gebhart/patrepeval huggingface dataset:
New 2-Piperazinylbenzimidazole Derivatives as 5-HT<sub>3</sub>Antagonists. Synthesis and Pharmacological Evaluation (1997)

A series of 2-piperazinylbenzimidazole derivatives were prepared and evaluated as 5-HT3 receptor antagonists. Their 5-HT3 receptor affinities were evaluated by radioligand binding assays, and their abilities to inhibit the 5-HT-induced Bezold-Jarisch reflex in anesthetized rats were determined. Compound 7e (lerisetron, pKi = 9.2) exhibited higher affinity for the 5-HT3 receptor than did tropisetron and granisetron, while compound 7q (pKi = 7.5) had very low affinity for this receptor, showing that substitution on the N1 atom of the benzimidazole ring is essential for affinity and activity. The effect of substitution on the aromatic ring of benzimidazole by several substituents in different positions is also discussed. A strong correlation between the 5-HT3 antagonistic activity of the studied compounds and the position of substitution on the aromatic ring was established. Thus, while the 4-methoxy derivative 7m showed weak affinity for the 5-HT3 receptor (pKi = 6.7), the 7-methoxy derivative 7n exhibited the highest affinity (pKi = 9.4). Compounds 7e and 7n are now under further investigation as drugs for the treatment of nausea and emesis evoked by cancer chemotherapy and radiation.
Implementing interior point linear programming methods in the Optimization Subroutine Library (1992)

This paper discusses the implementation of interior point (barrier) methods for linear programming within the framework of the IBM Optimization Subroutine Library. This class of methods uses quite different computational kernels than the traditional simplex method. In particular, the matrices we must deal with are symmetric and, although still sparse, are considerably denser than those assumed in simplex implementations. Severe rank deficiency must also be accommodated, making it difficult to use off-the-shelf library routines. These features have particular implications for the exploitation of the newer IBM machine architectural features. In particular, interior methods can benefit greatly from use of vector architectures on the IBM 3090™ series computers and “super-scalar“ processing on the RISC System/6000™ series.
Switchable Reflections Make Electronic Ink (1999)

At a meeting of the Canadian Association of Physicists in New Brunswick last month, physicists demonstrated an electronic version of paper and print that combines the optical principle used in reflective signs with a scheme for squelching the reflections at will. Although the team has not yet shown how to build a working display screen, researchers are enthusiastic that the technique could lead to displays with faster response times and lower power needs than other electronic ink schemes.
Probabilistic Routing Protocol for Intermittently Connected Networks (2012)

This document is a product of the Delay Tolerant Networking Research Group and has been reviewed by that group.No objections to its publication as an RFC were raised.This document defines PRoPHET, a Probabilistic Routing Protocol using History of Encounters and Transitivity.PRoPHET is a variant of the epidemic routing protocol for intermittently connected networks that operates by pruning the epidemic distribution tree to minimize resource usage while still attempting to achieve the best-case routing capabilities of epidemic routing.It is intended for use in sparse mesh networks where there is no guarantee that a fully connected path between the source and destination exists at any time, rendering traditional routing protocols unable to deliver messages between hosts.These networks are examples of networks where there is a disparity between the latency requirements of applications and the capabilities of the underlying network (networks often referred to as delay and disruption tolerant).The document presents an architectural overview followed by the protocol specification. Status of This MemoThis document is not an Internet Standards Track specification; it is published for examination, experimental implementation, and evaluation.This document defines an Experimental Protocol for the Internet community.This document is a product of the Internet Research Task Force (IRTF).The IRTF publishes the results of Internet-related research and development activities.These results might not be suitable for deployment.
Combination therapy: the next opportunity and challenge of medicine (2011)

From an historical point of view, combination therapy was the basis for the care of important diseases like infection diseases or cancer. Today the "cocktail drug" of the Highly Active Anti Retroviral Therapy (HAART) has reduced the death for HIV infection changing the outcome of such disease. Moreover, the combination of different strategies changed the course of transplants (both in haematology and surgical transplant). Different diseases with high social impact including cardiovascular, metabolic (obesity, hypercholesterolaemia and diabetes) and autoimmune diseases, have better results with combinations of different drug classes of drugs. After recent successes in the immunotherapy field (Sepuleucel-T, ipilimumab) and the new promising small molecule therapies, cancer should be the next challenge for combination strategies.
P53 and oncogenes expression in psoriasis. (1989)

Activity of p53, H-ras, c-myc and c-fos in psoriatic lesions was studied using monoclonal antibodies (MoAbs) performing a sensitive immunohistochemical method on frozen sections. Normal skin from surgery was used as control. Reactivity of p53, H-ras and c-myc is remarkable in psoriatic plaques but, in contrast, c-fos expression does not show differences compared to control skin. These findings led us to speculate about the importance of cellular oncogenes in the pathogenesis of psoriasis.
Src-mediated Inter-receptor Cross-talk between the Na+/K+-ATPase and the Epidermal Growth Factor Receptor Relays the Signal from Ouabain to Mitogen-activated Protein Kinases (2002)

Binding of ouabain to Na(+)/K(+)-ATPase activates tyrosine phosphorylation of the epidermal growth factor receptor (EGFR), Src, and p42/44 mitogen-activated protein kinases (MAPKs) in both cardiac myocytes and A7r5 cells. Here, we explored the roles of Src and the EGFR in the ouabain-invoked pathways that lead to the activation of MAPKs. Exposure of A7r5 and LLC-PK1 cells to ouabain caused a dose-dependent inhibition of Na(+)/K(+)-ATPase activity, which correlated well with ouabain-induced activation of Src and MAPKs in these cells. Immunoprecipitation experiments showed that ouabain stimulated Src binding to Na(+)/K(+)-ATPase in a dose- and time-dependent manner and increased phosphorylation of Src at Tyr(418) but had no effect on Tyr(529) phosphorylation. Ouabain failed to activate MAPKs in A7r5 cells that were pretreated with the Src inhibitor PP2 and in SYF cells in which Src family kinases are knocked out. Preincubation with AG1478, but not AG1295, also blocked the effects of ouabain on p42/44 MAPKs in A7r5 cells. Significantly, both herbimycin A and PP2 abrogated ouabain-induced but not epidermal growth factor-induced Src binding to the EGFR and the subsequent EGFR tyrosine phosphorylation. Ouabain also failed to affect tyrosine phosphorylation of the EGFR in SYF cells. In addition, unlike epidermal growth factor, ouabain did not increase EGFR autophosphorylation at Tyr(1173). These findings clearly indicate that ouabain transactivates the EGFR by activation of Src and stimulation of Src binding to the EGFR. Furthermore, we found that the transactivated EGFR was capable of recruiting and phosphorylating the adaptor protein Shc. This resulted in increased binding of another adaptor protein Grb2 to the Src-EGFR complex and the subsequent activation of Ras and MAPKs. Taken together, these new findings suggest that Src mediates the inter-receptor cross-talk between Na(+)/K(+)-ATPase and the EGFR to transduce the signals from ouabain to the Ras/MAPK cascade.
Holography, 1948-1971 (1972)

Lecture delivered by Dennis Gabor on the occasion of his receiving the 1971 Nobel Prize for Physics, Stockholm, Sweden, December 13 1971. Copyright (c) The Nobel Foundation 1972.
Hemoglobin switching in unicellular erythroid culture of sibling erythroid burst-forming units: kit ligand induces a dose-dependent fetal hemoglobin reactivation potentiated by sodium butyrate (2000)

Abstract Mechanisms underlying fetal hemoglobin (HbF) reactivation in adult life have not been elucidated; particularly, the role of growth factors (GFs) is controversial. Interestingly, histone deacetylase (HD) inhibitors (sodium butyrate, NaB, trichostatin A, TSA) reactivate HbF. We developed a novel model system to investigate HbF reactivation: (1) single hematopoietic progenitor cells (HPCs) were seeded in serum-free unilineage erythroid culture; (2) the 4 daughter cells (erythroid burst-forming units, [BFU-Es]), endowed with equivalent proliferation/differentiation and HbF synthesis potential, were seeded in 4 unicellular erythroid cultures differentially treated with graded dosages of GFs and/or HD inhibitors; and (3) HbF levels were evaluated in terminal erythroblasts by assay of F cells and γ-globin content (control levels, 2.4% and 1.8%, respectively, were close to physiologic values). HbF was moderately enhanced by interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor treatment (up to 5%-8% γ-globin content), while sharply reactivated in a dose-dependent fashion by c-kit ligand (KL) and NaB (20%-23%). The stimulatory effects of KL on HbF production and erythroid cell proliferation were strictly correlated. A striking increase of HbF was induced by combined addition of KL and NaB or TSA (40%-43%). This positive interaction is seemingly mediated via different mechanisms: NaB and TSA may modify the chromatin structure of the β-globin gene cluster; KL may activate the γ-globin promoter via up-modulation of tal-1 and possibly FLKF transcription factors. These studies indicate that KL plays a key role in HbF reactivation in adult life. Furthermore, combined KL and NaB administration may be considered for sickle cell anemia and β-thalassemia therapy.
Adaptive multiple reference frame based scalable video coding algorithm (2003)

In this paper, we propose a novel scalable video coding algorithm based on adaptively weighted multiple reference frame method. To improve the coding efficiency in the enhancement layer, double reference picture and double motion vector algorithms are employed for motion compensated prediction. Furthermore, an enhancement layer frame is predicted from the adaptively weighted superposition of the corresponding base layer frame and the double motion compensated frames, according to the the input video characteristics and the feedback channel condition. By employing an adaptive reference selection scheme at the decoder, the proposed method can reduce the drift problem significantly. Experimental results show that the proposed algorithm yields higher PSNR performance than H.263+ both in error-free and severe packet loss channel conditions.
Laser therapy of rheumatoid arthritis (1980)

Thirty people with classical or definite rheumatoid arthritis received laser exposure to a Q-switch neodymium laser that operated at 1.06 micrometer with an output of 15 joules/cm2 for 30 nsec. One hand was lased at the proximal interphalangeal (PIP) and metacarpal phalangeal (MCP) joints, whereas the other hand was sham lased. The patient, physician, and occupational therapy evaluators did not know which hand was being lased. Twenty-one patients noted improvement of both their MCP and PIP joints of both hands during laser therapy. Twenty-seven noted improvement of their PIP joints and 26 noted improvement of the MCP joints during therapy. Heat, erythema, pain, swelling, and tenderness all improved with time in both hands, but the lased hand had more significant improvement in erythema and pain. There was also significant improvement in grasp and tip pressure on the lased side. The level of circulating immune complexes as measured by platelet aggregation decreased during lasing. The improvement may be related to laser exposure. The exact role that laser radiation has upon rheumatoid arthritis and its mechanism of action remain to be elucidated.
Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. (1992)

Single-chain antigen-binding proteins, or sFvs, represent potentially unique molecules for targeted delivery of drugs, toxins, or radionuclides to a tumor site. In previous studies (Cancer Res., 51:6363-6371, 1991) using a human colon carcinoma xenograft model, it was demonstrated that the sFv has an extremely rapid plasma and whole body clearance, as compared to intact IgG or Ig fragments. One potential consequence of the rapid sFv pharmacokinetic properties was the reduced percentage of injected dose/g of the radiolabeled sFv found in the tumor throughout a range of time points. The present study was designed to define the tumor penetration properties of a radiolabeled sFv in comparison with other Ig forms. 125I-labeled sFv, Fab', F(ab')2, and IgG forms of monoclonal antibody CC49, directed against the human pancarcinoma antigen TAG-72, were used to target the LS-174T human colon carcinoma xenograft in athymic mice. At various time points after systemic Ig administration, quantitative autoradiographic analyses of surgically removed tumors were used to define the rate and degree of penetration of the various Ig forms. These studies revealed that most of the intact IgG delivered to the tumor was concentrated in the region of or immediately adjacent to vessels, while the sFv was more evenly distributed throughout the tumor mass. The distributions of the Fab' and F(ab')2 fragments showed intermediate penetration in a size-related manner. The sFv demonstrated maximum tumor penetration at 0.5 h postinjection, while the intact IgG reached an equivalent degree of penetration at 48 to 96 h postinjection. These studies thus reveal a greater degree of uptake throughout the tumor for the sFv than would be expected by gross analyses of percentage injected dose/g and demonstrate an extremely rapid tumor penetration of the sFv. These studies should aid in the rational design of potential applications of drug-, toxin-, and radionuclide-conjugated sFvs in cancer therapy.
Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study (2012)

The EQ-5D-5L appears to be a valid extension of the 3-level system which improves upon the measurement properties, reducing the ceiling while improving discriminatory power and establishing convergent and known-groups validity.
QoS Management in Trunk-and-Branch (2002)

A likely architecture for the future broadband access network will consist of a trunk-and-branch topology, with very high bandwidth trunks (e.g., 1‐10 Gb/s), connected to high-bandwidth drops (or branches) to homes and businesses. A multihop switched Ethernet data transport can be used over this access network. In [1] we discussed the benefits of upgrading the hybrid fiber coax plant into a distributed switched Ethernet trunk-andbranch network capable of fiber-like transmission speeds. This article focuses on QoS management in the proposed next-generation broadband access network (NGBAN) based on a multihop switched Ethernet network architecture. This network architecture and QoS management framework are more generally applicable, and we anticipate they will form the basis for the “last mile” independent of the physical medium.
Solubility Enhancement of Indomethacin with Poly(amidoamine) Dendrimers and Targeting to Inflammatory Regions of Arthritic Rats (2004)

This work includes investigation on solubility enhancement of indomethacin (IND) in the presence of poly(amidoamine) (PAMAM) dendrimers and passive targeting of the PAMAM/IND complex so formed to the inflamed regions in an animal model. The complex formation was confirmed by infrared and (1)H nuclear magnetic resonance spectroscopy methods. Solubility of IND in aqueous G4-PAMAM followed Higuchi's A(N) curve depending on pH of the solubilizing medium. The solubility was decreased upon addition of dendrimer to the IND saturated solution at various pH, indicating aggregation behavior of the PAMAM/IND complex and conforming to the Higuchi's A(N) solubility profile. The in vitro release of IND from the PAMAM/IND complex through a cellophane membrane, from a Franz diffusion cell, showed 79 +/- 3.2% drug release in 24 h. The drug release was further retarded in the presence of human serum albumin (HSA) suggesting the significance of complex HSA binding in altering in vivo behavior of the complex. Intravenous administration of the PAMAM/IND complex formulation in rats showed a two-compartment pharmacokinetic profile. Enhanced effective IND concentrations in the inflamed regions were obtained for the prolonged time period with the PAMAM/IND complex compared to the free drug in arthritic rats indicating preferred accumulation of IND to the inflamed region. The targeting efficiency of PAMAM/IND complex was 2.29 times higher compared to free drug. In contrast to the previous investigations, two interesting findings reported here are: (a) solubility behavior of IND in G4-PAMAM dendrimer deviates from linearity with increasing concentrations of dendrimer at acidic to neutral pH values and (b) inspite of lymphatic drainage, retention of PAMAM/IND complexes occurs at the inflammatory site.
Why does pulmonary venous pressure rise after onset of LV dysfunction: a theoretical analysis (1993)

One of the most important consequences of acute left ventricular dysfunction (LVD) is pulmonary edema resulting from a rise in pulmonary venous pressure (PVP). It is generally believed that the PVP rise is a direct hemodynamic consequence of LVD. While this paradigm seems plausible, especially if the LV is viewed as a sump pump, there is no specific evidence to support this simple explanation. A theoretical analysis was performed to assess the hemodynamic mechanisms responsible for the dramatic rise in PVP after acute LVD. The ventricles were modeled as time-varying elastances; pulmonary and systemic vascular systems were modeled as series of resistive and capacitive elements. In response to a 50% decrease in LV contractile strength [end-systolic elastance (Ees)], cardiac output (CO) and mean arterial pressure (MAP) dropped substantially, while PVP increased minimally from its baseline of 12 to approximately 15 mmHg. With LV Ees set at 50% of normal, the effects of sympathetic activation were tested. When heart rate and total peripheral resistance were increased, CO and MAP improved, yet PVP still did not rise. The only intervention that caused a substantial increase in PVP was to simulate the decrease in unstressed volume (VU) of the venous system known to occur with sympathetic activation. When VU was decreased by about 15-20% (comparable to experimentally observed shifts with acute heart failure), PVP increased above 25 mmHg. The effects of pericardial constraints were investigated, and the results suggest a major role of this organ in determining the overall hemodynamic response to acute LVD, sympathetic activation, and explaining the responses to therapy. Thus this analysis suggests that elevations of PVP do not occur simply as a direct hemodynamic consequence of acute LVD. Rather, changes in PVP may be dictated more by sympathetic control on venous capacity. If confirmed, recognition of this as a primary mechanism may prove important in directing development of new therapies and in understanding the mechanisms of disease progression in heart failure.
Flexible dielectric waveguides with powder cores (1988)

Flexible dielectric waveguides have been demonstrated at 10 GHz and 94 GHz using thin-wall polymer tubing filled with low-loss, high-dielectric-constant powders. Absorptive losses of the order of 10 dB/m were measured at 94 GHz. with nickel-aluminium titanate and barium tetratitanate powder in polytetrafluoroethylene (PTFE) lightweight electrical tubing. Bending losses at 94 GHz were negligible for curvature radii greater than 4 cm. M.H. Kuhn's (1974) theory of three-region cylindrical dielectric waveguide was used to calculate dispersion curves for the lower-order modes for several combinations of dimensions and dielectric constants. Good agreement was obtained between experimental and theoretical values of guide wavelength. A scheme is proposed for classifying hybrid modes of three-region guides based on the ratio mod E/sub z//H/sub z/ mod . For two-region guides, this reduces to E. Snitzer's (1961) familiar scheme.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intrathecal administration of single-chain immunotoxin, LMB-7 [B3(Fv)-PE38], produces cures of carcinomatous meningitis in a rat model. (1995)

LMB-7 [B3(Fv)-PE38] is a single-chain immunotoxin constructed from the murine monoclonal antibody B3 and a truncated from of Pseudomonas exotoxin PE38. Antibody B3 recognizes a carbohydrate epitope found on solid tumors that frequently invade the intrathecal space and cause neoplastic meningitis. We tested the therapeutic value of intrathecally administered LMB-7 by using a model of human neoplastic meningitis in athymic rats. This model is representative of a clinical situation in that antibody B3 cross-reacts with a number of normal tissues that can be used to monitor potential systemic toxicity. Treatment was begun 3 days after A431 tumor implantation. Without treatment, the animals median survival was 10 days. Intrathecal administration of 10 micrograms of LMB-7 in 40 microliters on days 3, 5, and 7 produced 4 of 10 and 8 of 10 long-term survivors (> 170 days) in two experiments. Of the long-term survivors, 2 of 4 and 7 of 8 survivors had no microscopic evidence of tumor and were considered histologic cures. Lack of significant toxicity in the effective dose range and specificity make LMB-7 an excellent candidate for intrathecal treatment of neoplastic meningitis in humans.
Similarities between Gelation and Long Chain Branching Viscoelastic Behavior (2001)

ADVERTISEMENT RETURN TO ISSUECommunication to the...Communication to the EditorNEXTSimilarities between Gelation and Long Chain Branching Viscoelastic BehaviorCésar A. García-Franco, Srivatsan Srinivas, David J. Lohse, and Patrick BrantView Author Information ExxonMobil Chemical Company, Baytown Polymers Center, 5200 Bayway Drive, Baytown, Texas 77522, and ExxonMobil Research and Engineering, Corporate Strategic Research Labs, 1545 Route 22 East, Annandale, New Jersey 08801 Cite this: Macromolecules 2001, 34, 10, 3115–3117Publication Date (Web):April 10, 2001Publication History Received21 December 2000Revised18 March 2001Published online10 April 2001Published inissue 1 May 2001https://pubs.acs.org/doi/10.1021/ma0021794https://doi.org/10.1021/ma0021794rapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1014Altmetric-Citations84LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Fluid dynamics,Gelation,Polymers,Stiffness Get e-Alerts