gebhart/patrepeval huggingface dataset:
Emerging applications of network and pathway analysis in drug discovery and development. (2008)

Molecular pathway and network analysis tools that have been developed over the past decade provide an emerging systems-wide perspective for the analysis of gene expression, proteomic and metabolomic data. These tools link relevant extracted literature information available from structured knowledge bases with user-friendly features that enable analysis and interpretation of the global impact of a disease stage or drug treatment. Pathway and network analysis tools have been found to have broad applicability within the biomedical community, most specifically in cancer research to elucidate mechanisms of tumor progression and for biomarker discovery, and more recently in the area of drug discovery and development. This review discusses recent applications of pathway and network analysis for predictive in silico modeling in the area of drug discovery and development, including theoretical and practical advances and the implications for their application.
Structure and trafficking of NMDA and GABAA receptors (2006)

The fidelity of synaptic function is dependent on the expression of the appropriate neurotransmitter receptor subtype, the targeting and trafficking of receptors to synapses as well as the regulation of the actual number of receptors at synapses. GABAA (gamma-aminobutyric acid type A) receptors and NMDA (N-methyl-D-aspartate) receptors are both examples of ligand-gated, heteromeric neurotransmitter receptors whose cell-surface expression is dynamic and tightly regulated. NMDA receptors are localized at excitatory synapses. These synapses are highly structured but dynamic, with the interplay between NMDA receptors and NMDA receptor-associated scaffolding proteins regulating the expression of functional cell-surface synaptic and extrasynaptic receptors. Based on current information, inhibitory synapses seem to be less ordered, and a GABAA receptor equivalent of PSD-95 (postsynaptic density-95), the scaffolding molecule pivotal to the organization of NMDA receptor complexes at synapses, is yet to be validated. In the present paper, processes regulating the trafficking, assembly and molecular organization of both NMDA receptors and GABAA receptors will be discussed.
Two-dimensional electro-optic imaging of THz beams (1996)

We report on a novel electro-optic sampling system for real-time terahertz (THz) imaging applications. By illuminating a 6×8 mm2 ZnTe crystal with a 300 μW optical sampling beam and detecting the beam with a digital CCD camera, we achieved time-resolved images of pulsed far-infrared radiation emitted from an unbiased GaAs wafer. At the focal point of the peak far-infrared field, the THz beam diameter is approximately 0.75 mm (full width at half-maximum). The temporal and spatial resolutions of this imaging system are mainly limited by the laser pulse duration and the diffraction limit of the THz beam, respectively.
TOTAL THORACIC AND PARTIAL TO TOTAL LUMBAR SYMPATHECTOMY AND CELIAC GANGLIONECTOMY IN THE TREATMENT OF HYPERTENSION* (1941)

TOTAL THORACIC AND PARTIAL TO TOTAL LUMBAR SYMPATHECTOMY AND CELIAC GANGLIONECTOMY IN THE TREATMENT OF HYPERTENSION: PDF Only
Antiangiogenic Therapy of a Recurrent Giant Cell Tumor of the Mandible With Interferon Alfa-2a (1999)

We report a 5-year-old girl with a large rapidly growing giant cell tumor of the mandible that recurred 2 months after the first surgical excision and 3 months after a second resection. An angiogenic protein, (bFGF), was abnormally elevated in her urine. The patient was treated with interferon alfa-2a for 1 year because this agent inhibits angiogenesis by suppressing bFGF overexpression in infantile hemangiomas and in other human tumors. During this time the bone tumor regressed and disappeared, the urinary bFGF fell to normal levels, and the mandible regenerated. She has remained tumor-free and has been off therapy for 3 years at this writing. This first successful use of interferon alfa-2a to treat a mandibular tumor in a child demonstrates: 1) low grade tumors that overexpress bFGF may respond to interferon alfa-2a, in a manner similar to life-threatening infantile hemangiomas; 2) antiangiogenic therapy, given without interruption for 1 year, was safe and effective in this patient; and 3) treatment may be continued for 1 year without the development of drug resistance.
Poly(ethylene glycol)-Modification of the Phospholipid Vesicles by Using the Spontaneous Incorporation of Poly(ethylene glycol)-Lipid into the Vesicles (2000)

The critical micelle concentrations of 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[monomethoxy poly(ethylene glycol) (5000)] (PEG-DPPE) and its distearoyl analogue (PEG-DSPE) were 70 and 9 microM, respectively, in buffer solutions ([Tris] = 20 mM, [NaCl] = 140 mM, pH 7.4) at 37 degrees C. When these PEG-lipid micelle dispersions were mixed with the dispersions of phospholipid vesicles comprised of a C16 membrane, of which the carbon number is 16, or a C18 membrane, the PEG-lipid micelles were dissociated into monomers and then spontaneously incorporated into the surface of the preformed vesicles. The incorporation rates and the enthalpy changes during incorporation were measured with an isothermal titration microcalorimeter. The incorporation rate of PEG-DPPE was faster than that of PEG-DSPE, because the dissociation rate of the PEG-DPPE micelles was faster than that of PEG-DSPE micelles. The incorporation equilibrium constant of PEG-DSPE was larger than that of PEG-DPPE due to its slow dissociation rate from the membrane, caused by the stronger hydrophobic interaction. The combination of PEG-DSPE and the C18 membrane was the most thermodynamically stabilized pair. Furthermore, the dispersion stability of the surface-modified vesicles prepared by this spontaneous incorporation was analyzed by using the critical molecular weight of the polymer for the aggregation of vesicles. The aggregation of the vesicles was successfully supressed with an increase in the molecular weight of the PEG in the PEG-lipid and its incorporation ratio.
Transition Metal Complexes in Organic Synthesis, Part 69.Total Synthesis of theAmaryllidaceaeAlkaloids Anhydrolycorinone and Hippadine Using Iron- and Palladium-Mediated Coupling Reactions (2003)

A novel synthesis of the Amaryllidaceae alkaloids anhydrolycorinone and hippadine has been developed using an iron-mediated oxidative alkylamine cyclization and an intramolecular palladium-mediated biaryl coupling as the key steps.
Personal Computer Programs to Assist with Self-Monitoring of Blood Glucose and Self-Adjustment of Insulin Dosage (1986)

We have developed computer programs in compiled BASIC for the IBM-PC and compatible microcomputers for use by physicians, paramedical personnel, and/or patients to assist with self-monitoring of blood glucose (SMBG) and self-adjustment of insulin dosage. The programs can potentially assist with patient education and motivation, and provide: a customized "electronic notebook" for storage and retrieval of information on blood glucose, insulin dosage, hypoglycemic reactions, urinary ketones, diet, activity, weight, illness, apparent explanations for hypoglycemic reactions or glucose values outside target ranges, and comments; graphic displays of glucose and insulin versus date, and of a "glucose profile" versus time of day or versus day of the week; simple and detailed statistical analyses; a legible summary of data; a facility to permit the physician to prepare a "customized treatment plan" for each patient, involving a choice of six regimens, target levels for each of eight time periods, four supplement tables (when well or sick, before meals, or at bedtime), rules to reduce insulin in response to hypoglycemic reactions or documented hypoglycemia, rules to increase routine insulin doses in response to persistent unexplained hyperglycemia, and rules when the patient should call the physician; suggestions regarding compensatory supplements and adjustments of routine insulin dosage; explanations why various insulin dosages should or should not be altered, and why various glucose values should be tested; comparisons of the insulin dosage administered by the patient and the recommendations of the program, together with explanations for discrepancies offered by the patient, to help evaluate compliance. The program is "user-friendly," easy to learn, and easy to use.(ABSTRACT TRUNCATED AT 250 WORDS)
Nanometer-Sized Electrochemical Sensors (1997)

Nanometer-sized glass-sealed metal ultramicroelectrodes (UMEs) have been prepared using a laser-based micropipet puller. The tip was exposed to solution either by etching away a small portion of glass insulator or by micropolishing. The characterization of the UMEs was carried out by a combination of steady-state voltammetry, scanning electron microscopy (SEM), and scanning electrochemical microscopy (SECM). The cyclic voltammograms obtained have a regular shape with very small capacitive and resistive background. The effective electrode radii obtained from voltammetry were between 2 and 500 nm. From the SEM micrographs, the shape of polished tips appears to be close to a microdisk, while the geometry of etched electrodes is closer to conical. Accordingly, the SECM current−distance curves (iT−d) obtained with polished electrodes fit well the theory for a disk-shaped tip, while a 20-nm-radius etched electrode was shown to be a fairly sharp cone with a height-to-radius ratio of about 2.5. The experimental data were compared to the theory developed for disk-shaped, conical, and recessed tips to demonstrate suitability of the produced electrodes for quantitative electrochemical experiments. The prospects of steady-state measurements of the rates of fast heterogeneous reactions are discussed. Submicrometer-sized ion selective electrodes (ISEs) were prepared by coating etched Ag tips with silver iodide. The concentration response of such ISEs remained stable and linear after coating of the ISEs with protective Nafion film.
The Triterpenoid 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic Acid and Its Derivatives Elicit Human Lymphoid Cell Apoptosis through a Novel Pathway Involving the Unregulated Mitochondrial Permeability Transition Pore (2007)

2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its C(28) imidazole and dinitrile derivatives are novel oleanane triterpenoids exhibiting promise as both therapeutic and preventative agents for cancer. Herein we show that these triterpenoids induce normal and malignant B-lymphoid cell apoptosis, with the C(28) derivatives being more potent than CDDO, through a novel mitochondrial mechanism. We show using both normal and malignant human B cells, as well as isolated rat mitochondria, that CDDO directly interacts with a limited number of as yet undefined mitochondrial proteins. Such an interaction results in the loss of mitochondrial thiol status and the secondary modification of numerous mitochondrial protein thiols. Our data further suggest that such modifications result in the formation of high molecular weight protein aggregates that form "unregulated," constitutively open, cyclosporin A-insensitive permeability transition (PT) pores. The formation of such PT pores results in the subsequent generation of mitochondrial superoxide and cell death. In total, our studies (a) suggest a novel mechanism of action for triterpenoid-induced cell death; (b) are among the first to directly support the existence of an unregulated PT pore formed by mitochondrial protein aggregates, as first proposed by Lemasters and colleagues; and (c) validate such an unregulated PT pore as a viable target for the development of new cancer therapeutics.
Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1 (2001)

Muscle tissue is the major site for insulin-stimulated glucose uptake in vivo, due primarily to the recruitment of the insulin-sensitive glucose transporter (GLUT4) to the plasma membrane. Surprisingly, virtually all cultured muscle cells express little or no GLUT4. We show here that adenovirus-mediated expression of the transcriptional coactivator PGC-1, which is expressed in muscle in vivo but is also deficient in cultured muscle cells, causes the total restoration of GLUT4 mRNA levels to those observed in vivo. This increased GLUT4 expression correlates with a 3-fold increase in glucose transport, although much of this protein is transported to the plasma membrane even in the absence of insulin. PGC-1 mediates this increased GLUT4 expression, in large part, by binding to and coactivating the muscle-selective transcription factor MEF2C. These data indicate that PGC-1 is a coactivator of MEF2C and can control the level of endogenous GLUT4 gene expression in muscle.
Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. (1990)

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.
Enhancing 5-Fluorouracil Efficacy in a Primary Colorectal Cancer by Long-lasting Calcium Supplementation (2017)

Sustained calcium supplementation was able to enhance the potency of 5-FU targeting the primary CRC.
A Magnetic Amplifier for Radio Telephony (1916)

A magnetic amplifying device is described for permitting the control of radio frequency currents by varying the saturation of the iron core of an inductance included in the radio frequency circuit. The arrangement of windings of the amplifier is such that the controlling winding has no radio frequency E. M. F. induced in it, nor does it induce currents in the radio frequency coils. Various arrangements of this amplifier in connection with a solid steel rotor, radio frequency alternator are shown, notably those in series with the alternator and those in parallel. "Short-circuiting" condensers are connected to each of the radio frequency coils. A shunt condenser across both coils and their "short-circuiting" condensers increases the sensitiveness for reasons which are given. Another condenser inserted in series with the entire amplifier is employed to obtain linear proportionality of amplification and increased sensitiveness. The ratio of amplification is found to be proportional to the ratio of the frequency of the radio current to that of the controlling current. The control of the output of a 75 K. W. alternator of radio frequency for telephonic purposes is then shown by oscillograms to be accurate, and the numerical characteristics of alternator and amplifier separately and in combination are given.
INTEGRATIVE BIOLOGY OF PROSTATE CANCER PROGRESSION (2006)

Prostate cancer displays considerable clinical, morphological, and biological heterogeneity. Classical genetic techniques have provided only limited information about the pathogenesis of prostate cancer progression. Nevertheless, several candidate genes and pathways have been implicated in prostate cancer development. High-throughput techniques have exponentially expanded the number of candidate genes, including some whose role in prostate cancer pathogenesis has been studied. However, the techniques used to study the prostate cancer genome, transcriptome, and proteome generate massive amounts of data that have yet to be integrated and explored. To move beyond candidate gene identification and develop a comprehensive understanding of cancer pathogenesis, integrative approaches need to analyze this data on a global level. This review addresses candidate genes involved in prostate cancer pathogenesis in a biological and clinical context and demonstrates how integrated analysis of high-throughput data augments our understanding of prostate cancer.
Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia (2002)

Interleukin 18 (IL-18) was discovered as an interferon-gamma (IFN-gamma)-inducing factor and plays important roles in natural killer (NK) cell activation. IL-18 also induces proinflammatory cytokines; chemokines; helper T-cell 2 (T(H)2) cytokines (eg, IL-4, IL-13); and immunoglobulin E (Ig-E) and IgG1 production. The combination of IL-18 plus IL-2 or IL-12 up-regulates IFN-gamma gene expression and NK cytotoxicity and has synergistic antitumor activity in vivo and in vitro. Here it is reported that daily administration of IL-18 with IL-2, but not of IL-18 or IL-2 alone, induces lethal lung injury in normal mice, but not in IL-18 receptor alpha (IL-1 receptor-related protein)-deficient (IL-18 receptor alpha(-/-)) mice. Marked interstitial infiltration of lymphocytes, composed mainly of NK cells, was found in the lungs of IL-18/IL-2-treated mice. Increased cytokine and chemokine levels were observed in the sera and lungs of IL-18/IL-2-treated mice. Administration of IL-18/IL-2 was also lethal to mice treated with a metalloproteinase inhibitor, which inhibited tumor necrosis factor-alpha and Fas-ligand release. While IFN-gamma(-/-) mice were partially resistant to the treatment, IL-4(-/-), IL-13(-/-), IL-4/IL-13(-/-), and Stat6(-/-) mice were sensitive to IL-18/IL-2, indicating that these genes were not involved in the host response. The lethal effect by IL-18/IL-2 was completely eliminated in severe combined immunodeficient mice pretreated with antiasialo-GM1 antibody and normal mice pretreated with anti-NK1.1 but not with anti-CD4 or anti-CD8, monoclonal antibody. These results suggest that specific cytokines, chemokines, and NK cells are involved in the pathogenesis of interstitial pneumonia. These results suggest that the clinical use of this interleukin may result in unexpected physiological consequences.
A Controlled Trial of Two Acellular Vaccines and One Whole-Cell Vaccine against Pertussis (1996)

The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.
Monomeric and Dimeric Amidinate Complexes of Magnesium (2001)

Treatment of anhydrous magnesium bromide with 2 equiv of (1,3-di-tert-butylacetamidinato)lithium, (1,3-di-tert-butylbenzamidinato)lithium, (1,3-diisopropylacetamidinato)lithium, or (1-tert-butyl-3-ethylacetamidinato)lithium (prepared in situ from the corresponding carbodiimide and alkyllithium) in diethyl ether at ambient temperature afforded bis(N,N'-di-tert-butylacetamidinato)magnesium (81%), bis(N,N'-di-tert-butylbenzamidinato)magnesium (82%), bis[bis(N,N'-diisopropylacetamidinato)magnesium] (70%), or bis[bis(1-tert-butyl-3-ethylacetamidinato)magnesium] (93%), respectively, as colorless crystalline solids. These complexes were characterized by spectral and analytical data and by single-crystal X-ray crystallography for bis(N,N'-di-tert-butylbenzamidinato)magnesium, bis[bis(N,N'-diisopropylacetamidinato)magnesium], and bis[bis(1-tert-butyl-3-ethylacetamidinato)magnesium]. In the solid-state structure, bis[bis(1-tert-butyl-3-ethylacetamidinato)magnesium] was found to contain mu,eta(2):eta(1)-amidinato ligands. Bis[bis(N,N'-diisopropylacetamidinato)magnesium] exists in a monomer-dimer equilibrium in toluene-d(8) between -20 and +60 degrees C. A van't Hoff analysis of this equilibrium afforded DeltaH degrees = -14.7 +/- 0.2 kcal/mol, DeltaS degrees = -44.9 +/- 0.2 cal/(mol.K), and DeltaG degrees (298 K) = -1.32 +/- 0.2 kcal/mol. The potential application of the new compounds in the chemical vapor deposition of magnesium-doped group 13 compound semiconductor films is discussed.
Conceptual model for production and composition of exopolymers in biofilms (1997)

The presence and the transformations of organic fractions within biofilms are not usually included in biofilm models, mainly owing to the lack of knowledge of the important processes, the stoichiometry and the kinetics. A conceptual biofilm model taking into account microbial physiology with regard to production of extracellular polymers and their transformation within the biofilm is suggested. The suggested components in the biofilm are the cell biomass and the various extracellular polymeric substances (EPS), such as polysaccharides, protein, humic substances and nucleic acids. In addition, environmental factors that influence the microbial exopolymer production and composition are taken into account. The suggested conceptual model can be helpful in structuring the design and evaluation of biofilm experiments focusing on biofilm structure and properties.
Cutting Edge: The IκB Kinase (IKK) Inhibitor, NEMO-Binding Domain Peptide, Blocks Inflammatory Injury in Murine Colitis (2007)

Inflammatory mediators such as TNF-alpha, IL-6, and IL-1 are important in the pathogenesis of inflammatory bowel diseases and are regulated by the activation of NF-kappaB. The aim of the present study was to investigate whether the NF-kappaB essential modulator (NEMO)-binding domain (NBD) peptide, which has been shown to block the association of NEMO with the IkappaB kinasebeta subunit (IKKbeta) and inhibit NF-kappaB activity, reduces inflammatory injury in mice with colitis. Two colitis models were established by the following: 1) inclusion of dextran sulfate sodium salt (DSS) in the drinking water of the mice; and 2) a trinitrobenzene sulfonic acid enema. Marked NF-kappaB activation and expression of proinflammatory cytokines were observed in colonic tissues. The NBD peptide ameliorated colonic inflammatory injury through the down-regulation of proinflammatory cytokines mediated by NF-kappaB inhibition in both models. These results indicate that an IKKbeta-targeted NF-kappaB blockade using the NBD peptide could be an attractive therapeutic approach for inflammatory bowel disease.
Polymer Light-Emitting Electrochemical Cells (1995)

A device configuration for light emission from electroactive polymers is described. In these light-emitting electrochemical cells, a p-n junction diode is created in situ through simultaneous p-type and n-type electrochemical doping on opposite sides of a thin film of conjugated polymer that contains added electrolyte to provide the necessary counterions for doping. Light-emitting devices based on conjugated polymers have been fabricated that operate by the proposed electrochemical oxidation-reduction mechanism. Blue, green, and orange emission have been obtained with turn-on voltages close to the band gap of the emissive material.