gebhart/patrepeval huggingface dataset:
An update on measurement and monitoring of cough: what are the important study endpoints? (2014)

Considerable progress has been achieved in the development of tools that assess cough. The visual analogue scale (VAS) for cough severity is widely used in clinical practice because it's simple and practical. The Leicester cough questionnaire (LCQ) and the cough-specific quality of life questionnaire (CQLQ) are the most widely used health status questionnaires for adults with chronic cough. They are well validated for assessing the impact of cough. Cough can be assessed objectively with challenge tests that measure the sensitivity of the cough reflex. Cough challenge tests are better used to determine the mechanism of action of therapy, rather than efficacy. Cough frequency monitoring, the preferred tool to objectively assess cough, is increasingly being used as primary end-points in clinical trials. The most widely used cough monitors are the Leicester cough monitor (LCM) and VitaloJak. They are ambulatory devices that consist of a microphone and recording device. Cough frequency monitors do not reflect the intensity or the impact of cough; hence their relationship with subjective measures of cough is weak. Cough should therefore be assessed with a combination of subjective and objective tools. There is a paucity of studies that have investigated the minimal important difference of cough frequency monitors, rendering further investigations needed.
Convection-Enhanced Drug Delivery: Increased Efficacy and Magnetic Resonance Image Monitoring (2005)

Convection-enhanced drug delivery (CED) is a novel approach to directly deliver drugs into brain tissue and brain tumors. It is based on delivering a continuous infusion of drugs via intracranial catheters, enabling convective distribution of high drug concentrations over large volumes of the target tissue while avoiding systemic toxicity. Efficient formation of convection depends on various physical and physiologic variables. Previous convection-based clinical trials showed significant diversity in the extent of convection among patients and drugs. Monitoring convection has proven to be an essential, yet difficult task. The current study describes the application of magnetic resonance imaging for immediate assessment of convection efficiency and early assessment of cytotoxic tissue response in a rat brain model. Immediate assessment of infusate distribution was obtained by mixing Gd-diethylenetriaminepentaacetic acid in the infusate prior to infusion. Early assessment of cytotoxic tissue response was obtained by subsequent diffusion-weighted magnetic resonance imaging. In addition, the latter imaging methodologies were used to establish the correlation between CED extent and infusate's viscosity. It was found that low-viscosity infusates tend to backflow along the catheter track, whereas high-viscosity infusates tend to form efficient convection. These results suggest that CED formation and extent may be significantly improved by increasing the infusate's viscosities, thus increasing treatment effects.
Morpholino and Phosphorothioate Antisense Oligomers Compared in Cell-Free and In-Cell Systems (1997)

Morpholino and phosphorothioate (S-DNA) antisense oligos were compared in both cell-free and in-cell translation systems. In the most stringent test of specificity in the cell-free system, a globin-targeted S-DNA oligo was found to inhibit its target sequence at concentrations of 10 nM and above, but the sequence-specific component of this inhibition dropped below 50% at concentrations of 100 nM and above. A corresponding Morpholino oligo achieved even higher inhibition at 10 nM, but in contrast to the S-DNA, with the Morpholino, the sequence-specific component of this inhibition remained above 93% at a concentration of 3000 nM. In this same cell-free test system, several S-DNA oligos exhibited substantial undesired nonantisense effects at concentrations of 300 nM and above, whereas corresponding Morpholino oligos exhibited little or no nonantisense activity through a concentration of 3000 nM. In scrape-loaded HeLa cells, both globin-targeted and HBV-targeted S-DNAs (both antisense and control oligos) generally failed to achieve significant translational inhibition at extracellular concentrations up to 3000 nM. In contrast, the Morpholino oligos achieved effective and specific translational inhibition at extracellular concentrations ranging from 30 nM to 3000 nM.
Fibrotic Skin Diseases (1990)

Tissue fibrosis, characterized by excessive deposition of collagen and other connective tissue components, is the major histopathologic feature of a variety of clinical conditions. Excessive collagen deposition can occur in internal organs as, for example, in the case of pulmonary fibrosis or liver cirrhosis. Skin is often affected by fibrotic processes, and dermal fibrosis is the pathologic hallmark of several acquired and heritable cutaneous disorders<sup>1-3</sup>(Table). The prototype of fibrotic skin diseases is scleroderma, which can be divided into systemic and localized forms.<sup>4,5</sup>Progressive systemic sclerosis (PSS) is a generalized connective tissue disorder, the fibrotic processes affecting not only the skin but also the lungs, heart, kidneys, and the gastrointestinal tract. A subset of systemic scleroderma, the CREST syndrome, demonstrates<i>c</i>alcinosis cutis,<i>R</i>aynaud's phenomenon,<i>e</i>sophageal dysfunction, sclerodactyly, and telangiectasia. In most instances, visceral involvement in the CREST syndrome is limited or absent, and, consequently, the prognosis of this form is
Metabolic Implications of Dietary Trans‐fatty Acids (2009)

Dietary trans-fatty acids are associated with increased risk of cardiovascular disease and have been implicated in the incidence of obesity and type 2 diabetes mellitus (T2DM). It is established that high-fat saturated diets, relative to low-fat diets, induce adiposity and whole-body insulin resistance. Here, we test the hypothesis that markers of an obese, prediabetic state (fatty liver, visceral fat accumulation, insulin resistance) are also worsened with provision of a low-fat diet containing elaidic acid (18:1t), the predominant trans-fatty acid isomer found in the human food supply. Male 8-week-old Sprague-Dawley rats were fed a 10% trans-fatty acid enriched (LF-trans) diet for 8 weeks. At baseline, 3 and 6 weeks, in vivo magnetic resonance spectroscopy (1H-MR) assessed intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content. Euglycemic-hyperinsulinemic clamps (week 8) determined whole-body and tissue-specific insulin sensitivity followed by high-resolution ex vivo 1H-NMR to assess tissue biochemistry. Rats fed the LF-trans diet were in positive energy balance, largely explained by increased energy intake, and showed significantly increased visceral fat and liver lipid accumulation relative to the low-fat control diet. Net glycogen synthesis was also increased in the LF-trans group. A reduction in glucose disposal, independent of IMCL accumulation was observed in rats fed the LF-trans diet, whereas in rats fed a 45% saturated fat (HF-sat) diet, impaired glucose disposal corresponded to increased IMCLTA. Neither diet induced an increase in IMCLsoleus. These findings imply that trans-fatty acids may alter nutrient handling in liver, adipose tissue, and skeletal muscle and that the mechanism by which trans-fatty acids induce insulin resistance differs from diets enriched with saturated fats.
BG-12 (Dimethyl Fumarate) Pharmacodynamic Responses Have Distinct Temporal Profiles and Are Dose-Dependent (P05.146) (2013)

OBJECTIVE: To characterize BG-12 (dimethyl fumarate)-dependent pharmacodynamic responses in mice.
T-Cell Killing of Target Cells Induced by Hybrid Antibodies: Comparison of Two Bispecific Monoclonal Antibodies (1987)

Two different bispecific hybrid antibodies were generated by cell fusion of pairs of existing hybrid-myeloma cell lines. Both hybrid antibodies had similar specificity for human CD3 and mouse Thy-1 but differed in the isotypes of the immunoglobulin heavy chains. Hybrid HA2b/2b was a hybrid between a rat IgG2b (CD3) and a rat IgG2b anti-Thy-1, whereas HA2b/2c was a hybrid between the same rat IgG2b (CD3) and a rat IgG2c anti-Thy-1. Both hybrid antibodies were found to be very potent in inducing the killing of Thy-1-positive targets by human T-cell blasts, with the hetero-hybrid HA2b/2c showing a higher titer. T-cell blasts generated from resting peripheral blood mononuclear cells by a novel mitogenic antibody, YTH361, were exploited as effector cells. In addition to the CD3-dependent killing, the rat IgG2b anti-Thy-1 antibody and the hybrid antibody HA2b/2b but not the rat IgG2c anti-Thy-1 or the hybrid antibody HA2b/2c were also able to elicit antibody-dependent cell-mediated cytotoxicity (ADCC). This ADCC was inhibited by an anti-FcRlow (CD16) monoclonal antibody, which suggests that these effectors were K-cells. Toxicity toward the T-cell blast effector population was also observed, but in this instance the hetero-hybrid HA2b/2c had a lower cytotoxic titer. In conclusion, mixed isotype hybrid antibodies may have some advantages for eliciting T-cell-mediated killing of tumor cell targets by exhibiting a better therapeutic ratio of target cell to effector cell cytotoxicity.
Translational control of interleukin 2 messenger RNA as a molecular mechanism of T cell anergy. (1996)

T cell stimulation by triggering through the T cell receptor (TCR) in the absence of costimulatory signals or by calcium ionophore induces unresponsiveness in T cells to further stimulation, a phenomenon known as anergy. In freshly isolated T cells, calcium ionophore induces expression of interleukin (IL)-2 messenger (mRNA), but this mRNA is not translated and not loaded with ribosomes. In addition, while plate-bound anti-CD3 stimulation of resting T cells leads to IL-2 mRNA expression and IL-2 secretion, in cells pretreated with calcium ionophore before anti-CD3 stimulation, the IL-2 mRNA remains polysome unloaded and no IL-2 is produced. These observations show that IL-2 expression is controlled at the translational level, by differential ribosome loading. Furthermore, our data suggest that translational control of IL-2 mRNA may be a molecular mechanism by which anergy is attained.
On the cusp of change for Learning in the Oil & Gas Industry (2018)

Learning Systems for geophysicists have been traditionally founded upon a strong basis of mathematics and physics and supported with real-life and work experiences that mature their ability to positively contribute to the Oil & Gas Industry. Although other data types have brought important contributions to the Industry, seismic data has played the single, most influential role in Exploration & Production, and the rapid development of seismic data acquisition, processing and interpretation methods has formed the basis for the bulk of training that geophysicists have received. This type of technical knowledge transfer lends itself to proven historical learning methods and geophysical curriculums that were initiated at universities, and which were subsequently built upon by Industry employers. This Learning System focused upon the geophysical discipline, and although effective, was slow, expensive and limited in its maturation of future O&G Industry leadership. The geophysicist of today is facing increased pressure to contribute to industry success quickly, and to demonstrate a broader set of skills across an increasingly diverse portfolio. The traditional Learning Systems of the past are not well-suited to this new environment which is characterized by cross-disciplinary collaboration and integration, and by a growing data richness and complexity! Learning Systems will have to change to meet increasing industry demands, and to meet today’s emerging professional’s style. This change in Learning Systems will include changes in learning topics and materials, changes in delivery systems, and a rebalancing of responsibility across learning providers. Such a system will focus upon supporting the geophysicist of the future who will serve as an equal collaborator on a multi-disciplinary team immersed in real-time data streams. Presentation Date: Tuesday, October 16, 2018 Start Time: 1:50:00 PM Location: 204C (Anaheim Convention Center) Presentation Type: Oral
Effects of a highly basic region of human immunodeficiency virus Tat protein on nucleolar localization (1990)

Human immunodeficiency virus type 1 encodes a positive trans-activator protein, Tat, which is located predominantly in the cell nucleolus. To study the role of the basic region of Tat in nucleolar localization, we constructed fusion genes encoding serially deleted segments of Tat joined to the amino-terminal end of the Escherichia coli beta-galactosidase molecule. We show that the basic region of Tat was sufficient for nuclear localization but not for nucleolar localization. Addition of three amino acids (59, 60, and 61) of the Tat sequence at the C-terminal end of the basic region was necessary for the chimeric beta-galactosidase to localize in the nucleus as well as in the nucleolus. We demonstrate that a short amino acid sequence (G-48 RKKRRQRRRA HQ N-61), when fused to the amino terminus of beta-galactosidase, can act as a nucleolar localization signal.
Contamination of peripheral blood stem cell harvests by circulating neuroblastoma cells (1990)

Abstract Peripheral blood stem cells (PBSC) are being used as one alternative to autologous marrow rescue for patients with neuroblastoma and other solid malignancies. Some physicians prefer use of PBSC because less risk of tumor contamination is believed to exist. This hypothesis was evaluated by immunocytologic analysis of blood samples and concurrently drawn bone marrow (BM) samples and of PBSC harvests obtained from 31 patients with disseminated neuroblastoma. We found circulating neoplastic cells in 75% of specimens analyzed at diagnosis, in 36% during therapy, and in 14% of PBSC harvests. Tumor cells in blood obtained during therapy did not appear until 3 months after the time of diagnosis. Clearance of circulating neuroblastoma cells was documented after two courses of induction chemotherapy. Six of 13 patients with minimal or no BM disease had positive blood specimens. We conclude that substantial risk of tumor contamination of PB harvests exists and recommend that induction chemotherapy be administered before hematopoietic progenitor cells are collected from blood.
ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas (2010)

Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.
Stack-propagation: Improved Representation Learning for Syntax (2016)

Traditional syntax models typically leverage part-of-speech (POS) information by constructing features from hand-tuned templates. We demonstrate that a better approach is to utilize POS tags as a regularizer of learned representations. We propose a simple method for learning a stacked pipeline of models which we call "stack-propagation". We apply this to dependency parsing and tagging, where we use the hidden layer of the tagger network as a representation of the input tokens for the parser. At test time, our parser does not require predicted POS tags. On 19 languages from the Universal Dependencies, our method is 1.3% (absolute) more accurate than a state-of-the-art graph-based approach and 2.7% more accurate than the most comparable greedy model.
Time-dependent whole-body fluorescence tomography of probe bio-distributions in mice (2005)

We present a fast scanning fluorescence optical tomography system for imaging the kinetics of probe distributions through out the whole body of small animals. Configured in a plane parallel geometry, the system scans a source laser using a galvanometer mirror pair (tauswitch~1ms) over flexible source patterns, and detects excitation and emission light using a high frame rate low noise, 5 MHz electron multiplied charge-coupled device (EMCCD) camera. Phantom studies were used to evaluate resolution, linearity, and sensitivity. Time dependent (deltat=2.2 min.) in vivo imaging of mice was performed following injections of a fluorescing probe (indocyanine green). The capability to detect differences in probe delivery route was demonstrated by comparing an intravenous injection, versus an injection into a fat pocket (retro orbital injection). Feasibility of imaging the distribution of tumor-targeted molecular probes was demonstrated by imaging a breast tumor-specific near infrared polypeptide in MDA MB 361 tumor bearing nude mice. A tomography scan, at 24 hour post injection, revealed preferential uptake in the tumor relative to surrounding tissue.
Immunoregulatory activity of adenosine and its role in human cancer progression (2014)

The adenosinergic pathway plays an important role in cancer progression. Aside from regulating functions of tumor cells and tissue cells present in the tumor microenvironment, extracellular adenosine is an autocrine or paracrine factor with powerful immunoregulatory activity. Adenosine signaling downregulates functions of most immune effector cells but enhances expansion and activity of immune cells responsible for suppression of anti-tumor immune responses. Adenosine is critical for limiting potential tissue-destructive effects of activated immune cells. It also facilitates tumor escape from the immune control. This review illustrates the involvement of adenosine and its four receptors, A1R, A2AR, A2BR and A3R, in the complex regulation of cellular and molecular cross talk that contributes to cancer progression. It also considers the potential of therapeutics targeting the adenosinergic pathway for benefiting cancer patients.
Microarray Temperature Optimization Using Hybridization Kinetics (2009)

In any microarray hybridization experiment, there are contributions at each probe spot due to the match and numerous mismatch target species (i.e., cross-hybridizations). One goal of temperature optimization is to minimize the contribution of mismatch species; however, achieving this goal may come at the expense of obtaining equilibrium reaction conditions. We employ two-component thermodynamic and kinetic models to study the trade-offs involved in temperature optimization. These models show that the maximum selectivity is achieved at equilibrium, but that the mismatch species controls the time to equilibrium via the competitive displacement mechanism. Also, selectivity is improved at lower temperatures. However, the time to equilibrium is also extended, so that greater selectivity cannot be achieved in practice. We also employ a two-color real-time microarray reader to experimentally demonstrate these effects by independently monitoring the match and mismatch species during multiplex hybridization. The only universal criterion that can be employed is to optimize temperature based upon attaining equilibrium reaction conditions. This temperature varies from one probe to another, but can be determined empirically using standard microarray experimentation methods.
Orphan Nuclear Receptors: Shifting Endocrinology into Reverse (1999)

Steroid and thyroid hormones and vitamin A metabolites (retinoids) regulate the expression of complex gene programs by binding to members of the nuclear receptor family of ligand-activated transcription factors. The nuclear receptor family also includes many "orphan" members that currently lack known ligands but that represent candidate receptors for new hormones. Recently, natural and synthetic ligands have been identified for several orphan receptors and used to dissect their biological roles. This "reverse endocrinology" strategy has resulted in the discovery of unanticipated nuclear signaling pathways for retinoids, fatty acids, eicosanoids, and steroids with important physiological and pharmacological ramifications.
Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy (2015)

Chemoimmunotherapy combines chemotherapy based on anticancer drugs with immunotherapy based on immune activators to eliminate or inhibit the growth of cancer cells. In this study, water-insoluble paclitaxel (PTX) was dispersed in water using hyaluronic acid (HA) to generate a tumor-associated antigen in the tumor microenvironment. Cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) were used to enhance the T helper (Th) 1 immune response. However, CpG ODNs also induced the secretion of interleukin-10 (IL-10) that reduces the Th1 response and enhances the T helper 2 (Th2) response. Therefore, RNA interference was used to downregulate IL-10 secretion from bone marrow-derived den-dritic cells (BMDCs). For the combined immunomodulation of BMDCs, we fabricated two types of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing CpG ODNs to activate BMDCs via Toll-like receptor 9 (CpG ODN-encapsulated PLGA NPs, PCNs) or a small interfering RNA to silence IL-10 (IL-10 small interfering RNA-encapsulated PLGA NPs, PINs). Treatment of BMDCs with both types of PLGA NPs increased the Th1/Th2 cytokine (IL-12/IL-10) expression ratio, which is important for the effective induction of an antitumor immune response. After primary injection with the HA/PTX complex, the tumor-associated antigen was generated and taken up by tumor-recruited BMDCs. After a secondary injection with immunomodulating PCNs and PINs, the BMDCs became activated and migrated to the tumor-draining lymph nodes. As a result, the combination of chemotherapy using the HA/PTX complex and immunotherapy using PCNs and PINs not only efficiently inhibited tumor growth but also increased the animal survival rate. Taken together, our results suggest that the sequential treatment of cancer cells with a chemotherapeutic agent and immunomodulatory nanomaterials represents a promising strategy for efficient cancer therapy.