gebhart/patrepeval huggingface dataset:
Antitumor effects of a bispecific antibody targeting CA19-9 antigen and CD16. (1992)

Bispecific murine monoclonal antibodies that target tumor and Fc gamma RIII (CD16) can promote relevant tumor lysis by large granular lymphocytes. For these antibodies to be clinically useful, their properties should be maintained in vivo, where competing human immunoglobulin, shed target antigen, and shed CD16 may be encountered. At a minimum, bispecific antibody antitumor effects should be preserved in whole blood. Furthermore, potentiation of tumor lysis should be reflected by demonstrating the ability of bispecific antibody-retargeted effector cells to infiltrate and mediate lysis of organized tumor. If these characteristics are demonstrated, and there is evidence of in vivo efficacy of bispecific antibody-based therapy in a relevant animal model, further clinical development of such antibodies would be warranted. In this report the ability of CL158 bispecific antibody supernatants to mediate lysis of SW948 tumor growing in monolayer is shown to be preserved in the presence of interleukin 2-activated whole blood. When SW948 cells were grown in vitro as multicellular human tumor spheroids, incubation with interleukin 2-activated lymphocytes (LAK cells) and CL158 led to structural and widespread necrosis. This was dependent on CL158 and resistant to competition by pooled human immunoglobulin or interleukin 2-exposed whole blood. These effects were not promoted by the monospecific antibodies produced by the parent clones of CL158 and were not observed when the IgG2a variant of CA19-9 antibody, which mediates conventional antibody-dependent cellular cytotoxicity, was used instead of its bispecific derivative. To examine the efficacy of bispecific antibody-based treatments on in vivo tumor, scid mice bearing early s.c. SW948 xenografts were treated with interleukin 2 for 5 consecutive days, supplemented by three i.v. injections of 10(7) human LAK cells and various antibodies. Treatment of mice bearing SW948 tumors with LAK cells did not retard tumor growth, but when CL158 was added, significant delays in tumor growth were observed. Tumor growth delay required treatment with both LAK cells and the bispecific antibody. Treatment with the IgG2a variant of CA19-9 antibody, alone or with LAK cells, had no effects on tumor growth. Although the mechanisms of these antitumor effects require further study, it is clear that human LAK cell treatment of animals bearing early, established s.c. tumors is enhanced by the addition of bispecific antibodies with relevant binding characteristics. When compared with the IgG2a isotype variant of CA19-9 monoclonal antibody, this bispecific antibody offers the advantages of preservation of activity in physiological conditions, infiltration and disruption of organized tumor in vitro, and antitumor effects in a relevant xenograft model.(ABSTRACT TRUNCATED AT 400 WORDS)
Interaction of Ethanol with Biological Membranes: The Formation of Non-bilayer Structures within the Membrane Interior and their Significance (2009)

To gain a better understanding of how ethanol affects biological membranes, we have performed a series of atomic-scale molecular dynamics simulations of phospholipid membranes in aqueous solution with ethanol, whose concentration was varied from 2.5 to 30 mol % (lipid-free basis). At concentrations below the threshold value of approximately 12 mol % (30.5 v/v %) ethanol induces expansion of the membrane, accompanied by a drop in the membrane thickness as well as disordering and enhanced interdigitation of lipid acyl chains. These changes become more pronounced with increase in ethanol concentration, but the bilayer structure of the membrane is maintained. Above the threshold concentration the appearance of multiple transient defects in the lipid/water interface eventually gives rise to desorption and assembly of some of the lipids into non-bilayer structures within the membrane interior. These structures, being small and irregular, resemble inverted micelles and have a long-lived character. Furthermore, formation of the non-bilayer structures is accompanied by mixing of lipids that belong to the opposite membrane leaflets, thereby leading to irreversible changes in the membrane structure. Remarkably, this observation of the formation of non-bilayer structures within the membrane interior, being in good agreement with experimental data, is found to be robust with respect to both the simulation conditions (the system size and the presence of salt) and the type of lipids (phosphatidylcholine and phosphatidylethanolamine). We discuss the significance of these non-bilayer structures in relation with the well-known ability of ethanol to promote membrane hemifusion as well as with the possible role of the micelle-like structures as a delivery system for polar solutes and ions. The ethanol-induced "damage" to the bilayer structure also suggests that strong alcoholic beverages ( approximately 40 v/v %) might be potentially hazardous to the epithelial tissues of the human body (such as lips, mouth, throat, gullet, and stomach) that come in direct contact with high-concentrations of ethanol.
The Physiologic and Pathologic Effects of Localized Cerebral Hypothermia (1958)

WOODHALL, BARNES; REYNOLDS, DAVID H.; MAHALEY, STEPHEN JR.; SANDERS, AARON P. Author Information
Design and Pharmacokinetic Characterization of Novel Antibody Formats for Ocular Therapeutics (2015)

We demonstrated that protein molecular weight and Fc region do not play a critical role in ocular PK, as they do systemically. Moreover, the mathematical model supports the selection of the "ideal therapeutic" by predicting ocular and systemic PK of any antibody format for any dose regimen. These findings have important implications for the design and selection of ocular therapeutics according to treatment needs, such as maximizing ocular half-life and minimizing systemic exposure.
Electrolyte Systems for High Withstand Voltage and Durability I. Linear Sulfones for Electric Double-Layer Capacitors (2011)

This study reports on new electrolyte systems utilizing linear sulfones. The characteristics of linear sulfones have been evaluated with the primary focus on higher withstand voltage. Investigations have been made on eight different types of linear sulfones with relatively low molecular weights. They were subjected to screening with regard to the melting and boiling point, dielectric constant, viscosity and the solubility of electrolyte salts. The results of the investigations were that Ethyl isopropyl sulfone (EiPS) and Ethyl isobutyl sulfone (EiBS) emerged as solvents with great potential. The EiPS has a relatively low melting point (−8°C) and a high boiling point (265°C), higher than that (242°C) of propylene carbonate (PC). Also, it was possible to dissolve the electrolyte salt in EiPS at 1.5 mol l−1 or higher. The EiPS system showed a high withstand voltage (3.3–3.7 V), exceeding that of PC (2.5–2.7 V). This high withstand voltage was found to have been caused by the high stability of EiPS at the interface between the activated carbon electrode and the electrolyte. By taking into consideration the degradation mechanisms of the EiPS system, we were able to clarify that one of the reasons for the high stability was the low reactivity between EiPS and H2O.
Electrical Alternans of the ST Segment in Non‐PrinzmetaPs Angina (1980)

Elevated electrical alternans of the elevated ST segment (STEA) was documented in a patient with non‐Prinzmetal's or classical angina and severe atherosclerotic coronary artery disease. STEA was precipitated during graded exercise testing. The disappearance of this phenomenon after aortocoronary bypass surgery suggests that the coronary obstructions were the etiologic factors. These findings emphasize that the STEA may occur in myocardial ischemia caused by conditions other than Prinzmetal's angina.
A New General Preparation of Polyfunctional Diarylamines by the Addition of Functionalized Arylmagnesium Compounds to Nitroarenes (2002)

The addition of functionalized arylmagnesium halides to nitroarenes in THF (-20 degrees C, 2 h) provides, after reductive workup (FeCl(2), NaBH(4)), various polyfunctional diarylamines in 63-86% yield. Heterocyclic arylated amines can be prepared by this one-pot procedure. A mechanistic rationale of this reaction is given.
Biotinylated antisense methylphosphonate oligodeoxynucleotides. Inhibition of spliceosome assembly and affinity selection of U1 and U2 small nuclear RNPs. (1991)

Methylphosphonate (PC) backbone oligodeoxynucleotides complementary to the 5'-terminal nucleotides of U1 and U2 small nuclear (sn) RNAs do not elicit RNase H action under conditions in which natural (phosphodiester) oligodeoxynucleotides yield extensive RNase H cleavage. We show here that antisense PC oligonucleotides can mask sites in U1 and U2 snRNPs that are required for spliceosome formation. We further report that biotinylated derivatives of antisense PC oligos can be used for affinity selection of U1 and U2 snRNPs.
Mechanisms of insulin resistance in human obesity: evidence for receptor and postreceptor defects. (1980)

(a) decreased cellular insulin receptors contribute to the insulin resistance associated with human obesity in all subjects; (b) in the least hyperinsulinemic, insulin-resistant patients, decreased insulin receptors are the sole defect, whereas in the more hyperinsulinemic, insulin-resistant patients, the insulin resistance is the result of a combination of receptor and postreceptor abnormalities; (c) all obese patients were insensitive to insulin's suppressive effects on hepatic glucose output; this was entirely the result of decreased insulin receptors; no postreceptor defect in this insulin effect was demonstrated.
[The role of population migration in the spread of opisthorchiasis from an Ob'-Irtysh invasion focus]. (1989)

The first quantitative indicators of opisthorchiasis irradiation from the invasion focus at the social level are obtained. It was demonstrated that 114.000 out of 1 mln. people leaving the helminthiasis invasion focus had suffered from opisthorchiasis. Invasion irradiation may be limited by means of reduction of emigration from the area by improvement of working and living conditions and reduction of the invasion rate, which can be attained by creation of a system of immigrants' protection and activization of preventive measures and medical treatment of local population.
Inhibitors of Human Histone Deacetylase:  Synthesis and Enzyme and Cellular Activity of Straight Chain Hydroxamates (2002)

Inhibitors of histone deacetylase (HDAC) have been shown to induce terminal differentiation of human tumor cell lines and to have antitumor effects in vivo. We have prepared analogues of suberoylanilide hydroxamic acid (SAHA) and trichostatin A and have evaluated them in a human HDAC enzyme inhibition assay, a p21(waf1) (p21) promoter assay, and in monolayer growth inhibition assays. One compound, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-benzamide, was found to affect the growth of a panel of eight human tumor cell lines differentially.
Mouse β-Defensin 1 Is a Salt-Sensitive Antimicrobial Peptide Present in Epithelia of the Lung and Urogenital Tract (1998)

One component of host defense at mucosal surfaces appears to be epithelium-derived peptides with antimicrobial activity called defensins. Human beta-defensin 1 (hBD-1) represents the first member of the beta-defensin family isolated from humans and has been implicated in the pathogenesis of cystic fibrosis. We describe in this report the isolation and characterization of a murine homolog of hBD-1 called mouse beta-defensin 1 (mBD-1). The predicted amino acid sequence shows the hallmark features of other known epithelial beta-defensins, including the ordered array of six cysteine residues. Analysis of a genomic clone of mBD-1 revealed two exons separated by a 15-kb intron. By use of fluorescence in situ hybridization, the mBD-1 gene was localized at the proximal portion of chromosome 8, the site where mouse alpha-defensins are found. Lysates from cells transfected with the mBD-1 cDNA showed antibacterial activity against gram-positive and gram-negative bacteria. mBD-1 transcripts were found in kidney, liver, and female reproductive organ tissues. In the airways, mBD-1 is expressed diffusely throughout the epithelial cells of the large proximal airways with less expression in the small distal airways and no expression in alveolar cells. The present study demonstrates that a beta-defensin potentially homologous to human beta-defensin 1 is present in the respiratory system and other mucosal surfaces in mice.
Interferon α may be back on track to treat acute myeloid leukemia (2013)

Our own experience and a thorough literature review suggest that interferon α (IFNα) should be reconsidered for the treatment of acute myeloid leukemia patients. Most likely, the success of such treatment depends on the achievement of high serum levels of IFNα for several months, which can be obtained by using pegylated IFNα.
Clinical features, epidemiology, and therapy of lymphangioleiomyomatosis (2015)

Lymphangioleiomyomatosis (LAM) is a multisystem disease of women, characterized by proliferation of abnormal smooth muscle-like LAM cells, leading to the formation of lung cysts, fluid-filled cystic structures in the axial lymphatics (eg, lymphangioleiomyomas), and renal angiomyolipomas. LAM is caused by mutations of the TSC1 or TSC2 genes, which encode, respectively, hamartin and tuberin, two proteins with a major role in control of the mammalian target of rapamycin (mTOR) signaling pathway. LAM occurs sporadically or in association with tuberous sclerosis complex, an autosomal-dominant syndrome characterized by widespread hamartomatous lesions. LAM may present with progressive dyspnea, recurrent pneumothorax, or chylothorax. Pulmonary function tests show reduced flow rates (forced expiratory volume in the first second) and diffusion capacity. Exercise testing may reveal gas exchange abnormalities, ventilatory limitation, and hypoxemia. The severity and progression of disease may be assessed by lung histology scores, quantification of computed tomography, pulmonary function testing, 6-minute walk tests, cardiopulmonary exercise testing, and measurement of serum vascular endothelial growth factor D levels. Sirolimus and everolimus, two mTOR inhibitors, are effective in stabilizing lung function and reducing the size of chylous effusions, lymphangioleiomyo-mas, and angiomyolipomas. However, inhibition of mTOR complex 1 increases autophagy, possibly enhancing LAM cell survival. Inhibition of autophagy with hydroxychloroquine, in combination with sirolimus, has been proposed as a possible treatment for LAM. Deficiency of tuberin results in increased RhoA GTPase activity and cell survival, an effect that is mediated through mTOR complex 2 signaling. Because sirolimus and everolimus only affect the activity of mTOR complex 1, therapies targeting RhoA GTPases with simvastatin, which inhibits Rho GTPases and promotes apoptosis, are being investigated. As in the case of cancer, LAM may be best treated with multiple drugs targeting signaling pathways considered important in the pathogenesis of disease.
Tubulin-Targeting Chemotherapy Impairs Androgen Receptor Activity in Prostate Cancer (2010)

Recent insights into the regulation of the androgen receptor (AR) activity led to novel therapeutic targeting of AR function in prostate cancer patients. Docetaxel is an approved chemotherapy for treatment of castration-resistant prostate cancer; however, the mechanism underlying the action of this tubulin-targeting drug is not fully understood. This study investigates the contribution of microtubules and the cytoskeleton to androgen-mediated signaling and the consequences of their inhibition on AR activity in human prostate cancer. Tissue microarrays from docetaxel-treated and untreated prostate cancer patients were comparatively analyzed for prostate-specific antigen (PSA) and AR immunoreactivity. The AR transcriptional activity was determined in prostate cancer cells in vitro, based on PSA mRNA expression and the androgen response element reporter activity. The interaction of AR with tubulin was examined by immunoprecipitation and immunofluorescence. Treatment of prostate cancer patients with docetaxel led to a significant translocation of AR. In untreated specimens, 50% prostate tumor cells exhibited nuclear accumulation of AR, compared with docetaxel-treated tumors that had significantly depleted nuclear AR (38%), paralleled by an increase in cytosolic AR. AR nuclear localization correlated with PSA expression. In vitro, exposure of prostate cancer cells to paclitaxel (1 μmol/L) or nocodazole (5 μg/mL) inhibited androgen-dependent AR nuclear translocation by targeting AR association with tubulin. Introduction of a truncated AR indicated the requirement of the NH(2)-terminal domain for AR-tubulin interaction. Our findings show that in addition to blocking cell division, docetaxel impairs AR signaling, evidence that enables new insights into the therapeutic efficacy of microtubule-targeting drugs in prostate cancer.
Human T-Cell γ Chain Genes: Organization, Diversity, and Rearrangement (1986)

The human T-cell gamma chain genes have been characterized in an attempt to better understand their role in immune response. These immunoglobulin-like genes are encoded in the genome in variable, joining, and constant segments. The human gamma genes include at least six variable region genes, two joining segments, and two constant-region genes in germline DNA. Variable and joining segments recombine during the development of T cells to form rearranged genes. The diversity of human gamma genes produced by this recombinational mechanism is greater than that produced by the murine genome but is more limited than that of other immunoglobulin-like genes.
Rapid Point-Of-Care Breath Test for Biomarkers of Breast Cancer and Abnormal Mammograms (2014)

A pilot study of a six-minute point-of-care breath test for volatile biomarkers accurately identified women with breast cancer and with abnormal mammograms. Breath testing could potentially reduce the number of needless mammograms without loss of diagnostic sensitivity.
Cutting Edge: The Common γ-Chain Is an Indispensable Subunit of the IL-21 Receptor Complex (2001)

The common gamma-chain (gamma(c)) is an indispensable subunit of the functional receptor complexes for IL-4, IL-7, IL-9, and IL-15 as well as IL-2. Here we show that the gamma(c) is also shared with the IL-21R complex. Although IL-21 binds to the IL-21R expressed on gamma(c)-deficient ED40515(-) cells, IL-21 is unable to transduce any intracytoplasmic signals. However, in EDgamma-16 cells, a gamma(c)-transfected ED40515(-) cell line, IL-21 binds to the IL-21R and can activate Janus kinase (JAK)1, JAK3, STAT1, and STAT3. The chemical cross-linking study reveals the direct binding of IL-21 to the gamma(c). These data clearly demonstrate that the gamma(c) is an indispensable subunit of the functional IL-21R complex.
Membrane proteins of chromaffin granules. Dopamine β-hydroxylase, a major constituent (1972)

1. Soluble lysates and membranes were prepared from chromaffin granules isolated from bovine adrenal medulla. The detergent N-cetylpyridinium chloride was used for solubilizing the membrane proteins, including the membrane-bound dopamine (2,4-dihydroxyphenethylamine) beta-hydroxylase. The solubilized proteins were fractionated by Sephadex chromatography in the presence of N-cetylpyridinium chloride. The major component of the membrane proteins, i.e. chromomembrin A, was identified as the enzyme dopamine beta-hydroxylase. 2. The addition of N-cetylpyridinium chloride to the soluble lysate caused precipitation of up to 96% of the proteins, but only a small proportion of the dopamine beta-hydroxylase activity was precipitated. The only protein demonstrable in the supernatant by polyacrylamide-gel electrophoresis was the protein that has a lower mobility than chromogranin A in disc gel electrophoresis. This component has been identified previously as dopamine beta-hydroxylase. Thus, this method provides an extremely simple isolation procedure for dopamine beta-hydroxylase. 3. A comparison of the membrane-bound and soluble dopamine beta-hydroxylases revealed the identity of these two preparations. Both were activated by N-cetylpyridinium chloride, they migrated identically in polyacrylamide-gel electrophoresis, their amino acid composition was very similar and an immunological cross-reaction could be demonstrated.
Building task-specific interfaces to high volume conversational data (1997)

Article Free Access Share on Building task-specific interfaces to high volume conversational data Authors: Loren G. Terveen AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJ AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJView Profile , William C. Hill AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJ AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJView Profile , Brian Amento AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJ AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJView Profile , David McDonald AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJ AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJView Profile , Josh Creter AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJ AT&T Labs - Research, 600 Mountain Avenue, Murray Hill, NJView Profile Authors Info & Claims CHI '97: Proceedings of the ACM SIGCHI Conference on Human factors in computing systemsMarch 1997 Pages 226–233https://doi.org/10.1145/258549.258712Published:27 March 1997Publication History 16citation432DownloadsMetricsTotal Citations16Total Downloads432Last 12 Months20Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Alkaline Urea Electrolysis and Possible Applications (2008)

Abstract not Available.
Flow in the Major Branches of the Left Coronary Artery during Experimental Coronary Insufficiency in the Unanesthetized Dog (1968)

The dynamic changes in the coronary circulation and the response to drugs were studied following experimentally induced coronary insufficiency. Flow measurements were made in the left circumflex and descending branches of the coronary artery, and in the ascending aorta; pressures were measured in the ascending aorta and the left ventricle. As the left circumflex coronary artery branch was gradually constricted, reactive hyperemia following a 10-second occlusion of that vessel decreased. When the Degrees of constriction became such that the control resting flow began to fall, there was no reactive hyperemia, and the contractility index of the heart decreased. Within less than 24 hours, flow in the descending branch of the left coronary artery rose, and the cardiac contractility index returned to control; peak flow rate in the descending branch during reactive hyperemia after a 10-second occlusion also increased. The response to isoproterenol, nitroglycerin, and dipyridamole was similar in direction before and after the partial reduction of flow in the left circumflex coronary artery branch. The response was less in the coronary vessel with partial occlusion; in the unimpeded descending coronary artery branch, the response increased progressively. These results are consistent with the development of collateral vessels.