Miracle-dz/UniFAR-FTUs huggingface dataset:
ncidence and prevalence of hepatitis c virus infection among persons ho inject drugs in New York City : 2006 – 2013 shly

Background: Hepatitis C virus infection is a source of significant preventable morbidity and mortality among persons who inject drugs (PWID). We sought to assess trends in hepatitis C virus (HCV) infection among PWID from 2006 to 2013 in New York City (NYC). Methods: Annual cross-sectional surveys of PWID entering a large drug abuse treatment program were performed. Risk behavior questionnaires were administered, and HIV and HCV testing were conducted. Comparisons were made with prior prevalence and incidence estimates in 1990–1991 and 2000–2001 reflecting different periods of combined prevention and treatment efforts. Results: HCV prevalence among PWID (N: 1535) was 67% (95% CI: 66–70%) during the study period, and was not significantly different from that observed in 2000–2001. The estimated HCV incidence among new injectors (persons injecting for ≤6 years) during 2006–2013 was 19.5/100 PYO (95% CI: 17–23) and eedle/syringe exchange program did not differ from that observed in 2000–2001 (18/100 PYO, 95% CI: 14–23/100). Conclusions: Despite the expansion of combined prevention programming between 2000–2001 and 2006–2013, HCV prevalence remained high. Estimated HCV incidence among new injectors also remained high, and not significantly lower than in 2000–2001, indicating that expanded combined prevention efforts are needed to control the HCV epidemic among PWID in NYC.
Pharmacokinetic overview of ethinyl estradiol dose and bioavailability using two transdermal contraceptive systems and a standard combined oral contraceptive

Objective: To determine the relative bioavailability of ethinyl estradiol (EE) and gestodene (GSD) after application of a novel transdermal contraceptive patch vs. a standard combined oral contraceptive (COC) pill (study 1), and to evaluate the pharmacokinetics (PK) of EE after application of the EE/GSD patch compared with an EE/norelgestromin (NGMN) patch (study 2). Materials: Participants were healthy, non-obese women aged 18 – 45 years (study 1) or 18 – 35 years (study 2). Compositions of study treatments were as follows: 0.55 mg EE/2.1 mg GSD (EE/GSD patch); 0.02 mg EE/0.075 mg GSD (standard COC); 0.6 mg EE/6 mg NGMN (EE/NGMN patch). Methods: In study 1, which consisted of 3 treatment periods (each followed by 7 patch- or pill-free days), treatments were administered in one of two randomized orders: either P–M–E (EE/GSD patch (P) every 7 days for 28 days → COC (M) once-daily for 21 days → two 7-day patch-wearing periods followed by one 10-day patch-wearing phase (E)), or the same treatments administered in sequence M–P–E. For study 2, participants received either the EE/GSD patch or EE/NGMN patch for seven treatment cycles (one patch per week for 3 weeks followed by a 7-day patch-free interval). Results: In study 1, average daily exposure to EE was similar for treatments P and M; the mean daily area under the concentration-time curve (AUC) ratio of treatment P vs. treatment M for EE was 1.06 (90% confidence interval (CI): 0.964 – 1.16), indicating average daily delivery similar to oral administration of 0.019 – 0.023 mg EE. For unbound GSD, average daily exposure was lower for treatment P vs. treatment M. The mean AUC ratio of treatment P vs. treatment M for unbound GSD was 0.820 (90% CI: 0.760 – 0.885), indicating average daily delivery from the patch of 0.057 – 0.066 mg GSD. Prolonged patch wearing did not result in a distinct decline in GSD and EE serum concentrations. In study 2, AUC at steady state (AUC0–168,ss), average steady-state serum concentration, and maximum steady-state serum concentration for EE was 2.0 – 2.7-fold higher for the EE/NGMN patch vs. the EE/GSD patch. The EE/GSD patch was well tolerated in both studies. Conclusions: Based on the 90% CI of the AUC ratio of oral treatment vs. patch application for unbound GSD and EE, the daily doses of GSD and EE released from the EE/GSD patch over the 7-day application period provided the same systemic exposure as those recorded after daily oral administration of a COC containing 0.02 mg EE and 0.06 mg GSD. The EE/GSD patch showed reduced EE exposure compared with the EE/NGMN patch. Together with its good tolerability, these properties support the EE/GSD patch as an effective and well-tolerated alternative to available transdermal and oral contraceptives.
Mechanical properties, Payne effect, and Mullins effect of thermoplastic vulcanizates based on high-impact polystyrene and styrene–butadiene rubber compatibilized by styrene–butadiene–styrene block copolymer

Thermoplastic vulcanizates (TPVs) based on high-impact polystyrene (HIPS)/styrene–butadiene rubber (SBR) blends were prepared by dynamic vulcanization technique, and the TPVs were compatibilized by styrene–butadiene–styrene block copolymer (SBS). Experimental results indicate that SBS had a good compatibilization effect on the HIPS/SBR TPVs. A rubber process analyzer reveals that elastic modulus increased with increasing frequency and increasing SBR content in the TPVs led to obvious decrease in elastic modulus. A softening phenomenon could be observed in the stress–stretch curves of HIPS/SBR and HIPS/SBS/SBR TPVs during the uniaxial loading–unloading cycles. Compatibilized HIPS/SBR TPV had the relatively lower stress and internal friction loss.
Sorting of Yeast Membrane Proteins into an Endosome-to-Golgi Pathway Involves Direct Interaction of Their Cytosolic Domains with Vps35p

Resident late-Golgi membrane proteins in Saccharomyces cerevisiae are selectively retrieved from a prevacuolar–endosomal compartment, a process dependent on aromatic amino acid–based sorting determinants on their cytosolic domains. The formation of retrograde vesicles from the prevacuolar compartment and the selective recruitment of vesicular cargo are thought to be mediated by a peripheral membrane retromer protein complex. We previously described mutations in one of the retromer subunit proteins, Vps35p, which caused cargo-specific defects in retrieval. By genetic and biochemical means we now show that Vps35p directly associates with the cytosolic domains of cargo proteins. Chemical cross-linking, followed by coimmunoprecipitation, demonstrated that Vps35p interacts with the cytosolic domain of A-ALP, a model late-Golgi membrane protein, in a retrieval signal–dependent manner. Furthermore, mutations in the cytosolic domains of A-ALP and another cargo protein, Vps10p, were identified that suppressed cargo-specific mutations in Vps35p but did not suppress the retrieval defects of a vps35 null mutation. Suppression was shown to be due to an improvement in protein sorting at the prevacuolar compartment. These data strongly support a model in which Vps35p acts as a “receptor” protein for recognition of the retrieval signal domains of cargo proteins during their recruitment into retrograde vesicles.
Statistics of the Spectral Kurtosis Estimator

Spectral kurtosis (SK) is a statistical approach for detecting and removing radio-frequency interference (RFI) in radio astronomy data. In this article, the statistical properties of the SK estimator are investigated and all moments of its probability density function are analytically determined. These moments provide a means to determine the tail probabilities of the estimator that are essential to defining the thresholds for RFI discrimination. It is shown that, for a number of accumulated spectra M≥24, the first SK standard moments satisfy the conditions required by a Pearson type IV probability density function (pdf), which is shown to accurately reproduce the observed distributions. The cumulative function (CF) of the Pearson type IV is then found, in both analytical and numerical forms, suitable for accurate estimation of the tail probabilities of the SK estimator. This same framework is also shown to be applicable to the related time-domain kurtosis (TDK) estimator, whose pdf corresponds to Pearson type IV when the number of time-domain samples is M≥46. The pdf and CF also are determined for this case.
Emotion in Schizophrenia

Our understanding of the nature of emotional difficulties in schizophrenia has been greatly enhanced by translational research over the past two decades. By incorporating methods and theories from affective science, researchers have been able to discover that people with schizophrenia exhibit very few outward displays of emotion but report experiencing strong feelings in the presence of emotionally evocative stimuli or events. Recent behavioral, psychophysiological, and brain imaging research has pointed to the importance of considering the time course of emotion in schizophrenia. This work has shown that people with schizophrenia have the ability to experience emotion in the moment; however, they appear to have difficulties when anticipating future pleasurable experiences, and this perhaps affects their motivation to have such experiences. While advancements in our understanding of emotional experience and expression in individuals with schizophrenia have been made, these developments have led to a new collection of research questions directed at understanding the time course of emotion in schizophrenia, including the role of memory and anticipation in motivated behavior, translating laboratory findings to the development of new assessment tools and new treatments targeting emotional impairments in people with this disorder.
The Epstein-Barr virus EBNA-1 promoter Qp requires an initiator-like element

Expression of the Epstein-Barr virus (EBV) EBNA-1 protein within EBV-positive tumor cells and subpopulations of latently infected B lymphocytes in vivo is mediated by the promoter Qp. Previous studies have established that Qp is a TATA-less promoter whose activation requires only proximal regulatory elements and that it is negatively autoregulated through two EBNA-1 binding sites downstream of the transcription initiation sites. The objective of this study was to better define the properties of an essential positive regulatory element (QRE-2) adjacent to a major transcription start site of Qp and to evaluate the contributions of other potential regulatory elements proximal to the Qp start site. Using DNA affinity purification and UV cross-linking, we have identified the QRE-2-binding protein as a single polypeptide of approximately 40 kDa. The DNA-binding properties of this protein are clearly distinct from those of the TATA-binding protein, suggesting that in the absence of a TATA box, QRE-2 may function as an initiator element to direct assembly of TFIID near the transcription start site. Mutational analysis of potential regulatory elements, furthermore, indicated that the putative E2F binding sites within the EBNA-1 binding domain can exert a positive influence on Qp that is EBNA-1 independent, suggesting that these regulatory elements play an additional if not different role in Qp regulation than previously proposed. A model for the regulation of Qp consistent with the current and previous findings which provides for a simple but efficient mechanism of ensuring the EBNA-1 expression necessary to sustain long-term latency is presented.
Side effect machines for quaternary edit metric decoding

DNA edit metric codes are used as labels to track the origin of sequence data. This study is the first to treat sophisticated decoders for these error-correcting codes. Side effect machines can provide efficient decoding algorithms for such codes. Two methods for automatically producing decoding algorithms are presented. Side Effect Machines (SEMs), generalizations of finite state automata, are used in both. Single Classifier Machines (SCMs) use a single side effect machine to classify all words within a code. Locking Side Effect Machines (LSEMs) use multiple side effect machines to create a tree structured iterated classification. This study examines these techniques and provides new decoders for existing codes. Presented are ideas for best practises for the creation of these two types of new edit metric decoders. Codes of the form (n,M,d)4 are used in testing due to their suitability for bioinformatics problems. A group of (12, 54–56, 7)4 codes are used as an example of the process.
CONSTRUCTING WEB SERVER PERFORMANCE MODELS

Much of the explosive growth of the Internet can be attributed to the popularity of web service. Corporate intranets are also becoming web-centric as web based distribution is becoming a popular method of distributing data. Thus, analyzing the performance of web servers is a crucial component in analyzing the performance of data networks. This paper highlights facets of web server software and hardware design that may impact its performance and discusses model parameterization.
Failure of Brain-Derived Neurotrophic Factor-Dependent Neuron Survival in Mouse Trisomy 16

The neurotrophin, brain derived neurotrophic factor (BDNF), exerts multiple effects on the development and maintenance of the nervous system, including regulating synaptic plasticity and promoting neuron survival. Here we report the selective failure of BDNF-dependent survival in cultured hippocampal neurons from the trisomy 16 (Ts16) mouse, an animal model of Down syndrome. This failure is accompanied by overexpression of a truncated, kinase-deficient isoform (T1) of the BDNF receptor tyrosine receptor kinase B (trkB). Adenovirus-mediated introduction of exogenous full-length trkB into Ts16 neurons fully restored BDNF-dependent survival, whereas exogenous truncated trkB expression in normal, euploid neurons reproduced the Ts16 BDNF signaling failure. Thus, the failure of Ts16 neurons to respond to BDNF is caused by dysregulation of trkB isoform expression. Such a neurotrophin signaling defect could contribute to developmental and degenerative disorders of the nervous system.
Combined Effect of Cameo2 and CBP on the Cellular Uptake of Lutein in the Silkworm, Bombyx mori

Formation of yellow-red color cocoons in the silkworm, Bombyx mori, occurs as the result of the selective delivery of carotenoids from the midgut to the silk gland via the hemolymph. This process of pigment transport is thought to be mediated by specific cellular carotenoids carrier proteins. Previous studies indicated that two proteins, Cameo2 and CBP, are associated with the selective transport of lutein from the midgut into the silk gland in Bombyx mori. However, the exact roles of Cameo2 and CBP during the uptake and transport of carotenoids are still unknown. In this study, we investigated the respective contributions of these two proteins to lutein and β-carotene transport in Bombyx mori as well as commercial cell-line. We found that tissues, expressed both Cameo2 and CBP, accumulate lutein. Cells, co-expressed Cameo2 and CBP, absorb 2 fold more lutein (P<0.01) than any other transfected cells, and the rate of cellular uptake of lutein was concentration-dependent and reached saturation. From immunofluorescence staining, confocal microscopy observation and western blot analysis, Cameo2 was localized at the membrane and CBP was expressed in the cytosol. What’s more, bimolecular fluorescence complementation analysis showed that these two proteins directly interacted at cellular level. Therefore, Cameo2 and CBP are necessarily expressed in midguts and silk glands for lutein uptake in Bombyx mori. Cameo2 and CBP, as the membrane protein and the cytosol protein, respectively, have the combined effect to facilitate the cellular uptake of lutein.
Characterization of Hair Follicle Development in Engineered Skin Substitutes

Generation of skin appendages in engineered skin substitutes has been limited by lack of trichogenic potency in cultured postnatal cells. To investigate the feasibility and the limitation of hair regeneration, engineered skin substitutes were prepared with chimeric populations of cultured human keratinocytes from neonatal foreskins and cultured murine dermal papilla cells from adult GFP transgenic mice and grafted orthotopically to full-thickness wounds on athymic mice. Non-cultured dissociated neonatal murine-only skin cells, or cultured human-only skin keratinocytes and fibroblasts without dermal papilla cells served as positive and negative controls respectively. In this study, neonatal murine-only skin substitutes formed external hairs and sebaceous glands, chimeric skin substitutes formed pigmented hairs without sebaceous glands, and human-only skin substitutes formed no follicles or glands. Although chimeric hair cannot erupt readily, removal of upper skin layer exposed keratinized hair shafts at the skin surface. Development of incomplete pilosebaceous units in chimeric hair corresponded with upregulation of hair-related genes, LEF1 and WNT10B, and downregulation of a marker of sebaceous glands, Steroyl-CoA desaturase. Transepidermal water loss was normal in all conditions. This study demonstrated that while sebaceous glands may be involved in hair eruption, they are not required for hair development in engineered skin substitutes.
Nuclear p120 catenin unlocks mitotic block of contact-inhibited human corneal endothelial monolayers without disrupting adherent junctions

Summary Contact inhibition ubiquitously exists in non-transformed cells that are in contact with neighboring cells. This phenomenon explains the poor regenerative capacity of in vivo human corneal endothelial cells during aging, injury and surgery. This study demonstrated that the conventional approach of expanding human corneal endothelial cells by disrupting contact inhibition with EDTA followed by bFGF activated canonical Wnt signaling and lost the normal phenotype to endothelial–mesenchymal transition, especially if TGF&bgr;1 was added. By contrast, siRNA against p120 catenin (CTNND1) also uniquely promoted proliferation of the endothelial cells by activating trafficking of p120 catenin to the nucleus, thus relieving repression by nuclear Kaiso. This nuclear p120-catenin–Kaiso signaling is associated with activation of RhoA–ROCK signaling, destabilization of microtubules and inhibition of Hippo signaling, but not with activation of Wnt–&bgr;-catenin signaling. Consequently, proliferating human corneal endothelial cells maintained a hexagonal shape, with junctional expression of N-cadherin, ZO-1 and Na+/K+-ATPase. Further expansion of human corneal endothelial monolayers with a normal phenotype and a higher density was possible by prolonging treatment with p120 catenin siRNA followed by its withdrawal. This new strategy of perturbing contact inhibition by selective activation of p120-catenin–Kaiso signaling without disrupting adherent junction could be used to engineer surgical grafts containing normal human corneal endothelial cells to meet a global corneal shortage and for endothelial keratoplasties.
Parallel processing of robot-arm control computation on a multimicroprocessor system

A parallel-processing scheme is described for robot-arm control computation on any number of parallel processors. The scheme employs two multiprocessor scheduling algorithms called, respectively, depth first/implicit heuristic search (DF/IHS) and critical path/most immediate successors first (CP/MISF); these were recently developed by the authors. The scheme is applied to the parallel processing of dynamic control computation for the Stanford manipulator. In particular, the proposed algorithms are applied to the computation of the Newton-Euler equations of motion for the Stanford manipulator and implemented on a multimicroprocessor system. The test result was so successful that the use of six processor pairs in parallel could attain the processing time of 5.37 ms. It is also shown that the proposed parallel-processing scheme is applicable to an arbitrary number of processors.
Dynamical description of the keyhole in deep penetration laser welding

We study the keyhole geometry as a function of the main operating parameters such as welding speed, laser incident intensity, or sample material. This model is based on a drilling velocity whose combination with the welding velocity causes the inclination of the front keyhole wall (FKW). This front inclination is shown to be stationary and stable all along the FKW. The penetration depth results from the product of this drilling velocity and a characteristic time defined as the beam diameter divided by the welding speed. By using a ray-tracing procedure, the dynamics and the complete keyhole geometry can be determined by taking into account the multiple reflections inside the keyhole and a description of the closure process of the rear keyhole wall (RKW). We show that this RKW cannot be stationary all along its surface and only an adequate laser intensity distribution can make it stationary. The interest of elongated focal spots or twin spots is then demonstrated. At high welding velocity the front wall is.
The Mating Type Switch-Activating Protein Sap1 Is Required for Replication Fork Arrest at the rRNA Genes of Fission Yeast

ABSTRACT Schizosaccharomyces pombe rRNA genes contain three replication fork barriers (RFB1-3) located in the nontranscribed spacer. RFB2 and RFB3 require binding of the transcription terminator factor Reb1p to two identical recognition sequences that colocalize with these barriers. RFB1, which is the strongest of the three barriers, functions in a Reb1p-independent manner, and cognate DNA-binding proteins for this barrier have not been identified yet. Here we functionally define RFB1 within a 78-bp sequence located near the 3′ end of the rRNA coding region. A protein that specifically binds to this sequence was purified by affinity chromatography and identified as Sap1p by mass spectrometry. Specific binding to RFB1 was confirmed by using Sap1p expressed in Escherichia coli. Sap1p is essential for viability and is required for efficient mating-type switching. Mutations in RFB1 that precluded formation of the Sap1p-RFB1 complex systematically abolished replication barrier function, indicating that Sap1p is required for replication fork blockage at RFB1.
Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks

Homologous recombination (HR) deficient cells are sensitive to methyl methanesulfonate (MMS). HR is usually involved in the repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae implying that MMS somehow induces DSBs in vivo. Indeed there is evidence, based on pulsed-field gel electrophoresis (PFGE), that MMS causes DNA fragmentation. However, the mechanism through which MMS induces DSBs has not been demonstrated. Here, we show that DNA fragmentation following MMS treatment, and detected by PFGE is not the consequence of production of cellular DSBs. Instead, DSBs seen following MMS treatment are produced during sample preparation where heat-labile methylated DNA is converted into DSBs. Furthermore, we show that the repair of MMS-induced heat-labile damage requires the base excision repair protein XRCC1, and is independent of HR in both S.cerevisiae and mammalian cells. We speculate that the reason for recombination-deficient cells being sensitive to MMS is due to the role of HR in repair of MMS-induced stalled replication forks, rather than for repair of cellular DSBs or heat-labile damage.