gebhart/patrepeval huggingface dataset:
Therapeutic plasma exchange in antisynthetase syndrome with severe interstitial lung disease (2015)

Antisynthetase syndrome (ASS) is a rare condition characterized by interstitial lung disease (ILD), inflammatory myositis, fever, Raynaud phenomenon, mechanic's hand, and inflammatory polyarthritis in the setting of antibodies to amino acyl-transfer RNA synthetases, with anti-Jo-1 antibody being the most common. Prognosis is very poor especially when there is associated ILD. To date, there is no standardized treatment for ILD associated ASS. Therapy is based on the use of steroids alone or in combination with other immunosuppressive agents, especially in severe or refractory cases. The role of therapeutic plasma exchange (TPE) in the management of this rare condition has not been established. Here, we report a case of severe ILD associated ASS in a 41-year-old woman who did not show clinical or laboratory response after six doses of high dose steroids and a dose of IV cyclophosphamide. Because of the aggressive nature of her disease and poor prognostic indices present, a decision was made to add TPE to her treatment. She underwent five sessions of TPE. At the end of the 5th session, the anti-Jo-1 antibody levels dropped to 3.6 AI (antibody index) and her creatinine kinase (CK) level from 875 to 399 U L(-1) (Units per liter) with overall improvement in her respiratory status. This case suggests TPE may be a promising treatment option in patients with ILD associated ASS refractory to steroids and other immunosuppressive therapy, particularly those with severe disease.
Enzymatic basis for changes in fucoganglioside during chemical carcinogenesis. Induction of a specific alpha-fucosyltransferase and status of an alpha-galactosyltransferase in precancerous rat liver and hepatoma. (1983)

Previous studies indicated that accumulation of a-fucosyI-GM1 (IVZFucIT3NeuAcGgOse4Cer) and a-galactosyl-a-fucosy~-G~~ (IV3GalIV2FucI13NeuAcGgOse~Cer) ' Glycolipid abbreviations are according to the recommendations of the Nomenclature Committee, International Union of the Pure and Applied Chemistry (36).The basic designation of gangliosides (in parentheses) are based on the Svennerholm system (37).The abbreviations used are: GM,, II'NeuAcGgOse,Cer, Galpl+ 3GalNAc/3l+4[NeuAca2~3]Gal~l-+4Glc+Cer; 1I'NeuAcGgOse~-Cer ( G M ~) , GalNAc/31-.4[NeuAca2+3]Ga1/31+4G1c-.Cer; IV'Neu-AcIIJNeuAcGgOse4Cer (Gola), NeuAca2+3Gal/31-+3GaLNAc/31+ 4[NeuAca2+3]Gal/31-+4Glc+Cer; I13(NeuAc)2GgOse4Cer ( G D ] ~) , Gal~l~3GalNAc~l+3[NeuAca2+8NeuAca2+3]Gal/31-*4Glc~ Cer; GgOseXer (asialo-Gm), GalNAc/31-t4Gal/31
A Dynamically Microprogrammable Computer with Low-Level Parallelism (1980)

A new microprogrammable computer with low-level parallelism was built and has been utilized as a research vehicle for solving different classes of research-oriented applications such as real-time processings on static/dynamic images, pictures and signals, and emulations of both existing and virtual machines including high (intermediate) level language machines. The design goal of the machine was to achieve a high degree of processing enhancement in research- oriented applications by means of a low-level parallel processing organization combined with dynamically microprogrammable control. The machine has the capability to process multiple data streams, performing parallel operations with four 16-bit ALU's. These ALU's are independently controlled by the different fields of a 160-bit horizontal-type microinstruction, and have simultaneous access to 15 working registers. This microprogrammed MIMD organization is expected to provide a greater degree of flexibility for low-level parallel processing. In addition, not only does the machine contain powerful ALU's and a large number of registers, but also it employs flexible control structures and a hierarchical organization of control storage. All of these combine to yield extensive microprogramming capability which the user can effectively tailor to a wide spectrum of applications.
Cyclization characteristics of cyclodextrin glucanotransferase are conferred by the NH2-terminal region of the enzyme (1992)

Cyclodextrin glucanotransferase (CGTase; EC 2.4.1.19) is produced mainly by Bacillus strains. CGTase from Bacillus macerans IFO3490 produces alpha-cyclodextrin as the major hydrolysis product from starch, whereas thermostable CGTase from Bacillus stearothermophilus NO2 produces alpha- and beta-cyclodextrins. To analyze the cyclization characteristics of CGTase, we cloned different types of CGTase genes and constructed chimeric genes. CGTase genes from these two strains were cloned in Bacillus subtilis NA-1 by using pTB523 as a vector plasmid, and their nucleotide sequences were determined. Three CGTase genes (cgt-1, cgt-5, and cgt-232) were isolated from B. stearothermophilus NO2. Nucleotide sequence analysis revealed that the three CGTase genes have different nucleotide sequences encoding the same amino acid sequence. Base substitutions were found at the third letter of five codons among the three genes. Each open reading frame was composed of 2,133 bases, encoding 711 amino acids containing 31 amino acids as a signal sequence. The molecular weight of the mature enzyme was estimated to be 75,374. The CGTase gene (cgtM) of B. macerans IFO3490 was composed of 2,142 bases, encoding 714 amino acids containing 27 residues as a signal sequence. The molecular weight of the mature enzyme was estimated to be 74,008. The sequence determined in this work was quite different from that reported previously by other workers. From data on the three-dimensional structure of a CGTase, seven kinds of chimeric CGTase genes were constructed by using cgt-1 from B. stearothermophilus NO2 and cgtM from B. macerans IFO3490. We examined the characteristics of these chimeric enzymes on cyclodextrin production and thermostability. It was found that the cyclization reaction was conferred by the NH2-terminal region of CGTase and that the thermostability of some chimeric enzymes was lower than that of the parental CGTases.
Development and use of analytical systems based on mass spectrometry. (1977)

Contemporary analytical systems based on mass spectrometry include as components a gas chromatograph, a mass spectrometer, and a computer. The form of operation is usually in electron impact ionization mode for identification and structural studies, and in chemical ionization mode for quantitative analyses. Important stages in the development of these systems included the design of "molecule separators" for the concentration of solutes in the gas phase, the use of mass spectrometers as specific ion detectors, the introduction of chemical ionization techniques, and the development of computer-based operation, data acquisition, and data analysis capabilities. A current line of investigation is concerned with the design and use of systems based on atmospheric pressure ionization. Samples are ionized in a small reaction chamber external to the low-pressure region of a quadrupole mass analyzer. The primary source of electrons is a 63Ni foil or a corona discharge. The ionization process leading to positive ions involves a sequence of ion molecule reactions, usually electrons leads to carrier gas ions leads to reagent ions leads to sample component ions. Negative ions may be formed by direct electron attachment, or by ion molecule reactions that include new types of elimination reactions. The source will accept a variety of gases and solvents. The sample may be introduced in the gas phase without solvents, by probe injection, or in the effluent stream from a gas chromatograph. Samples may be introduced in the liquid phase in solvents by injection after the fashion of gas chromatography or in the effluent stream from a high-performance liquid chromatograph. The novel aspects of atmospheric pressure ionization mass spectrometry lie in its versatility and high sensitivity of detection. Few clinical chemistry laboratories now use these systems. Significant future uses are likely to be in analytical work involving therapeutic drug monitoring and studies of drug metabolism, and in analyses for environmental biohazards including pesticides, herbicides, polyhalobiphenyls, dibenzodioxins, and other toxic compounds.
An Anti-B7-H4 Antibody–Drug Conjugate for the Treatment of Breast Cancer (2015)

B7-H4 has been implicated in cancers of the female reproductive system and investigated for its possible use as a biomarker for cancer, but there are no preclinical studies to demonstrate that B7-H4 is a molecular target for therapeutic intervention of cancer. We provide evidence that the prevalence and expression levels of B7-H4 are high in different subtypes of breast cancer and that only a few normal tissues express B7-H4 on the cell membrane. These profiles of low normal expression and upregulation in cancer provide an opportunity for the use of antibody-drug conjugates (ADCs), cytotoxic drugs chemically linked to antibodies, for the treatment of B7-H4 positive cancers. We have developed an ADC specific to B7-H4 that uses a linker drug consisting of a potent antimitotic, monomethyl auristatin E (MMAE), linked to engineered cysteines (THIOMAB) via a protease labile linker. We will refer to ADCs that use the THIOMAB format as TDCs to help distinguish the format from standard MC-vc-MMAE ADCs that are conjugated to the interchain disulfide bonds. Anti-B7-H4 (h1D11)-MC-vc-PAB-MMAE (h1D11 TDC) produced durable tumor regression in cell line and patient-derived xenograft models of triple-negative breast cancer. It also binds rat B7-H4 with similar affinity to human and allowed us to test for target dependent toxicity in rats. We found that our anti-B7-H4 TDC has toxicity findings similar to untargeted TDC. Our results validate B7-H4 as an ADC target for breast cancer and support the possible use of this TDC in the treatment of B7-H4(+) breast cancer.
Overexpression of vimentin: role in the invasive phenotype in an androgen-independent model of prostate cancer. (2003)

The androgen-sensitive LNCaP prostate cancer cell line is less invasive than hormone-insensitive lines. CL1, an aggressive, hormone-insensitive LNCaP subline derived by continuous passaging in hormone-depleted medium, was compared with the parental cell line by cDNA microarray analysis. The gene coding for the intermediate filament protein vimentin was found to be highly up-regulated in the CL1 subline. This difference was confirmed by Northern and Western blots and visualized by immunofluorescence microscopy. To assess the contribution of vimentin to the invasive phenotype, LNCaP cells were stably transfected to overexpress vimentin, and the CL1 cells were transfected with vimentin antisense construct. The invasiveness of the transfected cells was tested using an in vitro invasion assay. We were able to demonstrate that decreasing vimentin expression in the constitutively vimentin-expressing CL1 cells led to a significant decrease in their invasiveness but that forcing expression of vimentin in the LNCaP cells did not augment their invasiveness. These findings imply that vimentin expression contributes to the invasive phenotype but cannot confer it alone.
The Role of Intranasal Oxytocin in the Treatment of Patients with Schizophrenia: A Systematic Review (2013)

Oxytocin is a nonapeptide mammalian hormone, best known for its role in childbirth, parturition and lactation. It has been implicated in the control of social behaviors and relationships, such as monogamy or promiscuous behaviors. The putative involvement of oxytocin in schizophrenia was first postulated following several pioneer reports of oxytocin use in schizophrenia and observations of increased oxytocin levels in the cerebrospinal fluid of schizophrenic patients, although this latter finding has subsequently been challenged. More recently, oxytocin plasma levels have been found to be decreased in schizophrenic individuals, particularly in those exhibiting hyponatremic polydipsia and emotional dysregulation. Some authors report that intranasal oxytocin administration to schizophrenic patients may reduce symptomatology. The aim of the present paper was to review studies investigating symptomatology, social cognition and emotion recognition changes in DSM-IV-TR schizophrenic patients, after administration of intranasal oxytocin at different doses. Literature search was conducted in March, 2012. PubMed and Scopus databases were used to find studies for inclusion in the systematic review. Oxytocin may represent an important novel adjunctive treatment for patients with schizophrenia. However, some limitations of current studies cannot be overlooked and further investigations are certainly needed.
Stability of Religious Orientation and Academic Dishonesty (1998)

This study examines the probable influence of individual religiosity on academic cheating among a group of Seventh-day Adventist youth, grades 6 through 12. A multiple-regression analysis was used to determine the relationship between academic beliefs or behaviors and academic dishonesty. The following research questions were investigated: (1) Is there a relationship between students' religious experience or religious activities and academic honesty? (2) What religious variables influence academic honesty? and (3) What is the correlation between the stability of religious orientation and academic honesty? Although the final model proved to be statistically significant, the findings suggest no direct impact on academic honesty. The implications of this study and the influential factors are discussed.
Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and phospholipidosis (2008)

Oxysterols are 27-carbon atom molecules resulting from autoxidation or enzymatic oxidation of cholesterol. They are present in numerous foodstuffs and have been demonstrated to be present at increased levels in the plasma of patients with cardiovascular diseases and in atherosclerotic lesions. Thus, their role in lipid disorders is widely suspected, and they might also be involved in important degenerative diseases such as Alzheimer's disease, osteoporosis, and age-related macular degeneration. Since atherosclerosis is associated with the presence of apoptotic cells and with oxidative and inflammatory processes, the ability of some oxysterols, especially 7-ketocholesterol and 7beta-hydroxycholesterol, to trigger cell death, activate inflammation, and modulate lipid homeostasis is being extensively studied, especially in vitro. Thus, since there are a number of essential considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols, it is important to determine their biological activities and identify their signaling pathways, when they are used either alone or as mixtures. Oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or none whatsoever. Moreover, a substantial accumulation of polar lipids in cytoplasmic multilamellar structures has been observed with cytotoxic oxysterols, suggesting that cytotoxic oxysterols are potent inducers of phospholipidosis. This basic knowledge about oxysterols contributes to a better understanding of the associated pathologies and may lead to new treatments and new drugs. Since oxysterols have a number of biological activities, and as oxysterol-induced cell death is assumed to take part in degenerative pathologies, the present review will focus on the cytotoxic activities of these compounds, the corresponding cell death signaling pathways, and associated events (oxidation, inflammation, and phospholipidosis).
Reducing dynamin 2 expression rescues X-linked centronuclear myopathy (2014)

Centronuclear myopathies (CNM) are congenital disorders associated with muscle weakness and abnormally located nuclei in skeletal muscle. An autosomal dominant form of CNM results from mutations in the gene encoding dynamin 2 (DNM2), and loss-of-function mutations in the gene encoding myotubularin (MTM1) result in X-linked CNM (XLCNM, also called myotubular myopathy), which promotes severe neonatal hypotonia and early death. Currently, no effective treatments exist for XLCNM. Here, we found increased DNM2 levels in XLCNM patients and a mouse model of XLCNM (Mtm1(-/y)). Generation of Mtm1(-/y) mice that were heterozygous for Dnm2 revealed that reduction of DNM2 in XLCNM mice restored life span, whole-body strength, and diaphragm function and increased muscle strength. Additionally, classic CNM-associated histological features, including fiber atrophy and nuclei mispositioning, were absent or reduced. Ultrastructural analysis revealed improvement of sarcomere organization and triad structures. Skeletal muscle-specific decrease of Dnm2 during embryogenesis or in young mice after disease onset revealed that the rescue associated with downregulation of Dnm2 is cell autonomous and is able to stop and potentially revert XLCNM progression. These data indicate that MTM1 and DNM2 regulate muscle organization and force through a common pathway. Furthermore, despite DNM2 being a key mechanoenzyme, its reduction is beneficial for XLCNM and represents a potential therapeutic approach for patients.
miR-338 inhibits the metastasis of lung cancer by targeting integrin β3 (2016)

miR-338 as an intronic miRNA from apoptosis-associated tyrosine kinase (AATK) is involved in tumor proliferation and apoptosis, but its function and regulatory mechanism in lung cancer is still obscure. In the present study, we found that miR-338 was strikingly downregulated in 115 lung cancer tissues and 5 lung cancer cell lines. Besides, low level of miR-338 was associated with tumor emboli, TNM stage, tumor recurrence and poor survival. Regaining the expression of miR-338 in lung cancer cell lines significantly impaired cellular adhesion, migration, invasion and lung tumor formation in nude mice. Furthermore, we also identified a metastasis related protein, integrin β3 (ITGB3), as a novel target gene of miR-338. Our results reveal a new regulatory mechanism of miR-338 which may help us better understand the metastasis of lung cancer.
Sulfotyrosines of the Kaposi's Sarcoma-Associated Herpesvirus G Protein-Coupled Receptor Promote Tumorigenesis through Autocrine Activation (2010)

The Kaposi's sarcoma-associated herpesvirus (KSHV) G protein-coupled receptor (vGPCR) is a bona fide signaling molecule that is implicated in KSHV-associated malignancies. Whereas vGPCR activates specific cellular signaling pathways in a chemokine-independent fashion, vGPCR binds a broad spectrum of CC and CXC chemokines, and the roles of chemokines in vGPCR tumorigenesis remain poorly understood. We report here that vGPCR is posttranslationally modified by sulfate groups at tyrosine residues within its N-terminal extracellular domain. A chemokine-binding assay demonstrated that the tyrosine sulfate moieties were critical for vGPCR association with GRO-alpha (an agonist) but not with IP-10 (an inverse agonist). A sulfated peptide corresponding to residues 12 through 33 of vGPCR, but not the unsulfated equivalent, partially inhibited vGPCR association with GRO-alpha. Although the vGPCR variant lacking sulfotyrosines activated downstream signaling pathways, the ability of the unsulfated vGPCR variant to induce tumor growth in nude mice was significantly diminished. Furthermore, the unsulfated vGPCR variant was unable to induce the secretion of proliferative cytokines, some of which serve as vGPCR agonists. This implies that autocrine activation by agonist chemokines is critical for vGPCR tumorigenesis. Indeed, GRO-alpha increased vGPCR-mediated AKT phosphorylation and vGPCR tumorigenesis in a sulfotyrosine-dependent manner. Our findings support the conclusion that autocrine activation triggered by chemokine agonists via sulfotyrosines is necessary for vGPCR tumorigenesis, thereby providing a rationale for future therapeutic design targeting the tumorigenic vGPCR.
catELISA: a facile general route to catalytic antibodies. (1993)

The low abundance and activity of catalytic antibodies are major obstacles to their selection from the virtually unlimited repertoire of antibody binding sites. The requirement for new screening methodologies is further emphasized by the availability of combinatorial libraries, in which a functional polypeptide has to be selected out of millions of possibilities. We present a simple and sensitive screening approach (termed catELISA) based on immobilized substrates and immunodetection of the end product of the catalyzed reaction. The feasibility of catELISA is demonstrated here by the generation of potent ester-hydrolyzing antibodies by direct screening of hybridoma supernatants. We show that this approach is not only facile but general: it is not limited by type of reaction, substrate, or catalyst (enzymes, catalytic antibodies, chemical catalysts). catELISA opens a route to catalytic antibodies that replaces existing lengthy and arduous methods, thus allowing us to expand their number and improve their quality and to address questions that would otherwise be difficult to answer.
Performance and Properties of a Solid Amine Sorbent for Carbon Dioxide Removal in Space Life Support Applications (2001)

NASA is currently using a solid amine sorbent known as HSC+ for regeneratively removing CO2 in space shuttle applications. This sorbent may also be of value for CO2 removal in various industrial processes such as greenhouse gas control, industrial syntheses, and natural gas purification. To design novel sorbents and to design a CO2 scrubber based on HSC+, physical and thermochemical property data are required. In this paper, we present a detailed experimental investigation of property data and long-term performance results using HSC+ as a CO2 sorbent. Differential scanning calorimetry was used to determine the heat capacity of the material. Cyclic and equilibrium capacities of the material for CO2 pickup were determined and long-term test data show excellent performance. In addition, we have determined the heat of adsorption associated with CO2 pickup by HSC+ and the effect of moisture, using isothermal flow calorimetry. We have also performed thermal gravimetric analyses on the materials to gain insight into the stability of the material and determine the temperatures at which CO2 and constituents of HSC+ leave the surface of the material.
Low Bit-Rate Coding of High Quality Digital Audio: Algorithms and Evaluation of Quality (1989)

Based on frequency domain techniques, coding of high quality digital audio with bit rates of down to 64 kbit/s is possible.The NMR (Noise-to-Mask Ratio) has been introduced for quality evaluation and optimization for low bit rate coding schemes. Real time implementations of low bit rate codecs and a measurement system have been developed. Several coding schemes (Optimal Coding in the Frequency domain (OCF), Low-Complexity Adaptive Transform Coding (LC-ATC), Sub-Band Coding (SBC)) are compared using NMR. Comparison results for different types of music and testsignals are presented.
Relative Toxicity of Certain Antiseptics Containing Soap and Alcohol—With Special Reference to Mouth Washes (1942)

Relative Toxicity of Certain Antiseptics Containing Soap and Alcohol—With Special Reference to Mouth Washes Henry Welch, and Charles M. Brewer CopyRight*Read before the Laboratory Section of the American Public Health Association at the Seventieth Annual Meeting in Atlantic City, N. J., October 14, 1941. https://doi.org/10.2105/AJPH.32.3.261 Published Online: August 29, 2011