Miracle-dz/UniFAR-FTUs huggingface dataset:
ChREBP•Mlx Is the Principal Mediator of Glucose-induced Gene Expression in the Liver*

In mammals, glucose-regulated gene expression has been best characterized in the liver, where increased glucose metabolism induces transcription of genes encoding enzymes involved in de novo lipogenesis. ChREBP and Mlx dimerize and function together as a glucose-responsive transcription factor to regulate target genes, such as liver-type pyruvate kinase, acetyl-CoA carboxylase 1, and fatty acid synthase. To identify additional glucose-responsive genes in the liver, we used microarray analysis to compare gene expression patterns in low and high glucose conditions in hepatocytes. Target genes of ChREBP·Mlx were simultaneously identified by gene profiling in the presence or absence of a dominant negative Mlx. Of 224 genes that are induced by glucose, 139 genes (62%) were also inhibited by the dominant negative Mlx. Lipogenic enzyme genes involved in the entire pathway of de novo lipogenesis were found to be glucose-responsive target genes of ChREBP·Mlx. Genes encoding enzymes in other metabolic pathways and numerous regulators of metabolism were also identified. To determine if any of these genes are direct targets of ChREBP·Mlx, we searched for ChoRE-like sequences in the 5′-flanking regions of several genes that responded rapidly to glucose. ChoRE sequences that bound to ChREBP·Mlx and supported a glucose response were identified in two additional genes. Combining all of the known ChoRE sequences, we generated a modified ChoRE consensus sequence, CAYGNGN5CNCRTG. In summary, ChREBP·Mlx is the principal transcription factor regulating glucose-responsive genes in the liver and coordinately regulates a family of genes required for glucose utilization and energy storage.
Mitigation choices impact carbon budget size compatible with low temperature goals

Global-mean temperature increase is roughly proportional to cumulative emissions of carbon-dioxide (CO2). Limiting global warming to any level thus implies a finite CO2 budget. Due to geophysical uncertainties, the size of such budgets can only be expressed in probabilistic terms and is further influenced by non-CO2 emissions. We here explore how societal choices related to energy demand and specific mitigation options influence the size of carbon budgets for meeting a given temperature objective. We find that choices that exclude specific CO2 mitigation technologies (like Carbon Capture and Storage) result in greater costs, smaller compatible CO2 budgets until 2050, but larger CO2 budgets until 2100. Vice versa, choices that lead to a larger CO2 mitigation potential result in CO2 budgets until 2100 that are smaller but can be met at lower costs. In most cases, these budget variations can be explained by the amount of non-CO2 mitigation that is carried out in conjunction with CO2, and associated global carbon prices that also drive mitigation of non-CO2 gases. Budget variations are of the order of 10% around their central value. In all cases, limiting warming to below 2 °C thus still implies that CO2 emissions need to be reduced rapidly in the coming decades.
Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis*

The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but only when the diet contains lipids. This drop is significant 1 h after a lipid supply and associates with ubiquitination of CD36. Using CHO cells expressing CD36, it is shown that the digestion products LCFA and diglycerides trigger CD36 ubiquitination. In vivo treatment with the proteasome inhibitor MG132 prevents the lipid-mediated degradation of CD36. In vivo and ex vivo, CD36 is shown to be required for lipid activation of ERK1/2, which associates with an increase of the key chylomicron synthesis proteins, apolipoprotein B48 and microsomal triglyceride transfer protein. Therefore, intestinal CD36, possibly through ERK1/2-mediated signaling, is involved in the adaptation of enterocyte metabolism to the postprandial lipid challenge by promoting the production of large triglyceride-rich lipoproteins that are rapidly cleared in the blood. This suggests that CD36 may be a therapeutic target for reducing the postprandial hypertriglyceridemia and associated cardiovascular risks.
Ryanodine Calcium Channel: A Novel Channelopathy for Seizures

IntroductionCatecholamine-induced polymorphic ventricular tachycardia (CPVT) is one of the most severe inherited arrhythmogenic disorders, where patients clinically present with syncope or seizures. CaseAn 18-year-old white male with a history of mild developmental delay and CPVT, was brought to the ED after an episode of unresponsiveness for several minutes. The EMS documented a rhythm strip showing sinus tachycardia. The patient was awake and alert with no clinical evidence of any focal neurologic deficits, but unable to recall the event. Initial blood works including cardiac enzymes were normal. EKG showed sinus rhythm at 86 bpm, along with bigeminy and couplets of bidirectional QRS morphology with a QT interval of 0.3 seconds. Imaging studies including computed tomography scans of head, magnetic resonance imaging of brain, and 2D cardiac echo were normal. A routine EEG revealed abnormal bursts of spike and aftergoing slow wave complexes, highly suggestive of a potential for seizure activity. A 24-hour video EEG-EKG confirmed abnormal brain activity in the presence of normal sinus rhythm. A recent experimental study showed that knock in models of mice mutated with leaky calcium channels in the heart and brain exhibited seizures independent of arrhythmias. ConclusionsOur patient is probably the clinical paradigm of this study. This episode of unresponsiveness, most probably a complex partial seizure, may have been caused by the same mutations known to precipitate CPVT.
INTESTINAL AND HEPATIC TRANSPORT OF CHOLATE AND ORGANIC DYES.

The 3-hr cumulative biliary appearance of a bile salt and three representative organic dyes was studied in rats anesthetized with sodium pentobarbital. The substances were administered in one of the following locations: a branch of the portal vein, a 20-cm isolated loop of proximal jejunum, or a similar loop of distal ileum. Average biliary recoveries of 10 mg cholate, bromsulfonphthalein, diiodotetrachlorofluorescein (rose bengal) or phenolsulfonphthalein (phenol red) introduced slowly into the portal circulation were 97, 97, 68, and 23%, respectively. The respective recoveries of 30-mg quantities of these four substances placed in the intestinal loops were 43, 5, 2, and 1% proximally and 90, 5, 5, and 0.4% distally. These observations confirm the presence of a specific intestinal transport mechanism for cholate with maximal activity in the distal ileum. However, the three representative organic dyes are shown not to be carried by the intestinal bile salt transport mechanism and their movement from gut lumen to portal vein blood should be ascribed to a passive process.
Hepatic Heat Shock and Acute-phase Gene Expression Are Induced Simultaneously after Celiotomy in the Anesthetized Pig

Background The liver plays a central role in the whole organism's response to injury. Expression of hepatic acute-phase and heat-shock genes likely contributes to the restoration of homeostasis after stressful events. However, after prolonged ischemia, hepatic transcription of heat-shock genes can exclude the simultaneous transcription of acute-phase genes. The issue of whether hepatic 72-kd heat-shock protein (hsp72) gene expression is induced under perioperative conditions that do not result in prolonged liver ischemia and whether this might further affect the expression of the acute-phase reactant inter-alpha-trypsin inhibitor (alpha-Ti) was examined.
Animal Models of Hepatic Allograft Rejection

Progress in clinical liver transplantation has been built on extensive experimental liver grafting in animal^. '. ^ Experience with liver transplantation in different species has consistently shown that, in appropriate donor-recipient combinations, the liver behaves as an immunologically favored organ and survives without use of immunosuppressive agents where skin, renal, or cardiac allografts in the same combinations would be rejected. This has been studied most thoroughly in the rat, where the availability of inbred and congenic lines, together with reliable surgical techniques, have made it possible to examine the process of rejection in detail. RECIPIENT HYPOREACTIVITY IN LIVER TRANSPLANTATION
It Feels Like Deja Vu All Over Again

This chapter begins with a quote by editor-in-chief Bruce Shriver in January 1984 for the first issue of IEEE Software, and goes on explain why words that described the software industry so well then are still so appropriate. The truth of software industry lies somewhere between the extremes of progress and stagnation. We do tend to make the same mistakes repeatedly. On the other hand, we are able to solve increasingly complex problems. Their software-dependent solutions do work and do integrate seamlessly into our societal tapestry. Having a large dose of both views is probably healthy. After all, if we believe only the progress view we might become complacent or careless, and create more disasters than we otherwise would. On the other hand, if we believe only the stagnation view, then we become obsessive or depressed.
Effect of carbohydrate feedings on muscle glycogen utilization and exercise performance.

Ten men were studied during 4 h of cycling to determine the effect of solid carbohydrate (CHO) feedings on muscle glycogen utilization and exercise performance. In the experimental trial (E) the subjects ingested 43 g of sucrose in solid form along with 400 ml of water at 0, 1, 2 and 3 h of exercise. During the control trial (C) they received 400 ml of an artificially sweetened drink without solid CHO. No differences in VO2, heart rate, or total energy expenditure were observed between trials; however, respiratory exchange ratios were significantly (P less than 0.05) higher during E. Blood glucose was significantly (P less than 0.05) elevated 20 min post-feeding in E; however, by 50 min no differences were observed between trials until 230 min (E = 4.5 +/- 0.2 mmol X l-1 vs C = 3.9 +/- 0.2, means +/- SE; P less than 0.05). Muscle glycogen utilization was significantly (P less than 0.05) lower during E (100.7 +/- 10.2 mmol X kg-1 w.w.) than C (126.2 +/- 5.5). During a sprint (100% VO2max) ride to exhaustion at the end of each trial, subjects performed 45% longer when fed CHO (E = 126.8 +/- 24.7 s vs C = 87.2 +/- 17.5; P less than 0.05). It was concluded that repeated solid CHO feedings maintain blood glucose levels, reduce muscle glycogen depletion during prolonged exercise, and enhance sprint performance at the end of such activity.
Performance Analysis for Integrating Biometrics

Due to the performance limitation of using a single biometric, many researchers have been investigating ways to integrate multiple biometrics for the purpose of authentication. To this end, there have been numerous articles on promoting multiple biometric identifiers. It is thus important to know when integrating improves the performance and when it does not. This research focuses on integrating biometrics at the decision level. In this article, the formulas are first derived for the probabilities of a False Accept and a False Reject when n Biometric tests are combined. The conditions are then obtained for performance improvement and degradation of combing two biometric identifiers. To the end, some other interesting results of integrating biometric solutions are also presented.
ANÁLISE DA ADOÇÃO DAS PRÁTICAS DE CONTABILIDADE GERENCIAL EM EMPRESAS INDUSTRIAIS, COMERCIAIS E DE SERVIÇOS

O objetivo do estudo e identificar e analisar os estagios de adocao das praticas de contabilidade gerencial em empresas industriais, comerciais e de prestacao de servicos. Para tanto, foi realizada uma pesquisa empirica com a aplicacao de questionario junto a 95 empresas da regiao Oeste de Santa Catarina. Para realizar as analises foram aplicados testes estatisticos de proporcao, para verificar a utilizacao dos 4 estagios da Contabilidade Gerencial, e Analise de Conglomerados ou Cluster Analisys, para analise das caracteristicas internas. Os resultados demonstram que as praticas de 4o estagio sao menos utilizadas, seja em empresas comerciais, industriais e de servicos. Um destaque apenas para as empresas prestadoras de servicos que nao apresentaram diferencas estatisticas na proporcao de utilizacao das praticas de 1o e 4o estagios. Observou-se que 47% das empresas, com predominância da atividade industrial, com mais de 10 anos de mercado e faturamento entre R$ 3.600. 000,00 e R$ 78.000. 000,00, possuem pelo menos uma pratica de 1o, 2o e 3o estagios. Tambem foi percebido que, de maneira geral, as empresas comerciais utilizam menos praticas gerenciais nos quatro estagios, do que as empresas industriais e de servicos. De modo geral, o estudo corrobora na evidenciacao de que os estagios das praticas de contabilidade gerencial possui relacao com as atividades empresariais, a idade das empresas e o tamanho definido pelo faturamento. Ainda, ressalta-se a importância da analise das praticas de contabilidade gerencial no contexto brasileiro, no intuito de contribuir com melhorias no desempenho organizacional.
Low-level mixing height detection in coastal locations with a scanning Doppler lidar

Abstract. Mixing layer height (MLH) is one of the key parameters in describing lower tropospheric dynamics and capturing its diurnal variability is crucial, especially for interpreting surface observations. In this paper we introduce a method for identifying MLH below the minimum range of a scanning Doppler lidar when operated at vertical. The method we propose is based on velocity variance in low-elevation-angle conical scanning and is applied to measurements in two very different coastal environments: Limassol, Cyprus, during summer and Loviisa, Finland, during winter. At both locations, the new method agrees well with MLH derived from turbulent kinetic energy dissipation rate profiles obtained from vertically pointing measurements. The low-level scanning routine frequently indicated non-zero MLH less than 100 m above the surface. Such low MLHs were more common in wintertime Loviisa on the Baltic Sea coast than during summertime in Mediterranean Limassol.
Topical tacrolimus for recalcitrant vulvar lichen sclerosus.

Auteur(s) : Eleni Sotiriou, Zoi Apalla, Aikaterini Patsatsi, Despina Panagiotidou First dermatologic department, Medical school, Aristotle university Thessaloniki, 8, Papakyriazi str, 54645 Thessaloniki, Greece Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disorder of uncertain origin predominantly affecting postmenopausal women. As immunological alterations seem to be important in the aetiopathogenesis of VLS, tacrolimus – an immunomodulating topical agent – could be an alternative [. ]
Binding of platinum(II) intercalation reagents to deoxyribnonucleic acid. Dependence on base-pair composition, nature of the intercalator, and ionic strength.

The DNA binding of three platinum(II) intercalation reagents has been studied and found to depend upon base composition, the nature of the intercalator, and the ionic strength of the solvent medium. In 0.2 M NaCl, binding data for calf thymus DNA show the association constants to be approximately 10(4) M-1. The binding constants decrease in the order [(o-phen)Pt(en)]2+ greater than or equal to [(terpy)Pt(HET)]+ greater than [(bipy)Pt(en)]2+. The number of available intercalation sites for the doubly charged intercalators is only 70% of the number expected from the nearest-neighbor exclusion model. Binding of [(o-phen)Pt(en)]2+ and [(terpy)Pt(HET)]+ to various DNAs depends linearly on G.C content. Both reagents exhibit essentially the same degree of G.C specificity. Intercalative binding is a function of ionic strength. Increasing the salt concentration minimizes the importance of metallointercalator charge, and extrapolation to 1 M salt reveals the intercalative abilities, as reflected in binding constants, to be equivalent for [(terpy)Pt(HET)]+ and [o-phen)Pt(en)]2+ and about 1 order of magnitude less than that of ethidium.
A Coding-Based Incremental Traceback Scheme against DDoS Attacks in MANET

Due to constrained resources, DDoS attack is one of the biggest threats to MANET. IP traceback technique is useful to defend against such type of attacks, since it can identify the attack sources. Several types of traceback schemes have been proposed for wired networks. Among all the existing schemes, probabilistic packet marking (PPM) scheme might be the most promising scheme for MANET. However its performance in MANET is not as good as that in Internet. In this paper, a new scheme based on the codingtechnique (CT) is proposed for traceback in MANET. Furthermore, a new idea of Incremental traceback is raised to cope with the situation of incremental attack (ICT). We present the protocol design and conduct theoretical analysis of this scheme. Additionally, we conduct experiments to compare it with the traditional PPM scheme. The experimental results show that the new coding-based traceback scheme outperforms the PPM scheme in MANET.
Inhibition of the elicitation phase of contact hypersensitivity by thymidine dinucleotides is in part mediated by increased expression of interleukin‐10 in human keratinocytes

Abstract: The production of immunomodulatory cytokines such as interleukin‐10 (IL‐10) from keratinocytes and other target cells in the skin plays a crucial role in UV‐induced immunosuppression. Substantial evidence supports an association between DNA damage and immunomodulation. It is also known that small DNA fragments such as thymidine dinucleotides (pTpT) can mimic several UV‐induced effects, including inhibition of the induction phase of the contact hypersensitivity response and up‐regulation of tumor necrosis factor‐alpha (TNF‐α). To determine whether pTpT also induces IL‐10 secretion by keratinocytes, and by inference whether IL‐10 production after UV irradiation is a response to DNA damage, we compared the effects of pTpT with those of UV irradiation on primary human keratinocyte cultures. Subconfluent cultures of primary human keratinocytes were treated either with 10 µM or 100 µM pTpT or diluent alone, or exposed to solar‐simulated light (100 J/m2 of UVB) or sham irradiated. An increase in IL‐10 mRNA expression was observed 6–24 h after irradiation and at 24–48 h after treatment with pTpT. Detection of secreted IL‐10 protein coincided with up‐regulation of IL‐10 gene expression at 48 and 72 h as determined by ELISA. Conditioned media from human keratinocytes treated with pTpT, like that from irradiated cells, significantly inhibited lymphocyte proliferation in the allogeneic‐mixed lymphocyte reaction (MLR) assay. To determine whether pTpT mimics the suppressive influence of UVB on the elicitation phase of contact hypersensitivity, believed to result largely from IL‐10 release, we compared the effects of topical application of pTpT with those of UVB irradiation on C57Bl/6 mice sensitized with dinitrofluorobenzene. Sensitized mice treated with pTpT or UVB irradiation showed markedly suppressed elicitation of ear‐swelling responses. These results demonstrate that increased keratinocyte IL‐10 mRNA level and IL‐10 protein release are among the effects of pTpT and support the hypothesis that pTpT treatment triggers many of the biologic effects of UV irradiation by mimicking UV‐induced DNA damage. Finally, regardless of mechanism, the data suggest that topical treatment with pTpT may provide a novel means of suppressing contact hypersensitivity or other lymphocyte‐mediated reactions in skin.
Improved design criteria of gain-boosted CMOS OTA with high speed optimizations

A comprehensive study on gain-boosted regulated cascode operational transconductance amplifiers (OTA) is discussed. These amplifiers are usually good for power optimized high-speed designs. However location of an additional pole-zero pair in the transfer function makes the transient response much slower than expected. A new design is proposed along with the systematic approach which get rid of this pole-zero pair and deliberately puts a pair of complex poles to make the design faster.
Functional characterization of temperature-sensitive mutants of simian virus 40 large T antigen

We investigated the molecular properties of eight temperature-sensitive mutants of simian virus 40 large T antigen (tsA mutants). The mutants have single amino acid substitutions that block DNA replication at 39 to 41 degrees C in vivo. In vitro, five of the mutant proteins were highly sensitive to a brief heat shock at 39 degrees C, while the three remaining proteins were only partially sensitive at 41 degrees C. We characterized the five most defective mutant proteins, using a variety of biochemical assays for replication functions of T antigen. Heat shock of purified T antigen with a mutation at amino acid 422 significantly impaired the oligomerization, origin-binding, origin-unwinding, ATPase, and helicase functions of T antigen. In contrast, substitution of amino acid 186, 357, 427, or 438 had more selective, temperature-sensitive effects on T-antigen functions. Our findings are consistent with the conclusion that T antigen functions via a hierarchy of interrelated domains. Only the ATPase activity remained intact in the absence of all other functions. Hexamer formation appears to be necessary for core origin-unwinding and helicase activities; the helicase function also requires ATPase activity. All five tsA mutants were impaired in functions important for the initiation of DNA replication, but three mutants retained significant elongation functions.
Talking, looking, flying, searching: information seeking behaviour in Second Life

Purpose – This research seeks to answer, “How do everyday Second Life users go about finding needed information? ” as the primary research question.Design/methodology/approach – A virtual ethnographic approach couched in grounded theory was utilized to conduct semi‐structured interviews with everyday users of Second Life, accompanied by participant observation.Findings – Information seeking behaviors within the virtual world of Second Life were found to be rich, complex interaction with multiple facets. Five themes emerged to illuminate how users seek information.Research limitations/implications – This research took place over a six‐week period, although most enthographies last at least one year. Conclusions were drawn solely from interviews because participant observation did not penetrate a given community with enough depth to adequately address the research question.Practical implications – Virtual worlds offer the promise of becoming an integrated part of the information seeking landscape for an incre.