gebhart/patrepeval huggingface dataset:
Identification of L2 Open Reading Frame Gene Products of Bovine Papillomavirus Type 1 Using Monoclonal Antibodies (1989)

Four hybridoma cell lines producing monoclonal antibodies (MAbs) to bovine papillomavirus type 1 (BPV-1) L2 open reading frame (ORF) gene products have been established from mice immunized with a BPV-1 L2-beta-galactosidase fusion protein. Hybridomas were selected and cloned (from over 700 hybridomas) on the basis of specific reactivity of supernatant fluids with BPV-1 L2 epitopes on disrupted BPV-1 particles and L2-beta-galactosidase fusion proteins by ELISA and Western blotting, and with acetone-fixed frozen sections of BPV-1-induced fibropapillomas by immunofluorescence. These MAbs were not reactive with intact BPV-1 particles or BPV-1 L1-beta-galactosidase fusion proteins by ELISA or with beta-galactosidase by ELISA and Western blotting. The four MAbs detected viral structural proteins of Mr 76K, 68K and possibly 55K in purified BPV-1 preparations by Western blotting. Two of the four MAbs were cross-reactive with BPV-2-induced fibropapillomas. These findings suggest that (i) the BPV-1 L2 ORF encodes the minor capsid protein(s), (ii) the gene products of the BPV-1 L2 ORF have Mr values of 76K, 68K and possibly 55K, (iii) minor capsid epitopes are internal to the BPV-1 particle, and (iv) MAbs reactive with genetically engineered truncated BPV-1 L2 ORF gene products can distinguish between BPV-1 and BPV-2 productive infections.
Dimerization of a Phage-Display Selected Peptide for Imaging of αvβ6- Integrin: Two Approaches to the Multivalent Effect (2014)

The integrin αvβ6 is an emerging biomarker for non-small cell lung cancer (NSCLC). An αvβ6-binding peptide was previously selected from a phage-displayed peptide library. Here, we utilize a multivalent design to develop a peptidic probe for positron emission tomography (PET) imaging of αvβ6+ NSCLC tumors. Multimeric presentation of this peptide, RGDLATLRQL, on a bifunctional copper chelator was achieved using two approaches: dimerization of the peptide followed by conjugation to the chelator (H2-D10) and direct presentation of two copies of the peptide on the chelator scaffold (H2-(M10)2). Binding affinities of the divalent peptide conjugates are four-fold higher than their monovalent counterpart (H2-M10), suggestive of multivalent binding. PET imaging using the bivalent 64Cu-labeled conjugates showed rapid and persistent accumulation in αvβ6+ tumors. By contrast, no significant accumulation was observed in αvβ6- tumors. Irrespective of the dimerization approach, all divalent probes showed three-fold higher tumor uptake than the monovalent probe, indicating the role of valency in signal enhancement. However, the divalent probes have elevated uptake in non-target organs, especially the kidneys. To abrogate nonspecific uptake, the peptide's N-terminus was acetylated. The resultant bivalent probe, 64Cu- AcD10, showed drastic decrease of kidney accumulation while maintaining tumor uptake. In conclusion, we developed an αvβ6-integrin specific probe with optimized biodistribution for noninvasive PET imaging of NSCLC. Further, we have demonstrated that use of multivalent scaffolds is a plausible method to improve library selected peptides, which would be suboptimal or useless otherwise, for imaging probe development.
Immunomodulatory Effects of CpG Oligodeoxynucleotides on Established Th2 Responses (2002)

CpG oligodeoxynucleotides (CpG ODNs) are known to induce type 1 T-helper-cell (Th1) responses. We have previously demonstrated that CpG ODNs administered during sensitization prevent Th2-mediated eosinophilic airway inflammation in vivo. We also reported that key Th1 cytokines, gamma interferon (IFN-gamma) and interleukin 12 (IL-12), are not necessary for this protection. Recent in vivo data suggest that CpG ODNs might also reverse established pulmonary eosinophilia. In order to clarify how CpG ODNs can inhibit established Th2 responses, we evaluated the cytokine production from splenocytes from antigen- and alum-immunized mice. Restimulation with antigen induced IL-5, which was clearly inhibited by coculture with CpG ODNs in a concentration-dependent manner. CpG ODNs also induced IFN-gamma, but in a concentration-independent manner. The inhibition of IL-5 production was not mediated through natural killer cells or via CD8(+) T lymphocytes. Although IFN-gamma plays an important role in inhibition of antigen-induced IL-5 production by CpG ODNs, IFN-gamma was not the sole factor in IL-5 inhibition. CpG ODNs also induced IL-10, and this induction correlated well with IL-5 inhibition. Elimination of IL-10 reduced the anti-IL-5 effect of CpG ODNs, although incompletely. This may be because IFN-gamma, induced by CpG ODNs, is also inhibited by IL-10, serving as a homeostatic mechanism for the Th1-Th2 balance. Overproduction of IFN-gamma was downregulated by CpG ODN-induced IL-10 via modulation of IL-12 production. These data suggest that CpG ODNs may inhibit established Th2 immune responses through IFN-gamma and IL-10 production, the latter serving to regulate excessive Th1 bias. These properties of CpG ODNs might be a useful feature in the development of immunotherapy adjuvants against allergic diseases such as asthma.
Manifestations and treatment of laryngeal sarcoidosis. (1980)

Sarcoidosis involving the larynx presents with hoarseness, cough, dysphagia, and dyspnea secondary to upper airway obstruction. it may occur in patients with previously diagnosed sarcoidosis, or it may be the first or the only manifestation of the disease. Laryngoscopy reveals mucosal alterations including erythema and edema, punctate nodules, and mass lesions. The epiglottis is the most frequently affected area, but any portion of the larynx may be involved. The diagnosis is established by demonstrating granulomatous inflammation on laryngeal biopsy and excluding other causes of granulomatous laryngitis. Systemic corticosteroid therapy is the treatment of choice in most cases, but local steroid injection or surgical excision of affected areas may be useful in selected patients. Symptomatic laryngeal sarcoidosis can be managed successfully, but if it is left untreated, life-threatening upper airway obstruction may occur.
Synthesis of a Metal-Free Texaphyrin (2001)

The synthesis of a metal-free form of texaphyrin, an aromatic porphyrin-like macrocycle, is described. Previously, texaphyrins could only be obtained reproducibly in the form of metal complexes. Using ferrocenium cation as the oxidizing agent and starting with a reduced porphyrinogen-like nonaromatic form of texaphyrin, we isolated, in good yield, the metal-free oxidized texaphyrin as its HPF(6) salt. This product was characterized by X-ray diffraction analysis, UV-vis spectroscopy, and cyclic voltammetry. [structure: see text]
Ligands for Molecular Imaging: The Synthesis of Bis(thiosemicarbazone) Ligands (2006)

Bis(thiosemicarbazones) have been of interest to chemists for over fifty years; they display antitumour, antibiotic and antiviral properties. Recently it has become apparent that they may also provide a convenient way of labelling biologically active molecules by using metallic radionuclides and/or fluorescence. Although apparently simple, the synthesis of bis(thiosemicarbazone) ligands can be problematic. This article provides a summary of the published literature, based on the synthetic strategies used and indicates some of the difficulties that may arise.
Association between dental health and acute myocardial infarction. (1989)

Known risk factors for coronary heart disease do not explain all of the clinical and epidemiological features of the disease. To examine the role of chronic bacterial infections as risk factors for the disease the association between poor dental health and acute myocardial infarction was investigated in two separate case-control studies of a total of 100 patients with acute myocardial infarction and 102 controls selected from the community at random. Dental health was graded by using two indexes, one of which was assessed blind. Based on these indexes dental health was significantly worse in patients with acute myocardial infarction than in controls. The association remained valid after adjustment for age, social class, smoking, serum lipid concentrations, and the presence of diabetes. Further prospective studies are required in different populations to confirm the association and to elucidate its nature.
Highly Efficient Targeted Mutagenesis in Mice Using TALENs (2013)

Targeted mouse mutants are instrumental for the analysis of gene function in health and disease. We recently provided proof-of-principle for the fast-track mutagenesis of the mouse genome, using transcription activator-like effector nucleases (TALENs) in one-cell embryos. Here we report a routine procedure for the efficient production of disease-related knockin and knockout mutants, using improved TALEN mRNAs that include a plasmid-coded poly(A) tail (TALEN-95A), circumventing the problematic in vitro polyadenylation step. To knock out the C9orf72 gene as a model of frontotemporal lobar degeneration, TALEN-95A mutagenesis induced sequence deletions in 41% of pups derived from microinjected embryos. Using TALENs together with mutagenic oligodeoxynucleotides, we introduced amyotrophic lateral sclerosis patient-derived missense mutations in the fused in sarcoma (Fus) gene at a rate of 6.8%. For the simple identification of TALEN-induced mutants and their progeny we validate high-resolution melt analysis (HRMA) of PCR products as a sensitive and universal genotyping tool. Furthermore, HRMA of off-target sites in mutant founder mice revealed no evidence for undesired TALEN-mediated processing of related genomic sequences. The combination of TALEN-95A mRNAs for enhanced mutagenesis and of HRMA for simplified genotyping enables the accelerated, routine production of new mouse models for the study of genetic disease mechanisms.
Co-expression of aFGF and FGFR-1 is predictive of a poor prognosis in patients with esophageal squamous cell carcinoma (2007)

Overexpression of aFGF, bFGF and FGFR-1 has been reported in various cancers, and it has been suggested that it may be a poor prognostic factor in cases with solid tumors. Therefore, we attempted to determine whether overexpression of aFGF, bFGF and FGFR-1 might also be a poor prognostic factor in patients with esophageal squamous cell carcinoma, and examined the expression of aFGF, bFGF and FGFR-1 in esophageal cancer tissue specimens to clarify their clinical significance. Seventy-nine patients with squamous cell carcinoma of the esophagus who underwent resection at the Department of Surgery, Keio University Hospital, were enrolled as the subjects of this study. None of the patients had received any previous treatment. Formalin-fixed and paraffin-embedded sections of esophageal cancer tissue were stained by immunohistochemical methods and examined for expression of the angiogenetic factors and their receptors, and also to determine the microvascular density (MVD). We examined the correlations between the expression of aFGF, bFGF and FGFR-1, and the MVD, clinicopathological background factors and survival of the patients by conducting statistical analyses of the data. The results revealed that positive aFGF expression was associated with a larger tumor area (p=0.009), and co-expression of both aFGF and FGFR-1 was associated with a larger tumor area (p=0.01) and poorer prognosis (p=0.04). There were positive correlations between the expression of aFGF and FGFR-1 (p<0.0001), and between those of bFGF and FGFR-1 (p=0.04). aFGF may promote proliferation of esophageal cancer cells in an angiogenesis-independent and autocrine manner, and may contribute to rapid growth of esophageal cancer on recurrence after esophageal resection.
Abnormalities of Neurogenesis in the R6/2 Mouse Model of Huntington's Disease Are Attributable to theIn VivoMicroenvironment (2005)

Huntington's disease (HD) is an autosomal dominant neurodegenerative condition characterized by movement disorders, psychiatric disturbance, and cognitive decline. There are no treatments to halt or reverse the disease. Mammalian neurogenesis persists into adulthood in the subventricular zone (SVZ) and dentate gyrus (DG) of the hippocampus. In 2001, our laboratory published the hypothesis that neurogenesis is impaired in neurodegenerative diseases and that this may contribute to disease progression. Since then, it has been shown that neurogenesis is reduced in the DG of transgenic HD mice but increased in the SVZ of HD patients. We sought to characterize neurogenesis further. We found that, in the DG of the transgenic R6/2 mouse model of HD, newborn cell proliferation and morphology, but not differentiation or survival, was compromised. In R6/2 mice, neurogenesis failed to upregulate in the DG in response to seizures. Basal SVZ neurogenesis was similar between R6/2 mice and their wild-type littermates. There was no difference in the in vitro growth of adult neural precursor cells (NPCs) between genotypes. These results suggest that abnormal neurogenesis in the R6/2 mouse is not attributable to an intrinsic impairment of the NPC itself but is attributable to the environment in which the cell is located.
ITS4: a static vulnerability scanner for C and C++ code (2002)

We describe ITS4, a tool for statically scanning security-critical C source code for vulnerabilities. Compared to other approaches, our scanning technique stakes out a new middle ground between accuracy and efficiency. This method is efficient enough to offer real-time feedback to developers during coding while producing few false negatives. Unlike other techniques, our method is also simple enough to scan C++ code despite the complexities inherent in the language. Using ITS4 we found new remotely-exploitable vulnerabilities in a widely distributed software package as well as in a major piece of e-commerce software. The ITS4 source distribution is available at http://www.rstcorp.com/its4.
The Effect of Screening for Deep Vein Thrombosis on the Prevalence of Pulmonary Embolism in Patients With Fractures of the Pelvis or Acetabulum (2005)

Discontinuation of screening for the diagnosis of deep vein thrombosis did not change the rate of pulmonary embolism.
AffyProbeMiner: a web resource for computing or retrieving accurately redefined Affymetrix probe sets (2007)

The web interface and software (GPL open source license), are publicly-accessible at http://discover.nci.nih.gov/affyprobeminer.
Solution Structure of the Amino-Terminal Fragment of Urokinase-Type Plasminogen Activator (1994)

The amino-terminal fragment (ATF) of urokinase-type plasminogen activator is a two domain protein which consists of a growth factor and a kringle domain. The 1H, 13C, and 15N chemical shifts of this protein have been assigned using heteronuclear two- and three-dimensional NMR experiments on selective and uniformly 15N- and 15N/13C-labeled protein isolated from mammalian cells that overexpress the protein. The chemical shift assignments were used to interpret the NOE data which resulted in a total of 1299 NOE restraints. The NOE restraints were used along with 27 phi angle restraints and 21 hydrogen-bonding restraints to produce 15 low energy structures. The individual domains in the structures are highly converged, but the two domains are structurally independent. The root mean square deviations (rmsd) between residues 11-46 in the growth factor domain and the mean atomic coordinates were 0.99 +/- 0.2 for backbone heavy atoms and 1.65 +/- 0.2 for all non-hydrogen atoms. For residues 55-130 in the kringle domain, the rmsd was 0.84 +/- 0.2 for backbone heavy atoms and 1.42 +/- 0.2 for all non-hydrogen atoms. The overall structures of the individual domains are very similar to the structures of homologous proteins. However, important structural differences between the growth factor and other homologous proteins were observed in the region which has been implicated in binding the urokinase receptor which may explain, in part, why other growth factors show no appreciable affinity for the urokinase receptor.
Antisense oligonucleotide therapeutics for human leukemia (1998)

The development of reliable gene disruption strategies, and their application in living cells, has proven to be an extraordinary important advance for cell and molecular biologists. Using the various available approaches, the specific functions of any given gene may now be investigated directly in the relevant cell type. Application of similar experimental tools in a clinical setting might prove to be equally valuable and could well form the basis of a monumental advance in the practice of clinical medicine. This seems particularly true at the present time because much progress has been made in understanding the molecular pathogenesis of many diseases, including cancer. For these reasons a tremendous amount of interest has been generated in the use of oligodeoxynucleotides to modify gene expression. However, in spite of some notable successes which are detailed in this review, oligonucleotides have generated controversy in regard to their mechanism of action, reliability, and ultimate therapeutic utility. Nevertheless, the potential power of the "antisense" approach remains undisputed, and its ultimate therapeutic utility is far reaching. Accordingly, the problems associated with the use of these compounds are clearly worth solving. It remains the hope of many laboratories that the day will soon come when these techniques will make an important contribution to the management of chronic myelogenous leukemia and other neoplastic disorders.
Escherichia coli 0157:H7 and other shiga toxin-producing E. coli strains (1998)

Epidemiology of STEC in Humans STEC in the Food Chain Pathogenic Mechanisms: Bacterial Factors Pathogenic Mechanisms: Animal Models and Host Response Pathogenesis of Hemolytic Uremic Syndrome (HUS) Diagnosis and Treatment of STEC Infections Vaccines against STEC
Fas and Fas ligand expression in the salivary glands of patients with primary Sjögren's syndrome (1997)

Infiltrating lymphocytes in the focal lesions of the salivary glands of patients with SS are blocked in their ability to commit to apoptosis, even though they may express Fas. The presence of bcl-2 in these cells may explain their inability to undergo apoptosis. The acinar epithelial cells, in contrast, may undergo Fas-mediated apoptosis. These results suggest that the Fas death pathway may be an important mechanism leading to the glandular destruction found in SS.
Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants (2020)

Interpretation of the colossal number of genetic variants identified from sequencing applications is one of the major bottlenecks in clinical genetics, with the inference of the effect of amino acid-substituting missense variations on protein structure and function being especially challenging. Here we characterize the three-dimensional (3D) amino acid positions affected in pathogenic and population variants from 1,330 disease-associated genes using over 14,000 experimentally solved human protein structures. By measuring the statistical burden of variations (i.e., point mutations) from all genes on 40 3D protein features, accounting for the structural, chemical, and functional context of the variations' positions, we identify features that are generally associated with pathogenic and population missense variants. We then perform the same amino acid-level analysis individually for 24 protein functional classes, which reveals unique characteristics of the positions of the altered amino acids: We observe up to 46% divergence of the class-specific features from the general characteristics obtained by the analysis on all genes, which is consistent with the structural diversity of essential regions across different protein classes. We demonstrate that the function-specific 3D features of the variants match the readouts of mutagenesis experiments for BRCA1 and PTEN, and positively correlate with an independent set of clinically interpreted pathogenic and benign missense variants. Finally, we make our results available through a web server to foster accessibility and downstream research. Our findings represent a crucial step toward translational genetics, from highlighting the impact of mutations on protein structure to rationalizing the variants' pathogenicity in terms of the perturbed molecular mechanisms.
Serial Granulocyte Transfusions as a Treatment for Sepsis Due to Multidrug-Resistant Pseudomonas aeruginosa in a Neutropenic Patient (2003)

The emergence of multidrug-resistant Pseudomonas aeruginosa (MRPA) has become a major clinical problem. We successfully treated MRPA sepsis in a neutropenic patient undergoing peripheral blood stem cell transplantation with serial granulocyte transfusions. Granulocyte transfusion should be considered as a treatment for severe infection in patients with neutropenia.
Influence of Alloying Elements on Hardness Distribution after Nitrocarburizing in Medium Carbon Steel (2004)

Nitrocarburizing is widely applied to automobile parts such as crankshafts and gears. For improvement in strength of these parts, it is important to give the optimal hardness distribution by nitrocarburizing. Therefore, influence of alloying elements on hardness distribution after nitrocarburizing in normalized medium carbon steel was investigated in this study. Steels with different levels of carbon, silicon, manganese, and chromium contens were nitrocarburized at 873K for 7.2ks. The hardness distributions of these steels were measured. Effects of alloying elements on surface hardness (H1) and core hardness (H0) were shown by the following equations respectively. H0(HV)=14.8+288×[C]eq.;[[C] eq.=C+0.07×Si+0.16×Mn+0.19×Cu+0.17×Ni+0.20×Cr]H1(HV)=65.8+392×[Cr]eq.:[[C]eq.=0.48×C+0.16×Si+0.24×Mn+Cr] The hardness distribution of nitrocarburized steels has been estimated with the following equation. H(x,t)=H0+(H1-H0)(1-erf(x⁄2(αDt)1⁄2));[α=exp(-2.53×C-2.71×Si-1.82×Mn-6.81×Cr+3.84)] These equations have made it possible that the hardness profile of nitrocarburized parts can be controlled with alloying elements.
Is there a vitamin E paradox? (2001)

In addition to epidemiologic studies that suggest a benefit for high intakes of alpha-tocopherol, studies of supplementation in humans have clearly shown that alpha-tocopherol decreases lipid peroxidation, platelet aggregation, and functions as a potent anti-inflammatory agent. In the five large prospective clinical trials with alpha-tocopherol therapy, four have shown a beneficial effect on cardiovascular end-points (two studies on a primary end-point and two studies on other cardiovascular end-points). Thus, the totality of evidence based on the epidemiologic data, in-vitro studies and animal models, and the clinical trials appears to support a benefit for alpha-tocopherol supplementation in patients with pre-existing cardiovascular disease. However, definitive recommendations must await ongoing clinical trials.
Nucleotide Sequence of the Oncogene Encoding the p21 Transforming Protein of Kirsten Murine Sarcoma Virus (1982)

The transforming protein of Kirsten murine sarcoma virus (Ki-MuSV) is a virally encoded 21-kilodalton protein called p21 kis. The sequences encoding p21 kis were genetically localized to a 1.3-kilobase segment near the 5' end of the viral genome by assaying the capacity of a series of defined deletion mutants of molecularly cloned Ki-MuSV DNA to induce focal transformation of mouse cells. Nucleotide sequencing of a portion of this region has led to the identification of an open reading frame of 567 nucleotides coding for p21 kis protein.