gebhart/patrepeval huggingface dataset:
pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐up (1991)

Morphological assessment of the degree of differentiation has been shown in numerous studies to provide useful prognostic information in breast cancer, but until recently histological grading has not been accepted as a routine procedure, mainly because of perceived problems with reproducibility and consistency. In the Nottingham/Tenovus Primary Breast Cancer Study the most commonly used method, described by Bloom & Richardson, has been modified in order to make the criteria more objective. The revised technique involves semiquantitative evaluation of three morphological features--the percentage of tubule formation, the degree of nuclear pleomorphism and an accurate mitotic count using a defined field area. A numerical scoring system is used and the overall grade is derived from a summation of individual scores for the three variables: three grades of differentiation are used. Since 1973, over 2200 patients with primary operable breast cancer have been entered into a study of multiple prognostic factors. Histological grade, assessed in 1831 patients, shows a very strong correlation with prognosis; patients with grade I tumours have a significantly better survival than those with grade II and III tumours (P less than 0.0001). These results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained. Histological grade forms part of the multifactorial Nottingham prognostic index, together with tumour size and lymph node stage, which is used to stratify individual patients for appropriate therapy.
Metal-assisted coupling to hollow-core photonic crystal fibres (2005)

Selective coupling to the fundamental mode of short hollow-core photonic bandgap fibres without exciting cladding modes is improved by gold-coated fibre end facets. Cladding modes are suppressed by 20–30 dB for single-and multimode fibre launch, respectively, while in-band power loss is 3–8 dB.
The region of the thrombin receptor resembling hirudin binds to thrombin and alters enzyme specificity. (1991)

A thrombin receptor has recently been cloned and the sequence deduced. The sequence reveals a thrombin cleavage site that accounts for receptor activation. The receptor also has an acidic region with some similarities to the carboxyl-terminal region of the leech thrombin inhibitor, hirudin. Synthetic peptides corresponding to the receptor cleavage site (residues 38-45), the hirudin-like domain (residues 52-69), and the covalently associated domains (residues 38-64) were evaluated for their ability to bind to thrombin. Peptides 38-45 and 38-64 were competitive inhibitors of thrombin's chromogenic substrate activity (Ki = 0.96 mM and 0.6 microM, respectively. Residues 52-69 altered the chromogenic substrate specificity, resulting in accelerated cleavage of some substrates and inhibited cleavage of others. The same peptide binds to thrombin and alters the fluorescence emission intensity of 5-dimethylaminonaphthalene-1-sulfonyl (dansyl)-thrombin in which the dansyl is attached directly to the active site serine (Kd = 32 +/- 7 microM). Residues 52-69 displace the carboxyl-terminal peptide of hirudin, indicating that they share a common binding site in the anion exosite of thrombin. These data suggest that the thrombin receptor has high affinity for thrombin due to the presence of the hirudin-like domain and that this domain alters the specificity of thrombin. This change in specificity may account for the ability of the receptor to serve as an excellent thrombin substrate despite the presence of an Asp residue in the P3 site, which is normally inhibitory to thrombin activity.
SUBGROUPS OF AMINO ACID SEQUENCES IN THE VARIABLE REGIONS OF IMMUNOGLOBULIN HEAVY CHAINS (1969)

The amino acid sequence of the first 133 residues of the heavy (gamma) chain from a human gammaG immunoglobulin (He) has been determined. This gamma-chain is identical in Gm type to that of protein Eu, the complete sequence of which has been reported. Comparison of the two sequences substantiates the previous suggestion that there are subgroups of variable regions of heavy chains. The variable region of Eu has been assigned to subgroup I and that of He to subgroup II; on the other hand, the constant regions of the two proteins appear to be identical. Comparison of the sequence of the heavy chain of He with the heavy chain sequences determined in other laboratories suggests that the variable region of subgroup II is at least 118 residues long. The nature and distribution of amino acid variations in this heavy chain subgroup resemble those observed in light chain subgroups. These studies provide evidence that the translocation hypothesis applies to heavy as well as to light chains, viz., genes for variable regions (V) are somatically translocated to genes for constant regions (C) to form complete VC structural genes.
Expanding the detectable HLA peptide repertoire using electron-transfer/higher-energy collision dissociation (EThcD) (2014)

The identification of peptides presented by human leukocyte antigen (HLA) class I is tremendously important for the understanding of antigen presentation mechanisms under healthy or diseased conditions. Currently, mass spectrometry-based methods represent the best methodology for the identification of HLA class I-associated peptides. However, the HLA class I peptide repertoire remains largely unexplored because the variable nature of endogenous peptides represents difficulties in conventional peptide fragmentation technology. Here, we substantially enhanced (about threefold) the identification success rate of peptides presented by HLA class I using combined electron-transfer/higher-energy collision dissociation (EThcD), reporting over 12,000 high-confident (false discovery rate <1%) peptides from a single human B-cell line. The direct importance of such an unprecedented large dataset is highlighted by the discovery of unique features in antigen presentation. The observation that a substantial part of proteins is sampled across different HLA alleles, and the common occurrence of HLA class I nested sets, suggest that the constraints of HLA class I to comprehensively present the health states of cells are not as tight as previously thought. Our dataset contains a substantial set of peptides bearing a variety of posttranslational modifications presented with marked allele-specific differences. We propose that EThcD should become the method of choice in analyzing HLA class I-presented peptides.
Plasmacytoid dendritic cells and regulatory T cells in the tumor microenvironment (2013)

Tumor-infiltrating plasmacytoid dendritic cells (pDCs) have been associated with poor patient prognosis. We have recently uncovered the ability of pDCs to activate and expand a subset of tumor-infiltrating FOXP3<sup>+</sup> regulatory T cells that express inducible costimulator (ICOS), providing new insights into the mechanisms that govern the escape of cancer from immunosurveillance.
Closed wound suction drainage. (1985)

Closed wound suction drainage may have application to certain podiatric surgical procedures. It can be used to reduce postoperative edema and hematoma formation, decrease the possibility of infection, and minimize the chance of external contamination of the surgical site. Certain conditions that may occur after podiatric surgical procedures and that are detrimental to the healing and rehabilitation of the patient but can be obviated by the use of closed suction drainage are illustrated. Drains should be considered in any podiatric surgical procedure that results in the creation of large voids or causes substantial bleeding as occurs in large resections of bone. Included in this would be any plastic surgical procedures or amputations of the foot.
A Convenient Route To Cyanoguanidines (1999)

Abstract A facile and versatile method for the preparation of cyanoguanidines 7 from amines 3 and isothiocyanates 4 via a methylation, cyanamide-treatment sequence is described.
A self correcting clock recovery curcuit (1985)

Conventional approaches to the problem of extracting clock from NRZ data do not automatically hold the clock in the center of the data eye. Other means must be used to keep the clock properly centered in the eye at the decision flip-flop. A new approach to the problem is described. The circuit is both simple and self correcting.
Phase precoding for frequency-selective Rayleigh and Rician slowly fading channels (1997)

This paper presents a novel phase precoding (pre-equalization) technique to equalize frequency-selective Rayleigh and Rician slowly fading channels for personal communication systems using phase modulation. In order to achieve intersymbol interference (ISI)-free transmission, the precoding technique pre-distorts the signal transmitted from a base station to a portable unit. The novelty of the technique lies in using a spiral curve design: (1) to ensure the stability of the precoder even in equalizing a non-minimum-phase channel; (2) to obtain an ISI-free received signal; and (3) to keep a constant transmitted signal amplitude. Using the precoder can improve the bit-error-rate (BER) transmission performance without increasing the complexity of the portable unit receiver. The BER performance of coherent quadrature phase-shift-keying (QPSK) with the channel pre-equalization is analyzed theoretically for both Rayleigh and Rician fading channels. Analytical and simulation results demonstrate that coherent QPSK using the proposed channel precoder has a significantly lower BER than that using a conventional decision-feedback equalizer (DFE) because the precoder does not suffer from error propagation.
Multi-task Neural Networks for QSAR Predictions (2014)

Although artificial neural networks have occasionally been used for Quantitative Structure-Activity/Property Relationship (QSAR/QSPR) studies in the past, the literature has of late been dominated by other machine learning techniques such as random forests. However, a variety of new neural net techniques along with successful applications in other domains have renewed interest in network approaches. In this work, inspired by the winning team's use of neural networks in a recent QSAR competition, we used an artificial neural network to learn a function that predicts activities of compounds for multiple assays at the same time. We conducted experiments leveraging recent methods for dealing with overfitting in neural networks as well as other tricks from the neural networks literature. We compared our methods to alternative methods reported to perform well on these tasks and found that our neural net methods provided superior performance.
Comorbid Insomnia and Psychiatric Disorders: An Update. (2018)

Insomnia is a clinical problem of significant public health importance. Insomnia can be a symptom or harbinger of other psychiatric disorders. Insomnia can also be comorbid with other psychiatric disorders, thereby adding to the medical burden and increasing the risk of psychiatric relapse. Insomnia can also be associated with medical and neurological disorders. Some medications can also cause insomnia. Treatment of insomnia can lead to positive outcomes, not only by alleviating symptoms and moderating these comorbid disorders, but by preventing new episodes. Therefore, it is vital to be aware of the relationship between insomnia and psychiatric illness. This article reviews this relationship and provides recommendations for management.
Effect of chromium picolinate on growth and serum and carcass traits of growing-finishing pigs (1993)

Three experiments were conducted to evaluate chromium picolinate (CrPic) in growing-finishing pigs. Treatments were replicated four times within each experiment with three pigs per replicate in Exp. 1 and four pigs per replicate in Exp. 2 and 3. Average initial weights were 37.8, 30.5, and 22.4 kg in Exp. 1, 2, and 3, respectively. In Exp. 1, the basal corn-soybean meal diet (B, 120% NRC Lys) was supplemented with 0, 25, 50, 100, or 200 ppb of Cr from CrPic. Daily gain was increased (Cr cubic, P < .02) and serum cholesterol decreased (Cr cubic, P < .08) by addition of CrPic. In Exp. 2, the basal diet was supplemented with 0, 100, 200, 400, or 800 ppb of Cr from CrPic. Daily gain and ADFI were decreased (Cr linear, P < .05) by CrPic. Serum cholesterol also was decreased (Cr quadratic, P < .05) by CrPic. Longissimus muscle area (LMA) and percentage of muscling (MUS) were increased (Cr quadratic, P < .01) and 10th rib fat (TRF) was decreased (Cr quadratic, P < .01) by CrPic. In Exp. 3, pigs were allotted to the following treatments: 1) B, 2) B + 1,467 ppb of picolinate (Pic), 3) B + 200 ppb of Cr from CrCl3.6H2O, 4) B + 1,467 ppb of Pic + 200 ppb of Cr from CrCl3.6H2O, 5) B + 100 ppb of Cr from CrPic, or 6) B + 200 ppb of Cr from CrPic. Longissimus muscle area and MUS were increased (P < .01) and TRF decreased (P < .01) in pigs fed CrPic but not in pigs fed CrCl3.6H2O and(or) Pic.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of cytokines in myocardial ischemia and reperfusion (1997)

Mediators of myocardial inflammation, predominantly cytokines, have for many years been implicated in the healing processes after infarction. In recent years, however, more attention has been paid to the possibility that the inflammation may result in deleterious complications for myocardial infarction. The proinflammatory cytokines may mediate myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. A growing body of literature suggests that inflammatory mediators could play a crucial role in ischemia-reperfusion injury. Furthermore, ischemia-reperfusion not only results in the local transcriptional and translational upregulation of cytokines but also leads to tissue infiltration by inflammatory cells. These inflammatory cells are a ready source of a variety of cytokines which could be lethal for the cardiomyocytes. At the cellular level it has been shown that hypoxia causes a series of well documented changes in cardiomyocytes that includes loss of contractility, changes in lipid metabolism and subsequent irreversible cell membrane damage leading to cell death. For instance, hypoxic cardiomyocytes produce interleukin-6 (IL-6) which could contribute to the myocardial dysfunction observed in ischemia reperfusion injury. Ischemia followed by reperfusion induces a number of other multi-potent cytokines, such as IL-1, IL-8, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1) as well as an angiogenic cytokine/ growth factor, vascular endothelial growth factor (VEGF), in the heart. Intrestingly, these multipotent cytokines (e.g. TNF-alpha) may induce an adaptive cytoprotective response in the reperfused myocardium. In this review, we have included a number of cytokines that may contribute to ventricular dysfunction and/or to the cytoprotective and adaptive changes in the reperfused heart.
Myeloid dendritic cells (1999)

There is considerable but as yet incomplete evidence for two developmental lineages of dendritic cells: a myeloid lineage shared with phagocytes and a lymphoid lineage shared with T cells. The two corresponding functional states, which may not require the existence of two formal lineages, are that myeloid dendritic cells capture antigens in the periphery and then migrate to the lymphoid organs to initiate immunity, whereas lymphoid dendritic cells are found in the thymic medulla and lymph node T cell areas and are responsible for tolerance. The latter may occur through immune regulation and/or deletion. Myeloid dendritic cells undergo many activities that contribute to the initiation of immunity. These are summarized here and include mobilization from progenitors and precursors in the blood and marrow, maturation from immature cells in the skin and interstitial spaces, formation of MHC-peptide complexes in MHC class II compartments or MIICs, migration to the T cell areas, and finally, mortality. The death of migratory dendritic cells seems to be accompanied by their phagocytosis and processing by other dendritic cells in the T area. We speculate that this transfer of antigens, including self-peptides captured by the uptake of apoptotic cells in peripheral tissues, is an important prelude to the regulatory function of resident or lymphoid dendritic cells in the T cell area. These features of dendritic cell biology provide targets to manipulate the immune response in vivo.
Pathologic Role and Temporal Appearance of Newly Emerging Autoepitopes in Relapsing Experimental Autoimmune Encephalomyelitis (2000)

Relapsing experimental autoimmune encephalomyelitis (R-EAE) is a CD4+ T cell-mediated demyelinating disease model for multiple sclerosis. Myelin destruction during the initial relapsing phase of R-EAE in SJL mice initiated by immunization with the proteolipid protein (PLP) epitope PLP139-151 is associated with activation of T cells specific for the endogenous, non-cross-reactive PLP178-191 epitope (intramolecular epitope spreading), while relapses in R-EAE induced with the myelin basic protein (MBP) epitope MBP84-104 are associated with PLP139-151-specific responses (intermolecular epitope spreading). Here, we demonstrate that T cells specific for endogenous myelin epitopes play the major pathologic role in mediating clinical relapses. T cells specific for relapse-associated epitopes can serially transfer disease to naive recipients and are demonstrable in the CNS of mice with chronic R-EAE. More importantly, induction of myelin-specific tolerance to relapse-associated epitopes, by i.v. injection of ethylene carbodiimide-fixed peptide-pulsed APCs, either before disease initiation or during remission from acute disease effectively blocks the expression of the initial disease relapse. Further, blockade of B7-1-mediated costimulation with anti-B7-1 F(ab) during disease remission from acute PLP139-151-induced disease prevents clinical relapses by inhibiting activation of PLP178-191-specific T cells. The protective effects of anti-B7-1 F(ab) treatment are long-lasting and highly effective even when administered following the initial relapsing episode wherein spreading to a MBP epitope (MBP84-104) is inhibited. Collectively, these data indicate that epitope spreading is B7-1 dependent, plays a major pathologic role in disease progression, and follows a hierarchical order associated with the relative encephalitogenic dominance of the myelin epitopes (PLP139-151 > PLP178-191 > MBP84-104).
Effect of exogenous testosterone replacement on prostate‐specific antigen and prostate‐specific membrane antigen levels in hypogonadal men (1995)

Previous studies have suggested that serum prostate-specific antigen (PSA) levels are under androgenic influence, especially in patients with adenocarcinoma of the prostate. PSMA (prostate-specific membrane antigen) is thought to reflect hormonal or clonal resistance or an independence with respect to testosterone regulation. The influence of testosterone on serum PSA expression in normal men is not clear. We studied the effect of exogenous testosterone administration on the serum levels of PSA and PSMA in hypogonadal men. Serial serum PSA, serum PSMA by Western blot, and serum total testosterone levels were obtained at intervals of every 2-4 weeks in 10 hypogonadal men undergoing treatment with exogenous testosterone, delivered as testosterone enanthate injection or by testosterone patch. Linear and quadratic orthogonal polynomial scores were calculated for PSMA, PSA, and testosterone. A 2-tailed, paired t-test failed to demonstrate a significant correlation between serum PSA (linear P = 0.432, quadratic P = 0.290) or PSMA (linear P = 0.162, quadratic P = 0.973) and serum testosterone levels. This study suggests that in hypogonadal men, neither PSMA nor PSA expression is testosterone-dependent.
Current primary open-angle glaucoma treatments and future directions (2012)

Primary open-angle glaucoma (POAG) is a leading cause of blindness with no known cure. Management of the disease focuses on lowering intraocular pressure (IOP) with current classes of drugs like prostaglandin analogs, beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors. These treatments have not helped all patients. Some patients continue to experience deterioration in the optic nerve even though their IOPs are within the normal range. New views have surfaced about other pathophysiological processes (such as oxidative stress, vascular dysfunction, and retinal cell apoptosis) being involved in POAG progression, and adjunctive treatments with drugs like memantine, bis(7)-tacrine, nimodipine, and mirtogenol are advocated. This review examines the current and proposed treatments for POAG. Some of the proposed drugs (bis(7)-tacrine, nimodipine, vitamin E, and others) have shown good promise, mostly as monotherapy in various clinical trials. It is recommended that both the current and proposed drugs be put through further robust trials in concurrent administration and evaluated.
Transient Expression of Genes Transferred In Vivo into Heart Using First-Generation Adenoviral Vectors: Role of the Immune Response (1995)

Gene therapy for heart diseases requires availability of an efficient vector for gene transfer into myocardium. Recombinant adenovirus expressing the Escherichia coli beta-galactosidase (beta-Gal) gene was shown to infect rat cardiocytes efficiently in vivo. However, a time course of gene expression showed that transgene expression was maximal during the first week following injection, then declined and disappeared by day 21. An immunosuppressive treatment prolonged beta-Gal expression for at least 21 days. On the contrary, a preimmunization of the animals by two intraperitoneal injections of the vector led to a decreased transgene expression 48 hr after intramyocardial injection and to a barely detectable expression at the sixth day. Appearance of adenovirus neutralizing antibodies in preimmunized animals could have contributed to such a refractoriness to further adenoviral infection. Finally, a neonatal intrathymic injection of the vector was able to induce long-term LacZ expression for more than 2 months after heart injection, although neutralizing as well as anti-beta-Gal antibodies were detected in sera of the animals. These results indicate that an immune response against first-generation replication-defective adenoviral vectors is a major cause of transient transgene expression, a cellular response being most probably responsible for ablation of transgene expression in immunocompetent animals.