gebhart/patrepeval huggingface dataset:
Rapamycin inhibits clonal expansion and adipogenic differentiation of 3T3-L1 cells. (1995)

Differentiating 3T3-L1 cells express an immunophilin early during the adipocyte conversion program as described in this issue [Yeh, W.-C., Li, T.-K., Bierer, B. E. & McKnight, S. L. (1995) Proc. Natl. Acad. Sci. USA 92, 11081-11085]. The temporal expression profile of this protein, designated FK506-binding protein (FKBP) 51, is concordant with the clonal-expansion period undertaken by 3T3-L1 cells after exposure to adipogenic hormones. Having observed FKBP51 synthesis early during adipogenesis, we tested the effects of three immunosuppressive drugs--cyclosporin A, FK506, and rapamycin--on the terminal-differentiation process. Adipocyte conversion was not affected by either cyclosporin A or FK506 and yet was significantly reduced by rapamycin at drug concentrations as low as 10 nM. Clonal expansion was impeded in drug-treated cultures, as was the accumulation of cytoplasmic lipid droplets normally seen late during differentiation. Rapamycin treatment likewise inhibited the expression of CCAAT/enhancer binding protein alpha, a transcription factor required for 3T3-L1 cell differentiation. All three of these effects were reversed by high FK506 concentrations, indicating that the operative inhibitory event was mediated by an immunophilin-rapamycin complex.
Inhibitory Regulation of Hypertrophy by Endogenous Atrial Natriuretic Peptide in Cultured Cardiac Myocytes (2000)

Atrial natriuretic peptide (ANP) may function as an endogenous regulator of cardiac hypertrophy, because the natriuretic peptide receptor has been found in the heart and because mice lacking its receptor have been shown to have a markedly elevated ventricular mass. We examined the role of endogenous ANP in cardiac hypertrophy in vitro. The effects of the blockade of endogenous ANP by its receptor antagonist, HS-142-1, on cell hypertrophy were investigated with the use of cultured neonatal rat ventricular myocytes. HS-142-1 increased the basal and phenylephrine (PE, 10(-5) mol/L)-stimulated protein syntheses in a concentration-dependent manner (1 to 300 microg/mL). A significant increase in the cell size of myocytes was also induced by this antagonist. In addition, the expression levels of skeletal alpha-actin, beta-myosin heavy chain, and ANP genes, markers of hypertrophy, were partially elevated by treatment with HS-142-1 (100 microg/mL) under nonstimulated or PE-stimulated conditions. A cGMP-specific phosphodiesterase inhibitor, zaprinast (5x10(-4) mol/L), and a cGMP analogue (10(-4) mol/L) suppressed the basal and PE-stimulated protein syntheses. Our observations suggest that endogenous ANP inhibits cardiac myocyte hypertrophy under basal and PE-stimulated conditions, probably through a cGMP-dependent process. ANP may play a role as an autocrine factor in the regulation of cardiac myocyte growth.
A mouse model for the delta F508 allele of cystic fibrosis. (1995)

The most common cause of cystic fibrosis is a mutation that deletes phenylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR). The delta F508 protein is misprocessed and degraded rather than traveling to the apical membrane. We used a novel strategy to introduce the delta F508 mutation into the mouse CFTR gene. Affected epithelia from homozygous delta F508 mice lacked CFTR in the apical membrane and were Cl-impermeable. These abnormalities are the same as those observed in patients with delta F508 and suggest that these mice have the same cellular defect. 40% of homozygous delta F508 animals survived into adulthood and displayed several abnormalities found in human disease and in CFTR null mice. These animals should provide an excellent model to investigate pathogenesis and to examine therapies directed at correcting the delta F508 defect.
Pd-Mediated C-C and C-S Bond Formation on Solid Support: A Scope and Limitations Study (1998)

The scope and limitations of Pd(0)-mediated coupling reactions between aromatic halides linked to a polystyrene resin and boronic acid derivatives (Suzuki coupling), aromatic and vinylic tin compounds (Stille coupling), as well as thiols are reported. For all reactions, conditions were optimized and evaluated with various reagents. In many cases, upon cleavage from the solid support, products were obtained in excellent yields. In most cases, the optimized reaction conditions are superior to those previously reported in the literature.
Small Heat Shock Proteins and Vasospasm in Human Umbilical Artery Smooth Muscle1 (1997)

Human umbilical artery smooth muscle is uniquely refractory to cyclic nucleotide-dependent vasorelaxation. Small heat shock proteins (HSPs) have been implicated as contractile regulatory proteins. Thus, we hypothesized that alterations in the phosphorylation of small HSPs may contribute to human umbilical artery smooth muscle vasospasm. Physiologic contractile responses were determined in a muscle bath and compared with phosphorylation events determined with whole-cell phosphorylation and 2-dimensional gel electrophoresis. Precontraction of bovine carotid artery smooth muscle with serotonin followed by relaxation with forskolin was associated with increases in the phosphorylation of HSP27 and HSP20. Precontraction of umbilical artery with serotonin followed by forskolin treatment led to increases in the phosphorylation of HSP27. However, the umbilical artery smooth muscle did not relax, nor was there an increase in the phosphorylation of HSP20 with forskolin treatment. These data suggest that impaired cyclic nucleotide-dependent relaxation of umbilical artery smooth muscle is associated with a lack of phosphorylation of HSP20.
The Multiassembly Problem: Reconstructing Multiple Transcript Isoforms From EST Fragment Mixtures (2004)

Recent evidence of abundant transcript variation (e.g., alternative splicing, alternative initiation, alternative polyadenylation) in complex genomes indicates that cataloging the complete set of transcripts from an organism is an important project. One challenge is the fact that most high-throughput experimental methods for characterizing transcripts (such as EST sequencing) give highly detailed information about short fragments of transcripts or protein products, instead of a complete characterization of a full-length form. We analyze this "multiassembly problem"-reconstructing the most likely set of full-length isoform sequences from a mixture of EST fragment data-and present a graph-based algorithm for solving it. In a variety of tests, we demonstrate that this algorithm deals appropriately with coupling of distinct alternative splicing events, increasing fragmentation of the input data and different types of transcript variation (such as alternative splicing, initiation, polyadenylation, and intron retention). To test the method's performance on pure fragment (EST) data, we removed all mRNA sequences, and found it produced no errors in 40 cases tested. Using this algorithm, we have constructed an Alternatively Spliced Proteins database (ASP) from analysis of human expressed and genomic sequences, consisting of 13,384 protein isoforms of 4422 genes, yielding an average of 3.0 protein isoforms per gene.
Effects of bisphosphonates on isolated Rat osteoclasts as examined by reflected light microscopy (1990)

The bisphosphonates 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP), 3-amino-1,1-hydroxypropane-1,1-diphosphonic acid (APD), and 1-hydroxyethane-1,1-diphosphonic acid (EHDP) were compared for their ability to inhibit the osteoclastic resorption of bone in culture. This was achieved by measuring the effect of bisphosphonate concentration on the number of resorption pits formed and the total area of resorption. During this analysis, a new application of reflected polarized light microscopy was developed that has advantages over other microscopy techniques, including scanning electron microscopy (SEM), as applied to the analysis of resorbed bone surfaces. Based on area analysis, the bisphosphonates were effective for the range 10(-7)-10(-8) M, with ABP about two to five times more effective than EHDP or APD. Similar data were obtained by counting the number of resorption pits but with EC50 10 times higher. At lower concentrations (10(-9) M), bisphosphonates may enhance the formation of resorption pits. APD was found to be more toxic (10 times) than ABP or EHDP to osteoclasts and mononuclear cells, but toxic concentrations were at least 10(2) times higher than the resorption EC50. These data plus immunofluorescence, SEM, and transient incubation experiments show that it is the bisphosphonate-bone complex that directly inhibits the excavation of resorption pits by mature osteoclasts. The mechanism of action does not appear to require inhibition of osteoclast differentiation or toxic elimination of osteoclasts. Bisphosphonates, however, subtly affect the cytoskeleton of osteoclasts.
Inhibitory effects of interleukin‐10 on synovial cells of rheumatoid arthritis (1997)

This paper describes the immunoregulatory effects of interleukin-10 (IL-10) on synovial cells in vitro. Synovial cells were cultured with IL-10 in the presence or absence of various cytokines. Following incubation, the costimulatory molecule expression on synovial cells and cytokine production in culture supernatants were analysed by an indirect immunofluorescence method and enzyme-linked immunosorbent assay, respectively. We also examined the effect of IL-10 on the function of synovial cells as antigen-presenting cells (APC). Synovial cells spontaneously express several kinds of costimulatory molecule and produce various kinds of cytokines. Stimulation of synovial cells with interferon-gamma (IFN-gamma), IL-1 beta, or 12-O-tetradecanoyl phorbol 13-acetate (TPA) markedly enhanced the expression of costimulatory molecules and cytokine production of these cells. Both spontaneous and up-regulated costimulatory molecule expression and cytokine production were significantly suppressed by the addition of IL-10. Autologous T-cell proliferation was stimulated by purified protein derivative (PPD) in IFN-gamma-treated synovial cells and treatment of these synovial cells with IL-10 also suppressed T-cell proliferation. Our results suggest that IL-10 has an inhibitory effect on synovial cells and is an important immunoregulatory component of the cytokine network in rheumatoid arthritis.
Strength of Fabric Reinforced Blackglas Composites (2008)

In brittle matrix composites the role of matrix porosity; interface; and matrix/fiber properties degradation due to processing are especially critical for the strength of the composite. In this paper, the Fabric Geometry Model (FGM) is modified to predict the strength of fabric composites. An incremental strain approach in conjunction with strain energy criterion is presented in order to account for the potentially nonlinear behavior of the materials, as seen in the experimental stress-strain curves of Nextel/Blackglas composites. The failure of the composite is determined by use of a modified maximum strain energy criterion, which is based on the relative magnitudes of the various energy terms in corresponding direction. The effects of porosity, microcracks, fiber and matrix degradation, and fiber/matrix interface are also considered in the modified model.
Molecular prognostic factors in rectal cancer treated by radiation and surgery (2000)

Tumor response to radiation is associated with improved tumor control and overall survival rate, and p21 expression is a marker of tumor radiosensitivity in patients with rectal cancer. Furthermore, a high proliferating cell nuclear antigen labeling index and a low microvessel count in the preradiation biopsy specimen may be prognostic indicators for tumor recurrence.
PathogenMip Assay: A Multiplex Pathogen Detection Assay (2007)

The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer progression. Probe construction was based on a novel, cost-effective, ligase-based protocol. The assay was validated by performing pyrosequencing and Microarray chip detection in parallel experiments. HPV plasmids were used to validate sensitivity and selectivity of the assay. In addition, 20 genomic DNA extracts from primary tumors were genotyped with the PathogenMip Assay results and were in 100% agreement with conventional sequencing using an L1-based HPV genotyping protocol. The PathogenMip Assay is a widely accessible protocol for producing and using highly discriminating probes, with experimentally validated results in pathogen genotyping, which could potentially be applied to the detection and characterization of any microbe.
An Official American Thoracic Society/American College of Chest Physicians Policy Statement: Implementation of Low-Dose Computed Tomography Lung Cancer Screening Programs in Clinical Practice (2015)

Following the strategies delineated in this policy statement may help sites to develop comprehensive LDCT screening programs that are safe and effective.
SYNTHESIS OF HALOGEN-SUBSTITUTED 3-DEAZAADENOSINE AND 3-DEAZAGUANOSINE ANALOGUES AS POTENTIAL ANTITUMOR/ANTIVIRAL AGENTS (2001)

Various 2-halogen-substituted analogues (38, 39, 43 and 44), 3-halogen-substituted analogues (51 and 52), and 2',3'-dihalogen-substituted analogues (57-60) of 3-deazaadenosine and 3-halogen-substituted analogues (61 and 62) of 3-deazaguanosine have been synthesized as potential anticancer and/or antiviral agents. Among these compounds, 3-deaza-3-bromoguanosine (62) showed significant cytotoxicity against L1210, P388, CCRF-CEM and B16F10 cell lines in vitro, producing IC50 values of 3, 7, 9 and 7 microM, respectively. Several 3-deazaadenosine analogues (38, 51, 57 and 59) showed moderate to weak activity against hepatitis B virus.
Surfactant protein B: disulfide bridges, structural properties and kringle similarities (1991)

The disulfide bridges in porcine hydrophobic surfactant protein B (SP-B) were determined. Results show that three intrachain bridges link half-cystine residues 8 and 77, 11 and 71, and 35 and 46, respectively. This gives SP-B an appearance of three loops, a central big loop surrounded by two smaller ones. In the major form of SP-B, the remaining half-cystine, Cys-48, is probably interchain-linked to its counterpart in another molecule, compatible with the existence of dimeric molecules. A minor fraction, with monomeric SP-B but also lacking free thiols, could be due to polypeptides having Cys-57 (instead of Leu in the major form) and hence an additional intrachain bond (Cys-48-Cys-57). Notably, one of the three intrachain bonds common to all SP-B molecules is analogous to one of the disulfide linkages in the kringle structure of complex serine proteases. SP-B and kringles are also similar in size and in positions of half-cystine residues. SP-B and the kringle of coagulation factor XII exhibit 26% residue identity. This structural similarity of SP-B to a binding domain could reflect functional homology, compatible with the notion that SP-B interacts with surfactant anionic phospholipids, which is also in agreement with an SP-B excess of basic residues. Finally, weak similarities between the perform of SP-B and complex serine proteases are also found. This has implications on further possible relationships between kringles, serine proteases, and antiproteases.
Automatic target recognition by matching oriented edge pixels (1997)

This paper describes techniques to perform efficient and accurate target recognition in difficult domains. In order to accurately model small, irregularly shaped targets, the target objects and images are represented by their edge maps, with a local orientation associated with each edge pixel. Three dimensional objects are modeled by a set of two-dimensional (2-D) views of the object. Translation, rotation, and scaling of the views are allowed to approximate full three-dimensional (3-D) motion of the object. A version of the Hausdorff measure that incorporates both location and orientation information is used to determine which positions of each object model are reported as possible target locations. These positions are determined efficiently through the examination of a hierarchical cell decomposition of the transformation space. This allows large volumes of the space to be pruned quickly. Additional techniques are used to decrease the computation time required by the method when matching is performed against a catalog of object models. The probability that this measure will yield a false alarm and efficient methods for estimating this probability at run time are considered in detail. This information can be used to maintain a low false alarm rate or to rank competing hypotheses based on their likelihood of being a false alarm. Finally, results of the system recognizing objects in infrared and intensity images are given.
EMS in the pueblos. (1994)

Imagine creating a movie by excerpting scenes from "Dances With Wolves," splicing it with footage from "Code 3" or "Emergency Response" and then flavoring the script with the mystery of a Tony Hillerman novel. A film producer would probably find it quite difficult to choreograph a finished product from such a compilation of material. To hundreds of Native American EMS providers, however, such a movie is played out every day in Indian country. And with this movie come some real-life problems, including trauma, which is the number-one cause of premature death among Native Americans. But a high trauma rate is just one of the challenges facing tribal EMS responders. There's also prolonged response and transport, the problems involved in maintaining the unique culture and standard of care, the challenges of tribal EMS administration and EMS education of Native American students, and the unsure future of Native American EMS. Beyond that, there's the fact that EMS is a s unique to each Indian reservation as are the cultures of the native peoples who reside on these lands. Yet while no two systems are alike, most tribal EMS providers face similar challenges.
HIF-1α dysfunction in diabetes (2010)

Diabetic wounds are a significant public health burden, with slow or nonhealing diabetic foot ulcers representing the leading cause of non-traumatic lower limb amputation in developed countries. These wounds heal poorly as a result of compromised blood vessel formation in response to ischemia. We have recently shown that this impairment in neovascularization results from a high glucose-induced defect in transactivation of hypoxia-inducible factor-1alpha (HIF-1alpha), the transcription factor regulating vascular endothelial growth factor (VEGF) expression. HIF-1 dysfunction is the end result of reactive oxygen species-induced modification of its coactivator p300 by the glycolytic metabolite methylglyoxal. Use of the iron chelator-antioxidant deferoxamine (DFO) reversed these effects and normalized healing of humanized diabetic wounds in mice. Here, we present additional data demonstrating that HIF-1alpha activity, not stability, is impaired in the high glucose environment. We demonstrate that high glucose-induced impairments in HIF-1alpha transactivation persist even in the setting of constitutive HIF-1alpha protein overexpression. Further, we show that high glucose-induced hydroxylation of the C-terminal transactivation domain of HIF-1alpha (the primary pathway regulating HIF-1alpha/p300 binding) does not alter HIF-1alpha activity. We extend our study of DFO's therapeutic efficacy in the treatment of impaired wound healing by demonstrating improvements in tissue viability in diabetic mice with DFO-induced increases in VEGF expression and vascular proliferation. Since DFO has been in clinical use for decades, the potential of this drug to treat a variety of ischemic conditions in humans can be evaluated relatively quickly.
Identification of a New Peptide for Fibrosarcoma Tumor Targeting and Imaging In Vivo (2010)

A 12-mer amino acid peptide SATTHYRLQAAN, denominated TK4, was isolated from a phage-display library with fibrosarcoma tumor-binding activity. In vivo biodistribution analysis of TK4-displaying phage showed a significant increased phage titer in implanted tumor up to 10-fold in comparison with normal tissues after systemic administration in mouse. Competition assay confirmed that the binding of TK4-phage to tumor cells depends on the TK4 peptide. Intravenous injection of (131)I-labeled synthetic TK4 peptide in mice showed a tumor retention of 3.3% and 2.7% ID/g at 1- and 4-hour postinjection, respectively. Tumor-to-muscle ratio was 1.1, 5.7, and 3.2 at 1-, 4-, and 24-hour, respectively, and tumors were imaged on a digital γ-camera at 4-hour postinjection. The present data suggest that TK4 holds promise as a lead structure for tumor targeting, and it could be further applied in the development of diagnostic or therapeutic agent.
The hydrolysis of maleimide in alkaline solution (1976)

The hydrolysis of maleimide has been investigated in the pH range 8.5–14. Polarographic limiting currents were well-defined, so that the bulk concentration of reactant during reduction could be clearly followed as a function of time. Logarithmic analysis of derived data indicated an arrest in the rate of reaction at circa pH 12, and a reaction scheme is proposed to explain this. In this scheme, the neutral maleimide molecule exists in equilibrium with its anion, and both of these species may undergo hydrolysis at the appropriate pH. From derived rate equations, the pK a of maleimide was found to be 10.0, whilst estimates of the rates of hydrolysis were also calculated.
Cramming More Sequencing Reactions onto Microreactor Chips (2007)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCramming More Sequencing Reactions onto Microreactor ChipsJohn H. Leamon and Jonathan M. RothbergView Author Information RainDance Technologies, Inc., 530 Whitfield Street, Guilford, Connecticut 06437, and The Rothberg Institute for Childhood Diseases, 530 Whitfield Street, Guilford Connecticut 06437 Cite this: Chem. Rev. 2007, 107, 8, 3367–3376Publication Date (Web):July 10, 2007Publication History Received19 December 2006Published online10 July 2007Published inissue 1 August 2007https://doi.org/10.1021/cr068297sCopyright © 2007 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1072Altmetric-Citations13LEARN 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 InReddit Read OnlinePDF (281 KB) Get e-AlertsSUBJECTS:Genetics,Homopolymers,Monomers,Peptides and proteins,Quality management Get e-Alerts