gebhart/patrepeval huggingface dataset:
Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis (2009)

While topical non-steroidal anti-inflammatory drugs are considered safe, their long-term efficacy for osteoarthritis has been suspect. We conducted a 12-week, double-blind, double-dummy, randomized controlled trial of topical diclofenac (TDiclo) in a vehicle solution containing dimethyl sulfoxide (DMSO) in 775 subjects with radiologically confirmed, symptomatic primary osteoarthritis of the knee. This 5-arm study compared TDiclo with a placebo solution, the DMSO vehicle, oral diclofenac (ODiclo) and the combination of TDiclo+ODiclo for relieving the signs and symptoms of knee osteoarthritis. Subjects applied study solution, 40 drops four times daily, and took one study tablet daily for 12 weeks. Co-primary efficacy variables were WOMAC pain and physical function and a patient overall health assessment. Secondary variables were WOMAC stiffness and patient global assessment (PGA) of the knee osteoarthritis. TDiclo was superior to placebo for pain (-6.0 vs. -4.7, P=0.015), physical function (-15.8 vs. -12.3, P=0.034), overall health (-0.95 vs. -0.37, P<0.0001), and PGA (-1.36 vs. -1.01, P=0.016), and was superior to DMSO vehicle for all efficacy variables. No significant difference was observed between DMSO vehicle and placebo or between TDiclo and ODiclo. The commonest adverse event associated with TDiclo was dry skin (18.2%). Fewer digestive system and laboratory abnormalities were observed with TDiclo than with ODiclo. Addition of TDiclo to ODiclo did not increase the incidence of systemic adverse events. TDiclo in DMSO vehicle is an effective treatment option for knee osteoarthritis with efficacy similar to, but tolerability better than ODiclo. DMSO vehicle was no more efficacious than placebo.
Expression and Characterization of HIV Type 1 Envelope Protein Associated with a Broadly Reactive Neutralizing Antibody Response (1999)

We have studied envelope protein from a donor with nonprogressive HIV-1 infection whose serum contains broadly cross-reactive, primary virus NA. DNA was extracted from lymphocytes, which had been collected approximately 6 and 12 months prior to the time of collection of the cross-reactive serum, and env genes were synthesized, cloned, expressed on pseudoviruses, and phenotyped in NA assays. Two clones from each time point had identical V3 region nucleotide sequences, utilized CCR5 but not CXCR4 for cell entry, and had similar reactivities with reference sera. Analysis of the full nucleotide sequence of one clone (R2) demonstrated it to be subtype B and have normal predicted glycosylation. R2 pseudovirus was compared with others expressing env genes of various clades for neutralization by sera from U.S. donors (presumed or known subtype B infections), and from individuals infected with subtypes A, C, D, E, and F viruses. Neutralization by the U.S. sera of R2 and other clade B pseudoviruses was low to moderate, although R2 was uniquely neutralized by all. R2 was neutralized by 3/3, 3/3, 2/5, 5/8, and 3/4 clade A, C, D, E, and F sera, respectively. R2 and a clade E pseudovirus were neutralized by largely complementary groups of sera, potentially defining two antigenic subgroups of HIV-1. The results suggest that the epitope(s) that induced the cross-clade reactive NA in donor 2 may be expressed on the R2 envelope.
Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes. (1991)

Abasic (AP) sites are common, potentially mutagenic DNA damages that are attacked by AP endonucleases. The biological roles of these enzymes in metazoans have not been tested. We have cloned the human cDNA (APE) that encodes the main nuclear AP endonuclease. The predicted Ape protein, which contains likely nuclear transport signals, is a member of a family of DNA repair enzymes that includes two bacterial AP endonucleases (ExoA protein of Streptococcus pneumoniae and exonuclease III of Escherichia coli) and Rrp1 protein of Drosophila melanogaster. Purified Ape protein lacks the 3'-exonuclease activity against undamaged DNA that is found in the bacterial and Drosophila enzymes, but the lack of obvious amino acid changes to account for this difference suggests that the various enzyme functions evolved by fine tuning a conserved active site. Expression of the active human enzyme in AP endonuclease-deficient E. coli conferred significant resistance to killing by the DNA-alkylating agent methyl methanesulfonate. The APE cDNA provides a molecular tool for analyzing the role of this central enzyme in maintaining genetic stability in humans.
Optimizing cost and performance for multihoming (2004)

Multihoming is often used by large enterprises and stub ISPs to connect to the Internet. In this paper, we design a series of novel smart routing algorithms to optimize cost and performance for multihomed users. We evaluate our algorithms through both analysis and extensive simulations based on realistic charging models, traffic demands, performance data, and network topologies. Our results suggest that these algorithms are very effective in minimizing cost and at the same time improving performance. We further examine the equilibrium performance of smart routing in a global setting and show that a smart routing user can improve its performance without adversely affecting other users.
KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules. (1999)

Radicicol, a macrocyclic antifungal antibiotic, has been shown to bind to the heat shock protein 90 (Hsp90) chaperone, interfering with its function. Hsp90 family chaperones have been shown to associate with several signaling molecules and play an essential role in signal transduction, which is important for tumor cell growth. Because radicicol lacks antitumor activity in vivo in experimental animal models, we examined the antitumor activity of a novel radicicol oxime derivative, radicicol 6-oxime (KF25706), on human tumor cell growth both in vitro and in vivo. KF25706 showed potent antiproliferative activities against various human tumor cell lines in vitro and inhibited v-src- and K-ras-activated signaling as well as radicicol. In addition, Hsp90 family chaperone-associated proteins, such as p185erbB2, Raf-1, cyclin-dependent kinase 4, and mutant p53, were depleted by KF25706 at a dose comparable to that required for antiproliferative activity. KF25706 was also shown to compete with geldanamycin for binding to Hsp90. KF29163, which is an inactive derivative of radicicol, was less potent both in p185erbB2 depletion and Hsp90 binding. More importantly, KF25706 showed significant growth-inhibitory activity against human breast carcinoma MX-1 cells transplanted into nude mice at a dose of 100 mg/kg twice daily for five consecutive i.v. injections. KF25706 was also shown to possess antitumor activity against human breast carcinoma MCF-7, colon carcinoma DLD-1, and vulval carcinoma A431 cell lines in vivo in an animal model. Finally, we confirmed the depletion of Hsp90-associated signaling molecules (Raf-1 and cyclin-dependent kinase 4) with ex vivo Western blotting analysis using MX-1 xenografts. In agreement with in vivo antitumor activity, KF25706 depleted Hsp90-associated molecules in vivo, whereas KF29163 and radicicol did not show this activity in vivo. Taken together, these results suggest that antitumor activity of KF25706 may be mediated, at least in part, by binding to Hsp90 family proteins and destabilization of Hsp90-associated signaling molecules.
Integrating noninterfering versions of programs (1989)

The need to integrate several versions of a program into a common one arises frequently, but it is a tedious and time consuming task to integrate programs by hand. To date, the only available tools for assisting with program integration are variants of text-based differential file comparators; these are of limited utility because one has no guarantees about how the program that is the product of an integration behaves compared to the programs that were integrated. This paper concerns the design of a semantics-based tool for automatically integrating program versions. The main contribution of the paper is an algorithm that takes as input three programs A , B , and Base , where A and B are two variants of Base . Whenever the changes made to Base to create A and B do not “interfere” (in a sense defined in the paper), the algorithm produces a program M that integrates A and B . The algorithm is predicated on the assumption that differences in the behavior of the variant programs from that of Base , rather than differences in the text , are significant and must be preserved in M . Although it is undecidable whether a program modification actually leads to such a difference, it is possible to determine a safe approximation by comparing each of the variants with Base . To determine this information, the integration algorithm employs a program representation that is similar (although not identical) to the dependence graphs that have been used previously in vectorizing and parallelizing compilers. The algorithm also makes use of the notion of a program slice to find just those statements of a program that determine the values of potentially affected variables. The program-integration problem has not been formalized previously. It should be noted, however, that the integration problem examined here is a greatly simplified one; in particular, we assume that expressions contain only scalar variables and constants, and that the only statements used in programs are assignment statements, conditional statements, and while-loops.
POMDP-Based Statistical Spoken Dialog Systems: A Review (2013)

Statistical dialog systems (SDSs) are motivated by the need for a data-driven framework that reduces the cost of laboriously handcrafting complex dialog managers and that provides robustness against the errors created by speech recognizers operating in noisy environments. By including an explicit Bayesian model of uncertainty and by optimizing the policy via a reward-driven process, partially observable Markov decision processes (POMDPs) provide such a framework. However, exact model representation and optimization is computationally intractable. Hence, the practical application of POMDP-based systems requires efficient algorithms and carefully constructed approximations. This review article provides an overview of the current state of the art in the development of POMDP-based spoken dialog systems.
Uniaxial Cyclic Strain Drives Assembly and Differentiation of Skeletal Myocytes (2011)

Ex vivo engineering of skeletal muscle represents an exciting new area of biotechnology. Although the ability of skeletal muscle cells to sense and respond to mechanical forces is well known, strategies based on the use of mechanical stimuli to optimize myogenesis in vitro remain limited. In this work, we describe a simple but powerful method based on uniaxial cyclic tensile strain (CTS) to induce assembly and differentiation of skeletal myocytes in vitro. Confluent mouse myoblastic precursors cultured on flexible-bottomed culture plates were subjected to either uniaxial or equibiaxial CTS. The uniaxial CTS protocol resulted in a highly aligned array of cross-striated fibers, with the major axis of most cells aligned perpendicularly to the axis of strain. In addition, a short period of myogenin activation and significant increase in the myotube/myoblast ratio and percentage of myosin-positive myotubes was found, indicating an enhanced cell differentiation. In contrast, cells under equibiaxial strain regimen had no clear orientation and displayed signs of membrane damage and impaired differentiation. These results, thus, demonstrate that the selection of a proper paradigm is a key element when discussing the relevance of mechanical stimulation for myogenesis in vitro. This study provides a rational framework to optimize engineering of functional skeletal muscle.
The Prognostic Significance of Plasma Interleukin-6 Levels in Patients with Metastatic Hormone-Refractory Prostate Cancer: Results from Cancer and Leukemia Group B 9480 (2005)

Plasma IL-6 level has prognostic significance in patients with metastatic HRCaP from CALGB 9480. These findings support using IL-6 levels in prognostic models and support the rationale for IL-6-targeted therapy in patients with HRCaP.
Challenges and New Technologies of Oral Controlled Release (2010)

This chapter contains sections titled: Introduction Oral Controlled Delivery for Water-Insoluble Drugs New Formulation Designs in Achieving Desired Release Profiles Oral Delivery of Biopharmaceuticals New Platform Technologies for Oral Controlled Release New Materials for Oral Controlled Release Summary References
High yield, directed immobilization of a peptide-ligand onto a beaded cellulose support. (1995)

Aminopropyl derivatized Perloza beaded cellulose was acylated with alpha-bromoacetic anhydride to give alpha-bromo-acetamidopropyl Perloza. (N-Acetyl)-Cys-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, the 7 C-terminal amino acids of the decapeptide luteinizing hormone-releasing hormone with a cysteine added to the N-terminus, was synthesized using Fmoc chemistry. The purified peptide (1.35-1.9 eq) was coupled to alpha-bromoacetamidopropyl Perloza in 0.1 M NaHCO3 solution, pH 8.3, for 1-2 hours. The peptide was anchored to the support via a thioether linkage. Analysis of the peptide-Perloza conjugate indicated near-quantitative displacement of support-bound bromine by the peptide. The peptidic affinity matrix was able to bind ovine antibodies to luteinizing hormone-releasing hormone (LHRH). Thioether immobilization offers directed, chemically stable, high-yield anchoring of synthetic peptides onto a chromatographic support. The high reaction efficiency means there is little waste of valuable synthetic peptide.
Revision after early aseptic failures in primary total knee arthroplasty (2008)

The purpose of this study was to evaluate cases of early aseptic failures presented during the first 5-year follow-up in a group of 981 primary total knee arthroplasty (primary TKA). Predisposing factors as well causes of failures and postoperative complications in different groups of aseptic failures were re-assessed and compared to a control group. A retrospective and cohort study compared one group of 944 primary TKA without surgical revision (890 patients) (Group A) with 22 primary TKA (22 patients) (Group B) that had revision TKA secondary to aseptic failure during the first five years follow-up. The cases of isolated patellar button replacement (n = 8) and infection (n = 7) were not considered in this study. All patients underwent a systematic assessment that included clinical and radiographic examinations, and IKS scores. Aseptic failure was more prevalent at the first 2-year follow-up (63%). TKA loosening (n = 11) and undiagnosed pain (n = 7) were considered the most frequent modes of failures, and laxity (n = 1) was a very rare early cause of failure. The aseptic failure group was characterized as average 5 years younger with a greater number of previous knee surgeries, lower IKS scores improvement, and more postoperative pain compared to control group, despite the fact that the aseptic failure group showed a prevalence of cases during the first 2-year follow-up. Inside this group, the undiagnosed pain group had lower improvement of IKS scores, a remarkable prevalence in prior surgical procedure (71%) and a minor mean interval between primary and revision TKA (11.6 months).
Light-Switchable Polymer Adhesive Based on Photoinduced Reversible Solid-to-Liquid Transitions (2019)

The development of switchable adhesives for reversible bonding and debonding can overcome the problems associated with conventional adhesives in separating, recycling, and repairing glued surfaces. Here, a photoresponsive azobenzene-containing polymer (azopolymer) is developed for photocontrolled adhesion. The azopolymer P1 (poly(6-(4-(<i>p</i>-tolyldiazenyl)phenoxy)hexyl acrylate)) exhibits photoinduced reversible solid-to-liquid transitions due to trans-cis photoisomerization. Trans P1 is a solid that glues two substrates with a stiffness comparable to that of conventional adhesives. UV light induces trans-to-cis isomerization, liquefies P1, weakens the adhesion, and facilitates the separation of glued substrates. Conversely, visible light induces cis-to-trans isomerization, solidifies P1, and enhances the adhesion. P1 enables photocontrolled reversible adhesion for various substrates with different wettability, chemical compositions, and surface roughness. P1 can also be implemented in both dry and wet environments. Light can control the adhesion process with high spatiotemporal resolution when using P1 as a switchable adhesive. Photoinduced reversible solid-to-liquid transitions represent a strategy for materials recycling and automated production processes that require reversible bonding and debonding.
Marked Improvement of PAC and BAC Cloning Is Achieved Using Electroelution of Pulsed-Field Gel-Separated Partial Digests of Genomic DNA (1997)

We describe a simple electroelution method for purifying large, gel-fractionated DNA molecules that alleviates the need for melting of the agarose and subsequent enzymatic agarose digestion. The method yields DNA that is visibly more intact than that purified from a standard agarose-digestion protocol and is more amenable to large-fragment cloning with PAC and BAC vectors. These findings are notable in that PAC and BAC library construction is a very labor-intensive and costly procedure, such that any net improvement in cloning efficiency is highly advantageous. This method also should prove useful towards other applications which require purification of very large DNA molecules, such as YAC cloning.
Materials design of ionic conductors for solid state batteries (2020)

Abstract All-solid-state batteries, employing inorganic ion conductors as electrolytes, can surpass the current Li-ion technology in terms of energy density, battery safety, specific power, as well as a fast-charging capability; however, a highly conductive solid electrolyte is essential. While recent extensive explorations of solid ion conductors have led to a list of candidate materials, there are still enormous variations of the ionic conductivity even within the same class of the materials, indicating the strong influence of structural modifications on the ion transport. In this review, besides revisiting general strategies of materials design for fast ion transport, we summarize the present state of affairs of promising classes of crystalline solid electrolytes, including a structural description and an overview of the observed static lattice effects alongside with open questions specific for the pertinent material classes. In the end, future directions and open questions to design and develop solid electrolytes, i.e. upcoming classes of materials, influence of lattice dynamics and inductive effects, the origin of energy landscape flattening, and the impact of synthesis routes are discussed. We hope this review provides a shape of the current status of the field of crystalline ion conductors.
Production systems for recombinant antibodies (2008)

Recombinant antibodies are the fastest growing class of therapeutic proteins. Furthermore, antibodies are key detection reagents in research and diagnostics. The increasing demand for antibodies with regards to amount and quality resulted in the development of a variety of recombinant production systems employing gram-negative and gram-positive bacteria, yeast and filamentous fungi, insect cell lines as well as mammalian cell lines. More recently, antibodies were also successfully produced in transgenic plants and animals. Currently, the production of recombinant antibodies for therapy is performed in mammalian cell lines to reduce the risk of immunogenicity caused by non-human post-translational modifications, in particular glycosylation. However, novel strategies already allow human-like glycosylation patterns in yeast, insect cell lines and transgenic plants. Furthermore, therapeutic strategies not requiring glycosylation of the Fc portion have been conceived, most prominently using bispecific antibodies or scFv fusion proteins, which can be produced in bacteria. Here, we review all current antibody production systems considering their advantages and limitations with respect to intended applications.
A lazy object-space shading architecture with decoupled sampling (2010)

We modify the Reyes object-space shading approach to address two inefficiencies that result from performing shading calculations at micropolygon grid vertices prior to rasterization. Our system samples shading of surface sub-patches uniformly in the object's parametric domain, but the location of shading samples need not correspond with the location of mesh vertices. Thus we perform object-space shading that efficiently supports motion and defocus blur, but do not require micropolygons to achieve a shading rate of one sample per pixel. Second, our system resolves surface visibility prior to shading, then lazily shades 2x2 sample blocks that are known to contribute to the resulting fragments. We find that in comparison to a Reyes micropolygon rendering pipeline, decoupling geometric sampling rate from shading rate permits the use of meshes containing an order of magnitude fewer vertices with minimal loss of image quality in our test scenes. Shading on-demand after rasterization reduces shader invocations by over two times in comparison to pre-visibility object-space shading.
Requirement for T cells and effect of lymphokines in successful chemotherapy for an intracellular infection. Experimental visceral leishmaniasis. (1989)

Although directly microbicidal, pentavalent antimony has failed as treatment for visceral leishmaniasis in patients who also have AIDS or are receiving immunosuppressive therapy. To define the role of T cells in the successful host response to chemotherapy, we examined the efficacy of pentavalent antimony (sodium stibogluconate, Pentostam) in normal and T cell-deficient BALB/c mice infected with Leishmania donovani. In euthymic (nu/+) mice, single injections of 250 and 500 mg/kg of Pentostam induced the killing of 67% and 89% of intracellular liver amastigotes, respectively. In contrast, in athymic nude (nu/nu) mice, up to three injections of 500 mg/kg achieved no L. donovani killing and did not retard visceral parasite replication. Once nude mice were reconstituted with nu/+ spleen cells, however, Pentostam exerted strong leishmanicidal activity, an effect that appeared to be transferred by either L3T4+ or Lyt-2+ cells. Responsiveness to chemotherapy could also be induced by providing nude mice with either interferon-gamma or interleukin 2 alone. The absence of this T cell- and probably lymphokine-dependent mechanism is a likely explanation for treatment failures in immunocompromised patients infected with L. donovani and perhaps other systemic intracellular pathogens as well.