Miracle-dz/UniFAR-FTUs huggingface dataset:
Src promotes delta opioid receptor (DOR) desensitization by interfering with receptor recycling

An important limitation in the clinical use of opiates is progressive loss of analgesic efficacy over time. Development of analgesic tolerance is tightly linked to receptor desensitization. In the case of delta opioid receptors (DOR), desensitization is especially swift because receptors are rapidly internalized and are poorly recycled to the membrane. In the present study, we investigated whether Src activity contributed to this sorting pattern and to functional desensitization of DORs. A first series of experiments demonstrated that agonist binding activates Src and destabilizes a constitutive complex formed by the spontaneous association of DORs with the kinase. Src contribution to DOR desensitization was then established by showing that pre‐treatment with Src inhibitor PP2 (20 μM; 1 hr) or transfection of a dominant negative Src mutant preserved DOR signalling following sustained exposure to an agonist. This protection was afforded without interfering with endocytosis, but suboptimal internalization interfered with PP2 ability to preserve DOR signalling, suggesting a post‐endocytic site of action for the kinase. This assumption was confirmed by demonstrating that Src inhibition by PP2 or its silencing by siRNA increased membrane recovery of internalized DORs and was further corroborated by showing that inhibition of recycling by monensin or dominant negative Rab11 (Rab11S25N) abolished the ability of Src blockers to prevent desensitization. Finally, Src inhibitors accelerated recovery of DOR‐Gαl3 coupling after desensitization. Taken together, these results indicate that Src dynamically regulates DOR recycling and by doing so contributes to desensitization of these receptors.
Presumptive self-diagnosis of malaria and other febrile illnesses in Sierra Leone

Introduction The objective of this study was to evaluate the prevalence of self-diagnosis of malaria and other febrile illnesses in Bo, Sierra Leone. Methods All households in two neighboring sections of Bo were invited to participate in a cross-sectional survey. Results A total of 882 households (an 85% participation rate) that were home to 5410 individuals participated in the study. Of the 910 individuals reported to have had what the household considered to be malaria in the past month, only 41% were diagnosed by a healthcare professional or a laboratory test. Of the 1402 individuals reported to have had any type of febrile illness within the past six months, only 34% had sought a clinical or laboratory diagnosis. Self-diagnosis of influenza, yellow fever, typhoid, and pneumonia was also common. Conclusion Self-diagnosis and presumptive treatment with antimalarial drugs and other antibiotic medications that are readily available without a prescription may compromise health outcomes for febrile adults and children.
Neurally Coupled Subspace Learning of Movement

Neural decoding of motor control of hand and arm movements in primates is a challenging task that requires developing statistical models that explain how the recorded neural population activity relates to motor behavior. Until recently, much of the work in this area has focused on learning linear models of decoding for low-dimensional motor control, such as 2D control of a computer cursor. Capturing a richer set of motor behaviors such as hand and arm posture during object grasping and manipulation tasks introduces much higher dimensional representations of motor control. Understanding the underlying degrees of freedom in complex kinematics that are explained by the neural activity is a central question. One way of learning these “effective” degrees of freedom has been to employ dimensionality reduction techniques, such as Principal Component Analysis, to find a linear kinematic subspace that accounts for the observed motor behavior, separate from the observed neural activity. The orthonormal bases that span this subspace are then considered as the underlying latent variables, or “motor primitives” that describe behavior. These motor primitives are not guaranteed to be optimally correlated with the observed neural activity however. In this paper we devise an objective function and optimize it to learn a linear subspace of the motor activity that tries to maximize the correlation between the latent variables of this subspace and the neural activity, while still explaining the motor behavior with reasonable fidelity.
Evaluation of Weight Matrix Models in the splice junction recognition problem

The amount of data produced by the several genomic sequencing projects has increased dramatically in recent years. One of the main goals of bioinformatics is to analyze biological data aiming at identifying genes. The splice junction recognition problem is an important part of the gene detection problem. This work evaluates the performance of two classification models, derived from the Weight Matrix Model, when applied to the splice junction recognition problem. Two splice junction data sets were used in this work and some measures of predictive accuracy were reported. Based on the experiments, classification thresholds were established, which can be useful for further implementation of an automatic gene detection system.
R5 HIV productively infects Langerhans cells, and infection levels are regulated by compound CCR5 polymorphisms

Langerhans cells (LCs) are suspected to be initial targets for HIV after sexual exposure (by becoming infected or by capturing virus). Here, productive R5 HIV infection of LC ex vivo and LC-mediated transmission of virus to CD4+ T cells were both found to depend on CCR5. By contrast, infection of monocyte-derived dendritic cells and transfer of infection from monocyte-derived dendritic cells to CD4+ T cells were mediated by CCR5-dependent as well as DC-specific ICAM-3-grabbing nonintegrin-dependent pathways. Furthermore, in 62 healthy individuals, R5 HIV infection levels in LCs ex vivo were associated with CCR5 genotype. Specifically, genotyping for ORFΔ32 revealed that LCs isolated from ORFΔ32/wt individuals were significantly less susceptible to HIV when compared with LCs isolated from ORFwt/wt individuals (P = 0.016). Strikingly, further genetic analyses of the A-2459G CCR5 promoter polymorphism in ORFΔ32/wt heterozygous individuals revealed that LCs isolated from -2459A/G + ORFΔ32/wt individuals were markedly less susceptible to HIV than were LCs from -2459A/A + ORFΔ32/wt individuals (P = 0.012). Interestingly, these genetic susceptibility data in LCs parallel those of genetic susceptibility studies performed in cohorts of HIV-infected individuals. Thus, we suggest that CCR5-mediated infection of LCs, and not capture of virus by LCs, provides a biologic basis for understanding certain aspects of host genetic susceptibility to initial HIV infection.
Optimized multipartite table methods for elementary function computation

This paper presents an optimization method for computing an optimum lookup table size for two well-known look up table elementary function approximation methods; Symmetric Table Additional Method (STAM) and Multipartite Table Method (MTM). Using a discrete optimization algorithm called Leapfrogging, this paper utilizes a method to find the best decomposition of the coefficients to optimize look up table sizes. The resulting designs can easily be utilized for any approximation for functions up 24-bits of precision with significantly smaller requirements for lookup table sizes. Results show that the proposed optimized method is able to achieve higher memory efficiency than the best existing MTM. For the sine function, the optimized method saves 85.29 percent of memory for 16-bit accuracy and 53.89 percent for 24-bit accuracy when comparing to the best existing result obtained by the unified Multipartite Table Method.
Creating an Interest in Research and Development as a Means of Reducing the Gap between Theory and Practice in Primary Care: An Interventional Study Based on Strategic Communication

Today, healthcare professionals are faced with the challenge of implementing research results in an optimal way. It is therefore important to create a climate that is conducive to research and development (R&D). For this reason, new strategies are required to enhance healthcare professionals’ interest in innovative thinking and R&D. Strategic communication with roots in sociology, psychology and political science was employed as a means of achieving long-term behavioural change. The aim of this study was to describe, follow up and evaluate a primary care intervention based on strategic communication intended to increase healthcare professionals’ interest in R&D over time. An interventional cohort study comprising all staff members (N = 1276) in a Swedish primary care area was initiated in 1997 and continued for 12 years. The intention to engage in R&D was measured on two occasions; at 7 and 12 years. Both descriptive statistics and bivariate analyses were employed. The results demonstrated that the positive attitude to R&D increased over time, representing a first step towards new thinking and willingness to change work practices for the benefit of the patient. Strategic communication has not been previously employed as a scientific tool to create a long-term interest in R&D within primary care.
RNA Silencing of Mcl-1 Enhances ABT-737-Mediated Apoptosis in Melanoma: Role for a Caspase-8-Dependent Pathway

Background Malignant melanoma is resistant to almost all conventional forms of chemotherapy. Recent evidence suggests that anti-apoptotic proteins of the Bcl-2 family are overexpressed in melanoma and may contribute to melanoma's striking resistance to apoptosis. ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xl and Bcl-w, has demonstrated efficacy in several forms of leukemia, lymphoma as well as solid tumors. However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance. Methodology/Principal Findings Here we report that knockdown of Mcl-1 greatly reduces cell viability in combination with ABT-737 in six different melanoma cell lines. We demonstrate that the cytotoxic effect of this combination treatment is due to apoptotic cell death involving not only caspase-9 activation but also activation of caspase-8, caspase-10 and Bid, which are normally associated with the extrinsic pathway of apoptosis. Caspase-8 (and caspase-10) activation is abrogated by inhibition of caspase-9 but not by inhibitors of the death receptor pathways. Furthermore, while caspase-8/-10 activity is required for the full induction of cell death with treatment, the death receptor pathways are not. Finally, we demonstrate that basal levels of caspase-8 and Bid correlate with treatment sensitivity. Conclusions/Significance Our findings suggest that the combination of ABT-737 and Mcl-1 knockdown represents a promising, new treatment strategy for malignant melanoma. We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity.
N-Acylethanolamine Metabolism Interacts with Abscisic Acid Signaling in Arabidopsis thaliana Seedlings[W][OA]

N-Acylethanolamines (NAEs) are bioactive acylamides that are present in a wide range of organisms. In plants, NAEs are generally elevated in desiccated seeds, suggesting that they may play a role in seed physiology. NAE and abscisic acid (ABA) levels were depleted during seed germination, and both metabolites inhibited the growth of Arabidopsis thaliana seedlings within a similar developmental window. Combined application of low levels of ABA and NAE produced a more dramatic reduction in germination and growth than either compound alone. Transcript profiling and gene expression studies in NAE-treated seedlings revealed elevated transcripts for a number of ABA-responsive genes and genes typically enriched in desiccated seeds. The levels of ABI3 transcripts were inversely associated with NAE-modulated growth. Overexpression of the Arabidopsis NAE degrading enzyme fatty acid amide hydrolase resulted in seedlings that were hypersensitive to ABA, whereas the ABA-insensitive mutants, abi1-1, abi2-1, and abi3-1, exhibited reduced sensitivity to NAE. Collectively, our data indicate that an intact ABA signaling pathway is required for NAE action and that NAE may intersect the ABA pathway downstream from ABA. We propose that NAE metabolism interacts with ABA in the negative regulation of seedling development and that normal seedling establishment depends on the reduction of the endogenous levels of both metabolites.
Comparative characterization of a novel cad-cam polymer-infiltrated-ceramic-network

Background The field of dental ceramics for CAD-CAM is enriched with a new innovative material composition having a porous three-dimensional structure of feldspathic ceramic infiltrated with acrylic resins.The aim of this study is to determine the mechanical properties of Polymer-Infiltrated-Ceramic-Network (PICN) and compare its performance with other ceramics and a nano-ceramic resin available for CAD-CAM systems. Material and Methods In this study a total of five different materials for CAD-CAM were investigated. A polymer-infiltrated ceramic (Vita Enamic), a nano-ceramic resin (Lava Ultimate), a feldspathic ceramic (Mark II), a lithium disilicate ceramic (IPS-e max CAD) and finally a Leucite based ceramic (Empress - CAD). From CAD-CAM blocks, 120 bars (30 for each material cited above) were cut to measure the flexural strength with a three-point-bending test. Strain at failure, fracture stress and Weibull modulus was calculated. Vickers hardness of each material was also measured. Results IPS-EMAX presents mechanical properties significantly better from the other materials studied. Its strain at failure, flexural strength and hardness exhibited significantly higher values in comparison with the others. VITA ENAMIC and LAVA ULTIMATE stand out as the next most resistant materials. Conclusions The flexural strength, elastic modulus similar to a tooth as well as having less hardness than ceramics make PICN materials an option to consider as a restorative material. Key words:Ceramic infiltrated with resin, CAD-CAM, Weibull modulus, flexural strength, micro hardness.
Hybrid magnetorheological fluid–elastomeric lag dampers for helicopter stability augmentation

A laboratory demonstration of a hybrid magnetorheological fluid–elastomeric (MRFE) damper is investigated for adjustable or programmable lag mode damping in helicopters, so that damping requirements can be varied as a function of different flight conditions. The laboratory demonstration of this hybrid MRFE lag damper consists of a double lap shear elastomeric damper in parallel with two magnetorheological (MR) flow mode dampers. This is compared to a damper where only elastomeric materials are implemented, i.e., a double lap shear specimen. The relationship between the output force and the quasi-steady harmonic displacement input to a flow mode MR damper is exploited, where the output force can be adjusted as a function of applied magnetic field. Equivalent viscous damping is used to compare the damping characteristics of the hybrid damper to a conventional elastomeric damper under steady-state sinusoidal displacement excitation. To demonstrate feasibility, a hybrid MRFE damper test setup is designed, and single frequency (lag frequency or rotor in-plane bending frequency) and dual frequency (lag frequency and rotor frequency) tests are conducted under different magnetic fields. The hybrid MRFE damper exhibits amplitude-dependent damping behavior. However, with application of a magnetic field, the damping level is controlled to a specific damping level objective as a function of displacement amplitude. Similarly, under dual frequency conditions, damping degradation at the lag frequency, because of lag motion at the rotor frequency, can also be recovered by increasing magnetic field. A time-domain analysis is developed to study the nonlinear dynamic behavior of the hybrid MRFE damper. Using rate-dependent elasto-slides, the amplitude-dependent behavior of the hybrid MRFE damper is accurately reconstructed using both constant and current-dependent (i.e. controllable) parameters. The analysis is physically motivated and can be applied to the elastomer and MR fluid damper components separately.
HIV-1 Variation Diminishes CD4 T Lymphocyte Recognition

Effective long-term antiviral immunity requires specific cytotoxic T lymphocytes and CD4+ T lymphocyte help. Failure of these helper responses can be a principle cause of viral persistence. We sought evidence that variation in HIV-1 CD4+ T helper epitopes might contribute to this phenomenon. To determine this, we assayed fresh peripheral blood mononuclear cells from 43 asymptomatic HIV-1+ patients for proliferative responses to HIV-1 antigens. 12 (28%) showed a positive response, and we went on to map dominant epitopes in two individuals, to p24 Gag restricted by human histocompatibility leukocyte antigen (HLA)-DR1 and to p17 Gag restricted by HLA-DRB52c. Nine naturally occurring variants of the p24 Gag epitope were found in the proviral DNA of the individual in whom this response was detected. All variants bound to HLA-DR1, but three of these peptides failed to stimulate a CD4+ T lymphocyte line which recognized the index sequence. Antigenic variation was also detected in the p17 Gag epitope; a dominant viral variant present in the patient was well recognized by a specific CD4+ T lymphocyte line, whereas several natural mutants were not. Importantly, variants detected at both epitopes also failed to stimulate fresh uncultured cells while index peptide stimulated successfully. These results demonstrate that variant antigens arise in HIV-1+ patients which fail to stimulate the T cell antigen receptor of HLA class II–restricted lymphocytes, although the peptide epitopes are capable of being presented on the cell surface. In HIV-1 infection, naturally occurring HLA class II–restricted altered peptide ligands that fail to stimulate the circulating T lymphocyte repertoire may curtail helper responses at sites where variant viruses predominate.
Towards Neural Phrase-based Machine Translation

In this paper, we present Neural Phrase-based Machine Translation (NPMT). Our method explicitly models the phrase structures in output sequences using Sleep-WAke Networks (SWAN), a recently proposed segmentation-based sequence modeling method. To mitigate the monotonic alignment requirement of SWAN, we introduce a new layer to perform (soft) local reordering of input sequences. Different from existing neural machine translation (NMT) approaches, NPMT does not use attention-based decoding mechanisms. Instead, it directly outputs phrases in a sequential order and can decode in linear time. Our experiments show that NPMT achieves superior performances on IWSLT 2014 German-English/English-German and IWSLT 2015 English-Vietnamese machine translation tasks compared with strong NMT baselines. We also observe that our method produces meaningful phrases in output languages.
Two Modes of Vesicle Recycling in the Rat Calyx of Held

Vesicle recycling was studied in the rat calyx of Held, a giant brainstem terminal involved in sound localization. Stimulation of brain slices containing the calyx-type synapse with a high extracellular potassium ion concentration in the presence of horseradish peroxidase resulted within several minutes in a reduction of the number of neurotransmitter vesicles and in the appearance of labeled endosome-like structures. After returning to normal solution, the endosome-like structures disappeared over a period of several minutes, whereas simultaneously the number of labeled vesicles increased. A comparison with afferent stimulation suggested that the endosome-like structures normally do not participate in the vesicle cycle. Afferent stimulation at 5 Hz resulted in sustained synaptic transmission, without vesicle depletion but with an estimated endocytotic activity of <0.2 synaptic vesicles per active zone per second. At 20 Hz, the presynaptic action potentials generally failed during prolonged stimulation. In identified synapses, the number of vesicles labeled by photoconversion after stimulation at 5 Hz in the presence of the styryl dye RH414 was much lower than the number of vesicles that were released, as determined by measuring EPSCs. No more than ∼5% of the vesicles were labeled after 20 min stimulation at 5 Hz, whereas this stimulation protocol was sufficient to largely destain a terminal after previous loading. The results support a scheme for recycling in which two different modes coexist. At physiological demands, a pool of ∼5% of all vesicles provides sufficient vesicles for release. During intense stimulation, such as occurs in the presence of high extracellular K+, the synapse resorts to bulk endocytosis, a very slow mode of recycling.
Sensitivity Comparison between Rapid Immuno-Chromatographic Device Test and ELISA in Detection and Sero-Prevalence of HBsAg and Anti-HCV antibodies in Apparently Healthy Blood Donors of Lahore, Pakistan

Hepatitis B and hepatitis C are among the most significant hepatic infections all around the world that may lead to hepatocellular carcinoma. This study is first time performed at the blood transfussion centre of Omar hospital, Lahore. It aims to determine the sero-prevalence of these diseases by screening the apparently healthy blood donors who might be the carriers of HBV or HCV and pose a high risk in the transmission. It also aims the comparison between the sensitivity of two diagnostic tests; chromatographic immunoassay – one step test device and Enzyme Linked Immuno Sorbant Assay (ELISA). Blood serum of 855 apparently healthy blood donors was screened for Hepatitis B surface antigen (HBsAg) and for anti HCV antibodies. SPSS version 12.0 and X2 (Chi-square) test were used for statistical analysis. The seroprevalence of HCV was 8.07% by the device method and by ELISA 9.12% and that of HBV was 5.6% by the device and 6.43% by ELISA. The unavailability of vaccination against HCV makes it more prevalent. Comparing the two diagnostic methods, ELISA proved to be more sensitive. Keywords—ELISA, Sensitivity comparison of diagnostic tests, seroprevalence of Hepatitis B and C
The Interfacial Transition Zone in Alkali-Activated Slag Mortars

The interfacial transition zone (ITZ) is known to strongly influence the mechanical and transport properties of mortars and concretes. This paper studies the ITZ between siliceous (quartz) aggregates and alkali activated slag binders in the context of mortar specimens. Backscattered electron images (BSE) generated in an environmental scanning electron microscope (ESEM) are used to identify unreacted binder components, reaction products and porosity in the zone surrounding aggregate particles, by composition and density contrast. X-ray mapping is used to exclude the regions corresponding to the aggregates from the BSE image of the ITZ, thus enabling analysis of only the binder phases, which are segmented into binary images by grey level discrimination. A distinct yet dense ITZ region is present in the alkali-activated slag mortars, containing a reduced content of unreacted slag particles compared to the bulk binder. The elemental analysis of this region shows that it contains a (C,N)-A-S-H gel which seems to have a higher content of Na (potentially deposited through desiccation of the pore solution) and a lower content of Ca than the bulk inner and outer products forming in the main binding region. These differences are potentially important in terms of long-term concrete performance, as the absence of a highly porous interfacial transition zone region is expected to provide a positive influence on the mechanical and transport properties of alkali-activated slag concretes.