Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequential 2′-O-Methylation of Archaeal Pre-tRNATrp Nucleotides Is Guided by the Intron-encoded but trans-Acting Box C/D Ribonucleoprotein of Pre-tRNA*

Haloferax volcanii pre-tRNATrp processing requires box C/D ribonucleoprotein (RNP)-guided 2′-O-methylation of nucleotides C34 and U39 followed by intron excision. Positioning of the box C/D guide RNA within the intron of this pre-tRNA led to the assumption that nucleotide methylation is guided by the cis-positioned box C/D RNPs. We have now investigated the mechanism of 2′-O-methylation for the H. volcanii pre-tRNATrp in vitro by assembling methylation-competent box C/D RNPs on both the pre-tRNA and the excised intron (both linear and circular forms) using Methanocaldococcus jannaschii box C/D RNP core proteins. With both kinetic studies and single nucleotide substitutions of target and guide nucleotides, we now demonstrate that pre-tRNA methylation is guided in trans by the intron-encoded box C/D RNPs positioned in either another pre-tRNATrp or in the excised intron. Methylation by in vitro assembled RNPs prefers but does not absolutely require Watson-Crick pairing between the guide and target nucleotides. We also demonstrate for the first time that methylation of two nucleotides guided by a single box C/D RNA is sequential, that is, box C′/D′ RNP-guided U39 methylation first requires box C/D RNP-guided methylation of C34. Methylation of the two nucleotides of exogenous pre-tRNATrp added to an H. volcanii cell extract also occurs sequentially and is also accomplished in trans using RNPs that pre-exist in the extract. Thus, this trans mechanism is analogous to eukaryal pre-rRNA 2′-O-methylation guided by intron-encoded but trans-acting box C/D small nucleolar RNPs. This trans mechanism could explain the observed accumulation of the excised H. volcanii pre-tRNATrp intron in vivo. A trans mechanism would also eliminate the obligatory refolding of the pre-tRNA that would be required to carry out two cis-methylation reactions before pre-tRNA splicing.
Informal Taxation

Informal payments are a frequently overlooked source of local public finance in developing countries. We use microdata from ten countries to establish stylized facts on the magnitude, form, and distributional implications of this "informal taxation. " Informal taxation is widespread, particularly in rural areas, with substantial in-kind labor payments. The wealthy pay more, but pay less in percentage terms, and informal taxes are more regressive than formal taxes. Failing to include informal taxation underestimates household tax burdens and revenue decentralization in developing countries. We discuss various explanations for and implications of these observed stylized facts.
The Ccr7 Ligand ELC (Ccl19) Is Transcytosed in High Endothelial Venules and Mediates T Cell Recruitment

Lymphocyte homing to secondary lymphoid tissue is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial selectin-mediated tethering and rolling, firm adhesion of lymphocytes requires rapid upregulation of lymphocyte integrin adhesiveness. This step is mediated in part by the HEV-derived chemokine SLC (secondary lymphoid-tissue chemokine, or CCL21) that binds to the CC chemokine receptor (CCR)7 on lymphocytes. However, the CC chemokine ELC (Epstein-Barr virus–induced molecule 1 ligand chemokine, or CCL19) shares the same receptor, and ELC transcripts have been observed in the T cell areas of lymphoid organs. Here, we show that perivascular ELC is transcytosed to the luminal surfaces of HEVs and enables efficient T cell homing to lymph nodes. In situ hybridization on sections of human tonsil showed no ELC mRNA in HEVs, but immunostaining revealed ELC protein in cytoplasmic vesicles of HEV cells. Furthermore, ELC injected into the footpads of mice entered the draining lymph nodes and was presented by HEVs. Finally, intracutaneous injections of ELC in mice lacking functionally relevant ELC and SLC (plt/plt mice) restored T cell trafficking to draining lymph nodes as efficiently as SLC. We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest.
A kinetic model of sugar metabolism in peach fruit reveals a functional hypothesis of a markedly low fructose‐to‐glucose ratio phenotype

The concentrations of sugars in fruit vary with fruit development, environment and genotype. In general, there were weak correlations between the variations in sugar concentrations and the activities of enzymes directly related with the synthesis or degradation of sugars. This finding suggests that the relationships between enzyme activities and metabolites are often non-linear and are difficult to assess. To simulate the concentrations of sucrose, glucose, fructose and sorbitol during the development of peach fruit, a kinetic model of sugar metabolism was developed by taking advantage of recent profiling data. Cell compartmentation (cytosol and vacuole) was described explicitly, and data-driven enzyme activities were used to parameterize equations. The model correctly accounts for both annual and genotypic variations, which were observed in 10 genotypes derived from an interspecific cross. They provided important information on the mechanisms underlying the specification of phenotypic differences. In particular, the model supports the hypothesis that a difference in fructokinase affinity could be responsible for a low fructose-to-glucose ratio phenotype, which was observed in the studied population.
Escalating Methamphetamine Regimen Induces Compensatory Mechanisms, Mitochondrial Biogenesis, and GDNF Expression, in Substantia Nigra

Methamphetamine (MA) produces long‐lasting deficits in dopaminergic neurons in the long‐term use via several neurotoxic mechanisms. The effects of MA on mitochondrial biogenesis is less studied currently. So, we evaluated the effects of repeated escalating MA regimen on transcriptional factors involved in mitochondrial biogenesis and glial‐derived neurotrophic factor (GDNF) expression in substantia nigra (SN) and striatum of rat. In male Wistar rats, increasing doses of MA (1–14 mg/kg) were administrated twice a day for 14 days. At the 1st, 14th, 28th, and 60th days after MA discontinuation, we measured the PGC1α, TFAM and NRF1 mRNA levels, indicator of mitochondrial biogenesis, and GDNF expression in SN and striatum. Furthermore, we evaluated the glial fibrillary acidic protein (GFAP) and Iba1 mRNA levels, and the levels of tyrosine hydroxylase (TH) and α‐synuclein (α‐syn) using immunohistochemistry and real‐time polymerase chain reaction (PCR). We detected increments in PGC1α and TFAM mRNA levels in SN, but not striatum, and elevations in GDNF levels in SN immediately after MA discontinuation. We also observed increases in GFAP and Iba1 mRNA levels in SN on day 1 and increases in Iba1 mRNA on days 1 and 14 in striatum. Data analysis revealed that the number of TH+ cells in the SN did not reduce in any time points, though TH mRNA levels was increased on day 1 after MA discontinuation in SN. These data show that repeated escalating MA induces several compensatory mechanisms, such as mitochondrial biogenesis and elevation in GDNF in SN. These mechanisms can reverse MA‐induced neuroinflammation and prevent TH‐immunoreactivity reduction in nigrostriatal pathway. J. Cell. Biochem. 118: 1369–1378, 2017. © 2016 Wiley Periodicals, Inc.
Sarcoidosis and Tuberculosis Cytokine Profiles: Indistinguishable in Bronchoalveolar Lavage but Different in Blood

Background The clinical, radiological and pathological similarities between sarcoidosis and tuberculosis can make disease differentiation challenging. A complicating factor is that some cases of sarcoidosis may be initiated by mycobacteria. We hypothesised that immunological profiling might provide insight into a possible relationship between the diseases or allow us to distinguish between them. Methods We analysed bronchoalveolar lavage (BAL) fluid in sarcoidosis (n = 18), tuberculosis (n = 12) and healthy volunteers (n = 16). We further investigated serum samples in the same groups; sarcoidosis (n = 40), tuberculosis (n = 15) and healthy volunteers (n = 40). A cross-sectional analysis of multiple cytokine profiles was performed and data used to discriminate between samples. Results We found that BAL profiles were indistinguishable between both diseases and significantly different from healthy volunteers. In sera, tuberculosis patients had significantly lower levels of the Th2 cytokine interleukin-4 (IL-4) than those with sarcoidosis (p = 0.004). Additional serum differences allowed us to create a linear regression model for disease differentiation (within-sample accuracy 91%, cross-validation accuracy 73%). Conclusions These data warrant replication in independent cohorts to further develop and validate a serum cytokine signature that may be able to distinguish sarcoidosis from tuberculosis. Systemic Th2 cytokine differences between sarcoidosis and tuberculosis may also underly different disease outcomes to similar respiratory stimuli.
ECG Signal Preprocessing and SVM Classifier-Based Abnormality Detection in Remote Healthcare Applications

Medical expert systems are part of the portable and smart healthcare monitoring devices used in day-to-day life. Arrhythmic beat classification is mainly used in electrocardiogram (ECG) abnormality detection for identifying heart related problems. In this paper, ECG signal preprocessing and support vector machine-based arrhythmic beat classification are performed to categorize into normal and abnormal subjects. In ECG signal preprocessing, a delayed error normalized LMS adaptive filter is used to achieve high speed and low latency design with less computational elements. Since the signal processing technique is developed for remote healthcare systems, white noise removal is mainly focused. Discrete wavelet transform is applied on the preprocessed signal for HRV feature extraction and machine learning techniques are used for performing arrhythmic beat classification. In this paper, SVM classifier and other popular classifiers have been used on noise removed feature extracted signal for beat classification. Results indicate that the performance of SVM classifier is better than other machine learning-based classifiers.
Pain Management During Newborn Screening: Using YouTube to Disseminate Effective Pain Management Strategies

To assess the reach, acceptability, and effect of the BSweet2Babies video showing breast-feeding, skin-to-skin care, and sucrose during blood sampling on intention to recommend the video or advocate for use of the interventions. In July 2014, the video and an electronic survey were produced and posted. After 1 year, the online viewer survey responses and YouTube analytics were analyzed. One year after posting, the BSweet2Babies video had 10 879 views from 125 countries and 187 (1.7%) viewers completed the survey. Most respondents were aware of the analgesic effects of breast-feeding, skin-to-skin care, and sucrose. Nearly all respondents (n = 158, 92%) found the BSweet2Babies video to be a helpful resource and 146 (84%) answered that they would recommend the video to others. After viewing the video, 183 (98%) respondents answered that they would advocate for 1 or more of the interventions. The BSweet2Babies video showing effective pain treatment during blood sampling had a large reach but a very small response rate for the survey. Therefore, analysis of acceptability and effect on intention to recommend the video and advocate for the interventions depicted are limited. Further research is warranted to explore how to best evaluate videos delivered through social media and to determine the effect of the video to promote knowledge translation into clinical practice.
Diagnostic dilemmas and pitfalls in ThinPrep® cytology of breast fine needle aspiration biopsy:

Fine needle aspirations (FNA) of the breast for primary diagnoses have become less popular in the USA and are usually performed for lesions with low or extremely high clinical suspicion. They are also performed for lesions in close proximity to a breast implant. Liquid‐based cytological preparations, such as ThinPrep® (TP), provide a practical alternative to clinicians who are performing FNA. Using a selection of cases that represent challenging diagnoses, we describe common diagnostic pitfalls of breast FNA that are specifically associated with this preparation. Well known breast cytology pitfalls, such as fibroadenoma, when solely examined using a TP slide can be even more challenging since the usual stripped bipolar cells seen in the background of smeared slides, can appear singly dispersed with preserved cytoplasm, resembling carcinoma. We describe that large fragments of solid papillary carcinoma are represented by mostly singly dispersed cells with plasmacytoid features that mimic those of a lobular carcinoma. Since nuclear features are more pronounced in TP, prominent nucleoli and cytological atypia can potentially be overcalled. TP processing might also lead to clumping of epithelioid histiocytes that appear atypical, which increases the suspicion of malignancy. The presence of atypical cells in a TP slide of a peri implant seroma should always undergo additional testing, especially in patients with a prior history of breast carcinoma, to determine if it represents recurrent carcinoma or an implant associated anaplastic large cell lymphoma. Familiarity with the aforementioned artifacts associated with TP is essential to avoid diagnostic misinterpretations. Diagn. Cytopathol. 2017;45:655–661. © 2017 Wiley Periodicals, Inc.
Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform

ABSTRACT Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens. IMPORTANCE While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.
A Major Gene for Flowering Time in Chickpea

Water availability is a major yield-limiting factor in semi-arid regions. Hence, efficient utilization of soil water for grain production depends on correct timing of flowering. Following winter (December-January) sowing, modern Israeli chickpea (Cicer arietinum L.) cultivars begin flowering during the last week of March and their reproductive period extends throughout April to June. In the Middle East, April, May, and June are often dry and hot months. The objectives of this study were (i) to assess the potential range of chickpea germplasm as a source for early flowering, and (ii) to study the inheritance of the time to flowering trait. Germplasm evaluation was carried out by measuring days from germination to flowering and calculating phenotypic correlations between days to first flower, grain weight, and pod number along main branches. A number of early-flowering genotypes were identified, and weak association between flowering time genes and seed weight loci was observed. Crosses were made between types of contrasting photoperiod response. In F 2 populations derived from crosses between an early-flowering breeding line (desi) with weak photoperiodic response and a late-tlowering high-yielding (kabuli) cultivar with a strong photoperiod response, a 3:1 ratio of late-flowering : early-flowering types was observed. This segregation is consistent with action of a major photoperiod response gene (Ppd) affecting time to flowering. Considerable genotype × environment interaction was observed among F 3 progeny of these crosses. The relatively simple inheritance of the photoperiodic response observed in this study suggests that the early-flowering trait may be easily introduced into popular late-flowering genetic backgrounds.
Low complexity adaptive antenna selection for cognitive radio MIMO broadcast channels

A multi-antenna cognitive radio network, with a single pair of primary users and a secondary broadcast channel, is considered. Under perfect channel state information (CSI), the rate-optimal strategy for the primary link is waterfilling, resulting in possibly unused dimensions. The secondary base station, supplied with perfect and global CSI, employs block diagonalization for interference-free message precoding and opportunistic interference alignment to avoid disturbing primary communication. In the absence of sufficient resources to serve all secondary users, a low complexity adaptive antenna selection strategy is proposed. This scheme constructs, in each time-slot, the set of active antennas by opportunistically reusing information and resources from the preceding selection round. Numerical results indicate a complexity reduction at a small rateloss penalty, in comparison with existing selection methods.
Removal of organic matter of electrodialysis reversal brine from a petroleum refinery wastewater reclamation plant by UV and UV/H202 process

ABSTRACT Direct (UV) and hydrogen peroxide-assisted (UV/H2O2) photolysis were investigated in bench-scale for removing the organic compounds present in the electrodialysis reversal (EDR) brine from a refinery wastewater reclamation plant. In the UV/H2O2 experiments, a COD:H2O2 molar ratios of 1:1, 1:2 and 1:3 were tested by recirculating the brine in the UV reactor for 120 min. Results showed a significant reduction in UVA254, whereas no reduction was observed for chemical oxygen demand (COD), in the UV process, suggesting great cleavage but limited mineralization of the organic matter. UV/H2O2 with C:H2O2 ratio of 1:3 exhibited high efficiency in removing the organic matter (COD removal of 92% with an electrical energy per removal order (EEO) value of 22 kW h m−3). Although the EDR brine has high salinity, no strong scavenging effect of •OH was found in the water matrix due to the high concentration of anions, especially chloride and bicarbonate. Finally, UV/H2O2 with C:H2O2 ratio of 1:3 and residence time of 120 min is an efficient alternative for organic matter removal of EDR brine from refinery wastewater reclamation plant showing total capital cost (CapEx) estimated at US$ 369,653.00 and total operational cost (OpEx), at US$ 1.772 per cubic meter of effluent.
Generic hybridization of MOEA/D with learning for permutation flow shop scheduling problem

In this paper, we study the effect of Meta-Lamarckian learning on the performance of a generic hybrid Multi-objective Evolutionary Algorithm based on Decomposition (MOEA/D) to solve a well-known combinatorial Multi-Objective Optimization (MOO) problem. We study the hybridization of MOEA/D with a pool of six general-purpose heuristics so as to locally optimize the solutions during the evolution. We initially consider the six individualistic hybrid MOEA/D's, in which at every step of the evolution the same local search heuristic from the generic pool is applied. MOEA/D is then enriched with a learning strategy that, based on the problem's properties and objective functions, adaptively selects at each step of the evolution and for each problem neighbourhood the best performing local search heuristic from the generic pool of heuristics. The proposed method is evaluated on various test instances of a multi-objective Permutation Flow Shop Scheduling Problem (MO-PFFSP): given a set of jobs and a series of machines, the corresponding processing time of each job on every machine and the due dates of each job, determine a processing order of the jobs on each machine, so as to simultaneously minimize the makespan (total completion time), and the maximum job tardiness. The results of our experimental studies suggest that the proposed method successfully learns the behaviour of individual local search heuristics during the evolution outperforming in terms of both convergence and diversity the conventional MOEA/D and the individualistic hybrid MOEA/D's. The proposed method does not utilize any problem-specific heuristics, and as a result, is readily applicable to other combinatorial MOO problems.
Opponent Modeling in

The goal of our ongoing project is to develop and test various methods of modeling one's opponent in adversarial domains. The texas hold'em domain will be used because it has the key features of imperfect information, stochasticity, and the ability to deceive. These three components allow for a very wide range of human behavior making it difficult to create feasible models using traditional artificial intelligence techniques. It is precisely in these situations where models based on human cognition are most helpful. Their adaptive and flexible methods can overcome the uncertainty and deceptiveness intrinsic to human behavior aiding with naturally difficult domains. In other words, to understand a human it is helpful to think like one.
T Cell Receptor Engagement Leads to Phosphorylation of Clathrin Heavy Chain during Receptor Internalization

T cell receptor (TCR) internalization by clathrin-coated vesicles after encounter with antigen has been implicated in the regulation of T cell responses. We demonstrate that TCR internalization after receptor engagement and TCR signaling involves inducible phosphorylation of clathrin heavy chain (CHC) in both CD4+ and CD8+ human T cells. Studies with mutant Jurkat T cells implicate the Src family kinase Lck as the responsible enzyme and its activity in this process is influenced by the functional integrity of the downstream signaling molecule ZAP-70. CHC phosphorylation positively correlates with ligand-induced TCR internalization in both CD4+ and CD8+ T cells, and CHC phosphorylation as a result of basal Lck activity is also implicated in constitutive TCR endocytosis by CD4+ T cells. Remarkably, irreversible CHC phosphorylation in the presence of pervanadate reduced both constitutive and ligand-induced TCR internalization in CD4+ T cells, and immunofluorescence studies revealed that this inhibition affected the early stages of TCR endocytosis from the plasma membrane. Thus, we propose that CHC phosphorylation and dephosphorylation are involved in TCR internalization and that this is a regulatory mechanism linking TCR signaling to endocytosis.