gebhart/patrepeval huggingface dataset:
Autocrine Regulation of Inducible Nitric-oxide Synthase in Macrophages by Atrial Natriuretic Peptide (1998)

Atrial natriuretic peptide (ANP), a cardiovascular hormone, has been shown to inhibit synthesis of nitric oxide in lipopolysaccharide (LPS)-activated mouse bone marrow-derived macrophages via activation of its guanylate cyclase-coupled receptor. The goal of the present study was to elucidate the potential sites of inducible nitric-oxide synthase (iNOS) regulation affected by ANP and revealed the following. 1) ANP and dibutyryl-cGMP did not inhibit catalytic iNOS activity measured by the conversion rate of L-[3H]arginine to L-[3H]citrulline in homogenates of LPS-treated cells. 2) Pretreatment of cells with ANP dose-dependently reduced the LPS-induced L-[3H]citrulline production that has been shown to be due to reduced iNOS protein levels detected by Western blot. 3) ANP does not alter the ratio of catalytically active iNOS dimer versus inactive iNOS monomer considered to be a major post-translational regulatory mechanism for the enzyme. 4) Macrophages exposed to ANP display decreased LPS-induced iNOS mRNA levels. 5) Importantly, two basic mechanisms seem to be responsible for this observation, i.e. ANP specifically induced acceleration of iNOS mRNA decay and ANP reduced binding activity of NF-kappaB, the transcription factor predominantly responsible for LPS-induced iNOS expression in murine macrophages. Moreover, 6) ANP acts via an autocrine mechanism since recently ANP was shown to be secreted by LPS-activated macrophages, and we demonstrated here that LPS-induced NO synthesis was increased after blocking the binding of endogenous ANP by a receptor antagonist. These observations suggest ANP as a new autocrine macrophage factor regulating NO synthesis both transcriptionally and post-transcriptionally. ANP may help to balance NO production of activated macrophages and thus may allow successful immune response without adverse effects on host cells.
Comparison of DPP-4 Inhibitors (2013)

(incretin effect) , 1960 [1]. [2], [3]. GIP (glucosedependent insulinotropic peptide), GLP-1 (glucagon like peptide-1) DPP-4 (dipeptidyl peptidase-4) GLP-1 agonist DPP-4 . GLP-1 agonist ( ) , DPP-4 GLP-1 agonist . DPP-4 2 ,
SNMP Security Protocols (1992)

This document specifies an IAB standards track protocol
Heat Shock Protein 90 (HSP90) Is a Rational Therapeutic Target in Diffuse Large B-Cell Lymphoma. (2006)

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease that is currently treated with a homogeneous approach based on empiric combination chemotherapy. To elucidate molecular differences in DLBCL subsets and identify more rational treatment targets, coordinate transcriptional profiling was used to define three groups of DLBCLs: “Oxidative Phosphorylation” (OxPhos), “B-cell Receptor/Proliferation” (BCR), and “Host Response” (HR). Of interest, the HSP90 α and β isoforms were differentially expressed in the DLBCL subsets; the stress-induced α isoform was more abundant in OxPhos tumors (p &amp;lt; .0001) whereas the constitutively expressed β isoform was increased in BCR DLBCLs (p &amp;lt; .0001). HSP90 α and β differ in the length of their N-termini but share a common ATP binding domain, the target site for recently developed HSP90 inhibitors, such as IPI-504 (Infinity Pharmaceuticals, Cambridge, MA). Although differential HSP90 isoform expression likely reflects underlying biological differences in the DLBCL subsets, the shared ATP binding domain suggests that both isoforms, and the majority of DLBCLs, may be effectively targeted with HSP90 inhibitors. For these reasons, we determined the IC50 and cytotoxic potential of IPI-504 in an extensive series of DLBCL cell lines. IPI-504 inhibited the proliferation of DLBCL cell lines at IC50s ranging from 0.04 μM in the most sensitive line to 12.67 μM in the most resistant line. Annexin V/PI staining revealed that IPI-504 was cytotoxic to most DLBCL cell lines at low micromolar doses; even cell lines that were relatively resistant to IPI-504 at lower doses (2 μM) underwent apoptosis with prolonged exposure to increased IPI-504 doses (72 hrs. and 8 μM). Cell lines that were most sensitive to IPI-504 expressed high levels of a major HSP90 client protein, pAKT, and exhibited a dose-dependent decrease in pAKT levels following IPI-504 treatment. For these reasons, we assessed the efficacy of IPI-504 in association with a PI3K/AKT pathway inhibitor, LY24009, in the DLBCL panel. Combined treatment with the HSP90 and PI3K inhibitors was highly synergistic (Method of Chou and Talalay; Calcusyn software, Biosoft, Ferguson, MO), inhibiting cellular proliferation by over 95% in evaluated DLBCL cell lines. In contrast, the combination of concurrent IPI-504 and an empiric chemotherapeutic agent, doxorubicin, was antagonistic, underscoring the importance of rational combination therapy. We conclude that: 1) HSP90 isoforms are differentially expressed in primary DLBCL subsets; and 2) inhibition of HSP90, via the conserved ATP binding domain, leads to dose-dependent apoptosis that is associated with depletion of pAKT in DLBCL cell lines. The HSP90 inhibitor IPI-504 possesses both single-agent efficacy as well as synergy when combined with PI3K inhibitors, suggesting that this rational targeted approach warrants further clinical investigation.
Multimodal interaction for 2D and 3D environments [virtual reality] (1999)

The allure of immersive technologies is undeniable. Unfortunately, the user's ability to interact with these environments lags behind the impressive visuals. In particular, it's difficult to navigate in unknown visual landscapes, find entities, access information and select entities using six-degrees-of-freedom (6-DOF) devices. We believe multimodal interaction-specifically speech and gesture-will make a major difference in the usability of such environments.
Evaluation of Long-term Transgene Expression in piggyBac-Modified Human T Lymphocytes (2012)

The piggyBac transposon system is a promising nonviral method to genetically modify T cells for immunotherapeutic applications. To evaluate the regulation and stability of transgene expression in human T cells modified with piggyBac-transposons, peripheral blood mononuclear cells were nucleofected with transposase and an enhanced green fluorescence protein (eGFP)-expressing transposon. Single-cell clones that were subsequently stimulated and expanded exhibited homogenous eGFP expression for >26 weeks in culture. CD3 stimulation of the T-cell receptor together with CD28-mediated costimulation resulted in an approximate 10-fold transient increase in eGFP expression, but immunomodulatory cytokines, including interferon-γ, interleukin-12, interleukin-4, and transforming growth factor-β, did not alter transgene expression in actively dividing, activated, or resting T cells. Epigenetic modification with 5-azacytidine or trichostatin-A increased transgene expression indicating that piggyBac-mediated transgene expression could be modulated by methylation or histone acetylation, respectively. We performed transposon copy number analysis of populations of stably transfected T cells, comparing transposon plasmids of 5.6 and 3.5 kb. The smaller vector achieved an average of 22 transposon copies per cell, whereas the larger vector achieved 1.6 copies/cell, implying that transposon copy number can be engineered to be low or high depending on the vector used. Our results provide important insight into the ability of piggyBac to achieve stable genetic modification of T cells for immunotherapy applications and how transgene expression might be regulated by TCR activation, cytokines, and epigenetic mechanisms.
Adenovirus-mediated mda-7 (IL24) gene therapy suppresses angiogenesis and sensitizes NSCLC xenograft tumors to radiation (2004)

Melanoma differentiation-associated gene-7 (mda-7), recently classified as interleukin-24 (approved gene symbol IL24), is thought to be a tumor suppressor gene based on the loss of its expression in many different types of cancer. Gene therapy by adenovirus-mediated mda-7 (Ad-mda7) gene transfer has been shown to inhibit the growth of several different tumor cell lines, in vitro and in vivo. We previously demonstrated that Ad-mda7 radiosensitized non-small-cell lung cancer (NSCLC) cell lines by enhancing an apoptosis pathway through the activation of JNK and c-Jun. In the present study, we investigated the efficacy of intratumoral administration of Ad-mda7 combined with ionizing radiation for treating A549 xenograft tumors in nude mice. Substantial and long-lasting inhibition of tumor growth was evident following the combined treatment. Histological examination revealed marked reduction of angiogenic factors (bFGF, VEGF) and microvessel density and enhanced apoptosis in the tumors treated with the combination therapy compared to those treated with Ad-mda7 alone or radiation alone. To confirm the radiosensitizing effect of secreted MDA-7 protein, we performed clonogenic survival assays using human umbilical vein endothelial cells (HUVECs), A549 cells, and normal human lung fibroblasts, CCD16 cells, pretreated with the conditioned medium from 293 cells that had been stably transfected with mda-7 or a control vector. The results showed that MDA-7 protein sensitized HUVECs to ionizing radiation but not A549 cells or CCD16 cells. Our results suggest that Ad-mda7 in combination with radiation enhances apoptosis in the tumors and that secreted MDA-7 protein inhibits angiogenesis by sensitizing endothelial cells to ionizing radiation without affecting other normal cells. We conclude that the combination of mda-7 gene therapy and radiotherapy may be a feasible and effective strategy for treatment of NSCLC.
Multiple Cleavage Activities of Endonuclease V from Thermotoga maritima:  Recognition and Strand Nicking Mechanism (2001)

Endonuclease V is a deoxyinosine 3'-endonuclease which initiates removal of inosine from damaged DNA. A thermostable endonuclease V from the hyperthermophilic bacterium Thermotoga maritima has been cloned and expressed in Escherichia coli. The DNA recognition and reaction mechanisms were probed with both double-stranded and single-stranded oligonucleotide substrates which contained inosine, abasic site (AP site), uracil, or mismatches. Gel mobility shift and kinetic analyses indicate that the enzyme remains bound to the cleaved inosine product. This slow product release may be required in vivo to ensure an orderly process of repairing deaminated DNA. When the enzyme is in excess, the primary nicked products experience a second nicking event on the complementary strand, leading to a double-stranded break. Cleavage at AP sites suggests that the enzyme may use a combination of base contacts and local distortion for recognition. The weak binding to uracil sites may preclude the enzyme from playing a significant role in repair of such sites, which may be occupied by uracil-specific DNA glycosylases. Analysis of cleavage patterns of all 12 natural mismatched base pairs suggests that purine bases are preferrentially cleaved, showing a general hierarchy of A = G > T > C. A model accounting for the recognition and strand nicking mechanism of endonuclease V is presented.
Direct annotation: a drag-and-drop strategy for labeling photos (2002)

Annotating photographs is such a time-consuming, tedious and error-prone data entry task that it discourages most owners of personal photo libraries. By allowing the user to drag labels, such as personal names, from a scrolling list and drop them onto a photo, we believe we can make the task faster, easier and more appealing. Since the names are entered in a database, searching for all photos of a friend or family member is dramatically simplified. We describe the user interface design and the database schema to support direct annotation, as implemented in our PhotoFinder prototype.
Effects of receptor-selective retinoids on CYP26 gene expression and metabolism of all-trans-retinoic acid in intestinal cells. (2001)

Retinoids mediate most of their function via interaction with retinoid receptors [retinoic acid receptors (RARs) and retinoid X receptors (RXRs)], which act as ligand-activated transcription factors controlling the expression of a number of target genes. The complex mechanistic pattern of retinoid-induced effects on gene expression of CYP26 and intestinal metabolism of all-trans-retinoic acid (RA) was investigated here by studying the effects of retinoid ligands with relative selectivity for binding and transactivation of the retinoid acid receptors, RARs and RXRs, in human intestinal Caco-2 cells. We show here that CYP26 is expressed in human duodenum and colon. In Caco-2 cells not only all-trans-RA but also synthetic agonists of the RAR induced intestinal CYP26 gene expression and all-trans-RA metabolism as well. The RARalpha ligand Am580 induced the CYP26 gene expression more than the RARbeta ligand CD2019 or the RARgamma ligand CD437 suggesting the highest specificity for RARalpha on intestinal CYP26 gene regulation. RXR ligands alone did not induce CYP26 gene expression or RA metabolism in Caco-2 cells at all. But together with the RARalpha ligand, Am580, there were enhanced effects on the induction of CYP26 gene expression and on the induction of the metabolism of all-trans-RA. We conclude that gene regulation of CYP26 and the metabolism of all-trans-RA in intestinal cells is regulated through RXR and RAR heterodimerization. When coadministered, RAR agonists showed the highest potency for CYP26 gene regulation. Receptor-selective retinoids showed enhanced effects on induction of CYP26 gene expression and all-trans-retinoic acid metabolism.
LIPOLYSIS:Contribution from Regional Fat (1997)

In vitro studies of adipocytes taken from different body fat regions suggest substantial differences in lipolysis between intra-abdominal, lower-body subcutaneous, and abdominal subcutaneous regions. Gender and obesity appear to influence these regional differences. In situ measurements of glycerol release from adipose tissue provided further evidence that regional heterogeneity of lipolysis occurs in humans. In vivo studies of regional free fatty acid (FFA) release have confirmed that adipose tissue lipolysis varies between upper- and lower-body fat. Release of FFA from lower-body adipose tissue is less than that from upper-body adipose tissue in both obese and non-obese men and women. In non-obese men and women, meal ingestion suppresses FFA release from all adipose tissue regions, and adrenergic stimulation activated FFA release from different sites in a gender-specific fashion. Significant regional and gender differences in adipose tissue lipolysis occur in humans, and this could contribute to differences in the health effects of adipose tissue and could theoretically influence body fat distribution.
Multifunctional Dendronized Peptide Polymer Platform for Safe and Effective siRNA Delivery (2013)

In this study, we designed and synthesized a biodegradable dendronized polypeptide (denpol) platform for delivery of small interfering RNA (siRNA). The novel denpol architecture combines the multivalency of dendrimers and conformational flexibility of linear polymers for optimal siRNA binding. Multifunctional amino acids were incorporated onto the dendrons and the structure was tuned both systematically and combinatorially to select optimal vectors. By screening a focused library, we identified several denpols that can effectively deliver siRNA to NIH 3T3 cells in vitro and exhibit minimal toxicity. For comparison, the best-performing denpol showed significantly improved transfection efficiency over Lipofectamine in serum-containing media. Fluorescence intracellular trafficking studies indicated that amphiphilicity is important for cell uptake and that the buffering capacity of histidine facilitates endosomal membrane rupture and therefore enhances the transfection efficiency. The combination of high delivery efficiency in serum and low cytotoxicity suggests the denpol system as a promising new carrier for siRNA delivery.
Various bonding configurations of transition-metal atoms on carbon nanotubes: Their effect on contact resistance (2000)

Our investigations reveal that the bonding of the transition-metal atoms on a single-wall carbon nanotube (SWCN) depends on the detailed contact conditions. On the basis of our results, we suggest that the early 3-d elements (Sc, Ti, and V) can be expected to be good candidates for making metal–SWCN contacts of low resistance, while contacts employing the late 3-d elements (Fe, Co, and Ni) and Cu are expected to exhibit large contact resistance.
Enhancement of cell-mediated immunity in melanoma patients immunized with murine anti-idiotypic monoclonal antibodies (MELIMMUNE) that mimic the high molecular weight proteoglycan antigen. (1998)

The purpose of this study was to determine whether a combination of two anti-idiotypic antibodies that mimic the high molecular weight proteoglycan antigen found on most melanoma tumors was capable of enhancing cellular immunity in vaccinated high-risk patients with melanoma. Twenty-eight stage I-IV high-risk patients with melanoma were immunized with a mixture of variable concentrations of MELIMMUNE-1 and MELIMMUNE-2, along with the adjuvant SAF-m, using two immunization schedules. Peripheral blood mononuclear cells were collected before the first immunization and 4 weeks after the final immunization and tested for in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 and for cytotoxicity against 51Cr-labeled target cell lines. Additionally, supernatants from in vitro proliferation cultures were tested for interleukin 10 and IFN-gamma levels. Significant in vitro proliferation to MELIMMUNE-1 and MELIMMUNE-2 were observed in postimmunization samples but not in prevaccination samples. The mean stimulation index for MELIMMUNE-2 (33.7 +/- 0.6) was significantly higher than that for MELIMMUNE-1 (13.9 +/- 0.3; P < 0.025). Supernatants obtained from 78% of the in vitro stimulated cultures pre- or postvaccination contained significant levels of interleukin 10 (range, 0.43-142 pg/ml), whereas IFN-gamma levels were elevated in 53% of postvaccination samples (range, 3-245 pg/ml) but not prevaccination samples. More importantly, we were able to generate specific CTL responses in 43% of the patients, which correlated with elevated IFN-gamma levels. These results indicate that MELIMMUNE enhances cell-mediated immunity in patients with melanoma.
Optimization of oxidative folding methods for cysteine‐rich peptides: a study of conotoxins containing three disulfide bridges (2010)

The oxidative folding of small, cysteine-rich peptides to selectively achieve the native disulfide bond connectivities is critical for discovery and structure-function studies of many bioactive peptides. As the propensity to acquire the native conformation greatly depends on the peptide sequence, numerous empirical oxidation methods are employed. The context-dependent optimization of these methods has thus far precluded a generalized oxidative folding protocol, in particular for peptides containing more than two disulfides. Herein, we compare the efficacy of optimized solution-phase and polymer-supported oxidation methods using three disulfide-bridged conotoxins, namely µ-SIIIA, µ-KIIIA and ω-GVIA. The use of diselenide bridges as proxies for disulfide bridges is also evaluated. We propose the ClearOx-assisted oxidation of selenopeptides as a fairly generalized oxidative folding protocol.
Enhancing Mammalian Target of Rapamycin (mTOR)–Targeted Cancer Therapy by Preventing mTOR/Raptor Inhibition-Initiated, mTOR/Rictor-Independent Akt Activation (2008)

It has been shown that mammalian target of rapamycin (mTOR) inhibitors activate Akt while inhibiting mTOR signaling. However, the underlying mechanisms and the effect of the Akt activation on mTOR-targeted cancer therapy are unclear. The present work focused on addressing the role of mTOR/rictor in mTOR inhibitor-induced Akt activation and the effect of sustained Akt activation on mTOR-targeted cancer therapy. Thus, we have shown that mTOR inhibitors increase Akt phosphorylation through a mechanism independent of mTOR/rictor because the assembly of mTOR/rictor was inhibited by mTOR inhibitors and the silencing of rictor did not abrogate mTOR inhibitor-induced Akt activation. Moreover, Akt activation during mTOR inhibition is tightly associated with development of cell resistance to mTOR inhibitors. Accordingly, cotargeting mTOR and phosphatidylinositol 3-kinase/Akt signaling prevents mTOR inhibition-initiated Akt activation and enhances antitumor effects both in cell cultures and in animal xenograft models, suggesting an effective cancer therapeutic strategy. Collectively, we conclude that inhibition of the mTOR/raptor complex initiates Akt activation independent of mTOR/rictor. Consequently, the sustained Akt activation during mTOR inhibition will counteract the anticancer efficacy of the mTOR inhibitors.
Effects of Branched-Chain Amino Acids Supplementation in Patients With Cirrhosis and a Previous Episode of Hepatic Encephalopathy: A Randomized Study (2011)

Diet supplementation with BCAA after an episode of HE does not decrease recurrence of HE. However, supplementation with BCAA improves minimal HE and muscle mass. Identification of risk factors for recurrence of HE may allow the development of new preventive therapies that could decrease the neuropsychological sequelae of repeated episodes of HE.
Nearfield of a large acoustic transducer. Part III: General results (1984)

The theory presented in two previous papers [Part I, J. Acoust. Soc. Am. 72, 1056–1061 (1982) and Part II, J. Acoust. Soc. Am. 74, 1013–1020 (1983)] is further developed and generalized to the case of no axisymmetry. Emphasis is given to a study of the parametric generated sound. Asymptotic formulas are presented, showing the development of the difference frequency sound from the source (transducer) into the farfield. New numerical results for the axisymmetric case are given for the linear and the parametric field of a source which is not radiating uniformly. New experimental results are reported and compared with the theory.
Bandwidth allocation for multiservice access on EPONs (2005)

Ethernet passive optical networks are a low-cost high-speed solution to the bottleneck problem of the broadband access network. A major characteristic of EPONs is the shared upstream channel among end users, mandating efficient medium access control to facilitate statistical multiplexing and provision multiple services for different types of traffic. This article addresses and provides an overview of the upstream bandwidth allocation issue for multiservice access provisioning over EPONs, and proposes an algorithm for dynamic bandwidth allocation with service differentiation. Based on the multipoint control protocol (MPCP) and bursty traffic prediction, our algorithm enhances QoS metrics such as average frame delay, average queue length, and frame loss probability over other existing protocols.