Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic knockdown of estrogen receptor alpha (ERα) in the subfornical organ 2 augments angiotensin II-induced hypertension in female mice estrogen receptor-α and ANG II-induced hypertension

The present study tested the hypotheses that 1) ERα in the brain plays a key role in the 27 estrogen protective effects against angiotensin (ANG) II-induced hypertension, and 2) 28 that the subfornical organ (SFO) is a key site where ERα mediates these protective 29 actions. In this study, a “floxed” ERα transgenic mouse line (ERα flox ) was used to create 30 models in which ERα was knocked down in the brain or just in the SFO. Female mice 31 with ERα ablated in the nervous system (Nestin-ERα¯ mice) showed greater increases in 32 blood pressure (BP) in response to ANG II. Furthermore, females with ERα knockdown 33 specifically in the SFO [SFO adenovirus-Cre (Ad-Cre) injected ERα flox mice] also 34 showed an enhanced pressor response to ANG II. Immunohistochemical, RT-PCR and 35 Western blot analyses revealed a marked reduction in the expression of ERα in nervous 36 tissues and, in particular, in the SFO. These changes were not present in peripheral 37 tissues in Nestin-ERα ¯ mice or Ad-Cre injected ERα flox mice. mRNA expression of 38 components of the renin-angiotensin system in the lamina terminalis were up-regulated in 39 Nestin-ERα - mice. Moreover, ganglionic blockade on day 7 after ANG II infusions 40 resulted in a greater reduction of BP in Nestin-ERα ¯ mice or SFO Ad-Cre injected mice 41 suggesting that knockdown of ERα in the nervous system or the SFO alone augments 42 central ANG II-induced increase in sympathetic tone. The results indicate that interfering 43 with the action of estrogen on SFO ERα is sufficient to abolish the protective effects of 44 estrogen against ANG II-induced hypertension.
Investigating the Determinants of the Social Performance of Non-Business Entities

— The main objective of this study is to analyze the effects of customer centeredness, the firm ambidexterity and the Entrepreneurial collaboration on the social performance of non-business entities in the Western Gyeongnam and Busan Regions in Korea. For this analysis, this model is to examine various theories related to have effects on the concept of non-business entities, and is to suggest the customer centeredness, the firm ambidexterity and the social performance by reviewing previous studies and setting research model and hypotheses. To collect data by distributing 142 questionnaires, this research performed the hierarchical multiple regression analysis. As a result, the customer centeredness and the entrepreneurial collaboration were shown to have significant effects on the social performance, the adaptiveness of the firm ambidexterity was also significant. In contrast, the proactivenss of the firm ambidexterity was not shown to have a significant effect. As this research holds quite a value by showing a direction in the current emphasis, it is to imply the practical point by developing non-business entities. It proposes the lack of sufficient resources of non-business entities and sector, to put a priority in keeping a close the non-profit organization, to go with the organizational reinforcement focused on the customer centeredness, the adaptiveness of firm ambidexterity and the entrepreneurial collaboration, eventually to differentiate their internal organization from others. managerial performance. et al. also found that the relationship between customer centeredness and organizational performance and that it has a direct impact. These results show that there is a positive (+) relationship between customer centered firms and social performance. Based on these prior studies, the following research hypotheses were established.
EFFECT OF AZADIRACHTA INDICA ON THE PHARMACODYNAMICS OF PIOGLITAZONE IN NORMAL AND ALLOXAN INDUCED DIABETIC RATS

The objective of the study is to find out the effect of Azadirachta indica on pharmacodynamic interactions with concomitant administration with pioglitazone in both normal and diabetic rats. Blood samples were collected from rats by retro orbital puncture at regular intervals of time 0, 1, 2, 3, 4, 6, 8, 10, 12 hr. During the single dose administration of Pioglitazone and Azadirachta indica showed reduction of blood glucose levels dose dependently. The pioglitazone (10mg/kg) showed peak glucose reduction at 2hr, Azadirachta indica (200mg/kg) at 4hr, the combination at single and multiple dose combinations showed peak glucose reduction at 2hr in both normal and diabetic rats. The insulin levels were also found to be increased according to the blood glucose reduction at peak hours. It indicates that the combination of Azadirachta indica and pioglitazone producing the significant synergistic action in producing hypoglycemia and antihyperglycemia. Hence, care must be taken while prescribing the combination in clinical situation.
MAP kinase cascade is required for p27 downregulation and S phase entry in ﬁbroblasts and epithelial cells

MAP kinase cascade is required for p27 downregulation and S phase entry in ﬁbroblasts and epithelial cells. Am. J. Physiol. 277 ( Cell Physiol. 46): C652– C664, 1999. —The present report delineates the critical pathway in the G 1 phase involved in downregulation of p27 Kip1 , a cyclin-dependent kinase inhibitor, which plays a pivotal role in controlling entry into the S phase of the cell cycle. In resting CCL39 ﬁbroblasts and IEC-6 intestinal epithelial cells, protein levels of p27 Kip1 were elevated but dramatically decreased on serum stimulation, along with hyperphosphorylation of pRb and increased CDK2 activity. In both cell types, expression of ras resulted in an increase of basal and serum-stimulated E2F-dependent transcriptional activity and a reduction in p27 Kip1 protein levels as well. The role of the mitogen-activated protein (MAP) kinase cascade in p27 Kip1 reduction and S phase reentry was reinforced by the block-ades of serum-induced E2F-dependent transcriptional activity and p27 Kip1 downregulation with the MKK-1/2 inhibitor PD-98059. In both cell lines, downregulation of p27 Kip1 was associated with a repression of its synthesis, an event mediated by the p42/p44 MAP kinase pathway. Using an antisense approach, we demonstrated that p27 Kip1 may control cell cycle exit in both cell types. These data indicate that activation of the MAP kinase cascade is required for S phase entry and p27 Kip1 downregulation in ﬁbroblasts and epithelial cells. 1 mM EDTA, 0.2 mM sodium vanadate, 0.2 mM PMSF). Antibodies were then added over- night at 4°C (dilution 1:500). After addition of the protein A-Sepharose, the samples were rocked for 1–2 h. Immune complexes were pelleted and washed four to ﬁve times in 1 ml of buffer A . The ﬁnal pellets were recovered in gel loading buffer and separated on 10% SDS-PAGE. Gels were then ﬁxed in 10% acetic acid for 30 min and dried for autoradiography. Autoradiograms were scanned for quantitation (Fuji Phospho-Imager). Data presentation. Assays were performed in duplicate or triplicate. The data are from representative experiments performed at least twice. Results obtained with the luciferase assays were analyzed by a Student’s t -test. Results were considered signiﬁcantly different at P , 0.05.
The Ca 2 + -activated Cl − Current from Human Bestrophin-4 in Excised Membrane Patches

Bestrophins are a newly discovered family of Cl − channels, some members of which are activated by intracellular Ca 2 + . So far, all studies were carried out with whole-cell recordings from plasmid-transfected cultured cells, so it is unclear whether Ca 2 + activates bestrophin through a metabolic mechanism or in a more direct way. We report here experiments that addressed this question with excised, inside-out membrane patches. We chose human bestrophin-4 (hBest4) for heterologous expression because it gave particularly large Cl − currents when expressed, thus allowing detection even in excised membrane patches. hBest4 gave a negligible Cl − current in a Ca 2 + -free solution on the cytoplasmic (bath) side, but produced a Cl − current that was activated by Ca 2 + in a dose-dependent manner, with a K 1/2 of 230 nM. Thus, Ca 2 + appears to activate the bestrophin Cl − channel without going through a freely diffusible messenger or through protein phosphorylation. Because the activation and deactivation kinetics were very slow, however, we cannot exclude the involvement of a membrane-associated messenger.
Infrared flux excesses from hot subdwarfs.

In our search, started in February, 1994, for JHK excess fluxes among the hot subdwarf population as an indicator for the presence of binary companions, results for 72 more hot objects (=63 hot subdwarfs + 1 Horizontal Branch B star + 7 white dwarfs + 1 nonsubdwarf object) observed with the Carlos Sanchez CVF IR photometer (in June and October, 1994), are presented. The exact number of binary hot subdwarfs has gained renewed importance after the recent discovery of pulsators with G-F companions. The total number of candidates we propose may help to set some constraints; for example, out of 41 objects with excesses, 13 may have G-type binary companions. From our new sample, 14 discoveries of binary candidates have been found: BD+25 4655, Feige 108, HD 4539, HD 149382, HD 216135, KPD 2109+440, LSI+63 198, LSIV+10 9, LSV+22 38, PG 0011+221, PG 0116+242, PG 0314+103, PG 2151+100 and TON 139. Besides, 2 more from reanalysis of February, 1994, data – BD+37 1977 and BD+48 1777, may now be found to be IR excess candidates. Two suspected binaries, PB 8555 and SB 7, are also confirmed. By fitting Kurucz (1993) model spectra and assuming zero-age main sequence companions, we find upper limits on the subdwarf gravities. The distributions of upper limits on log(g), mostly between about 5.25 and 6.5, are nearly identical for both sdBs and sdOs.
RNase H Cleavage of the 5 (cid:2) End of the Human Immunodeﬁciency Virus Type 1 Genome

The synthesis of retroviral DNA is initiated near the 5 (cid:1) end of the RNA. DNA synthesis is transferred from the 5 (cid:1) end to the 3 (cid:1) end of viral RNA in an RNase H-dependent step. In the case of human immunodeﬁciency virus type 1 (HIV-1) (and certain other retroviruses that have complex secondary structures at the ends of the viral RNA), there is the possibility that DNA synthesis can lead to a self-priming event that would block viral replication. The extent of RNase H cleavage must be sufﬁcient to allow the strand transfer reaction to occur, but not so extensive that self-priming occurs. We have used a series of model RNA substrates, with and without a 5 (cid:1) cap, to investigate the rules governing RNase H cleavage at the 5 (cid:1) end of the HIV-1 genome. These in vitro RNase H cleavage reactions produce an RNA fragment of the size needed to block self-priming but still allow strand transfer. The cleavages seen in vitro can be understood in light of the structure of HIV-1 reverse transcriptase in a complex with an RNA/DNA substrate. The
The ALPINE-ALMA [CII] survey

Context. The Lyman-α line in the ultraviolet (UV) and the [CII] line in the far-infrared (FIR) are widely used tools to identify galaxies in the early Universe and to obtain insights into interstellar medium (ISM) properties in high-redshift galaxies. By combining data obtained with ALMA in band 7 at ∼320 GHz as part of the ALMA Large Program to INvestigate [CII] at Early Times (ALPINE) with spectroscopic data from DEIMOS at the Keck Observatory, VIMOS and FORS2 at the Very Large Telescope, we assembled a unique sample of 53 main-sequence star-forming galaxies at 4.4 < z < 6 in which we detect both the Lyman-α line in the UV and the [CII] line in the FIR. Aims. The goal of this paper is to constrain the properties of the Lyα emission in these galaxies in relation to other properties of the ISM. Methods. We used [CII], observed with ALMA, as a tracer of the systemic velocity of the galaxies, and we exploited the available optical spectroscopy to obtain the Lyα-[CII] and ISM-[CII] velocity offsets. Results. We find that 90% of the selected objects have Lyα-[CII] velocity offsets in the range 0 < ΔvLyα − [CII] < 400 km s−1, in line with the few measurements available so far in the early Universe, and significantly smaller than those observed at lower redshifts. At the same time, we observe ISM-[CII] offsets in the range −500 < ΔvISM−[CII] < 0 km s−1, in line with values at all redshifts, which we interpret as evidence for outflows in these galaxies. We find significant anticorrelations between ΔvLyα−[CII] and the Lyα rest-frame equivalent width EW0(Lyα) (or equivalently, the Lyα escape fraction fesc(Lyα)): galaxies that show smaller ΔvLyα−[CII] have larger EW0(Lyα) and fesc(Lyα). Conclusions. We interpret these results in the framework of available models for the radiative transfer of Lyα photons. According to the models, the escape of Lyα photons would be favored in galaxies with high outflow velocities, producing large EW0(Lyα) and small ΔvLyα-[CII], in agreement with our observations. The uniform shell model would also predict that the Lyα escape in galaxies with slow outflows (0 < vout < 300 km s−1) is mainly determined by the neutral hydrogen column density (NHI) along the line of sight, while the alternative model by Steidel et al. (2010, ApJ, 717, 289) would more highly favor a combination of NHI at the systemic velocity and covering fraction as driver of the Lyα escape. We suggest that the increase in Lyα escape that is observed in the literature between z ∼ 2 and z ∼ 6 is not due to a higher incidence of fast outflows at high redshift, but rather to a decrease in average NHI along the line of sight, or alternatively, a decrease in HI covering fraction.
Radar investigations of breaking water waves at low grazing angles with simultaneous high‐speed optical imagery

This paper describes the results of radar scattering experiments carried out at the wavetank facility at the University of Maryland, College Park. Spilling and plunging breakers with a water wavelength of approximately 80 cm were generated through dispersive focusing of a chirped wave packet, and were then imaged with a high‐speed camera in conjunction with a laser sheet. Simultaneously, the radar backscatter generated by the breakers when viewed with an “up‐wave” look direction was measured by an ultrawideband, dual‐polarized, X‐band radar with a range resolution of approximately 4 cm. The nominal grazing angle of the radar was 12°. In addition to providing both quantitative profiles of the evolving water surface and the corresponding ultrahigh resolution radar backscatter, this experimental setup also included a moving instrument carriage that allowed the sensors to follow the breakers throughout their entire evolution. Numerical scattering simulations that use the measured surface profiles as inputs were also conducted in order to further dissect the scattering mechanism. An analysis of the results shows that for the spilling breaker, over 90% of the horizontally (HH) polarized radar backscatter is generated during the initial stage of breaking by the small bulge near the wave crest. For vertical (VV) polarization, the crest bulge produces about 60% of the total backscattered energy. For both polarizations, the Doppler velocity associated with this energy is very close to that of the phase speed of the dominant wave in the water wave packet. For VV, the remainder of the backscattered energy is generated by the turbulent, postbreaking surface, and in fact a close correlation is observed between increases in the VV backscatter amplitude and the shedding of vortex ripples after the wave breaks. For the plunging breaker, the initial feature on the crest (an overturning jet) generates a lower percentage of the total backscattered energy. For the spilling breaker, agreement between the experimental and numerical results is good, particularly in the Doppler domain. The simulations also indicate uncertainty in the polarization ratio measurements that is related to multipath scattering. To the extent that they can be applied to the open ocean, these results can serve as a guide for the development of future breaker models.
Reverse Line Blot Hybridization Assay for Identiﬁcation of Medically Important Fungi from Culture and Clinical Specimens (cid:1)

We evaluated a combined panfungal PCR-reverse line blot (RLB) hybridization assay based on internal transcribed spacer 1 (ITS1) and ITS2 region polymorphisms to identify 159 Candida , Cryptococcus neoformans , and Aspergillus isolates (22 species). Its utility to identify fungal pathogens directly from 27 clinical specimens was also determined. ITS sequence analysis was performed to resolve discrepant identiﬁcations or where no RLB result was obtained. Species-speciﬁc ITS2- and ITS1-based probes correctly identiﬁed 155 of 159 isolates (98%) and 149 (93.7%) isolates, respectively. All strains were unambiguously differentiated with the exception of cross-reactivity between the Candida norvegensis probe and Candida haemulonii DNA product. Species identiﬁcation of the pathogen was made for all 21 specimens (sensitivity of 100%) where species-speciﬁc probes were included in the RLB; however, there was no ITS2 probe-based hybridization signal for two specimens. Results were concordant with the culture results for 18 (85.7%) specimens. The assay was able to provide species identiﬁcation in the absence of a culture result (two specimens) and to detect mixed infection (one specimen). The results indicate that the RLB assay is capable of reliably detecting yeasts and Aspergillus spp. in clinical specimens and that the incorporation of both ITS1- and ITS2-targeted probes is required for optimal sensitivity. The test has potential utility in the early diagnosis of invasive fungal infection, since “fungal” DNA was detected in all 27 specimens. Prior to incorporation of probes to detect other fungal species, ITS sequencing may be performed to achieve species identiﬁcation.
DNA Methylation in Mammalian Cells DNA Methylation in Mammalian Cells

Epigenetic regulation was first studied in the 1970s and has quickly gained global interest. It is involved at many different stages of mammalian cell development. The broad nature of epigenetic regulation has led to it being referred to as an ‘ all stage ’ mechanism of regulation as it is implicated in many developmental stages including embryonic development, ageing and in cancer progression. The term ‘ epigenetic ’ refers to the alteration of gene expression without changing the genomic sequence. Epigenetic regulation involves the main subtypes of DNA methylation and histone modification, and microRNA expression. Epigenetic alteration is used by mammalian cells to ‘ turn-on and -off ’ the gene expression. During embryonic development this process is used to induce cell apoptosis of genes that are no longer useful. During cancer development, epigenetics works to repress tumour suppressor gene expression and activate oncogene expression. The stability and sustainability for the detec- tion of epigenetic markers make it an attractive area for biomarker and drug discovery. In this book chapter we will discuss the key epigenetic processes involved in mammalian cell development and disease progression, specifically in cancer.
Optimizing BAO measurements with non-linear transformations of the Lyman-α forest

We explore the effect of applying a non-linear transformation to the Lyman-α forest transmitted flux F=e−τ and the ability of analytic models to predict the resulting clustering amplitude. Both the large-scale bias of the transformed field (signal) and the amplitude of small scale fluctuations (noise) can be arbitrarily modified, but we were unable to find a transformation that increases significantly the signal-to-noise ratio on large scales using Taylor expansion up to the third order. In particular, however, we achieve a 33% improvement in signal to noise for Gaussianized field in transverse direction. On the other hand, we explore an analytic model for the large-scale biasing of the Lyα forest, and present an extension of this model to describe the biasing of the transformed fields. Using hydrodynamic simulations we show that the model works best to describe the biasing with respect to velocity gradients, but is less successful in predicting the biasing with respect to large-scale density fluctuations, especially for very nonlinear transformations.
The Open Science Framework

There currently exists a gap between scientific values and scientific practices. This gap is strongly tied to the current incentive structure that rewards publication over accurate science. Other problems associated with this gap include reconstructing exploratory narratives as confirmatory, the file drawer effect, an overall lack of archiving and sharing, and a singular contribution model publication through which credit is obtained. A solution to these problems is increased disclosure, transparency, and openness. The Open Science Framework (http://openscienceframework.org) is an infrastructure for managing the scientific workflow across the entirety of the scientific process, thus allowing the facilitation and incentivization of openness in a comprehensive manner. The current version of the OSF includes tools for documentation, collaboration, sharing, archiving, registration, and exploration.
Integrated Bioinformatics Analysis of Differentially-Expressed Genes and Immune Cell In�ltration Characteristics in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is a life-threatening thoracic tumor with a poor prognosis. Identifying the best-targeted therapy, appropriate biomarkers and individual treatment for patients with ESCC remains a signi�cant challenge. The present study aimed to elucidate key candidate genes and immune cell in�ltration characteristics in ESCC by integrated bioinformatics analysis. We downloaded nine gene expression datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ESCC tissues and normal tissues in each dataset were identi�ed by the “limma” R package, and a total of 152 robust DEGs were identi�ed by robust rank aggregation (RRA) algorithm. Functional enrichment analyses of the robust DEGs showed that these genes were signi�cantly associated with extracellular matrix related process. Immune cell in�ltration analysis was also conducted by CIBERSORT algorithm. We found that M0 and M1 macrophages were increased dramatically in ESCC while M2 macrophages decreased. Nine hub genes were picked out from a protein-protein interaction (PPI) network used by the CytoHubba plugin in Cytoscape. According to the receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis, the genes PLAU, SPP1 and VCAN had high diagnostic and prognostic values for ESCC patients. Based on univariate and multivariate regression analyses, seven genes (IL18, PLAU, ANO1, SLCO1B3, CST1, NELL2 and MAGEA11) from the robust DEGs were used to construct a good prognostic model. A nomogram that incorporates seven genes signature was established to develop a quantitative method for ESCC prognosis. Our results might provide aid for exploring potential therapeutic targets and prognosis evaluation in ESCC. analyzed nine mRNA gene chip datasets from GEO and identi�ed robust (DEGs) between ESCC and normal Functions of these robust DEGs were then explored by Gene Ontology (GO) Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The in�ltration characteristics of 22 types of immune cells were conducted by CIBERSORT algorithm. Nine hub genes were elected from robust DEGs by constructing the protein-protein interaction (PPI) network. The genes PLAU, SPP1 and VCAN had high diagnostic and prognostic values for with ESCC. A seven-gene signature for the prognosis of patients with ESCC by Univariate and Multivariable Cox regression analyses, which may serve as an independent prognostic factor for ESCC. Our results would help understand the molecular mechanisms of tumorigenesis and develop new therapeutic targets in ESCC.