gebhart/patrepeval huggingface dataset:
Transforming Growth Factor β1 Is Up-regulated by Activated Raf in Skeletal Myoblasts but Does Not Contribute to the Differentiation-defective Phenotype (2004)

The Raf/MEK/MAPK signaling module elicits a strong negative impact on skeletal myogenesis that is reflected by a complete loss of muscle gene transcription and differentiation in multinucleated myocytes. Recent evidence indicates that Raf signaling also may contribute to myoblast cell cycle exit and cytoprotection. To further define the mechanisms by which Raf participates in cellular responses, a stable line of myoblasts expressing an estrogen receptor-Raf chimeric protein was created. The cells (23A2RafER(DD)) demonstrate a strict concentration-dependent increase in chimeric Raf protein synthesis and downstream phosphoMAPK activation. Initiation of low-level Raf activity in these cells augments contractile protein expression and myocyte fusion. By contrast, induction of high level Raf activity in 23A2RafER(DD) myoblasts inhibits the formation of myocytes and muscle reporter gene expression. Interestingly, treatment of myoblasts with conditioned medium isolated from Raf-repressive cells inhibits all of the aspects of myogenesis. Closer examination indicates that the transforming growth factor-beta(1) (TGF-beta(1)) gene is up-regulated in Raf-repressive myoblasts. The cells also direct elevated levels of Smad transcriptional activity, suggesting the existence of a TGF-beta(1) autocrine loop. However, extinguishing the biological activity of TGF-beta(1) does not restore the myogenic program. Our results provide evidence for the involvement of Raf signal transmission during myocyte formation as well as during inhibition of myogenesis.
Myocardial suppression in vivo by spin locking with composite pulses (1996)

Improved myocardium-blood contrast by myocardial suppression resulting from T1 rho-weighting in contrast-enhanced, gradient-echo, bright-blood cine images, acquired at 1.5T, is shown. In the standard images, blood has twice the intensity of muscle. In similar T1 rho-weighted images, it has 3-4 times the intensity of muscle. A composite spin-lock pulse before each observation pulse provides T1 rho-weighting. A typical pulse was: 90y-135x-360x-135x-90(-y) with element durations: 0.84, 1.26, 8.12, 1.26, and 0.84 ms. The tolerance of this composite pulse to shimmering and frequency errors allows spin locking with comparatively weak RF and therefore low specific absorption rate (SAR). Initial clinical evaluation on patients with poor ventricular function demonstrates both a qualitative and quantitative improvement in delineation of myocardial borders.
Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization. (1998)

The analysis of genetic changes in primary cutaneous melanoma has been limited by the need for fixation for diagnostic purposes. However, comparative genomic hybridization is able to analyze such specimens. We have applied comparative genomic hybridization to 32 primary melanomas to discover and map genomic regions with aberrant DNA copy numbers. The analysis was performed on native, nonamplified DNA extracted from manually dissected tumor sections. Loss of chromosome 9 was detected in 81% of the tumors, most commonly affecting the p arm. Additional common losses occurred on chromosomes 10 (63%), 6q (28%), and 8p (22%). Gains in copy number involved chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%), 20 (13%), 17 (13%), and 2 (13%). Amplifications indicating areas harboring potential oncogenes were seen at 4q12, 5p14.3-pter, 7q33-qter, 8q12-13, 11q13.3-14.2, and 17q25. Correlations among the regions with copy number changes indicate that losses of chromosomes 9 and 10 occur early on in melanoma progression, whereas gains of chromosome 7 occur later. This sequence of events was further substantiated by an intratumoral comparison of copy number changes in areas with radial and vertical growth phase patterns. The overall pattern of regions affected by copy number changes is consistent with cytogenetic data from metastatic melanoma; however, the frequencies of involvement differ, providing further insight into the course of genetic events.
The Human IL-17F/IL-17A Heterodimeric Cytokine Signals through the IL-17RA/IL-17RC Receptor Complex (2008)

IL-17A and IL-17F, produced by the Th17 CD4(+) T cell lineage, have been linked to a variety of inflammatory and autoimmune conditions. We recently reported that activated human CD4(+) T cells produce not only IL-17A and IL-17F homodimers but also an IL-17F/IL-17A heterodimeric cytokine. All three cytokines can induce chemokine secretion from bronchial epithelial cells, albeit with different potencies. In this study, we used small interfering RNA and Abs to IL-17RA and IL-17RC to demonstrate that heterodimeric IL-17F/IL-17A cytokine activity is dependent on the IL-17RA/IL-17RC receptor complex. Interestingly, surface plasmon resonance studies indicate that the three cytokines bind to IL-17RC with comparable affinities, whereas they bind to IL-17RA with different affinities. Thus, we evaluated the effect of the soluble receptors on cytokine activity and we find that soluble receptors exhibit preferential cytokine blockade. IL-17A activity is inhibited by IL-17RA, IL-17F is inhibited by IL-17RC, and a combination of soluble IL-17RA/IL-17RC receptors is required for inhibition of the IL-17F/IL-17A activity. Altogether, these results indicate that human IL-17F/IL-17A cytokine can bind and signal through the same receptor complex as human IL-17F and IL-17A. However, the distinct affinities of the receptor components for IL-17A, IL-17F, and IL-17F/IL-17A heterodimer can be exploited to differentially affect the activity of these cytokines.
Sequence features responsible for intron retention in human (2007)

Although our results confirmed that weaker splice sites are associated with IR, they showed that this feature alone cannot explain a non-negligible fraction of events. Our analysis suggests that cis-regulatory elements are likely to play a crucial role in regulating IR and also reveals previously unknown features that seem to influence its occurrence. These results highlight the importance of considering the interplay among these features in the regulation of the relative frequency of IR.
Universal GFP reporter for the study of vascular development (2000)

We report the generation and characterization of transgenic mouse and zebrafish expressing green fluorescent protein (GFP) specifically in vascular endothelial cells in a relatively uniform fashion. These reporter lines exhibit fluorescent vessels in developing embryos and throughout adulthood, allowing visualization of the general vascular patterns with single cell resolution. Furthermore, we show the ability to purify endothelial cells from whole embryos and adult organs by a single step fluorescence activated cell sorting. We expect that these transgenic reporters will be useful tools for imaging vascular morphogenesis, global gene expression profile analysis of endothelial cells, and high throughput screening for vascular mutations.
The PI3K–Akt mediates oncogenic Met-induced centrosome amplification and chromosome instability (2010)

The oncogenic ability of aberrant hepatocyte growth factor receptor (Met) signaling is thought to mainly rely on its mitogenic and anti-apoptotic effects. Recently, however, cumulating evidences suggest that genomic instability may be a crucial factor in tumorigenesis. Here, we address whether oncogenic Met receptor is linked to the centrosome abnormality and genomic instability. We showed that expression of the constitutive active Met (CA-Met) induced supernumerary centrosomes probably due to deregulated centrosome duplication, which was accompanied with multipolar spindle formation and aneuploidy. Interestingly, LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, significantly suppressed the appearance of supernumerary centrosomes. Moreover, knockdown of Akt with small interfering RNAs and overexpression of phosphatase and tensin homolog or dominant-negative Akt abrogated supernumerary centrosome formation, evidencing the involvement of PI3K signaling. We further showed that expression of CA-Met significantly increased aneuploidy in p53(-/-) HCT116 cells, but not in p53(+/+) HCT116 cells, indicating that the ability of CA-Met to induce chromosomal instability (CIN) phenotype is related with p53 status. Together, our data demonstrate that aberrant hepatocyte growth factor/Met signaling induces centrosome amplification and CIN via the PI3K-Akt pathway, providing an example that oncogenic growth factor signals prevalent in a wide variety of cancers have cross talks to centrosome abnormality and CIN.
Fabrication of focused poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) copolymer 40–50 MHz ultrasound transducers on curved surfaces (2004)

Copolymer films such as poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) have lower acoustic impedance compared to their ceramic counterparts, allowing for a better acoustic match to tissues in the human body. Because of this, copolymer ultrasonic transducers are capable of yielding the desirable characteristics of broad bandwidth and short pulse duration that allow better image resolution to be achieved. In the past, such transducers in the frequency range from 40 to 80 MHz have frequently been fabricated by spin coating the copolymer film onto a flat substrate and then applying the film to a curved backing using an adhesive layer. The adhesive layer may cause spurious signals at these frequencies, in addition to the film damage that may occur as a result of such processing. In order to avoid these problems, a copolymer film can be directly spin coated onto a curved substrate. The resulting devices had an operating frequency of over 40 MHz and approximately a 75% bandwidth. The potential of several approaches that could be further explored to increase the level of performance of such devices is also discussed.
Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease (2003)

The efficacy and safety of budesonide/formoterol in a single inhaler compared with placebo, budesonide and formoterol were evaluated in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In a 12-month, randomised, double-blind, placebo-controlled, parallel-group study in 812 adults (mean age 64 yrs, mean forced expiratory volume in one second (FEV1) 36% predicted normal), patients received two inhalations twice daily of either budesonide/formoterol (Symbicort) 160/4.5 microg (delivered dose), budesonide 200 microg (metered dose), formoterol 4.5 microg or placebo. Severe exacerbations and FEV1 (primary variables), peak expiratory flow (PEF), COPD symptoms, health-related quality of life (HRQL), mild exacerbations, use of reliever beta2-agonist and safety variables were recorded. Budesonide/formoterol reduced the mean number of severe exacerbations per patient per year by 24% versus placebo and 23% versus formoterol. FEV1 increased by 15% versus placebo and 9% versus budesonide. Morning PEF improved significantly on day 1 versus placebo and budesonide; after 1 week, morning PEF was improved versus placebo, budesonide and formoterol. Improvements in morning and evening PEF versus comparators were maintained over 12 months. Budesonide/formoterol decreased all symptom scores and use of reliever beta2-agonists significantly versus placebo and budesonide, and improved HRQL versus placebo. All treatments were well tolerated. These results suggest a role for budesonide/formoterol in the long-term management of moderate-to-severe chronic obstructive pulmonary disease.
Testing gene function early in the B cell lineage in mb1-cre mice (2006)

The mb1 gene encodes the Ig-alpha signaling subunit of the B cell antigen receptor and is expressed exclusively in B cells beginning at the very early pro-B cell stage in the bone marrow. We examine here the efficacy of the mb1 gene as a host locus for cre recombinase expression in B cells. We show that by integrating a humanized cre recombinase into the mb1 locus we obtain extraordinarily efficient recombination of loxP sites in the B cell lineage. The results from a variety of reporter genes including the splicing factor SRp20 and the DNA methylase Dnmt1 suggest that mb1-cre is probably the best model so far described for pan-B cell-specific cre expression. The availability of a mouse line with efficient cre-mediated recombination at an early developmental stage in the B lineage provides an opportunity to study the role of various genes specifically in B cell development and function.
A bandwidth-optimized reduced-complexity equalized multicarrier transceiver (1997)

A bandwidth-optimized and equalized multicarrier transceiver that achieves near-optimum performance at a practical complexity level is described. The equalizer used is a relatively short FIR filter whose taps and delay are set to optimize the performance of the multicarrier transceiver. Simulation results on a set of carrier-serving-area digital subscriber loops are also presented to demonstrate the separate and joint effects of bandwidth optimization and equalization on performance. Finally, the intriguing idea of using a pole-zero equalizer to achieve the high performance of long FIR equalizers at a much lower implementation cost is investigated.
Enhanced adhesion and compliance of film-terminated fibrillar surfaces (2007)

We present studies of a bio-inspired film-terminated fibrillar surface that has significantly enhanced adhesion and contact compliance compared with a flat control. We show that adhesion hysteresis arises from the architecture of the interfacial region. Measured in cyclic indentation experiments, it can be nearly five times the absolute work of adhesion for a flat control. Using a two-dimensional model, we propose that hysteresis develops as a result of crack trapping by fibril edges. The crack propagation mode is consistent with this model, as is the observation that with increasing hysteresis crack opening adhesion energy increases whereas crack closing adhesion energy decreases compared with a flat control. Contact compliance of the fibrillar structure is up to seven times more than that of a flat control. We present a model for the contact compliance of such structures which is in good agreement with measurements.
Metabolic Characteristics of Oxcarbazepine (®Trileptal) and their Beneficial Implications for Enzyme Induction and Drug Interactions (1990)

Hepatic oxygenases of the cytochrome P-450 family play a major role in the clearance of various anti-epileptic drugs. These enzymes are susceptible both to induction and to inhibition. Phenytoin, carbamazepine (CBZ), primidone, and phenobarbitone, for instance, are potent enzyme inducers. Other drugs, such as chloramphenicol, propoxyphene, verapamil, and viloxazine, inhibit cytochrome P-450. Pharmacokinetic behaviour is thus often altered, especially in combined medication, so that the dosage has to be re-adjusted if an optimum therapeutic outcome is to be ensured. Oxcarbazepine (OXC) is a keto analogue of CBZ. In the human liver the keto group is readily reduced, and the resulting monohydroxy metabolite is cleared by glucuronidation. The two enzymes mediating these reactions, i.e. aldo-keto reductase and UDP-glucuronyltransferase, do not depend on cytochrome P-450. The monohydroxy metabolite is the major active substance in plasma. Its elimination is not enhanced by OXC. Moreover, OXC seems to have little effect on cytochrome P-450. Aldo-keto reductases and glucuronyltransferases are in general less sensitive to induction and inhibition than are P-450 dependent enzymes. On the whole, OXC possesses very little potential for metabolic drug interactions, and thus differs favourably from other anti-epileptic drugs.
Continuous positive airway pressure improves nocturnal baroreflex sensitivity of patients with heart failure and obstructive sleep apnea (2000)

In CHF patients with OSA, CPAP increases acutely BRS during sleep, lowers heart rate and resets the operating point for BRS to a lower blood pressure. These effects of CPAP persist after its withdrawal, suggesting that nocturnal CPAP therapy may cause sustained improvement in the neural control of heart rate.
Role of the RANK/RANKL Pathway in Multiple Myeloma (2018)

Receptor activator of nuclear factor-kappa B (RANK) and its ligand, RANKL, are expressed in a variety of tissues throughout the body; their primary role is in the regulation of bone remodeling and development of the immune system. Consistent with these functions, evidence exists for a role of RANK/RANKL in all stages of tumorigenesis, from cell proliferation and carcinogenesis to epithelial-mesenchymal transition to neoangiogenesis and intravasation to metastasis to bone resorption and tumor growth in bone. Results from current studies also point to a role of RANK/RANKL signaling in patients with multiple myeloma, who have increased serum levels of soluble RANKL and an imbalance in RANKL and osteoprotegerin. Current therapies for patients with multiple myeloma demonstrate that RANKL may be released by tumor cells or osteoprogenitor cells. This article will review currently available evidence supporting a role for RANK/RANKL signaling in tumorigenesis, with a focus on patients with multiple myeloma.
The Expression of Migration Stimulating Factor, a Potent Oncofetal Cytokine, Is Uniquely Controlled by 3′-Untranslated Region–Dependent Nuclear Sequestration of Its Precursor Messenger RNA (2005)

Migration stimulating factor (MSF) is a truncated oncofetal fibronectin isoform expressed by fetal and tumor-associated cells. MSF mRNA is distinguished from other fibronectin isoforms by its size (2.1 kb) and the inclusion of a specific intronic sequence at its 3' end. Initial Northern blot analysis with a MSF-specific probe indicated the presence of this 2.1-kb transcript and an additional unexpected 5.9-kb RNA present in both MSF-secreting (fetal) and nonsecreting (adult) fibroblasts. Our investigations into the nature of these transcripts and their relationship to MSF protein secretion revealed that the 5.9-kb mRNA is a second MSF-encoding transcript. Both these mRNAs have identical coding sequence and differ only in the length of their intron-derived 3'-untranslated region (UTR). The 5.9-kb MSF mRNA is retained in the nucleus whereas the 2.1-kb mRNA is not. MSF-secreting fetal fibroblasts have significantly lower nuclear levels of the 5.9-kb mRNA and correspondingly higher cytoplasmic levels of the 2.1-kb transcript than their nonsecreting adult counterparts. Adult fibroblasts induced to secrete MSF by treatment with transforming growth factor-beta1 displayed similar changes in their respective levels of MSF mRNA, but not those of a control gene. When cloned downstream of a reporter gene, only the longer 3'-UTR retained coding sequence within the nucleus. We conclude that expression of MSF protein is regulated by 3'-UTR truncation of the 5.9-kb nuclear-sequestered "precursor" MSF mRNA and nuclear export of mature 2.1-kb message. Inducible 3'-UTR processing represents a novel regulatory mechanism involved in cancer pathogenesis that may open new avenues for therapeutic gene delivery.
Kinematics from Lines in a Single Rolling Shutter Image (2007)

Recent work shows that recovering pose and velocity from a single view of a moving rigid object is possible with a rolling shutter camera, based on feature point correspondences. We extend this method to line correspondences. Owing to the combined effect of rolling shutter and object motion, straight lines are distorted to curves as they get imaged with a rolling shutter camera. Lines thus capture more information than points, which is not the case with standard projection models for which both points and lines give two constraints. We extend the standard line reprojection error, and propose a nonlinear method for retrieving a solution to the pose and velocity computation problem. A careful inspection of the design matrix in the normal equations reveals that it is highly sparse and patterned. We propose a blockwise solution procedure based on bundle-adjustment-like sparse inversion. This makes nonlinear optimization fast and numerically stable. The method is validated using real data.
The Reactions of Phosphonic Acid Esters with Acid Chlorides. A Very Mild Hydrolytic Route (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Reactions of Phosphonic Acid Esters with Acid Chlorides. A Very Mild Hydrolytic RouteRobert RabinowitzCite this: J. Org. Chem. 1963, 28, 11, 2975–2978Publication Date (Print):November 1, 1963Publication History Published online1 May 2002Published inissue 1 November 1963https://pubs.acs.org/doi/10.1021/jo01046a008https://doi.org/10.1021/jo01046a008research-articleACS PublicationsRequest reuse permissionsArticle Views1523Altmetric-Citations120LEARN 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
c-Met Is a Potentially New Therapeutic Target for Treatment of Human Melanoma (2007)

These results support the role of c-Met in proliferation, apoptosis, differentiation, and tumor progression of melanoma. SU11274 could be used in the therapeutic inhibition of melanoma.
Susceptibility of Msh2-deficient mice to inflammation-associated colorectal tumors. (2002)

Patients with longstanding extensive ulcerative colitis have an increased risk of developing colorectal cancer (CRC). There are significant differences in the early pathogenesis of colitis-associated tumors compared with common CRC, whereas the frequency, degree, and significance of microsatellite instability (MSI) as a marker of mismatch repair deficiency in colitis tumors remain unclear. Here we describe the application of the DSS model of chronic colitis to mice with a defect in the Msh2 mismatch repair gene to discern these early events. These mice do not develop CRC spontaneously without an external trigger. The aim of this study was to determine the effect of the Msh2 defect on the frequency and grade of colitis-associated colorectal dysplasia and adenocarcinoma in Msh2-/-, Msh2+/-, and wild-type (Msh2+/+) mice and on the MSI status of the tumors. We show that in mice with chronic colitis, 60% of the Msh2-/- and 29% of the wild-type mice developed high-grade dysplasia or adenocarcinoma, but heterozygosity for the Msh2 defect did not increase tumor susceptibility over wild-type genotype. The largest difference between genotypes was in the frequency of high-grade dysplasia, with 46.7, 8, and 12.5% in Msh2-/-, Msh2+/-, and Msh2+/+ mice, respectively. The Msh2-/- mice developed MSI-high tumors, whereas the majority of the Msh2+/- and wild-type tumors had no MSI. In the Msh2-/- mice, MSI appeared early in non-neoplastic colon tissue, presumably as a result of markedly increased epithelial cell proliferation associated with inflammation. These observations suggest that a homozygous mismatch repair defect predisposes to tumors triggered by chronic inflammation but is not the only factor involved because tumors also developed in the wild-type mice. This model of colitis offers opportunities to characterize the different molecular pathways of carcinogenesis operating in chronic colitis.