Miracle-dz/UniFAR-FTUs huggingface dataset:
The mesoderm determinant Snail collaborates with related zinc‐finger proteins to control Drosophila neurogenesis

The Snail protein functions as a transcriptional regulator to establish early mesodermal cell fate. Later, in germ band‐extended embryos, Snail is also expressed in most neuroblasts. Here we present evidence that this expression of Snail is required for central nervous system (CNS) development. The neural function of snail is masked by two closely linked genes, escargot and worniu. Both Escargot and Worniu contain zinc‐finger domains that are highly homologous to that of Snail. Although not affecting expression of early neuroblast markers, the deletion of the region containing all three genes correlates with loss of expression of CNS determinants including fushi tarazu, pdm‐2 and even‐skipped. Transgenic expression of each of the three Snail family proteins can rescue efficiently the fushi tarazu defects, and partially the pdm‐2 and even‐skipped CNS patterns. These results demonstrate that the Snail family proteins have essential functions during embryonic CNS development, around the time of ganglion mother cell formation.
Evidence for Rho-kinase activation in patients with pulmonary arterial hypertension.

BACKGROUND Direct evidence for Rho-kinase activation in patients with pulmonary hypertension (PH) is still lacking. METHODS AND RESULTS Rho-kinase activity in circulating neutrophils was examined by determining the ratio of phosphorylated/total forms of myosin-binding subunit, a substrate of Rho-kinase, in 40 consecutive PH patients and 40 healthy controls. Next, Rho-kinase expression and activity was examined in isolated human lung tissues (5 patients with idiopathic pulmonary arterial hypertension [IPAH], 5 controls) and vascular reactivity of isolated small human pulmonary arteries in vitro (4 IPAH, 4 controls). Rho-kinase activity in circulating neutrophils was significantly increased in the PH patients overall compared with controls (P<0.0001). Significant correlations were noted between Rho-kinase activity and the severity and duration of PAH (all P<0.05). Rho-kinase expression and activity in isolated lung tissues also were significantly increased in the IPAH patients compared with the controls (both P<0.0001). Endothelium-dependent relaxation was markedly impaired and serotonin-induced contraction (in the absence of the endothelium) markedly enhanced in the PAH patients compared with the controls, and the hypercontraction to serotonin was abolished by hydroxyfasudil, a specific Rho-kinase inhibitor. CONCLUSIONS These results provide the first direct evidence for Rho-kinase activation in patients with PAH, suggesting the therapeutic importance of Rho-kinase in the disorder.
miRNA Expression Profile and Effect of Wenxin Granule in Rats with Ligation-Induced Myocardial Infarction

Wenxin Granule (WXKL) is a traditional Chinese medicine used for treatment of myocardial infarction (MI) and arrhythmias. However, the genomic pathological mechanisms of MI and mechanisms of WXKL are largely unknown. This study aims to investigate a comprehensive miRNA expression profile, and the predicted correlation pathways to be targeted by differentially expressed miRNAs in MI, and mechanisms of WXKL from a gene level. MI rat model was established by a coronary artery ligation surgery. miRNA expression microarrays were performed and the data were deposited in Gene Expression Omnibus (GEO number GSE95855). And, pathway analysis was performed by using the DIANA-miRPath v3.0 online tool. The expressions of miR-1, miR-133, Cx43, and Cx45 were detected by quantitative real-time PCR. It was found that 35 differentially expressed miRNAs and 23 predicted pathways, including miR-1, miR-133, and gap junction pathway, are involved in the pathogenesis of MI. And, WXKL increased the expressions of miR-1 and miR-133, while also increased the mRNA levels of Cx43 and Cx45, and, especially, recovered the Cx43/Cx45 ratio near to normal level. The results suggest that regulatory effects on miR-1, miR-133, Cx43, and Cx45 might be a possible mechanism of WXKL in the treatment of MI at the gene level.
Downstream sequences affect transcription initiation from the adenovirus major late promoter

We analyzed a set of adenovirus-simian virus 40 (SV40) hybrids in which the SV40 T antigen coding sequences are inserted downstream from the adenovirus major late promoter within the first, second, and third segments of the tripartite leader. In infected cells, these viruses give rise to a matched set of hybrid SV40 mRNAs that differ only in the number of tripartite leader segments attached to the complete SV40 T antigen coding region. We found that the number of tripartite leader segments present at the 5' end of the hybrid SV40 mRNAs had little effect on the efficiency of T antigen translation. Surprisingly, insertion of SV40 sequences within the first leader segment, at +33 relative to the start of transcription, significantly reduced the frequency of transcription initiation from the major late promoter. The 3' boundary of this downstream transcriptional control element was mapped between +33 and +190 by showing that insertion of SV40 sequences within the intron after the first leader segment at +190 had very little effect on transcription initiation from the late promoter. A transient expression assay was used to show that the effect of downstream sequences on transcription initiation from the major late promoter is dependent on a trans-acting factor encoded or induced by adenovirus.
Selective Coexpression of NMDAR2A/B and NMDAR1 Subunit Proteins in Dysplastic Neurons of Human Epileptic Cortex

NR1 and NR2 are the two gene families for the NMDA receptor. In vitro studies show that while NR2 alone is nonfunctional, NR1 alone produces weak currents to glutamate or NMDA. We previously showed by immunocytochemistry (ICC) that in normal appearing, nonepileptic human cortical neurons, only NR1 and not NR2 proteins were expressed, in contrast to the presence of both NR1 and NR2 in normal rat cortical neurons. We also showed, in dysplastic epileptic cortex, that both NR1 and NR2 were highly expressed using ICC on adjacent 30-microm sections. However, the relative coexpressions of NR1 and NR2 proteins in single neurons in single sections of human epileptic cortex were unknown. In this study, we used double-labeled immunofluorescence and confocal microscopy to examine the distribution and coexpression of subunit proteins for NR1 and NR2A/B in both nondysplastic (control comparison) and dysplastic regions of human brain resected for the treatment of intractable epilepsy (11 patients). In nondysplastic regions, cortical neurons did not have immunoreactivity (ir) for NR2A/B, whereas NR1-ir was abundant. By contrast, dysplastic neurons in the regions with epileptic cortical dysplasia showed intense NR2A/B-ir in the somata and their dendritic processes. These same NR2A/B-ir dysplastic neurons were colabeled by NR1. These results demonstrate directly that dysplastic neurons express both NR2A/B and NR1 proteins, whereas nondysplastic cortical neurons express only NR1 proteins. Selective coexpression of NR2A/B and NR1 in dysplastic neurons suggests that NR2A/B may form heteromeric NR1-NR2 coassemblies and hyperexcitability in dysplastic neurons that could contribute to focal seizure onset.
Meta‐analysis of type‐specific human papillomavirus prevalence in Iranian women with normal cytology, precancerous cervical lesions and invasive cervical cancer: Implications for screening and vaccination

To predict the impact of current vaccines on cervical cancer and for the improvement of screening programs, regional data on distribution of human papillomavirus (HPV) types in women with or without cervical cancer is crucial. The present meta‐analysis intend to comprehensively evaluate the HPV burden in women with invasive cervical cancer, high‐grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low‐grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology, as these data will help decision making in regards with screening programs and HPV vaccination in Iran. To determine the HPV prevalence and type distribution in Iranian women with or without cervical cancer, 20 published studies were included in this meta‐analysis. In total, 713, 124, 104, 60, and 2577 women invasive cervical cancer, high‐grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low‐grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal were reviewed, respectively. Overall HPV prevalence in women with invasive cervical cancer, high‐grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low‐grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology were 77.4%, 71.8%, 65.3%, 61.7%, and 8.4%, respectively. The six most common types were HPV 16, 18, 6/11, 31, and 33; among them HPV 16 was the most frequent type in all five different groups. According to this study, it was estimated that HPV vaccines could have a great impact on prevention of cervical cancer in Iran. In conclusion, this meta‐analysis highlights the necessity of introducing vaccination program in Iran. J. Med. Virol. 87:287–295, 2015. © 2014 Wiley Periodicals, Inc.
Therapeutic drug monitoring of antiretrovirals in human immunodeficiency virus infection.

The era of antiviral therapy directed against HIV-1 has now entered its second decade. In the twelve years since the FDA approved the first antiretroviral drug zidovudine there have been a number of seminal developments that have revolutionized the approach to therapy. These advances converged to change the treatment paradigm from one of therapeutic nihilism to that of cautious optimism. First, several trials demonstrated that combination therapy of nucleoside reverse transcriptase inhibitors (NRTIs) is superior to monotherapy in extending survival and delaying disease progression. Second, the concept of virologic latency in asymptomatic HIV-infected patients was revised. Mathematic modelling demonstrated that there is an ongoing high level of virus production driving a rapid turnover of CD4 cells at all stages of infection. Hence it was concluded that the aim of antiretroviral therapy (ART) should be to "hit early and hit hard. " Third, significant advances in molecular virology facilitated the development of quantitative methods to measure the circulating HIV plasma RNA. HIV viral load has been shown to be a sensitive predictor of disease progression and a valuable marker of response to therapy. However, none of these developments would have translated into improved patient care without the advent of two new classes of drugs-the protease inhibitors (PIs) and the nonnucleoside reverse transcriptase inhibitors (NNRTIs).
Exertional dyspnoea in patients with airway obstruction, with and without CO2 retention

BACKGROUND Dyspnoea is a common and disabling symptom in patients with cardiopulmonary disease. Unfortunately the mechanisms that produce dyspnoea are still poorly understood. The relationship between dyspnoea and the load on the ventilatory muscles, chemical drive, and ventilatory indices was therefore assessed in patients with obstructive pulmonary disease during an incremental exercise test. METHODS Fifty patients with a wide range of obstructive pulmonary disease (mean forced expiratory volume in one second (FEV1) 66.1 (28.8)% predicted) performed an incremental cycle ergometer test. A subdivision was made between subjects with CO2 retention (ΔPaco 2 ⩾0, n = 22) and subjects without CO2 retention (ΔPaco 2 <0, n = 28) during exercise. During the test dyspnoea (Borg score), oesophageal pressures (mechanical load on the ventilatory muscles (time tension index (TTI)), blood gas tensions, and minute ventilation were measured. Correlations for changes in mechanical and chemical factors with changes in dyspnoea score were calculated to assess relevant factors. An analysis of covariance was used to examine whether there was a relationship between dyspnoea score and each of these factors and whether this relationship was different between the subgroups with and without CO2 retention. Multiple regression analysis was used to assess the independent effect of each parameter on dyspnoea sensation. Furthermore, the amplitude of pleural pressure swing ((Pi + Pe)act) generated at maximal work load (Ptot, an indication of the load on all respiratory muscles) was calculated. Analysis of covariance was used to assess whether there was a relationship between tidal volume (Vt) and Ptot and whether this relationship was different between the groups (slopes are an expression of the length-tension inappropriateness, LTI). RESULTS In the total group and the group without CO2 retention a significant correlation between dyspnoea and the increase in the inspiratory time tension index (TTIi) was present. In the group with CO2retention a significant correlation was seen between dyspnoea and ΔPaco 2. The factors ΔPao 2, ΔVE%MVV and Δ(Vt/Ti) showed a correlation with a p value of ⩽0.10 both in the total group and in those without CO2 retention. In an analysis of covariance the relationship between dyspnoea score and ΔPaco 2 appeared to be significantly different between the two subgroups, being more pronounced in the group with CO2 retention. No other relationships with change in dyspnoea score were found. There was no significant relationship between Vt and Ptot in the total group nor in the two subgroups, indicating some length-tension inappropriateness in both groups. CONCLUSION In patients with distinctive pulmonary disease who are normocapnic or hypocapnic the mechanical load (ΔTTIi) and length-tension inappropriateness (LTI) on ventilatory muscles seem to be the main determinant of exertional dyspnoea. As soon as hypercapnia occurs, this seems to override all other inputs for dyspnoea.
New Policy at HSR New Policy on Disclosures at Health Services Research

The appropriate role of scientific journals is to disseminate the best scienceavailable to the public and the research community. Two principal mecha-nismstofulﬁllthisrolearepeerreviewandopendisclosureofpotentialbiasesin conducting and reporting results. Peer review primarily focuses on what ispresented in the submitted manuscript——reviewers cannot easily assess whathas been omitted or whether the authors made choices in the design or exe-cution of the study that mayhavebiased their results. For example, it appearssome key adverse data were omitted from the Vioxx Gastrointestinal Out-comesResearch(VIGOR)trialreportedintheNewEnglandJournalofMedicine(Curfman, Morrissey, and Drazen 2005a,b). Some authors claimed to havebeen unaware of the problems, raising questions about what are the roles andresponsibilities of all authors in ensuring ‘‘the best science available’’ is pub-lished in scientific journals. Increasingly, journals have adopted more explicitpoliciesaboutwhattodiscloseandwhoshouldbeinformedduringtheprocessof review and publication.There are also studies showing that a project’s sponsorship may be re-lated to the ﬁndings reported. Most of these have focused on trials reportinguse of drugs and devices, comparing studies sponsored by the for-proﬁt man-ufacturers with those sponsored by not-for-proﬁt and government entities(Lexchinetal.2003;RidkerandTorres2006),oronstudiesrelatingtotobaccouse (Barnes and Bero 1996). Publication of biased studies is an insidiousproblem because the submitted ﬁndings may not be incorrect per se and thusare unlikely to be caught by peer reviewers. Absent or incomplete disclosure,however,preventstheconsumerofsuchpublishedinformationfromapplyingthe appropriate skepticism.
A Theoretical Framework for Surveying Citizens' Fiscal Preferences

Survey research has been advocated as a vehicle for eliciting information relevant to the policy decisions of public administrators as evidenced by recent articles in the Public Administration Review. ' To the extent that public policy makers feel entrusted to satisfy constituent preferences, it is imperative they be cognizant of citizens' attitudes toward fiscal policy issues. The citizen, in effect, should be viewed as a consumer. Random sample surveys of the population provide data which increase the public administrator's awareness of citizen attitudes and, thus, facilitate the satisfying of citizen preferences. Sample survey data permit inferences to be made about the fiscal preferences of all citizens, not just those who actively participate in the political process via special interest groups.2 The potential of attitudinal surveys of individuals' public sector preferences for improving public sector budgeting and financing decisions is underscored by the closer scrutiny given to public expenditure and revenue policies in an era of fiscal retrenchment. Properly designed survey instruments can elicit information pertaining to various dimensions of public sector expenditure and revenue decisions: (1) desired spending levels and (2) desired financing schemes.3 In ascertaining citizen fiscal preferences, it is desirable to develop survey instruments based on an explicit theory. A theoretical framework aids in questionnaire design. It permits development of attitudinal questions which accurately reflect the preferences of interest to policy makers as well as the identification of relevant social, economic, and demographic attributes of the respondents necessary for analysis and interpretation. Equally important, survey research based on an explicit theoretical framework provides a better understanding of the determinants of citizen preferences. This knowledge permits the prediction of shifts in fiscal preferences resulting from changes in the socio-demographic profile of the constituency or the fiscal environment. Wellarticulated and properly designed survey research provides public officials making public spending and financing decisions with additional information of citizens' fiscal preferences. Such information will enhance their ability to make responsive decisions. The purpose of this paper is to articulate a model of citizen public sector fiscal preferences which serves these purposes. Based on the economic theory of consumer
Restoring primacy in amnesic free recall: Evidence for the recency theory of primacy

Primacy and recency effects at immediate recall are thought to reflect the independent functioning of a long-term memory store (primacy) and a short-term memory store (recency). Key evidence for this theory comes from amnesic patients who show severe long-term memory storage deficits, coupled with profoundly attenuated primacy. Here we challenge this dominant dual-store theory of immediate recall by demonstrating that attenuated primacy in amnesic patients can reflect abnormal working memory rehearsal processes. D.A. , a patient with severe amnesia, presented with profoundly attenuated primacy when using her preferred atypical noncumulative rehearsal strategy. In contrast, despite her severe amnesia, she showed normal primacy when her rehearsal was matched with that of controls via an externalized cumulative rehearsal schedule. Our data are in keeping with the “recency theory of primacy” and suggest that primacy at immediate recall is dependent upon medial temporal lobe involvement in cumulative rehearsal rather than long-term memory storage.
A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons

Generation of mammalian circadian rhythms involves molecular transcriptional and translational feedback loops. It is not clear how membrane events interact with the intracellular molecular clock or whether membrane activities are involved in the actual generation of the circadian rhythm. We examined the role of membrane potential and calcium (Ca2+) influx in the expression of the circadian rhythm of the clock gene Period 1 (Per1) within the rat suprachiasmatic nucleus (SCN), the master pacemaker controlling circadian rhythmicity. Membrane hyperpolarization, caused by lowering the extracellular concentration of potassium or blocking Ca2+ influx in SCN cultures by lowering [Ca2+], reversibly abolished the rhythmic expression of Per1. In addition, the amplitude of Per1 expression was markedly decreased by voltage-gated Ca2+ channel antagonists. A similar result was observed for mouse Per1 and PER2. Together, these results strongly suggest that a transmembrane Ca2+ flux is necessary for sustained molecular rhythmicity in the SCN. We propose that periodic Ca2+ influx, resulting from circadian variations in membrane potential, is a critical process for circadian pacemaker function.
IL-1α and IL-1β Recruit Different Myeloid Cells and Promote Different Stages of Sterile Inflammation

The immune system has evolved to protect the host from invading pathogens and to maintain tissue homeostasis. Although the inflammatory process involving pathogens is well documented, the intrinsic compounds that initiate sterile inflammation and how its progression is mediated are still not clear. Because tissue injury is usually associated with ischemia and the accompanied hypoxia, the microenvironment of various pathologies involves anaerobic metabolites and products of necrotic cells. In the current study, we assessed in a comparative manner the role of IL-1α and IL-1β in the initiation and propagation of sterile inflammation induced by products of hypoxic cells. We found that following hypoxia, the precursor form of IL-1α, and not IL-1β, is upregulated and subsequently released from dying cells. Using an inflammation-monitoring system consisting of Matrigel mixed with supernatants of hypoxic cells, we noted accumulation of IL-1α in the initial phase, which correlated with the infiltration of neutrophils, and the expression of IL-1β correlated with later migration of macrophages. In addition, we were able to show that IL-1 molecules from cells transfected with either precursor IL-1α or mature IL-1β can recruit neutrophils or macrophages, respectively. Taken together, these data suggest that IL-1α, released from dying cells, initiates sterile inflammation by inducing recruitment of neutrophils, whereas IL-1β promotes the recruitment and retention of macrophages. Overall, our data provide new insight into the biology of IL-1 molecules as well as on the regulation of sterile inflammation.
Applying shuffled frog leaping algorithm and bottom left fill algorithm in rectangular packing problem

Modern industry has been applying various optimization methods in solving problems and increasing productivity. The bin packing problem is one of the well-known problems in many industries, such as, glass manufacturing industry, paper packaging industry and garment industry that commonly require optimization techniques to improve the productivity. This paper introduces the use of the shuffled frog leaping algorithm (SFLA), a meta-heuristic approach for optimization, combined with the bottom left fill algorithm (BLF) as an approach for optimizing the arrangement of the 2D shapes in limited space. The objective is to arrange the set of rectangular box items in a given 2D space as efficiently as possible in order to minimize the waste from the process. The algorithm performance in converging to the optimal solution is presented. The proposed approach could be applied to various related manufacturing problems.