gebhart/patrepeval huggingface dataset:
Castration-induced apoptosis of androgen-dependent shionogi carcinoma is associated with increased expression of genes encoding insulin-like growth factor-binding proteins. (1999)

Insulin-like growth factor (IGF)-I has well-characterized mitogenic and antiapoptotic effects that are essential for maintenance of the normal prostate and may be important during regression of the normal prostate and/or prostate tumors induced by androgen-targeting therapies for prostate cancer. IGF-I activity is modulated by IGF-binding proteins (IGFBPs). Here we examine IGFBP expression during regression of androgen-dependent Shionogi carcinoma tumors after castration. In this model, we observe a 90% reduction in Shionogi tumors by 10 days postcastration. Northern blotting of RNA from tumors collected at various times after castration indicates a rapid induction of IGFBP-5 concomitant with apoptotic regression of tumors, as detected by Apoptag staining of tumor sections after castration. IGFBP-5 mRNA was not detectable in tumors from control animals, but levels increased 120-fold in tumors 3 days after castration. The mRNAs for IGFBP-3 and 4 were abundant in Shionogi tumors from intact mice and decreased to -33% and -20% of control, respectively. Castration had no significant effect on IGFBP-2 expression. Treatment with calcium channel blockers inhibited castration-induced apoptosis and tumor regression and also significantly inhibited up-regulation of IGFBP-5 after castration. These data provide strong evidence for a functional role of IGFBP-5 expression in mediating the apoptosis induced by androgen deprivation in androgen-dependent neoplasia.
Triggering CD 28 molecules synergize with CD 2 (T11.1 and T11,2)‐mediated T cell activation (1988)

Pairs of monoclonal antibodies (mAb) defining epitopes T 11.1 and T 11.2 on the CD 2 molecule are mitogenic for purified human T cells in the presence of a submitogenic dose of 12-O-tetradecanoylphorbol 13-acetate (TPA). Anti-CD 28 mAb can substitute for the action of TPA in the anti-CD 2-induced proliferative response of resting T cells, whereas each signal alone is unable to mediate this effect. Co-stimulation by anti-CD 2 plus anti-CD 28 mAb is monocyte independent and besides resting T cells also induces strong proliferation of thymocytes and pre-activated T cells. Modulation of the CD 3-T cell receptor complex does not inhibit the co-stimulatory effects of anti-CD 2 plus anti-CD 28 mAb. The effect is largely dependent on endogenously produced interleukin 2, since the response is strongly inhibited in the presence of mAb against the 55-kDa interleukin 2 receptor chain.
425. Formulation Development for AAV2 Vectors: Identification of Excipients That Inhibit Vector Aggregation (2004)

Successful development of AAV-based vectors for therapeutic use in humans requires the development of vector formulations that ensure optimal in vivo efficacy and safety. Prevention of vector particle aggregation is a critical challenge for parenteral formulation development. The objective of this study was to investigate the mechanism of AAV2 vector aggregation, and to identify classes of excipients to prevent the phenomenon. Previous studies have shown that aggregation of AAV vectors can occur following freeze-thaw cycling and during concentration of purified rAAV (Huang et al, Mol Therapy 1:S286). We have observd that vector aggregation can also be induced following reduction of the ionic strength (μ) by dilution of buffered solutions containing rAAV, and have used this as a model system to investigate the ability of various excipients to inhibit aggregation. Studies were performed on three independent AAV2 vector preparations, one purified by column chromatography (containing empty capsids), a second by CsCl gradient centrifugation (no empty capsids), the third by a hybrid method utilizing both purification process steps (no empty capsids). Dynamic light scattering (DLS) was used to assess aggregation. The contribution of hydrophobic interactions to aggregation was investigated by including Polysorbate 80, Polysorbate 20, or Pluronic F68 (concentrations from 0.01–10%) to inhibit interparticle hydrophobic interactions. At the concentrations examined, these surfactants did not reduced aggregation relative to buffer-only controls in the dilution model. We also examined the effect of glycerol, sorbitol, mannitol, or polyethyleneglycol (0.1–5%), and similarly observed no reduction of aggregation. Based on our previous report that AAV2 aggregation is pH dependent, suggesting involvement of charged amino acids on the vector particle surface (Qu et al, Mol Therapy 7:S348), we examined the ability of charged amino acids (Lys, Arg, Asp, Glu) to reduce aggregation. These amino acids inhibited aggregation only to the degree observed with an equivalent molar concentration of NaCl. The exponential dependence of ionic strength on the valency of contributing ionic species (μ=1/2 ∑cizi2) led us to investigate ionic excipients with valency >1. We observed that a number of these excipients inhibited aggregation more efficiently than NaCl. For example, the divalent salt Mg2+ SO42− inhibited aggregation at a molar concentration approximately 4-fold lower than that required using NaCl. Cumulatively, these data confirm that ionic interactions play a major role in AAV2 vector aggregation, and that use of excipients that maximize ionic strength is a promising strategy to reduce aggregation potential, providing optimal long-term stability and clinical dosing potential for AAV vectors.
Role of training data variability on classifier performance and generalizability (2018)

Large, high-quality training datasets are necessary for machine learning classifiers to achieve high performance. Due to the high cost of collecting quality annotated data, dataset sizes for medical imaging applications are typically small and collected at a single institution. The use of small, single-site datasets results in classifiers that do not generalize well to data collected at different institutions or under different imaging protocols. Previous attempts to address this problem resulted in development of transfer learning and domain adaptation algorithms. Our work investigates the improvement of generalization performance by increasing training data variability. We use data from multiple sites (one from a local clinic and two from publicly available sets) to train support vector machines (SVMs) and Convolutional Neural Networks (CNNs) to distinguish tissue patches of hematoxylin and eosin (H&amp;E) stained tissue of colorectal cancer (CRC). To measure the effect of increasing training set variability on classifier robustness, we create different training combinations of two datasets for training and validation, and use the third set is reserved for testing. SVM accuracy on the testing dataset ranged from 50% to 59% when training with data from a single site, which increases to 61% when data from both sites was combined in training. Using CNNs, the testing accuracy was 56% and 67% when training on single-site data, which increased to 70% with data from both sites. Thus, the increase in generalization performance exists for both traditional and deep learning algorithms, and is essential for building larger datasets for medical image classification.
Regioselective Oxidation of 3-Substituted Pyridinium Salts (2000)

(1'R)-(+)-3-Hydroxymethyl-1-(1'-phenyl-ethyl)-pyridinium chloride (1), 1-benzyl-3-[1', 3']-dioxolan-2'-yl-pyridinium chloride (2) and (2'S, 4'S, 5'R)-(-)-1-benzyl-3-(3',4'-dimethyl-5'-phenyl-oxazolidin-2'-yl)-pyridinium bromide (3), were transformed by oxidation with potassium ferricyanide into the corresponding 1H-pyridin-2-ones in excellent yields with high regioselectivity.
Laser materials for the 0. 67- to 2. 5-micrometers range. Contractor report (1987)

Basic requirements for obtaining injection laser action in III-V semiconductors are discussed briefly. A detailed review is presented of materials suitable for lasers emitting at 0.67, 1.44, 1.93, and 2.5 micrometers. A general approach to the problem is presented, based on curves of materials properties published by Sasaki et al. It is also shown that these curves, although useful, may need correction in certain ranges. It is deduced that certain materials combinations, either proposed in the literature or actually tried, are not appropriate for double heterostructure lasers, because the refractive index of the cladding material is higher than the index of the active material, thus resulting in no waveguiding, and high threshold currents. Recommendations are made about the most promising approach to the achievement of laser action in the four wavelengths mentioned above.
Decreasing acetic acid accumulation by a glycerol overproducing strain of Saccharomyces cerevisiae by deleting the ALD6 aldehyde dehydrogenase gene (2002)

Glycerol is a major fermentation product of Saccharomyces cerevisiae that contributes to the sensory character of wine. Diverting sugar to glycerol overproduction and away from ethanol production by overexpressing the glycerol 3-phosphate dehydrogenase gene,GPD2, caused S. cerevisiae to produce more than twice as much acetic acid as the wild-type strain (S288C background) in anaerobic cell culture. Deletion of the aldehyde dehydrogenase gene, ALD6, in wild-type and GPD2 overexpressing strains (GPD2-OP) decreased acetic acid production by three- and four-fold, respectively. In conjunction with reduced acetic acid production, the GPD2-OP ald6Delta strain produced more glycerol and less ethanol than the wild-type. The growth rate and fermentation rate were similar for the modified and wild-type strains, although the fermentation rate for the GPD2 ald6Delta strain was slightly less than that of the other strains from 24h onwards. Analysis of the metabolome of the mutants revealed that genetic modification affected the production of some secondary metabolites of fermentation, including acids, esters, aldehydes and higher alcohols, many of which are flavour-active in wine. Modification of GPD2 and ALD6 expression represents an effective strategy to increase the glycerol and decrease the ethanol concentration during fermentation, and alters the chemical composition of the medium such that, potentially, novel flavour diversity is possible. The implications for the use of these modifications in commercial wine production require further investigation in wine yeast strains.
The Various Sendai Virus C Proteins Are Not Functionally Equivalent and Exert both Positive and Negative Effects on Viral RNA Accumulation during the Course of Infection (1998)

Recombinant Sendai viruses were prepared which cannot express their Cprime, C, or Cprime plus C proteins due to mutation of their respective start codons ([Cprime-minus], [C-minus] and [double mutant], respectively). The [Cprime-minus] and [C-minus] stocks were similar to that of wild-type (wt) virus in virus titer and plaque formation, whereas the double-mutant stock had a much-reduced PFU or 50% egg infective dose/particle ratio and produced very small plaques. Relative to the wt virus infection, the [Cprime-minus] and [C-minus] infections of BHK cells resulted in significantly greater accumulation of viral RNAs, consistent with the known inhibitory effects of the Cprime and C proteins. The double-mutant infection, in contrast, was delayed in its accumulation of viral RNAs; however, once accumulation started, overaccumulation quickly occurred, as in the single-mutant infections. Our results suggest that the Cprime and C proteins both provide a common positive function early in infection, so that only the double mutant undergoes delayed RNA accumulation and exhibits the highly debilitated phenotype. Later in infection, the same proteins appear to act as inhibitors of RNA accumulation. In infections of mice, [Cprime-minus] was found to be as virulent as wt virus whereas [C-minus] was highly attenuated. These results suggest that the Cprime and C proteins cannot be functionally equivalent, since C can replace Cprime for virulence in mice whereas Cprime cannot replace C.
Oral human recombinant epidermal growth factor in the treatment of patients with duodenal ulcer. (1996)

The epidermal growth factor has been shown to be mucoprotective and to accelerate healing of gastroduodenal ulcers in animals. A prospective, positively controlled clinical trial was conducted. Seventy five patients with duodenal ulcer were randomly distributed in three groups to receive oral human recombinant epidermal growth factor in 1% carboxymethyl cellulose at two different doses (450 mg or 600 mg/day), or cimetidine. Treatment was administered up to a maximum of 6 weeks. The most important assessment criteria was the proportion of patients healed after 2, 4 and 6 weeks of treatment determined by endoscopy. Treatment with both doses of epidermal growth factor showed a long-term healing effect in 76.5% at 6 weeks vs 92.5% with cimetidine (p = N.S.). The evolution of the clinical symptoms was similar in the three groups. Adverse reactions were not detected in any of the patients included in this study. To our knowledge, this is the first report on the oral use of epidermal growth factor in humans.
MUSCLE: multiple sequence alignment with improved accuracy and speed (2004)

We present MUSCLE, a new program for creating multiple alignments of protein sequences. MUSCLE achieves the highest scores so far reported on four alignment benchmarks: Balibase, PREFAB, SABmark and SMART, achieving accuracy from 1% to 2.5% higher than T-Coffee and execution times that are generally lower than CLUSTALW for typical input data. With options designed for high-throughput applications, MUSCLE gives average accuracy statistically indistinguishable from T-Coffee and is the fastest published method for large numbers of sequences, able to align 5,000 sequences of length 300 in 7 minutes on a desktop computer. MUSCLE is freely available at http://www.drive5.com/muscle.
CD28 ligation by monoclonal antibodies or B7/BB1 provides an accessory signal for the cyclosporin A-resistant generation of cytotoxic T cell activity (1993)

Ligation of the T cell membrane Ag CD28 with mAb 9.3 or with its natural ligand B7/BB1 on accessory cells has been shown to provide a helper signal for stimulation through the TCR/CD3 complex. The present study was undertaken to investigate whether CD28 could function as an accessory signal receptor in the generation and effector phase of CTL activity. Purified resting human T cells were activated for 3 to 4 days with immobilized anti-CD3 mAb as the primary stimulus, and CTL activity was then measured by an anti-CD3-redirected 4-hr 51Cr release assay on Fc gamma R-bearing P815 target cells. When the concentration of immobilized anti-CD3 mAb as the primary signal for CTL generation was below threshold, CTL activity could be generated by addition of mAb 9.3 to the cultures. At optimal concentrations of immobilized anti-CD3, the addition of anti-CD28 did not further enhance the generation of CTL activity, but under these conditions generation of CTL activity was almost completely resistant to cyclosporin A (CsA) as a result of CsA-resistant IL-2 production. When 3T6 mouse fibroblasts, transfected with Fc gamma RII and B7, were used as accessory cells, anti-CD3 and B7 were also found to generate cytotoxic activity. Cytotoxic T cell generation under these conditions could be blocked by anti-B7 mAb, but was totally resistant to CsA. CTL activity could be generated by CD3 and CD28 ligation in both CD4(+) and CD8(+) subpopulations. Finally, we found that the activity of CTL lines (isolated from ascitic fluid of a patient with ovarian carcinoma and cultured in IL-2) was higher on B7-transfected targets than on the B7(-) targets. We conclude that CD28 ligation provides a major accessory signal for the CsA-resistant generation of CTL activity and that CD28-B7 interaction also enhances cytotoxic effector functions of CTL. These findings might have important implications for immunotherapeutic interventions.
Tamponade in the surgical management of retinal detachment (2016)

Despite treatment advances, rhegmatogenous retinal detachment (RD) can have poor visual outcomes even with prompt and appropriate therapy. Pars plana vitrectomy is a leading management modality for the treatment of RD. This procedure is generally accompanied by the use of internal tamponade. Various gases and silicone oils may yield beneficial outcomes. Heavy silicone oils have been approved in some European nations but are not available in the USA. Different tamponade agents have unique benefits and risks, and choice of the agent should be individualized according to the characteristics of the patient and RD, as well as perioperative and postoperative factors.
Noradrenaline Release and the Pathophysiology of Primary Human Hypertension (1989)

Measurements of the overflow of norepinephrine to plasma from individual organs (using radiotracer methodology) were used to delineate the pattern of sympathetic nervous system activation present in primary human hypertension. Mean total norepinephrine (NE) spillover in hypertensive patients was 418 ng/min, 42% (124 ng/min) higher than in subjects with normal blood pressure (BP)(P less than .05). Norepinephrine spillover among hypertensive patients was a function of age, only being elevated in patients under 40 years of age. Half of the excess in total norepinephrine release in hypertensive patients was accounted for by increased cardiorenal spillover. Mean renal norepinephrine spillover was 120 ng/min, compared with 69 ng/min in healthy subjects (P less than .02). Renal spillover was highest in younger patients. Corresponding cardiac norepinephrine spillover values were 12.6 ng/min and 5.1 ng/min (P less than .01). The balance of the excess total norepinephrine spillover comes from undetermined sites, but not the lungs or hepatomesenteric circulation. These measurements of regional norepinephrine overflow suggest that sympathetic nervous outflow to the kidneys and heart is selectively activated in early hypertension.
Application of phylogenetic microarrays to interrogation of human microbiota (2011)

Human-associated microbiota is recognized to play vital roles in maintaining host health, and it is implicated in many disease states. While the initial surge in the profiling of these microbial communities was achieved with Sanger and next-generation sequencing, many oligonucleotide microarrays have also been developed recently for this purpose. Containing probes complementary to small ribosomal subunit RNA gene sequences of community members, such phylogenetic arrays provide direct quantitative comparisons of microbiota composition among samples and between sample groups. Some of the developed microarrays including PhyloChip, Microbiota Array, and HITChip can simultaneously measure the presence and abundance of hundreds and thousands of phylotypes in a single sample. This review describes the currently available phylogenetic microarrays that can be used to analyze human microbiota, delineates the approaches for the optimization of microarray use, and provides examples of recent findings based on microarray interrogation of human-associated microbial communities.
Spread-spectrum multiple-access performance of orthogonal codes for indoor radio communications (1990)

Direct-sequence spread spectrum, with its inherent resistance to multipath, is a promising technique for indoor wireless communication. To allow multiple users within a limited bandwidth, code division multiple access (CDMA) is needed. The bandwidth efficiency of M-ary CDMA systems in fading multipath indoor radio channels is analyzed. It is shown that M-ary signaling improves the bandwidth efficiency significantly when compared to binary signaling.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Lesser Response to Angiotensin-Converting–Enzyme Inhibitor Therapy in Black as Compared with White Patients with Left Ventricular Dysfunction (2001)

Enalapril therapy is associated with a significant reduction in the risk of hospitalization for heart failure among white patients with left ventricular dysfunction, but not among similar black patients. This finding underscores the need for additional research on the efficacy of therapies for heart failure in black patients.
Trastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer (2013)

Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody-drug conjugate. T-DM1 consists of the potent antimicrotubule agent DM1, linked via a noncleavable linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1 to the HER2-positive (HER2(+)) tumor cell combined with trastuzumab's activation of antibody-dependent cell-mediated cytotoxicity and inhibition of HER2-mediated signal transduction. In phase II studies, T-DM1 was active in patients with trastuzumab- and lapatinib-refractory metastatic breast cancer and led to improved progression-free survival compared with the combination of trastuzumab and docetaxel in the first-line setting. In a recent phase III trial in patients with metastatic breast cancer who previously received trastuzumab and a taxane, T-DM1 resulted in improved progression-free and overall survival compared with capecitabine and lapatinib. T-DM1 is associated with a favorable toxicity profile; reversible thrombocytopenia and hepatic transaminase elevations are the only grade ≥3 adverse event present in 5% or more of patients. Alopecia, peripheral neuropathy, and neutropenia are distinctly uncommon. On the basis of its improved efficacy and toxicity compared with capecitabine/lapatinib, T-DM1 should be considered the standard for patients with HER2(+) metastatic breast cancer who have previously progressed on trastuzumab and a taxane. Results from additional randomized studies in metastatic breast cancer are pending, and trials in the (neo)adjuvant setting are being initiated.
Products of Allicin Transformation: Ajoenes and Dithiins, Characterization and their Determination by HPLC* (1990)

Constituents of crushed garlic bulbs ( ALLIUM SATIVUM L.), such as allicin, ( E/Z)-ajoene, and the vinyldithiins, were synthesized and purified by an LC method. Purity was proved by TLC, HPLC, and GC systems. Identity was confirmed by comparison with spectral data from the literature. In order to establish external standards, silica gel adsorbates of the respective substances were prepared. For quantitative determination of allicin and its transformation products, an isocratic HPLC method was developed. Calibration was performed by the use of these external standards, and by comparison to an internal standard. The influence of different media on allicin transformation, including the ( E/Z)-ratio of the ajoenes, has been elaborated.
A Formal Definition of Data Flow Graph Models (1986)

In this paper, a new model for parallel computations and parallel computer systems that is based on data flow principles is presented. Uninterpreted data flow graphs can be used to model computer systems including data driven and parallel processors. A data flow graph is defined to be a bipartite graph with actors and links as the two vertex classes. Actors can be considered similar to transitions in Petri nets, and links similar to places. The nondeterministic nature of uninterpreted data flow graphs necessitates the derivation of liveness conditions.