gebhart/patrepeval huggingface dataset:
233. Gene Control as a Therapeutic Intervention: Zinc-Finger Protein Transcription Factors as Regulators of the Molecular Determinants of Neuropathic Pain (2004)

Neuropathic (or chronic) pain is a complex disorder resulting from injury to the nerve, spinal chord or brain. The American Pain Society estimates that nearly 50 million Americans are totally or partially disabled by pain, however, few effective yet well-tolerated treatments are available. Indeed, existing therapeutics cause a range of undesirable side effects primarily due to the difficulty in developing small-molecule drugs capable of specifically targeting the receptor/channel of choice. Treatment of chronic pain is a therefore a promising target for gene therapy strategies.
Investigation of Sternal Photoplethysmography – Design of a Vital Sign Patch (2016)

It is important to obtain reliable measures of vital sign parameters, e.g. heart rate, respiratory rate (RR), and the oxygen saturation of the blood (SpO2). In current clinical practice the RR is assessed by manual count of the chest movements and pulse oximetry probes have been limited to the fingertip or the earlobe. These methods are documented to be time consuming or inaccurate when monitoring patients with low blood flow or decreased perfusion at the extremities (e.g. patients with obstructive lung diseases, diabetes, or heart failure). Furthermore, they are obtrusive for long-term recordings. The main focus of this project is to investigate the clinical applicability of photoplethysmography (PPG) measured at the chest bone (sternum). PPG is an optical method from which the RR and the SpO2 level can be obtained. For this purpose we have developed a prototype of a wearable PPG sensor and conducted three clinical studies both on healthy participants and on patients with obstructive lung diseases. The first clinical study was a controlled desaturation study. All 14 subjects were exposed to hypoxia by breathing an air mixture of reduced oxygen concentration in a closed system. We obtained an average root mean squared error (Arms) of 1.75 % compared to invasive measures of the oxygen saturation in the radial artery (SaO2) which is within the clinically and commercially accepted range. Furthermore, this study served as a calibration of the PPG sensor in a clinical relevant range (100 % - 70 %). In the second study, sternal PPG recording was conducted from 30 admitted patients with either asthma or Chronic Obstructive Pulmonary Disease (COPD). We compared the SpO2 levels simultaneously obtained from the sternal PPG recording and a conventional finger pulse oximeter. The Pearson correlation between the SpO2 levels estimated from the two body locations was found to be 0.89 (p < 0:05) and the mean system bias was only 0.052 % with upper and lower limits of agreement of 2.5 % and -2.4 %, respectively. The RR was also obtained from sternal PPG and compared to conventional capnography. In a range of 11 to 36 breaths/min the Pearson correlation was 0.93 (p < 0:001) and the system mean bias was 0.6 breaths/min. The upper and lower limits of agreement was found to be -2.8 to 4 breaths/min. In the last clinical study, the focus was to investigate the clinical reliability of long-term PPG recordings from the sternum. Fifteen admitted patients were included in the study and were monitored with the sternal PPG sensor for approximately 20 hours. On average it was found that clinically reliable SpO2 and RR estimates could be calculated for 58 % of the recording time. Furthermore, the average longest period of time with unreliable data in terms of the SpO2 level and the RR was only 23.6 minutes and 20 minutes, respectively. The results of this project show that it is possible to obtain reliable quasi-continuous recording of the SpO2 level and the RR from sternal PPG in many different clinical applications in the future.
Ergotamine and Dihydroergotamine: History, Pharmacology, and Efficacy (2003)

Ergotamine and dihydroergotamine share structural similarities with the adrenergic, dopaminergic, and serotonergic neurotransmitters. As a result, they have wide-ranging effects on the physiologic processes that they mediate. Ergotamine and dihydroergotamine are highly potent at the 5-HT1B and 5-HT1D antimigraine receptors and, as a consequence, the plasma concentrations that are necessary to produce the appropriate therapeutic and physiologic effects are very low. The broad spectrum of activity at other monoamine receptors is responsible for their side effect profile (dysphoria, nausea, emesis, unnecessary vascular effects). Both ergotamine and dihydroergotamine have sustained vasoconstrictor actions. In acute migraine treatment, their mechanisms of action involve constricting the pain-producing intracranial extracerebral blood vessels at the 5-HT1B receptors and inhibiting the trigeminal neurotransmission at the peripheral and central 5-HT1D receptors. The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine. Their wide use is based on long-term experience.
Identification of a novel gene expressed in activated natural killer cells and T cells (1992)

We have isolated a cDNA clone from a human activated NK cell-derived cDNA library that identifies a transcript (NK4) that is selectively expressed in lymphocytes. The expression of this transcript is increased after activation of T cells by mitogens or activation of NK cells by IL-2 (lymphokine-activated killer cells). The transcript levels demonstrated by Northern blot analysis increase by 12 h after activation, remain high for at least 48 h, and require protein synthesis for expression. Southern blot analysis of B lymphoblastoid lines derived from 18 unrelated individuals reveal variable banding patterns suggestive of polymorphism within the NK4 gene. No homology was found between the sequence of the coding region of this transcript and any sequences in the GenBank data base. Sequence homology to the U1 small nuclear RNA was found within the 3' untranslated region immediately upstream of the site of polyadenylation, suggesting a possible role for U1 in the polyadenylation process. Sequence analysis indicates the transcript would encode a protein having a mass of 27 kDa. The presence of a signal sequence and lack of a transmembrane region suggests that the protein is secreted. In addition, the protein contains an RGD sequence that may be involved in cellular adhesion. This transcript appears to encode a novel product common to the activation pathways of both NK cells and T cells.
Expression of calcyclin in human melanocytic lesions. (1993)

When comparing two subsequent stages of melanocytic tumor progression we identified calcyclin as a new potential progression marker, the expression of which was correlated with metastatic behavior of various human melanoma cell lines in nude mice. In this study, we describe a good correlation between RNA and protein levels in the xenografts of these cell lines and extended these experiments to a panel of 120 routinely processed human melanocytic cutaneous lesions. Northern blot analysis demonstrated that calcyclin RNA expression was elevated in melanoma metastases as compared to several types of nevocellular nevi. Calcyclin staining using a specific polyclonal antiserum showed a more complex pattern. A stronger staining in a higher percentage of positive cells was observed in thick primary melanoma (> or = 1.5 mm) as compared to thin primary melanoma (< 1.5 mm). Calcyclin expression was also present in a higher percentage of cells showing a stronger staining in melanomas with higher Clark levels (> II) corresponding to the vertical growth phase of primary melanomas. Protein expression in nevocellular nevi was confined to the dermal part and was highest in the lower parts of the dermis. Remarkably, dysplastic nevi (atypical moles), potential precursors of melanoma, did not show any expression at all, either in junctional or dermal parts. Confinement of the expression to the dermal part of nondysplastic nevi and primary melanomas may reflect interactions with the microenvironment of the reticular dermis that occurs with vertical growth.
Influence of decorin on fibroblast adhesion to fibronectin. (1991)

Decorin is a ubiquitous small dermatan sulfate proteoglycan carrying a single glycosaminoglycan chain. It is known for its ability to bind, via its core protein, to interstitial collagens. Decorin was purified from the secretions of cultured human skin fibroblasts under non-denaturing conditions. The intact proteoglycan and its glycosaminoglycan-free core protein were tested for their interference with fibroblast adhesion to a fibronectin substrate. Concentrations of 40 nmoles or more of hexuronic acid/ml of decorin or equivalent amounts of core protein inhibited cell adhesion. Inhibition was caused by an interaction of core protein with fibronectin and not by masking of the fibronectin receptor. When cell-binding fragments of fibronectin were used as substrates, a similar inhibition of cell adhesion by decorin core protein was found, and in vitro assays demonstrated an interaction of core protein with the cell-binding domain of fibronectin. Decorin core protein also inhibited the low degree of cell adhesion to heparin-binding fragments on the N-terminus and near the C-terminus of the fibronectin molecules.
Effects of trimethoprim and rifampin on the pharmacokinetics of the cytochrome P450 2C8 substrate rosiglitazone (2004)

Trimethoprim raises and rifampin reduces the plasma concentrations of rosiglitazone by inhibiting and inducing, respectively, the CYP2C8-catalyzed biotransformation of rosiglitazone.
Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation (2003)

The innate immune system is the most ancestral and ubiquitous system of defence against microbial infection. The microbial sensing proteins involved in innate immunity recognize conserved and often structural components of microorganisms. One class of these pattern-recognition molecules, the Toll-like receptors (TLRs), are involved in detection of microbes in the extracellular compartment whereas a newly discovered family of proteins, the NBS-LRR proteins (for nucleotide-binding site and leucine-rich repeat), are involved in intracellular recognition of microbes and their products. NBS-LRR proteins are characterized by three structural domains: a C-terminal leucine-rich repeat (LRR) domain able to sense a microbial motif, an intermediary nucleotide binding site (NBS) essential for the oligomerization of the molecule that is necessary for the signal transduction induced by different N-terminal effector motifs, such as a pyrin domain (PYD), a caspase-activating and recruitment domain (CARD) or a baculovirus inhibitor of apoptosis protein repeat (BIR) domain. Two of these family members, Nod1 and Nod2, play a role in the regulation of pro-inflammatory pathways through NF-kappaB induced by bacterial ligands. Recently, it was shown that Nod2 recognizes a specific peptidoglycan motif from bacteria, muramyl dipeptide (MDP). A surprising number of human genetic disorders have been linked to NBS-LRR proteins. For example, mutations in Nod2, which render the molecule insensitive to MDP and unable to induce NF-kappaB activation when stimulated, are associated with susceptibility to a chronic intestinal inflammatory disorder, Crohn's disease. Conversely, mutations in the NBS region of Nod2 induce a constitutive activation of NF-kappaB and are responsible for Blau syndrome, another auto-inflammatory disease. Nalp3, which is an NBS-LRR protein with an N-terminal Pyrin domain, is also implicated in rare auto-inflammatory disorders. In conclusion, NBS-LRR molecules appear as a new family of intracellular receptors of innate immunity able to detect specific bacterial compounds and induce inflammatory response; the dysregulation of these processes due to mutations in the genes encoding these proteins is involved in numerous auto-inflammatory disorders.
Rejection of cardiac allografts by T cells expressing a restricted repertoire of T‐cell receptor Vβ genes (1997)

We have recently shown that T cells infiltrating cardiac allografts early in graft rejection use a limited T-cell receptor (TCR) V beta repertoire. In this study we tested whether this limited repertoire of V beta genes is important for graft rejection. A cell line, AL2-L3, was established from LEW lymphocytes infiltrating ACI heart allografts 2 days after transplantation. This cell line is composed of CD4+ T cells that primarily recognize the class II RTI.B major histocompatibility complex (MHC) molecule expressed by the donor graft. This cell line precipitated acute rejection of donor hearts with a median survival time (MST) of 10.5 days following adoptive transfer to sublethally irradiated LEW recipients. This rate of graft rejection was significantly (P < 0.0007) accelerated when compared with a MST of 60 days for allografts in irradiated control recipients. The AL2-L3-mediated acceleration of graft rejection was donor specific as WF third-party heart allografts were rejected with a delayed tempo (MST = 28.5 days). The V beta repertoire of this cell line was primarily restricted to the expression of V beta 4, 15 and 19 genes. The nucleotide sequence analysis of the beta-chain cDNAs from this cell line demonstrated that the restricted use of the V gene repertoire was not shared with the N, D and J regions. A wide variety of CDR3 loops and J beta genes were used in association with selected V beta genes. These data provide evidence for the role a restricted repertoire of V beta genes plays in cardiac allograft rejection in this model. The restricted usage of the V beta repertoire in an early T-cell response to allografts may provide the opportunity to therapeutically disrupt the rejection reaction by targeting selected T-cell populations for elimination at the time of organ transplantation.
Recipe For Building Robust Spoken Dialog State Trackers: Dialog State Tracking Challenge System Description (2013)

For robust spoken conversational interaction, many dialog state tracking algorithms have been developed. Few studies, however, have reported the strengths and weaknesses of each method. The Dialog State Tracking Challenge (DSTC) is designed to address this issue by comparing various methods on the same domain. In this paper, we present a set of techniques that build a robust dialog state tracker with high performance: wide-coverage and well-calibrated data selection, feature-rich discriminative model design, generalization improvement techniques and unsupervised prior adaptation. The DSTC results show that the proposed method is superior to other systems on average on both the development and test datasets. 1
Chemical procedure for preparing surface-enhanced Raman scattering active silver films (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical procedure for preparing surface-enhanced Raman scattering active silver filmsFan. Ni and Therese M. CottonCite this: Anal. Chem. 1986, 58, 14, 3159–3163Publication Date (Print):December 1, 1986Publication History Published online1 May 2002Published inissue 1 December 1986https://pubs.acs.org/doi/10.1021/ac00127a053https://doi.org/10.1021/ac00127a053research-articleACS PublicationsRequest reuse permissionsArticle Views853Altmetric-Citations113LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Extracting contract elements (2017)

We study how contract element extraction can be automated. We provide a labeled dataset with gold contract element annotations, along with an unlabeled dataset of contracts that can be used to pre-train word embeddings. Both datasets are provided in an encoded form to bypass privacy issues. We describe and experimentally compare several contract element extraction methods that use manually written rules and linear classifiers (logistic regression, SVMs) with hand-crafted features, word embeddings, and part-of-speech tag embeddings. The best results are obtained by a hybrid method that combines machine learning (with hand-crafted features and embeddings) and manually written post-processing rules.
Faceting of a growing crystal surface by surface diffusion (2003)

Consider faceting of a crystal surface caused by strongly anisotropic surface tension, driven by surface diffusion and accompanied by deposition (etching) due to fluxes normal to the surface. Nonlinear evolution equations describing the faceting of 1+1 and 2+1 crystal surfaces are studied analytically, by means of matched asymptotic expansions for small growth rates, and numerically otherwise. Stationary shapes and dynamics of faceted pyramidal structures are found as functions of the growth rate. In the 1+1 case it is shown that a solitary hill as well as periodic hill-and-valley solutions are unique, while solutions in the form of a solitary valley form a one-parameter family. It is found that with the increase of the growth rate, the faceting dynamics exhibits transitions from the power-law coarsening to the formation of pyramidal structures with a fixed average size and finally to spatiotemporally chaotic surfaces resembling the kinetic roughening.
Volume Learning Algorithm Artificial Neural Networks for 3D QSAR Studies (2001)

The current study introduces a new method, the volume learning algorithm (VLA), for the investigation of three-dimensional quantitative structure-activity relationships (QSAR) of chemical compounds. This method incorporates the advantages of comparative molecular field analysis (CoMFA) and artificial neural network approaches. VLA is a combination of supervised and unsupervised neural networks applied to solve the same problem. The supervised algorithm is a feed-forward neural network trained with a back-propagation algorithm while the unsupervised network is a self-organizing map of Kohonen. The use of both of these algorithms makes it possible to cluster the input CoMFA field variables and to use only a small number of the most relevant parameters to correlate spatial properties of the molecules with their activity. The statistical coefficients calculated by the proposed algorithm for cannabimimetic aminoalkyl indoles were comparable to, or improved, in comparison to the original study using the partial least squares algorithm. The results of the algorithm can be visualized and easily interpreted. Thus, VLA is a new convenient tool for three-dimensional QSAR studies.
Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules (2006)

Palmitate, a 16-carbon saturated fatty acid, is attached to more than 100 proteins. Modification of proteins by palmitate has pleiotropic effects on protein function. Palmitoylation can influence membrane binding and membrane targeting of the modified proteins. In particular, many palmitoylated proteins concentrate in lipid rafts, and enrichment in rafts is required for efficient signal transduction. This Review focuses on the multiple effects of palmitoylation on the localization and function of ligands, receptors, and intracellular signaling proteins. Palmitoylation regulates the trafficking and function of transmembrane proteins such as ion channels, neurotransmitter receptors, heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors, and integrins. In addition, immune receptor signaling relies on protein palmitoylation at many levels, including palmitoylated co-receptors, Src family kinases, and adaptor or scaffolding proteins. The localization and signaling capacities of Ras and G proteins are modulated by dynamic protein palmitoylation. Cycles of palmitoylation and depalmitoylation allow H-Ras and G protein alpha subunits to reversibly bind to and signal from different intracellular cell membranes. Moreover, secreted ligands such as Hedgehog, Wingless, and Spitz use palmitoylation to regulate the extent of long- or short-range signaling. Finally, palmitoylation can alter signaling protein function by direct effects on enzymatic activity and substrate specificity. The identification of the palmitoyl acyltransferases has provided new insights into the biochemistry of this posttranslational process and permitted new substrates to be identified.
The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy (2012)

CYP3A ranks among the most abundant cytochrome P450 enzymes in the liver, playing a dominant role in metabolic elimination of clinically used drugs. A main member in CYP3A family, CYP3A4 expression and activity vary considerably among individuals, attributable to genetic and non-genetic factors, affecting drug dosage and efficacy. However, the extent of genetic influence has remained unclear. This review assesses current knowledge on the genetic factors influencing CYP3A4 activity. Coding region CYP3A4 polymorphisms are rare and account for only a small portion of inter-person variability in CYP3A metabolism. Except for the promoter allele CYP3A4*1B with ambiguous effect on expression, common CYP3A4 regulatory polymorphisms were thought to be lacking. Recent studies have identified a relatively common regulatory polymorphism, designated CYP3A4*22 with robust effects on hepatic CYP3A4 expression. Combining CYP3A4*22 with CYP3A5 alleles *1, *3 and *7 has promise as a biomarker predicting overall CYP3A activity. Also contributing to variable expression, the role of polymorphisms in transcription factors and microRNAs is discussed.
Determining optimal sleep position in patients with positional sleep‐disordered breathing using response surface analysis (2009)

A lateral position (LP) during sleep is effective in reducing sleep disorder symptoms in mild or moderate sleep apnea patients. However, the effect of head and shoulder posture in LP on reducing sleep disorders has not been reported. In this study, effective sleeping positions and a combination of sleep position determinants were evaluated with respect to their ability to reduce snoring and apnea. The positions evaluated included the following: cervical vertebrae support with head tilting (CVS-HT), scapula support (SS), and LP. A central composite design was applied for response surface analysis (RSA). Sixteen patients with mild or moderate positional sleep apnea and snoring who underwent polysomnography for two nights were evaluated. Based on an estimated RSA equation, LP (with a rotation of at least 30 degrees) had the most dominant effect [P = 0.0057 for snoring rate, P = 0.0319 for apnea-hypopnea index (AHI)]. In addition, the LP was found to interact with CVS-HT (P = 0.0423) for snoring rate and CVS-HT (P = 0.0310) and SS (P = 0.0265) for AHI. The optimal sleep position reduced mild snoring by more than 80% (i.e. snoring rate in the supine position was <20%) and the snoring rate was approximately zero with a 40 degrees rotation. To achieve at least 80% reduction of AHI, LP and SS should be >30 degrees and/or 20 mm respectively. To determine an effective sleep position, CVS-HT and SS, as well as the degree of the LP, should be concurrently considered in patients with positional sleep apnea or snoring.