Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of parity between IL-2 and IL-21 in the NOD Idd3 locus

IL-2 and IL-21 are two cytokines with great potential to affect autoimmune infiltration of nonlymphoid tissue, and are contained within the strongest non-MHC-linked locus for type 1 diabetes (T1D) susceptibility on the nonobese diabetic (NOD) mouse (Idd3). IL-21 is necessary for the development of diabetes in the NOD mouse, but a number of important studies argue that decreased expression of IL-2 explains Idd3. In this study, we demonstrate that the amount of IL-21, but not IL-2, correlated with T1D incidence. During our analyses of the IL-2/IL-21 interval, we found that mice segregate into one of two distinct expression profiles. In the first group, which includes the C57BL/6 strain, both Il2 and Il21 were expressed at low levels. In the other group, which includes the NOD strain, Il2 and Il21 were both highly expressed. However, because NOD IL-2 mRNA was relatively unstable, IL-2 production was remarkably similar between strains. The increased production of IL-21 in NOD mice was found to result from two single nucleotide polymorphisms within the distal promoter region that conferred increased binding affinity for the transcription factor Sp1. Our findings indicate that a loss of locus parity after decreased IL-2 mRNA stability ensures that the high-expressing IL-21 allele persists in nature and provides a basis for autoimmunity.
Wrong About Rights: Public Knowledge of Key Areas of Consumer, Housing and Employment Law in England and Wales

Over many decades, processes of juridification have brought about huge growth in legal rights, responsibilities and protections, yet citizens appear to poorly understand this ‘law thick’ world. This impacts citizens’ capacity to ‘name, blame and claim’ in the legal domain at a time of retreat from public funding of civil legal services. This article examines public knowledge of rights in key areas relating to consumer, housing and employment law. Drawing on data from the 2010–2012 English and Welsh Civil and Social Justice Survey, the article uses responses to a series of hypothetical scenarios to explore public knowledge of rights and characteristics associated with knowledge. Our findings highlight a substantial deficit in individuals’ understanding of legal rights and responsibilities – even among those for whom particular rights and responsibilities have specific bearing. We also consider what these findings mean for public legal education and the efficiency, efficacy and legitimacy of the law.
Presynaptic Kainate Receptor Mediation of Frequency Facilitation at Hippocampal Mossy Fiber Synapses

Inhibition of transmitter release by presynaptic receptors is widespread in the central nervous system and is typically mediated via metabotropic receptors. In contrast, very little is known about facilitatory receptors, and synaptic activation of a facilitatory autoreceptor has not been established. Here we show that activation of presynaptic kainate receptors can facilitate transmitter release from hippocampal mossy fiber synapses. Synaptic activation of these presumed ionotropic kainate receptors is very fast (<10 ms) and lasts for seconds. Thus, these presynaptic kainate receptors contribute to the short-term plasticity characteristics of mossy fiber synapses, which were previously thought to be an intrinsic property of the synapse.
Cost-Effectiveness of a Dual Non-Treponemal/Treponemal Syphilis Point-of-Care Test to Prevent Adverse Pregnancy Outcomes in Sub-Saharan Africa

Background: A dual nontreponemal/treponemal point-of-care test (Dual-POC) that simultaneously detects both nontreponemal and treponemal antibodies has been developed and evaluated. In this study, we compare the health and economic outcomes of the new test with existing syphilis tests/testing algorithms in a high prevalence setting. Methods: We used a cohort decision analysis model to examine 4 testing/screening algorithms; the Dual-POC test, the laboratory-based rapid plasma reagin and Treponema pallidum haemagglutination assay (RPR+TPHA) algorithm, an onsite RPR testing, and point-of-care treponemal immunochromatographic strip (ICS) testing. Outcomes included miscarriage, stillbirth, congenital syphilis, low birth weight, and neonatal death. Disability-adjusted life-years were estimated for all health outcomes. The analytic horizon was the life expectancy for the mother and child. Results: For a cohort of 1000 pregnant women in a historically high syphilis prevalence population (10% infected and 15% previously infected), the model predicted a total of 39 adverse pregnancy outcomes if no serologic screening were performed; 13 for the laboratory-based RPR+TPHA; 11 for the on-site RPR strategy; 5 for the Dual-POC strategy; and 2 for the ICS strategy. On the basis of assumption that the cost of ICS and the Dual-POC tests were the same, the ICS strategy was the most cost saving (saved $30,000) followed by the Dual-POC strategy (saved $27,000). Conclusions: The dual-POC test may help save cost in resource-poor settings where disease prevalence (and loss to follow-up) is high, while substantially reducing overtreatment.
Implementation of management agents for an OSGi-based residential gateway

This paper presents a concept of management agent and its implementing approach in an OSGi-based residential gateway. The role of management agent has been defined by OSGi (Open Service Gateway initiatives) alliance but the detailed interfaces have not been specified yet. In this paper, we propose servlet-based management agents and implement them to support their roles defined by OSGi specification. Implemented management agents consist of small function component, thus these can be extended easily according to the change of OSGi release.
Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementias

Objective: To evaluate the inter-rater reliability and validity of clinical diagnostic criteria for neurodegenerative dementias. Background: Inter-rater accuracy of the diagnosis of AD has been explored, but there are few accuracy studies for progressive supranuclear palsy (PSP) and frontotemporal lobe dementia (FTD). Furthermore, there have been no simultaneous accuracy studies in a mixed sample of patients with cortical and subcortical neurodegenerative processes. Methods: Four experienced clinicians reviewed first-visit clinical data abstracted from the records of 40 pathologically diagnosed demented subjects. They were asked to apply the NINCDS-ADRDA criteria for AD, the NINDS-SPSP clinical criteria for PSP, the Lund and Manchester criteria for FTD, and the Consensus Guidelines for the Clinical Diagnosis of Dementia with Lewy Bodies (DLB). Results: The generalized κ for AD was 0.73, for PSP 0.82, for FTD 0.75, and for DLB 0.37. The κ pool test showed a statistically significant difference between DLB and the other disease processes, and no differences were observed among AD, FTD, and PSP. The mean sensitivity for AD was 95%, for PSP 75%, for FTD 97%, and for DLB 34%. The mean specificity for AD was 79%, for PSP 98.5%, for FTD 97%, and for DLB 94%. Conclusions: We found improved inter-rater reliability for the diagnosis of AD among clinicians compared with earlier studies. Similarly, there was a near-perfect and substantial inter-rater agreement for the diagnosis of PSP and FTD. The sensitivity for the diagnosis of AD was high, although clinicians overdiagnosed this condition. However, there was a reasonable accuracy for the diagnosis of PSP and FTD. Heterogeneity of the clinical presentation of DLB significantly affected inter-rater agreement and accuracy. The use of multiple diagnostic criteria for cortical and subcortical dementia increases the level of clinical diagnostic accuracy.
Continuous-time distributed convex optimization on time-varying directed networks

We introduce a general class of continuous-time distributed control systems, where the control input to the dynamics of each agent relies on an observer that estimates the average state. The dynamics of these observers are nonlinear, but the agents only need to have access to local information to implement them. We show that under a general condition on the structure of the underlying time-varying directed graphs, the difference of the agents' estimates and the true average is upper bounded. Using this result, we show that when we have a class P* weakly exponentially ergodic flow and the agent's objective functions are differentiable with bounded gradients, any trajectory of the proposed continuous-time dynamics is globally asymptotically convergent to a minimizer. Finally, we demonstrate that the class P* weakly exponentially ergodic flow property can be achieved by assuming that the sequence of Laplacians are measurable, cut-balanced, and has a minimum instantaneous flow. As a by-product, we show that the proposed continuous-time dynamics for distributed convex optimization is convergent on any sequence of time-varying strongly connected directed graph.
Effect of the conceptus and lack of effect of uterine space on endometrial protein secretion during mid-gestation in swine.

The effect of the conceptus and of reduced uterine space on endometrial protein secretion was examined on Days 40, 60, and 80 of gestation in white crossbred gilts. Twenty-nine gilts were checked daily for estrus, and 15 were given 5 mg estradiol valerate daily from Days 11 to 15 (Day 0 = day of estrus) of the estrous cycle to induce pseudopregnancy. The remaining 14 pigs were mated during estrus. All pigs were laparotomized on Day 4, and one uterine horn was ligated to produce one crowded and one roomy uterine environment. Pigs were killed on Days 40, 60, and 80 of pregnancy or pseudopregnancy. The reproductive tracts were collected, and placental tissues from pregnant pigs and endometrial tissues from all pigs were cultured in the presence of 3H-leucine to evaluate protein secretion. Conditioned medium was dialyzed, measured for incorporation of radioactivity into nondialyzable macromolecules, and then subjected to two-dimensional (2D)-PAGE to determine the effect of uterine space and day of pregnancy or pseudopregnancy on overall protein secretion rate and secretion of specific proteins. Fetal survival, fetal weight, and placental weight were decreased (p < 0.01) in the crowded uterine environment compared to the roomy uterine environment. Incorporation of 3H-leucine into nondialyzable macromolecules by endometrial tissue in culture was not affected by uterine space. Secretion of nondialyzable macromolecules by endometrium from pregnant pigs was not different from that by endometrium from pseudopregnant pigs on Day 40 but was greater (p < 0.01) on Days 60 and 80. (ABSTRACT TRUNCATED AT 250 WORDS)
Influência da Opinião do Auditor no Retorno das Ações das Empresas Brasileiras de Capital Aberto

No que diz respeito a reducao da assimetria informacional em decisoes de investimentos, os investidores podem diminuir incertezas na avaliacao de uma empresa, ao analisar o relatorio de auditoria independente, uma vez que ele e capaz de atestar a fidelidade as normas contabeis das informacoes divulgadas pelas empresas. Nesse contexto, o objetivo deste estudo foi analisar a relacao entre a opiniao divulgada no relatorio do auditor independente e o retorno das acoes das empresas brasileiras de capital aberto. Foi considerado o periodo de 2010 a 2014, mediante analise de correlacao, teste de Mann Whitney e regressao com dados dispostos em painel. Estatisticamente, os resultados nao foram conclusivos quanto ao impacto do tipo de opiniao da auditoria no retorno das acoes. Houve indicios de que ha reacao negativa do mercado frente aos relatorios com enfase e reacao positiva na presenca de relatorios limpos e com ressalva, o que pode significar que a publicacao de um relatorio com ressalva pode gerar maior ganho para a empresa do que o prejuizo dessa publicacao. A pesquisa aponta para a necessidades de revisao e reflexao, tanto pelas empresas de auditoria quanto pelos orgaos reguladores, quanto a representatividade da atuacao do auditor no mercado de capitais.
[Clinical efficacy of Q-switched Alexandrite laser for pigmentary skin diseases in 4656 patients].

OBJECTIVE To evaluate the clinical efficacy and safety of Q-switched Alexandrite laser in the treatment of pigmentary skin, diseases ( PSDs). METHODS Totally 4 656 patients with PSDs were treated with Q-switched Alexandrite laser. These PDSs included nevus of Ota, seborrheic keratosis, tattoo, naevus fusco-caeruleus zygomaticus, cafe-au-lait-spots, lentigo, naevus of Ito, and spilus naevus. The outcomes and adverse events after treatment were oberserved. RESULTS The response rate was 92.31% and the cure rate was 55.39% for nevus of Ota after six times of treatment, and the cure rate was 100% after nine times of treatment. The response rate was 100% for freckles, seborrheic keratosis, and naevus fuscocaeruleus zygomaticus after four times of treatment. The response rate was more than 77.18% and the cure rate was more than 50% for tattoos after three times of treatment, including amateur tattoo, artificial eyebrow, eyelid lines, and traumatic tattoo. However, after four times of treatment, the response rate and the cure rate were only 50. 00% and 21.43% for cafe-au-lait spots, and 50.00% and 25.00% for spilus naevus, respectively. The response rate was 35.29% for lentigo and 25.00% for naevus of Ito/ spilus naevus after four times of treatment. CONCLUSION Q-switched Alexandrite laser is effective in the treatment of nevus of Ota, seborrheic keratosis, tattoo, and naevus fusco-caeruleus zygomaticus, but has limited efficacy for cafe-au-lait-spots, lentigo, naevus of Ito, and spilus naevus.
Association between Depression Symptoms with Inflammation and Cardiovascular Risk Factors in Patients Undergoing Peritoneal Dialysis

Despite medical progress, high morbidity and mortality rates, due primarily to cardiovascular diseases, have persisted in patients with end-stage renal disease (ESRD). Recently, nontraditional risk factors, such as inflammation and malnutrition, have been emphasized in the development or progression of atherosclerosis in ESRD patients. Depression, the most common psychological problem in the ESRD population, is also known to be associated with inflammation and malnutrition, suggesting a possible link between depression with inflammation and cardiovascular diseases. The purpose of this study was to investigate the relationship between depression with cardiovascular risk factors and inflammation in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Eighty-one stable CAPD patients were enrolled. Depressive symptoms were assessed with the Beck Depression Inventory. Various cardiovascular risk factors and inflammatory markers were measured. Forty-three patients had depressive symptoms (53.8%). Patients with depressive symptoms showed significantly lower levels of albumin and IL-10, but higher levels of inflammatory markers than patients without depressive symptoms. Left ventricular hypertrophy was also found more frequently and pulse wave velocity and asymmetric dimethylarginine were all significantly increased in patients with depressive symptoms. Depression in CAPD patients was associated with inflammation and cardiovascular risk factors, and might be used as a predictor of cardiovascular diseases.
In Vitro Selection and Characterization of Hepatitis C Virus Serine Protease Variants Resistant to an Active-Site Peptide Inhibitor

ABSTRACT The hepatitis C virus (HCV) serine protease is necessary for viral replication and represents a valid target for developing new therapies for HCV infection. Potent and selective inhibitors of this enzyme have been identified and shown to inhibit HCV replication in tissue culture. The optimization of these inhibitors for clinical development would greatly benefit from in vitro systems for the identification and the study of resistant variants. We report the use HCV subgenomic replicons to isolate and characterize mutants resistant to a protease inhibitor. Taking advantage of the replicons' ability to transduce resistance to neomycin, we selected replicons with decreased sensitivity to the inhibitor by culturing the host cells in the presence of the inhibitor and neomycin. The selected replicons replicated to the same extent as those in parental cells. Sequence analysis followed by transfection of replicons containing isolated mutations revealed that resistance was mediated by amino acid substitutions in the protease. These results were confirmed by in vitro experiments with mutant enzymes and by modeling the inhibitor in the three-dimensional structure of the protease.
Overexpression of GRP78 mitigates stress induction of glucose regulated proteins and blocks secretion of selective proteins in Chinese hamster ovary cells.

GRP78 is a resident protein of the endoplasmic reticulum (ER) and a member of the glucose regulated protein (GRP) family. Many secretion incompetent proteins are found in stable association with GRP78 and are retained in the ER. Some proteins which are destined for secretion transiently associate with GRP78. To further increase our understanding of the role of GRP78 in secretion, we have stably overexpressed GRP78 in Chinese hamster ovary (CHO) cells and examined the effect on protein secretion and the stress response. GRP78 overexpressing cells treated with tunicamycin or A23187 exhibited a reduced induction of endogenous GRP78 and GRP94 mRNAs compared to wild‐type CHO cells. This suggests that GRP78 overexpression either alleviates the stress or is directly involved in signaling stress‐induced expression of GRPs. Transient expression of secreted proteins was used to measure secretion efficiency in the GRP78 overexpressing cells. Secretion of von Willebrand factor and a mutant form of factor VIII, two proteins which transiently associate with GRP78, was reduced by GRP78 overexpression. In contrast, secretion of M‐CSF, which was not detected in association with GRP78, was unaffected. This indicates that elevated levels of GRP78 may increase stable association and decrease the secretion efficiency of proteins which normally transiently associate with GRP78. These results indicate that one function of GRP78 is selective protein retention in the ER.
Infant sleep position: associated maternal and infant factors.

OBJECTIVE To determine the maternal and infant characteristics associated with the back sleep position for infants to guide efforts to increase its use and reduce the risk of Sudden Infant Death Syndrome. METHODS Cross-sectional survey of 3349 mothers delivering in California, February-May 1999. RESULTS Fifty-two percent of infants were placed in the back sleep position. Factors associated with a lower likelihood of using the back position included all levels of maternal education less than college (eg, for education eighth grade or less--adjusted odds ratio [OR] 0.59; 95% confidence interval [CI], 0.40-0.86); income at or below federal poverty level (OR, 0.65; 95% CI, 0.47-0.90); multiparity (OR, 0.80; 95% CI, 0.67-0.95); race/ethnicity African American (OR, 0.49; 95% CI, 0.37-0.65) and Asian/Pacific Islander (OR, 0.65; 95% CI, 0.48-0.89); speaking a non-English language (OR, 0.69; 95% CI, 0.55, 0.86); and infant age over 7 months (OR, 0.70, 95% CI, 0.52-0.96). Women in Los Angeles (OR, 0.57; 95% CI, 0.42-0.77) and urban areas other than San Diego (OR, 0.70; 95% CI, 0.53-0.92) were less likely to use the back position than those in San Francisco. CONCLUSIONS Greater efforts are needed to promote the back sleep position among families with mothers who lack education beyond some college; live in poverty; and who are African American, Asian/Pacific Islander, multiparous, or non-English speaking.
Distinct Sensory Requirements for Unimodal and Cross-Modal Homeostatic Synaptic Plasticity

Loss of a sensory modality elicits both unimodal changes in the deprived cortex and cross-modal alterations in the remaining sensory systems. Unimodal changes are proposed to recruit the deprived cortex for processing the remaining senses, while cross-modal changes are thought to refine processing of spared senses. Hence coordinated unimodal and cross-modal changes are likely beneficial. Despite this expectation, we report in mice that losing behaviorally relevant patterned vision is sufficient to trigger cross-modal synaptic changes in the primary somatosensory cortex barrel fields, but is insufficient to drive unimodal synaptic plasticity in visual cortex (V1), which requires a complete loss of visual activity. In addition, cross-modal changes depend on whisker inputs. Our results demonstrate that unimodal and cross-modal synaptic plasticity occur independently of each other and rely on distinct sensory requirements.
Toxic Effects of Chromium(VI) on Anaerobic and Aerobic Growth of Shewanella oneidensis MR‐1

Cr(VI) was added to early‐ and mid‐log‐phase Shewanella oneidensis ( S. oneidensis) MR‐1 cultures to study the physiological state‐dependent toxicity of Cr(VI). Cr(VI) reduction and culture growth were measured during and after Cr(VI) reduction. Inhibition of growth was observed when Cr(VI) was added to cultures of MR‐1 growing aerobically or anaerobically with fumarate as the terminal electron acceptor. Under anaerobic conditions, there was immediate cessation of growth upon addition of Cr(VI) in early‐ and mid‐log‐phase cultures. However, once Cr(VI) was reduced below detection limits (0.002 mM), the cultures resumed growth with normal cell yield values observed. In contrast to anaerobic MR‐1 cultures, addition of Cr(VI) to aerobically growing cultures resulted in a gradual decrease of the growth rate. In addition, under aerobic conditions, lower cell yields were also observed with Cr(VI)‐treated cultures when compared to cultures that were not exposed to Cr(VI). Differences in response to Cr(VI) between aerobically and anaerobically growing cultures indicate that Cr(VI) toxicity in MR‐1 is dependent on the physiological growth condition of the culture. Cr(VI) reduction has been previously studied in Shewanella spp. , and it has been proposed that Shewanella spp.may be used in Cr(VI) bioremediation systems. Studies of Shewanella spp. provide valuable information on the microbial physiology of dissimilatory metal reducing bacteria; however, our study indicates that S. oneidensis MR‐1 is highly susceptible to growth inhibition by Cr(VI) toxicity, even at low concentrations [0.015 mM Cr(VI)].