Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Drug Resistant Mutations in HIV-1 CRF07_BC Variants Selected by Nevirapine In Vitro

Since the antiretroviral therapy (ART) was introduced to patients infected by human immunodeficiency virus (HIV), the HIV related mortality and morbidity have been significantly reduced. The major obstacle for long-term successful anti-HIV treatment is the emergence of drug resistant mutants. Current data of drug resistance was mainly obtained on HIV-1 subtype B but rarely on non-B virus, even more rare with newly emerged circulating recombinant forms (CRFs). The lack of such data limits the rational management of ART for the increasing number of patients infected by non-subtype B virus. In this study, a HIV-1 CRF07_BC strain CNGZD was isolated from a HIV patient and its genome was sequenced and deposited in GenBank (JQ423923). Potential drug resistant mutants of this CRF07_BC virus strain were selected in PBMCs cultures in the presence of Nevirapine (NVP), which is the most frequently used antiretroviral drug in China. Four combination profiles of mutations were identified in the NVP-selected mutants, which were initiated with A98G, V108I, Y181C and I135T/I382L and followed by more than two other mutations at the end of the selections, respectively. A total of seven previously reported mutations (A98G, V106M, V108I, I135T, Y181C, V189I, K238N) and seven novel mutations (P4H, T48I, I178M, V314A, I382L/V, T386A) in the reverse transcriptase gene were found in these NVP-selected mutants. Phenotypic analysis in the NVP-selected mutants showed that all the mutations, except P4H, contribute to NVP resistance. Among them, V106M and Y181C reduce NVP susceptibility for more than 20-fold, while the other mutations cause less than 20 folds drug resistance. Although the information obtained in this in vitro selection study may not fully cover resistant mutations which will actually occur in patients, it has still provided useful information for rational management of ART in patients infected with HIV CRF_BC subtype.
Postsurgical Depressive Symptoms and Proinflammatory Cytokine Elevations in Women Undergoing Primary Treatment for Breast Cancer

Objective Depression and inflammation may independently promote breast cancer (BCa) disease progression and poorer clinical outcomes. Depression has been associated with increased levels of inflammatory markers in medically healthy individuals and patients with cancer. However, inconsistencies in study time frames complicate interpretation of results within specific cancer types. This study examined relationships between depressive symptoms and inflammation in women with early-stage BCa before beginning adjuvant treatment. Methods Women with Stage 0-III BCa were recruited approximately 4 to 8 weeks after surgery. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression, and blood samples were collected to quantify circulating levels of interleukin (IL)-1&bgr;, IL-6, and tumor necrosis factor &agr; (TNF-&agr;) by enzyme-linked immunosorbent assay. Analyses of covariance were used to test for group differences (elevated versus low depressive symptoms) in levels of cytokines. Multiple regression analyses were used to examine relationships between continuous severity of depressive symptoms and levels of cytokines adjusting for relevant biobehavioral covariates. Results Thirty-six (40%) of 89 patients showed elevated levels of depressive symptoms and, in adjusted models, had marginally higher levels of IL-1&bgr; (mean [M] = 14.49 [95% confidence interval {CI} = 6.11–32.65] versus M = 4.68 [95% CI = 1.96–9.86] and IL-6 [M = 88.74 {95% CI = 33.28–233.96} versus M = 61.52 {95% CI = 27.44–136.40}]) significantly higher levels of TNF-&agr; (M = 17.07 [95% CI = 8.27–34.32] versus M = 6.94 [95% CI = 3.58–12.80]) than did women with low depressive symptoms. Across the spectrum of depressive symptoms, greater magnitude of depressive symptoms was related to greater levels of IL-1&bgr; (&bgr; = 0.06, p = .006, R2 = 0.25) and TNF-&agr; (&bgr; = 0.06, p = .003, R2 = 0.27). Conclusions Postsurgery and preadjuvant treatment for early-stage BCa, depressive symptoms covary with elevated levels of multiple proinflammatory cytokines. Findings have implications for psychosocial and biological interventions concurrently focusing on depression and inflammation. Trial Registration: NCT01422551.
Keystone nonconsumptive effects within a diverse predator community

Abstract The number of prey killed by diverse predator communities is determined by complementarity and interference among predators, and by traits of particular predator species. However, it is less clear how predators' nonconsumptive effects (NCEs) scale with increasing predator biodiversity. We examined NCEs exerted on Culex mosquitoes by a diverse community of aquatic predators. In the field, mosquito larvae co‐occurred with differing densities and species compositions of mesopredator insects; top predator dragonfly naiads were present in roughly half of surveyed water bodies. We reproduced these predator community features in artificial ponds, exposing mosquito larvae to predator cues and measuring resulting effects on mosquito traits throughout development. Nonconsumptive effects of various combinations of mesopredator species reduced the survival of mosquito larvae to pupation, and reduced the size and longevity of adult mosquitoes that later emerged from the water. Intriguingly, adding single dragonfly naiads to ponds restored survivorship of larval mosquitoes to levels seen in the absence of predators, and further decreased adult mosquito longevity compared with mosquitoes emerging from mesopredator treatments. Behavioral observations revealed that mosquito larvae regularly deployed “diving” escape behavior in the presence of the mesopredators, but not when a dragonfly naiad was also present. This suggests that dragonflies may have relaxed NCEs of the mesopredators by causing mosquitoes to abandon energetically costly diving. Our study demonstrates that adding one individual of a functionally unique species can substantially alter community‐wide NCEs of predators on prey. For pathogen vectors like mosquitoes, this could in turn influence disease dynamics.
The Generalized Topological Overlap Matrix for Detecting Modules in Gene Networks

Systems biologic studies of gene and protein interaction networks have found that these networks are comprised of ‘modules’ (groups of tightly interconnected nodes). Module identification is an essential step towards understanding the whole network architecture. Here we will focus on module identification methods that are based on using a node dissimilarity measure in conjunction with a clustering method. More specifically, we introduce a general class of node dissimilarity measures based on the notion of ‘topological’ overlap, which has been found to be biologically meaningful in several applications. The resulting generalized topological overlap measure (GTOM) generalizes the standard topological overlap measure (TOM) introduced by (2002). Specifically, the m-th order version of this family is constructed by (i) counting the number of m-step neighbors that a pair of nodes share and (ii) normalizing it to take a value between 0 and 1. The main use of the GTOM measures is the identification of network modules (sets of tightly connected nodes). But it can also be used to define novel measures of node connectivity. These GTOM based connectivity measures go beyond the usual nodal degree (number of connections) by taking into account higher-order connections. We discuss the properties of the GTOM measures and provide empirical evidence that they are useful in the context of gene co-expression network analysis. We show that the original TOM proposed by (2002) favors the discovery of smaller modules whereas the higher-order GTOM’s favor larger modules.
Effect of shadowing on the performance of space-time trellis-coded systems

We analyze the performance of space-time trellis codes over shadowed Rician fading channels. The shadowed Rician channel is a generalization of the Rician model, where the line-of-sight path is subjected to a lognormal transformation due to foliage attenuation, also referred to as shadowing. Using the moment generating function method, we derive an exact expression for the pairwise error probability (PEP) of space-time trellis coded systems operating over this channel. The asymptotic analysis of PEP shows that the design criteria of space-time trellis codes proposed for Rayleigh fading still hold when used over shadowed Rician channels. We also present simulation results for bit-error rate performance under various degrees of shadowing.
Optimization of Fast-Fluorescence in situ Hybridization with Repetitive α-Satellite Probes

Abstract A rapid FISH (fluorescence in situ hybridization) technique (Fast-FISH) for quantitative microscopy has been recently introduced. For highly repetitive D N A probes the hybridization (renaturation) time and the number of necessary washing steps were reduced considerably by omitting formamide or equivalent denaturing chemical agents. Due to low stringency conditions major and minor binding sites of the probes used showed visible FISH signals well suited for quantitative image-microscopy. The discrimination of minor and major binding sites was possible by automated image-processing. Here, a further, quantitative optimization of the Fast-FISH technique is described that allows to clearly discriminate major and minor binding sites of a-satellite probes by an easy image classification parameter. With respect to the optimization it was necessary to verify two sensitive parameters (hybridization time and temperature) of the given rapid FISH protocol. A s examples the systematic optimization for the two probes D 12 Z 2 (major binding site on the centromere of chromosome 12) and D 8 Z 2 (major binding site on the centromere of chromosom e 8) are shown. The optimal hybridization conditions concerning rapidness and quality of chromosome morphology were obtained using a hybridization temperature of 70 °C and a hybridization time of 60 min. For these conditions major and minor binding sites were clearly discriminated by the intensity maxi mum Smax of the corresponding FISH-spots.
Ser‐256 phosphorylation dynamics of aquaporin 2 during maturation from the endoplasmic reticulum to the vesicular compartment in renal cells

Aquaporin 2 (AQP2) phosphorylation at Ser‐256 by protein kinase A (PKA) is a key signal for vasopressin‐stimulated AQP2 insertion into the plasma membrane in renal cells. This study underscores the possible role of phosphorylation at Ser‐256 in regulating AQP2 maturation. AQP2‐transfected renal CD8 cells were incubated with brefeldin A (BFA) to accumulate newly synthesized AQP2 in the endoplasmic reticulum (ER), and AQP2 flow from ER to the vesicular compartment was analyzed after BFA washout. We found that a) in the ER, AQP2 is weakly phosphorylated; b) the amount of phosphorylated AQP2 (p‐AQP2) at Ser‐256 increased significantly during transit in the Golgi, even in the presence of the PKA inhibitor H89; and c) AQP2 transport from the Golgi to the vasopressin‐regulated vesicular compartment occurred with a concomitant decrease in p‐AQP2 at Ser‐256. These results support the hypothesis that AQP2 transition in the Golgi apparatus is associated with a PKA‐independent increase in AQP2 phosphorylation at Ser‐256. Conversely, impaired constitutive phosphorylation in a Golgiassociated compartment occurring in cells expressing mutated S256A‐AQP2 or E258K‐AQP2 causes phosphorylation‐defective AQP2 routing to lysosomes. This result might explain the molecular basis of the dominant form of nephrogenic diabetes insipidus caused by the mutation E258K‐AQP2, in which the phenotype is caused by an impaired routing of AQP2.
Phytochrome Regulation and Differential Expression of Gibberellin 3β-Hydroxylase Genes in Germinating Arabidopsis Seeds

Despite extensive studies on the roles of phytochrome in photostimulated seed germination, the mechanisms downstream of the photoreceptor that promote germination are largely unknown. Previous studies have indicated that light-induced germination of Arabidopsis seeds is mediated by the hormone gibberellin (GA). Using RNA gel blot analyses, we studied the regulation of two Arabidopsis genes, GA4 and GA4H (for GA4 homolog), both of which encode GA 3β-hydroxylases that catalyze the final biosynthetic step to produce bioactive GAs. The newly isolated GA4H gene was expressed predominantly during seed germination. We show that expression of both GA4 and GA4H genes in imbibed seeds was induced within 1 hr after a brief red (R) light treatment. In the phytochrome B–deficient phyB-1 mutant, GA4H expression was not induced by R light, but GA4 expression still was, indicating that R light–induced GA4 and GA4H expression is mediated by different phytochromes. In contrast to the GA4 gene, the GA4H gene was not regulated by the feedback inhibition mechanism in germinating seeds. Our data demonstrate that expression of GA 3β-hydroxylase genes is elevated by R light, which may result in an increase in biosynthesis of active GAs to promote seed germination. Furthermore, our results suggest that each GA 3β-hydroxylase gene plays a unique physiological role during light-induced seed germination.
Computation of Smooth Optical Flow in a Feedback Connected Analog Network

In 1986, Tanner and Mead [1] implemented an interesting constraint satisfaction circuit for global motion sensing in a VLSI. We report here a new and improved a VLSI implementation that provides smooth optical flow as well as global motion in a two dimensional visual field. The computation of optical flow is an ill-posed problem, which expresses itself as the aperture problem. However, the optical flow can be estimated by the use of regularization methods, in which additional constraints are introduced in terms of a global energy functional that must be minimized . We show how the algorithmic constraints of Hom and Schunck [2] on computing smooth optical flow can be mapped onto the physical constraints of an equivalent electronic network.
Assessment and treatment of physical health problems among people with schizophrenia: national cross-sectional study.

BACKGROUND In the UK and other high-income countries, life expectancy in people with schizophrenia is 20% lower than in the general population. AIMS To examine the quality of assessment and treatment of physical health problems in people with schizophrenia. Method Retrospective audit of records of people with schizophrenia or schizoaffective disorder aged ⩾18. We collected data on nine key aspects of physical health for 5091 patients and combined these with a cross-sectional patient survey. RESULTS Body mass index was recorded in 2599 (51.1%) patients during the previous 12 months and 1102 (21.6%) had evidence of assessment of all nine key measures. Among those with high blood sugar, there was recorded evidence of 53.5% receiving an appropriate intervention. Among those with dyslipidaemia, this was 19.9%. Despite this, most patients reported that they were satisfied with the physical healthcare they received. CONCLUSIONS Assessment and treatment of common physical health problems in people with schizophrenia falls well below acceptable standards. Cooperation and communication between primary and secondary care services needs to improve if premature mortality in this group is to be reduced.
Auditory and Cognitive Deficits Associated with Acquired Amusia after Stroke: A Magnetoencephalography and Neuropsychological Follow-Up Study

Acquired amusia is a common disorder after damage to the middle cerebral artery (MCA) territory. However, its neurocognitive mechanisms, especially the relative contribution of perceptual and cognitive factors, are still unclear. We studied cognitive and auditory processing in the amusic brain by performing neuropsychological testing as well as magnetoencephalography (MEG) measurements of frequency and duration discrimination using magnetic mismatch negativity (MMNm) recordings. Fifty-three patients with a left (n = 24) or right (n = 29) hemisphere MCA stroke (MRI verified) were investigated 1 week, 3 months, and 6 months after the stroke. Amusia was evaluated using the Montreal Battery of Evaluation of Amusia (MBEA). We found that amusia caused by right hemisphere damage (RHD), especially to temporal and frontal areas, was more severe than amusia caused by left hemisphere damage (LHD). Furthermore, the severity of amusia was found to correlate with weaker frequency MMNm responses only in amusic RHD patients. Additionally, within the RHD subgroup, the amusic patients who had damage to the auditory cortex (AC) showed worse recovery on the MBEA as well as weaker MMNm responses throughout the 6-month follow-up than the non-amusic patients or the amusic patients without AC damage. Furthermore, the amusic patients both with and without AC damage performed worse than the non-amusic patients on tests of working memory, attention, and cognitive flexibility. These findings suggest domain-general cognitive deficits to be the primary mechanism underlying amusia without AC damage whereas amusia with AC damage is associated with both auditory and cognitive deficits.
Iteration in Systems Analysis and Design: Cognitive Processes and Representational Artifacts

The idea of iteration is inherent to systems analysis and design methodologies and practices. In this essay we explore the notion of iteration, and distinguish two dimensions of iteration: iterations inherent in cognitive processes and iterations over representational artifacts. Cognitive iterations can be concerned with the design; the design process; or stages within the design process. Representational artifacts can take the form of documentation or the software code itself. We identify and discuss the promise of âiterative developmentâ and compare this promise to empirical findings on the effects of iterative methods. The findings are generally consistent with expected outcomes. We conclude with an observation that the difference between âiterative developmentâ and more traditional methodologies lies not in the presence of iteration, but in the locus of visibility and control, and the associated timing and granularity.
Inadequate use of asthma medication in the United States: results of the asthma in America national population survey.

BACKGROUND Studies of the use of anti-inflammatory asthma therapy have been limited to selected populations or have been unable to assess the appropriateness of therapy for individuals. OBJECTIVE We sought to describe the current use of asthma medication in the United States population and to examine the influence of symptoms and sociodemographics on medication use. METHODS This study was based on a cross-sectional, national, random-digit-dial household telephone survey in 1998 designed to identify adult patients and parents of children with current asthma. Respondents were classified as having current asthma if they had a physician's diagnosis of asthma and were either taking medication for asthma or had asthma symptoms during the past year. RESULTS One or more persons met the study criteria for current asthma in 3273 (7.8%) households in which a screening questionnaire was completed. Of these, 2509 persons (721 children <16 years) with current asthma were interviewed. Current use of anti-inflammatory medication was reported by 507 (20.1%). Of these, most were using inhaled corticosteroids (72.5%), with use of antileukotrienes reported by 11.4% and use of cromolyn-nedocromil reported by 18.6%. Of persons with persistent asthma symptoms in the past month, 26.2% reported current use of some form of anti-inflammatory medication. In bivariate analysis persons reporting lower income, less education, and present unemployment, as well as smokers, were significantly (P <.001) less likely to report current anti-inflammatory use than were other populations. In a multiple regression model nonsmokers and those of white, non-Hispanic ethnicity, as well as persons reporting less asthma control, were more likely to report current anti-inflammatory medication use. CONCLUSION In the United States use of appropriate asthma therapy remains inadequate. Strategies to increase use of anti-inflammatory therapy among patients with asthma are needed. These might include methods to increase access to asthma care for minorities and the socioeconomically disadvantaged.
Tegaserod for Female Patients Suffering From IBS With Mixed Bowel Habits or Constipation: A Randomized Controlled Trial

OBJECTIVES:Though the greatest proportion of irritable bowel syndrome (IBS) patients report a mixed bowel pattern (IBS-Mixed), no available therapies have been rigorously evaluated in this subgroup. This study aimed to evaluate the efficacy and safety of the 5-HT4 agonist tegaserod in women with IBS-Mixed and IBS with constipation (IBS-C). METHODS:This prospective, double-blind, randomized, placebo-controlled, multicenter study was conducted in 100 centers in North America, South America, and Europe. Women with IBS-Mixed or IBS-C received tegaserod 6 mg or placebo twice daily. The primary efficacy variable was the patient's assessment of satisfactory relief over the 4-wk treatment period. The proportion of patients reporting satisfactory relief for ≥3 of 4 treatment weeks (75% rule) and individual IBS symptoms were assessed.RESULTS:In total, 661 women were randomized (IBS-Mixed 324, IBS-C 337). Baseline symptom assessments identified clear differences between the two cohorts. Tegaserod provided significant improvement in satisfactory relief of IBS symptoms over 4 wk (OR 1.75, 95% CI 1.35–2.25, P < 0.001) in both IBS-Mixed and IBS-C patients. Using the 75% rule, 52.3% of tegaserod-receiving IBS-M patients and 43.3% of IBS-C patients were responders (vs 36.3, OR 1.88, 95% CI 1.16–3.04, P < 0.010; and 28.9, OR 1.90, 95% CI 1.19–3.05, P < 0.008 for placebo, respectively). The most frequent adverse events leading to study discontinuation in tegaserod-treated patients were diarrhea (1.5%) and abdominal pain (0.9%). Overall 7% of IBS-C patients reported diarrhea compared to 12% of IBS-Mixed (placebo 2.4%, 1.8%, respectively). CONCLUSIONS:Tegaserod is effective in treating overall IBS symptoms in patients with IBS-Mixed and IBS-C.
Chimeras in Two-Dimensional Domains: Heterogeneity and the Continuum Limit

We consider three different two-dimensional networks of nonlocally coupled heterogeneous phase oscillators. These networks were previously studied with identical oscillators, and a number of spatiotemporal patterns were found, mostly as a result of direct numerical simulation. Here we take the continuum limit of an infinite number of oscillators and use the Ott--Antonsen ansatz to derive continuum level evolution equations for order parameter--like quantities. Most of the patterns previously found in these networks correspond to relative fixed points of these evolution equations, and we show the following results of extensive numerical investigations of these fixed points: their existence and stability, and the bifurcations involved in their loss of stability as parameters are varied. Our results answer a number of questions posed by previous authors who studied these networks, and provide a better understanding of these networks' dynamics.