gebhart/patrepeval huggingface dataset:
Activation of purified soluble guanylate cyclase by protoporphyrin IX. (1982)

Soluble guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] purified from bovine lung is markedly activated (30- to 40-fold) by protoporphyrin IX (Ka, 15-25 nM) and is inhibited by hematin (Ki, 3.7 microM) when MgGTP is used as substrate. Guanylate cyclase possesses specific activities (mumol of cGMP per min/mg of protein) of 0.1-0.2 (MgGTP) and 0.3-0.5 (MnGTP) and can attain values of 2-8 (MgGTP) or 1-1.4 (MnGTP) in the presence of protoporphyrin IX. Guanylate cyclase purified in this study contains heme and is activated by nitric oxide and nitrosyl-heme to the same magnitude as that by protoporphyrin IX. With the exception of hematoporphyrin IX, close structural analogs of protoporphyrin IX, including precursors and metabolites, do not activate guanylate cyclase. The insertion of iron into protoporphyrin IX to form heme or hematin renders the metalloporphyrin an inhibitor of unactivated or activated guanylate cyclase. The data suggest that protoporphyrin IX and heme could function to modulate guanylate cyclase activity.
Number of Samples and Wavelengths Required for the Training Set in Near-Infrared Reflectance Spectroscopy (1984)

Near-infrared reflectance spectroscopy uses a learning algorithm to derive a set of weighting coefficients from the reflectance spectra of a reference sample set. These coefficients, when applied to the reflectance values of an unknown sample at specific wavelengths, can be used to calculate constituent concentrations. Having enough samples in the training set and enough wavelengths in the calculation procedures is essential, but there are severe drawbacks to picking too large a number. This paper describes the principles and implementation of a working procedure for objectively calculating the minimum number of training samples required.
Signal Transduction Pathways Involved in Rheumatoid Arthritis Synovial Fibroblast Interleukin-18-induced Vascular Cell Adhesion Molecule-1 Expression (2002)

Vascular cell adhesion molecule (VCAM)-1 has been implicated in interactions between leukocytes and connective tissue, including rheumatoid arthritis (RA) synovial tissue fibroblasts. Such interactions within the synovium contribute to RA inflammation. Using phosphoinositide 3-kinase (PI3-kinase) inhibitor LY294002 and Src inhibitor PP2, we show that interleukin (IL)-18-induced ERK1/2 activation is Src kinase-dependent. Antisense (AS) c-Src oligonucleotide (ODN) treatment reduced IL-18-induced ERK1/2 expression by 32% compared with control, suggesting an upstream role of Src in ERK1/2 activation. AS c-Src ODN treatment also inhibited Akt expression by 74% compared with sense control. PI3-kinase inhibitor LY294002 or AS PI3-kinase ODN inhibited Akt expression. AS c-Src ODN inhibited Akt phosphorylation, confirming Src is upstream of PI3-kinase in IL-18-induced RA synovial fibroblast signaling. IL-18 induced a time-dependent activation of c-Src, Ras, and Raf-1, suggesting this signaling cascade plays a role in ERK activation. IL-18 directly activated Src kinase by more than 4-fold over basal levels by enzymatic assay. Electrophoretic mobility shift assay showed that activator protein-1 (AP-1) is activated by IL-18 through ERK and Src but not through PI3-kinase. In an alternate pathway, inhibition of IL-1 receptor-associated kinase-1 (IRAK) with AS ODN to IRAK reduced IL-18-induced expression of nuclear factor kappaB (NFkappaB). Finally, IL-18-induced cell surface VCAM-1 expression was inhibited by treatment with AS ODNs to c-Src, IRAK, PI3-kinase, and ERK1/2 by 57, 43, 41, and 32% compared with control sense ODN treatment, respectively. These data support a role for IL-18 activation of three distinct pathways during RA synovial fibroblast stimulation: two Src-dependent pathways and the IRAK/NFkappaB pathway. Targeting VCAM-1 signaling mechanisms may represent therapeutic approaches to inflammatory and angiogenic diseases characterized by adhesion molecule up-regulation.
Endocrine and Non-Endocrine Actions of Ghrelin (2003)

Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach. Substantially lower amounts were detected in bowel, pancreas, kidneys, the immune system, placenta, testes, pituitary, and hypothalamus. Ghrelin displays strong growth hormone (GH)-releasing action mediated by the activation of the so-called GH secretagogue (GHS) receptor (GHS-R) type 1a. GHS-R are concentrated in the hypothalamus-pituitary unit but are also distributed in other central and peripheral tissues. Apart from the potent GH-releasing action, ghrelin has other actions including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, influence on exocrine and endocrine pancreatic function as well as on glucose metabolism, cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system. The discovery of ghrelin opened many new perspectives of research in neuroendocrinology and metabolism, and even also in other fields of internal medicine as gastroenterology, immunology, oncology and cardiology. The possibility that ghrelin and/or GHS analogs, acting as either agonists or antagonists on different activities, might have clinical impact is obviously suggested and is receiving great attention.
Tuning Neural Phase Entrainment to Speech (2017)

Musical rhythm positively impacts on subsequent speech processing. However, the neural mechanisms underlying this phenomenon are so far unclear. We investigated whether carryover effects from a preceding musical cue to a speech stimulus result from a continuation of neural phase entrainment to periodicities that are present in both music and speech. Participants listened and memorized French metrical sentences that contained (quasi-)periodic recurrences of accents and syllables. Speech stimuli were preceded by a rhythmically regular or irregular musical cue. Our results show that the presence of a regular cue modulates neural response as estimated by EEG power spectral density, intertrial coherence, and source analyses at critical frequencies during speech processing compared with the irregular condition. Importantly, intertrial coherences for regular cues were indicative of the participants' success in memorizing the subsequent speech stimuli. These findings underscore the highly adaptive nature of neural phase entrainment across fundamentally different auditory stimuli. They also support current models of neural phase entrainment as a tool of predictive timing and attentional selection across cognitive domains.
Serum Exosomal Long Noncoding RNAs ENSG00000258332.1 and LINC00635 for the Diagnosis and Prognosis of Hepatocellular Carcinoma (2018)

Abstract Background: Increasing studies suggest that long noncoding RNAs (lncRNAs) are involved in carcinogenesis of human cancers and might be used as diagnostic biomarkers for cancers. Methods: A total of 301 participants were recruited in the first part of the study, including a hepatocellular carcinoma (HCC) group (n = 60), liver cirrhosis (LC) group (n = 85), chronic hepatitis B (CHB) group (n = 96), and healthy subjects (n = 60). In the second part, we collected 55 HCC patients, 60 CHB patients, and 60 healthy subjects as an independent cohort to validate the ability of the experiential lncRNAs for identifying HCC from CHB. A commercial kit was used to isolate serum exosomes and total RNA. The relative levels of lnRNAs and GAPDH mRNA were measured with TaqMan PCR. Results: The results showed that the levels of ENSG00000258332.1 and LINC00635 in the HCC group were significantly higher than those in the other groups (all P &amp;lt; 0.05). A high ENSG00000258332.1 level in HCC was associated with portal vein tumor emboli, lymph node metastasis, TNM stage, and overall survival (OS; all P &amp;lt; 0.05), and a high LINC00635 level was related to lymph node metastasis, TNM stage, and OS (all P &amp;lt; 0.05). ENSG00000258332.1 discriminated HCC from CHB, gaining an area under the ROC curve (AUC) of 0.719 (cutoff value of 1.345); LINC00635 gained an AUC of 0.750 (cutoff value of 1.690). Furthermore, the AUC for the combination of the 2 lncRNAs and serum AFP (cutoff value of 20 μg/L) was 0.894. The abilities of the 2 lncRNAs for identifying HCC from CHB were validated by an independent cohort. Conclusions: The results suggested that the combination of serum exosomal ENSG00000258332.1, LINC00635, and AFP may be a valuable assay in diagnosis and prognosis of HCC. Impact: Our data will shed light on exosomal lncRNAs as biomarkers for HCC. Cancer Epidemiol Biomarkers Prev; 27(6); 710–6. ©2018 AACR.
Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients (2011)

In chronic viral infections, CD8⁺ T cells become functionally deficient and display multiple molecular alterations. In contrast, only little is known of self- and tumor-specific CD8⁺ T cells from mice and humans. Here we determined molecular profiles of tumor-specific CD8⁺ T cells from melanoma patients. In peripheral blood from patients vaccinated with CpG and the melanoma antigen Melan-A/MART-1 peptide, we found functional effector T cell populations, with only small but nevertheless significant differences in T cells specific for persistent herpesviruses (EBV and CMV). In contrast, Melan-A/MART-1-specific T cells isolated from metastases from patients with melanoma expressed a large variety of genes associated with T cell exhaustion. The identified exhaustion profile revealed extended molecular alterations. Our data demonstrate a remarkable coexistence of effector cells in circulation and exhausted cells in the tumor environment. Functional T cell impairment is mediated by inhibitory receptors and further molecular pathways, which represent potential targets for cancer therapy.
Plantar Fascia: Imaging Diagnosis and Guided Treatment (2010)

Plantar fasciopathy is a common cause of heel pain. This article covers the imaging anatomy of the hindfoot, the imaging findings on ultrasound and magnetic resonance imaging (MRI) of plantar fasciopathy, plantar fibromas, trauma, Achilles tendonopathy, neural compression, stress fractures of the os calcis and other heel pad lesions. Thickening of the plantar fascia insertion more than 5 mm either on ultrasound or MRI is suggestive of plantar fasciopathy. Ultrasound is superior to MRI for diagnosis of plantar fibroma as small low signal lesions on MRI are similar to the normal plantar fascia signal. Ultrasound demonstrates low echogenicity compared with the echogenic plantar fascia. Penetrating injuries can appear bizarre due to associated foreign body impaction and infection. Achilles tendonopathy can cause heel pain and should be considered as a possible diagnosis. Treatment options include physical therapy, ECSWT, corticosteroid injection, and dry needling. Percutaneous US guided treatment methods will be described.
Anti‐tumor effect of combined treatment with thymosin alpha 1 and interleukin‐2 after 5‐fluorouracil in liver metastases from colorectal cancer in rats (1994)

We studied the effect of combined chemo-immunotherapy, 5-FU followed by thymosin alpha 1 (T alpha 1) and interleukin-2 (IL-2) at low doses, on liver metastases from colorectal cancer, induced by splenic injection of DHD/K12 cells (1,2-dimethylhydrazine-induced colon adenocarcinoma) in syngeneic BDIX rats. The presence of liver metastases was checked by laparotomy 14 days after tumor-cell injection. Evaluable rats were assigned randomly to 5 experimental groups designated as control, 5-FU, IL-2, 5-FU/IL-2 and 5-FU/T alpha 1/IL-2. 5-FU was administered i.v. as a continuous infusion for 7 days by an osmotic device implanted surgically. T alpha 1 and IL-2 were administered for 4 days and repeated after 11 days. Combined chemo-immunotherapy was shown both to significantly reduce the growth of liver metastases and to prevent extra-hepatic spread. 5-FU/T alpha 1/IL-2 also improved survival rate. Combined immunotherapy after 5-FU restored NK activity of the peripheral-blood-mononuclear-cell (PBMC) in tumor and/or 5-FU immunodepressed rats and enhanced PBMC cytotoxic activity against the DHD/K12 autologous cell line. This model was devised to mimic the clinical situation of unresectable liver metastases.
Growth and continued function of rat marrow cells in x-radiated mice. (1956)

Summary Leukocytes in rat blood and bone marrow smears stained black or brown when treated histochemically for alkaline phosphatase. Mouse leukocytes in similar smears were uniformly phosphatase-negative. Following intravenous injection of rat marrow cells into x-radiated (810 r) mice, phosphatase-positive cells were present in marrow smears within 2 hours. With beginning marrow “regeneration” at 7 days, the phosphatase-positive cells rapidly increased in numbers. By 14–28 days, when “regeneration” was nearly complete, essentially all the cells were phosphatase-positive, and the smears were indistinguishable from rat marrow. Smears from mice injected with mouse bone marrow remained uniformly phosphatase-negative throughout all stages of regeneration. These findings indicate that injected rat marrow cells survive, divide, and eventually repopulate the marrow cavity of irradiated mice. Prolonged survival of these mice, in some cases beyond 30 days, appears to be correlated with the continued growth of phosphatase-positive marrow. This suggests that transplanted rat marrow is actually functioning hematopoietically in the heterologous host.
Decision support for drug prescription integrated with computer-based patient records in primary care (1993)

A conceptual model of an information system that integrates a controlled vocabulary, a patient database, and a knowledge base is described. Methods, design and components for the implementation of the system are discussed. It is argued that the key issue for the successful introduction of computer-based decision support in primary care today is integration with a computer-based patient record. Also important is that the knowledge acquisition process is based on the general practitioner's real needs. This has been achieved by, first, providing general practitioners with real patient data from a series of retrospective database studies; and second, letting a panel of general practitioners select, discuss and decide which computer reminders to implement. A hybrid representation scheme was chosen for the knowledge base. The combination of a standard procedural representation (the so-called Arden syntax) for the reminder knowledge with a semantic net representation for the medical factual knowledge facilitates knowledge sharing with other systems and knowledge reuse within the system.
Chemoprevention of heterocyclic amine‐induced mammary carcinogenesis in rats (2002)

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most prevalent carcinogenic heterocyclic amines in the environment, targeting the colon, prostate, pancreas, and mammary gland in rodents. Chemopreventive effects of synthetic and naturally occurring compounds on PhIP-induced rat mammary carcinogenesis were investigated in a series of experiments. In a PhIP feeding model, groups of 20-21 female F344 rats each, were treated with 0.02% PhIP alone or PhIP plus 0.5% 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), 1% green tea catechins, 1% alpha-tocopherol, 0.1% ellagic acid, or 1% chlorophyllin, each in the diet, or 0.1% caffeine in drinking water for 52 weeks. To assess the mechanism of HTHQ and caffeine inhibition of PhIP-induced carcinogenesis, effects of these compound on the in vitro metabolic activation of PhIP were examined in the presence of S9 mix. In the next series of experiments, the PhIP intragastric dose model was applied to allow separate investigation of the effects of chemicals during the initiation and postinitiation periods. In these experiments, female Sprague-Dawley rats were given eight intragastric doses of 100 mg/kg body weight during the first 4-8 weeks for initiation. Either during initiation or after initiation, or only after initiation, animals were treated with either corn or perilla oil at doses of 5 and 20%, conjugated fatty acid derived from safflower oil (CFA-S) or perilla oil (CFA-P) at a dose of 1%, arctiin at doses of 0.02 and 0.2% in the diet, or sodium nitrite (NaNO(2)) at a dose of 0.2% in drinking water. In the PhIP feeding model, administration of PhIP alone for 52 weeks induced adenocarcinomas in 40% of rats, but the incidence was remarkably reduced to 5% by the simultaneous treatment with 0.5% HTHQ, a strong lipophilic phenolic antioxidant, or to 10% by 0.1% caffeine. Administration of 1% chlorophyllin exerted similar, albeit weaker, effects. alpha-Tocopherol at a dose of 0.5% only reduced the multiplicity of carcinomas, and 1% green tea catechins only the mean size of mammary tumors. In a metabolic activation study of PhIP, HTHQ and caffeine clearly inhibited the formation of metabolites. In the PhIP gastric dose model, among the naturally occurring compounds examined, a plant lignan arctiin, perilla oil, which contains a large amount of n-6 alpha-linolenic acid, and CFA-S or CFA-P inhibited mammary tumor development, particularly in the postinitiation period, although a clear dose response was not observed. Treatment with 0.2% NaNO(2) in the initiation period was found to lower the volume of mammary tumors. The present results indicate that a number of compounds may be candidate chemopreventive agents against PhIP-induced mammary carcinogenesis, acting through different mechanisms and depending on the stage of carcinogenesis.
Room‐Temperature Gas Sensing Based on Electron Transfer between Discrete Tin Oxide Nanocrystals and Multiwalled Carbon Nanotubes (2009)

A new gas-sensing platform for low-concentration gases (NO2, H2, and CO) comprises discrete SnO2 nanocrystals uniformly distributed on the surface of multiwalled carbon nanotubes (CNTs). The resulting hybrid nanostructures are highly sensitive, even at room temperature, because their gas sensing abilities rely on electron transfer between the nanocrystals and the CNTs.
Synthesis, Antitumor Evaluation, and Apoptosis-Inducing Activity of Hydroxylated (E)-Stilbenes (2005)

The parallel solution-phase synthesis of a series of 30 monohydroxylated (E)-stilbene analogues is described. In vitro screening revealed low micromolar activity (GI(50)) against the MDA MB 468 breast cancer cell line. Activity in MDA MB 468 cells correlated with the ability to induce apoptosis following drug treatment by the most potent agents in the series, e.g., 5dy and 5jy, an observation further reinforced by AnnexinV-FITC analysis and fluorescence microscopy.
Kinetics of decarburisation of levitating liquid iron drops by carbon dioxide (1998)

Decarburisation experiments were carried out by levitating liquid iron droplets in a flowing gas stream containing carbon dioxide at 1723K. Decarburisation of liquid iron droplets by carbon dioxide can be adequately described by the mixed control of gas phase mass transport and dissociative chemisorption of carbon dioxide. Carbon monoxide in the gas phase does not have any significant effect on the rate of decarburisation. The rate of decarburisation decreases significantly with increase in sulphur content in the melt and this effect can be quantitatively explained using the Langmuir isotherm. Adsorption coefficient of sulphur is found to be 200. Influence of phosphorus and chromium in the melt on the rate of decarburisation is negligibly small.
Evidence of Association of Interleukin-1 Receptor-Like 1 Gene Polymorphisms with Chronic Rhinosinusitis (2009)

Pending replication of these results, this study suggests that polymorphisms within the IL1RL1 gene may be associated with CRS, conferring a protective effect, particularly among those with severe disease.
Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. (1990)

A33 is a mouse immunoglobulin G2a (IgG2a) monoclonal antibody (mAb) that detects a heat-stable, protease- and neuraminidase-resistant epitope. The antigen is homogeneously expressed by virtually all colon cancers and in the colon mucosa but not other epithelial tissues. The biodistribution and imaging characteristics of iodine-131 (131I)-mAbA33 were studied in colorectal carcinoma patients with hepatic metastases. Antibody labeled with 2 to 5 mCi of 131I was administered intravenously (IV) 7 to 8 days before surgery at five dose levels, ranging from 0.2 mg to 50 mg, with three or more patients entered at each dose level. In addition, three patients received 2 mg 131I-mAbTA99 (an isotype-matched control mAb) together with 125I-mAbA33. Evaluation included whole-body imaging with a gamma camera, technetium-99 (99mTc)-human serum albumin blood pool scans, liver/spleen scans, abdominal computed tomographic (CT) scans, hepatic arteriograms, antibody pharmacokinetics, and assessment of antibody distribution in biopsied malignant and normal tissues. Selective mAbA33 localization to tumor tissue was demonstrated in 19 of 20 patients, and external imaging correlated with surgical inspection, pathologic examination, and tissue radioactivity. One week after antibody administration, tumor:liver ratios ranged from 6.9:1 to 100:1 and tumor:serum ratios from 4.1:1 to 25.2:1. 99mTc-albumin blood pool studies showed that liver metastases were hypovascular, emphasizing the selective localization of mAbA33 despite poor tumor-blood flow. Control mAbTA99 studies showed mAbA33 localization was antigen-specific; tumor:liver ratios were 2.3- to 45-fold higher for specific antibody. In metastatic lesions, radioisotope was localized primarily in the viable periphery; however, even the necrotic tumor core concentrated specific antibody. External imaging showed isotope visualization in some patients' large bowel; whether this represents specific antibody uptake or gastric iodine secretion is unclear.
MADS-box genes are involved in floral development and evolution. (2001)

MADS-box genes encode transcription factors in all eukaryotic organisms thus far studied. Plant MADS-box proteins contain a DNA-binding (M), an intervening (I), a Keratin-like (K) and a C-terminal C-domain, thus plant MADS-box proteins are of the MIKC type. In higher plants most of the well-characterized genes are involved in floral development. They control the transition from vegetative to generative growth and determine inflorescence meristem identity. They specify floral organ identity as outlined in the ABC model of floral development. Moreover, in Antirrhinum majus the MADS-box gene products DEF/GLO and PLE control cell proliferation in the developing flower bud. In this species the DEF/GLO and the SQUA proteins form a ternary complex which determines the overall "Bauplan" of the flower. Phylogenetic reconstructions of MADS-box sequences obtained from ferns, gymnosperms and higher eudicots reveal that, although ferns possess already MIKC type genes, these are not orthologous to the well characterized MADS-box genes from gymnosperms or angiosperms. Putative orthologs of floral homeotic B- and C-function genes have been identified in different gymnosperms suggesting that these genes evolved some 300-400 million years ago. Both gymnosperms and angiosperms also contain a hitherto unknown sister clade of the B-genes, which we termed Bsister. A novel hypothesis will be described suggesting that B and Bsister might be involved in sex determination of male and female reproductive organs, respectively.