fracture index and other factors of posterior wall acetabular fracture on functional outcome

Objective To analyze the effects of the acetabular fracture index (AFI) and other factors on the functional outcome of patients with acetabular fractures involving the posterior wall. Methods Forty-eight patients who underwent surgery in our department were reviewed. According to the AFI, which indicates the percentage of remaining intact posterior acetabular arc, the patients were divided into Group A (AFI ≤ 25%, 11 patients), Group B (25% < AFI ≤ 50%, 23 patients), Group C (50% < AFI ≤ 75%, 7 patients), and Group D (75% < AFI ≤ 100%, 7 patients). The AFI was measured with a computed tomography picture archiving and communication system or calculated with the cosine theorem. A nonparametric test and ordinal regression were used to determine the role of the AFI and other factors on the functional outcome. Perioperative information, including demographic and fracture-related data, reduction quality, physical therapy duration, association with a lower limb fracture and avascular necrosis of the femoral head were prospectively gathered. Results The mean AFIs of A, B, C, and D groups were 14.3%, 35.9%, 59.5%, and 81.2%, respectively. No statistically significant differences were observed among the groups for demographic and fracture-related data. A better reduction quality (OR = 4.21, 95%CI 1.42 ∼ 12.43, χ2 = 6.781, P = 0.009) and a larger value of AFI (OR = 2.56, 95%CI 1.18 ∼ 5.55, χ2 = 5.648, P = 0.017) result in a higher functional score. The functional outcome of a physical therapy duration of more than 12 months (OR = 0.15, 95%CI 0.02 ∼ 0.90, χ2 = 4.324, P = 0.038) was better than that of less than 12 months. Lower limb fracture (OR = 0.13, 95%CI 0.02 ∼ 0.74, χ2 = 5.235, P = 0.022) and avascular necrosis of femoral head (OR = 0.02, 95%CI 0.00 ∼ 0.87, χ2 = 4.127, P = 0.042) were found to correlate with a lower functional score. Conclusion With a greater of AFI, the functional outcome score would be better. Other factors, including reduction quality, physical therapy duration, association with a lower limb fracture, and avascular necrosis of the femoral head, most likely also affect hip functional recovery.