Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved survival among HIV-infected individuals following initiation of antiretroviral therapy.

CONTEXT Clinical trials have established the efficacy of antiretroviral therapy with double- and triple-drug regimens for individuals infected with the human immunodeficiency virus (HIV), but the effectiveness of these regimens in the population of patients not enrolled in clinical trials is unknown. OBJECTIVE To characterize survival following the initiation of antiretroviral therapy among HIV-infected individuals in the province of British Columbia. DESIGN Prospective, population-based cohort study of patients with antiretroviral therapy available free of charge (median follow-up, 21 months). SETTING Province of British Columbia, Canada. PATIENTS All HIV-positive men and women 18 years of age or older in the province who were first prescribed any antiretroviral therapy between October 1992 and June 1996 and whose CD4+ cell counts were less than 0.350 x 10(9)/L. MAIN OUTCOME MEASURES Rates of progression from initiation of antiretroviral therapy to death or a primary acquired immunodeficiency syndrome (AIDS) diagnosis for subjects who initially received zidovudine-, didanosine-, or zalcitabine-based therapy (ERA-I) and for those who initially received therapy regimens including lamivudine or stavudine (ERA-II). RESULTS A total of 1178 patients (951 ERA-I, 227 ERA-II) were eligible. A total of 390 patients died (367 ERA-I, 23 ERA-II), yielding a crude mortality rate of 33.1%. ERA-I group subjects were almost twice as likely to die as ERA-II group subjects, with a mortality risk ratio of 1.86 (95% confidence interval [CI], 1.21 -2.86; P=.005). After adjusting for Pneumocystis carinii and Mycobacterium avium prophylaxis use, AIDS diagnosis, CD4+ cell count, sex, and age, ERA-I participants were 1.93 times (95% CI, 1.25-2.97; P=.003) more likely to die than ERA-II participants. Among patients without AIDS when treatment was started, ERA-I participants were 2.50 times (95% CI, 1.59-3.93; P<.001) more likely to progress to AIDS or death than ERA-II participants. CONCLUSION The HIV-infected individuals who received initial therapy with regimens including stavudine or lamivudine had significantly lower mortality and longer AIDS-free survival than those who received initial therapy with regimens limited to zidovudine, didanosine, and zalcitabine.
An approach to localization scheme of wireless sensor networks based on artificial neural networks and Genetic Algorithms

Localization of nodes in wireless sensor networks without the use of GPS is important for applications such as military surveillance, environmental monitoring, robotics, domotics, animal tracking, and many others. Low cost and energy efficient sensors require methods that compute their position using indirect information such as RSSI (Received Signal Strength Indicator). This work presents an artificial neural networks (ANNs) approach to localization in wireless sensor networks through the adjustment of the ANNs structures using Genetic Algorithms. A population of feedforward ANNs containing their structure in a genetic code is evolved during 20 generations. Each individual is evaluated through the training of the artificial neural network and further calculation of its root mean square error for all the testing set. The RSSI measurements were used as the artificial neural networks inputs to localize the nodes. The approach was tested using the MATLAB-based Probabilistic Wireless Network Simulator (Prowler) to collect the artificial neural networks input data, under simulated static indoor network environment of 26×26 meters with 8 anchor nodes, i.e., nodes with awareness of their positions. The MATLAB's genetic algorithms and artificial neural networks toolboxes were used. Results using the best artificial neural network structure found after optimization had a root mean square error of 0.41 meters, a maximum error of 1.07 meters and a minimum error of 0.014 meters.
Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14.

AIM To evaluate the effects of prenatal marijuana exposure (PME) on the age of onset and frequency of marijuana use while controlling for identified confounds of early marijuana use among 14-year-olds. DESIGN In this longitudinal cohort study, women were recruited in their fourth prenatal month. Women and children were followed throughout pregnancy and at multiple time-points into adolescence. SETTING AND PARTICIPANTS Recruitment was from a hospital-based prenatal clinic. The women ranged in age from 18 to 42, half were African American and half Caucasian, and most were of lower socio-economic status. The women were generally light to moderate substance users during pregnancy and subsequently. At 14 years, 580 of the 763 offspring-mother pairs (76%) were assessed. A total of 563 pairs (74%) was included in this analysis. MEASUREMENTS Socio-demographic, environmental, psychological, behavioral, biological and developmental factors were assessed. Outcomes were age of onset and frequency of marijuana use at age 14. PME predicted age of onset and frequency of marijuana use among the 14-year-old offspring. This finding was significant after controlling for other variables including the child's current alcohol and tobacco use, pubertal stage, sexual activity, delinquency, peer drug use, family history of drug abuse and characteristics of the home environment including parental depression, current drug use and strictness/supervision. CONCLUSIONS Prenatal exposure to marijuana, in addition to other factors, is a significant predictor of marijuana use at age 14.
Microbial magnesium transport: unusual transporters searching for identity

Mg2+ is unique among biological cations because of its charge density and solution chemistry. This is abundantly reflected in its transport systems, studied primarily in Salmonella typhimurium. The constitutively expressed CorA transport system is the primary Mg2+ influx pathway for the Bacteria and the Archaea. Its structure of a large N‐terminal soluble periplasmic domain with three transmembrane segments at the C‐terminus is unique among membrane carriers, and its protein sequence bears no resemblance to other known proteins. The MgtE transport system can also mediate Mg2+ uptake, but whether this is its primary function is not known. MgtE also lacks homology to other known proteins. In contrast, the MgtA and MgtB Mg2+ transport systems of enteric bacteria are P‐type ATPases by sequence homology, mediating Mg2+ influx with, rather than against, the Mg2+ electrochemical gradient. They are closely related to mammalian Ca2+‐ATPases. Expression of MgtA and MgtB is under the control of the PhoPQ two‐component regulatory system, important in bacterial virulence. In S. typhimurium, MgtB is encoded by a two‐gene operon mgtCB ; the function of the MgtC protein is unknown, and it lacks close homologues. The ligand for the PhoQ membrane sensor kinase is Mg2+ and, at decreased extracellular Mg2+ concentrations, transcription of mgtA and mgtCB are enormously induced. All three genes are also induced upon S. typhimurium invasion of epithelial or macrophage cells. Mutation of these genes has no effect on invasion efficiency, but an insertion in mgtC renders S. typhimurium essentially avirulent in the mouse. The physiological roles of the known Mg2+ transport systems are not yet completely defined. Nonetheless, the singular sequence and apparent structure of the CorA and MgtE transport proteins, the complex regulation of MgtA, MgtB and MgtC and their involvement in pathogenesis suggests that further study will be rewarding.
Not All Factor Exposures Are Created Equal

Approaches to quantitative equity investing have evolved markedly. Thirty years ago, the focus was on alpha generation, but with the recent decade’s acceptance of smart (alternative) beta, the focus is turning to transparent methods of construction for factor investing. In this article, the authors present an approach for evaluating various methods of portfolio construction that lead to the same factor exposures. Four portfolios are of interest: factor weighted, cap weighted, equal weighted, and risk parity weighted. The authors compare these portfolios based on standard performance statistics as well as new metrics of value-added, such as performance participation rates and portfolio sector concentrations. The results indicate that once the desired factor exposure is achieved, it is beneficial to build the portfolio with the most desirable characteristics in terms of diversification.
Electrical wiring capacity and study of wireless network under desert temperature conditions: A case study

This work presents the analysis of electrical safety for buildings based on IET wiring regulations to decide the conductor size of cable based on ampere carrying capacity under 220–240 V electrical supply. First literature review is carried out with the introduction of significance of power-flow study and re­configuration to understand the voltage-limits from the source to the load point. Then important few 17th wiring regulations discussed during the design of current capacity calculations of conductors for the fixed and varying environmental temperature. Further, the earthing techniques of are analyzed to avoid from electric shock. According to IET regulations, design current (Ib), nominal current (In), perspective current (Iz), short circuit current (Isc) and percentage voltage drop are calculated for the 2-core, “clipped direct” grouped cabling system. The results and discussions are found useful to set the “time of operation” of MCB fuse, which help to protect from electric shock. The, sizes of clipped detect conductors are mapped with opted desert temperature conditions such as 34 0C, 44 0C and 54 0C around the cable using standard wiring regulations. According to the temperate variation, it is found that the significant variation in the conductor size of cables and grouping of cable on wall and wall with thermal insulation of used to connect from source to load. Furthermore, in the second part of this case study, the impact of temperature change in Signal Strength, Data Collection and Localization parameters of a Wireless Sensor Network under same desert temperature conditions are reported.
Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1‐directed internalization

The pharmacological desensitization of receptors is a fundamental mechanism for regulating the activity of neuronal systems. The TRPA1 channel plays a key role in the processing of noxious information and can undergo functional desensitization by unknown mechanisms. Here we show that TRPA1 is desensitized by homologous (mustard oil; a TRPA1 agonist) and heterologous (capsaicin; a TRPV1 agonist) agonists via Ca2+‐independent and Ca2+‐dependent pathways, respectively, in sensory neurons. The pharmacological desensitization of TRPA1 by capsaicin and mustard oil is not influenced by activation of protein phosphatase 2B. However, it is regulated by phosphatidylinositol‐4,5‐bisphosphate depletion after capsaicin, but not mustard oil, application. Using a biosensor, we establish that capsaicin, unlike mustard oil, consistently activates phospholipase C in sensory neurons. We next demonstrate that TRPA1 desensitization is regulated by TRPV1, and it appears that mustard oil‐induced TRPA1 internalization is prevented by coexpression with TRPV1 in a heterologous expression system and in sensory neurons. In conclusion, we propose novel mechanisms whereby TRPA1 activity undergoes pharmacological desensitization through multiple cellular pathways that are agonist dependent and modulated by TRPV1.
Pharmacokinetic variability of voriconazole and N-oxide voriconazole measured as therapeutic drug monitoring

Voriconazole (VRC), a triazole agent is extensively metabolized by CYP2C19, CYP2C9, and to a lesser extent, by CYP3A4. Few data are available regarding disposition of the main VRC metabolite (MVRC; UK121,265). The aim of this study was to investigate the pharmacokinetic variability of VRC and MVRC plasma concentrations on the basis of 115 drug monitoring samples from patients treated with VRC. Plasma concentrations of VRC and MVRC were determined by HPLC assay. During the study period, therapeutic drug monitoring (TDM) of 39 adult in- and out-patients were realized. The residual interquartile range (IQR) were 0.5–2.6 mg/l (median: 1.4 mg/l) for VRC plasma concentrations and 1.6–3.4 mg/l for MVRC (median: 2.5 mg/l). Median IQR metabolic ratio [VRC]/[MVRC] was 0.2–1.1 (median: 0.6 mg/l). VRC Cmin was <1 mg/l in 41% of cases and <0.5 mg/l in 25% of them. Patients with VRC Cmin <1 mg/l have a lower [VRC]/[MVRC] ratio than patients with VRC Cmin ≥1 mg/l (median ratio 0.1 vs. 1.0 p < 0.0001). VRC TDM is now recommended to optimize their benefit/risk ratio. In addition, measurement of MVRC in unstable patients could quickly detect patients with impaired metabolism, in cases of subtherapeutic (Cmin <1 mg/l) or toxic (Cmin >5 mg/l) VRC plasma levels.
The Contribution of Thaler to Behavioural Economics

Richard Thaler was awarded the Nobel Memorial Prize in Economic Sciences in 2017 for his contribution to behavioural economics. The main purpose of behavioural economics is to build a bridge between economic thinking and the results of psychological research. Below, I present the fields where the work of Thaler stands out the most, such as limited rationality, lack of self-control and social preference. In addition, his findings also laid the foundations for behavioural finance. His unwavering, successful and high-standard research over more than forty years has laid the foundations for a number of new research directions, not only in sciences. The elaboration of the theory of libertarian paternalism, among others, is also associated with his name, which has substantially shaped many decision-makers and regulations over the past decade.
Activation mechanisms of the HACI‐mediated unfolded protein response in filamentous fungi

The unfolded protein response (UPR) is a regulatory pathway activating genes involved in multiple functions related to folding, quality control and transport of secreted proteins. Characterization of the hac1/hacA genes encoding the UPR transcription factors from the filamentous fungi Trichoderma reesei and Aspergillus nidulans is described in this article. The corresponding gene in Saccharomyces cerevisiae is activated through a non‐spliceosomal intron‐splicing reaction. The T. reesei hac1 and A. nidulans hacA mRNAs undergo an analogous splicing reaction of a 20‐nt‐long intron during UPR induction. This splicing changes the reading frame of the mRNA and thus could bring in an activation domain to the HACI/HACA proteins. In addition to the non‐spliceosomal splicing, the hac1/A mRNAs of the filamentous fungi are truncated at the 5′‐flanking region upon UPR induction. An upstream open reading frame is omitted from the mRNAs due to the truncation, and evidence is presented showing that the truncated T. reesei hac1 mRNA is translated more efficiently than a full‐length mRNA. This paper reports a novel combination of two different regulatory mechanisms of a transcription factor gene, both operational at the mRNA level.
Work and play take school time away? The impact of extracurricular and work time on educational time for live-at-home college students

ABSTRACT We use data from the 2003–2014 American Time Use Survey to estimate the effects of time allocated to work and extracurriculars on time spent in educational activities (class and homework) for live-at-home college students, who make up a large share of the college population. Our instrumental variables strategy indicates that students are more likely to substitute time away from homework than from class, and that the effects are generally stronger for work than for extracurriculars. These findings, which remain even after correcting for selection on unobservables through non-parametric matching methods, show that work leads to decreases in the amount of time spent in class by 47 min and on homework by 56 min, whereas extracurriculars lead to a loss of 22 min of homework time. Thus, while after-school activities (extracurriculars and work) may be beneficial with respect to human capital development, they may also have a counteracting, unintended effect due to students’ substitution away from educational pursuits.
Functional interaction between the dorsal hippocampus and the striatum in visual discrimination learning

The hippocampus and the striatum have traditionally been considered as part of different and independent memory systems. However, there is evidence that supports a functional interaction between the hippocampus and the dorsal striatum at least in particular learning tasks. Here, we evaluated the functional contribution of both brain regions in a visual discrimination learning task using cytochrome c oxidase (CO) quantitative histochemistry. Compared with other brain metabolic mapping techniques, CO activity reflects steady‐state neuronal energy demand. Rats were trained for 6 days in a water T‐maze to find a hidden escape platform associated with an intramaze visual cue. A control group of animals swam for an equivalent amount of time compared as the trained group but without any escape platform available. After finishing the behavioral task, CO activity was measured in subdivisions of the dorsal hippocampus and the dorsal striatum in both groups. Results show significantly higher CO activity in the CA1 area and the dentate gyrus of the dorsal hippocampus in the trained rats compared with the control group. In addition, a significant negative functional cross‐correlation between area CA1 of the dorsal hippocampus and the anterodorsal striatum was found. Our results support current theories on competitive interaction of different memory systems during visual discrimination learning. © 2011 Wiley Periodicals, Inc.
Picturing Borders, Boundaries, Barriers, and Bridges and Sowing Seeds of Sociopolitical Consciousness Through Alliteration and Analogy

ABSTRACT Developing preservice and inservice teachers’ sociopolitical consciousness remains an important part of supporting the success of P-12 student experiences. The authors recognize that one way to enhance the sociopolitical consciousness aspect of culturally responsive pedagogy/teaching is through experiential opportunities that support teacher development in this area. The authors propose the use of an alliterative framework (borders, boundaries, barriers, and bridges) and an analogy (seeds) to advance the sociopolitical consciousness of teachers. In this article, the authors (1) discuss culturally responsive pedagogy/teaching and the reported challenges of developing the sociopolitical consciousness aspects; (2) review the use of metaphors, analogies, allegories, and alliterations as tools to support teacher conceptualizations and practice of teaching; (3) detail two projects informed by an alliterative framework designed to advance sociopolitical consciousness; and (4) share implications for educators.
Identification of a Signal That Distinguishes between the Chloroplast Outer Envelope Membrane and the Endomembrane System in Vivo

Certain small outer envelope membrane proteins of chloroplasts are encoded by the nuclear genome without a cleavable N-terminal transit peptide. We investigated in vivo the targeting mechanism of AtOEP7, an Arabidopsis homolog of the small outer envelope membrane protein. AtOEP7 was expressed as a fusion protein with the green fluorescent protein (GFP) either transiently in protoplasts or stably in transgenic plants. In either case, fluorescence microscopy of transformed cells and protein gel blot analysis of fractionated proteins confirmed that the AtOEP7:GFP fusion protein was targeted to the chloroplast outer envelope membrane. In vivo targeting experiments revealed that two regions, the transmembrane domain (TMD) and its C-terminal neighboring seven–amino acid region, were necessary and sufficient for targeting to the chloroplast outer membrane. Substitution of aspartic acid or lysine residues with glycine residues or scrambling of the amino acid sequence of the seven–amino acid region caused mistargeting to the plasma membrane. Although the amino acid sequence of the TMD is not important for targeting, amino acid residues with large side chains inhibited targeting to the chloroplasts and resulted in the formation of large aggregates in the protoplasts. In addition, introduction of a proline residue within the TMD resulted in inhibition of targeting. Finally, a fusion protein, AtOEP7:NLS:GFP, was targeted efficiently to the chloroplast envelope membranes despite the presence of a nuclear localization signal. On the basis of these results, we conclude that the seven–amino acid region and the TMD are determinants for targeting to the chloroplast outer envelope membrane. The seven–amino acid region plays a critical role in AtOEP7 evading the endomembrane system and entering the chloroplast pathway, and the TMD plays critical roles in migration to the chloroplasts and/or subsequent insertion into the membrane.
Supramolecular structure of the Shigella type III secretion machinery: the needle part is changeable in length and essential for delivery of effectors

We investigated the supramolecular structure of the Shigella type III secretion machinery including its major components. Our results indicated that the machinery was composed of needle and basal parts with respective lengths of 45.4 ± 3.3 and 31.6 ± 0.3 nm, and contained MxiD, MxiG, MxiJ and MxiH. spa47, encoding a putative F1‐type ATPase, was required for the secretion of effector proteins via the type III system and was involved in the formation of the needle. The spa47 mutant produced a defective, needle‐less type III structure, which contained MxiD, MxiG and MxiJ but not MxiH. The mxiH mutant produced a defective type III structure lacking the needle and failed to secrete effector proteins. Upon overexpression of MxiH in the mxiH mutant, the bacteria produced type III structures with protruding dramatically long needles, and showed a remarkable increase in invasiveness. Our results suggest that MxiH is the major needle component of the type III machinery and is essential for delivery of the effector proteins, and that the level of MxiH affects the length of the needle.
The nuclear factor‐κB pathway down‐regulates expression of the NKG2D ligand H60a in vitro: implications for use of nuclear factor‐κB inhibitors in cancer therapy

NKG2D ligands are cell surface proteins that activate NKG2D, a receptor used by natural killer (NK) cells to detect virus‐infected and transformed cells. When tumour cells express high levels of NKG2D ligands, they are rejected by the immune system. Hence, reagents that increase NKG2D ligand expression on tumour cells can be important for tumour immunotherapy. To identify genes that regulate the NKG2D ligand H60a, we performed a microarray analysis of 3′‐methylcholanthrene‐induced sarcoma cell lines expressing high versus low H60a levels. A20, an inhibitor of nuclear factor‐κB (NF‐κB) activation, was differentially expressed in H60a‐hi sarcoma cells. Correspondingly, treatment of tumour cells with inhibitors of NF‐κB activation, such as sulfasalazine (slz), BAY‐11‐7085, or a non‐phosphorylatable IκB, led to increased levels of H60a protein, whereas transduction of cells with an active form of IκB kinase‐β (IKKβ) led to decreased levels of H60a. The regulation probably occurred at the transcriptional level, because NF‐κB pathway inhibition led to increased H60a transcripts and promoter activity. Moreover, treatment of tumour cells with slz enhanced their killing by NK cells in vitro, suggesting that NF‐κB inhibition can lead to tumour cell rejection. Indeed, when we blocked the NF‐κB pathway specifically in tumour cells, there was decreased tumour growth in wild‐type but not immune‐deficient mice. Our results suggest that reagents that can block NF‐κB activity specifically in the tumour and not the host immune cells would be efficacious for tumour therapy.