gebhart/patrepeval huggingface dataset:
Differential regulation of the tumor suppressor molecules, retinoblastoma susceptibility gene product (Rb) and p53, during cell cycle progression of normal human T cells (1991)

We have activated resting human T lymphocytes to study the roles of the putative cell cycle control gene products, retinoblastoma susceptibility gene product (Rb) and p53, in regulating cell proliferation. After stimulation with phorbol, 12,13, dibutyrate and the calcium ionophore, ionomycin, which triggers a rapid entry of cells into G1 phase, we demonstrated Rb phosphorylation 24 h later, well before the onset of DNA synthesis. This finding, in contrast to reports using proliferating cell lines, implies that Rb phosphorylation is not a proximal event regulating the G1 to S transition. The production of p53 became detectable 3 to 6 h after addition of phorbol, 12,13,-dibutyrate and ionomycin, and peaked at 30 to 42 h. To further delineate the relationship of the synthesis and metabolism of the proteins to cell cycle progression, we used three agents to arrest progression of activated T cells at various points in the cell cycle. Aphidicolin arrested the cells at the G1/S boundary, whereas deferoxamine, an iron chelator, arrested the cells at an earlier stage of the cell cycle. Cyclosporin A blocked T cell activation at the earliest point in the cell cycle. In the presence of aphidicolin, Rb phosphorylation and p53 production proceeded normally whereas cyclosporin A inhibited both events. Although deferoxamine completely prevented Rb phosphorylation, p53 production was unaffected, suggesting a differential regulation of the two molecules. Our results place Rb phosphorylation and p53 production in the hierarchy of genetic events that are thought to regulate T lymphocyte progression through the cell cycle.
Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo (1999)

Specific inhibitors for cathepsin L and cathepsin S have been developed with the help of computer-graphic modeling based on the stereo-structure. The common fragment, N-(L-trans-carbamoyloxyrane-2-carbonyl)-phenylalanine-dimethyla mide, is required for specific inhibition of cathepsin L. Seven novel inhibitors of the cathepsin L inhibitor Katunuma (CLIK) specifically inhibited cathepsin L at a concentration of 10(-7) M in vitro, while almost no inhibition of cathepsins B, C, S and K was observed. Four of the CLIKs are stable, and showed highly selective inhibition for hepatic cathepsin L in vivo. One of the CLIK inhibitors contains an aldehyde group, and specifically inhibits cathepsin S at 10(-7) M in vitro.
Induced sputum matrix metalloproteinase‐9 correlates with lung function and airway inflammation in children with cystic fibrosis (2005)

Matrix metalloproteinases (MMPs) degrade extracellular matrix and are implicated in causing airway damage in chronic inflammatory lung diseases, including cystic fibrosis (CF). Our primary objective was to examine the relationship between matrix metalloproteinase-9 (MMP-9) and pulmonary function, as measured by forced expiratory volume in 1 sec (FEV1), in children with CF. We measured MMP-9 and its natural tissue inhibitor of metalloproteinase-1 (TIMP-1) in induced sputum from 18 clinically stable CF children with normal to mildly abnormal lung function and 7 healthy control children. Measures of airway inflammation from induced sputum included cell counts and differentials, interleukin-8 (IL-8), neutrophil elastase, MMP-9, and TIMP-1. Infection was assessed through quantitative bacterial counts. Induced sputum levels of MMP-9 and TIMP-1 were significantly increased in children with CF compared with healthy controls. Also, the MMP-9/TIMP-1 molar ratio was higher in the CF group. Among CF children, there was a significant inverse relationship between MMP-9 and FEV1. In addition, sputum MMP-9 and TIMP-1 concentrations significantly correlated with total white cells and neutrophils, IL-8, and neutrophil elastase. Neither MMP-9 nor TIMP-1 correlated with airway infection. We conclude that clinically stable CF children with normal to mildly abnormal lung function have an increased burden of MMP-9 in their airways. The observed relationships of MMP-9 with lung function and other measures of airway inflammation suggest that this enzyme may be a useful marker of airway injury and airflow obstruction in persons with CF.
Glycine-Extended Gastrin Promotes the Growth of Lung Cancer (2004)

The less processed forms of gastrin have recently been shown to act as trophic factors for both normal and malignant colonic cells. Although incompletely processed forms of gastrin such as glycine-extended gastrin and progastrin are also expressed in human lung cancers, the clinical significance of this expression has not been addressed. Consequently, we investigated the effects of overexpression of glycine-extended gastrin in a mouse strain that is prone to developing lung cancer and also examined the expression of incompletely processed gastrins in primary human lung cancers. We found that transgenic overexpression of glycine-extended gastrin in FVB/N mice resulted in a significant increase in the prevalence and growth of bronchoalveolar carcinoma. In addition, a substantial subset of human lung cancers was found to express progastrin and/or glycine-extended gastrin. Overexpression of glycine-extended gastrin by human lung cancers was associated with a significantly decreased survival. Taken together, these results suggest that glycine-extended gastrin may play a role in the growth and progression of some human lung cancers.
Targeting Metastatic Melanoma (2011)

Metastatic melanoma has historically been one of the most treatment-refractory types of cancer. Recent headway has been made in understanding the genetic underpinnings of this cancer. A subset of oncogenic events is amenable to targeting with drug therapy. BRAF-targeted therapies represent the first major breakthrough in systemic therapy for melanoma leveraging the new genetic knowledge. Ongoing translational research seeks to identify the most scientifically rational combination treatment strategies to build on single-agent targeted therapy.
Trenbolone acetate/estradiol combinations in feedlot steers: dose-response and implant carrier effects2 (1992)

Two experiments were conducted at three locations to determine the correct dosage and carrier for trenbolone acetate (TBA) and estradiol (E2) implants in feedlot steers. In the dose-response experiment, 1,296 steers were allotted to six implant treatments (48 pens per location): control, 140 mg of TBA (140/0), 30 mg of E2 (0/30), 20 mg of TBA + 4 mg of E2(20/4), 80 mg of TBA + 16 mg of E2(80/16), and 140 mg of TBA + 28 mg of E2 (140/28). In the carrier experiment, 575 steers were allotted to five implant treatments (25 pens per location): control, 140 mg of TBA + 28 mg of E2 in lactose (140/28-LA), 140 mg of TBA + 28 mg of E2 in cholesterol (140/28-CH), 140 mg of TBA + 20 mg of E2 in LA (140/20-LA), and 200 mg of progesterone + 20 mg of E2 benzoate (SS, reimplanted). In both experiments steers were fed a finishing diet for 140 to 168 d. In the dose-response experiment, response to TBA alone (140/0) did not differ from control (P greater than .2). Estradiol alone (0/30) improved ADG by 7% (P less than .01) and tended to improve feed efficiency over control (3%, P = .17). The highest dosage (140/28) improved ADG by 18% (P less than .001) and feed efficiency by 10% (P less than .001) over control and 10% (P less than .001) and 7% (P less than .01) over E2 alone, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Benefits of Colonoscopic Surveillance and Prophylactic Colectomy in Patients with Hereditary Nonpolyposis Colorectal Cancer Mutations (1998)

Colonoscopic surveillance is an effective method of reducing risk for cancer in carriers of a mutation for hereditary nonpolyposis colorectal cancer. The individual patient's choice between prophylactic surgery and surveillance is a complex decision in which personal preferences weigh heavily.
Air Quality and Thermal Comfort in Office Buildings: Results of a Large Indoor Environmental Quality Survey (2006)

This paper presents results of over 34,000 survey responses to air quality and thermal comfort questions in 215 buildings in US, Canada, and Finland. Results show that 80% or more of the occupants expressed satisfaction with their thermal comfort in only 11% of the buildings surveyed. Air quality scores were somewhat higher, with 26% of buildings having 80% or occupant satisfaction. With respect to thermal comfort and air quality performance goals set out by standards, most buildings appear to be falling far short. Occupant surveys offer a means to systematically measure this performance, and also to provide diagnostic information for building designers and operators.
The production of biofuels and renewable chemicals by fast pyrolysis of biomass (2007)

Bio-energy can provide more renewable energy requirements than any other technology. This paper focuses on fast pyrolysis as the only thermal process that directly delivers a high yield of liquid. This can be used on site or transported to centralised facilities for utilisation. This offers the potential for optimisation, greater economies of scale and exploitation of bio-refineries. The overall technology is described, particularly the reaction systems. The primary liquid product is characterised, and the potential for production of chemicals and transport fuels is explored. The main barriers to the market deployment of the various technologies are identified and briefly discussed.
T‐Cell Immunity to Oncogenic Proteins Including Mutated RAS and Chimeric BCR‐ABLa (1993)

The process of malignant transformation can be ascribed to a series of characteristics and definable mutations of genes which encode proteins that control cell growth and differentiation. During the course of malignant transformation the cancer-related genes are altered by a variety of mechanisms including translocations, deletions, and point mutations which commonly result in the expression of aberrant proteins. Our laboratory has focused on determining the extent to which cancer-specific proteins expressed by aberrant cancer-related genes can function as tumor-specific antigens. The current paper reviews our studies with two prototype cancer-specific proteins, mutated p21ras protein and chimeric p210bcr-abl protein. Ras protooncogenes are activated by point mutation in approximately 20% of human malignancies. The mutations occur primarily at codons 12 or 61 and result in the expression of p21ras proteins with single substituted amino acids. Only a limited number of amino acid substitutions occur. Murine studies demonstrate that immunization with synthetic peptides corresponding to the mutated segment can elicit both class II restricted CD4+ helper/inducer T-cell responses and class I restricted CD8+ cytotoxic T-cell responses specific for mutated p21ras protein. In addition, the existence in vivo of tumors expressing mutated ras proteins can be detected by assaying for T-cell immunity to the mutated segment of ras protein. Preliminary human studies show that some patients with colon cancer have existent antibody responses to p21ras protein, implying the possible existence of autochthonous T-cell immunity to mutated ras proteins in those patients. In chronic myelogenous leukemia the human c-abl protooncogene from chromosome 9 is translocated to the specific breakpoint cluster (bcr) region on chromosome 22. The translocation results in the formation of a bcr-abl fusion gene that encodes at 210-kD chimeric protein. The joining region segment of chimeric bcr-abl protein is composed of a unique combination of c-abl and bcr amino acids and is expressed only by malignant cells. Studies demonstrate that immunization of mice with synthetic peptides corresponding to the joining region segment can elicit class II restricted CD4+ T-cell responses to p210bcr-abl proteins. Preliminary studies show that bcr-abl peptides can bind in the groove of both murine and human class I MHC molecules and can elicit bcr-abl peptide-specific cytotoxic T lymphocytes (CTL). Whether bcr-abl peptide-specific CTL can lyse cells expressing bcr-abl protein is a yet unknown. In summary, the results of the studies reviewed confirm that cancer-specific oncogenic proteins can serve as tumor-specific antigens.
Telephone-based conversational speech recognition in the JUPITER domain (1998)

This paper describes our experiences with developing a telephone-based speech recognizer as part of a conversational system in the weather information domain. This system has been used to collect spontaneous speech data which has proven to be extremely valuable for research in a number of different areas. After describing the corpus we have collected, we describe the development of the recognizer vocabulary, pronunciations, language and acoustic models for this system, and report on the current performance of the recognizer under several different conditions.
Bond length alternation effects on the static electronic polarizability and second hyperpolarizability of polyacetylene chains (1999)

The static electronic longitudinal polarizability (α) and second hyperpolarizability (γ) of all-trans planar polyacetylene chains have been computed at different levels of approximation by varying the bond length alternation (BLA) along the conjugated backbone. Although the restricted Hartree–Fock (RHF) and second-order Møller–Plesset (MP2) approaches exhibit the expected behavior, i.e., the smaller the BLA, the larger the γ, the density functional schemes based on the SVWN and B3LYP exchange correlation functionals behave in a totally different way: when BLA increases, γ first increases, attains a maximum, and then decreases. Moreover, the RHF approach is found to overestimate by a factor of 2–3 the BLA dependence of α with respect to the MP2 procedure. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 75: 441–447, 1999
Intranuclear Trafficking of Messenger RNA (1999)

Within the nucleus, protein-encoding genes are transcribed into messenger RNA by RNA polymerase II. Messenger RNAs migrate to the cytoplasm, but before reaching their final destination the primary transcripts must undergo a series of modifications that include 5'-capping, splicing, and 3'-cleavage/polyadenylation. Errors in these processing events can originate aberrant products that, if translated, would produce abnormal proteins. Therefore, it is not surprising that eukaryotes have evolved a surveillance mechanism that recognizes and rapidly degrades aberrant mRNAs. Recent experiments provide exciting insights into how proper mRNAs are distinguished and selected for export. Transcription by RNA polymerase II is directly coupled to pre-mRNA processing, and the mechanism that targets the processing machinery to the polymerase complex suggests a model for co-transcriptional proofreading. Furthermore, there is evidence that at least some mRNAs move randomly throughout the nucleus, presumably by free diffusion. In this light, retention of aberrant mRNAs by the transcription/processing machinery is crucial to prevent their diffusion to the nuclear pores and eventual translocation to the cytoplasm.
Template assembled synthetic proteins (1989)

A symposium report. A new concept for the construction of artificial proteins with a non-natural chain assembly (template assembled synthetic proteins) is exemplified for 2 prototypes of this new generation of macromols. [on SciFinder (R)]
Polarization-Independent Wideband High-Index-Contrast Grating Mirror (2015)

Island-type two-dimensional high-index-contrast grating mirror based on a standard silicon-on-insulator wafer have been experimentally demonstrated. The measured spectra shows a bandwidth of ~192 nm with a reflectivity over 99% as well as polarization independence. Numerical simulations show that the designed mirror has large tolerance to fabrication errors.
Pediatrician and Family Physician Prescription of Selective Serotonin Reuptake Inhibitors (2000)

The overall response rate was 66% (55% family physicians and 76% pediatricians). Of the physicians, 72% had prescribed an SSRI for a child or adolescent. Depression was the most common reason for prescribing an SSRI; over two thirds of respondents had prescribed an SSRI for depression in a child 18 years of age or younger. Over half of the physicians reported they had prescribed an SSRI for a diagnosis other than depression in a child 18 years of age or younger. Attention-deficit/hyperactivity disorder was the most frequent use cited other than depression, followed by obsessive-compulsive disorder, aggression, eating disorders, and enuresis. Primary care physicians prescribed SSRIs for adolescents more commonly than for younger children. Only 6% of the respondents had ever prescribed an SSRI for a child younger than 6 years of age. In terms of SSRI prescriptions written for depression in the last 6 months, 32% of the physicians had recently prescribed SSRIs for adolescent patients and 6% for patients younger than 12 years of age. Family physicians were more likely than pediatricians to have recently prescribed SSRIs for adolescent patients (41% vs 26%), but there was no difference in recent SSRI prescriptions for children <12 years of age by physician specialty (4% vs 6%). Prescription of SSRIs was not associated with decreased use of counseling for treatment of depression, but prescription of SSRIs was associated with decreased use of referrals (63% vs 74%). There was no difference in the use of counseling between family physicians and pediatricians (61% vs 59%). However, pediatricians were more likely to use referrals in their usual approach to depression (77% vs 48%) compared with family physicians. More family physicians had prescribed SSRIs for pediatric patients compared with pediatricians (91% vs 58%), and more family physicians had prescribed SSRIs in combination with other psychotropic medications (54% vs 31%). For the majority of respondents, SSRI prescriptions constituted most of the medications used to treat childhood depression (75% of family physicians vs 61% of pediatricians). Family physicians were more likely to report a belief in the safety (63% vs 48%) and effectiveness (40% vs 32%) of SSRIs. Only 8% of physicians reported adequate training in the treatment of childhood depression and just 16% were comfortable with the treatment of depression. There were no specialty differences in training for the treatment of childhood depression; however, more family physicians than pediatricians agreed that they were comfortable with the management of childhood depression (22% vs 11%). (ABSTRACT TRUNCATED)
Sarcopenia: European consensus on definition and diagnosis (2010)

The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics-European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as 'presarcopenia', 'sarcopenia' and 'severe sarcopenia'. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.
Thermoelectric Properties of Silicon Microchannel Plates Structures (2011)

We have fabricated silicon microchannel plates (MCPs) by photo-assisted electrochemical etching (PAECE) and determined the thermoelectric properties by measuring the Seebeck coefficient of the samples. The samples are composed of regular arrayed lattices with a width of about 5 μm and spacing of about 1 μm. The Seebeck coefficient along the edge of the lattice is 466 μV/K. The silicon MCPs are potential materials for power generation and refrigeration. After oxidation from 30 minutes to 70 minutes and removing the silicon dioxide layer by buffered hydrofluoric acid, the samples show an improved coefficient as high as 1019 μV/K after repeating oxidation and etching 5 times. Our results show that the Seebeck coefficient increases when the wall of the silicon MCPs is thinned.
Neutral fucolipids and fucogangliosides of rat hepatoma HTC and H35 cells, rat liver, and hepatocytes. (1979)

Neutral fucolipids and fucogangliosides of normal rat liver, normal rat hepatocytes, and rat hepatoma H35 and HTC cells have been compared. H35 cells were characterized by accumulation of a relatively large quantity of a few neutral fucolipids and a major fucoganglioside. HTC cells were characterized by accumulation of several neutral fucolipids and by the absence of fucogangliosides. Those fucolipids which accumulated in hepatoma cells were absent in normal rat liver and normal hepatocytes. Normal hepatocytes and normal rat liver contained a low quantity of fucolipids which migrated differently on thin-layer chromatography from those which accumulated in hepatoma cells. In addition to these qualitative differences, the quantity of total fucose in purified glycolipid fraction was much higher in H35 and significantly higher in HTC cells than that in rat liver. A fucoganglioside which accumulated in H35 cells was tentatively characterized as a fucosylated GM1 ganglioside with the following structure: (formula: see text). The results indicate that anomalous fucosylation on glycolipid may take place in hepatoma cells.