gebhart/patrepeval huggingface dataset:
The Effects of Glucagon-like Peptide-I (GLP-I) on Hormone Secretion from Isolated Human Pancreatic Islets (1995)

Glucagon-like peptide-I (GLP-I) is a potent in-cretin hormone that is now considered as a new therapeutic tool in the treatment of diabetes mellitus. In this study we characterized the effects of GLP-I on peptide hormone release from isolated human pancreatic islets. GLP-I stimulated insulin release in the presence of 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 166%; 10 mM glucose + 10 nM GLP-I, 222%) but had only a weak insulinotropic effect (128%) at 2.8 mM glucose. Glucagon release was inhibited by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 72%) and by 10 nM GLP-I at 2.8 mM glucose (67%). Somatostatin secretion was increased by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 166%). GLP-I stimulated somatostatin release in the presence of 2.8 mM glucose (172%). Pancreatic polypeptide (PP) secretion was enhanced by 10 mM glucose (2.8 mM glucose, 100%; 10 mM glucose, 236%). GLP-I induced PP release only in the presence of 2.8 mM glucose (184%).
Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model (2017)

Alzheimer's disease is characterized by the deposition of amyloid-β as extracellular plaques and hyperphosphorylated tau as intracellular neurofibrillary tangles. Tau pathology characterizes not only Alzheimer's disease, but also many other tauopathies, presenting tau as an attractive therapeutic target. Passive tau immunotherapy has been previously explored; however, because only a small fraction of peripherally delivered antibodies crosses the blood-brain barrier, enters the brain and engages with tau that forms intracellular aggregates, more efficient ways of antibody delivery and neuronal uptake are warranted. In the brain, tau exists as multiple isoforms. Here, we investigated the efficacy of a novel 2N tau isoform-specific single chain antibody fragment, RN2N, delivered by passive immunization in the P301L human tau transgenic pR5 mouse model. We demonstrate that, in treated mice, RN2N reduces anxiety-like behaviour and phosphorylation of tau at distinct sites. When administration of RN2N was combined with focused ultrasound in a scanning mode (scanning ultrasound), RN2N delivery into the brain and uptake by neurons were markedly increased, and efficacy was significantly enhanced. Our study provides evidence that scanning ultrasound is a viable tool to enhance the delivery of biologics across the blood-brain barrier and improve therapeutic outcomes and further presents single-chain antibodies as an alternative to full-length antibodies.
Experimental results using methanol and methanol/gasoline blends as automotive engine fuel (1977)

Comparative emission and fuel energy economy data were generated using 1975 model vehicles adjusted for gasoline fuel and using gasoline and gasoline blended with 5 and 10% methanol; tests were made at temperatures of 20/sup 0/, 75/sup 0/, and 100/sup 0/F on a chassis dynamometer in a climate-controlled test chamber. Results suggest that emissions and fuel energy economy are generally affected to the extent that methanol addition affects air-fuel stoichiometry, fuel heat content, and fuel vapor pressure. The term ''fuel energy economy'' is used to denote calculations on the basis of fuel energy content in lieu of fuel quantity. Vehicle emissions and fuel economy were essentially unchanged during approximately 7,500 miles of road testing; no engine or fuel system component failures were encountered during that testing. Road octane measurements were made for the fuels containing 5, 10, and 15% methanol in base gasolines of 84, 87, and 91 research octane quality. Results show significantly better octane improvement in blending methanol with the lower octane fuels as compared with the improvement in blending with the higher octane fuels. Steady-state engine emission and fuel energy economy data were generated using a late model automotive engine fueled with 5, 10, 15, and 100% methanol/gasoline blend. Test variables and engine parametric adjustments included engine speed, exhaust gas recirculation rate, air-fuel ratio, ignition timing, and compression ratio. Results suggest that operation with pure methanol may allow use of high-compression engines to realize improved fuel energy economy with relatively low oxides of nitrogen emission.
Subsurface defect detection in ceramics by high-speed high-resolution optical coherent tomography (1997)

We use optical coherence tomography with a new configuration to determine the size and location of subsurface defects in solid ceramic and composite ceramic materials. Cross-sectional subsurface regions either parallel or perpendicular to the surface were examined. We present experimental results showing that the size and distribution of small subsurface defects can be determined with depth and lateral resolutions of 10 and 4 microm, respectively.
Resolution, Detection, and Characterization of Redox Conformers of Human HSF1 (2001)

We describe here an experimental protocol for the resolution, detection, and quantitation of the reduced and oxidized conformers of human heat shock factor 1 (hHSF1) and report on the effects in vitro and in vivo of redox-active agents on the redox status, structure, and function of hHSF1. We showed that diamide, a reagent that promotes disulfide bond formation, caused a loss of immunorecognition of the monomeric hHSF1 protein in a standard Western blot detection procedure. Modification of the Western blot procedure to include dithiothreitol in the equilibration and transfer buffers after gel electrophoresis allowed for the detection of a compact, intramolecularly disulfide cross-linked oxidized hHSF1 (ox-hHSF1) in the diamide-treated sample. The effect of diamide was blocked by pretreatment with N-ethylmaleimide and was reversed by dithiothreitol added to the sample prior to gel electrophoresis. Incubation with nitrosoglutathione at 42 degrees C also promoted the conversion of HSF1 to ox-HSF1; at 25 degrees C, however, nitrosoglutathione was by itself without effect but blocked the formation of ox-hHSF1 in the presence of diamide. The disulfide cross-linked ox-hHSF1 was monomeric and resistant to the in vitro heat-induced trimerization and activation. The possibility that ox-HSF1 may occur in oxidatively stressed cells was evaluated. Treatment of HeLa cells with 2 mm l-buthionine sulfoximine promoted the formation of ox-HSF1 and blocked the heat-induced activation of HSF DNA binding activity. Our result suggests that hHSF1 may have integrated redox chemistry of cysteine sulfhydryl into its functional responses.
Differentiation of hematopoietic stem cells in irradiated mouse thymic lobes. Kinetics and phenotype of progeny. (1990)

To define cell populations which participate in the very early stages of T cell development in the mouse thymus, we enriched hematopoietic stem cells from mouse bone marrow and injected them into thymic lobes of irradiated Ly-5 congenic recipients. The progeny of the stem cells were identified and their phenotypes were determined by two-color flow cytometry for the expression of various cell surface differentiation Ag during the course of their subsequent intrathymic development. The majority of the differentiation which occurred in the first 10 days after intrathymic cell transfer was myeloid in nature; hence, this study demonstrates that the irradiated thymus is not strictly selective for T cell development. Further, the maximum rate of T cell development was observed after intrathymic injection of 200 stem cells. Donor-derived cells which did not express Ag characteristic of the myeloid lineage could be detected and their phenotypes could be determined by flow cytometry as early as 7 days after intrathymic injection. At this time, the cells were still very similar phenotypically to the bone marrow hematopoietic stem cells. Exceptions to this were the expression of stem cell Ag 2 and a decrease in the level of MHC class I Ag expression. After 9 days, the donor-derived cells expressed high levels of the Thy-1 Ag and proceeded to change in cell surface phenotype as differentiation continued. These cell phenotypes are described for the time frame ending 18 days after injection, when most donor-derived cells were phenotypically small CD4+ CD8+ (double-positive) thymocytes.
Apoptotic Bodies (1998)

To evaluate the occurrence of apoptotic bodies in endocervical adenocarcinoma in situ (AIS) and investigate the relationship of apoptosis to mitotic activity, we performed counts of apoptotic bodies and mitotic figures in 43 patients with AIS and in a comparable control group with nonneoplastic endocervical glandular epithelium. The ages of the patients with AIS ranged from 27 to 74 years (mean = 40). Mitotic figures were present in all AIS cases, and apoptotic bodies were seen in all but two extremely small lesions. In 28 AIS cases in which lesions were large enough to count 10 consecutive high-power fields (HPF), counts of apoptotic bodies ranged from 1 to 36/10 HPF (mean and median = 16), and counts of mitotic figures ranged from 1 to 53 mitotic figures/10 HPF (mean and median = 18). Counts of apoptotic bodies correlated directly with counts of mitotic figures. The ages of the 28 control patients ranged from 32 to 56 years (mean = 43). Counts of apoptotic bodies in the control cases ranged from 0 to 10 per case (mean = 1.1). Apoptotic bodies were present in only 13 (46%) control cases. The highest counts in these cases ranged from 1 to 6 apoptotic bodies/10 HPF (mean = 2.3). Mitotic figures were present in only 4 (14%) control cases. The counts in these cases ranged from 1 to 3 mitotic figures/10 HPF (mean = 1.8). Counts per 10 HPF were significantly (p < 0.001) more for AIS cases than for controls for apoptotic bodies and mitotic figures. Our results indicate that apoptotic bodies, as well as mitotic figures, occur almost universally in AIS. Both occur significantly more often and in greater numbers in AIS than in nonneoplastic endocervical glandular epithelium. Apoptotic bodies are a consistent morphologic feature of AIS, and their identification may be diagnostically useful.
Ca 125 Assay Used in Conjunction with Ca 15–3 and Tag-72 Assays for Discrimination Between Malignant and Non-Malignant Diseases of the Ovary (1989)

It has previously been suggested by the authors that elevated serum CA 125 levels may be of value in discriminating malignant from non-malignant pathologies among women with pelvic masses. Enhancement of this discrimination capacity might be achieved by utilizing additional serum assays. To test this hypothesis CA 125, CA 15-3 and TAG-72 levels were determined in double-blind fashion on 219 sera from patients undergoing diagnostic laparotomy for pelvic masses at six gynecological departments in the Stockholm area. Patient diagnoses were verified by chart review. Of the 219 patients, 27 (12%) had non-mucinous ovarian carcinoma, of whom 26 (96%) had CA 125 levels of 35 U/ml or greater 23 (85%) had levels in excess of 65 U/ml. Of 27 patients with mucinous or borderline ovarian carcinoma and patients with other malignancies 18 (67%) had CA 125 levels greater than 35 U/ml. Of 165 women with non-malignant diagnoses 26 (16%) had CA 125 levels in excess of 35 U/ml and 8 (5%) greater than 65 U/ml. Using reference values of 35 U/ml, 30 U/ml and 10 U/ml for the CA 125, CA 15-3 and TAG-72 assay respectively, only 3 of 165 (2%) of non-malignant patients were categorized as positive, compared to 23 of 27 (85%) of those with non-mucinous ovarian carcinoma. Moreover, an analysis of postmenopausal women revealed that the combination of assays--in a model controlling for the effect of CA 125--increased the specificity for diagnosis of benign diseases in women with pelvic masses.
Derivation of HLA-A11/Kb transgenic mice: functional CTL repertoire and recognition of human A11-restricted CTL epitopes (1997)

Transgenic mice expressing chimeric human (alpha1 and alpha2 HLA-A11 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2Kb domains) class I molecules were derived. These mice were used as a model system to study the immunogenicity of human CTL epitopes and also to examine the aspects of Ag processing differences of mice vs man. Immunization of these mice with seven known HLA-A11-restricted CTL epitopes emulsified in IFA resulted in vigorous specific CTL responses. A larger panel of 45 A11-binding peptides was used to examine the relationship between immunogenicity in the HLA-A11/Kb transgenic mice and HLA-A11 binding capacity. Twenty-one of 28 (75%) peptides with high binding affinities (50% inhibitory concentration (IC50), 2-50 nM) and 7 of 13 (54%) intermediate binding peptides (IC50, 50-500 nM range) were immunogenic. In parallel, 19 of these peptides were used for in vitro primary immunizations of PBMC derived from HLA-A11 healthy human donors. It was found that 8 of 8 peptides that were able to elicit CTL in primary human in vitro cultures were also immunogenic in HLA-A11/Kb mice. Finally, HLA-A11/Kb transgenic mice were found to generate an A11/Kb restricted CTL response following immunization with influenza virus A/PR/8/34, suggesting that, at least to some extent, A11 epitopes are generated by transgenic mice as a result of natural in vivo processing and presentation.
A recombinant diphtheria toxin related human CD4 fusion protein specifically kills HIV infected cells which express gp120 but selects fusion toxin resistant cells which carry HIV. (1992)

A chimeric toxin made by a genetic fusion between the DNA encoding the 389 N-terminal amino acids of diphtheria toxin and that coding for the V1 and V2 domains of human CD4 (amino acids 1-178) was produced, purified and examined for ADP ribosylation activity, gp120 binding and effects on acutely and chronically HIV infected cells. The fusion toxin DAB389CD4 possesses enzymatic activity and binds to gp120. DAB389CD4 was found to kill CEM and U937 cells infected by HIV selectively and efficiently in a dose dependent manner, however, fusion toxin treatment did not eliminate the virus from acutely infected cell cultures. In addition, treatment of chronically infected cells with DAB389CD4 rapidly led to the appearance of HIV infected cells which were resistant to the chimeric toxin. The experimental results reported here suggest that the potential use of gp120 targeted cytotoxic agents for the treatment of HIV infection should be viewed with caution.
Lead Exposure and Amyotrophic Lateral Sclerosis (2002)

These results are consistent with previous reports and suggest a potential role for lead exposure in the etiology of ALS.
Biophysical and enzymatic properties of the catalytic domain of HIV-1 integrase. (1994)

A deletion derivative of the integrase protein from human immunodeficiency virus type-1 (HIV-1) consisting of the central core domain (amino acids 50-212) has been characterized biophysically and biochemically. This deletion mutant is of particular interest for structural studies as it can carry out the disintegration reaction suggesting the presence of an active site and, under certain conditions, is more soluble than full-length integrase. The circular dichroism and fluorescence of the deletion mutant and the 288-residue full-length integrase were similar, indicating that the core residues maintain similar overall conformations in both proteins. The deletion mutant is approximately 10% more alpha-helical than the full-length protein. Analytical centrifugation demonstrated that both proteins undergo monomer-dimer association although the truncated protein showed slightly less tendency to dimerize; the dissociation constants were 2.5 x 10(-5) M for the full-length protein and 8.0 x 10(-5) M for the truncated protein. The disintegration activity of both proteins was also compared. Although a higher concentration of the truncation mutant was required for optimal activity, the mutant did not have altered pH or Mn2+ requirements relative to the full-length protein. The combined biophysical and enzymatic studies suggest that this truncated form of HIV-1 integrase is likely to be useful for structural studies.
Site-Specific Polysialylation of an Antitumor Single-Chain Fv Fragment (2009)

Protein pharmacokinetic modulation is becoming an important tool in the development of biotherapeutics. Proteins can be chemically or recombinantly modified to alter their half-lives and bioavailability to suit particular applications as well as improve side effect profiles. The most successful and clinically used approach to date is chemical conjugation with poly(ethylene glycol) polymers (PEGylation). Here, therapeutic protein half-life can be increased significantly while retaining biological function, reducing immunogenicity and cross-reaction. Naturally occurring alternatives to such synthetic polymers could have major advantages such as lower side effects due to biodegradability and metabolism. Polysialic acid (PSA) has been investigated as a pharmacokinetic modulatory biopolymer with many successful examples in preclinical and clinical development. Single-chain Fvs (scFvs) are a choice antibody format for human therapeutic antibody discovery. Because of their small size, they are rapidly eliminated from the circulation and often are rebuilt into larger proteins for drug development and a longer half-life. Here we show that chemical polysialylation can increase the half-life of an antiplacental alkaline (PLAP) and anticarcinoembryonic antigen (CEA) scFv (F1 and MFE-23, respectively) 3.4-4.9-fold, resulting in a 10.6-15.2-fold increase in blood exposure. Amine-directed coupling of the MFE-23 scFv reduced its immunoreactivity 20-fold which was resolved by site-specific polysialylation through an engineered C-terminal thiol residue. The site-specifically polysialylated MFE-23 scFv demonstrated up to 30-fold improved tumor uptake while displaying favorable tumor:normal tissue specificity. This suggests that engineering antibody fragments for site-specific polysialylation could be a useful approach to increase the half-life for a variety of therapeutic applications.
Introduction of a Pore Geometrical Factor Defined by the Capillary Pressure Curve (1960)

Abstract A method is presented that provides a mathematical description of capillary pressure curves and, probably, of differences in pore geometry of samples. The technique is based on the observation that the location and shape of a capillary pressure curve reflect characteristics of the pore structure of the sample. Introduction It has been noted that the observed differences in shape and location of capillary pressure curves reflect some basic properties regarding the pore geometry of the samples. For example, according to basic concepts of capillarity, the following statements can be made regarding the location and shape of a capillary pressure curve. The location of the curve with respect to the (Vb)pc and Pc axes is a measure of the interconnected pore volume and of the cross-sectional area of the pore first entered by mercury, respectively. The shape of the curve depends on the interconnection of the pores and the sorting of the pore sizes. It has been the object of this study to use this information as a starting point in an attempt to find a unique mathematical description of the Pc - (Vb)Pc relations of different samples. It may be expected that parameters in such a relation can then be used to describe differences in pore geometry of these samples. For a practical description of the Pc - (Vb)Pc relation, however, it appears desirable to describe each curve (i.e., each sample) by a limited number of parameters so that the curves taken from all samples form a family, each member of which is uniquely determined by one single combination of values of all parameters.
Myxococcus xanthus induces actinorhodin overproduction and aerial mycelium formation by Streptomyces coelicolor (2010)

Interaction of the predatory myxobacterium Myxococcus xanthus with the non-motile, antibiotic producer Streptomyces coelicolor was examined using a variety of experimental approaches. Myxococcus xanthus cells prey on S. coelicolor, forming streams of ordered cells that lyse the S. coelicolor hyphae in the contact area between the two colonies. The interaction increases actinorhodin production by S. coelicolor up to 20-fold and triggers aerial mycelium production. Other bacteria are also able to induce these processes in S. coelicolor though to a lesser extent. These studies offer new clues about the expression of genes that remain silent or are expressed at low level in axenic cultures and open the possibility of overproducing compounds of biotechnological interest by using potent inducers synthesized by other bacteria.
Crystal Composition and Afterglow in Mixed Silicates: The Role of Melting Temperature (2015)

Scintillator materials convert high-energy radiation into visible or near-ultraviolet photons, and are used in medical diagnostics, high-energy physics, and security applications. Often a scintillation response on the nanosecond time scale is required because afterglow interferes with readings of interest, and so fast scintillators are the key to progress. The authors elucidate the microscopic mechanism that allows elimination of afterglow in mixed-crystal scintillators based on Lu and Gd ions, showing a way forward in terms of both basic physics and a strategy for controlled materials preparation.
Role of ABC transporters in secretion of cholesterol from liver into bile (2002)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
[Circulating prostate cancer specific antigens in benign hypertrophy and localized cancer of the prostate]. (1991)

In benign hypertrophy of the prostate (88 patients) there is a good correlation between the circulating specific prostate antigen (SPA) and the size of the prostate or of the adenoma. This correlation disappears with an adenocarcinoma where tumor volume increases (46 patients). Used as a screening test for cancer, serum levels of SPA, with a threshold value of 2.5 ng/ml, has a 91 per cent sensitivity and a 37 per cent specificity. At 15 ng/ml the sensitivity is 50 per cent and the specificity is 85 per cent. Alone, the SPA level is a poor diagnostic tool: using the low threshold (2.5 ng/ml) leads to needle biopsy in most all benign hypertrophies; with the high threshold (15-23 ng/ml), 50 per cent of the localized cancers go undetected. However, for a level greater than 15 ng/ml, SPA is an argument strongly suggesting prostate adenocarcinoma. The capacity of benign hypertrophy of the prostate to "secrete" SPA is 5 times greater than the normal peripheral prostate; the capacity of cancer is 20 times greater than that of the adenoma. Individual variability in serum levels of SPA, expressed per cm3 of prostate tissue is too great to give a precise interpretation as a function of volume.
Relation of the hypertonic saline responsiveness of the airways to exercise induced asthma symptom severity and to histamine or methacholine reactivity. (1993)

These findings suggest that hypertonic saline responsiveness bears a closer relationship to the severity of exercise induced asthma symptoms than to the non-specific bronchial hyperresponsiveness measured by histamine or methacholine reactivity.