gebhart/patrepeval huggingface dataset:
Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC®) and morphine sulfate immediate release (MSIR®) (2001)

Oral transmucosal fentanyl citrate (OTFC); Actiq) is a drug delivery formulation used for management of breakthrough cancer pain. Previous studies with open-label comparisons indicated OTFC was more effective than patients' usual opioid for breakthrough pain. The objective of this study was to compare OTFC and morphine sulfate immediate release (MSIR) for management of breakthrough pain in patients receiving a fixed scheduled opioid regimen. This double-blind, double-dummy, randomized, multiple crossover study was conducted at 19 US university- and community-based hospitals and clinics and comprised 134 adult ambulatory cancer patients. Patients were receiving a fixed scheduled opioid regimen equivalent to 60-1000 mg/day oral morphine or 50-300 microg/h transdermal fentanyl, were using a 'successful' MSIR dose (15-60 mg) as defined by entry criteria, and were experiencing 1-4 episodes of breakthrough pain per day. In open-label fashion, OTFC was titrated such that a single unit (200-1600 microg) provided adequate pain relief with acceptable side effects. Successfully titrated patients entered the double-blind phase of the study and received ten prenumbered sets of randomized capsules and oral transmucosal units. Five sets were the successful OTFC dose paired with placebo capsules, and five sets were placebo OTFC paired with capsules containing the successful MSIR dose. Patients took one set of study medication for each episode of target breakthrough pain. Pain intensity (PI), pain relief (PR) and global performance of medication (GP) scores were recorded. Pain intensity differences (PID) were calculated and 15-min PID was the primary efficacy variable. Adverse events were recorded. Sixty-nine percent of patients (93/134) found a successful dose of OTFC. OTFC yielded outcomes (PI, PID, and PR) at all time points that were significantly better than MSIR. GP also favored OTFC and more patients opted to continue with OTFC than MSIR following the study. Somnolence, nausea, constipation, and dizziness were the most common drug-associated side effects. In conclusion, OTFC was more effective than MSIR in treating breakthrough cancer pain.
Low Temperature Silicon Epitaxy by Partially Ionized Vapor Deposition (1977)

Silicon films were formed on single crystal silicon substrates by partially ionized vapor deposition. Single crystal films were obtained on (111) p-type silicon substrates at room temperature when the silicon ion current density, which was about 25% of the total incident silicon atoms, exceeded 80 µA/cm2. Anneal behaviors of epitaxial films grown at room temperature and 400°C at an ion current density of 100 µA/cm2 were investigated by He+ backscattering measurements and by measurement of change in resistivity.
Nonlinear stabilizing control of multimachine systems (1989)

A novel approach is presented to nonlinear control design for multimachine systems using differential geometric theory. A mathematical model in the form of an affine nonlinear system is set up for the design of a large-scale power system. As an example, the approach is applied to nonlinear steam-valving control. The control law obtained is implemented by purely local feedback. The stability of a global multimachine system with the nonlinear control is illustrated by the results of simulation on a six-machine system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
CB2receptors in the brain: role in central immune function (2007)

Recently, it has been recognized that the cannabinoid receptor CB2 may play a functionally relevant role in the central nervous system (CNS). This role is mediated primarily through microglia, a resident population of cells in the CNS that is morphologically, phenotypically, and functionally related to macrophages. These cells also express the cannabinoid receptor CB1. The CB1 receptor (CB1R) is constitutively expressed at low levels while the CB2 receptor (CB2R) is expressed at higher levels and is modulated in relation to cell activation state. The relatively high levels of the CB2R correspond with microglia being in 'responsive' and 'primed' states, suggesting the existence of a 'window' of functional relevance during which activation of the CB2R modulates microglial activities. Signature activities of 'responsive' and 'primed' microglia are chemotaxis and antigen processing, respectively. The endocannabinoid 2-arachidonylglycerol has been reported to stimulate a chemotactic response from these cells through the CB2R. In contrast, we have shown in vivo and in vitro that the exogenous cannabinoids delta-9-tetrahydrocannabinol and CP55940 inhibit the chemotactic response of microglia to Acanthamoeba culbertsoni, an opportunistic pathogen that is the causative agent of Granulomatous Amoebic Encephalitis, through activation of the CB2R. It is postulated that these exogenous cannabinoids superimpose an inhibitory effect on pro-chemotactic endocannabinoids that are elicited in response to Acanthamoeba. Furthermore, the collective results suggest that the CB2R plays a critical immune functional role in the CNS.
Los museos universitarios australianos e Internet (2000)

Les Australiens ont employe deux methodes differentes pour faciliter l�acces sur l�Internet aux informations et aux images significatives des musees et des collections de leurs universites. Apres avoir ete conservatrice en chef du Musee de la centrale electrique de Sydney, Vanessa Mack dirige aujourd�hui le musee Macleay, a l�universite de Sydney. Elle est membre du comite de redaction d� Archives and Museum Informatics : cultural heritage informatics quaterly (Kluwer Academic Publishers), presidente du Groupe de reference charges des elements mobiliers du patrimoine culturel au sein du Conseil du patrimoine de la Nouvelle-Galles du Sud, et membre de divers comites de l�Universite de Sydney relatifs au patrimoine et aux musees. En 1997, elle a coordonne un projet pilote finance par le gouvernement federal, qui � sous le titre d�Australian University Museums on line (AUMOL) � avait pour but de creer un catalogue illustre, disponible sur l�Internet, des collections conservees dans les musees des universites australiennes. Elle fait aussi partie du comite de coordination du projet National Teaching and Learning Data Base [Base Nationale de donnees pedagogiques], issu du projet AUMOL. Ancien conservateur en chef du Monument aux morts d�Australie, a Canberra, Richard Llewellyn a ete nomme en 1997 directeur du projet AUMOL ; depuis, il a ete l�instigateur et le directeur du projet National Teaching and Learning Data Base et d�autres projets de collections sur l�Internet.
Prophylactic and therapeutic efficacy of a chimeric monoclonal antibody specific for H5 haemagglutinin against lethal H5N1 influenza (2009)

Passive immunotherapy using chimeric mAb 3B1 can be an effective tool in both the prophylaxis and treatment of highly pathogenic H5N1 infection, providing the immediate immunity needed to contain a future influenza pandemic.
Determination of minimum effective dose and optimal dosing schedule for liposomal curcumin in a xenograft human pancreatic cancer model. (2009)

The MED for liposomal curcumin is 20 mg/kg given once daily three times per week to achieve optimal tumor growth inhibition. This was dose recommended for additional preclinical studies to define safety and tolerability of liposomal curcumin in rat and dog models.
Conservation and Variation in Human and Common Chimpanzee CD94 and NKG2 Genes (2002)

To assess polymorphism and variation in human and chimpanzee NK complex genes, we determined the coding-region sequences for CD94 and NKG2A, C, D, E, and F from several human (Homo sapiens) donors and common chimpanzees (Pan troglodytes). CD94 is highly conserved, while the NKG2 genes exhibit some polymorphism. For all the genes, alternative mRNA splicing variants were frequent among the clones obtained by RT-PCR. Alternative splicing acts similarly in human and chimpanzee to produce the CD94B variant from the CD94 gene and the NKG2B variant from the NKG2A gene. Whereas single chimpanzee orthologs for CD94, NKG2A, NKG2E, and NKG2F were identified, two chimpanzee paralogs of the human NKG2C gene were defined. The chimpanzee Pt-NKG2CI gene encodes a protein similar to human NKG2C, whereas in the chimpanzee Pt-NKG2CII gene the translation frame changes near the beginning of the carbohydrate recognition domain, causing premature termination. Analysis of a panel of chimpanzee NK cell clones showed that Pt-NKG2CI and Pt-NKG2CII are independently and clonally expressed. Pt-NKG2CI and Pt-NKG2CII are equally diverged from human NKG2C, indicating that they arose by gene duplication subsequent to the divergence of chimpanzee and human ancestors. Genomic DNA from 80 individuals representing six primate species were typed for the presence of CD94 and NKG2. Each species gave distinctive typing patterns, with NKG2A and CD94 being most conserved. Seven different NK complex genotypes within the panel of 48 common chimpanzees were due to differences in Pt-NKG2C and Pt-NKG2D genes.
Prospective Temporal Analysis of the Onset of Preinfarction Angina Versus Outcome (1998)

These temporal observations are consistent with the concept of preconditioning by preinfarction angina but do not rule out other mechanisms.
Randomized Phase II Study of BR96-Doxorubicin Conjugate in Patients With Metastatic Breast Cancer (1999)

The BR96-doxorubicin immunoconjugate has limited clinical antitumor activity in metastatic breast cancer. The gastrointestinal toxicities likely represent binding of the agent to normal tissues expressing the target antigen and may have compromised the delivery of the immunoconjugate to the tumor sites.
Modulation of CD4+ T-cell activation by CD95 co-stimulation (2010)

CD95 is a dual-function receptor that exerts pro- or antiapoptotic effects depending on the cellular context, the state of activation, the signal threshold and the mode of ligation. In this study, we report that CD95 engagement modulates TCR/CD3-driven signaling pathways in resting T lymphocytes in a dose-dependent manner. While high doses of immobilized CD95 agonists silence T cells, lower concentrations augment activation and proliferation. We analyzed the co-stimulatory capacity of CD95 in detail in resting human CD4(+) T cells, and demonstrate that low-dose ligand-induced co-internalization of CD95 and TCR/CD3 complexes enables non-apoptotic caspase activation, the prolonged activation of MAP kinases, the upregulation of antiapoptotic proteins associated with apoptosis resistance, and the activation of transcription factors and cell-cycle regulators for the induction of proliferation and cytokine production. We propose that the levels of CD95L on antigen-presenting cells (APCs), neighboring T cells or epithelial cells regulate inhibitory or co-stimulatory CD95 signaling, which in turn is crucial for fine-tuning of primary T-cell activation.
Deposition pattern of nasal sprays in man. (1988)

The intranasal distribution from an aqueous pump spray has been assessed in 13 normal subjects, using insoluble Teflon particles labelled with 99Tcm which were intended to simulate a suspension of drug particles. Three different combinations of metered volume and spray cone angle were compared. The main deposition of particles was in the anterior, non-ciliated, part of the nose, but some particles also penetrated more posteriorly into the main nasal passages and were cleared subsequently to the nasopharynx. No particles were detected in the lungs. With a single puff of 100 microliters volume, 46.5 +/- 4.4 (mean +/- SEM)% of the spray was retained in the anterior part of the nose after 30 minutes, but this was increased to 57.1 +/- 4.5% (P less than 0.05) with two puffs of 50 microliters. The latter were deposited over a significantly (P less than 0.05) smaller area in the nasal cavity. There was a trend towards lower particle retention and a greater area of deposition when the spray cone angle was decreased from 60 degrees to 35 degrees. These results indicate that the drug particles released from nasal pump sprays are distributed both to ciliated and non-ciliated zones, and that the choice of metered volume and possibly spray cone angle may play a role in determining the amount which penetrates to the main nasal passages.
Kinetics of DNA and RNA Hybridization in Serum and Serum-SDS (2010)

Cancer is recognized as a serious health challenge both in the United States and throughout the world. While early detection and diagnosis of cancer leads to decreased mortality rates, current screening methods require significant time and costly equipment. Recently, increased levels of certain micro-ribonucleic acids (miRNAs) in the blood have been linked to the presence of cancer. While blood-based biomarkers have been used for years in cancer detection, studies analyzing trace amounts of miRNAs in blood and serum samples are just beginning. Recent developments in deoxyribonucleic acid (DNA) nanotechnology and DNA computing have shown that it is possible to construct nucleic-acid-based chemical networks that accept miRNAs as inputs, perform Boolean logic functions on those inputs, and generate as an output a large number of DNA strands that can readily be detected. Since miRNAs occur in blood in low abundance, these networks would allow for amplification without using polymerase chain reaction. In this study, we report initial progress in the development of a DNA-based cross-catalytic network engineered to amplify specific cancer-related miRNAs. Subcomponents of the DNA network were tested individually, and their operation in serum, as well as a mixture of serum with sodium dodecyl sulfate, is demonstrated. Preliminary simulations of the full cross-catalytic network indicate successful operation.
Heat shock protein and innate immunity. (2004)

In addition to serving as molecular chaperones, heat shock proteins (HSPs) have been implicated in autoimmune diseases, antigen presentation and tumor immunity. Extensive work in the last 10 years has also suggested that HSPs such as Hsp60, Hsp70, Hsp90 and gp96, may be potent activators of the innate immune system capable of inducing the production of pro-inflammatory cytokines by the monocyte-macrophage system, and the activation and maturation of dendritic cells via the Toll-like receptor 2 and 4 signal transduction pathways. However, recent evidence suggests that the reported cytokine effects of HSPs may be a result of the contaminating bacterial cell-wall products. This concise review summarizes the current controversy over the role of HSPs in innate immunity.
Insulator to Semimetal Transition in Graphene Oxide (2009)

Transport properties of progressively reduced graphene oxide (GO) are described. Evolution of the electronic properties reveals that as-synthesized GO undergoes insulator−semiconductor−semimetal transitions with reduction. The apparent transport gap ranges from 10 to 50 meV and approaches zero with extensive reduction. Measurements at varying degrees of reduction reveal that transport in reduced GO occurs via variable-range hopping and further reduction leads to an increased number of available hopping sites.
Specific tumoricidal activity of a secreted proapoptotic protein consisting of HER2 antibody and constitutively active caspase-3. (2003)

In this study, a novel approach to antitumor therapy was devised by generating a chimeric tumor-targeted killer protein, referred to as immunocasp-3, that comprises a single-chain anti-erbB2/HER2 antibody with a NH(2)-terminal signal sequence, a Pseudomonas exotoxin A translocation domain, and a constitutively active caspase-3 molecule. In principle, cells transfected with the immunocasp-3 gene would express and secrete the chimeric protein, which then binds to HER2-overexpressing tumor cells. Subsequent cleavage of the constitutively active capase-3 domain from the immunocasp-3 molecule and its release from internalized vesicles would lead to apoptotic tumor cell death. To test this strategy, we transduced human lymphoma Jurkat cells with a chimeric immunocasp-3 gene expression vector and showed that they not only expressed and secreted the fusion protein but also selectively killed tumor cells overexpressing HER2 in vitro. i.v. injection of the transduced Jurkat cells led to tumor regression in a mouse xenograft model because of continuous secretion of immunocasp-3 by the transduced cells. The growth of HER2-positive tumor cells in this model was inhibited by i.m. as well as intratumor injection of immunocasp-3 expression plasmid DNA, indicating that the immunocasp-3 molecules secreted by transfected cells have systematic antitumor activity. We conclude that the immunocasp-3 molecule, combining the properties of a tumor-specific antibody with the proapoptotic activity of a caspase, has potent and selective antitumor activity, either as cell-based therapy or as a DNA vaccine. These findings provide a compelling rationale for therapeutic protocols designed for erbB2/HER2-positive tumors.
Cold Lake Project Recovery and the Role of Foamy Emulsion (1995)

Abstract Cyclic steam injection stimulates an effective foamy emulsion expansion drive at Imperial's Cold Lake Project. Projected bitumen recovery is 25% of the Clearwater bitumen-in-place on developed pads. Ultimate recovery is estimated to be 232 million cubic metres of bitumen from the development area accessible from the current plants.
Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma (2013)

Follicular lymphoma (FL) is currently incurable using conventional chemotherapy or immunotherapy regimes, compelling new strategies. Advances in high-throughput sequencing technologies that can reveal oncogenic pathways have stimulated interest in tailoring therapies toward actionable somatic mutations. However, for mutation-directed therapies to be most effective, the mutations must be uniformly present in evolved tumor cells as well as in the self-renewing tumor-cell precursors. Here, we show striking intratumoral clonal diversity within FL tumors in the representation of mutations in the majority of genes as revealed by whole exome sequencing of subpopulations. This diversity captures a clonal hierarchy, resolved using immunoglobulin somatic mutations and IGH-BCL2 translocations as a frame of reference and by comparing diagnosis and relapse tumor pairs, allowing us to distinguish early versus late genetic eventsduring lymphomagenesis. We provide evidence that IGH-BCL2 translocations and CREBBP mutations are early events, whereas MLL2 and TNFRSF14 mutations probably represent late events during disease evolution. These observations provide insight into which of the genetic lesions represent suitable candidates for targeted therapies.
Treatment of Pleural Mesothelioma in an Immunocompetent Rat Model Utilizing Adenoviral Transfer of the Herpes Simplex Virus Thymidine Kinase Gene (1996)

Previously, we have treated malignant mesothelioma (MM) growing in the peritoneal cavity of immunodeficient mice utilizing a recombinant adenovirus vector carrying the herpes simplex virus-thymidine kinase gene (Ad.RSVtk) followed by administration of the anti-viral drug ganciclovir (GCV). To mimic more closely the clinical situation in human MM, a syngeneic model of pleural MM was developed in immunocompetent Fischer rats. Administration of Ad.RSVtk into the pleural space of animals with established multifocal tumor followed by systemic GCV therapy resulted in significant tumor regression at 20 days in HSVtk/GCV-treated animals (average tumor weight 0.6 +/- 0.2 gram; n = 12) versus control animals (average weight 5.4 +/- 0.2 grams; n = 21; p < 0.001). In additional studies, Ad.RSVtk/GCV-treated animals had a mean survival of 34 days (average tumor weight 1.0 +/- 0.3 gram at death) versus 26 days in control animals (average tumor weight 6.2 +/- 0.6 grams at death). A significant reduction in tumor burden was also seen when more advanced, bulkier disease was treated. These studies demonstrate the Ad.RSVtk/GCV system is effective in the treatment of pleural-based tumors in an immunocompetent host. However, there are limitations to this treatment approach that result in only small increments in survival.
ERdj5 sensitizes neuroblastoma cells to ER stress-induced apoptosis via regulation of eLF2a signaling (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5266 

The accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) (ER stress) induces a coordinated adaptive program called the unfolded protein response (UPR). The UPR alleviates stress by upregulating protein folding and degradation pathways and inhibiting protein synthesis. Translational repression is mediated by increased phosphorylation of eukaryotic translation initiation factor 2a (eIF2a). Although the activation of the UPR normally succeeds in restoring ER homeostasis, persistent or intense ER stress can trigger apoptosis. Here we demonstrate that the Thioredoxin domains-containing novel ER-resident chaperone molecule ERdj5 affects cell survival and controls eIF2a phosphorylation and signaling in response to ER stress. We show that overexpression of ERdj5 induces both G1/S cell cycle arrest and apoptosis in neuroblastoma cells in response to ER stress. ERdj5 overexpression delays the eIF2a dephosphorylation and the translational recovery normally observed late in the stress response by decreasing the expression of GADD34, a subunit of the PP1-holophosphatase complex that dephosphorylates eIF2a when the stress is overcome. Furthermore, defective recovery of protein synthesis impairs translation of stress-induced proteins in the ERdj5-overexpressing cells. These observations indicate that ERdj5-mediated delay of translational recovery decreases cancer cell resistance to apoptosis induced by ER stress.
DNA Vaccine Combinations Expressing Either Tissue Plasminogen Activator Signal Sequence Fusion Proteins or Ubiquitin-Conjugated Antigens Induce Sustained Protective Immunity in a Mouse Model of Pulmonary Tuberculosis (2002)

DNA vaccination has emerged as a powerful approach in the search for a more efficacious vaccine against tuberculosis. In this study, we evaluated the effectiveness of immunizing with combinations of 10 different tuberculosis DNA vaccines that expressed mycobacterial proteins fused at the N terminus to eukaryotic intracellular targeting sequences. In one vaccine combination, the genes were fused to the tissue plasminogen activator signal sequence (TPA), while in a second combination the same 10 genes were expressed as ubiquitin (Ub)-conjugated proteins. In ex vivo studies in which the secretion of gamma interferon was measured, cellular immune responses were detected in mice vaccinated with either the TPA DNA vaccine combination or the Ub DNA vaccine combination at 7 and 14 days following a low-dose Mycobacterium tuberculosis challenge. Moreover, mice vaccinated with the TPA combination, the Ub combination, and Mycobacterium bovis BCG were able to limit the growth of tubercle bacilli in the lung and spleen after a virulent tuberculous aerosol challenge. Histopathological analyses also showed that mice immunized with the DNA vaccine combinations had substantially improved postinfection lung pathology relative to the naïve controls. Finally, in three different long-term experiments, the survival periods following aerogenic challenge were extended as much as sevenfold for vaccinated mice compared to naïve controls. Interestingly, in all three experiments, no significant differences were detected in the mean times to death for mice immunized with the TPA combination or the Ub combination relative to the BCG controls. In conclusion, these studies demonstrate the effectiveness of immunization with DNA vaccine combinations against tuberculosis and suggest that further testing of these plasmid cocktails is warranted.