gebhart/patrepeval huggingface dataset:
“Mowat-Wilson” syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene (2002)

Recently mutations in the gene ZFHX1B (SIP1) were shown in patients with “syndromic Hirschsprung disease” with mental retardation (MR) and multiple congenital anomalies (MCA), but it was unclear if Hirschsprung disease is an obligate symptom of these mutations and if the distinct facial phenotype delineated by Mowat et al. [1998: J Med Genet 35: 617–623] is specific for ZFHX1B mutations. In order to address these open questions we analyzed the ZFHX1B gene in five patients, three of whom had “syndromic Hirschsprung disease” two with and one without the facial phenotype described by Mowat et al. [1998], and two of whom had the distinct facial gestalt without Hirschsprung disease. Analyses of microsatellite markers and newly identified SNPs, and/or FISH with BACs from the ZFHX1B region excluded large deletions in all five patients. Direct sequencing demonstrated truncating ZFHX1B mutations in all four patients with the characteristic facial phenotype, but not in the patient with syndromic Hirschsprung disease without the distinct facial appearance. We demonstrate that there is a specific clinical entity with a recognizable facial gestalt, mental retardation and variable MCAs which we propose be called the “Mowat-Wilson syndrome.” © 2002 Wiley-Liss, Inc.
PHOTOSENSITIZATION BY DIPORPHYRINS JOINED VIA METHYLENE BRIDGES (1988)

Abstract— Photodynamic and biophysical properties of three porphyrin dimers joined by methylene bridges were examined. Fluorescence emission spectra and fluorescence lifetimes of the methylene‐linked dimers were similar to values obtained with porphyrin monomers. Singlet oxygen quantum yields were not significantly different when the three diporphyrins were compared. The diporphyrins were short‐acting tumor photosensitizers in vivo, and were rapidly cleared from plasma. Of the 3 diporphyrins examined, one was essentially ineffective as a sensitizer in vivo. This could not have been predicted from in vitro studies which indicated photodamage to membrane and mitochondrial loci. The methyiene‐linked diporphyrins were hydrophilic dyes (water/octanol distribution ratio =120–200) and bound mainly to plasma high‐density lipoprotein. In contrast, the more hydrophobic diporphyrin ester/ether fraction from HPD was a long‐persisting photosensitizer in vivo. Compared with hematoporphyrin, this hematoporphyrin derivative (HPD) fraction demonstrated a red‐shift in fluorescence emission and a shortened fluorescence lifetime. These comparisons suggest that ring‐ring interactions occur in the ester/ether‐linked diporphyrins from HPD, but not in the methyiene‐linked diporphyrins.
Demonstration of enhanced surface mobility of adsorbate cluster species by surface acoustic wave excitation induced by a pulsed laser (2014)

Fluorescence microscopy is used to explore the efficacy of surface acoustic waves (SAWs), as generated by a pulsed laser “tapping” a surface, to enhance the surface mobility of molecular adsorbates. The candidate adsorbate system under investigation comprises a series of gold clusters that are directly prepared on a silicon (111) surface by laser ablation of nanoparticles. Within the debris field the gold cluster Au8 is tracked because the fluorescence spectrum is known. The gold cluster is distinguished by using band-pass filters and tracked by fluorescence. The SAW source is a pulsed UV (355nm) laser operating at a repetition rate of 100Hz, where the laser fluence is set below the damage threshold of silicon. The experiment measures the location of the emitted light for a particular cluster through a high magnification (100X) imaging microscope that is integrated with a water-cooled (512x512 pixel) EMCCD camera. Image processing algorithms are used to track the light emission. Initial results show that the cluster Au8 moves approximately 0.5 Angstroms/s (when the excitation source is approximately 0.65 cm away). Diffusion and displacement data of adsorbed atoms and molecules on surfaces is sparse, though this value is similar for displacements of gold clusters on polymer films at 440 K, some metal-on-metal adatoms at room temperatures, and other nonmetal-metal interactions. The experiment also includes a laser heterodyne probe which measures the frequency distribution of the surface displacement induced by the pulsed SAWs. Results show that even at a source-to-probe distance of 1.8cm, frequency components up to 120MHz are present. These results suggest that “growing”/synthesizing thin films via surface aggregation of cluster compounds may be feasible.
Cdc7 Inhibition Reveals a p53-Dependent Replication Checkpoint That Is Defective in Cancer Cells (2004)

Cdc7 is an evolutionarily conserved kinase that regulates S phase by promoting replication origin activation. Down-regulation of Cdc7 by small interfering RNA in a variety of tumor cell lines causes an abortive S phase, leading to cell death by either p53-independent apoptosis or aberrant mitosis. Unlike replication fork blockade, Cdc7-depleted tumor cells do not elicit a robust checkpoint response; thus, inhibitory signals preventing additional cell cycle progression are not generated. In normal fibroblasts, however, a p53-dependent pathway actively prevents progression through a lethal S phase in the absence of sufficient Cdc7 kinase. We show that in this experimental system, p53 is required for the lasting maintenance of this checkpoint and for cell viability. With this work we reveal and begin to characterize a novel mechanism that regulates DNA synthesis in human cells, and we suggest that inhibition of Cdc7 kinase represents a promising approach for the development of a new generation of anticancer agents.
Mechanism of the stimulatory action of okadaic acid on lipolysis in rat fat cells (2000)

Okadaic acid was found to induce concentration- and time-dependent lipolysis in rat fat cells in the absence of lipolytic hormones, but it did not significantly increase the total hormone-sensitive lipase (HSL) activity in these fat cells, the activity of HSL extracted from fat layer and that of HSL in the supernatant of homogenized fat cells. Western blotting of fat cell homogenate fractions with an antiserum raised against synthetic peptide derived from rat HSL showed that HSL protein shifted from the supernatant to the fat layer in response to okadaic acid, which increased the HSL protein content on the fat layer and concomitantly reduced that of the supernatant, concentration- and time-dependently. Sonication of the fat cells abolished their responsiveness to okadaic acid. The lipolytic action of okadaic acid was examined and its site was identified using a cell-free system comprising lipid droplets isolated from rat fat cells and HSL. Okadaic acid induced lipolysis in this cell-free system and sonication of the lipid droplets caused disappearance of lipolytic action of okadaic acid. Okadaic acid failed to stimulate lipolysis in a cell-free system comprising HSL and artificial lipid droplets (trioleoylglycerol emulsified with gum arabic) instead of lipid droplets isolated from rat fat cells. These results suggest that okadaic acid does not increase the catalytic activity of HSL but induces translocation of HSL to the lipid droplets isolated from rat fat cells. The site of the lipolytic action of okadaic acid in relation to the interaction between HSL and lipid droplet is discussed.
VEGF, basic-FGF, and TGF-β in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation (2001)

OBJECTIVE: Inflammatory bowel disease (IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation; ulcerative colitis (UC) and Crohn’s disease (CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assessed serum concentration levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), and plasma level of endothelin-1 (ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-β1,2,3 (TGF-β1,2,3) in tissue by immunostaining. METHODS: Blood samples were obtained from 11 patients with UC, 11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemical study. RESULTS: The concentration levels (in picograms per milliliter) were as follows: for ET-1, UC: 127 ± 47.0, CD: 167.3 ± 35.1, and controls (asthma: 38.5 ± 23.8, p < 0.01; diverticulitis: 40.5 ± 25.6, p < 0.01), for b-FGF, UC: 9.2 ± 1.9, CD: 9.1 ± 1.5, and controls (asthma: 5.0 ± 0, p < 0.01; diverticulitis: 5.0 ± 0, p < 0.01), for VEGF, UC: 659.8 ± 181.0, CD: 740.0 ± 182.3, and controls (asthma: 193.7 ± 58.7, p < 0.01; diverticulitis: 199.6 ± 59.7, p < 0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF and the plasma level of ET-1; that is, elevated VEGF, b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-β2 and TGF-β3 were found in inflammatory cells of active IBD, but no change was observed around the vessels in the controls. CONCLUSIONS: It is suggested that the reciprocal reaction of these cytokines may contribute to angiogenesis in IBD by inducing intestinal ischemia through vasoconstriction.
The role of lipid rafts in signalling and membrane trafficking in T lymphocytes (2001)

Combinatorial association of different lipid species generates microheterogeneity in biological membranes. The association of glycosphingolipids with cholesterol forms membrane microdomains – lipid rafts – that are involved in specialised pathways of protein/lipid transport and signalling. Lipid rafts are normally dispersed in cellular membranes and appear to require specialised machinery to reorganise them to operate. Caveolin-1 and MAL are members of two different protein families involved in reorganisation of lipid rafts for signalling and/or intracellular transport in epithelial cells. T cell activation induces a rapid compartmentalisation of signalling machinery into reorganised rafts that are used as platforms for the assembly of the signalling complex. Costimulatory molecules participate in this process by providing signals that mobilise raft lipids and proteins, and remodel the cytoskeleton to the contact site. As in epithelial cells, rafts are used also as vesicular carriers for membrane trafficking in T lymphocytes. Furthermore, there are potential similarities between the specialised protein machinery underlying raft-mediated processes in T lymphocytes and polarised epithelial cells.
SYMPOSIUM Molecular Pathogenesis of Staphylococcal Osteomyelitis 1 (2013)

ABSTRACT Staphylococcus aureus is the most prominent The possibility that a rare phenotype is conserved among musculoskeletal pathogen of man and animals. The per- isolates that cause a particular form of infection suggests sistent emergence of antibiotic-resistant strains has a cause-and-effect relationship in which the phenotype prompted renewed efforts to develop alternative proto- contributes to the pathogenesis of the disease. To further cols for the treatment and prevention of staphylococcal evaluate that hypothesis, we attempted to determine disease. These efforts have included attempts to develop whether Cna is the only collagen-binding adhesin pro-an effective staphylococcal vaccine. Among the potential duced by S. aureus and whether strains that encode cna vaccine candidates are a group of surface proteins that share additional characteristics that distinguish them act as adhesins by virtue of their ability to bind host from other S. aureus strains. We also studied whether proteins present in plasma and in the extracellular matrix. immunization with Cna induces a protective immune Because of our interest in the treatment and prevention response. Our results confirm that Cna is the primary
Critical Role of Endoplasmic Reticulum Aminopeptidase 1 in Determining the Length and Sequence of Peptides Bound and Presented by HLA–B27 (2013)

These results show that ERAP1 directly alters peptide binding and presentation by HLA-B27, thus demonstrating a potential pathogenic mechanism in AS. Inhibition of ERAP1 could potentially be used for treatment of AS and other ERAP1-associated diseases.
Analytical Model of a Vibrating Electromagnetic Harvester Considering Nonlinear Effects (2010)

In this paper, an analytical model of a vibrating electromagnetic harvester, taking into account nonlinear effects, is presented. Knowing the acceleration applied to the harvester system, the model is able to predict the performance of the harvester in terms of induced voltage on the load. The energy transducer consists of four magnets, two movable and two fixed, arranged in a way such that both fixed magnets repel the moveable one. The model was implemented in Simulink and exploits the results of a finite element method (FEM) solver (Flux2D) to estimate the non-linear electromagnetic repulsion force and the flux linkage by the coil. To evaluate the effect of a load applied to the harvester, the effect of the Lorentz's force, caused by the interaction of the current that flows in the coil and the flux density of the moveable magnet, was taken into account. As a consequence, the error in the estimate of induced voltage, at resonance, is reduced from about 80% to 7%. Finally, at resonance, the maximum power that could be delivered by the harvester and dissipated on a resistive load was estimated to be about 6 mW.
Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells. (1993)

A major theme of this review is that apoB secretion is regulated post-translationally, and that apoB secretion reacts rapidly to the current state of lipid metabolism in the cell. Therefore, as discussed by Fungwe et al. (122), the metabolism of triglyceride and of cholesteryl ester, in so far as both can be used as core lipids for apoB-containing LPs, are inextricably linked, and the shortage of one or both of these lipids could, by "allowing" increased intracellular degradation in the ER, inhibit the secretion of apoB. Another theme in this review is that the regulation of apoB secretion may be quite different in rat hepatocytes compared to cultured cells (HepG2) used as a model for human hepatocytes. Exogenous fatty acids appear to modulate the rate of apoB secretion in HepG2 cells, whereas they have only minimal effects on apoB secretion in rat hepatocytes or liver. Increased dietary cholesterol, on the other hand, appears to be an important modulator of apoB secretion in rats, but the evidence for effects of cholesterol on apoB secretion in HepG2 cells is less convincing. Finally, because HepG2 cells are an immortalized cell line, there could be many differences between these cells and human hepatocytes in vivo. Therefore, many of the results obtained with HepG2 cells should be corroborated in primary cultures of human hepatocytes. However, investigators utilizing primary human hepatocytes should be sure that the culture conditions are adequate to maintain the continued transcription of liver specific genes and to prevent the dedifferentiation of these cells in culture (85, 86).
CEO Pension and Auditors Going Concern Opinion (2018)

In U.S., CEO pension is common and sizable compensation recorded as off - balance sheet liabilities before CEOs’ retirement . Also, since it becomes unplayable after bankruptcy, CEOs awarded with pension plans are known to manage their firms conservatively to prevent such bankruptcies. Therefore, it was empirically examine d how auditors consider CEO pension in determining their going - concern opinions. O ur empirical results indicate that auditors are more likely to issue nega tive going - concern opinions for firms that provide their CEOs with pension plans. The results remain robust after controlling various endogeneity issues. Overall, our findings impl y that auditors recognize CEO pensions as liabilities rather than significan tly consider how CEO pensions provide incentives for conservative firm management .
Characterization of Photooxidized Self-Assembled Monolayers and Bilayers by Spontaneous Desorption Mass Spectrometry (2000)

We show that selected self-assembled monolayers (SAMs) and bilayers are readily characterized by the application of controlled photooxidation and spontaneous desorption mass spectrometry (SDMS) in the negative ion mode. Additionally, SDMS is used to characterize organic and inorganic anionic species adsorbed to the surface of a positively charged SAM surface, 2-aminoethanethiol (AET). Prominent peaks are observed that correspond both to the sulfonate form of each SAM and bilayer and to the anion form of each molecule adsorbed to AET. In addition, fragments of the oxidized thin films were also observed at m/z 80 (SO3-) and 97 (HSO4-). Other prominent fragment peaks more characteristic of the molecule are also seen in the mass spectra.
Neuroglial activation and neuroinflammation in the brain of patients with autism (2004)

Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh-frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.
Synthesis of 1,2- and 1,4-dihydropyridines (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 1,2- and 1,4-dihydropyridinesFrank W. FowlerCite this: J. Org. Chem. 1972, 37, 9, 1321–1323Publication Date (Print):May 1, 1972Publication History Published online1 May 2002Published inissue 1 May 1972https://pubs.acs.org/doi/10.1021/jo00974a009https://doi.org/10.1021/jo00974a009research-articleACS PublicationsRequest reuse permissionsArticle Views2246Altmetric-Citations156LEARN 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
Sensitivity and Specificity of Intraoperative Recurrent Laryngeal Nerve Stimulation in Predicting Postoperative Nerve Paralysis (2002)

Bilateral recurrent laryngeal nerve (RLN) paralysis after thyroidectomy is infrequent, but serious when it occurs. Intraoperative knowledge of the status of the nerve after dissection could potentially provide the surgeon with important decision-making information. The current study examines the sensitivity and specificity of intraoperative stimulation of the RLN during thyroid surgery for predicting postoperative RLN deficits. Eighty-one RLNs in 55 patients were identified to be at risk of injury during thyroidectomy or parathyroidectomy performed between January 1998 and February 2000. Intraoperative determination of RLN function was evaluated with a disposable nerve stimulator (Xomed, Jacksonville, Florida) set at 0.5 mA. Injury was assessed by palpating for a contraction of the posterior cricoarytenoid muscle while the stimulus was applied. Postoperative assessment of RLN integrity was determined by using indirect or direct laryngoscopy to visualize vocal fold mobility. Nine RLNs failed to elicit a posterior cricoarytenoid contraction after nerve stimulation, and 4 RLNs were determined to be deficient in the postoperative evaluation. The calculated sensitivity and specificity were 75% and 92.2% with a positive predictive value of 33.3% and negative predictive value of 98.6%. The RLN injury rate was 4.94%. We conclude that intraoperative RLN stimulation is a relatively safe and useful method of determining what RLN function will be after thyroid or parathyroid surgery.
Using Serum Creatinine To Estimate Glomerular Filtration Rate: Accuracy in Good Health and in Chronic Kidney Disease (2004)

The MDRD equation systematically underestimates GFR in healthy persons. A new equation developed with patients who have chronic kidney disease and healthy persons may be a step toward accurately estimating GFR when the diagnosis of chronic kidney disease is unknown.
Decreased BMD and Limb Deformities in Mice Carrying Mutations in Both Lrp5 and Lrp6 (2004)

Lrp6 and Lrp5 genetically interact in limb development in mice. Furthermore, heterozygosity for an inactivating mutation in Lrp6 further reduces BMD in both male and female mice lacking Lrp5.
Differential Effects of Sodium Butyrate and Dimethylsulfoxide on Gamma-Glutamyl Transpeptidase and Alkaline Phosphatase Activities in MCF-7 Breast Cancer Cells (1987)

Sodium butyrate and dimethylsulfoxide (DMSO), two known chemical inducers of cell differentiation, were examined on MCF-7 breast cancer cells. Both agents reduce the proliferative capacity of MCF-7 cells, as reflected by inhibition of colony formation in semisolid agar. Sodium butyrate is shown to enhance markedly the activity of two plasma membrane-bound enzymes, alkaline phosphatase and gamma-glutamyl transpeptidase. DMSO does not enhance the activity of these enzymes, but rather induces a small decrease in gamma-glutamyl transpeptidase activity. The present results show that although both agents inhibit cell proliferation, they have a distinct effect on phenotypic expression.