Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis B virus pX activates NF-kappa B-dependent transcription through a Raf-independent pathway

In this study, we characterized the molecular events involved in the activation of the ubiquitous transcription factor NF-kappa B by the viral transactivator pX. pX expression in HeLa cells determines a manyfold increase in NF-kappa B-dependent transcription, which is associated with an increase in p50/p65 heterodimer DNA-binding activity. Since the I kappa B-alpha inhibitory subunit proteolytic degradation, which follows its phosphorylation/modification, is a key event in NF-kappa B activation by different stimuli (such as growth factors, phorbol esters, tumor necrosis factor, UV irradiation, and oxygen radicals), we investigated pX effects on I kappa B-alpha, as well as the possible involvement of known signalling pathways in pX-induced NF-kappa B-dependent transcription. We observed that although pX had no direct effect on p50 or p65, it was able to restore the I kappa B-alpha-suppressed p50/p65 activity. More directly, the stable expression of pX in HeLa cells resulted in reduced levels of I kappa B-alpha in the cytoplasm. Pretreatment of the cells with H7, calphostin C, tyrphostin 25, or N-acetylcysteine did not impair the effects of pX on NF-kappa B, thus ruling out the involvement of protein kinase C, tyrosine kinases, and oxygen radicals. Finally, while most of the known NF-kappa B-activating agents converge on Raf-1 protein kinase, when Raf-1 activity is blocked by overexpression of a dominant negative mutant, the effects of pX on NF-kappa B are not impaired. Thus, we suggest that although pX is able to activate the Ras/Raf-1-signalling pathway, it triggers NF-kappa B activation by an as yet unidentified Raf-1-independent pathway.
Effects of Feiyanning Decoction on proliferation of lung adenocarcinoma cell line and their production of interleukin-6 and interleukin-8 induced by tumor necrosis factor-alpha.

OBJECTIVE To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on proliferation of lung adenocarcinoma cell line A549 cells and their production of interleukin-6 (IL-6) and IL-8 induced by tumor necrosis factor-alpha (TNF-alpha). METHODS A549 cells were incubated with rat serum containing Feiyanning Decoction at 15% for 24, 48 and 72 h respectively. The cell proliferation was examined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt assay (WST-8). The production of IL-6 and IL-8 was tested by enzyme-linked immunosorbent assay after 48-hour treatment of reagents, and the expressions of IL-6 and IL-8 mRNAs were detected by reverse transcription-polymerase chain reaction. RESULTS Serum containing Feiyanning Decoction had obvious inhibitive functions in A549 cell proliferation after 48- and 72-treatment. TNF-alpha (1 microg/L) strongly induced the production of IL-6 and IL-8 as compared with the control serum in A549 cells, and the induced cytokine production was significantly suppressed by 15% serum containing Feiyanning Decoction (P<0.01). In addition, serum containing Feiyanning Decoction could inhibit the mRNA expressions of IL-6 and IL-8 (P<0.01). CONCLUSION Feiyanning Decoction can inhibit IL-6 and IL-8 production induced by TNF-alpha. It is therefore expected to be a new strategy for treating lung cancer.
RNase III-dependent Regulation of Yeast Telomerase*

In bakers’ yeast, in vivo telomerase activity requires a ribonucleoprotein (RNP) complex with at least four associated proteins (Est2p, Est1p, Est3p, and Cdc13p) and one RNA species (Tlc1). The function of telomerase in maintaining chromosome ends, called telomeres, is tightly regulated and linked to the cell cycle. However, the mechanisms that regulate the expression of individual components of telomerase are poorly understood. Here we report that yeast RNase III (Rnt1p), a double-stranded RNA-specific endoribonuclease, regulates the expression of telomerase subunits and is required for maintaining normal telomere length. Deletion or inactivation of RNT1 induced the expression of Est1, Est2, Est3, and Tlc1 RNAs and increased telomerase activity, leading to elongation of telomeric repeat tracts. In silico analysis of the different RNAs coding for the telomerase subunits revealed a canonical Rnt1p cleavage site near the 3′ end of Est1 mRNA. This predicted structure was cleaved by Rnt1p and its disruption abolished cleavage in vitro. Mutation of the Rnt1p cleavage signal in vivo impaired the cell cycle-dependent degradation of Est1 mRNA without affecting its steady-state level. These results reveal a new mechanism that influences telomeres length by controlling the expression of the telomerase subunits.
Systematic Analysis of a Simple Adaptor Protein PDZK1: Ligand Identification, Interaction and Functional Prediction of Complex

PDZK1 is a simple adaptor protein with four protein interaction PDZ domains, but without any other known functional domains. Here, we used yeast two-hybrid screening of a random peptide library and high-throughput validation screening of a specialized PDZ ligand candidate library to systematically and comprehensively identify PDZK1 ligands. The potential functional associations of the ligands were predicted by functional annotations from a MILANO literature search and subcellular localizations. The ligands were considered more likely to be functionally associated if they had similar patterns of functions or closely related functions. For some functionally associated ligand pairs, interaction with one ligand was found to be influenced by another ligand in a yeast three-hybrid system. Many G-protein signaling pathway-related proteins were found to interact with PDZK1, and they were likely to be functionally associated with transporters based on their closely related functions. This strategy can be extended to the study of other adaptor proteins that contain peptide-binding domains.
Biomedical named entity recognition based on the two channels and sentence-level reading control conditioned LSTM-CRF

Biomedical named entity recognition (Bio-NER) is an important preliminary step for many biomedical text mining tasks. The current mainstream methods for NER are based on the neural networks to avoid the complex hand-designed features derived from various linguistic analyses. However, the performance of these methods is always limited to exploring dependencies across output label and ignoring some potential word-level and sentence-level semantic information. Therefore, we propose a novel Long Short Term Memory (LSTM) Networks model SC-LSTM-CRF integrating two channels and the sentence-level embeddings for Bio-NER. In our model, two channels word embeddings are introduced as the input to obtain more abundant potential information, and the sentence-level reading control gate (SC) is inserted into the networks to integrate the implicit meaning of an entire sentence. The experimental results conducted on the BioCreative II GM corpus show that our method can achieve an F-score of 89.49%, which outperforms all state-of-the-art systems and is 0.88% higher than the best performing neural networks.
Awareness, Practices and Treatment Seeking Behavior of Type 2 Diabetes Mellitus Patients in Delhi

Background: Type 2 diabetes mellitus is a multisystem disorder that is associated with number of complications. Patient’s awareness and practices are crucial components in reducing the burden of diseases and its complications. Aim: To assess patient’s knowledge about their disease and its complications, practices, treatment seeking behavior and average expenditure incurred by its management. Subjects and Methods: A community based cross sectional study was conducted in rural and urban slum areas of Delhi selecting a total of 98 diabetic patients diagnosed during the two community surveys and interviewed using pretested and predesigned questionnaire. Data were analyzed using SPSS software, version 17 (Chicago II, USA). Chi square, fisher or Mann–Whitney tests were used for test of significance and considered statistically significant at P < 0.05. Results: Of 98 participants, 31.6% (31/98) were from urban slum area, and 68.4% (67/98) were from the rural area. In both urban and rural areas, majority were Hindu, married, literate and unemployed. Significantly less subjects (61.3%, 19/31) of urban slum area than of rural area (85.1%, 57/67) could name at least one complication of DM (P < 0.01, odds ratio [OR] =3.6, 95% confidence interval [CI] =1.3–9.6). Majority of participants in both urban slum and rural area have knowledge about at least one component of management but significantly lesser in urban (83.9%, 26/31) than rural area (97.0%, 65/67) were reported (P = 0.02, OR = 6.2, 95% CI = 1.1–34.2). Significantly more subjects (29.0%, 9/31) in urban slum area than rural areas (7.5%, 5/67) reported that they were not taking any treatment for DM (P < 0.01, OR = 0.2, 95% CI = 0.1–0.6). In urban area, 32.2% (10/31) patients told that it is a burden on their family while in rural area 44.7% (30/67) of the patients told that they have to squeeze money from the family expenditure to afford drugs. Conclusion: Patients need to be made aware of the asymptomatic phase of DM and its long term complications. At the same time, efforts should be made to sensitize them about the importance of taking regular treatment and management.
Mothers' Responses to Children's Pain

ObjectivesThis study was aimed at identifying mothers' responses to children's pain, evaluating whether these could be organized into different types of responses, and developing a questionnaire to assess these responses. MethodsCommon responses to children's pain were identified on the basis of a review of the literature and interviews with mothers of pediatric patients with pain. Categories reflecting these parenting behaviors were generated for a questionnaire on Adult Responses to Children's Symptoms, which was administered to 145 mothers of pediatric patients aged between 8–18 years referred for medical evaluation of abdominal pain. ResultsFactor analysis using principal components extraction with oblique rotation yielded 3 factors. Factor 1, Protect, reflected caretaking behaviors that placed the child in a passive sick role. Factor 2, Minimize, reflected criticism of the child's pain behavior. Factor 3, Encourage and Monitor, reflected encouragement of the child's activity while monitoring the child's symptoms. Subscales based on these correlated factors had good internal consistency. DiscussionResults suggest that mothers' responses to children's pain behavior may be classified into 3 distinct categories. Additional research is needed to assess whether observational methodologies would yield a similar typology of parents' responses to children's pain. Psychometric properties of the Adult Responses to Children's Symptoms should be examined in larger samples and in studies of the relation of the subscales to related constructs (eg, measures of parenting beliefs and behavior) and to children's pain behavior.
IP3R-mediated Ca2+ release regulates protein metabolism in Drosophila neuroendocrine cells: implications for development under nutrient stress

Successful completion of animal development is fundamentally reliant on nutritional cues. Surviving periods of nutritional insufficiency requires adaptations that are coordinated, in part, by neural circuits. As neuropeptides secreted by neuroendocrine (NE) cells modulate neural circuits, we investigated NE cell function during development under nutrient stress. Starved Drosophila larvae exhibited reduced pupariation if either insulin signaling or IP3/Ca2+ signaling were downregulated in NE cells. Moreover, an IP3R (inositol 1,4,5-trisphosphate receptor) loss-of-function mutant displayed reduced protein synthesis, which was rescued by overexpression of either InR (insulin receptor) or IP3R in NE cells of the mutant, suggesting that the two signaling pathways might be functionally compensatory. Furthermore, cultured IP3R mutant NE cells, but not neurons, exhibited reduced protein translation. Thus cell-specific regulation of protein synthesis by IP3R in NE cells influences protein metabolism. We propose that this regulation helps developing animals survive in poor nutritional conditions. Summary: Intracellular Ca2+ signaling regulates protein translation and can compensate for insulin signaling in specialized neuro-hormonal cells, thus enabling Drosophila larval to pupal development under acute starvation.
Relationship of quality goals and measurement performance to the selection of quality control procedures for multi‐channel haematology analysers

Abstract: An approach is described for selecting QC procedures based on goals for analytical quality, the performance characteristics of the measurement procedure (imprecision, bias, frequency of errors), and the performance characteristics of the control procedure (probabilities for error detection and false rejection). Performance characteristics of stable sample QC procedures and patient data QC procedures (retained patient specimens, Bull's single‐rule algorithm, Bull's multi‐rule algorithm) are compared to determine when to apply these different QC procedures to multichannel hematology ! analysers. Precise, stable methods may be controlled using Bull's single‐rule algorithm; less precise, less stable methods require Bull's multi‐rule algorithm, retained patient specimens, or stable sample QC procedures; imprecise and unstable methods are best controlled using stable sample QC procedures. “Multi‐stage” designs may employ stable samples for “startup” testing, retained patient specimens for short term monitoring, and Bull's single‐rule algorithm for long term monitoring.
Membrane-associated farnesylated UCH-L1 promotes α-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is linked to Parkinson's disease (PD) and memory and is selectively expressed in neurons at high levels. Its expression pattern suggests a function distinct from that of its widely expressed homolog UCH-L3. We report here that, in contrast to UCH-L3, UCH-L1 exists in a membrane-associated form (UCH-L1M) in addition to the commonly studied soluble form. C-terminal farnesylation promotes the association of UCH-L1 with cellular membranes, including the endoplasmic reticulum. The amount of UCH-L1M in transfected cells is shown to correlate with the intracellular level of α-synuclein, a protein whose accumulation is associated with neurotoxicity and the development of PD. Reduction of UCH-L1M in cell culture models of α-synuclein toxicity by treatment with a farnesyltransferase inhibitor (FTI-277) reduces α-synuclein levels and increases cell viability. Proteasome function is not affected by UCH-L1M, suggesting that it may negatively regulate the lysosomal degradation of α-synuclein. Therefore, inhibition of UCH-L1 farnesylation may be a therapeutic strategy for slowing the progression of PD and related synucleinopathies.
Facts and myths about zero-point thermal noise, and information entropy versus thermal entropy

In this talk, we are briefly surveying our recent results [1–3] about two very popular yet often misunderstood concepts in physical informatics: (i) The existence of Johnson noise at near to absolute zero temperature has been debated many times yet it is generally accepted [1]. We point out the fundamental problems [2] with the particular approach the related quantum theories [4] of Fluctuation-Dissipation Theorem are using. Then we prove that the existence of zero-point noise would allow the construction of a perpetual motion machine [1]. Finally, we cite early works pointing out that the observed “zeropoint” noise in experiments [7] with phase-sensitive linear amplifiers is an amplifier-noise [5,6] due to the uncertainty principle, and it does not exist in the resistor in an objective way, independently from the measurement [1,2]. Thus a correct derivation of the Fluctuation-Dissipation Theorem must include [1] the type of experimental setup used for the measurement. (ii) The general opinion is that information entropy and thermal entropy are interchangeable. This belief triggered Brillouin's negentropy principle of information [8], and Landauer's claimed principle [9] about energy dissipation during information erasure that has been debated on many occasions [10–19]. Here we show the newest and perhaps the simplest arguments [3] proving that the two types of entropies are apples and oranges and are not interchangeable.
Multiplex PCR for detection of plasmid-mediated quinolone resistance qnr genes in ESBL-producing enterobacterial isolates.

OBJECTIVES To develop a rapid and reliable single-tube-based PCR technique for detecting simultaneously the plasmid-mediated quinolone resistance qnrA, qnrB and qnrS genes. METHODS After multiple alignments, primers were designed to detect known qnr variants (six for qnrA-, six for qnrB- and two for qnrS-like genes). They were used for screening a collection of 64 expanded-spectrum beta-lactamase (ESBL)-producing enterobacterial isolates from Kuwait, collected from 2002 to 2004, as ESBL genes have been often associated with qnr genes. Sequencing was performed to identify qnr and associated ESBL genes. RESULTS In optimized conditions, all positive controls (used separately or mixed) confirmed the specificity of the PCR primers. Out of 64 isolates, only 3 isolates were positive for a qnrB-like gene (4.7%), whereas no qnrA-like and qnrS-like gene was detected. A qnrB2 gene was detected in an Enterobacter cloacae K34 (SHV-12+) isolate, whereas qnrB1-like (termed qnrB7) and qnrB6-like (termed qnrB8) genes were identified from E. cloacae K37 (SHV-12+) and Citrobacter freundii K70 (VEB-1b+) isolates, respectively. CONCLUSIONS We report here a fast and reliable technique for rapid screening of qnr-positive strains to be used for epidemiological surveys. A low prevalence of Qnr determinants among ESBL-producing Enterobacteriaceae was identified in the study with Kuwaiti isolates.
SDR processing delay estimation applying correlation detection for structure health monitoring using multi-subcarrier multiple access

Wireless and battery-less structural health monitoring (SHM) that detect structural damage at low cost are required. To achieve this, the use of multi-subcarrier multiple access (MSMA) communication method is being considered. In MSMA, time synchronization of sensing data is shifted owing to software defined radio (SDR) processing. Therefore, when an SHM monitoring method requiring time synchronization of sensing data is used, time synchronization taking SDR processing delay into account is necessary. In this study, we propose a system that estimates SDR processing delay by correlation detection and acquires time synchronization of sensing data. We measured SDR delay estimation with time accuracy by installing this system on an experimental object. Results showed that the error of the allowable processing delay estimation was different, and time synchronization can be achieved by performing sensing once by the SDR processing delay estimation method using correlation detection.
Large Scale Graph Learning from Smooth Signals

Graphs are a prevalent tool in data science, as they model the inherent structure of the data. They have been used successfully in unsupervised and semi-supervised learning. Typically they are constructed either by connecting nearest samples, or by learning them from data, solving an optimization problem. While graph learning does achieve a better quality, it also comes with a higher computational cost. In particular, the current state-of-the-art model cost is $\mathcal{O}(n^2)$ for $n$ samples. In this paper, we show how to scale it, obtaining an approximation with leading cost of $\mathcal{O}(n\log(n))$, with quality that approaches the exact graph learning model. Our algorithm uses known approximate nearest neighbor techniques to reduce the number of variables, and automatically selects the correct parameters of the model, requiring a single intuitive input: the desired edge density.
Non‐parametric inference of adverse events under informative censoring

In long‐term treatments or in treatments associated with frequent severe adverse events (AEs) such as those for oncology, it is important to know the probability of occurrence of AEs over time and their severity. However, some patients discontinue treatment and drop out of the clinical trial. Assumption that the drop‐outs are non‐informative is not always true and are not validated by data.
Effect of yoga on the Myofascial Pain Syndrome of neck

Myofascial Pain Syndrome (MPS) refers to pain attributed to muscle and its surrounding fascia, which is associated with “myofascial trigger points” (MTrPs). MTrPs in the trapezius has been proposed as the main cause of temporal and cervicogenic headache and neck pain. Literature shows that the prevalence of various musculoskeletal disorders (MSD) among physiotherapists is high. Yoga has traditionally been used to treat MSDs in various populations. But there is scarcity of literature which explains the effects of yoga on reducing MPS of the neck in terms of various physical parameters and subjective responses. Therefore, a pilot study was done among eight physiotherapists with minimum six months of experience. A structured yoga protocol was designed and implemented for five days in a week for four weeks. The outcome variables were Disability of Arm, Shoulder and Hands (DASH) score, Neck Disability Index (NDI), Visual Analogue Scale (VAS), Pressure Pain Threshold (PPT) for Trigger Points, Cervical Range of Motion (CROM) - active & passive, grip and pinch strengths. The variables were compared before and after the intervention. Finally, the result revealed that all the variables (DASH: P<0.00, NDI: P<0.00, VAS: P<0.00, PPT: Left: P<0.00, PPT: Right: P<0.00, Grip strength: left: P<0.00, Grip strength: right: P<0.01, Key pinch: left: P<0.01, Key pinch: right: P<0.01, Palmar pinch: left: P<0.01, Palmar pinch: right: P<0.00, Tip pinch: left: P<0.01, Tip pinch: Right: P<0.01) improved significantly after intervention.
ATP6AP2/(Pro)renin Receptor Contributes to Glucose Metabolism via Stabilizing the Pyruvate Dehydrogenase E1 β Subunit*

Background: The mechanism of efficient energy generation in the highly evolved mammalian retina remains incompletely understood. Results: ATP6PA2 interacts with the E1 β subunit of pyruvate dehydrogenase, a key enzyme in aerobic energy generation, controlling its protein stability. Conclusion: ATP6AP2 contributes to glucose metabolism together with oxidative stress. Significance: The present data provide a novel insight into the biological function of ATP6AP2 in the retina. Aerobic glucose metabolism is indispensable for metabolically active cells; however, the regulatory mechanism of efficient energy generation in the highly evolved mammalian retina remains incompletely understood. Here, we revealed an unsuspected role for (pro)renin receptor, also known as ATP6AP2, in energy metabolism. Immunoprecipitation and mass spectrometry analyses identified the pyruvate dehydrogenase (PDH) complex as Atp6ap2-interacting proteins in the mouse retina. Yeast two-hybrid assays demonstrated direct molecular binding between ATP6AP2 and the PDH E1 β subunit (PDHB). Pdhb immunoreactivity co-localized with Atp6ap2 in multiple retinal layers including the retinal pigment epithelium (RPE). ATP6AP2 knockdown in RPE cells reduced PDH activity, showing a predilection to anaerobic glycolysis. ATP6AP2 protected PDHB from phosphorylation, thus controlling its protein stability. Down-regulated PDH activity due to ATP6AP2 knockdown inhibited glucose-stimulated oxidative stress in RPE cells. Our present data unraveled the novel function of ATP6AP2/(P)RR as a PDHB stabilizer, contributing to aerobic glucose metabolism together with oxidative stress.