gebhart/patrepeval huggingface dataset:
Metal .sigma.-hydrocarbyls, MRn. Stoichiometry, structures, stabilities, and thermal decomposition pathways (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetal .sigma.-hydrocarbyls, MRn. Stoichiometry, structures, stabilities, and thermal decomposition pathwaysPeter J. Davidson, Michael F. Lappert, and Ronald PearceCite this: Chem. Rev. 1976, 76, 2, 219–242Publication Date (Print):April 1, 1976Publication History Published online1 May 2002Published inissue 1 April 1976https://pubs.acs.org/doi/10.1021/cr60300a003https://doi.org/10.1021/cr60300a003research-articleACS PublicationsRequest reuse permissionsArticle Views871Altmetric-Citations313LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Plasma Biomarkers as Predictors of Outcome in Patients with Advanced Hepatocellular Carcinoma (2012)

The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC. In contrast, none of the biomarkers tested significantly predicted response to sorafenib.
Antitumor polyketide biosynthesis by an uncultivated bacterial symbiont of the marine sponge Theonella swinhoei (2004)

Bacterial symbionts have long been suspected to be the true producers of many drug candidates isolated from marine invertebrates. Sponges, the most important marine source of biologically active natural products, have been frequently hypothesized to contain compounds of bacterial origin. This symbiont hypothesis, however, remained unproven because of a general inability to cultivate the suspected producers. However, we have recently identified an uncultured Pseudomonas sp. symbiont as the most likely producer of the defensive antitumor polyketide pederin in Paederus fuscipes beetles by cloning the putative biosynthesis genes. Here we report closely related genes isolated from the highly complex metagenome of the marine sponge Theonella swinhoei, which is the source of the onnamides and theopederins, a group of polyketides that structurally resemble pederin. Sequence features of the isolated genes clearly indicate that it belongs to a prokaryotic genome and should be responsible for the biosynthesis of almost the entire portion of the polyketide structure that is correlated with antitumor activity. Besides providing further proof for the role of the related beetle symbiont-derived genes, these findings raise intriguing ecological and evolutionary questions and have important general implications for the sustainable production of otherwise inaccessible marine drugs by using biotechnological strategies.
Transesophageal Echocardiography To Assess Embolic Risk in Patients with Atrial Fibrillation (1998)

In outpatients with atrial fibrillation and without recent stroke, thrombi of the left atrium or left atrial appendage and length and width of the left atrial appendage were associated with stroke or embolism in univariate analysis. In a multivariate analysis, age, hypertension, and previous stroke were risk factors for stroke or embolism, and thrombi of the left atrium or left atrial appendage were possible risk factors. In these patients, history may be more useful than transesophageal echocardiography for the assessment of embolic risk.
Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury. (1991)

Complement activity was studied in patients with spinal cord transection. In some sera acute phase reactants: haptoglobin, C-reactive proteins, ceruloplasmin, as well as fibrinogen and fibrin degradation products, and immune complexes were monitored. Complement and acute phase reactants are increased in a majority of patients. Continuing inflammation and release of inflammatory mediators could be responsible for poor healing that commonly occurs in spinal cord injury. Urinary tract and other infections are associated with some but not all of the protein abnormalities. These proinflammatory proteins may contribute to the lack of healing of spinal transection.
Simultaneous Detection of Measles Virus, Rubella Virus, and Parvovirus B19 by Using Multiplex PCR (2002)

We describe here a multiplex reverse transcription-PCR (RTMNPCR) assay designed to detect and differentiate measles virus, rubella virus, and parvovirus B19. Serial dilution experiments with vaccine strains that compared cell culture isolation of measles in B95 cells and rubella in RK13 cells showed sensitivity rates of 0.004 50% tissue culture infective dose (TCID(50)) for measles virus and 0.04 TCID(50) for rubella virus. This RTMNPCR can detect as few as 10 molecules for measles virus and rubella virus and one molecule for parvovirus B19 in dilution experiments with plasmids containing inserts of the primary reaction amplification products. Five pharyngeal exudates from measles patients and 2 of 15 cerebrospinal fluid samples from measles-related encephalitis were found to be positive for measles virus by this RTMNPCR. A total of 3 of 27 pharyngeal exudates from vaccinated children and 2 pharyngeal exudates, plus one urine sample from a case of congenital rubella syndrome, were found to be positive for rubella virus by RTMNPCR, whereas 16 of 19 sera from patients with erythema infectiosum were determined to be positive for parvovirus B19 by RTMNPCR. In view of these results, we can assess that this method is a useful tool in the diagnosis of these three viruses and could be used as an effective surveillance tool in measles eradication programs.
Gene knockout and transgenic technologies in risk assessment: The next generation (1997)

Transgenic and knockout mice have been proposed as substitutes for one of the standard 2-yr rodent assays. The advantages of using genetically engineered mouse models is that fewer mice are needed, the time to develop disease is greatly reduced, and the mice are predisposed to developing cancer by virtue of gain or loss of functions. The models currently being used have yielded a large amount of data and have proved to be informative for risk assessment; however, they are still far from ideal. In fact, they inherently do not reflect the complexity of mutation and carcinogenesis in humans. Recent advances in technology and the creation of new knockout mice may produce more useful and more sensitive models. This review covers two recent advances in technology--inducible and regulatable gene expression and targeted genetic modifications in the genome--that will allow us to make better models. I also discuss new gene deletion and transgenic mouse models and their potential impact on risk-assessment assays. These models are presented in the context of four basic components or events that occur in the multistep process leading to cancer: maintenance of gene expression patterns, genome stability and DNA repair, cell-cell communication and signaling, and cell-cycle regulation. Finally, surrogate markers and utility in risk assessment are also discussed. This review is meant to stimulate further discussion in the field and to generate excitement about working toward the next generation of risk-assessment models.
Life-Long Echoes – A Critical Analysis of the Developmental Origins of Adult Disease Model (2004)

The hypothesis that there is a developmental component to subsequent adult disease initially arose from epidemiological findings relating birth size to either indices of disease risk or actual disease prevalence in later life. While components of the epidemiological analyses have been challenged, there is strong evidence that developmental factors contribute to the later risk of metabolic disease--including insulin resistance, obesity, and heart disease--as well as have a broader impact on osteoporosis, depression and schizophrenia. We suggest that disease risk is greater when there is a mismatch between the early developmental environment (i.e., the phase of developmental plasticity) versus that experienced in mature life (i.e., adulthood), and that nutritional influences are particularly important. It is also critical to distinguish between those factors acting during the developmental phase that disrupt development from those influences that are less extreme and act through regulated processes of epigenetic change. A model of the relationship between the developmental and mature environment is proposed and suggests interventional strategies that will vary in different population settings.
Flow Injection Renewable Surface Immunoassay: A New Approach to Immunoanalysis with Fluorescence Detection (1994)

This paper introduces a new methodology of carrying out heterogeneous immunoassays automatically, using a flow injection technique on a renewable surface. Flow injection renewable surface immunoassay (FIRSI) relies on the use of a minute amount of beads to form a reactive surface, which is interrogated by fluorescence spectrometry. Following the assay, on-line regeneration normally used in flow based immunoassays is avoided by fluidically removing the spent reactive surface and replacing it with a new layer of beads. This allows the monitoring of antibody-antigen binding at its early stages, dramatically increases the sampling frequency of a serial assay, and eliminates the problems associated with a decrease in surface reactivity caused by repetitive use. A model system utilizing anti-mouse IgG1-coated beads and mouse IgG1 protein is used to characterize the method with respect to reproducibility, flow rate, contact time, and amount of beads.
Studies on the regulatory domain of Ca2+/calmodulin-dependent protein kinase II by expression of mutated cDNAs in Escherichia coli. (1991)

The cDNAs encoding the alpha and beta subunits of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) were ligated into the bacterial expression vector pET and expressed in Escherichia coli. The bacterially expressed alpha and beta subunits exhibited Ca2+/calmodulin-dependent activity and were easily purified to apparent homogeneity from cell extracts. To determine the minimum size required for catalytic activity and the properties of the calmodulin-binding domain, mutated CaM kinase II cDNAs were expressed in E. coli and the enzymatic property of expressed proteins was examined. The replacement of Thr-286 of the alpha subunit with the negatively charged amino acid Asp or that of Arg-283 with the neutral amino acid Gly induced the partially Ca2+ independent activity. The mutant enzymes alpha-I(delta 283-478) and alpha-II(delta 359-478), which truncated the C-terminal region of the alpha subunit, exhibited CaM kinase II activity and the activities of alpha-I(delta 283-478) and alpha-II(delta 359-478) were completely independent of and partially dependent on Ca2+ and calmodulin, respectively. However, the truncated protein alpha(delta 250-478), which was only 33 amino acids shorter than the alpha-I(delta 283-478) protein had no enzymatic activity, indicating that alpha-I(delta 283-478) was close to the minimum size of the active form. The mutant enzyme alpha(delta 291-315), which lacked the calmodulin-binding domain exhibited Ca2+ independent activity. The molecular mass was, however, smaller than that expected from the amino acid sequence. The mutant enzyme alpha(delta 304-315), which lacked the C-terminal half of the calmodulin-binding domain of the alpha subunit, however, exhibited Ca(2+)-independent activity without a reduction in molecular size, indicating that residues 304-315 of the alpha subunit constituted the core calmodulin-binding domain.
Expression and function of pro‐inflammatory interleukin IL‐17 and IL‐17 receptor in normal, benign hyperplastic, and malignant prostate (2003)

Activated BPH-T-cells abundantly express IL-17. The increase of IL-17 in BPH-tissues goes hand in hand with elevated levels of IL-15, a pro-inflammatory cytokine with T-cell growth factor properties. A clinical relevance of increased IL-17 expression under pathological conditions is suggested by the demonstration of significant upregulation of IL-6 and IL-8 production of prostatic SC by IL-17.
Wide-bandwidth distributed Bragg reflectors usingoxide/GaAs multilayers (1994)

The authors have designed and fabricated a wide bandwidth high reflectivity distributed Bragg reflector (DBR) using the native oxide of AlAs as the low refractive index layer and GaAs as the high refractive index layer. Results show that the refractive index of the native oxide is 1.55±0.01, the peak reflectivity of the DBR is over 99%, and the reflectivity bandwidth is ~460 nm.
Development of CMOS Compatible Bonding Material and Process for Wafer Level MEMS Packaging Application under Harsh Environment (2012)

CMOS compatible metallic hermetic sealing using Al-Ge eutectic alloy for packaging MEMS devices for harsh environments has been developed. The effects of various bonding parameters on the bond quality have been extensively reported. The reliability of this eutectic joint subjected to high operating temperatures involved in deep oil well logging application has been investigated with the specific focus on shear strength and hermeticity. A new configuration for stacking Al-Ge thin films has been demonstrated in order to tackle the issue of loss of Ge prior to bonding since native Ge oxides are soluble in DI water. The impact of solid-state aging prior to Al-Ge eutectic bonding has also been investigated. It has been determined that solid-state aging prior to Al-Ge eutectic bonding is a pre- requisite in order to attain a reliable hermetic sealing. Furthermore, the changes in microstructure with respect to thermal aging at 300°C up to 500 hours have also been presented since the minimum requested continuous operating time by the energy industry is 500 hours at 300°C. No thermal degradation of the Al-Ge eutectic joint at 300°C for 500 hours was observed. This could be credited to its composite microstructure. Thus, the overall conclusion of this work is that Al-Ge eutectic bonding is a prospective candidate for this application.
High efficiency GaAs-on-Si solar cells with high V/sub oc/ using graded GeSi buffers (2002)

Single junction AlGaAs/GaAs and InGaP/GaAs solar cells and test structures have been grown by molecular beam epitaxy (MBE) and metalorganic chemical vapor deposition (MOCVD), respectively, on Si wafers coated with compositionally-graded GeSi buffers. The combination of controlled strain relaxation within the GeSi buffer and monolayer-scale control of the Ill-V layer nucleation is shown to reproducibly generate minority carrier lifetimes exceeding 10 nanoseconds within GaAs overlayers. The III-V layers are free of long-range antiphase domain disorder, with threading dislocation densities in the high-10/sup 5/ cm/sup -2/ range, consistent with the low residual dislocation density in the Ge cap of the graded buffer structure. Single junction GaAs cells grown by both MBE and MOCVD on the Ge/GeSi/Si substrates demonstrated high V/sub oc/ values for GaAs cells grown on Si. Record V/sub oc/ values for MOCVD-grown single junction InGaP/GaAs cells exceeded 980 mV (AMO) with fill factors of 0.79. Additionally, external quantum efficiency data indicates no degradation in carrier collection from GaAs homoepitaxial cells for current single-junction cell designs grown by MBE. Based on these results, cell efficiencies in excess of 18.5% under AM0 conditions should be attainable with cell designs demonstrating state of the art J/sub sc/ values. Such cell performance demonstrates the potential and viability of graded GeSi buffers for the development of Ill-V cells on Si wafers.
Complex Formation of Amphotericin B in Sterol-Containing Membranes As Evidenced by Surface Plasmon Resonance (2008)

Amphotericin B (AmB) is a membrane-active antibiotic that increases the permeability of fungal membranes. Thus, the dynamic process of its interaction with membranes poses intriguing questions, which prompted us to elaborate a quick and reliable method for real-time observation of the drug's binding to phospholipid liposomes. We focused on surface plasmon resonance (SPR) and devised a new modification method of sensor chips, which led to a significant reduction in the level of nonspecific binding of the drug in a control lane. With this method in hand, we examined the affinity of AmB for various membrane preparations. As expected, AmB exhibited much higher affinity for sterol-containing palmitoyloleoylphosphatidylcholine membranes than those without sterol. The sensorgrams recorded under various conditions partly fitted theoretical curves, which were based on three interaction models. Among those, a two-state reaction model reproduced well the sensorgram of AmB binding to an ergosterol-containing membrane; in this model, two states of membrane-bound complexes, AB and AB*, are assumed, which correspond to a simple binding to the surface of the membrane (AB) and formation of another assembly in the membrane (AB*) such as an ion channel complex. Kinetic analysis demonstrated that the association constant in ergosterol-containing POPC liposomes is larger by 1 order of magnitude than that in the cholesterol-containing counterpart. These findings support the previous notion that ergosterol stabilizes the membrane-bound assembly of AmB.
Intermittent Administration of MEK Inhibitor GDC-0973 plus PI3K Inhibitor GDC-0941 Triggers Robust Apoptosis and Tumor Growth Inhibition (2011)

Combinations of MAP/ERK kinase (MEK) and phosphoinositide 3-kinase (PI3K) inhibitors have shown promise in preclinical cancer models, leading to the initiation of clinical trials cotargeting these two key cancer signaling pathways. GDC-0973, a novel selective MEK inhibitor, and GDC-0941, a class I PI3K inhibitor, are in early stage clinical trials as both single agents and in combination. The discovery of these selective inhibitors has allowed investigation into the precise effects of combining inhibitors of two major signaling branches downstream of RAS. Here, we investigated multiple biomarkers in the mitogen-activated protein kinase (MAPK) and PI3K pathway to search for points of convergence that explain the increased apoptosis seen in combination. Using washout studies in vitro and alternate dosing schedules in mice, we showed that intermittent inhibition of the PI3K and MAPK pathway is sufficient for efficacy in BRAF and KRAS mutant cancer cells. The combination of GDC-0973 with the PI3K inhibitor GDC-0941 resulted in combination efficacy in vitro and in vivo via induction of biomarkers associated with apoptosis, including Bcl-2 family proapoptotic regulators. Therefore, these data suggest that continuous exposure of MEK and PI3K inhibitors in combination is not required for efficacy in preclinical cancer models and that sustained effects on downstream apoptosis biomarkers can be observed in response to intermittent dosing.
Detrusor inhibition induced by stimulation of pudendal nerve afferents (1986)

Abstract A critical analysis of therapeutic vesicoinhibitory electrical stimulation is presented based on a study of ten patients with suprasacral spinal cord lesions and detrusor hyperreflexia. The detrusor contraction was either completely abolished, or the threshold of the contraction significantly increased, with electrical stimulation delivered to the dorsal nerves of penis (or clitoris) via surface electrodes. A current strength of 0.09 to 3.5 times the bulbocavernosus reflex threshold was used.
Simultaneous inhibition of two regulatory T-cell subsets enhanced Interleukin-15 efficacy in a prostate tumor model (2012)

IL-15 has potential as an immunotherapeutic agent for cancer treatment because of its ability to effectively stimulate CD8 T cell, natural killer T cell, and natural killer cell immunity. However, its effectiveness may be limited by negative immunological checkpoints that attenuate immune responses. Recently a clinical trial of IL-15 in cancer immunotherapy was initiated. Finding strategies to conquer negative regulators and enhance efficacy of IL-15 is critical and meaningful for such clinical trials. In a preclinical study, we evaluated IL-15 combined with antibodies to block negative immune regulator cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death ligand 1 (PD-L1) in an established murine transgenic adenocarcinoma of mouse prostate (TRAMP)-C2 prostate tumor model. IL-15 treatment resulted in a significant prolongation of survival in tumor-bearing animals. Coadministration of anti-PD-L1 or anti-CTLA-4 singly with IL-15 did not improve animal survival over that of IL-15 alone. However, simultaneous administration of IL-15 with anti-CTLA-4 and anti-PD-L1 was associated with increased numbers of tumor antigen-specific tetramer-positive CD8 T cells, increased CD8 T-cell tumor lytic activity, augmented antigen-specific IFN-γ release, decreased rates of tumor growth, and improved animal survival compared with IL-15 alone. Furthermore, triple combination therapy was associated with inhibition of suppressive functions of CD4(+)CD25(+) regulatory T cells and CD8(+)CD122(+) regulatory T cells. Thus, simultaneous blockade of CTLA-4 and PD-L1 protected CD4 and/or CD8 T-cell activity from these regulatory T cells. Combining the immune stimulatory properties of IL-15 with simultaneous removal of two critical immune inhibitory checkpoints, we showed enhancement of immune responses, leading to increased antitumor activity.
Polycation-based DNA complexes for tumor-targeted gene delivery in vivo (1999)

Background Efficient and target-specific in vivo gene delivery is a major challenge in gene therapy. Compared to cell culture application, in vivo gene delivery faces a variety of additional obstacles such as anatomical size constraints, interactions with biological fluids and extracellular matrix, and binding to a broad variety of non-target cell types. Methods Polycation-based vectors, including adenovirus-enhanced transferrinfection (AVET) and transferrin-polyethylenimine (Tf-PEI), were tested for gene delivery into subcutaneously growing tumors after local and systemic application. DNA biodistribution and reporter gene expression was measured in the major organs and in the tumor. Results Gene transfer after intratumoral application was 10–100 fold more efficient with Tf-PEI/DNA or AVET complexes in comparison to naked DNA. Targeted gene delivery into subcutaneously growing tumors after systemic application was achieved using electroneutral AVET complexes and sterically stabilized PEGylated Tf-PEI/DNA complexes, whereas application of positively charged polycation/DNA complexes resulted in predominant gene expression in the lungs and was associated by considerable toxicity. Conclusion For systemic application, the physical and colloidal parameters of the transfection complexes, such as particle size, stability, and surface charge, determine DNA biodistribution, toxicity, and transfection efficacy. By controlling these parameters, DNA biodistribution and gene expression can be targeted to different organs. Copyright © 1999 John Wiley & Sons, Ltd.