gebhart/patrepeval huggingface dataset:
Construction of a human Fab phage display library from antibody repertoires of osteosarcoma patients. (2005)

Osteosarcoma is the commonest type of primary malignant bone tumor, frequently found in adolescents at sites of rapid bone growth. Despite current management protocols, up to half of the patients succumb to this disease. Moreover, there is no well-characterized molecular marker for diagnosis and prognosis. Since phage display methodology allows the selection of human antibody fragments with potential use in clinical applications, we applied this procedure to construct a recombinant Fab (antigen binding fragment) library from patients with osteosarcoma. We used peripheral blood lymphocyte total RNA from 11 osteosarcoma patients and cloned recombinant Fab representing the micro, gamma and kappa chain antibody repertoires of these individuals. The resulting library was cloned in the pComb3X vector and attained 1.45 x 10(8) different functional forms. BstO I fingerprinting and DNA sequencing analysis of randomly selected clones revealed the diversity of the library, demonstrating that Fab harbors Vkappa chains from subgroups I to V, biased towards the A27 fragment, as normally reported for the human repertoire. Analysis of the VH repertoire revealed that our library has a slight bias towards the VH4 family, instead of the usually reported VH3. This is the first description of a phage display library from osteosarcoma patients. We believe these human Fab fragments will provide a valuable tool for the study of this neoplasia and could also contribute to improvements in the diagnosis of this disease.
Evaluation in Nonhuman Primates of Vaccines against Ebola Virus (2002)

Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90% of cases in both humans and nonhuman primates. No vaccines or treatments are available for human use. We evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal EBOV infection. The following immunogens were used: RNA replicon particles derived from an attenuated strain of Venezuelan equine encephalitis virus (VEEV) expressing EBOV glycoprotein and nucleoprotein; recombinant Vaccinia virus expressing EBOV glycoprotein; liposomes containing lipid A and inactivated EBOV; and a concentrated, inactivated whole-virion preparation. None of these strategies successfully protected nonhuman primates from robust challenge with EBOV. The disease observed in primates differed from that in rodents, suggesting that rodent models of EBOV may not predict the efficacy of candidate vaccines in primates and that protection of primates may require different mechanisms.
OPTIMAL COMBINATIONS OF SYSTEMATIC SEXTANT AND LATERALLY DIRECTED BIOPSIES FOR THE DETECTION OF PROSTATE CANCER (2001)

The standard sextant protocol failed to detect a large proportion of cancers located laterally in the peripheral zone. A 10 core biopsy regimen that combined laterally directed cores at the base, mid gland and apex of the prostate with mid lobar biopsy cores at the base and apex maximizes the sensitivity of transrectal ultrasound guided systematic biopsy.
Aberrant crypt foci. (2006)

Colon cancer evolves through epithelial cell deregulation and inappropriate proliferation. These histopathological characteristics are exemplified in the biochemical, immunohistochemical, genetic and epigenetic elements detected within colonic mucosa. Early detection is paramount for the prevention of colon cancer deaths. Aberrant crypt foci (ACF) are thought to be the earliest identifiable neoplastic lesions in the colon carcinogenetic model. The progression of ACF to polyp and, subsequently, to cancer parallels the accumulation of several biochemical alterations and mutations whereby a small fraction of ACF evolve to colon cancer. Recent data indicate that, not uncommonly, some ACF bypass the polyp stage in their carcinogenesis thus reinforcing the importance of their early detection and our understanding of their pathogenesis. Since ACF were first detected in carcinogen-treated mice, research efforts have focused on these microscopically visible lesions both in animal and human models. ACF show variable histological features, characterized by Kudo (20) and, therefore, can be grouped into differing categories by in vivo examination with high-magnification-chromoscopic-colonoscopy (HMCC). As expected, ACF are more frequently detected in distal animal and human colons coinciding with the geographic distribution of colorectal cancer (CRC). Various proteomic (Prot) markers may be altered within ACF suggesting possible prospective pathological changes. These markers include Calreticulin, Transgelin, Serotransferrin, Triphosphate isomerase and Carbonic anhydrase II. Other markers of importance include carcinoembryonic antigen (CEA), B-catenin, placental cadherin (P-cadherin), epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2) and P16INK4a. Genetic mutations of K-ras, B-Raf APC and p53 have been demonstrated in ACF as well as the epigenetic alterations of CpG island methylation. Genomic instabilities (GI), illustrated by a higher GI Index (GII), microsatellite instability (MSI), loss of heterozygosity (LOH) and defects in mismatch repair (MMR) systems, are also expressed. These transformations may lead to the identification of the earliest pathological features initiating colon tumorigenesis. In this review, the advances in ACF research as precursors of CRCs are highlighted.
Capillary electrophoresis studies on the aggregation process of β‐amyloid 1‐42 and 1‐40 peptides (2004)

Abstract The possibility to monitor, in solution, the steps of β‐amyloid (Aβ) nucleation and therefore to describe this dynamic process by using capillary electrophoresis and under optimized experimental conditions is described. Striking differences in the electrophoretic patterns of Aβ 1‐42 and Aβ 1‐40 over time are here shown, and different aggregation states are elucidated, which reflect the very diverse oligomerization behavior of two very similar peptides. The isolation of one aggregated species of high molecular weight by ultracentrifugation allowed us to assess its role as toxic oligomer. The perturbation of the existing equilibrium among the identified species by the addition of small molecules can in principle interfere with the aggregation process of the peptides and ultimately prevent the plaque formation in vitro .
New insights into anti-HER-2 receptor monoclonal antibody research. (2000)

Abnormalities in the expression, structure, or activity of proto-oncogene products contribute to the development and maintenance of the malignant phenotype. For example, c-erbB-2 encodes the HER-2 receptor (also known as c-erbB-2 or c-neu) that is overexpressed, amplified, or both in a number of human malignancies including breast, ovarian, colon, lung, prostate, and cervical cancers. In addition to deregulation of cell-surface HER receptors, cancer cells often show excessive activation and/or nonattenuation of growth factor--inducible signaling components, as well as their downstream transcription factors. Current approaches to target HER-2 pathways include downregulation of HER-2 by the adenovirus 5E1A, antisense phosphothionate oligonucleotides, ribozyme, and targeting tyrosine kinase using specific inhibitors. Because growth factors regulate the proliferation of cancer cells by activating receptors on the surface of cells, one obvious approach to control cell proliferation is to interfere with the growth factor receptor-mediated autocrine/ paracrine growth stimulation by antireceptor-blocking monoclonal antibodies. Therefore, a large number of scientists are attempting to control the growth of cancer cells using agents that inhibit one or more of the above steps of growth factor action. Recently completed clinical trials established the usefulness of a humanized form of 4DS monoclonal antibody, trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA), against some forms of breast tumors overexpressing HER-2 receptors. Using in vitro models, recent studies have shown that HER-2 overexpression may not be a prerequisite for invasion of breast cancer cells, as HER-2 activation by heregulin, which binds to HER-3 or HER-4 and transphosphorylates HER in noninvasive breast cancer cells, could lead to increased motility, enhanced gelatinolytic activity, and invasion. Furthermore, these ligand-driven phenotypic changes were completely suppressed by trastuzumab, which also blocked interactions between HER-2 and HER-3 receptors in heregulin-treated breast cancer cells, and inhibited the phosphatidylinositol-3' kinase-dependent pathway, but not the mitogen-activated protein kinase pathway. These phenotypic effects of anti-HER-2 monoclonal antibody are of special interest, because they point to potential therapeutic effects of trastuzumab in inhibiting the invasion and metastasis of breast cancer with low receptor expression.
Blockade of tachykinin NK3receptor reverses hypertension through a dopaminergic mechanism in the ventral tegmental area of spontaneously hypertensive rats (2010)

The NK(3)R in the VTA is implicated in the maintenance of hypertension by increasing midbrain dopaminergic transmission in SHR. Hence, this receptor may represent a therapeutic target in the treatment of hypertension.
The pathogenesis of beta cell destruction in type I (insulin‐dependent) diabetes mellitus (1987)

In a study of pancreases from 75 patients who died at presentation of Type I diabetes there was selective destruction of beta cells associated with islet inflammation (insulitis). According to a recent hypothesis, aberrant expression of Class II major histocompatibility complex (MHC) products on a target cell may allow presentation of organ specific surface antigen(s) to potentially autoreactive T helper lymphocytes and thus lead to autoimmunity. Aberrant expression of Class II MHC was demonstrated immunohistochemically on beta cells in 21 out of 23 patients with recent onset diabetes. No such expression was seen on the other pancreatic endocrine cells. Ninety-four per cent of insulin-containing islets in these patients had marked hyperexpressions of Class I MHC affecting all endocrine cells in these islets. Insulin deficient islets were not thus affected. Both these abnormalities of MHC expression appeared to precede insulitis within a given islet and appeared to be unique to Type I diabetes, being absent in pancreases of patients with Type II diabetes, chronic pancreatitis, cystic fibrosis, graft-versus-host disease and Coxsackie B viral pancreatitis. The development of autoimmunity to beta cells in Type I diabetes may be a 'multistep' process in which abnormalities of MHC expression are crucial events.
Structure and mechanism of a proline-specific aminopeptidase from Escherichia coli (1998)

The structure of the proline-specific aminopeptidase (EC 3.4.11.9) from Escherichia coli has been solved and refined for crystals of the native enzyme at a 2.0-A resolution, for a dipeptide-inhibited complex at 2.3-A resolution, and for a low-pH inactive form at 2.7-A resolution. The protein crystallizes as a tetramer, more correctly a dimer of dimers, at both high and low pH, consistent with observations from analytical ultracentrifuge studies that show that the protein is a tetramer under physiological conditions. The monomer folds into two domains. The active site, in the larger C-terminal domain, contains a dinuclear manganese center in which a bridging water molecule or hydroxide ion appears poised to act as the nucleophile in the attack on the scissile peptide bond of Xaa-Pro. The metal-binding residues are located in a single subunit, but the residues surrounding the active site are contributed by three subunits. The fold of the protein resembles that of creatine amidinohydrolase (creatinase, not a metalloenzyme). The C-terminal catalytic domain is also similar to the single-domain enzyme methionine aminopeptidase that has a dinuclear cobalt center.
Open Channel Electrochromatography on a Microchip (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOpen Channel Electrochromatography on a MicrochipStephen C. Jacobson, Roland. Hergenroeder, Lance B. Koutny, and J. Michael. RamseyCite this: Anal. Chem. 1994, 66, 14, 2369–2373Publication Date (Print):July 1, 1994Publication History Published online1 May 2002Published inissue 1 July 1994https://pubs.acs.org/doi/10.1021/ac00086a024https://doi.org/10.1021/ac00086a024research-articleACS PublicationsRequest reuse permissionsArticle Views852Altmetric-Citations232LEARN 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
Proposals for Ballistocardiographic Nomenclature and Conventions: Revised and Extended (1956)

The committee's first report, published in Circulation for June 1953, recommended a terminology and certain conventions for recording ballistocardiograms of the type then in use. However, it soon became apparent that the committee's work was far from complete. Increasing knowledge of ballistic theory soon began to throw light on the relations of records secured by various instruments to one another, and a rapid advance in instrumentation began to provide records related to, but often not identical with, those which had been provided with a standard terminology by the committee in its first report. Accordingly, the committee has continued its labors to provide the rapidly advancing field with a uniform terminology. While they were thus engaged, attention was called to the fact that the designation of spatial axes previously recommended for vector ballistocardiograms differed from that which had been recommended for electrocardiograms by another committee of the American Heart Association. The advantages of a common system for designating spatial axes were obvious to all. Accordingly, as the electrocardiographic usage had priority and as little had been published in the field of ballistocardiographic vectors the committee voted to withdraw their original recommendation and substitute one conforming to that in use by electrocardiographers. In the present communication this new convention is also set forth. All members of the committee have shared in the deliberations and taken part in the decisions which form the basis of this report; but so much of the larger proportion of the actual work fell on Dr. Scarborough and Dr. Talbot that it was agreed without dissenting vote that only their names should appear as authors. This report has the endorsement of the committee as a whole, and the terminology it suggests is recommended as the official terminology of the American Heart Association.
Alphaviruses in Gene Therapy (2015)

Alphavirus vectors present an attractive approach for gene therapy applications due to the rapid and simple recombinant virus particle production and their broad range of mammalian host cell transduction. Mainly three types of alphavirus vectors, namely naked RNA, recombinant particles and DNA/RNA layered vectors, have been subjected to preclinical studies with the goal of achieving prophylactic or therapeutic efficacy, particularly in oncology. In this context, immunization with alphavirus vectors has provided protection against challenges with tumor cells. Moreover, alphavirus intratumoral and systemic delivery has demonstrated substantial tumor regression and significant prolonged survival rates in various animal tumor models. Recent discoveries of the strong association of RNA interference and disease have accelerated gene therapy based approaches, where alphavirus-based gene delivery can play an important role.
Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo (1998)

In early development of Xenopus laevis, it is known that activities of polypeptide growth factors are negatively regulated by their binding proteins. In this study, follistatin, originally known as an activin-binding protein, was shown to inhibit all aspects of bone morphogenetic protein (BMP) activity in early Xenopus embryos. Furthermore, using a surface plasmon resonance biosensor, we demonstrated that follistatin can directly interact with multiple BMPs at significantly high affinities. Interestingly, follistatin was found to be noncompetitive with the BMP receptor for ligand binding and to form a trimeric complex with BMP and its receptor. The results suggest that follistatin acts as an organizer factor in early amphibian embryogenesis by inhibiting BMP activities by a different mechanism from that used by chordin and noggin.
Functional Replacement of the Escherichia coli d- (−)-Lactate Dehydrogenase Gene ( ldhA ) with the l- (+)-Lactate Dehydrogenase Gene ( ldhL) from Pediococcus acidilactici (2003)

The microbial production of L-(+)-lactic acid is rapidly expanding to allow increased production of polylactic acid (PLA), a renewable, biodegradable plastic. The physical properties of PLA can be tailored for specific applications by controlling the ratio of L-(+) and D-(-) isomers. For most uses of PLA, the L-(+) isomer is more abundant. As an approach to reduce costs associated with biocatalysis (complex nutrients, antibiotics, aeration, product purification, and waste disposal), a recombinant derivative of Escherichia coli W3110 was developed that contains five chromosomal deletions (focA-pflB frdBC adhE ackA ldhA). This strain was constructed from a D-(-)-lactic acid-producing strain, SZ63 (focA-pflB frdBC adhE ackA), by replacing part of the chromosomal ldhA coding region with Pediococcus acidilactici ldhL encoding an L-lactate dehydrogenase. Although the initial strain (SZ79) grew and fermented poorly, a mutant (SZ85) was readily isolated by selecting for improved growth. SZ85 exhibited a 30-fold increase in L-lactate dehydrogenase activity in comparison to SZ79, functionally replacing the native D-lactate dehydrogenase activity. Sequencing revealed mutations in the upstream, coding, and terminator regions of ldhL in SZ85, which are presumed to be responsible for increased L-lactate dehydrogenase activity. SZ85 produced L-lactic acid in M9 mineral salts medium containing glucose or xylose with a yield of 93 to 95%, a purity of 98% (based on total fermentation products), and an optical purity greater than 99%. Unlike other recombinant biocatalysts for L-lactic acid, SZ85 remained prototrophic and is devoid of plasmids and antibiotic resistance genes.
Ethereum transaction graph analysis (2017)

Cryptocurrency platforms such as Bitcoin and Ethereum have become more popular due to decentralized control and the promise of anonymity. Ethereum is particularly powerful due to its support for smart contracts which are implemented through Turing complete scripting languages and digital tokens that represent fungible tradable goods. It is necessary to understand whether de-anonymization is feasible to quantify the promise of anonymity. Cryptocurrencies are increasingly being used in online black markets like Silk Road and ransomware like CryptoLocker and WannaCry. In this paper, we propose a model for persisting transactions from Ethereum into a graph database, Neo4j. We propose leveraging graph compute or analytics against the transactions persisted into a graph database.
Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment. (1983)

To assess the characteristics of chronic hepatitis in hepatitis B surface antigen (HBsAg) carriers with intrahepatic delta antigen, the hepatic histologic findings of 137 patients were reviewed; 101 patients were followed for 2 to 6 years. The predominant liver disease was chronic active hepatitis in 93 patients or cirrhosis in 32; minor forms of chronic persistent or lobular hepatitis were seen in 12 patients. Eight of the 26 patients with an initial diagnosis of cirrhosis died during the follow-up period. Cirrhosis developed in 31 of 75 patients (41%) without nodular regeneration seen in the first biopsy specimen; 5 of these patients died. Treatment with prednisone or azathioprine did not induce histologic amelioration of delta hepatitis or prevent cirrhosis. Chronic HBsAg hepatitis with intrahepatic expression of the delta antigen is an active, progressive disease unresponsive to conventional immunosuppressive treatment.
Specific Enrichment and Proteomics Analysis ofEscherichia coliPersisters from Rifampin Pretreatment (2018)

Bacterial persisters, a dormant and multidrug tolerant subpopulation that are able to resuscitate after antibiotic treatment, have recently received considerable attention as a major cause of relapse of various infectious diseases in the clinic. However, because of their low abundance and inherent transience, it is extremely difficult to study them by proteomics. Here we developed a magnetic-beads-based separation approach to enrich Escherichia coli persisters and then subjected them to shotgun proteomics. Rifampin pretreatment was employed to increase persister formation, and the resulting cells were exposed to a high concentration of ampicillin (10× MIC) to remove nonpersisters. The survivors were analyzed by spectral counting-based quantitative proteomics. On average, 710 proteins were identified at a false discovery rate of 0.01 for enriched E. coli persisters. By spectral counting-based quantification, 105 proteins (70 down-regulated, 35 up-regulated) were shown to be differentially expressed compared with normal cells. A comparison of the differentially expressed proteins between the magnetic beads-enriched persisters and nonenriched persisters (a mixture of persisters and intact dead cells) shows only around half (∼58%) overlap and different protein-protein interaction networks. This suggest that persister enrichment is important to eliminate the cumulative effect of dead cells that will obscure the proteome of persisters. As expected, proteins involved in carbohydrate metabolism, fatty acid and amino acid biosynthesis, and bacterial chemotaxis were found to be down-regulated in the persisters. Interestingly, membrane proteins including some transport proteins were up-regulated, indicating that they might be important for the drug tolerance of persisters. Knockout of the pal gene expressing peptidoglycan-associated lipoprotein, one of the most up-regulated proteins detected in persisters, led to 10-fold reduced persister formation under ampicillin treatment.
Common Sulfoglycolipid Receptor for Mycoplasmas Involved in Animal and Human Infertility1 (1990)

Sulfoglycolipids are ubiquitous components of the male germ cell membrane. Sulfogalactoglycerolipid (SGG) is restricted to mammalian cells and has recently been implicated in sperm/egg interactions. Mycoplasma infections have been implicated in infertility in a variety of species, including humans. Four such species-specific mycoplasmas, Ureaplasma urealyticum and Mycoplasma hominis (humans), Mycoplasma pulmonis (rodents), and Ureaplasma diversum (cattle) are not shown to specifically recognize SGG and the sphingolipid counterpart, sulfogalactosyl ceramide. This glycolipid receptor binding may relate to the reproductive pathogenesis of these organisms.