gebhart/patrepeval huggingface dataset:
Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti- CD19 immunotoxins (1988)

Extensive immunologic surface marker analyses and binding competition assays demonstrated that B43 monoclonal antibody (MoAb) is a new member of the CD19 cluster that recognizes the same surface epitope as several other anti-CD19 MoAbs. We used B43 MoAb to test for CD19 expression on neoplastic cells from 340 leukemia and 151 malignant lymphoma patients and on nonneoplastic cells in normal lymphohematopoietic and nonlymphohematopoietic tissues. Our study more than doubles the total number of cases with classified hematologic malignancies that have been examined for CD19 antigen expression. The data presented confirm that CD19 is the most reliable B lineage surface marker and support our view that this B lineage-restricted surface determinant may be an important functional receptor. Our findings provide unique and direct evidence that (a) CD19 is expressed on leukemic B lineage lymphoid progenitor cells freshly obtained from B lineage acute lymphoblastic leukemia patients but not on normal myeloid, erythroid, megakaryocytic, or multilineage bone marrow progenitor cells; (b) ligation of CD19 with B43 MoAb induces sustained increases in [Ca2+]i when crosslinked and inhibits high-molecular weight B cell growth factor (HMW-BCGF)-induced proliferation of activated B cells without affecting their low-molecular weight B cell growth factor (LMW-BCGF) response; therefore CD19 may be a unique signal receptor; (c) HMW-BCGF and LMW-BCGF augment expression of CD19, which suggests that CD19 and BCGF receptors may be under coordinate regulatory control; (d) approximately two million B43 MoAb molecules per cell can be bound to target B lineage lymphoma cells with a Ka of 1.9 x 10(8)/mol/L; (e) CD19 can undergo B43 MoAb-induced internalization; and (f) the opportunity is thus provided for using anti-CD19 MoAb to deliver toxins to B lineage neoplastic cells for more effective treatment of high-risk leukemia/lymphoma patients.
Automatic instant messaging dialogue using statistical models and dialogue acts (2008)

Despite current attempts by health professionals to detect postnatal depression, some mothers remain reluctant to disclose their true feelings. This qualitative report aims to explore the thoughts and feelings held by mothers who suffered postnatal depression in order to promote understanding of the condition. Unstructured interviews were conducted with 10 new mothers, and transcripts were analysed using Interpretative Phenomenological Analysis (IPA). Participants reported several commonly endorsed themes including difficulties associated with telling people about their thoughts and feelings, unrealistic expectations of motherhood, beliefs around being a bad mum and issues around attachment. Other themes were less commonly endorsed but offered new information to increase current understanding of the experiences of women suffering postnatal depression. Such themes included feeling unjustified in being depressed, self-doubt, and thoughts that someone in their family might die. The findings offer a valuable insight into the experience and perceptions of mothers suffering with postnatal depression. It is suggested that clinicians working with perinatal women should be proactive in routinely offering information about postnatal depression and of help available, as well as providing appropriate reassurance about the consequences of disclosure.
A controlled double blind study of azathioprine in the management of Crohn's disease. (1995)

While immunosuppressive agents are used widely in the management of Crohn's disease, their efficacy has not been well established in randomised controlled trials. This study was designed to examine whether azathioprine increases remission rate when used in conjunction with a diminishing dose regimen of prednisolone over a period of 12 weeks. It further examined whether azathioprine offers any therapeutic advantage over placebo in the maintenance of remission in Crohn's disease over a period of 15 months. Sixty three patients with active Crohn's disease were treated with a 12 weeks diminishing dose of prednisolone and at the same time entered into a randomised, double blind 15 month trial of either azathioprine (2.5 mg/kg) or placebo. Remission rates between the two groups were compared at 12 weeks and at 15 months. There was no significant difference in the proportion of patients who had achieved and maintained remission by week 12 but at 15 months there was a highly significant difference in the proportion of patients in remission (42% receiving azathioprine v 7% receiving placebo), p = 0.001. Using life tables this beneficial effect was reflected as the difference in the median number of days on the trial (p = 0.02). There were significantly greater decreases over the trial period in the median erythrocyte sedimentation rate, C reactive protein, and leucocyte count in the azathioprine group. There were no cases of severe bone marrow suppression or clinical pancreatitis. In conclusion, azathioprine offers a therapeutic advantage over placebo in the maintenance of remission in Crohn's disease.
3D Reservoir Geomechanical Modeling in Oil/Gas Field Production (2009)

Abstract The pore pressure, stress state and geological structures as well as their evolution during an oil/gas field life have widespread influence on implications for wellbore stability, hydraulic fracturing, fault-reactivation, early water-cut, top surface subsidence, reservoir compaction and water/gas flooding. These events have a significant impact on reservoir performance and their effects need to be taken into account in production surveillance, analysis and forecasting. A coupled reservoir geomechanical modeling approach is developed, using the static and dynamic models of VISAGETM System, to compute the change in reservoir pore pressure and stress state, the evolution of reservoir properties, the development of potential fracturing and the reactivation of existing faults. This geomechanical modeling consists of an initial stress simulation prior to production and a coupled reservoir simulation due to depletion and/or injection activities. A very representative initial stress state can be simulated using this approach and can be well calibrated with stress measurements from wireline logs, borehole breakouts and regional stress. Based on the simulated initial stress state, the change in pore pressure due to depletion and/or injection is used to compute the change in effective stress and associated reservoir deformation. The production history and observed reservoir deformation in the past can be simulated. Reservoir performance and associated reservoir deformation can also be predicted in the future production. A full field study using the VISAGETM System was performed to help assess the integrity of the development plan in South Arne field, North Sea. The predicted stress and strain changes that were induced by production/injection were used to assess the wellbore stability, potential for faults reactivation, cap rock integrity and rock fracturing. This study demonstrates that coupled geomechanical modeling lends direct support to drilling operations and reservoir management.
Amylin Agonists: A Novel Approach in the Treatment of Diabetes (2004)

Amylin is a peptide hormone that is cosecreted with insulin from the pancreatic beta-cell and is thus deficient in diabetic people. It inhibits glucagon secretion, delays gastric emptying, and acts as a satiety agent. Amylin replacement could therefore possibly improve glycemic control in some people with diabetes. However, human amylin exhibits physicochemical properties predisposing the peptide hormone to aggregate and form amyloid fibers, which may play a part in beta-cell destruction in type 2 diabetes. This obviously makes it unsuitable for pharmacological use. A stable analog, pramlintide, which has actions and pharmacokinetic and pharmacodynamic properties similar to the native peptide, has been developed. The efficacy and safety of pramlintide administration has been tested in a vast number of clinical trials. Approximately 5,000 insulin-treated patients have received pramlintide and approximately 250 for > or =2 years. The aims of this review are to 1) briefly describe actions of amylin as demonstrated in animal and human models and 2) primarily review results from clinical trials with the amylin analog pramlintide.
High-Dose Recombinant Apolipoprotein A-I Milano Mobilizes Tissue Cholesterol and Rapidly Reduces Plaque Lipid and Macrophage Content in Apolipoprotein E–Deficient Mice (2001)

A single high dose of recombinant apoA-I(m) rapidly mobilizes tissue cholesterol and reduces plaque lipid and macrophage content in apoE-deficient mice. These findings suggest that this strategy could rapidly change plaque composition toward a more stable phenotype.
Transient High Levels of Viremia in Patients with Primary Human Immunodeficiency Virus Type 1 Infection (1991)

Although p24 core antigenemia and viral isolation have previously been described during primary HIV-1 infection, this report documents the large viral burden during the acute phase of infection. The rapid and spontaneous decline in the viral load suggests an effective immune response in the host that, if understood, may be used to combat AIDS.
Studies on Electronic Effects in O‐, N‐ and S‐Chelated Ruthenium Olefin‐Metathesis Catalysts (2010)

A short overview on the structural design of the Hoveyda-Grubbs-type ruthenium initiators chelated through oxygen, nitrogen or sulfur atoms is presented. Our aim was to compare and contrast O-, N- and S-chelated ruthenium complexes to better understand the impact of electron-withdrawing and -donating substituents on the geometry and activity of the ruthenium complexes and to gain further insight into the trans-cis isomerisation process of the S-chelated complexes. To evaluate the different effects of chelating heteroatoms and to probe electronic effects on sulfur- and nitrogen-chelated latent catalysts, we synthesised a series of novel complexes. These catalysts were compared against two well-known oxygen-chelated initiators and a sulfoxide-chelated complex. The structures of the new complexes have been determined by single-crystal X-ray diffraction and analysed to search for correlations between the structural features and activity. The replacement of the oxygen-chelating atom by a sulfur or nitrogen atom resulted in catalysts that were inert at room temperature for typical ring-closing metathesis (RCM) and cross-metathesis reactions and showed catalytic activity only at higher temperatures. Furthermore, one nitrogen-chelated initiator demonstrated thermo-switchable behaviour in RCM reactions, similar to its sulfur-chelated counterparts.
Study of Molecular Trapping Inside Gold Nanofinger Arrays on Surface-Enhanced Raman Substrates (2011)

The binding of trans-1,2-bis(4-pyridyl)-ethylene (BPE) molecules on substrates arrayed with flexible gold nanofingers has been studied by surface-enhanced Raman spectroscopy (SERS) and angle-resolved X-ray photoelectron spectroscopy (AR-XPS). On the basis of the SERS and XPS results, BPE molecules are found to interact with the gold nanofingers through the lone pair electrons of pyridyl nitrogens, not through delocalized π electrons. Furthermore, after comparing the AR-XPS spectra of finger arrays preclosed before exposure to BPE with the spectra of arrays that closed after exposure to BPE, we observed in the latter case, at grazing takeoff angles, an increase in the component of the nitrogen photoelectron peak associated with pyridyl nitrogen atoms residing on bridging sites. These results demonstrate that a small percentage of BPE molecules was trapped between the neighboring gold finger tips during the finger closing process. However, because these trapped BPE molecules coincidently resided in the hot spots formed among the touching finger tips, the substantial increase in the observed SERS signal was dominated by the contribution from this small minority of BPE molecules.
Structural basis for strand-transfer inhibitor binding to HIV intasomes (2020)

The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretroviral drugs, integrase strand-transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy structures of HIV intasomes bound to the latest generation of INSTIs. These structures highlight how small changes in the integrase active site can have notable implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug-resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals.
Theoretical modeling for radiofrequencyablation: state-of-the-art and challenges for the future (2006)

Radiofrequency ablation is an interventional technique that in recent years has come to be employed in very different medical fields, such as the elimination of cardiac arrhythmias or the destruction of tumors in different locations. In order to investigate and develop new techniques, and also to improve those currently employed, theoretical models and computer simulations are a powerful tool since they provide vital information on the electrical and thermal behavior of ablation rapidly and at low cost. In the future they could even help to plan individual treatment for each patient. This review analyzes the state-of-the-art in theoretical modeling as applied to the study of radiofrequency ablation techniques. Firstly, it describes the most important issues involved in this methodology, including the experimental validation. Secondly, it points out the present limitations, especially those related to the lack of an accurate characterization of the biological tissues. After analyzing the current and future benefits of this technique it finally suggests future lines and trends in the research of this area.
Curcumin Potentiates Antitumor Activity of Gemcitabine in an Orthotopic Model of Pancreatic Cancer through Suppression of Proliferation, Angiogenesis, and Inhibition of Nuclear Factor-κB–Regulated Gene Products (2007)

Gemcitabine is currently the best treatment available for pancreatic cancer, but the disease develops resistance to the drug over time. Agents that can either enhance the effects of gemcitabine or overcome chemoresistance to the drug are needed for the treatment of pancreatic cancer. Curcumin, a component of turmeric (Curcuma longa), is one such agent that has been shown to suppress the transcription factor nuclear factor-kappaB (NF-kappaB), which is implicated in proliferation, survival, angiogenesis, and chemoresistance. In this study, we investigated whether curcumin can sensitize pancreatic cancer to gemcitabine in vitro and in vivo. In vitro, curcumin inhibited the proliferation of various pancreatic cancer cell lines, potentiated the apoptosis induced by gemcitabine, and inhibited constitutive NF-kappaB activation in the cells. In vivo, tumors from nude mice injected with pancreatic cancer cells and treated with a combination of curcumin and gemcitabine showed significant reductions in volume (P = 0.008 versus control; P = 0.036 versus gemcitabine alone), Ki-67 proliferation index (P = 0.030 versus control), NF-kappaB activation, and expression of NF-kappaB-regulated gene products (cyclin D1, c-myc, Bcl-2, Bcl-xL, cellular inhibitor of apoptosis protein-1, cyclooxygenase-2, matrix metalloproteinase, and vascular endothelial growth factor) compared with tumors from control mice treated with olive oil only. The combination treatment was also highly effective in suppressing angiogenesis as indicated by a decrease in CD31(+) microvessel density (P = 0.018 versus control). Overall, our results suggest that curcumin potentiates the antitumor effects of gemcitabine in pancreatic cancer by suppressing proliferation, angiogenesis, NF-kappaB, and NF-kappaB-regulated gene products.
Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma (2015)

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. The survival rate after the onset of symptoms is generally less than one year for the late presentation of HCC, and reliable tools for early diagnosis are lacking. Therefore, novel biomarkers for the early detection of HCC are urgently required. Recent studies show that the abnormal release of proteins by tumor cells can elicit humoral immune responses to self-antigens called tumor-associated antigens (TAAs). The corresponding autoantibodies can be detected before the clinical diagnosis of cancer. Therefore, there is growing interest in using serum autoantibodies as cancer biomarkers. In this review, we focus on the advances in research on autoantibodies against TAAs as serum biomarker for detection of HCC, the mechanism of the production of TAAs, and the association of autoantibodies with patients' clinical characteristics.
Visual programming support for graph-oriented parallel-distributed processing: Research Articles (2005)

GOP is a graph-oriented programming model which aims at providing high-level abstractions for configuring and programming cooperative parallel processes. With GOP, the programmer can configure the logical structure of a parallelsdistributed program by constructing a logical graph to represent the communication and synchronization between the local programs in a distributed processing environment. This paper describes a visual programming environment, called VisualGOP, for the design, coding, and execution of GOP programs. VisualGOP applies visual techniques to provide the programmer with automated and intelligent assistance throughout the program design and construction process. It provides a graphical interface with support for interactive graph drawing and editing, visual programming functions and automation facilities for program mapping and execution. VisualGOP is a generic programming environment independent of programming languages and platforms. GOP programs constructed under VisualGOP can run in heterogeneous parallelsdistributed systems. Copyright © 2005 John Wiley & Sons, Ltd.
Preorganization of the Bioactive Conformation of Sialyl LewisX Analogues Correlates with Their Affinity to E-Selectin (2001)

It pays to be organized: Steric repulsion between fucose and the methyl substituent of the adjacent tetrahydropyran reduces the distance between galactose and fucose in the E-selectin antagonist 1 compared to the distance in closely related compounds that lack the methyl group. This effect causes a solution conformation of 1 that already resembles its conformation when bound to E-selectin and, thus, leads to a significantly improved bioactivity.
Isohumulones, Bitter Acids Derived from Hops, Activate Both Peroxisome Proliferator-activated Receptor α and γ and Reduce Insulin Resistance (2004)

The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of fibrate drugs and the therapeutic benefits of the thiazolidinedione drugs are due to their activation of PPARalpha and -gamma, respectively. In this study, isohumulones, the bitter compounds derived from hops that are present in beer, were found to activate PPARalpha and -gamma in transient co-transfection studies. Among the three major isohumulone homologs, isohumulone and isocohumulone were found to activate PPARalpha and -gamma. Diabetic KK-Ay mice that were treated with isohumulones (isohumulone and isocohumulone) showed reduced plasma glucose, triglyceride, and free fatty acid levels (65.3, 62.6, and 73.1%, respectively, for isohumulone); similar reductions were found following treatment with the thiazolidinedione drug, pioglitazone. Isohumulone treatment did not result in significant body weight gain, although pioglitazone treatment did increase body weight (10.6% increase versus control group). C57BL/6N mice fed a high fat diet that were treated with isohumulones showed improved glucose tolerance and reduced insulin resistance. Furthermore, these animals showed increased liver fatty acid oxidation and a decrease in size and an increase in apoptosis of their hypertrophic adipocytes. A double-blind, placebo-controlled pilot study for studying the effect of isohumulones on diabetes suggested that isohumulones significantly decreased blood glucose and hemoglobin A1c levels after 8 weeks (by 10.1 and 6.4%, respectively, versus week 0). These results suggest that isohumulones can improve insulin sensitivity in high fat diet-fed mice with insulin resistance and in patients with type 2 diabetes.
VEGF-initiated blood-retinal barrier breakdown in early diabetes. (2001)

Early blood-retinal barrier breakdown in experimental diabetes is VEGF dependent and is restricted, in part, to the venules and capillaries of the superficial inner retinal vasculature. VEGF inhibition should prove a useful therapeutic approach in the treatment of early diabetic blood-retinal barrier breakdown.
Stability Guidelines for Routinely Refrigerated Drug Products (1983)

Information was collected from manufacturers on the stability of routinely refrigerated drugs under various temperature conditions. Surveys were mailed to 37 companies representing 80 different drug products. Stability data were requested for storage at room temperature (15–30 °C), in a cool place (8–15 °C), and under refrigeration (2–8 °C) after 24 hours at controlled room temperature. Responses were received from 84% of those surveyed. Information beyond that provided in product package inserts is presented as a general guide for pharmacists.
Increased spontaneous mutation and alkylation sensitivity of Escherichia coli strains lacking the ogt O6-methylguanine DNA repair methyltransferase (1991)

Escherichia coli expresses two DNA repair methyltransferases (MTases) that repair the mutagenic O6-methylguanine (O6MeG) and O4-methylthymine (O4MeT) DNA lesions; one is the product of the inducible ada gene, and here we confirm that the other is the product of the constitutive ogt gene. We have generated various ogt disruption mutants. Double mutants (ada ogt) do not express any O6MeG/O4MeT DNA MTases, indicating that Ada and Ogt are probably the only two O6MeG/O4MeT DNA MTases in E. coli. ogt mutants were more sensitive to alkylation-induced mutation, and mutants arose linearly with dose, unlike ogt+ cells, which had a threshold dose below which no mutants accumulated; this ogt(+)-dependent threshold was seen in both ada+ and ada strains. ogt mutants were also more sensitive to alkylation-induced killing (in an ada background), and overexpression of the Ogt MTase from a plasmid provided ada, but not ada+, cells with increased resistance to killing by alkylating agents. The induction of the adaptive response was normal in ogt mutants. We infer from these results that the Ogt MTase prevents mutagenesis by low levels of alkylating agents and that, in ada cells, the Ogt MTase also protects cells from killing by alkylating agents. We also found that ada ogt E. coli had a higher rate of spontaneous mutation than wild-type, ada, and ogt cells and that this increased mutation occurred in nondividing cells. We infer that there is an endogenous source of O6MeG or O4MeT DNA damage in E. coli that is prevalent in nondividing cells.