Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway

Significance Subcutaneous injections of insulin sustain life in mammals unable to produce insulin (type 1 diabetes) but do not prevent hyperglycemic and hypoglycemic swings or decrease hemoglobin A1c levels to normal amounts. In mice treated with insulin alone, repeated episodes of transient elevated blood glucose cause long-term damage. We show that in mice with type 1 diabetes treated with insulin, the transient high blood glucose levels require production of glucagon, a hormone that will cause the liver to produce more glucose. Blocking the action of glucagon with an antibody to the glucagon receptor completely normalizes blood glucose and hemoglobin A1c in the complete absence of insulin therapy. Suppressing glucagon action in combination with low-dose insulin would be a superior treatment for type 1 diabetes. Insulin monotherapy can neither maintain normoglycemia in type 1 diabetes (T1D) nor prevent the long-term damage indicated by elevated glycation products in blood, such as glycated hemoglobin (HbA1c). Here we find that hyperglycemia, when unaccompanied by an acute increase in insulin, enhances itself by paradoxically stimulating hyperglucagonemia. Raising glucose from 5 to 25 mM without insulin enhanced glucagon secretion ∼two- to fivefold in InR1-G9 α cells and ∼18-fold in perfused pancreata from insulin-deficient rats with T1D. Mice with T1D receiving insulin treatment paradoxically exhibited threefold higher plasma glucagon during hyperglycemic surges than during normoglycemic intervals. Blockade of glucagon action with mAb Ac, a glucagon receptor (GCGR) antagonizing antibody, maintained glucose below 100 mg/dL and HbA1c levels below 4% in insulin-deficient mice with T1D. In rodents with T1D, hyperglycemia stimulates glucagon secretion, up-regulating phosphoenolpyruvate carboxykinase and enhancing hyperglycemia. GCGR antagonism in mice with T1D normalizes glucose and HbA1c, even without insulin.
Early Holocene decadal-scale ocean variability recorded in Gulf of California laminated sediments

Scanning electron microscope examination of Holocene laminated sediment from Guaymas Basin, Gulf of California, resolves up to five depositional events per year. Each lamina/sublamina of an early Holocene section of continuously laminated sediment was recorded from backscattered electron imagery photomosaic analysis. Diatom mat laminae, composed predominantly of Thalassiothrix longissima, are associated with early winter mixed diatom flora laminae. Mats are probably brought into the Gulf with Pacific water during the summer, concentrated at the surface or at the pycnocline, and then rapidly deposited in the early winter as water column stratification breaks down. Time series analysis of one ∼300-year section from piston core JPC56 revealed significant periodicities in the deposition of mat laminae at ∼50 years, ∼11 years, and 22–24 years. An ∼50-year cycle in fish populations has been related to changing North Pacific ocean/atmosphere circulation. These Pacific-wide changes in circulation affect the currents dominant at the mouth of the Gulf. When the California Current is dominant, fewer diatom mats are imported into the Gulf, and when the north equatorial Pacific gyre is dominant, more are imported. The ∼11-year, 22- to 24-year, and ∼50-year cycles are all suggested to be influenced by solar cycles.
Study of acute diarrhoea among preschool children from below poverty line families of Lucknow district, North India

Background: Acute diarrheal illness remains one of the major causes of childhood morbidity and mortality especially among children under five in developing countries. Many of the risk factors for contracting diarrheal illnesses are associated with poverty, such as lacking access to safe water and sanitation, poor hygiene practices and unsafe human waste disposal. Objective of the study was to know the prevalence of acute diarrhoea and find out certain associated risk factors among preschool children from below poverty line family of Lucknow district.Methods: A community based cross sectional study was conducted using multistage sampling in rural and urban areas of Lucknow district from August, 2012 to July, 2013. Total 352 children aged 12-47 months from Below Poverty Line families were enrolled in this study. Mothers were interviewed after taking informed consent on pretested predesigned questionnaire.Results: A total of 352 children were participated in this study, of which 75 were suffering from acute diarrhea, thus giving a two-week prevalence of 21.3%. The main risk factors for acute diarrheal illness were found to be Unimproved/no toilet facility, unsafe disposal of children stool, having piped water supply, storage of drinking water at household level, not received complimentary feeding within specified period and no vitamin A supplementation.Conclusions: Approximately one-fifth of the children included in the study reported diarrheal disease. Building toilets and providing safe drinking water at the household level, interventions through effective health education of the community regarding appropriate complimentary feeding and immunization practices may reduce the burden of diarrhoea among these children.
Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement

Using the clone-specific rearrangement of the T cell receptor gene as the genetic marker of the clonotype, we analyzed the clonal origin of the interleukin 2 (IL-2)-dependent human T-lymphotrophic virus I (HTLV- I)-positive T cell lines established from various adult T cell leukemia (ATL) patients. From a patient with chronic ATL, whose leukemic cells proliferated in vitro in response to IL-2, we repeatedly established leukemic T cell clones having the same rearrangement profile of the T beta chain gene as the leukemic cells. By contrast, established cell lines from acute ATL patients had different beta chain gene rearrangements from those of the leukemic cells. These HTLV-I+ T cell lines might not be the direct progeny of the leukemic cells, but that of T cells infected either in vivo or in vitro. These IL-2-reactive nonleukemic T cells might have been selected in vitro, because their leukemic cells failed to respond to IL-2, despite the expression of IL- 2 receptor. The analysis of the T cell receptor gene rearrangement may give a new approach for the elucidation of the mechanism of leukemogenesis and the origin of the HTLV-I+ T cell lines in ATL.
Geochemistry of Pyrite from the Gangcha Gold Deposit, West Qinling Orogen, China: Implications for Ore Genesis

The Gangcha gold deposit was discovered in 2011 in the Xiahe‐Hezuo region, West Qinling Orogen, China. Five types of pyrite have been identified in the ore according to the detailed mineral paragenetic studies. Geochemical data are presented for type I pyrite (py1) rim‐core zonation and for the different types of pyrite based on in‐situ laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) and electron probe microanalysis (EPMA). The results show that pyrites are characterized with heterogeneous Au concentrations, which indicate that Au occurs mainly as micro‐ or nano‐particle native inclusions. Time‐resolved depth profiles demonstrate that As, Co and Ni occur as solid solutions in pyrite, whereas Cu, Pb, Zn and Ag occur mainly as inclusions. Trace element concentrations differ between rims and cores in py1, and the differences also exist within different pyrite types. These differences indicate complex chemical evolution of the ore‐forming fluids, and the overall geology, geochronology, and stable isotope and pyrite data suggest that the ore‐forming fluids were closely linked to magmatic activity during the Triassic Period in West Qinling orogenic belt.
KLF 5 promotes apoptosis induced by phorbol ester as an effector of the autocrine factor TNFα in LNCaP prostate cancer cells

Krüppel-like factor 5 (KLF5) is frequently deleted and inactivated in prostate cancer, and exerts tumor-suppressing function in prostate cancer cells. However, the function of KLF5 in the apoptosis of prostate cancer cells remains unclear. In the present study, the effect of KLF5 on phorbol 12-myristate 13-acetate (PMA)-induced apoptosis was investigated in prostate cancer LNCaP cells. It was demonstrated that PMA induced the expression of KLF5 at the mRNA and protein level. To identify whether KLF5 regulates the activity of the downstream pathway, stable KLF5 knockdown or overexpression cell lines were constructed with lentivirus harboring shRNA targeting KLF5 or full-length KLF5 in LNCaP cells. Knockdown of KLF5 significantly decreased PMA-induced apoptosis, while cell apoptosis was significantly increased following KLF5 overexpression compared with the corresponding control groups. Consistently, expression of cleaved poly(ADP-ribose) polymerase and caspase-3 induced by PMA was decreased following KLF5 knockdown and increased following KLF5 overexpression. Using the control medium from cells treated with PMA, it was demonstrated that KLF5 is required for the control medium to induce apoptosis. c-Jun N-terminal kinase (JNK) activity is essential for the apoptosis induced by PMA. It was revealed that knockdown of KLF5 decreased, while overexpression of KLF5 increased the phosphorylation of JNK induced by PMA and control medium treatment. Furthermore, inhibition of tumor necrosis factor α (TNFα) decreased KLF5 expression and significantly decreased cell apoptosis induced by PMA, and control medium. This data indicates that KLF5 is essential for the apoptosis induced by PMA in LNCaP prostate cancer cells. Furthermore, KLF5 is essential for activity of the autocrine factor TNFα, which is secreted by cells treated with PMA and mediates the function of PMA-induced apoptosis through regulating the activity of JNK signaling pathway. These results provide novel insights into the complexity of the signaling pathways regulating apoptosis in prostate cancer cells, which could aid in the development of novel treatments for patients with prostate cancer.
A Positive Autoregulatory Loop of LMP1 Expression and STAT Activation in Epithelial Cells Latently Infected with Epstein-Barr Virus

ABSTRACT STAT3 and STAT5 are constitutively activated and nuclear in nasopharyngeal carcinoma (NPC) cells. In normal signaling, STATs are only transiently activated. To investigate whether Epstein-Barr virus (EBV), and in particular the protein LMP1, contributes to sustained STAT phosphorylation and activation in epithelial cells, we examined STAT activity in two sets of paired cell lines, HeLa, an EBV-converted HeLa cell line, HeLa-Bx1, the NPC-derived cell line CNE2-LNSX, and an LMP1-expressing derivative, CNE2-LMP1. EBV infection was associated with a significant increase in the tyrosine-phosphorylated forms of STAT3 and STAT5 in HeLa-Bx1 cells. This effect correlated with LMP1 expression, since phosphorylated STAT3 and STAT5 levels were also increased in CNE2-LMP1 cells relative to the control CNE2-LNSX cells. No change was observed in STAT1 or STAT6 phosphorylation in these cell lines, nor was there a significant change in the levels of total STAT3, STAT5, STAT1, or STAT6 protein. Tyrosine phosphorylation allows the normally cytoplasmic STAT proteins to enter the nucleus and bind to their recognition sequences in responsive promoters. The ability of LMP1 to activate STAT3 was further established by immunofluorescence assays in which coexpression of LMP1 in transfected cells was sufficient to mediate nuclear relocalization of Flag-STAT3 and by an electrophoretic mobility shift assay which showed that LMP1 expression in CNE2-LNSX cells was associated with increased endogenous STAT3 DNA binding activity. In addition, the activity of a downstream target of STAT3, c-Myc, was upregulated in HeLa-Bx1 and CNE2-LMP1 cells. A linkage was established between interleukin-6 (IL-6)- and LMP1-mediated STAT3 activation. Treatment with IL-6 increased phosphorylated STAT3 levels in CNE2-LNSX cells, and conversely, treatment of CNE2-LMP1 cells with IL-6 neutralizing antibody ablated STAT3 activation and c-Myc upregulation. The previous observation that STAT3 activated the LMP1 terminal repeat promoter in reporter assays was extended to show upregulated expression of endogenous LMP1 mRNA and protein in HeLa-Bx1 cells transfected with a constitutively activated STAT3. A model is proposed in which EBV infection of an epithelial cell containing activated STATs would permit LMP1 expression. This in turn would establish a positive feedback loop of IL-6-induced STAT activation, LMP1 and Qp-EBNA1 expression, and viral genome persistence.
Multi-Path Model and Sensitivity Analysis for Galvanic Coupled Intra-Body Communication Through Layered Tissue

New medical procedures promise continuous patient monitoring and drug delivery through implanted sensors and actuators. When over the air wireless radio frequency (OTA-RF) links are used for intra-body implant communication, the network incurs heavy energy costs owing to absorption within the human tissue. With this motivation, we explore an alternate form of intra-body communication that relies on weak electrical signals, instead of OTA-RF. To demonstrate the feasibility of this new paradigm for enabling communication between sensors and actuators embedded within the tissue, or placed on the surface of the skin, we develop a rigorous analytical model based on galvanic coupling of low energy signals. The main contributions in this paper are: (i) developing a suite of analytical expressions for modeling the resulting communication channel for weak electrical signals in a three dimensional multi-layered tissue structure, (ii) validating and verifying the model through extensive finite element simulations, published measurements in existing literature, and experiments conducted with porcine tissue, (iii) designing the communication framework with safety considerations, and analyzing the influence of different network and hardware parameters such as transmission frequency and electrode placements. Our results reveal a close agreement between theory, simulation, literature and experimental findings, pointing to the suitability of the model for quick and accurate channel characterization and parameter estimation for networked and implanted sensors.
Effect of Different Essential Oils on the Shelf Life of Concentrated Yogurt

Aims: The objective of this study is to use different essential oils (cinnamon, clove, rosemary, almond sweet, sesame, wheat germ, and cedar wood) in concentrated yoghurt as antimicrobial agents to increase shelf life of concentrated yoghurt. Place and Duration of Study: Department of Food Technology, Faculty of Science and Technology, Al-Quds University, Palestine, between January 2015 to August 2016. Methodology: Essential oils were added to concentrated yogurt at a concentration of 250 μl\kg. Antibacterial activity and properties of major borne bacteria such as total aerobic count bacteria, yeast, mold, Staphylococcus aureus, were evaluated by plate count method, (pouring plate method). All yogurt samples were sensory evaluated for flavor, body and texture, and appearance. Total solid content, and titratable acidity of different yogurt samples were also determined. Results: Total solids and pH of concentrated yogurt samples treated with essential oils were only slightly affected. The best three essential oils used in terms of influence on total bacterial viable count and mold count were found to be cinnamon, clove and rosemary. The most acceptable organoleptic properties of treated concentrated yogurt were those samples treated with sesame and rosemary oils. Conclusion: The addition of cinnamon, clove and rosemary essential oils could increase the shelf life of concentrated yogurt.
Paclitaxel promotes differentiation of myeloid-derived suppressor cells into dendritic cells in vitro in a TLR4-independent manner

Myeloid cells play a key role in the outcome of anti-tumor immunity and response to anti-cancer therapy, since in the tumor microenvironment they may exert both stimulatory and inhibitory pressures on the proliferative, angiogenic, metastatic, and immunomodulating potential of tumor cells. Therefore, understanding the mechanisms of myeloid regulatory cell differentiation is critical for developing strategies for the therapeutic reversal of myeloid derived suppressor cell (MDSC) accumulation in the tumor-bearing hosts. Here, using an in vitro model system, several potential mechanisms of the direct effect of paclitaxel on MDSC were tested, which might be responsible for the anti-tumor potential of low-dose paclitaxel therapy in mice. It was hypothesized that a decreased level of MDSC in vivo after paclitaxel administration might be due to (i) the blockage of MDSC generation, (ii) an induction of MDSC apoptosis, or (iii) the stimulation of MDSC differentiation. The results revealed that paclitaxel in ultra-low concentrations neither increased MDSC apoptosis nor blocked MDSC generation, but stimulated MDSC differentiation towards dendritic cells. This effect of paclitaxel was TLR4-independent since it was not diminished in cell cultures originated from TLR4−/− mice. These results support a new concept that certain chemotherapeutic agents in ultra-low non-cytotoxic doses may suppress tumor progression by targeting several cell populations in the tumor microenvironment, including MDSC.
Polyethylene glycol-conjugated growth hormone-releasing hormone is long acting and stimulates GH in healthy young and elderly subjects.

OBJECTIVE The clinical use of growth hormone-releasing hormone (GHRH) is limited by its short half-life. Polyethylene glycol-conjugated GHRH (PEG-GHRH) was developed to provide increased stability compared with the currently available GHRH(1-29). This study aimed to evaluate the safety, tolerability and pharmacodynamics of PEG-GHRH. DESIGN PEG-GHRH was administered by subcutaneous injection to young healthy men (n = 12) and elderly men and women (aged > 60 years; n = 20). RESULTS In both groups, administration of PEG-GHRH generated a clear increase in circulating GH compared with placebo. Following single-dose (0.25, 0.5, 2 or 4 mg) administration to young subjects, the effect persisted for 12 h, but a sustained increase was observed on repeated administration to the elderly. Serum insulin-like growth factor-I also increased in response to PEG-GHRH treatment. Injection-site reactions were more frequent with PEG-GHRH compared with placebo, but these were mild and transient; other adverse events were similar to those observed after placebo. Some impairment of glucose tolerance was observed in the elderly following repeated administration of PEG-GHRH. Antibodies to GHRH were not observed. CONCLUSIONS PEG-GHRH offers the possibility of less frequent dosing compared with GHRH. This possibility deserves further clinical testing.
Post-aspiration in standard Italian: some first cross-regional acoustic evidence

Voiceless geminate stops in Italian are typically described as unaspirated in all positions (e.g. [1, 2]). However, recent acoustic phonetic analysis of part of a corpus of standard Italian speech data has shown that the geminate voiceless stops /pp tt kk/ are frequently realized with both preaspiration i.e. [ h p: h t: h k:] (cf. [3]) and post-aspiration. This paper focuses on the latter phenomenon, presenting acoustic phonetic evidence in the form of VOT duration values for /pp tt kk/ tokens recorded in 15 Italian cities (based on the CLIPS corpus of spoken Italian [4, 5]). The co-occurrence of post-aspiration with preaspiration is considered and results are discussed with a focus on regional patterns. Index Terms: post-aspiration, Italian, geminate, voiceless stop, preaspiration
Bitstream-based feature extraction for wireless speech recognition

In this paper, we propose a feature extraction method for a speech recognizer that operates in digital communication networks. The feature parameters are basically extracted by converting the quantized spectral information of a speech coder into a cepstrum. We also combine the voiced/unvoiced information obtained from the bitstream of the speech coder into the recognition feature set. From speaker-independent connected digit HMM recognition, we find that the speech recognition system employing the proposed bitstream-based front-end gives superior word and string accuracies over a recognizer constructed from decoded speech signals. Its performance is comparable to that of the wireline recognition system that uses only the cepstrum as a feature set.
Detecting Hotspot Information Using Multi-Attribute Based Topic Model

Microblogging as a kind of social network has become more and more important in our daily lives. Enormous amounts of information are produced and shared on a daily basis. Detecting hot topics in the mountains of information can help people get to the essential information more quickly. However, due to short and sparse features, a large number of meaningless tweets and other characteristics of microblogs, traditional topic detection methods are often ineffective in detecting hot topics. In this paper, we propose a new topic model named multi-attribute latent dirichlet allocation (MA-LDA), in which the time and hashtag attributes of microblogs are incorporated into LDA model. By introducing time attribute, MA-LDA model can decide whether a word should appear in hot topics or not. Meanwhile, compared with the traditional LDA model, applying hashtag attribute in MA-LDA model gives the core words an artificially high ranking in results meaning the expressiveness of outcomes can be improved. Empirical evaluations on real data sets demonstrate that our method is able to detect hot topics more accurately and efficiently compared with several baselines. Our method provides strong evidence of the importance of the temporal factor in extracting hot topics.
THE COEVOLUTIONARY DYNAMICS OF ANTAGONISTIC INTERACTIONS MEDIATED BY QUANTITATIVE TRAITS WITH EVOLVING VARIANCES

Abstract Quantitative traits frequently mediate coevolutionary interactions between predator and prey or parasite and host. Previous efforts to understand and predict the coevolutionary dynamics of these interactions have generally assumed that standing genetic variation is fixed or absent altogether. We develop a genetically explicit model of coevolution that bridges the gap between these approaches by allowing genetic variation itself to evolve. Analysis of this model shows that the evolution of genetic variance has important consequences for the dynamics and outcome of coevolution. Of particular importance is our demonstration that coevolutionary cycles can emerge in the absence of stabilizing selection, an outcome not possible in previous models of coevolution mediated by quantitative traits. Whether coevolutionary cycles evolve depends upon the strength of selection, the number of loci, and the rate of mutation in each of the interacting species. Our results also generate novel predictions for the expected sign and magnitude of linkage disequilibria in each species.