gebhart/patrepeval huggingface dataset:
Analysis of SNPs with an effect on gene expression identifies UBE2L3 and BCL3 as potential new risk genes for Crohn's disease (2010)

Genome-wide association studies (GWAS) for Crohn's disease (CD) have identified loci explaining approximately 20% of the total genetic risk of CD. Part of the other genetic risk loci is probably partly hidden among signals discarded by the multiple testing correction needed in the analysis of GWAS data. Strategies for finding these hidden loci require large replication cohorts and are costly to perform. We adopted a strategy of selecting SNPs for follow-up that showed a correlation to gene expression [cis-expression quantitative trait loci (eQTLs)] since these have been shown more likely to be trait-associated. First we show that there is an overrepresentation of cis-eQTLs in the known CD-associated loci. Then SNPs were selected for follow-up by screening the top 500 SNP hits from a CD GWAS data set. We identified 10 cis-eQTL SNPs. These 10 SNPs were tested for association with CD in two independent cohorts of Dutch CD patients (1539) and healthy controls (2648). In a combined analysis, we identified two cis-eQTL SNPs that were associated with CD rs2298428 in UBE2L3 (P=5.22x10(-5)) and rs2927488 in BCL3 (P=2.94x10(-4)). After adding additional publicly available data from a previously reported meta-analysis, the association with rs2298428 almost reached genome-wide significance (P=2.40x10(-7)) and the association with rs2927488 was corroborated (P=6.46x10(-4)). We have identified UBE2L3 and BCL3 as likely novel risk genes for CD. UBE2L3 is also associated with other immune-mediated diseases. These results show that eQTL-based pre-selection for follow-up is a useful approach for identifying risk loci from a moderately sized GWAS.
Getting a handhold on DNA: Design of poly-zinc finger proteins with femtomolar dissociation constants (1998)

Structure-based design was used to link zinc finger peptides and make poly-finger proteins that have dramatically enhanced affinity and specificity. Our studies focused on a fusion in which the three-finger Zif268 peptide was linked to a designed three-finger peptide (designated "NRE") that specifically recognizes a nuclear hormone response element. Gel shift assays indicate that this six-finger peptide, 268//NRE, binds to a composite 18-bp DNA site with a dissociation constant in the femtomolar range. We find that the slightly longer linkers used in this fusion protein provide a dramatic improvement in DNA-binding affinity, working much better than the canonical "TGEKP" linkers that have been used in previous studies. Tissue culture transfection experiments also show that the 268//NRE peptide is an extremely effective repressor, giving 72-fold repression when targeted to a binding site close to the transcription start site. Using this strategy, and linking peptides selected via phage display, should allow the design of novel DNA-binding proteins-with extraordinary affinity and specificity-for use in biological research and gene therapy.
Resistance of Gram-negative Bacteria to Purified Bactericidal Leukocyte Proteins (1980)

A B
Identification of HER2/neu‐derived peptide epitopes recognized by gastric cancer‐specific cytotoxic T lymphocytes (1998)

We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor-associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1+, HER2/neu+ gastric cancer cells, HER2/neu-transfected C1R/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1+, HER2+). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected C1R/A2 cells. Our results demonstrate that the HER2/neu-encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9106), HER2(9369), HER2(9689)], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2+ C1R/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer. Int. J. Cancer 78:202–208, 1998. © 1998 Wiley-Liss, Inc.
Transoesophageal echocardiography (2005)

ver the last decade, transoesophageal echocardiography (TOE) has evolved as an essential ultrasonographic technique for rapid bedside tomographic evaluation of the cardiovascular system. Imaging from the confines of the gastro-oesophageal track reduces signal attenuation and permits the use of higher ultrasound frequencies, thereby providing an enhanced spatial resolution. Although interpretation of the structural and haemodynamic information from TOE needs training, the technique can be readily integrated in day to day clinical algorithms, particularly those that demand quick medical decision making. TOE has a wide applicability and its role currently expands beyond the realm of clinical cardiology. An increasing number of anaesthetists, surgeons, and intensivists now use it routinely for monitoring and guiding operative procedures, interventions, and managing critically ill patients. This article provides a brief overview of the indications, imaging techniques, pitfalls, and the emerging trends in the application of TOE.
Gut mucosal immunization with reovirus serotype 1/L stimulates virus-specific cytotoxic T cell precursors as well as IgA memory cells in Peyer's patches. (1987)

In this report we have shown that reovirus 1/L is an effective mucosal immunogen capable of generating a cytotoxic T cell (CTL) and associated helper T cell response to the nominal antigens associated with reovirus 1/L. The effectors that mediate reovirus-specific cytotoxicity are Thy-1+, Lyt-2+, and major histocompatibility complex (MHC)-restricted in their recognition of reovirus antigens, and can therefore be classified as CTLs. Frequency analysis of precursor CTLs occurring in Peyer's patches (PP) and peripheral lymph nodes (PLN) 6 d and 6 mo after intraduodenal stimulation have demonstrated that a persistent gradient of precursors is established, with higher frequencies present in PP. The generation of a CTL response in PP may be important in preferentially repopulating mucosal tissues with effector CTLs that could result in the local containment of infections in the gut. We also found that reovirus 1/L generates a virus-specific B cell response that is dominated by IgA memory cells after intraduodenal immunization. We hypothesize that the efficacy of reovirus 1/L at stimulating T and B cells in the gut mucosa is related to its ability to selectively enter PP via microfold (M) cells after enteric application. In this study we have also demonstrated that PP cells, upon in vitro culture and unrelated to prior reovirus priming, can generate natural killer-like (NK) cytotoxic activity. This may be an in vitro correlate of the in vivo generation of effectors that may populate mucosal tissues (i.e., the intestinal epithelium) with NK-like effector cells.
DNA Triangles and Self-Assembled Hexagonal Tilings (2004)

We have designed and constructed DNA complexes in the form of triangles. We have created hexagonal planar tilings from these triangles via self-assembly. Unlike previously reported structures self-assembled from DNA, our structures appear to involve bending of double helices. Bending helices may be a useful design option in the creation of self-assembled DNA structures. It has been suggested that DNA self-assembly may lead to novel materials and efficient computational devices.
Enzymes in Nonaqueous Solvents (2001)

Enzymatic catalysis has gained considerable attention in recent years as an efficient tool in the preparation of natural products, pharmaceuticals, fine chemicals, and food ingredients. The high selec
Design and Fabrication of 3D Porous Scaffolds to Facilitate Cell-Based Gene Therapy (2008)

Biomaterials capable of efficient gene delivery by embedded cells provide a fundamental tool for the treatment of acquired or hereditary diseases. A major obstacle is maintaining adequate nutrient and oxygen diffusion to cells within the biomaterial. In this study, we combined the solid free-form fabrication and porogen leaching techniques to fabricate three-dimensional scaffolds, with bimodal pore size distribution, for cell-based gene delivery. The objective of this study was to design micro-/macroporous scaffolds to improve cell viability and drug delivery. Murine bone marrow-derived mesenchymal stromal cells (MSCs) genetically engineered to secrete erythropoietin (EPO) were seeded onto poly-L-lactide (PLLA) scaffolds with different microporosities. Over a period of 2 weeks in culture, an increase in cell proliferation and metabolic activity was observed with increasing scaffold microporosity. The concentration of EPO detected in supernatants also increased with increasing microporosity level. Our study shows that these constructs can promote cell viability and release of therapeutic proteins, and clearly demonstrates their capacity for a dual role as scaffolds for tissue regeneration and as delivery systems for soluble gene products.
Universal Approximation Using Radial-Basis-Function Networks (1991)

There have been several recent studies concerning feedforward networks and the problem of approximating arbitrary functionals of a finite number of real variables. Some of these studies deal with cases in which the hidden-layer nonlinearity is not a sigmoid. This was motivated by successful applications of feedforward networks with nonsigmoidal hidden-layer units. This paper reports on a related study of radial-basis-function (RBF) networks, and it is proved that RBF networks having one hidden layer are capable of universal approximation. Here the emphasis is on the case of typical RBF networks, and the results show that a certain class of RBF networks with the same smoothing factor in each kernel node is broad enough for universal approximation.
Cardiac arrhythmias in congenital heart diseases. (2009)

Arrhythmias figure prominently among the complications encountered in the varied and diverse population of patients with congenital heart disease, and are the leading cause of morbidity and mortality. The incidence generally increases as the patient ages, with multifactorial predisposing features that may include congenitally malformed or displaced conduction systems, altered hemodynamics, mechanical or hypoxic stress, and residual or postoperative sequelae. The safe and effective management of arrhythmias in congenital heart disease requires a thorough appreciation for conduction system variants, arrhythmia mechanisms, underlying anatomy, and associated physiology. We, therefore, begin this review by presenting the scope of the problem, outlining therapeutic options, and summarizing congenital heart disease-related conduction system anomalies associated with disorders of the sinus node and AV conduction system. Arrhythmias encountered in common forms of congenital heart disease are subsequently discussed. In so doing, we touch upon issues related to risk stratification for sudden death, implantable cardiac devices, catheter ablation, and adjuvant surgical therapy.
Relationship between the Growth of Carbon Nanofilaments and Metal Dusting Corrosion (2005)

Raman scattering, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were used to study the mechanism of the catalytic crystallization of carbon and metal dusting corrosion. A mechanism is proposed for both metal dusting and the growth of carbon fibers. Carbon cannot crystallize well by deposition from carburizing gases at low temperature without catalytic activation because of its strong C−C bonds and high melting temperature. To form good crystalline carbon, the carbon atoms must dissolve, diffuse through metal particles, and crystallize on an appropriate facet that can act as a template to help the epitaxial growth of carbon crystals. In this process, metal particles are liberated from the pure metal and alloys. This liberation leads to the metal dusting phenomenon. The catalytic growth of carbon filaments is due to the transportation of carbon from one facet of a metal or carbide particle that favors carbon deposition to another facet that favors carbon precipitation. The free energy of poor crystalline carbon is higher than that of good crystalline carbon. The decrease in free energy from highly disordered carbon to well-ordered carbon is the driving force for metal dusting and for growth of carbon filaments through metal particles.
A Neurohypophyseal Hormone Analog with Selective Oxytocin-Like Activities and Resistance to Enzymatic Inactivation: An Approach to the Design of Peptide Drugs (1974)

Stepwise, synthetic alteration of oxytocin, guided by conformational and enzymological considerations, has led to analogs with specifically modified activity profiles and resistance to enzymatic inactivation. General requirements for the design of peptides with therapeutic value are discussed.
GSH monoethyl ester rescues mitochondrial defects in cystic fibrosis models (2011)

Cystic fibrosis (CF), a multisystem disease caused by CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations, is associated with an abnormal inflammatory response and compromised redox homeostasis in the airways. Recent evidence suggests that dysfunctional CFTR leads to redox imbalance and to mitochondrial reduced glutathione (mtGSH) depletion in CF models. This study was designed to investigate the consequences of mtGSH depletion on mitochondrial function and inflammatory response. mtGSH depletion was confirmed in colonic epithelium of CFTR-null mice and in CFTR-mutated human epithelial cells. GSH uptake experiments performed on isolated mitochondria suggest that mtGSH depletion is not due to a defective GSH transport capacity by CF mitochondria, despite the decreased expression of two mtGSH carriers, oxoglutarate carrier and dicarboxylate carrier. CM-H(2)DCFDA [5 (and 6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester] fluorescence and aconitase activity showed an increase in reactive oxygen species levels in CFTR-defective cells and a pro-oxidative environment within CF mitochondria. The activities of respiratory chain complexes were further examined. Results showed a selective loss of Complex I (CI) function in CF models associated with an altered mitochondrial membrane potential (Δψ(m)). CI analysis showed normal expression but an overoxidation of its NADH-ubiquinone oxidoreductase Fe-S protein 1 subunit. GSH monoethyl ester (GSH-EE) significantly enhanced mtGSH levels in the IB3-1/C38 model and reversed CI inhibition, suggesting that mtGSH depletion is responsible for the loss of CI activity. Furthermore, GSH-EE attenuated Δψ(m) depolarization and restored normal IL-8 secretion by CFTR-defective cells. These studies provide evidence for a critical role of a mtGSH defect in mitochondrial dysfunction and abnormal IL-8 secretion in CF cells and reveal the therapeutic potential of mitochondria-targeted antioxidants in CF.
Diaminopimelic Acid and Lysine Auxotrophs of Pseudomonas aeruginosa 8602 (1971)

SUMMARY: Lysine auxotrophs have been isolated from Pseudomonas aeruginosa 8602. Three of the mutants were deficient in diaminopimelate decarboxylase and accumulated meso- and ll-diaminopimelic acid (DAP) but otherwise were indistinguishable from the parent strain. The fourth mutant required lysine for optimal growth, grew slowly on meso- but not ll-DAP, and the DAP which accumulated in large amounts was solely the ll-isomer. This mutant was deficient in diaminopimelate epimerase. No significant differences were detected between its wall composition and that of the parent strain but it was particularly sensitive to carbenicillin.
Neighboring group participation by sulfur involving four-membered-ring intermediates (RS-4) (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNeighboring group participation by sulfur involving four-membered-ring intermediates (RS-4)Ernest L. Eliel and David E. KnoxCite this: J. Am. Chem. Soc. 1985, 107, 10, 2946–2952Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/ja00296a019https://doi.org/10.1021/ja00296a019research-articleACS PublicationsRequest reuse permissionsArticle Views395Altmetric-Citations18LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Effect of ischaemia on sensory potentials of normal subjects of different ages (1973)

In 73 normal subjects, from 10 to 82 years of age, maximum orthodromic sensory nerve conduction velocity was measured in the median nerve before and during a 30 minute period of vascular occlusion. During ischaemia progressive slowing in conduction velocity, decrease in amplitude, and increase in duration of the sensory action potential evoked at wrist and elbow by supramaximal stimulation of digit III were observed. However, a statistically significant difference (P&lt;0·05 to P&lt;0·01) between subjects was noted by grouping them by age: the older the subject, the longer the persistence of sensory response and the less marked the slowing in conduction velocity. The mechanism of the phenomenon has been discussed in relation to a similar longer resistance to ischaemia found in peripheral nerves of diabetic and uraemic patients.
Recurrent haematuria: role of renal biopsy and investigative morbidity. (1976)

The usefulness of renal biopsy in investigating unexplained haematuria was assessed by a study of 33 adults referred consecutively with this syndrome. Unequivocal abnormalities were seen on light microscopy or immunofluorescence in 31 of the 33 specimens of renal tissue examined. In 18 patients deposits of IgA were present in the mesangium. Loin pain occurred in only two of the 18 patients with mesangial IgA deposits, compared with 11 of the 15 patients without these deposits. Seven of the nine women in this series had had loin pain compared with only six of the 24 men. Thus a woman with loin pain and haematuria was not likely to have mesangial IgA nephropathy but this was found in 14 of the 18 men with unexplained painless haematuria. Failure to appreciate the role of renal biopsy in the investigation of unexplained haematuria may result in unnecessary radiology, considerable morbidity, and even in unjustified nephrectomy.
Genetic segregation of airway disease traits despite redundancy of calcium-activated chloride channel family members (2006)

Complex airway diseases such as asthma and chronic obstructive pulmonary disease exhibit stereotyped traits (especially airway hyperreactivity and mucous cell metaplasia) that are variably expressed in each patient. Here, we used a mouse model for virus-induced long-term expression of these traits to determine whether individual traits can be genetically segregated and thereby linked to separate determinants. We showed that an F2 intercross population derived from susceptible and nonsusceptible mouse strains can manifest individual phenotypic extremes that exhibit one or the other disease trait. Functional genomic analysis of these extremes further indicated that a member of the calcium-activated chloride channel (CLCA) gene family designated mClca3 was inducible with mucous cell metaplasia but not airway hyperreactivity. In confirmation of this finding, we found that mClca3 gene transfer to mouse airway epithelium was sufficient to induce mucous cell metaplasia but not airway hyperreactivity. However, newly developed mClca3(-/-) mice exhibited the same degree of mucous cell metaplasia and airway hyperreactivity as wild-type mice. Bioinformatic analysis of the Clca locus led to the identification of mClca5, and gene transfer indicated that mClca5 also selectively drives mucous cell metaplasia. Thus, in addition to the capacity of CLCA family members to exhibit diverse functional activities, there is also preserved function so that more than one family member mediates mucous cell metaplasia. Nonetheless, Clca expression appears to be a selective determinant of mucous cell metaplasia so that shared homologies between CLCA family members may still represent a useful target for focused therapeutic intervention in hypersecretory airway disease.
Neural network for human cognitive state estimation (2002)

A neural network (NN) has been applied to the human cognitive state estimation based on the set of physiological measures, heart rate, blood pressure, respiration rate, skin potential response (SPR), blink rate and saccadic eye motion rate have been chosen as the representative metrical indices reflecting human mental state. The qualitative tendencies of these measures have been taken as the inputs of the NN. The human cognitive states are categorized into six pre-specified states: (1) information acquisition (IA); (2) memory related (MR); (3) thought (TH); (4) motor action (MA); (5) emotion (EM); and (6) others (OT). The adopted network a is three layer feedforward network trained with a backpropagation algorithm with forgetting. Sets of training data for learning have been collected through laboratory experiments, in which the subjects were induced to undergo a specific sequence of cognitive states. The resultant NN showed superior capability of discriminating human cognitive states based on the pattern of the physiological measures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>