gebhart/patrepeval huggingface dataset:
Herpesviruses of birds ‐ a review (1990)

The family of herpesviridae is divided into the subfamilies alpha-, beta- and gammaherpesvirinae. Members of the alphaherpesvirinae (infectious laryngo-tracheitis in gallinaceous birds and duck viral enteritis in waterfowl) may cause substantial economic and ecological losses. Marek's disease and turkey herpesviruses are the only members of the gammaherpesvirinae. Most herpesviruses from free-living and pet birds are tentatively classified as bctaherpesvirinae. These may induce diseases, with variably non-specific clinical signs but including respiratory distress, ocular lesions, enteritis and liver involvement. Prominent pathological lesions consist either of haemorrhages on respiratory or intestinal epithelium or of multi-focal necrotic lesions in livers, spleen and bone marrow. At least four different plaque types of betaherpersvirinae can be differentiated in infected chick embryo fibroblasts or chick kidney cell cultures. Infectivity may be cell-associated or detectable in supernatant fluids and transformed cultured cells. All avian herpesviruses are presently grouped on the basis of results of cross neutralisation tests into 11 different serotypes.
Infarct size limitation: Acute N‐acetylcysteine defense (ISLAND trial): Preliminary analysis and report after the first 30 patients (1996)

Our previous experimental research and initial clinical observations regarding the use of N-acetylcysteine in the treatment of ischemic and reperfusion injury in acute myocardial infarction gave rise to a study entitled the Infarct Size Limitation: Acute N-acetylcysteine Defense (ISLAND) trial. Today, this randomized, echocardiographically and angiographically controlled study includes the first 30 patients with a first anterior wall myocardial infarction: Group A (n = 10) consisting of patients with successful recanalization of the infarct-related left anterior descending artery by streptokinase without any further treatment, Group B (n = 10) consisting of patients with failed infarct-related artery recanalization, and Group C (n = 10) comprising patients who had successful streptokinase-induced recanalization of the left anterior descending artery plus N-acetylcysteine administration at a dose of 100 mg/kg body weight. The parameters monitored in our study include changes in global and regional left ventricular ejection fraction of the infarct-related segment using echocardiography and, using electrocardiograms and the Wagner QRS scoring system, the amounts of acutely jeopardized and finally infarcted myocardium. In Group A, global left ventricular ejection fraction rose nonsignificantly within 2 weeks from 37.5 +/- 9.6% to 38.5 +/- 13.8%; it declined significantly in Group B from 36.2 +/- 6.1% to 30.1 +/- 6.7% (p < 0.05), while it considerably improved in Group C from 41.7 +/- 4.1% to 59.6 +/- 8.1% (p < 0.001). Regional left ventricular ejection fraction changed significantly only in Group C: from -4.5 +/- 27.3 to 45.6 +/- 16.3 (p < 0.001). In Group A, in which the amount of acutely jeopardized myocardium was 21.7 +/- 7.2, infarction actually occurred in 20.4 +/- 9.7% (practically no myocardial salvage). In Group B, risk area was 18.1 +/- 4.3%, but infarct size rose to a resulting 29.1 +/- 6.0%. Significant myocardial salvage was accomplished only in Group C: of 26.2 +/- 8.1% of jeopardized myocardium, infarct size was reduced to 10.8 +/- 7.1% (salvage by 58.8%). Also, basic division of patients by therapy showed that, although those with nonidentical findings on their coronary arteries were included into the same groups, patients treated with streptokinase plus N-acetylcysteine had significantly more favorable values of the monitored parameters than those treated with streptokinase alone. We conclude our interim analysis suggests that N-acetylcysteine has a beneficial effect, reducing the functional and structural impacts of myocardial infarction.
An evolved ribosome-inactivating protein targets and kills human melanoma cells in vitro and in vivo (2010)

These results demonstrate that the evolution of a scRIP template can lead to the discovery of novel cancer cell-targeted compounds and in the case of SLT-1A IYSNKLM can specifically kill human melanoma cells in vitro and in vivo.
In Vivo Adenovirus-Mediated Gene Transfer Via the Pulmonary Artery of Rats (1995)

Gene transfer into the pulmonary vasculature has the potential to be a powerful technique for both investigation of pulmonary pathophysiology and development of genetic therapies for pulmonary vascular disease. To evaluate the potential for in vivo pulmonary arterial gene transfer, we infused adenoviral vectors into the left pulmonary artery of Sprague-Dawley and cotton rats. Access to the left pulmonary artery was obtained by a percutaneous transcatheter approach or through thoracotomy and pulmonary arteriotomy. With the thoracotomy approach, both pulmonary arterial inflow and pulmonary venous outflow were occluded during vector influsion and throughout a subsequent 20-minute dwell period. The success of gene transfer was assessed by staining for evidence of recombinant gene expression in lungs excised at time points ranging from 48 to 72 hours after virus infusion. With the thoracotomy technique, pulmonary gene transfer was successful in 15% of surviving Sprague-Dawley rats and 30% of surviving cotton rats. Percutaneous catheter-based pulmonary gene transfer was not successful. In rats with pulmonary gene transfer, 1% to 8% of total left lung cells expressed the recombinant gene. Recombinant gene expression was found in endothelial cells (0.2% to 18% of total transduced cells), smooth muscle cells (0% to 3%), macrophages (1% to 7%), airway epithelial cells (2% to 50%), and alveolar epithelial cells (38% to 94%). Investigation of the low rate of successful gene transfer in individual animals suggested that insufficient physical contact between the virions and pulmonary cells was the most likely cause. In vivo gene transfer into the rat pulmonary vasculature can be accomplished with adenovirus vectors.(ABSTRACT TRUNCATED AT 250 WORDS)
Canadian Association of Gastroenterology Position Statement: Fecal Microbiota Transplant Therapy (2014)

The increasing public interest in fecal microbiota transplant (FMT) raises serious concerns, when the application of this treatment is still in its infancy and long-term safety is not yet established. Indeed, there is evidence that anecdotal reports of success from initial results of uncontrolled studies are encouraging patients to try this line of treatment in the absence of medical direction or supervision. It is important that medical practitioners, the media and the general public are made aware of the safety issues involved in ‘stool transplant’. While FMT has been widely used in veterinary practice and the exchange of intestinal contents in humans is documented back to the fouth century (1), this intervention requires the exchange of body fluids with all its known and unknown risks. In the early 1980s in Canada, tainted blood and blood products for the treatment of hemophilia led to the serious outbreak of hepatitis C and HIV (2). The stool microbiome is complex, containing, bacterial, viral and fungal components in addition to prions and potentially unknown biologically active substances (3,4). Several excellent studies have indicated the important role of the microbiome in a variety of diseases. In addition to Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD), these include obesity, diabetes and behavioural disorders (5). There is an urgent requirement for further careful prospective and controlled research in a variety of these diseases but especially to protect the safety of patients who, understandably, may be frustrated with the poor efficacy of their current treatments. Here, we consider the evidence for the use of FMT in resistant C difficile infection and its current status as an intervention in IBD, together with a brief summary of the current evidence for the safety of FMT and recommendations for the future.
ChEMBL: a large-scale bioactivity database for drug discovery (2011)

ChEMBL is an Open Data database containing binding, functional and ADMET information for a large number of drug-like bioactive compounds. These data are manually abstracted from the primary published literature on a regular basis, then further curated and standardized to maximize their quality and utility across a wide range of chemical biology and drug-discovery research problems. Currently, the database contains 5.4 million bioactivity measurements for more than 1 million compounds and 5200 protein targets. Access is available through a web-based interface, data downloads and web services at: https://www.ebi.ac.uk/chembldb.
Sparse matrix solvers on the GPU (2005)

Many computer graphics applications require high-intensity numerical simulation. We show that such computations can be performed efficiently on the GPU, which we regard as a full function streaming processor with high floating-point performance. We implemented two basic, broadly useful, computational kernels: a sparse matrix conjugate gradient solver and a regular-grid multigrid solver. Real time applications ranging from mesh smoothing and parameterization to fluid solvers and solid mechanics can greatly benefit from these, evidence our example applications of geometric flow and fluid simulation running on NVIDIA's GeForce FX.
Synthesis and Pharmacology of Proteasome Inhibitors (2013)

Shortly after the discovery of the proteasome it was proposed that inhibitors could stabilize proteins which ultimately would trigger apoptosis in tumor cells. The essential questions were whether small molecules would be able to inhibit the proteasome without generating prohibitive side effects and how one would derive these compounds. Fortunately, "Mother Nature" has generated a wide variety of natural products that provide distinct selectivities and specificities. The chemical synthesis of these natural products finally provided access to analogues and optimized drugs of which two different classes have been approved for the treatment of malignancies. Despite these achievements, additional lead structures derived from nature are under investigation and will be discussed with regard to their biological potential and chemical challenges.
Synthesis of Symmetrical Tetraaryltetranaphtho[2,3]porphyrins (2005)

A new method of synthesis of meso-tetraaryltetranaphtho[2,3]porphyrins (Ar4TNP) has been developed. Ar4TNPs with peripheral functional groups are obtained by oxidative aromatization of meso-tetraarylporphyrins in which pyrrole units are fused with either octahydro- or dihydronaphthalene moieties. These precursor porphyrins are synthesized in four to five steps from readily available starting materials, such as naphthalene or 1,4-benzoquinone. The pathway originating in dihydronaphthalene, i.e., the "dialine" route, was found to be superior to the alternative "octaline"route in that it (1) enables the shortening of the overall reaction sequence, (2) has a broader scope in terms of the peripheral substitution in Ar4TNPs, and (3) affords higher yields of the target porphyrins. Pd complexes of the synthesized Ar4TNPs exhibit remarkably strong absorption bands at 710-720 nm (epsilon approximately 200,000 M(-1) cm(-1)) and phosphoresce at room temperature with moderate quantum yields (phi = 2-3%, lambda(max) = 900-1000 nm). The absorption maxima of naphthoporphyrins substituted with eight methoxy groups (Ar4TNP(OMe)8) were found to be about 15-20 nm red shifted compared to the corresponding maxima of unsubstituted Ar4TNPs. The X-ray crystallographic data suggest that these spectral shifts are caused not by the differences in nonplanar distortions of the macrocycles but by the purely electronic effects of the substituents.
Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors (2017)

Stem cell-based therapy for type 1 diabetes would benefit from implementation of a cell purification step at the pancreatic endoderm stage. This would increase the safety of the final cell product, allow the establishment of an intermediate-stage stem cell bank, and provide a means for upscaling β cell manufacturing. Comparative gene expression analysis revealed glycoprotein 2 (GP2) as a specific cell surface marker for isolating pancreatic endoderm cells (PECs) from differentiated hESCs and human fetal pancreas. Isolated GP2<sup>+</sup> PECs efficiently differentiated into glucose responsive insulin-producing cells in vitro. We found that in vitro PEC proliferation declines due to enhanced expression of the cyclin-dependent kinase (CDK) inhibitors CDKN1A and CDKN2A. However, we identified a time window when reducing CDKN1A or CDKN2A expression increased proliferation and yield of GP2<sup>+</sup> PECs. Altogether, our results contribute tools and concepts toward the isolation and use of PECs as a source for the safe production of hPSC-derived β cells.
Sequence and structural determinants of human APOBEC3H deaminase and anti-HIV-1 activities (2015)

The molecular and biological activities of A3H are more similar to those of the double-domain A3 proteins than to those of A3A or A3C. Importantly, A3H appears to use both deaminase-dependent and -independent mechanisms to target reverse transcription and restrict HIV-1 replication.
Naturally Occurring Autoantibodies against β-Amyloid: Investigating Their Role in Transgenic Animal andIn VitroModels of Alzheimer's Disease (2011)

Alzheimer's disease (AD) is a neurodegenerative disorder primarily affecting regions of the brain responsible for higher cognitive functions. Immunization against β-amyloid (Aβ) in animal models of AD has been shown to be effective on the molecular level but also on the behavioral level. Recently, we reported naturally occurring autoantibodies against Aβ (NAbs-Aβ) being reduced in Alzheimer's disease patients. Here, we further investigated their physiological role: in epitope mapping studies, NAbs-Aβ recognized the mid-/C-terminal end of Aβ and preferentially bound to oligomers but failed to bind to monomers/fibrils. NAbs-Aβ were able to interfere with Aβ peptide toxicity, but NAbs-Aβ did not readily clear senile plaques although early fleecy-like plaques were reduced. Administration of NAbs-Aβ in transgenic mice improved the object location memory significantly, almost reaching performance levels of wild-type control mice. These findings suggest a novel physiological mechanism involving NAbs-Aβ to dispose of proteins or peptides that are prone to forming toxic aggregates.
Collaborative iIslet Transplant Registry. (2003)

The Collaborative Islet Transplant Registry (CITR) was established in 2001 with support from the National Institute of Diabetes and Digestive Diseases to collect and analyze information on islet transplants in North America. Thirteen of 27 invited islet transplant centers from the United States and Canada were already participants as of January 2004 with 5 additional centers awaiting IRB approval. In October 2003, CITR had preliminary data on 58 recipients of 107 islet transplants performed at the 13 member centers. These islet recipients averaged 41 years of age (SD 8.9), had diabetes for almost 28 years (SD 10.2) and were predominantly (67%) female. Islets were procured from 118 deceased donors whose average age was 42 (SD 12.2), weight was 90 kg (SD 23.5), and BMI was 30.5 (SD 7.9). The time from cross-clamp to pancreas recovery averaged 56 minutes (SD 134.6). An average of 7,127 islets (SD 2,973) were infused per kg of the recipient's weight. Outcome data are still pending as the Registry prepares its first annual report. Here we describe the organization, goals and design of the data collection instruments for CITR.
Rapid development and delivery of converged services using APIs (2002)

To what extent will the emerging set of application programming interfaces (APIs), and environments that provide these APIs, support the vision of rapid service development for converged networks? In this paper, we report on lessons learned, both through participation in standards bodies and from recent prototyping using some of these APIs. We describe four API environments: Telecommunications Service Access and Subscription (TSAS), Parlay, Third-Generation Partnership Project (3GPP), and Java <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∗</sup> APIs for Integrated Networks (JAIN <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∗</sup> ). We then discuss how these API environments address several issues key to rapid service development and deployment.
Role of the Nuclear Localization Sequence in Fibroblast Growth Factor-1-stimulated Mitogenic Pathways (1996)

Fibroblast growth factor-1 (FGF-1) is a potent mitogen for mesoderm- and neuroectoderm-derived cell types in vitro. However, a mutant FGF-1 with deletion in its nuclear localization sequence (NLS, residues 21-27) is not mitogenic in vitro. We demonstrated that synthetic peptides containing this NLS were able to stimulate DNA synthesis in a FGF receptor-independent manner after they were delivered into living NIH 3T3 cells by a cell-permeable peptide import technique. The stimulation of maximal DNA synthesis by these peptides required the presence of peptides during the entire G1 phase of the cell cycle. The mitogenic effect was specific for the NLS of FGF-1 because a peptide with double point mutations at lysine residues was inactive in stimulating DNA synthesis. Our results suggest that the NLS plays an important role in the mitogenic pathway initiated by exogenous FGF-1 by its direct involvement in the nuclear transport and signaling of internalized FGF-1.
Single nucleotide polymorphism determination using primer extension and time-of-flight mass spectrometry (1999)

The high frequency of single nucleotide polymorphisms (SNPs) in the human genome makes them a valuable source of genetic markers for identity testing, genome mapping, and medical diagnostics. Conventional technologies for detecting SNPs are laborious and time-consuming, often prohibiting large-scale analysis. A rapid, accurate, and cost-effective method is needed to meet the demands of a high-throughput DNA assay. We demonstrate here that analysis of these genetic markers can now be performed routinely in a rapid, automated, and high-throughput fashion using time-of-flight mass spectrometry and a primer extension assay with a novel cleavable primer. SNP genotyping by mass spectrometry involves detection of single-base extension products of a primer immediately adjacent to the SNP site. Measurement of the mass difference between the SNP primer and the extension peak reveals which nucleotide is present at the polymorphic site. The primer is designed such that its extension products can be purified and chemically released from the primer in an automated format. The reduction in size of the products as a result of this chemical cleavage allows more accurate identification of the polymorphic base, especially in samples from a heterozygotic population. All six possible heterozygotes are resolved unambiguously, including an A/T heterozygote with extension products differing by only 9 Da. Multiplex SNP determination is demonstrated by simultaneously probing multiple SNP sites from a single polymerase chain reaction (PCR) product as well as from multiplexed PCR amplicons. Samples are processed in parallel on a robotic workstation, and analyzed serially in an automated mass spectrometer with analysis times of only a few seconds per sample, making it possible to process thousands of samples per day.
Novel naphthalenic ligands with high affinity for the melatonin receptor (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel naphthalenic ligands with high affinity for the melatonin receptorS. Yous, J. Andrieux, H. E. Howell, P. J. Morgan, P. Renard, B. Pfeiffer, D. Lesieur, and B. Guardiola-LemaitreCite this: J. Med. Chem. 1992, 35, 8, 1484–1486Publication Date (Print):April 1, 1992Publication History Published online1 May 2002Published inissue 1 April 1992https://pubs.acs.org/doi/10.1021/jm00086a018https://doi.org/10.1021/jm00086a018research-articleACS PublicationsRequest reuse permissionsArticle Views1402Altmetric-Citations190LEARN 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
Glyceraldehyde-3-Phosphate Dehydrogenase: A Promising Target for Molecular Therapy in Hepatocellular Carcinoma (2012)

Hepatocellular carcinoma (HCC) is one of the most highly lethal malignancies ranking as the third leading-cause of cancer-related death worldwide. Although surgical resection and transplantation are effective curative therapies, very few patients qualify for such treatments due to the advanced stage of the disease at diagnosis. In this context, loco-regional therapies provide a viable therapeutic alternative with minimal systemic toxicity. However, as chemoresistance and tumor recurrence negatively impact the success of therapy resulting in poorer patient outcomes it is imperative to identify new molecular target(s) in cancer cells that could be effectively targeted by novel agents. Recent research has demonstrated that proliferation in HCC is associated with increased glucose metabolism. The glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a multifunctional protein primarily recognized for its role in glucose metabolism, has already been shown to affect the proliferative potential of cancer cells. In human HCC, the increased expression of GAPDH is invariably associated with enhanced glycolytic capacity facilitating tumor progression. Though it is not yet known whether GAPDH up-regulation contributes to tumorigenesis sensu stricto, emerging evidence points to the existence of a link between GAPDH up-regulation and the promotion of survival mechanisms in cancer cells as well as chemoresistance. The involvement of GAPDH in several hepatocarcinogenic mechanisms (e.g. viral hepatitis, metabolic alterations) and its sensitivity to a new class of prospective anticancer agents prompted us to review the current understanding of the therapeutic potential of targeting GAPDH in HCC.