Miracle-dz/UniFAR-FTUs huggingface dataset:
Dose adjustment of the non-nucleoside reverse transcriptase inhibitors during concurrent rifampicin-containing tuberculosis therapy: one size does not fit all

Importance of the field: HIV/tuberculosis (TB) co-infection is common and associated with high mortality. Simultaneous highly active antiretroviral therapy during TB treatment is associated with substantial survival benefit but drug–drug interactions complicate NNRTI dosing. Areas covered in this review: We reviewed the impact of rifampicin-containing TB therapy on the NNRTIs pharmacokinetics and clinical outcome. PubMed database was searched from 1966 to July 2009 using the terms efavirenz, rifampicin, nevirapine, pharmacokinetics, pharmacogenetics, HIV, TB, CYP2B6, CYP3A4 and metabolism. References from identified articles and abstracts from meetings were also reviewed. What the reader will gain: A comprehensive review of the literature on this subject including pharmacokinetic and clinical studies. Most studies were small, observational or underpowered to detect the true effect of rifampicin on NNRTI-based therapy. None of the studies were controlled for genetic factors and there were limited data on children. Take home message: There were insufficient data to make definitive recommendations about dose adjustment of the NNRTIs during rifampin-containing therapy. Current data suggest that the standard dose of efavirenz or nevirapine is adequate in most HIV/TB co-infected adults. However, more research is needed in pediatric populations as well as to define role of drug–gene interactions.
The effects of the aromatase inhibitor anastrozole on bone metabolism and cardiovascular risk indices in ovariectomized, androgen-treated female-to-male transsexuals.

OBJECTIVE Cases of men with estrogen resistance and aromatase deficiency have highlighted the effects of estrogens on bone metabolism, the cardiovascular system and biochemical variables of the metabolic syndrome. In eugonadal men, administration of an aromatase inhibitor induces a substantial elevation of LH and testosterone due to the decreased negative-feedback signal of estrogen and may thwart the interpretation of results. As there is no gonad for LH to act on, no increase of serum testosterone concentration will be seen in female-to-male transssexuals. The aim of this study was to investigate the effects of estrogen deprivation on bone metabolism and vascular parameters without the interference of counter-regulatory effects as seen in eugonadal men. DESIGN Thirty ovariectomized female-to-male transsexuals participated in this double-blind, randomized trial. During 3 months, subjects received the aromatase inhibitor anastrozole 1 mg/day (n = 16) or a placebo (n = 14) in addition to parenteral testosterone esters (Sustanon 250 every 2 weeks). RESULTS Serum 17beta-estradiol (E(2)) concentration fell significantly from 134.0 +/- 78.8 to 77.7 +/- 130.6 pmol/l compared with placebo (P < 0.01). LH and FSH levels rose without the rise of testosterone levels observed in eugonadal men. Within the placebo group, E(2) remained at baseline levels. Of the endpoint variables measured (bone metabolism and vascular parameters) no significant changes were observed compared with placebo, or within the anastrozole-treated group. CONCLUSIONS These results may indicate that the negative effects of estrogen deprivation in men only become manifest when the concentration falls below the levels induced by our intervention with anastrozole (77 pmol/l). This assumption is supported by the observation in the anastrozole group that, although effects of the reduction of serum E(2) on vascular parameters could not be demonstrated in subjects as a group, there was a correlation between individual serum E(2) and several vascular parameters.
Diagnostic devices as biomaterials: a review of nucleic acid and protein microarray surface performance issues

This review of current DNA and protein microarray diagnostic and bio-analytical technologies focuses on the different surface chemistries used in these miniaturized surface-capture formats. Description of current strategies in bio-immobilization and coupling to create multiplexed affinity bioassays in micrometer-sized printed spots, problems with current formats and review of some detection methods are included. Recommendations for improving long-standing challenges in DNA- and protein-based arrays are forwarded. The biomaterials community can contribute relevant expertise to these formidable bio-interfacial problems that represent significant barriers to clinical implementation of microarray assays.
OUTWARD FDI FROM INDIA – ARE THERE ANY LESSONS FOR OTHER DEVELOPING COUNTRIES ?

The nineties onwards has witnessed strong economic performance and outward FDI from a number of developing countries including India. Until now literature has tried to explain the factors influencing outward investment from developed countries perspective. It is difficult to construe how the factors influencing outward investment from developed countries would explain the behaviour of developing countries multinationals. Under this backdrop, this study contributes to the literature by carrying out the analysis for India, to see a) what determines the choice between joint venture (JV) and wholly-owned subsidiary (WOS) for firms from developing country; and b) whether the factors are different than the one for the developed country foreign firms. The analysis is carried out on a sample of 250 entries (88 WOS and 162 JVs) made by 142 Indian manufacturing firms during 1992 to 1999. The analysis indicates that a number of transaction specific variables explain Indian firms’ outward investment. Size, age and experience influenced entry choice in more developed countries, whereas building of both upstream and downward capabilities is found crucial for firms investing in relatively underdeveloped countries. Based on results, the paper argues that if other developing countries especially in South Asian and African region wish to increase the south-south FDI inflow, they need to focus on improving the institutional structure that would enhance the status of their country index.
Opportunistic Routing in Multi-Sink Mobile Ad Hoc Wireless Sensor Networks

This thesis introduces the opportunistic routing and analyses a new algorithm for Wireless Sensor Networks a new routing technique for ad hoc mobile multi-hop wireless networks. The routing algorithm is created based on a mobility scenario. The network consists of multiple nodes and multiple sinks. All of them are mobile. A source node generates data packets, which must be routed to the nearest sink. Sinks send high power periodic beacon packets. When nodes move, the received signal strength of the received beacon packet changes. Nodes calculate their mobility direction according to this difference of power levels. Then these beacons are forwarded to the neighbour nodes with normal power. Data packets are routed according to the obtained mobility information, such as mobility gradient, neighborhood availability. According to this knowledge, an efficient direction of data packet routing is predicted. Decision is done by every node which participates in the routing process. In other words, each node evaluates the opportunity of packet handling to the neighbour nodes. The opportunistic routing algorithm is implemented and simulated in the OPNET simulator. The model is built on top of a partly implemented IEEE 802.15. 4 model. Implementation of non-beacon, unslotted CSMA/CA medium access layer is part of this work. The comparison of results is done with respect to the AODV routing protocol. An AODV model was implemented as hybrid structure of IEEE 802.15. 4 MAC and AODV routing over IP. The scope of the analysis is energy consumption, end-to-end delays and goodput of the opportunistic routing protocol.
Social Media as a Sentinel for Disease Surveillance: What Does Sociodemographic Status Have to Do with It?

Introduction: Data from social media have been shown to have utility in augmenting traditional approaches to public health surveillance. Quantifying the representativeness of these data is needed for making accurate public health inferences. Methods: We applied machine-learning methods to explore spatial and temporal dengue event reporting trends on Twitter relative to confirmed cases, and quantified associations with sociodemographic factors across three Brazilian states (São Paulo, Rio de Janeiro, and Minas Gerais) at the municipality level. Results: Education and income were positive predictors of dengue reporting on Twitter. In contrast, municipalities with a higher percentage of older adults, and males were less likely to report suspected dengue disease on Twitter. Overall, municipalities with dengue disease tweets had higher mean per capita income and lower proportion of individuals with no primary school education. Conclusions: These observations highlight the need to understand population representation across locations, age, and racial/ethnic backgrounds in studies using social media data for public health research. Additional data is needed to assess and compare data representativeness across regions in Brazil.
The Licensing Act 2003, five years on: taking stock and stumbling into the future

This paper will reflect on the impact of the Licensing Act 2003 (LA03). It will focus primarily on how the LA03 has been introduced to, and has influenced, the night‐time economy (NTE). More specifically, it will examine the impact of the LA03 on alcohol‐related crime, disorder and harm to health, within an urban context. It will review the evidence base for the impact of the LA03, suggesting reasons why the UK experience of extended trading hours is not consistent with international evidence. It will examine the mixed findings from evaluations as to its success/failures/limited influence, and discuss its impact on a number of organisations involved in the promotion and safety of the NTE. It will highlight the continued struggles encountered within the NTE, between the promotion of an enjoyable and profitable NTE, and those who have responsibility for maintaining a safe NTE environment. It will also discuss potential extraneous factors that have superseded the LA03, before concluding by offering and discussing some possible avenues for future direction.
Recherches collaboratives et constructivisme pragmatique : éclairages pratiques

Cet article apporte des eclairages pratiques sur une maniere rigoureuse de conduire une recherche collaborative destinee a elaborer des savoirs academiques pertinents pour la pratique gestionnaire. Ces eclairages valent plus particulierement dans le paradigme epistemologique constructiviste pragmatique et dans le cadre methodologique qu'offre le modele dialogique. Les demarches associees aux cinq etapes de ce modele sont precisement explicitees et illustrees par des exemples tires d'un projet de recherche mene dans une industrie nouvellement reglementee. Les reperes proposes integrent des elements de methodes qualitatives existantes en justifiant systematiquement leur utilisation en regard du contexte epistemologique considere.
Genetic Screening and Functional Characterization of PDGFRB Mutations Associated with Basal Ganglia Calcification of Unknown Etiology

Three causal genes for idiopathic basal ganglia calcification (IBGC) have been identified. Most recently, mutations in PDGFRB, encoding a member of the platelet‐derived growth factor receptor family type β, and PDGFB, encoding PDGF‐B, the specific ligand of PDGFRβ, were found implicating the PDGF‐B/PDGFRβ pathway in abnormal brain calcification. In this study, we aimed to identify and study mutations in PDGFRB and PDGFB in a series of 26 patients from the Mayo Clinic Florida Brain Bank with moderate to severe basal ganglia calcification (BCG) of unknown etiology. No mutations in PDGFB were found. However, we identified one mutation in PDGFRB, p.R695C located in the tyrosine kinase domain, in one BGC patient. We further studied the function of p.R695C mutant PDGFRβ and two previously reported mutants, p.L658P and p.R987W PDGFRβ in cell culture. We show that, in response to PDGF‐BB stimulation, the p.L658P mutation completely suppresses PDGFRβ autophosphorylation, whereas the p.R695C mutation results in partial loss of autophosphorylation. For the p.R987W mutation, our data suggest a different mechanism involving reduced protein levels. These genetic and functional studies provide the first insight into the pathogenic mechanisms associated with PDGFRB mutations and provide further support for a pathogenic role of PDGFRB mutations in BGC.
The ABACOC Algorithm: A Novel Approach for Nonparametric Classification of Data Streams

Stream mining poses unique challenges to machine learning: predictive models are required to be scalable, incrementally trainable, must remain bounded in size, and benon parametric in order to achieve high accuracy even in complex and dynamic environments. Moreover, the learning system must be parameterless - traditional tuning methods are problematic in streaming settings - and avoid requiring prior knowledge of the number of distinct class labels occurring in the stream. In this paper, we introduce a new algorithmic approach for nonparametric learning in data streams. Our approach addresses all above mentioned challenges by learning a model that covers the input space using simple local classifiers. The distribution of these classifiers dynamically adapts to the local (unknown) complexity of the classification problem, thus achieving a good balance between model complexity and predictive accuracy. By means of an extensive empirical evaluation against standard nonparametric baselines, we show state-of-the-art results in terms of accuracy versus model size. Our empirical analysis is complemented by a theoretical performance guarantee which does not rely on any stochastic assumption on the source generating the stream.
Cell Polarity in Cerebral Cortex Development—Cellular Architecture Shaped by Biochemical Networks

The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers. The establishment of specific morphological and physiological features in individual neurons needs to be regulated with high precision. Impairments in the sequential developmental programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture which is thought to represent the major underlying cause for several neurological disorders including neurodevelopmental and psychiatric diseases. In this review article we discuss the role of cell polarity at sequential stages during cortex development. We first provide an overview of morphological cell polarity features in cortical neural stem cells and newly-born postmitotic neurons. We then synthesize a conceptual molecular and biochemical framework how cell polarity is established at the cellular level through a break in symmetry in nascent cortical projection neurons. Lastly we provide a perspective how the molecular mechanisms applying to single cells could be probed and integrated in an in vivo and tissue-wide context.
Input Sparsity and Hardness for Robust Subspace Approximation

In the subspace approximation problem, we seek a k-dimensional subspace F of R<sup>d</sup> that minimizes the sum of p-th powers of Euclidean distances to a given set of n points a<sub>1</sub>,⋯, a<sub>n</sub> ∈ R<sup>d</sup>, for p ≥ 1. More generally than minimizing Σ<sub>i</sub> dist(a<sub>i</sub> F)<sup>p</sup>, we may wish to minimize Σ<sub>i</sub> M(dist(a<sub>i</sub>, F)) for some loss function M(), for example, M-Estimators, which include the Huber and Tukey loss functions. Such subspaces provide alternatives to the singular value decomposition (SVD), which is the p = 2 case, finding such an F that minimizes the sum of squares of distances. For p E [1, 2), and for typical M-Estimators, the minimizing F gives a solution that is more robust to outliers than that provided by the SVD. We give several algorithmic results for these robust subspace approximation problems. We state our results as follows, thinking of the n points as forming an n × d matrix A, and letting nnz(A) denote the number of non-zero entries of A. Our results hold for p ∈ [1, 2). We use poly(n) to denote n<sup>O(1)</sup> as n → ∞. 1) For minimizing Σ<sub>i</sub> dist(a<sub>i</sub>, F)<sup>p</sup>, we give an algorithm running in O(nnz(A) + (n + d)poly(k/ε) + exp(poly(k/ε))) 2) We show that the problem of minimizing Σ<sub>i</sub> dist(a<sub>i</sub>, F)<sup>p</sup> is NP-hard, even to output a (1 + 1/poly(d))-approximation. This extends work of Deshpande et al. (SODA, 2011) which could only show NP-hardness or UGC-hardness for p > 2; their proofs critically rely on p > 2. Our work resolves an open question of [Kannan Vempala, NOW, 2009]. Thus, there cannot be an algorithm running in time polynomial in k and 1/ε unless P = NP. Together with prior work, this implies that the problem is NP-hard for all p ≠ 2. 3) For loss functions for a wide class of M-Estimators, we give a problem-size reduction: for a parameter K = (log n)O(log k), our reduction takes O(nnz(A) logn + (n + d)poly(K/ε)) time to reduce the problem to a constrained version involving matrices whose dimensions are poly(Kε<sup>-1</sup> log n). We also give bicriteria solutions. 4) Our techniques lead to the first O(mmz(A) + poly(d/ε)) time algorithms for (1 + ε)-approximate regression for a wide class of convex M-Estimators. This improves prior results [1], which were (1 + ε)-approximation for Huber regression only, and O(1)-approximation for a general class of M-Estimators.
Investigating the molecular aetiology of Obsessive-compulsive disorder (OCD) and clinically-defined subsets of OCD

Obsessive-compulsive disorder (OCD), a debilitating psychiatric disorder, affects 2-3% of the general population, and represents a global health problem. Evidence from family studies suggests that genetic factors play a role in mediating disease development. However, the pattern of inheritance is not consistent with monogenic disorders, but is “genetically complex”. Case-control association analysis, which facilitates dissection of the genetic aetiology of complex disorders, has yielded many inconsistent results in OCD studies, making identification of predisposing alleles difficult. These discrepant findings can largely be attributed to inappropriate statistical methodology and the lack of OCD phenotypic resolution. Although classified as a single clinical entity according to structured algorithms, OCD probably represents a final common outcome of multiple underlying aetiologies. Thus, numerous clinical subtypes of the disorder have been proposed; these “intermediate” phenotypes may be more closely related to a particular genetic substrate than the higher order construct of OCD. Furthermore, although genes encoding serotonergic (5-HT) and dopaminergic components are most commonly investigated, it is likely that the behavioural manifestations of OCD are mediated by a broader network of interconnected neurotransmitter and signalling pathways. Consequently, the aim of the present study was two-fold: to address the factors that may have confounded previous genetic case-control association studies and to investigate the genetic aetiology of OCD phenotypes while accounting for these factors. Case and control individuals were drawn from the reportedly genetically homogeneous Afrikaner population. However, as no empirical evidence existed to support the absence of genetic substructure, which would confound genetic association studies, a Bayesian modelbased clustering algorithm (Structure), that groups individuals on the basis of observed genotype data, was employed to assess population stratification in both case and control Afrikaner subjects.
Integrating MOOCS into Traditional Higher Education: The Emerging “MOOC 3.0” Era

Change • November/December 2013 Cathy Sandeen (csandeen@acenet.edu) is vice president for education attainment and innovation at the American Council on Education (ACE). She is responsible for the organization’s national strategy to improve postsecondary attainment in the US. She currently oversees a large research project on massive open online courses (MOOCs). By Cathy Sandeen INTEGRATING MOOCS INTO TRADITIONAL HIGHER EDUCATION THE EMERGING “MOOC 3.0” ERA
Genome Sequence of Escherichia coli O157:H7 Strain 2886-75, Associated with the First Reported Case of Human Infection in the United States

ABSTRACT First identified in 1982 as a human pathogen, enterohemorrhagic Escherichia coli of the O157:H7 serotype is a major cause of food-borne acquired human infections. Here, we report the genome sequence of the first known strain of this serotype isolated in the United States.
The effects of drive level errors on optical SSB system performance

This paper presents a system performance analysis of an optical single sideband system (OSSB) when drive level errors occur in the modulating signal driving the dual arm Mach-Zehnder modulator (MZM). The performance is evaluated in terms of the optical sideband suppression, frequency response and power penalty measurements. Experiments are carried out and a mathematical model of the OSSB system incorporating the drive level error is developed. The theoretical and experimental results suggest that the drive level error leads to reduced system performance as a result of poor received subcarrier power. The overall frequency response of the system, which is affected by drive level errors, accumulated CD and subcarrier frequency, has a direct influence over the power penalty. However, reduction in power penalty slope is observed at peaks of the OSSB frequency response.
In Vitro Anti-Inflammatory Effects of Three Fatty Acids from Royal Jelly

Trans-10-hydroxy-2-decenoic acid (10-H2DA), 10-hydroxydecanoic acid (10-HDAA), and sebacic acid (SEA) are the three major fatty acids in royal jelly (RJ). Previous studies have revealed several pharmacological activities of 10-H2DA and 10-HDAA, although the anti-inflammatory effects and underlying mechanisms by which SEA acts are poorly understood. In the present study, we evaluated and compared the in vitro anti-inflammatory effects of these RJ fatty acids in lipopolysaccharide-stimulated RAW 264.7 macrophages. The results showed that 10-H2DA, 10-HDAA, and SEA had potent, dose-dependent inhibitory effects on the release of the major inflammatory-mediators, nitric oxide, and interleukin-10, and only SEA decreased TNF-α production. Several key inflammatory genes have also been modulated by these RJ fatty acids, with 10-H2DA showing distinct modulating effects as compared to the other two FAs. Furthermore, we found that these three FAs regulated several proteins involved in MAPK and NF-κB signaling pathways. Taken together, these findings provide additional references for using RJ against inflammatory diseases.
Comparative toxicity and hazards of pesticides to Apis and non-Apis bees. A chemometrical study

The adverse effects of 158 pesticides to the Honey bee (Apis mellifera), the alfalfa leafcutting bee (Megachile rotundata) and the alkali bee (Nomia melanderi) were compared by means of various linear and non-linear multivariate analyses. A comparison exercise including the bumble bee (Bombus spp.) was also performed from a more restricted set of 32 pesticides. While no difference of sensitivity was found between A. mellifera and Bombus spp. , M. rotundata appeared the most susceptible to pesticides followed by N. melanderi.