Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic behavior of hepatitis C virus quasispecies in patients undergoing orthotopic liver transplantation

We have studied the distribution of viral sequences from the 5' noncoding region and from a fragment of the E2/NS2 region of the hepatitis C virus (HCV) genome in samples obtained before and after liver transplantation in two patients with HCV cirrhosis. The population of viral sequences in both regions were established by sequencing cloned PCR products. In both cases, the complexity of the viral quasispecies decreased after transplantation, although the consensus nucleotide and amino acid sequences remained unchanged. It is suggested that both positive and negative selection and random sampling events contribute substantially in shaping the genetic composition of HCV quasispecies and that recurrence of HCV infection may occur under equilibrium conditions.
Low‐frequency trains of paired stimuli induce long‐term depression in area CA1 but not in dentate gyrus of the intact rat

We have examined the efficacy of a recently introduced protocol for inducing homosynaptic long‐term depression (LTD) in area CA1 of the anesthetized rat (Thiels et al. [1994] J Neurophysiol 72:3009–3116.). In area CA1 of the awake animal, this protocol, consisting of 200 pairs of pulses delivered at 0.5 Hz, with an interpulse interval of 25 ms, consistently produced LTD, provided the initial pulse was sufficiently strong to produce significant paired‐pulse depression of the evoked response. We extended these experiments to the dentate gyrus, using either paired pulses given to the perforant path in the awake adult rat, or, in the anesthetized adult, a two‐pathway pairing procedure, in which the first pulse was delivered to the commissural input to the dentate gyrus and the second to the perforant path. In both cases, the first pulse led to substantial suppression of the response evoked by the second pulse. With neither protocol, however, was there any evidence for LTD or depotentiation. Paired‐pulse stimulation of the perforant path of young rats (10–11 days) also failed to induce LTD or depotentiation of the population excitatory postsynaptic potential (EPSP). Thus, the dentate gyrus in the intact animal appears to be less susceptible to LTD and depotentiation than area CA1, a conclusion consistent with previous experiments in which we found that stimulation at 1–5 Hz produced LTD/depotentiation in area CA1 of young (but not adult) rats in vivo but was ineffective at any age in the dentate gyrus. Our results do not rule out the possibility that other, untested protocols may produce homosynaptic LTD and/or depotentiation in the dentate gyrus in vivo. © 1996 Wiley‐Liss, Inc.
Women, Men, and Leadership: A Critical Review of Assumptions, Practices, and Change in the Industrialized Nations

Our purpose here is to review critically the roles of women and men as leaders, with particular reference to the assumptions that have been promoted, but are changing, within the literature and practice of leadership in the industrialized nations. In discussing this we are concerned not with women and men in biological terms, but rather with the social construction of women and men as genders. Thus, although the social and biological demands on women are different from those on men (for example, in their functions as mothers), we do not assume that women's and men's roles are fixed and not subject to change. "Women" and "men" and femininity and masculinity are socially and culturally produced and vary with the society and the social context.
Recent Advances in Silicon Waveguide Devices Using Sub-Wavelength Gratings

As most integrated optics platforms, silicon offers only a fixed set of material refractive indices for designing devices. The ability of sub-wavelength patterned structures to synthesize arbitrary equivalent index values between nSi ~ 3.5 and nair=1 has thus enabled completely new design approaches that have led to silicon waveguide devices with breakthrough performance. This review covers the latest advances in sub-wavelength structured fiber-to-chip grating couplers and multimode interference couplers. We discuss, among others, single-etch grating couplers with high coupling efficiency ( -1.8 dB), and broad bandwidth ( 115 nm at 3 dB), as well as ultra-short, high performance multi-mode interference couplers. We furthermore introduce the concept of dispersion engineering with sub-wavelength structures, showing its potential to increase the bandwidth of waveguide devices, including multi-mode interference couplers covering a 450 nm wavelength span.
Aspartic Acid Homozygosity at Codon 57 of HLA-DQ β Is Associated with Susceptibility to Pulmonary Tuberculosis in Cambodia1

After infection with Mycobacterium tuberculosis, clinical disease usually remains latent, contained by the host immune response. Although polymorphisms of HLA loci have been hypothesized to play a major role in the breakdown of latency, a functional link has not been established. Molecular-based HLA-typing methods were used to test the association of sets of HLA alleles encoding an aspartic acid at codon 57 of the HLA-DQ β-chain (HLA-DQ β57-Asp) with susceptibility to tuberculosis in a cohort of 436 pulmonary tuberculosis patients and 107 healthy controls from Cambodia. HLA class II null cells were transduced with HLA-DQ β57-Asp or HLA-DQ β57-Ala and evaluated for their ability to bind peptides from two immunogenic M. tuberculosis specific proteins, ESAT-6 and CFP-10. In this study, we report a highly significant association between progressive pulmonary tuberculosis and homozygosity for HLA-DQ β57-Asp alleles. The presence of HLA-DQ β57-Asp resulted in a significantly reduced ability to bind a peptide from the central region of the ESAT-6 protein. Furthermore, when this peptide was presented by an HLA-DQ β57-Asp allele, Ag-specific IFN-γ production from CD4+ T cells from tuberculosis patients was significantly less than when this peptide was presented by an HLA-DQ-β allele encoding an alanine at codon 57. Multiple genetic loci and ethnic-specific factors are likely involved in the human immune response to tuberculosis. The data presented here provide a functional explanation for a highly significant association between an HLA polymorphism and tuberculosis in a highly characterized group of patients with susceptibility to progressive tuberculosis infection in Cambodia.
Distinct quaternary structures of the AAA+ Lon protease control substrate degradation

Significance Lon protease degrades unfolded or damaged proteins as well as numerous cellular regulatory proteins. How these different classes of substrates are recognized is poorly understood. We find that Lon hexamers assemble via a matrix of N-domain interactions to form a dodecamer with altered substrate-degradation properties. Access of protein substrates to the degradation machinery in the dodecamer appears to require passage through equatorial portals. As a consequence, large substrates that are efficiently degraded by hexamers seem to be preferentially excluded from dodecamers. This gating mechanism allows the substrate repertoire of Lon to be adjusted by its assembly state. Lon is an ATPase associated with cellular activities (AAA+) protease that controls cell division in response to stress and also degrades misfolded and damaged proteins. Subunits of Lon are known to assemble into ring-shaped homohexamers that enclose an internal degradation chamber. Here, we demonstrate that hexamers of Escherichia coli Lon also interact to form a dodecamer at physiological protein concentrations. Electron microscopy of this dodecamer reveals a prolate structure with the protease chambers at the distal ends and a matrix of N domains forming an equatorial hexamer–hexamer interface, with portals of ∼45 Å providing access to the enzyme lumen. Compared with hexamers, Lon dodecamers are much less active in degrading large substrates but equally active in degrading small substrates. Our results support a unique gating mechanism that allows the repertoire of Lon substrates to be tuned by its assembly state.
X‐linked imprinting: effects on brain and behaviour

Imprinted genes are monoallelically expressed in a parent‐of‐origin‐dependent manner and can affect brain and behavioural phenotypes. The X chromosome is enriched for genes affecting neurodevelopment and is donated asymmetrically to male and female progeny. Hence, X‐linked imprinted genes could potentially influence sexually dimorphic neurobiology. Consequently, investigations into such loci may provide new insights into the biological basis of behavioural differences between the sexes and into why men and women show different vulnerabilities to certain mental disorders. In this review, we summarise recent advances in our knowledge of X‐linked imprinted genes and the brain substrates that they may act upon. In addition, we suggest strategies for identifying novel X‐linked imprinted genes and their downstream effects and discuss evolutionary theories regarding the origin and maintenance of X‐linked imprinting. BioEssays 28:35–44, 2006. © 2005 Wiley Periodicals, Inc.
Preliminary experience with subcutaneous human ovarian cortex transplantation in the NOD-SCID mouse.

Xenogeneic transplantation of ovarian cortex into an immunodeficient animal host may be an approach toward fertility preservation for young female patients undergoing cancer therapy. Our objective was to evaluate the development of follicles in human ovarian cortex placed s.c. in non-obese diabetic-severe combined immune deficiency (NOD-SCID) mice (n = 54). The following variables were compared: 1) male versus female mice as hosts, 2) intact versus pituitary down-regulated mice, and 3) warm versus cold tissue transport. After 2 wk, 37 of 50 (74%) of the human xenografts contained follicles. At 12 wk after transplantation, exogenous gonadotropin stimulation resulted in follicle growth in 19 of 37 (51%) of the grafts, including the development of antral follicles, which could be palpated and visualized through the mouse skin. Significantly more developing follicles were identified in male versus female mice (13 of 17 vs. 6 of 20, respectively; p = 0.013) after stimulation. No difference was found between intact and pituitary down-regulated mice as hosts. Follicular survival was significantly increased by warm versus cold tissue transport. Our results suggest that s.c. ovarian cortex xenografting into NOD-SCID mice is feasible. Primordial follicles in ovarian xenografts retain their developmental potential and form antral follicles following gonadotropin stimulation.
Knockdown of mineralocorticoid or angiotensin II type 1 receptor gene expression in the paraventricular nucleus prevents angiotensin II hypertension in rats

Chronic subcutaneous infusion of Ang II causes a progressive increase in blood pressure (BP) associated with significant increases in angiotensin type 1 receptor (AT1R) and mineralocorticoid receptor (MR) expression in hypothalamic nuclei. Intra‐paraventricular nucleus (PVN) infusion of AAV‐ AT1aR‐siRNA or of AAV‐MR‐siRNA markedly knockdown AT1a‐R or MR expression in the PVN but not in the subfornical organ; or supraoptic nucleus, and prevent most of the increase in BP. These findings indicate that increased MR and AT1R activation in the PVN play a critical role in Ang II‐induced hypertension in rats on regular salt intake.
Extending influenza vaccination to individuals aged 50–64: A budget impact analysis

Objectives: Influenza (vernacular name, flu) is a viral infection that causes a high consumption of resources. Several studies have been carried out to provide an economic evaluation of the vaccination programs against influenza. Nevertheless, there is still a lack of evidence about the dynamic effects resulting from the reduction of the transmission power. This study considers the impact on contagiousness of alternative strategies against influenza in people aged 50–64 in Italy, France, Germany, and Spain. Methods: By using the Influsim 2.0 dynamic model, we have determined the social benefits of different coverage levels in every country compared with the ones currently recommended. We have subsequently performed a Budget Impact Analysis to determine whether the currently recommended coverage results from an optimal budget allocation. A probabilistic sensitivity analysis was also conducted. Results: We found that in Germany, the optimal coverage level is 38.5 percent, in France 32.4 percent, in Italy 32.75 percent, and 28.3 percent in Spain. By extending the coverage level, social saving tends to increase up to 100 percent for France and Italy and up to 80 percent for Germany and Spain. Conclusions: Decision makers should allocate the budget for vaccination against influenza consistently with the estimation of the optimal coverage level and with the dynamic effects resulting from the reduction of the transmission power.
Evidence of Autoinducer-Dependent and -Independent Heterogeneous Gene Expression in Sinorhizobium fredii NGR234

ABSTRACT Populations of genetically identical Sinorhizobium fredii NGR234 cells differ significantly in their expression profiles of autoinducer (AI)-dependent and AI-independent genes. Promoter fusions of the NGR234 AI synthase genes traI and ngrI showed high levels of phenotypic heterogeneity during growth in TY medium on a single-cell level. However, adding very high concentrations of N-(3-oxooctanoyl-)-l-homoserine lactone resulted in a more homogeneous expression profile. Similarly, the lack of internally synthesized AIs in the background of the NGR234-ΔtraI or the NGR234-ΔngrI mutant resulted in a highly homogenous expression of the corresponding promoter fusions in the population. Expression studies with reporter fusions of the promoter regions of the quorum-quenching genes dlhR and qsdR1 and the type IV pilus gene cluster located on pNGR234b suggested that factors other than AI molecules affect NGR234 phenotypic heterogeneity. Further studies with root exudates and developing Arabidopsis thaliana seedlings provide the first evidence that plant root exudates have strong effects on the heterogeneity of AI synthase and quorum-quenching genes in NGR234. Therefore, plant-released octopine appears to play a key role in modulation of heterogeneous gene expression.
Cognitive-behavioral therapy for adolescent depression: a meta-analytic investigation of changes in effect-size estimates.

OBJECTIVE To explicate differences between early and recent meta-analytic estimates of the effects of cognitive-behavioral therapy (CBT) for adolescent depression. METHOD Meta-analytic procedures were used to investigate whether methodological characteristics moderated mean effect sizes among 11 randomized, controlled trials of CBT focusing on adolescents meeting diagnostic criteria for unipolar depression. RESULTS Cumulative meta-analyses indicated that effects of CBT have decreased from large effects in early trials, and confidence intervals have become narrower. Effect sizes were significantly smaller among studies that used intent-to-treat analytic strategies, compared CBT to active treatments, were conducted in clinical settings, and featured greater methodological rigor based on CONSORT (Consolidated Standards of Reporting Trials) criteria. The mean posttreatment effect size of 0.53 was statistically significant. CONCLUSIONS Differences in estimates of the efficacy of CBT for depressed adolescents may stem from methodological differences between early and more recent investigations. Overall, results support the effectiveness of CBT for the treatment of adolescent depression.
Learning how to inform extension practices related to mandatory agri-environmental policy

Despite the existence and application of mandatory agri-environmental policy for many decades, significant environmental sustainability issues remain attributable to the agricultural sector. Participatory types of extension practices seem to have a potential for assisting extension organisations to enhance the supports provided to farmers in relation to meeting the requirements of these policies. To test this idea, this thesis used a learning process approach for exploring the interplay between farmer subjectivities, the European Union’s policy of cross compliance and the extension practices of Teagasc, the Agriculture and Food Development Authority of the Republic of Ireland. Three learning sub-systems were employed in the investigation. The first used the principles of Participatory Action Research for revealing stakeholders’ perceptions of Teagasc’s cross compliance extension service. This process resulted in the attainment of rich insights about extension practices, however it also revealed that a significant number of farmers were experiencing social difficulties with the application and enforcement of cross compliance. To better understand the implications of these subjectivities, a second sub-system was created to learn about farmers’ experiences of the policy. This process surfaced diverse insights about farmers’ personal experiences of cross compliance. A final sub-system employed systems thinking and practice for appraising the utility of the learning arising from the previous sub-systems for improving interactions between farmers, extension organisations and cross compliance. The combined findings suggest a considerable potential for extension organisations to use participatory practices for developing rich understandings of farmers’ preferences for mandatory agri-environmental policy and its related extension practices. A limitation in realising participant preferences is that extension organisations have little influence over the application and enforcement of mandatory agri-environmental policy. Overcoming this participatory barrier will require continued collective learning targeted at understanding how stakeholders can work together to develop agri-environmental policies that are socially, financially and environmentally sustainable.
Bayesian Random Vector Functional-Link Networks for Robust Data Modeling

Random vector functional-link (RVFL) networks are randomized multilayer perceptrons with a single hidden layer and a linear output layer, which can be trained by solving a linear modeling problem. In particular, they are generally trained using a closed-form solution of the (regularized) least-squares approach. This paper introduces several alternative strategies for performing full Bayesian inference (BI) of RVFL networks. Distinct from standard or classical approaches, our proposed Bayesian training algorithms allow to derive an entire probability distribution over the optimal output weights of the network, instead of a single pointwise estimate according to some given criterion (e.g., least-squares). This provides several known advantages, including the possibility of introducing additional prior knowledge in the training process, the availability of an uncertainty measure during the test phase, and the capability of automatically inferring hyper-parameters from given data. In this paper, two BI algorithms for regression are first proposed that, under some practical assumptions, can be implemented by a simple iterative process with closed-form computations. Simulation results show that one of the proposed algorithms, Bayesian RVFL, is able to outperform standard training algorithms for RVFL networks with a proper regularization factor selected carefully via a line search procedure. A general strategy based on variational inference is also presented, with an application to data modeling problems with noisy outputs or outliers. As we discuss in this paper, using recent advances in automatic differentiation this strategy can be applied to a wide range of additional situations in an immediate fashion.
Medial Impingement Syndrome of the Anterior Tibiotalar Fascicle of the Deltoid Ligament on the Talus

Eleven patients with medial impingement syndrome of the anterior tibio-talar fascicle (ATTF) of the deltoid ligament on the talus were identified. Six sustained inversion injuries, one talus and four ankle fractures. The mean preoperative Ankle-Hindfoot Scale (AHS) was 56 and the postoperative was 87. Surgical debridement of the ATTF was performed. A thickened ATTF and localized synovitis were seen. Talar osteophytes were removed in 8 patients. Mean follow up 4 years. Nine patients had good to excellent results and all patients returned to work.
Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow’s milk allergy in toddlers

Abstract Background: Food allergy is a common problem in France involving 4%–6% of toddlers. As opposed to IgE-mediated cow’s milk allergy (CMA), delayed-onset CMA, mostly, non-IgE-mediated, remains difficult to diagnose in toddlers. Our study assessed the diagnostic performances of intestinal permeability and of fecal markers, in comparison with the standard allergic work-up in children referred for CMA diagnosis. Methods: Twenty-five consecutive children, mean age (standard deviation) 6.3 months (4.8) with digestive and/or extra-digestive manifestations suggesting CMA, were prospectively studied based on a standardized allergic work-up (specific cow’s protein IgE and IgG, skin prick test, atopy patch test and oral open cow’s milk challenge) and digestive work-up including fecal microbiota analysis, intestinal permeability determination (urinary lactitol/mannitol ratio) and fecal markers measurement, i.e., α1-antitrypsin, tumor necrosis factor-α, calprotectin, β-defensin2, secretory IgA and eosinophil-derived neurotoxin (EDN). Receiver operating characteristic (ROC) curves were calculated for all markers in order to define cut-off levels. Results: The cow’s milk challenge was positive in 11 children and negative in 14. The global test performances, i.e., the number of true positive+negative cases/the total number of cases, were 76% for intestinal permeability; 72% for fecal EDN; contrasting with atopy patch test, 68%; IgE, 60%; skin prick test, 55% and IgG, 52%. Conclusions: In this routine diagnosis allergy work-up for CMA in toddlers, the best efficacy was seen for intestinal permeability compared to IgE, IgG, skin prick test and atopy patch test. Moreover, fecal EDN in a single spot sample displayed a similar performance.
High prevalence of hypertension among an ethnic group in Sudan: implications for prevention

Abstract Objective Hypertension is an emerging non-communicable disease in developing countries. Due to its silent nature and serious complications, active screening is essential in order to prevent complications. For instance, premature mortality from cardiovascular diseases could be prevented by the effective control of hypertension. The aim of this study was to determine the prevalence of undiagnosed hypertension among Nuba ethnic group living in Atbara city, north Sudan and to identify the associated risk factors. Subject and methods All consenting 500 adults from Nuba tribe who live in El Wihda District, Atbara were included. Blood pressure (BP) and body mass index were measured. Standard interviewing procedures were used to record medical history, socio-demographic data, and lifestyle characteristics. Results Among the 500 participants, females were 364 (72.8%) and males were 136 (27.2%). The overall prevalence of undiagnosed hypertension was 49.4% (30.8% stage 1 hypertension and 18.6% stage 2 hypertension). In addition, 41% of the population was having prehypertension. The significant risk factors for high BP were: male sex, age above 45 years, overweight, illiteracy, and alcohol consumption. Conclusion Undiagnosed high BP is very common among Nuba ethnic group; therefore, active screening and early management are recommended to prevent complications.
Nanoliter-Droplet Acoustic Streaming via Ultra High Frequency Surface Acoustic Waves

The relevant length scales in sub-nanometer amplitude surface acoustic wave-driven acoustic streaming are demonstrated. We demonstrate the absence of any physical limitations preventing the downscaling of SAW-driven internal streaming to nanoliter microreactors and beyond by extending SAW microfluidics up to operating frequencies in the GHz range. This method is applied to nanoliter scale fluid mixing.