gebhart/patrepeval huggingface dataset:
Androgen Receptor-Mediated Antagonism of Estrogen-Dependent Low Density Lipoprotein Receptor Transcription in Cultured Hepatocytes (1997)

Postmenopausal women receiving hormone replacement therapy have a lower risk of coronary heart disease than women who do not receive hormone treatment. Multiple mechanisms are likely to underlie estrogen's cardioprotective action, including lowering of plasma low density lipoprotein (LDL) cholesterol. Using an in vitro system exhibiting normal regulation of LDL receptor (LDLR) gene transcription, we show that 17beta-estradiol activates the LDLR promoter in transiently transfected HepG2 cells. LDLR activation by estrogen in HepG2 cells is dependent on the presence of exogenous estrogen receptor, and the estrogen-responsive region of the LDLR promoter colocalizes with the sterol response element previously identified. The estrogen response is concentration dependent, saturable, and sensitive to antagonism by estrogen receptor antagonists. Further, we show that compounds with androgen receptor agonist activity attenuate the estrogen-induced up-regulation of LDLR in our model system. Progestins with androgen receptor agonist activity, such as medroxyprogesterone acetate, also suppress estrogen's effects on LDLR expression through their androgenic properties. Characterization of the interplay between these hormone receptors on the LDLR in vitro system may allow a better understanding of the actions of sex steroids on LDLR gene expression and their roles in cardiovascular disease.
Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting (2011)

TALENs are important new tools for genome engineering. Fusions of transcription activator-like (TAL) effectors of plant pathogenic Xanthomonas spp. to the FokI nuclease, TALENs bind and cleave DNA in pairs. Binding specificity is determined by customizable arrays of polymorphic amino acid repeats in the TAL effectors. We present a method and reagents for efficiently assembling TALEN constructs with custom repeat arrays. We also describe design guidelines based on naturally occurring TAL effectors and their binding sites. Using software that applies these guidelines, in nine genes from plants, animals and protists, we found candidate cleavage sites on average every 35 bp. Each of 15 sites selected from this set was cleaved in a yeast-based assay with TALEN pairs constructed with our reagents. We used two of the TALEN pairs to mutate HPRT1 in human cells and ADH1 in Arabidopsis thaliana protoplasts. Our reagents include a plasmid construct for making custom TAL effectors and one for TAL effector fusions to additional proteins of interest. Using the former, we constructed de novo a functional analog of AvrHah1 of Xanthomonas gardneri. The complete plasmid set is available through the non-profit repository AddGene and a web-based version of our software is freely accessible online.
Iron−Sulfur Cluster Biosynthesis: Functional Characterization of the N- and C-Terminal Domains of Human NFU (2009)

Human NFU (also known as HIRIP5) has been implicated in cellular iron-sulfur cluster biosynthesis. Bacterial and yeast forms are smaller than the human protein and are homologous to the C-terminal domain of the latter. This C-terminal domain contains a pair of redox active cysteines and demonstrates thioredoxin-like activity by mediating persulfide bond cleavage of sulfur-loaded NifS (an IscS-type protein), the sulfide donor for [2Fe-2S] cluster assembly on ISU-type scaffold proteins. Herein, the affinity of full-length human NFU and the individual N- and C-terminal domains for sulfide donor and cluster scaffold proteins is assessed. The influence of the N-terminal domain on C-terminal NFU binding to NifS and persulfide reductase activity is also examined. Only the C-terminal domain is required for persulfide reductase activity, while complex formation of NifS with full-length NFU is similar to that of the C-terminal domain alone (K(D) approximately 9.7 +/- 0.7 and 10.1 +/- 0.6 microM, respectively). There is negligible affinity between the isolated C- and N-terminal domains, while the N-terminal domain has negligible affinity for either sulfide donor or cluster scaffold proteins. The temperature dependence of the binding enthalpy for formation of the complex between NifS and the C-terminal domain of NFU yields a change in molar heat capacity (DeltaC(p) approximately 138 cal mol(-1) K(-1)) that suggests bonding at the protein-protein interface is dominated by electrostatic interactions. This is consistent with electrostatic potential maps for bacterial homologues of the N- and C-terminal domains of human NFU, which most likely reflect the structural characteristics expected for full-length human NFU.
PCR of peripheral blood for diagnosis of meningococcal disease (1996)

Meningococcal disease is normally suspected on clinical grounds and is confirmed by isolation of Neisseria meningitidis bacteria from blood or cerebrospinal fluid or, more recently, by serology or PCR of cerebrospinal fluid. Achieving confirmation of a clinical diagnosis of meningococcal disease has become more difficult in the last few years. The pre-hospitalization administration of parenteral benzylpenicillin normally renders blood cultures sterile, and lumbar puncture is undertaken less frequently, especially in young children. We evaluated PCR for the detection of meningococcal DNA in 80 blood samples taken from patients with known or suspected meningococcal disease or from patients with other diagnoses (negative controls). Both the sensitivity and the specificity of the test were 100% for patients with confirmed cases of meningococcal disease when the blood buffy coat was used (83 to 100% sensitivity and 87 to 100% specificity with 95% confidence limits). Positive PCR results could be obtained from both blood buffy coat and serum samples. Sensitivity was unaffected by prior antibiotic treatment. PCR is a rapid, sensitive test that may be used to confirm a diagnosis of meningococcal disease by using peripheral blood samples. Introduction of this test into clinical laboratories may in some cases obviate the need for lumbar puncture to be performed on patients with suspected meningococcal disease. Our results demonstrate that a substantial number of cases of meningococcal disease are not confirmed by conventional techniques and remain undiagnosed. If the PCR test described here was widely applied, the number of cases of meningococcal disease ascertained might rise by as much as 60% greater than that recognized at present. It is likely that we are in a prevaccination era for meningococcal disease. Better case ascertainment is urgently required to assess the need for vaccines, to determine their costs and benefits, and to monitor their efficacies.
[Twist gene promotes the formation and migration of mammospheres of BT-549 breast cancer cells]. (2015)

Twist gene promotes the enrichment and migration of CSCs from the BT-549 cell line.
Oxysterols are agonist ligands of RORγt and drive Th17 cell differentiation (2014)

The RAR-related orphan receptor gamma t (RORγt) is a nuclear receptor required for generating IL-17-producing CD4(+) Th17 T cells, which are essential in host defense and may play key pathogenic roles in autoimmune diseases. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol and lipid metabolism. Here, we describe the identification of several naturally occurring oxysterols as RORγt agonists. The most potent and selective activator for RORγt is 7β, 27-dihydroxycholesterol (7β, 27-OHC). We show that these oxysterols reverse the inhibitory effect of an RORγt antagonist, ursolic acid, in RORγ- or RORγt-dependent cell-based reporter assays. These ligands bind directly to recombinant RORγ ligand binding domain (LBD), promote recruitment of a coactivator peptide, and reduce binding of a corepressor peptide to RORγ LBD. In primary cells, 7β, 27-OHC and 7α, 27-OHC enhance the differentiation of murine and human IL-17-producing Th17 cells in an RORγt-dependent manner. Importantly, we showed that Th17, but not Th1 cells, preferentially produce these two oxysterols. In vivo, administration of 7β, 27-OHC in mice enhanced IL-17 production. Mice deficient in CYP27A1, a key enzyme in generating these oxysterols, showed significant reduction of IL-17-producing cells, including CD4(+) and γδ(+) T cells, similar to the deficiency observed in RORγt knockout mice. Our results reveal a previously unknown mechanism for selected oxysterols as immune modulators and a direct role for CYP27A1 in generating these RORγt agonist ligands, which we propose as RORγt endogenous ligands, driving both innate and adaptive IL-17-dependent immune responses.
Terahertz Vibrational Modes of Inverse Micelles (2002)

A large absorption resonance has been observed in the far-infrared spectrum of water confined within inverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) in heptane. The amplitude and spectral position of this resonance depend on the size of the water pool. The origin of the THz absorption of these liquid pools is assigned to surface oscillations of the water pool, driven by the interfacial tension of the water−surfactant-oil interface. These data indicate a dramatic restructuring of the density of states of the liquid and are consistent with a theoretical model for the oscillatory modes of liquid droplets. The presence of a large excess in the vibrational density of states of confined water could have far-ranging implications in many biochemical and chemical processes where confined water is present.
An educational dialogue system with a user controllable dialogue manager (1998)

We have developed an educational environment for a modular spoken dialogue system.The aim of the environment is to provide students, with different backgrounds, means to understand the behaviour of spoken dialogue systems.Focus in this paper is on dialogue and dialogue management.The dialogue is recorded in a dialogue tree whose nodes are dialogue objects.The dialogue objects model the constituents of the dialogue and consist of parameters for modelling dialogue structure, focus structure and a process description describing the actions of the dialogue system.Various dialogue system behaviours can be achieved by modifying these parameters.This is done using the educational environment, which is interactive and facilitates examination, expansion and modification of the dialogue object parameters and hence the system.The educational system has been used in a number of courses at various universities in Sweden.
KNN Matting (2013)

This paper proposes to apply the nonlocal principle to general alpha matting for the simultaneous extraction of multiple image layers; each layer may have disjoint as well as coherent segments typical of foreground mattes in natural image matting. The estimated alphas also satisfy the summation constraint. As in nonlocal matting, our approach does not assume the local color-line model and does not require sophisticated sampling or learning strategies. On the other hand, our matting method generalizes well to any color or feature space in any dimension, any number of alphas and layers at a pixel beyond two, and comes with an arguably simpler implementation, which we have made publicly available. Our matting technique, aptly called KNN matting, capitalizes on the nonlocal principle by using $(K)$ nearest neighbors (KNN) in matching nonlocal neighborhoods, and contributes a simple and fast algorithm that produces competitive results with sparse user markups. KNN matting has a closed-form solution that can leverage the preconditioned conjugate gradient method to produce an efficient implementation. Experimental evaluation on benchmark datasets indicates that our matting results are comparable to or of higher quality than state-of-the-art methods requiring more involved implementation. In this paper, we take the nonlocal principle beyond alpha estimation and extract overlapping image layers using the same Laplacian framework. Given the alpha value, our closed form solution can be elegantly generalized to solve the multilayer extraction problem. We perform qualitative and quantitative comparisons to demonstrate the accuracy of the extracted image layers.
Kinetic Analysis of Chemical Vapor Deposition of Boron Nitride (1991)

BN was deposited on Al 2 O 3 substrates from the BCl 3 ─NH 3 ─Ar reagent system. An impinging jet reactor configuration was used to obtain kinetic data in the temperature range of 800° to 1000°C and in the pressure range of 4 to 20 kPa. The BN deposition could be described by a simple kinetic rate expression with an activation energy of about 39 kcal/mol and a first‐order dependency on BCl 3 concentration. The BN deposition rate increased with temperature, pressure, and BCl 3 concentration. The microstructure of the BN coatings was not strongly influenced by the process parameters.
Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues (2016)

Current sequencing methods are error-prone, which precludes the identification of low frequency mutations for early cancer detection. Duplex sequencing is a sequencing technology that decreases errors by scoring mutations present only in both strands of DNA. Our aim was to determine whether duplex sequencing could detect extremely rare cancer cells present in peritoneal fluid from women with high-grade serous ovarian carcinomas (HGSOCs). These aggressive cancers are typically diagnosed at a late stage and are characterized by TP53 mutations and peritoneal dissemination. We used duplex sequencing to analyze TP53 mutations in 17 peritoneal fluid samples from women with HGSOC and 20 from women without cancer. The tumor TP53 mutation was detected in 94% (16/17) of peritoneal fluid samples from women with HGSOC (frequency as low as 1 mutant per 24,736 normal genomes). Additionally, we detected extremely low frequency TP53 mutations (median mutant fraction 1/13,139) in peritoneal fluid from nearly all patients with and without cancer (35/37). These mutations were mostly deleterious, clustered in hotspots, increased with age, and were more abundant in women with cancer than in controls. The total burden of TP53 mutations in peritoneal fluid distinguished cancers from controls with 82% sensitivity (14/17) and 90% specificity (18/20). Age-associated, low frequency TP53 mutations were also found in 100% of peripheral blood samples from 15 women with and without ovarian cancer (none with hematologic disorder). Our results demonstrate the ability of duplex sequencing to detect rare cancer cells and provide evidence of widespread, low frequency, age-associated somatic TP53 mutation in noncancerous tissue.
Integrated Optical Beam Steerers (2013)

Beam steering plays an important role in ultra-fast switching and scanning applications. This paper discusses the possibilities of the silicon photonics platform to fabricate integrated beam steerers using active phase tuning or wavelength tuning.
Corneal Scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study (1999)

The data also suggest better agreement between clinicians and readers when Vogt's striae and corneal nerves were observed. The data also suggest better agreement when corneal staining was not observed by the photograph readers. The CLEK Study protocol for determining the presence of scars is highly repeatable.
Evaluation of N2-fixing cover legumes as green manures for N substitution in coconut (Cocos nucifera Linn.) palm. (2001)

A field experiment was conducted in an adult coconut (Cocos nucifera Linn.) plantation in an acidic laterite soil type to test the feasibility of partially substituting fertilizer-N with the N contributed by cover legume-Rhizobium system when grown as green manures in a coconut basin. The treatments included in situ cultivation and incorporation of two leguminous creepers, Mimosa invisa and Calopogonium mucunoides in a 1.8-m radius of basin area surrounding the palm, with inorganic N doses of 250 g and 375 g and a control (devoid of legume) with 500 g N palm-1 supplied as urea. Mimosa invisa and C. mucunoides produced 20.5 kg and 12.8 kg of above-ground wet biomass and 134.8 g N and 70.0 g N basin-1 respectively, when harvested after 140 days growth for incorporation. Higher N2-fixation efficiency was shown by M. invisa as evidenced by nodule biomass and acetylene reduction activity of the nodulated root system. Analysis of the coconut basin soils revealed a trend towards higher N in legumes + 375 g N treatment and K in Calopogonium treatments, and microbial biomass and dehydrogenase enzyme activity in integrated treatment of legume biomass and fertilizer-N when compared to that of the control. The yield data of coconut palms collected over a period of four years indicated the possibility of substituting 50% fertilizer-N with the N contributed by the leguminous crops.
Copper and gene regulation in yeast. (1993)

The essential trace element copper is also highly toxic when accumulated at high intracellular levels. Copper detoxification in the yeasts S.cerevisiae and C.glabrata is carried out, in large part, by small, cysteine-rich metal binding proteins known as metallothioneins (MTs). The biosynthesis of yeast metallothioneins, the S.cerevisiae copper, zinc superoxide dismutase, and presumably other important copper homeostatic proteins, is transcriptionally induced by elevated environmental copper concentrations through the action of copper metalloregulatory transcription factors (MRTFs). Copper coordination drives the formation of a structure distinct from the apo-protein, whereupon the DNA binding function of MRTFs is activated. The copper MRTFs, ACE1 from S.cerevisiae and AMT1 from C.glabrata, directly interact with specific copper-responsive cis-acting elements in the promotor regions of their respective target genes. The binding of copper, as a polynuclear cluster, to MRTFs provides a sensitive and rapid means of transducing the extracellular metal signal to activate gene transcription.
Physical properties of thin-film field emission cathodes with molybdenum cones (1976)

Field emission cathodes fabricated using thin-film techniques and electron beam microlithography are described, together with effects obtained by varying the fabrication parameters. The emission originates from the tip of molybdenum cones that are about 1.5 μm tall with a tip radius around 500 Å. Such cathodes have been produced in closely packed arrays containing 100 and 5000 cones as well as singly. Maximum currents in the range 50–150 μA per cone can be drawn with applied voltages in the range 100–300 V when operated in conventional ion-pumped vacua at pressures of 10−9 Torr or less. In the arrays, current densities (averaged over the array) of above 10 A/cm2 have been demonstrated. Life tests with the 100-cone arrays drawing 2 mA total emission (or 3 A/cm2) have proceeded in excess of 7000 h with about a 10% drop in emission current. Studies are presented of the emission characteristics and current fluctuation phenomena. It is tentatively concluded that the emission arises from only one or a few atomic sites on the cone tips.
Prostaglandin metabolism in human hair follicle (2007)

Prostaglandins regulate a wide number of physiological functions. Recently PGF(2alpha) analogue such as latanoprost was shown to have a real impact on hair regrowth. The aim of this study was to investigate and describe the expression profile in human hair follicle of prostaglandin metabolism key enzymes, i.e. carbonyl reductase-1 (CBR1), microsomal prostaglandin E synthase-1 (mPGES-1) and microsomal prostaglandin E synthase-2 (mPGES-2), cytosolic prostaglandin E synthase (cPGES), the aldoketoreductase AKR1C1 and the prostaglandin F synthase AKR1C3. Quantitative RT-PCR on plucked hair follicles revealed some sex-related differences, mPGES-2 and AKR1C3 expression levels being higher in women. Cell and hair follicle compartment specificity was investigated using Western blot, PGE(2) and PGF(2alpha) ELISA assays and immunohistochemistry. Most of the hair cell types were endowed with prostaglandin metabolism machinery and were thus able to produce PGE(2) and/or PGF(2alpha). The epithelial part of the hair bulb was identified by immunohistology and EIA assays as the main source of prostaglandin synthesis and interconversion. All these observations support the concept that prostaglandins might be involved in hair growth and differentiation control.
Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) (1996)

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.