gebhart/patrepeval huggingface dataset:
West Nile Virus in Brazil (2021)

<i>Background:</i> West Nile virus (WNV) was first sequenced in Brazil in 2019, when it was isolated from a horse in the Espírito Santo state. Despite multiple studies reporting serological evidence suggestive of past circulation since 2004, WNV remains a low priority for surveillance and public health, such that much is still unknown about its genomic diversity, evolution, and transmission in the country. <i>Methods:</i> A combination of diagnostic assays, nanopore sequencing, phylogenetic inference, and epidemiological modeling are here used to provide a holistic overview of what is known about WNV in Brazil. <i>Results:</i> We report new genetic evidence of WNV circulation in southern (Minas Gerais, São Paulo) and northeastern (Piauí) states isolated from equine red blood cells. A novel, climate-informed theoretical perspective of the potential transmission of WNV across the country highlights the state of Piauí as particularly relevant for WNV epidemiology in Brazil, although it does not reject possible circulation in other states. <i>Conclusion:</i> Our output demonstrates the scarceness of existing data, and that although there is sufficient evidence for the circulation and persistence of the virus, much is still unknown on its local evolution, epidemiology, and activity. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics with spill-over potential to humans.
Successful treatment of SAPHO syndrome with zoledronic acid (2004)

The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a chronic, relapsing, inflammatory condition with skin and osteoarticular manifestations. Its etiology remains unclear, and various treatment regimens with steroids and nonsteroidal antiinflammatory drugs frequently fail to control the disease, while exposing patients to the side effects of these drugs. Because the SAPHO syndrome manifests as a destructive inflammatory bone disease, use of bisphosphonates that possess antiosteoclastic and probably antiinflammatory properties has been suggested to be helpful. To our knowledge, this is the first reported case of successful treatment with zoledronic acid of SAPHO syndrome that was resistant to conventional treatment.
[Temporary sacral and tibial neuromodulation in treating patients with overactive urinary bladder]. (2002)

The effects of temporary sacral (S3) stimulation and posterior tibial nerve stimulation were studied in patients with the overactive urinary bladder. Unilateral temporal (10 days) electrical stimulation of the S3 sacral spinal nerve (32 patients) and posterior tibial nerve stimulation (18 patients) were used to treat this abnormality. There was a decrease in the average frequency of voiding, in the number of leakage episodes and used pads per day after both stimulations. An over 50% symptomatic improvement was achieved in 19 of the 32 patients and after temporary sacral (S3) stimulation and in 14 of the patients following posterior tibial nerve stimulation. Neuromodulation is an effective treatment in patients with the overactive bladder.
Oxygen Tension of Healing Fractures in the Rabbit (1972)

True appreciation of the structure and function of the knee joint meniscus is a relatively recent occurrence. Even decades after studies were published documenting the detrimental effects of meniscectomoy such as osteoarthritis, many physicians continued to advocate total meniscectomy for even minor meniscal pathology. Fortunately, the clinical approach to these problems has undergone dramatic change over the past 20 years. A review of the anatomy and ultrastructure of the meniscus, and its relationship to normal function in terms of load transmission, shock absorption, joint stability, lubrication, and nutrition will enable a better understanding of the rationale for meniscus preservation techniques, including meniscal repair and meniscal transplant.
Structural models for the cell surface Lipooligosaccharides ofNeisseria gonorrhoeae andHaemophilus influenzae (1990)

A structural model is proposed for the surface glycolipids, or lipooligosaccharides (LOS), of gram-negative pathogenic bacteria that colonize human mucosae, e.g. Neisseria gonorrhoeae and Haemophilus influenzae. The development of this model has involved analysis of a series of pyocin-resistant mutants with altered LOS and other recent immunochemical and structural data. A comprehensive approach to determining the necessary structural data has been constructed that utilizes liquid secondary ion mass spectrometry, tandem mass spectrometry, methylation analysis and nuclear magnetic resonance. To prepare purified oligosaccharides for these analyses, chromatographic and chemical techniques have been developed that include high-pH anion-exchange chromatography of underivatized oligosaccharides and reverse-phase chromatography after derivatization with hydrazino alkyl benzoates. The proposed LOS model has several unique features that distinguish it from models developed for the lipopolysaccharides of enteric bacteria. This information should lead to an understanding of the unique structure/function relationship of LOS and to the development of carbohydrate-based vaccines.
Vaccinia Virus 15-Kilodalton (A14L) Protein Is Essential for Assembly and Attachment of Viral Crescents to Virosomes (1998)

Early stages in vaccinia virus (VV) assembly involve the recruitment of cellular membranes from the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) to virus factories (or virosomes). The key viral factors involved in this process are not yet known. We have previously identified and characterized two viral proteins, of 21 kDa (A17L gene) and 15 kDa (A14L gene), that associate with tubulovesicular elements related to the ERGIC and are localized in viral membranes at all stages of virion assembly. We showed that the 21-kDa protein is not responsible for the recruitment of membranes from the ERGIC to viral factories. However, it appears to be essential for the organization of viral membranes. In this investigation we have generated a VV recombinant, VVindA14L, in which the expression of the A14L gene is inducibly regulated by the Escherichia coli lacI operator-repressor system. Repression of 15-kDa protein synthesis has a dramatic effect on virus yields and severely impairs plaque formation. Compared to wild-type VV, reduced amounts of 15-kDa protein are produced in VVindA14L-infected cells in the presence of IPTG (isopropyl-beta-D-thiogalactoside), and this correlates with a small-plaque phenotype and reduced VVindA14L yields under these conditions. In the absence of the 15-kDa protein, early and late viral protein syntheses proceed normally; however, proteolytic cleavage of the major core precursors is inhibited. Electron microscopic examination of cells infected with VVindA14L under nonpermissive conditions reveals the presence of numerous membranous elements that look like unfinished or disassembled crescents interspersed between electron-dense masses. These abnormal membrane elements are usually well separated from the surfaces of the dense structures. These findings show that the 15-kDa protein is essential for VV morphogenesis and indicate that this polypeptide is necessary both for the correct assembly of viral crescents and for their stable attachment to the surfaces of viral factories.
In Vitro and in Vivo Evaluation of Doxorubicin Conjugates with the Divalent Peptide E-[c(RGDfK)2] that Targets Integrin αvβ3 (2008)

Integrins, especially integrin alpha vbeta3, are attractive receptors for vascular targeting strategies. Recently, a divalent RGD peptidomimetic, E-[c(RGDfK)2], has been described that demonstrates increased uptake in human ovarian carcinoma OVCAR-3 xenograft tumors. Inspired by these results, we set out to develop doxorubicin conjugates with E-[c(RGDfK)2] by binding two different maleimide derivatives of doxorubicin to E-[c(RGDfK)2] that was thiolated with iminothiolane. In this way, two water-soluble derivatives were obtained, E-[c(RGDfK)2]-DOXO-1 and E-[c(RGDfK)2]-DOXO-2. In E-[c(RGDfK)2]-DOXO-1, doxorubicin was bound to the peptide through a stable amide bond, and in E-[c(RGDfK)2]-DOXO-2, a MMP-2/MMP-9 cleavable octapeptide was introduced between doxorubicin and the peptide. The rationale for a MMP-2/MMP-9-cleavable linker was that MMP-2 and MMP-9 bind to integrin alpha vbeta3 and both are overexpressed in tumor vasculature. In addition, analogous control doxorubicin-containing peptides bearing c(RADfK) that does not bind to integrin alpha vbeta3 were synthesized, i.e., c(RADfK)-DOXO-1 and c(RADfK)-DOXO-2. Whereas E-[c(RGDfK) 2]-DOXO-2 was cleaved effectively by MMP-2 and in OVCAR-3 tumor homogenates releasing a doxorubicin-tetrapeptide or doxorubicin as the final cleavage product, no release of doxorubicin was observed for E-[c(RGDfK)2]-DOXO-1. Proliferation of HUVEC in the presence of MMP-2-cleavable doxorubicin-containing peptides exhibited 6- to 10-fold increased inhibition compared to the amide-linked doxorubicin-containing peptides. In addition, inhibition of HUVEC sprouting during a 24 h exposure was approximately 3-fold stronger for E-[c(RGDfK) 2]-DOXO-2 and 20-fold stronger for the reference peptide conjugate c(RADfK)-DOXO-2 than for doxorubicin alone. In vivo studies in an OVCAR-3 xenograft model demonstrated no or only moderate antitumor efficacy for either E-[c(RGDfK)2], E-[c(RGDfK)2]-DOXO-1, E-[c(RGDfK)2]-DOXO-2, or c(RADfK)-DOXO-2, even at doses of 3 x 24 mg/kg doxorubicin equivalents, compared to an improved antitumor effect for doxorubicin at 2 x 8 mg/kg.
Towards a CIM Schema for RunTime Application Management (2001)

We describe new extensions to the Core, Application and System Schemas of the Common Information Model (CIM). While previous work on the CIM Application Schema mainly dealt with the distribution, deployment and installation aspects of software, a recent effort within the Distributed Management Task Force (DMTF) is targeted at defining schema extensions capable of dealing with the full lifecycle of distributed applications, especially the runtime stage. These application runtime extensions are currently developed by the DMTF Application Working Group in which the authors actively participate. In order to serve as a basis for a runtime model of distributed applications, various extensions had to be applied to the existing schemas. These schema extensions, described in this paper, have been adopted by the CIM Technical Committee and are part of the recently released version 2.5 of the CIM schema.
Anterior Inferior Iliac Spine Morphology Correlates With Hip Range of Motion: A Classification System and Dynamic Model (2013)

When the AIIS is classified into three variants based on the relationship between the AIIS and the acetabular rim in patients with impingement, Type II and III variants are associated with a decrease in hip flexion and internal rotation, supporting the rationale for considering AIIS decompression for variants that extend to and below the rim.
Immunoactive chimeric ST‐LT enterotoxins of Escherichia coli generated by in vitro gene fusion (1986)

Two different lengths of the gene encoding Escherichia coli heat-stable toxin (STa) were fused to the carboxy end of the gene coding for the E. coli heat-labile toxin A-subunit (LTA). The hybrid genes directed expression of chimeric LTA-STa proteins. Association of these chimeras with native heat-labile toxin B-subunit (LTB) resulted in protein complexes that bound to GM1 ganglioside and thereby could be assayed in a GM1 ELISA. The complexes reacted with monoclonal antibodies against either LTA, LTB or STa indicating that the STa and LT epitopes remained immunologically intact after fusion. Genetically constructed chimeric proteins exhibiting LT and STa antigens on the same molecule may represent a promising approach to development of broadly protective immunoprophylactic agents and/or useful immunodiagnostic reagents for diarrhoeal diseases caused by enterotoxinogenic E. coli.
Clinical and Etiological Profile of Heart Failure Patients (2014)

This study was undertaken to study the clinical and etiological profile of patients with heart failure at Mamata General Hospital, Khammam. This is a study of clinical and etiological profile of heart failure in patients of above 15 years of age, who were admitted in Mamata Medical College during the period December 2012 to November 2013. The incidence of heart failure (HF) in Mamata General Hospital is less compared to other cardiovascular diseases. The common age group for HF is between 45 and 65 years. The commonest cause of HF is ischemic heart disease (IHD) followed by HTN combined with IHD and then dilated cardiomyopathy (DCM). Other causes of HF are RHD, anemia, cor pulmonale, muscular dystrophy, and chronic renal failure. 2D Echo is essential for diagnosis and assessment of prognosis of HF. It is useful in IHD for showing regional wall motion abnormality and ejection fraction. It is also helpful in assessing the severity of valvular lesions. Keywords: Cardiomyopathy, ischemic heart disease, anemia, hypertension
Generation of protein isoform diversity by alternative initiation of translation at non‐AUG codons (2003)

The use of several translation initiation codons in a single mRNA, by expressing several proteins from a single gene, contributes to the generation of protein diversity. A small, yet growing, number of mammalian mRNAs initiate translation from a non-AUG codon, in addition to initiating at a downstream in-frame AUG codon. Translation initiation on such mRNAs results in the synthesis of proteins harbouring different amino terminal domains potentially conferring on these isoforms distinct functions. Use of non-AUG codons appears to be governed by several features, including the sequence context and the secondary structure surrounding the codon. Selection of the downstream initiation codon can occur by leaky scanning of the 43S ribosomal subunit, internal entry of ribosome or ribosomal shunting. The biological significance of non-AUG alternative initiation is demonstrated by the different subcellular localisations and/or distinct biological functions of the isoforms translated from the single mRNA as illustrated by the two main angiogenic factor genes encoding the fibroblast growth factor 2 (FGF2) and the vascular endothelial growth factor (VEGF). Consequently, the regulation of alternative initiation of translation might have a crucial role for the biological function of the gene product.
John Daly Lecture: Structure-guided Drug Design for Adenosine and P2Y Receptors (2014)

We establish structure activity relationships of extracellular nucleosides and nucleotides at G protein-coupled receptors (GPCRs), e.g. adenosine receptors (ARs) and P2Y receptors (P2YRs), respectively. We synthesize selective agents for use as pharmacological probes and potential therapeutic agents (e.g. A3AR agonists for neuropathic pain). Detailed structural information derived from the X-ray crystallographic structures within these families enables the design of novel ligands, guides modification of known agonists and antagonists, and helps predict polypharmacology. Structures were recently reported for the P2Y12 receptor (P2Y12R), an anti-thrombotic target. Comparison of agonist-bound and antagonist-bound P2Y12R indicates unprecedented structural plasticity in the outer portions of the transmembrane (TM) domains and the extracellular loops. Nonphosphate-containing ligands of the P2YRs, such as the selective P2Y14R antagonist PPTN, are desired for bioavailability and increased stability. Also, A2AAR structures are effectively applied to homology modeling of closely related A1AR and A3AR, which are not yet crystallized. Conformational constraint of normally flexible ribose with bicyclic analogues increased the ligand selectivity. Comparison of rigid A3AR agonist congeners allows the exploration of interaction of specific regions of the nucleoside analogues with the target and off-target GPCRs, such as biogenic amine receptors. Molecular modeling predicts plasticity of the A3AR at TM2 to accommodate highly rigidified ligands. Novel fluorescent derivatives of high affinity GPCR ligands are useful tool compounds for characterization of receptors and their oligomeric assemblies. Fluorescent probes are useful for characterization of GPCRs in living cells by flow cytometry and other methods. Thus, 3D knowledge of receptor binding and activation facilitates drug discovery.
Cell Cycle Analysis by Flow Cytometry (2014)

Abstract Flow cytometry, the methodology that provides a way to measure physical and chemical attributes of individual cells rapidly and with high accuracy, is widely used in cell cycle analysis. The most common assays are: univariate analysis of cellular deoxyribonucleic acid (DNA) content discloses frequencies of cells in G 0/1 , S and G 2 /M phases; bivariate analysis of DNA versus ribonucleic acid (RNA) content reveals frequencies of G 0 , G 1 , S and G 2 M cells, of DNA content versus histone H3 phosphorylated on Ser10 defines frequencies of G 0/1 , S, G 2 and M cells. Detection of cells that incorporated DNA precursor, such as 5‐bromo‐2′‐deoxyuridine (BrdU) or 5‐ethynyl‐2′‐deoxyuridine (EdU) identifies cells that replicated DNA. Immunocytochemical detection of cyclin D1, cyclin E, Cyclin A and cyclin B1 concurrent with DNA content reveals the proteins that are essential for driving the cell through the cell cycle. The stathmokinetic approach makes it possible to assess the kinetics of progression through the cell cycle. Key Concepts: Cellular DNA content identifies cell position in the cell cycle. Fractional cellular DNA content (‘sub‐G 1 ’ cells) is a marker of apoptotic cells. Low cellular RNA content is a biomarker of G 0 (quiescent) cells. Incorporation of BrdU or EdU identifies DNA replication cells. Phosphorylation of histone H3 on Ser10 is a marker of mitotic cells. Detection of cyclin proteins is a marker of cell progression machinery. Stathmokinetic approach based on cell arrest in metaphase makes it possible to assess the entry of cells to mitosis (‘mitotic rate’, ‘cell birth rate’) and reveals kinetics of cell progression through the cycle.
Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington’s disease pathology (1999)

Huntington's disease is a progressive neurodegenerative disorder caused by a polyglutamine [poly(Q)] repeat expansion in the first exon of the huntingtin protein. Previously, we showed that N-terminal huntingtin peptides with poly(Q) tracts in the pathological range (51-122 glutamines), but not with poly(Q) tracts in the normal range (20 and 30 glutamines), form high molecular weight protein aggregates with a fibrillar or ribbon-like morphology, reminiscent of scrapie prion rods and beta-amyloid fibrils in Alzheimer's disease. Here we report that the formation of amyloid-like huntingtin aggregates in vitro not only depends on poly(Q) repeat length but also critically depends on protein concentration and time. Furthermore, the in vitro aggregation of huntingtin can be seeded by preformed fibrils. Together, these results suggest that amyloid fibrillogenesis in Huntington's disease, like in Alzheimer's disease, is a nucleation-dependent polymerization.
Anomalous Concentration Effects of Zwitterionic Telechelic Polymer Solutions in Electric Fields (2002)

Transient electric birefringence (TEB) measurements have been made on a number of low molecular weight (4.8×103, 14.4×103 and 34.7×103 g·mol–1) α,ω-Zwitterionic telechelic polystyrene (ZT-PS) in dilute cyclohexanone solutions. Anomalous birefringence has been observed with a distinctive change in sign of the overall birefringence at a critical concentration, c*. From the analysis of the relaxation behaviour in terms of a bead-spring model chain dimensions and diffusion coefficients have been determined. These indicate that even at the lowest concentration, aggregation occurs with a transition to extended networks at c ⪈ c*.
Stability of Metal Halide Perovskite Solar Cells (2015)

In recent years, there has been an unprecedented rise in the performance of metal halide perovskite solar cells. They are now in a position to compete on performance with traditional crystalline solar cells, and as such the most pressing questions concern the long term operational stability of this class of solar cell. Here, recent developments in understanding and overcoming stability concerns of metal halide perovskite solar cells are highlighted. An overview of possible instability issues due to electrical, atmospheric, heat, and light stresses is provided and the different implications to the most commonly used device architectures are discussed.
The Diels-Alder Diene Synthesis. (1942)

ADVERTISEMENT RETURN TO ISSUEPREVArticleThe Diels-Alder Diene Synthesis.James A. NortonCite this: Chem. Rev. 1942, 31, 2, 319–523Publication Date (Print):October 1, 1942Publication History Published online1 May 2002Published inissue 1 October 1942https://pubs.acs.org/doi/10.1021/cr60099a003https://doi.org/10.1021/cr60099a003research-articleACS PublicationsRequest reuse permissionsArticle Views4306Altmetric-Citations103LEARN 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
Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy (2015)

Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models. We show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ = 0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density, and protein/lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density, and protein/lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery.