gebhart/patrepeval huggingface dataset:
Peptide factors as pharmaceuticals: Criteria for application (1983)

Abstract The increasing interest in the pharmaceutical use of peptide factors in human medicine presents formidable challenges for peptide chemistry. Fully reproducible multistage syntheses with a definite assessment of the degree of purity represent the crucial premise for the introduction of peptide factors as pharmaceuticals. Extensive studies of the stability of peptidic material on storage allows identification of the most suitable form of administration. Nevertheless, the high clearance rate of peptides as pharmaceuticals presents new challenges for improvement by structural modification of resistance to enzyme degradation without creating new problems related to metabolites.
Networks on Silicon: Combining Best-Effort and Guaranteed Services (2002)

We advocate a network on silicon (NOS) as a hardware architecture to implement communication between IP cores in future technologies, and as a software model in the form of a protocol stack to structure the programming of NOSs. We claim guaranteed services are essential. In the ETHEREAL NOS they pervade the NOS as a requirement for hardware design, and as foundation for software programming.
Superparamagnetic Iron Oxide Nanoparticles: Amplifying ROS Stress to Improve Anticancer Drug Efficacy (2013)

Superparamagnetic iron oxide nanoparticles (SPION) are an important and versatile nano- platform with broad biological applications. Despite extensive studies, the biological and pharmacological activities of SPION have not been exploited in therapeutic applications. Recently, β-lapachone (β-lap), a novel anticancer drug, has shown considerable cancer specificity by selectively increasing reactive oxygen species (ROS) stress in cancer cells. In this study, we report that pH-responsive SPION-micelles can synergize with β-lap for improved cancer therapy. These SPION-micelles selectively release iron ions inside cancer cells, which interact with hydrogen peroxide (H(2)O(2)) generated from β-lap in a tumor-specific, NQO1-dependent manner. Through Fenton reactions, these iron ions escalate the ROS stress in β-lap-exposed cancer cells, thereby greatly enhancing the therapeutic index of β-lap. More specifically, a 10-fold increase in ROS stress was detected in β-lap-exposed cells pretreated with SPION-micelles over those treated with β-lap alone, which also correlates with significantly increased cell death. Catalase treatment of cells or administration of an iron chelator can block the therapeutic synergy. Our data suggest that incorporation of SPION-micelles with ROS-generating drugs can potentially improve drug efficacy during cancer treatment, thereby provides a synergistic strategy to integrate imaging and therapeutic functions in the development of theranostic nanomedicine.
Double loading of cyclosporine A in liposomes using cyclodextrin complexes. (2009)

When liposomes are used as drug delivery systems, it is important that the therapeutic agent is efficiently and adequately encapsulated. In this study, cyclosporine A (CyA) was chosen as a model drug for two reasons. First, liposomes are a potential delivery system for CyA, as it has been shown that CyA has decreased side effects when encapsulated in liposomes. Secondly, if the aqueous solubility of a lipophilic drug can be increased, then it is possible to increase liposomal encapsulation by additionally loading the drug into the liposomes' aqueous compartments. Therefore, we investigated the use cyclodextrins (CDs) for complexing CyA to increase aqueous solubility as a strategy to increase liposomal loading. The effect of CyA loading on the liposomes' characteristics, stability and rigidity of the bilayer, and also the drug release profile were evaluated. Liposomes encapsulating CyA, liposomes containing CyA-CD complexes, and liposomes loaded with both plain drug and complex (double-loaded liposomes) were prepared. For evaluation of the effect of CD on bilayer rigidity and integrity, the permeability of the liposomal membrane in terms of carboxyfluorescein (CF) leakage was studied. Among liposomal formulations containing only CyA, 1, 2-distearoyl-sn-glycero-3-phosphocholine (DSPC):cholesterol (CHOL) (1:1) and hydrogenated soybean phosphatidylcholine (HSPC):CHOL (1:1) formulations demonstrated maximum drug entrapments of 65.94 +/- 4.68% and 75.03 +/- 4.87%, respectively. There was no significant difference in encapsulation efficiencies between different liposomal formulations for those containing CyA-CD complexes (P > 0.05). Measurement of encapsulation efficiency showed that the amount of drug entrapped in the lipid bilayers was identical when prepared in the form of CyA inclusion complexes. Drug entrapment in double-loaded liposomes was increased by approximately 2-fold. The release profile of all liposomal formulations was biphasic, with an initial rapid phase during the first 5 h followed by a continuous and slower release thereafter. During the first 5 h, CyA used as the complex was released to a greater extent than free CyA. Leakage of CF from liposomes was affected by the inclusion of CD. The leakage rate was minimum for CyA liposomes and maximum for double-loaded (CyA and CyA-CD) liposomes. In conclusion, it is possible to encapsulate CyA both in the aqueous and lipidbilayers of liposomes if the aqueous solubility of CyA is increased by complexation with CD. Although entrapment of a higher amount of drug was achieved, the stability of the liposomes was compromised and should therefore be considered.
Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain (2015)

HF10 therapy promises to substantially impact the management of back and leg pain with broad applicability to patients, physicians, and payers.
Antiguanosine antibodies in murine and human lupus have the internal image of G-binding proteins. (2003)

The finding that antiguanosine autoantibodies vary directly with specific features of SLE, especially nephritis and polyserositis, suggests that they may contribute to the pathology of SLE. Our findings that antiguanosine antibodies have G-binding protein active site homology support the possibility that this species of antibody might interfere with cell signal transduction.
Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics (2004)

Considerable progress has been made in molecular characterization of AML patients with normal cytogenetics. The challenge for the future is to incorporate these biologic discoveries into novel risk-adapted therapeutic strategies that will improve the currently disappointing cure rate (approximately 25-40%) of this group of patients.
Pancreatic stellate cells: New target in the treatment of chronic pancreatitis (2007)

Chronic pancreatitis (CP) is characterized by progressive fibrosis, pain and/or loss of exocrine and endocrine functions. Recent in vitro and in vivo experiments have proven objectively the role of activated pancreatic stellate cells (PSC) in fibrogenesis in CP. Molecular mediators shown to regulate the pathogenesis include transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha. Furthermore, molecular pathways involving mitogen-activated protein kinases (MAPK), phosphatidyl inositol 3-kinase (PI3K), Ras superfamily G proteins, serine threonine protein kinase Raf-1 and peroxisome proliferator activated receptor gamma (PPAR-gamma) have been elucidated. Understanding of the pathogenesis has led to identification of novel molecular targets and development of potential newer therapeutic agents. Those found to retard the progression of experimental CP and fibrosis in animal models include interferon (IFN) beta and IFN-gamma; a Japanese herbal medicine called Saiko-keishi-to (TJ-10); curcumin; PPAR-gamma ligand (troglitazone); antioxidants (vitamin A, vitamin E, DA 9601 and epigallocatechin-3-gallate); a protease inhibitor (camostat mesilate) and hydroxymethylglutaryl-CoA inhibitor (lovastatin). This review summarizes the current literature addressing the role of different pharmacological agents aimed at reducing or preventing inflammation and the consequent fibrogenesis in CP.
Abatacept and Glomerular Diseases: The Open Road for the Second Signal as a New Target is Settled Down (2015)

Glomerulopathy is the third most important cause of kidney disease. Proteinuria is the hallmark of glomerular damage, and a marker of progression of kidney disease, cardiovascular morbidity and mortality. Strategies to reduce proteinuria are partially successful, and despite proteinuria management, renal disease may still progress. Immunosuppression to treat glomerulopathies is nonspecific, partially effective and presents side-effects. It is critical to find safe drugs with specific podocyte molecular targets. Podocytes contain a complex array of proteins. Lymphocyte activation antigen B7-1 (CD80) is located on antigen presenting cells modulating CD4+ and CD8+ T cells by interacting with co-stimulator CD28, a glycoprotein located on T-cells, or with cytotoxic T-lymphocyte protein 4 (CTLA-4) co-inhibitor. Normally, podocytes do not express B7-1. However, certain glomerulopathies are associated with an increase on the surface of podocytes of B7-1, which reduces the ability of podocytes to attach to the surrounding glomerular basement membrane, favouring podocyturia and proteinuria. When the B7-1-CTLA-4 interaction takes place, the immune response is abrogated, while a B7-1-CD28 coupling leads to T cell activation. Abatacept binds to B7-1 by blocking the CD28 or potentiating the CTLA-4 signals. In B7-1 positive podocytes, abatacept may be a specific tool to decrease proteinuria. Selected patents are also briefly presented in this review.
Land in the Holiness Code (Lev 17-26) (2004)

The article attempts to describe the way in which land is presented and understood in the Holiness Code. Land as such has at least two faces in the Holiness Code. On the one hand we find a presentation of Egypt, Canaan and the land of the enemies that is hostile and threatening, and on the other hand Canaan is presented as a sustaining land that makes life possible. Another feature of land is that it has a certain amount of freedom and plays a role in the code along with two other “characters” namely JHWH and the addressees. The Holiness Code is also very clear that life is not possible without access to such a sustaining land.
High-Level Synthesis and Secretion of α-Amylase from Rice Callus (1989)

Rice seed callus was found to synthesize and secrete high levels of α-amylase for up to 17 months after initiation. Approximately 43% of the total secreted protein is α-amylase. This level of expression was not increased by exogenous gibberellic acid, nor was expression reduced by the gibberellin biosynthesis inhibitor paclobutrazol. Alpha-amylase expression, however, was reduced 41-fold in seed callus derived from Tan-ginbozu, a mutant lacking gibberellins, suggesting that gibberellins are involved in the regulation of α-amylase biosynthesis in the callus. This low expression in Tan-ginbozu callus, however, was not increased by exogenous gibberellic acid. Surprisingly, shoot-derived callus also secreted α-amylase at levels similar to seed-derived callus, even though shoot tissue normally produces only low levels of intracellular α-amylase.
Drug‐screening platform based on the contractility of tissue‐engineered muscle (2008)

A tissue-based approach to in vitro drug screening allows for determination of the cumulative positive and negative effects of a drug at the tissue rather than the cellular or subcellular level. Skeletal muscle myoblasts were tissue-engineered into three-dimensional muscle with parallel myofibers generating directed forces. When grown attached to two flexible micro-posts (mu posts) acting as artificial tendons in a 96-well plate format, the miniature bioartificial muscles (mBAMs) generated tetanic (active) forces upon electrical stimulation measured with a novel image-based motion detection system. mBAM myofiber hypertrophy and active force increased in response to insulin-like growth factor 1. In contrast, mBAM deterioration and weakness was observed with a cholesterol-lowering statin. The results described in this study demonstrate the integration of tissue engineering and biomechanical testing into a single platform for the screening of compounds affecting muscle strength.
Dietary administration of tannic acid lowers plasminogen activator activity in the liver of C3H hepatoma bearing male mice. (2001)

The decrease of PAA in the liver of C3H hepatoma bearing male mice, might be correlated with the chemopreventive activity of tannic acid in hepatoma development.
Improved retroviral vectors for gene transfer and expression. (1989)

We describe a set of murine retrovirus-based vectors that include unique cloning sites for insertion of cDNAs such that the cDNA can be driven by either the retroviral long terminal repeat, the immediate early promoter of human cytomegalovirus, or the simian virus 40 early promoter. The vectors carry the neomycin phosphotransferase gene expressed from an alternate promoter as a selectable marker. These vectors have been constructed to prevent viral protein synthesis from the remaining viral sequences, to yield high-titer virus stocks after introduction into retrovirus packaging cells, and to eliminate homologous overlap with viral DNAs present in retrovirus packaging cells in order to prevent helper virus production. Methods for generating high-titer virus are described.
Phase I Pharmacokinetic and Biologic Correlative Study of Mapatumumab, a Fully Human Monoclonal Antibody With Agonist Activity to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Receptor-1 (2007)

Mapatumumab can be administered safely and feasibly at 10 mg/kg IV every 14 days. The absence of severe toxicities and the attainment of plasma mapatumumab concentrations that are active in preclinical models warrant further disease-directed studies of this agent alone and in combination with chemotherapy in a broad array of tumors.
Induction of Interleukin 10–Producing, Nonproliferating Cd4+ T Cells with Regulatory Properties by Repetitive Stimulation with Allogeneic Immature Human Dendritic Cells (2000)

The functional properties of dendritic cells (DCs) are strictly dependent on their maturational state. To analyze the influence of the maturational state of DCs on priming and differentiation of T cells, immature CD83(-) and mature CD83(+) human DCs were used for stimulation of naive, allogeneic CD4(+) T cells. Repetitive stimulation with mature DCs resulted in a strong expansion of alloreactive T cells and the exclusive development of T helper type 1 (Th1) cells. In contrast, after repetitive stimulation with immature DCs the alloreactive T cells showed an irreversibly inhibited proliferation that could not be restored by restimulation with mature DCs or peripheral blood mononuclear cells, or by the addition of interleukin (IL)-2. Only stimulation of T cells with mature DCs resulted in an upregulation of CD154, CD69, and CD70, whereas T cells activated with immature DCs showed an early upregulation of the negative regulator cytotoxic T lymphocyte-associated molecule 4 (CTLA-4). These T cells lost their ability to produce interferon gamma, IL-2, or IL-4 after several stimulations with immature DCs and differentiated into nonproliferating, IL-10-producing T cells. Furthermore, in coculture experiments these T cells inhibited the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent, but antigen-nonspecific manner. These data show that immature and mature DCs induce different types of T cell responses: inflammatory Th1 cells are induced by mature DCs, and IL-10-producing T cell regulatory 1-like cells by immature DCs.
Regulation of the raffinose permease of Escherichia coli by the glucose-specific enzyme IIA of the phosphoenolpyruvate:sugar phosphotransferase system (1994)

In enteric bacteria, chromosomally encoded permeases specific for lactose, maltose, and melibiose are allosterically regulated by the glucose-specific enzyme IIA of the phosphotransferase system. We here demonstrate that the plasmid-encoded raffinose permease of enteric bacteria is similarly subject to this type of inhibition.
Interactive computer animation (1996)

Computer animation has been considered for many years as a new media for advertising and special effects in films. More recently, the fast development of powerful workstations has led to new areas like multimedia, interactive games and virtual reality. For these areas, interactive animation has become a key issue. Tackling the challenge of creating human motion through a computer, this book examines specific techniques such as cloth, hair and facial animation, and the co-ordination of animated objects.
A fine-scale comparison of the human and chimpanzee genomes: linkage, linkage disequilibrium and sequence analysis (1996)

We have performed a fine-scale comparative study of the human and chimpanzee genomes, using linkage, linkage disequilibrium and sequence analyses on microsatellite loci spanning a region of approximately 30 cM on human chromosome 4p. Our results extend the findings of previous studies that indicated virtually complete conservation between the human and chimpanzee genomes at the chromosomal and sub-chromosomal level and support the hypothesis, derived from previous analyses of mitochondrial DNA, that chimpanzee populations are more diverse than human ones. By sequencing several human and chimpanzee alleles of two microsatellites we showed that base substitutions that diminish the length of perfect repeats (but do not change allele sizes) are probably responsible for the low heterozygosity of these loci in chimpanzees; our results suggest that the evolutionary history of microsatellites should not be inferred from comparisons of mean allele lengths between populations or species.
Electrical stimulation of the nervous system. (1975)

Twenty-seven patients with chronic pain had dorsal column stimulators implanted for pain control over a period of three years. Technical factors of electrode placement and type of unit were not found to correlate with the degree of pain relief. The preoperative psychological attitude of the patient correlated highly with the degree of pain relief and was the single most important factor in patient selection and evaluation. Theoretical concepts of pain psychophysiology in relation to the gate theory and areas for more extensive investigation of pain are discussed.
[Recombinant colorimetric antibodies: genetic construction and production in E. coli]. (1992)

We constructed an expression vector comprising a transcription unit composed of (1) the gene of alkaline phosphatase from E. coli in which we inserted a DNA fragment encoding the VH and CH domains of an IgG2A; (2) a DNA fragment encoding the light chain of the same immunoglobulin. Bacteria, E. coli were transformed with the plasmid, and hence it produced a periplasmic and chimaeric protein having both the alkaline phosphatase enzymatic activity and the immunoglobulin binding function. The hybrid protein mimics a bivalent antibody whose Fc part is replaced by a dimer of alkaline phosphatase. Recombinant colorimetric antibodies offer interesting potentialities for future developments in the field of immuno-enzymatic diagnosis.
Ambipolar Pentacene Field-Effect Transistors and Inverters (2000)

Organic field-effect transistors based on pentacene single crystals, prepared with an amorphous aluminum oxide gate insulator, are capable of ambipolar operation and can be used for the preparation of complementary inverter circuits. The field-effect mobilities of carriers in these transistors increase from 2.7 and 1.7 square centimeters per volt per second at room temperature up to 1200 and 320 square centimeters per volt per second at low temperatures for hole and electron transport, respectively, following a power-law dependence. The possible simplification of the fabrication process of complementary logic circuits with these transistors, together with the high carrier mobilities, may be seen as another step toward applications of plastic electronics.
Safety of Recombinant Activated Factor VII in Randomized Clinical Trials (2010)

In a large and comprehensive cohort of persons in placebo-controlled trials of rFVIIa, treatment with high doses of rFVIIa on an off-label basis significantly increased the risk of arterial but not venous thromboembolic events, especially among the elderly. (Funded by Novo Nordisk.).
Effective eradication of established murine tumors with IL-12 gene therapy using a polycistronic retroviral vector. (1995)

Our recent studies using IL-12 protein or fibroblasts genetically engineered to secrete IL-12 have demonstrated profound antitumor effects of IL-12 in murine models. The antitumor effects of local, high level IL-12 expression were examined using a retroviral vector, which can express both IL-12 subunits (p35 and p40) and the neomycin phosphotransferase (Neo)-marker gene from a polycistronic message utilizing internal ribosome entry site sequences. All animals intradermally (i.d.) receiving MCA207 murine sarcoma cell line nontransfected or Neo-transfected had progressively growing tumor, whereas all animals injected with MCA207 transfected with IL-12 were tumor free and were subsequently determined to be immune to a rechallenge of nontransfected MCA207 i.d. Similar results were obtained in experiments using the poorly immunogenic MCA102 murine sarcoma cell line. The inoculation of live MCA207-IL-12 tumor cells also caused the regression of contralateral nontransfected MCA207 inoculated either at the same time (80% protection) or up to 3 days before (33% protection) to the therapeutic tumor inoculation. In vivo depletion studies suggest that NK cells and IFN-gamma play important roles in the development of the early phase of the antitumor response, but that T cells (both CD4+ and CD8+) play the major role in the subsequent events, leading to long-term immunity. The potent antitumor effects observed for paracrine gene-delivered administration of IL-12 have thus been confirmed for multiple tumor cell types and in multiple murine strains. We believe that these results support the feasibility of IL-12 gene therapy for the treatment of human cancer.
p53 immunodetection of liquid-based processed urinary samples helps to identify bladder tumours with a higher risk of progression (2005)

p53 could help identify bladder tumour cases with a risk of progression from superficial to invasive disease. Semiautomatic, liquid-based cytology (LBC) techniques offer an opportunity to standardise molecular techniques. The aim of our study was to investigate whether LBC could improve p53 immunolabelling, and to assess whether urinary p53 could have a prognostic value. Immunoreactivity for p53 was studied in 198 urine samples after treatment with the Cytyc Thinprep processor. After antigen retrieval, cells were labelled with a monoclonal antibody that recognises both wild-type and mutant form of the p53 protein (Clone DO-7, Dako), 1/1000. Positivity for p53 was assessed in 17.2% of the cases. High-grade (G3) tumours were positive in 74.1% of the cases. Comparatively, low-grade (G1-2) urothelial carcinomas were positive in 23.5% of the cases. During a median follow-up period of 26 months, recurrence was observed in 52.9% of the cases with p53 overexpression, and in only 10.9% of negative cases (P < 0.001). The progression rate was 35.3% of p53-positive cases vs 5.5% of p53-negative cases (P < 0.001). Progression-free survival was significantly shorter in patients with p53 accumulation (P = 0.007). In a multivariate analysis stratified on grade and stage, p53 was an independent predictor of overall survival (P = 0.042). The results show that using Thinprep LBC, p53 immunolabelling of voided urothelial cells allows most high-grade tumours to be detected and may help identify cases with a higher risk of recurrence and progression.