gebhart/patrepeval huggingface dataset:
Differential induction of cytolytic susceptibility by E1A, myc, and ras oncogenes in immortalized cells (1989)

The E1A oncogene of adenovirus serotypes 2 and 5 induces susceptibility to the cytolytic effects of natural killer lymphocytes and activated macrophages when expressed in infected and transformed mammalian cells (cytolysis-susceptible phenotype). E1A and the oncogenes v-myc, long-terminal-repeat-promoted c-myc, and activated c-ras share the ability to immortalize transfected low-passage rodent cells. The cytolytic phenotypes of well-characterized rodent cell lines immortalized by these three oncogenes were defined. In contrast to target cells expressing the intact E1A gene, myc- and ras-expressing, immortalized primary transfectants were resistant to lysis by both types of killer cell populations. The same patterns of susceptibility (E1A) and resistance (myc and ras) to cytolysis were observed in oncogene-transfected continuous rat (REF52) and mouse (NIH 3T3) cell lines, indicating that differences in the cytolytic phenotypes associated with expression of these oncogenes are not due to cell selection during immortalization. The results suggest that the E1A oncogene may possess a functional domain that is different from those of other oncogenes, such as myc and ras, and that the activity linked to this postulated domain is dissociable from the process of immortalization.
Cell‐free complements in vivo expression of the E. coli membrane proteome (2007)

Reconstituted cell-free (CF) protein expression systems hold the promise of overcoming the traditional barriers associated with in vivo systems. This is particularly true for membrane proteins, which are often cytotoxic and due to the nature of the membrane, difficult to work with. To evaluate the potential of cell-free expression, we cloned 120 membrane proteins from E. coli and compared their expression profiles in both an E. coli in vivo system and an E. coli-derived cell-free system. Our results indicate CF is a more robust system and we were able to express 63% of the targets in CF, compared to 44% in vivo. To benchmark the quality of CF produced protein, five target membrane proteins were purified and their homogeneity assayed by gel filtration chromatography. Finally, to demonstrate the ease of amino acid labeling with CF, a novel membrane protein was substituted with selenomethionine, purified, and shown to have 100% incorporation of the unnatural amino acid. We conclude that CF is a novel, robust expression system capable of expressing more proteins than an in vivo system and suitable for production of membrane proteins at the milligram level.
Coding mode adapted overlapped block motion compensation in H.264 (2006)

In the video coding standard H.264/AVC, various coding tools have been proposed to improve the efficiency of motion compensation (MC). In this paper, the overlapped block motion estimation and compensation (OBME/MC) is applied to the framework of H.264/AVC encoder to further increase the coding performance. Our main contribution is to adapt the overlapped weighting factors to the coding mode of neighboring blocks, thus allowing efficient integration of OBMC with variable block size motion compensation in H.264. The result shows that integration of OBMC will provide PSNR gain up to 0.21dB when the encoding bit-rate is high
Virtualization aware file systems: getting beyond the limitations of virtual disks (2006)

Virtual disks are the main form of storage in today’s virtual machine environments. They offer many attractive features, including whole system versioning, isolation, and mobility, that are absent from current file systems. Unfortunately, the low-level interface of virtual disks is very coarse-grained, forcing all-or-nothing whole system rollback, and opaque, offering no practical means of sharing. These problems impose serious limitations on virtual disks ’ usability, security, and ease of management. To overcome these limitations, we offer Ventana, a virtualization aware file system. Ventana combines the filebased storage and sharing benefits of a conventional distributed file system with the versioning, mobility, and access control features that make virtual disks so compelling. 1
Emissions Characteristics of a Turbine Engine and Research Combustor Burning a Fischer−Tropsch Jet Fuel (2007)

The emissions characteristics of two combustion platforms, a T63 turboshaft engine and an atmospheric swirl-stabilized research combustor, fueled with conventional military jet fuel (JP-8), a natural-gas-derived Fischer−Tropsch synthetic jet fuel (also referred herein as synjet or FT), and blends of the two were investigated. Nonvolatile particulate matter (PM) and gaseous emissions were analyzed to assess the impacts of the aromatic- and sulfur-free synjet fuel on the combustion products of the two platforms. The engine was operated at two power settings, and the combustor at several equivalence ratios, to evaluate the emission production over a wide range of combustion temperatures. Conventional aerosol instrumentation was used to quantify particle number (PN), size, and PM mass emissions, while a Fourier Transform Infrared analyzer was used to quantify the gaseous species. Planar laser-induced fluorescence and laser-induced incandescence techniques were employed on the research combustor to study the effects of the FT fuel on the formation and oxidation of particles in the combustor primary zone. Test results show dramatic reductions in particle concentrations and mean size on both combustion platforms with the neat FT and synjet fuel blends relative to operation with JP-8. Reductions of over 90% in PN were observed on both platforms for several operating conditions with neat FT fuel. For the engine, over an 80% reduction in smoke number was observed with neat synjet relative to operation on JP-8. As expected, reductions in sulfur oxide emissions and slight increases in water vapor (measured only in the atmospheric combustor) resulted due to the sulfur-free nature and higher hydrogen-to-carbon ratio of the synthetic fuel. Minor impacts were observed for other gaseous emissions. American Society for Testing and Materials fuel specification tests showed that JP-8/synjet blends up to 50/50% by volume satisfied the JP-8 military fuel requirements and that only the minimum specific gravity requirement was not satisfied at higher synjet concentrations. Impacts of the synjet fuel on the emissions of the atmospheric combustor and the T63 engine, a comparison of emissions between the two platforms, and results of in situ laser-based measurements in the combustor reaction zone are discussed.
Lipid domains in sperm plasma membranes (1995)

Mammalian sperm have unusual plasma membranes compared to those of somatic cells. After leaving the testes, sperm cease plasma membrane lipid and protein systhesis. A major fraction of mammalian sperm plasma membranes are lipid linked. A large fraction of their lipid chains are highly unsaturated. Biophysical studies reveal that lipids are regionalized on the sperm surface and are highly immobile. This immobile fraction evolves with sperm development. This non-diffusing fraction is also observed in bilayers reconstituted from lipid extracts of sperm head plasma membranes, suggesting the existence of gel phase domains in these membranes. This hypothesis is further supported by differential scanning calorimetry, which shares at least two relatively broad phase transitions with physiological temperature falling between these major transitions.
George Lyman Duff Memorial Lecture. Multifactorial etiology of hypercholesterolemia. Implications for prevention of coronary heart disease. (1991)

This review underlines the concept that multiple factors are responsible for hypercholesterolemia in the American public. Dietary factors (cholesterol, saturated fatty acids, and obesity) clearly raise the cholesterol level, and they are important causes of borderline-high cholesterol. Still, the unexplained decline of LDL receptor activity with aging contributes importantly to borderline-high levels and cannot be ignored. The loss of estrogen-stimulated LDL receptor synthesis after menopause is an important contributor to elevated cholesterol in postmenopausal women. In addition, several genetic defects inherited singly appear to be responsible for moderate hypercholesterolemia. Some of these defects may represent genetic hypersensitivity to diet, and dietary therapy alone may provide adequate cholesterol lowering. Other defects impart resistance to dietary control, and use of a single cholesterol-lowering drug may be required. With the exception of heterozygous FH, most cases of severe hypercholesterolemia appear to be the result of the coexistence of at least two defects in LDL metabolism, and as a rule, they can be treated successfully only by using cholesterol-lowering drugs in combination.
Direct Demonstration of Geranylgeranylation and Farnesylation of Ki-Ras in Vivo (1997)

It has recently been reported that Ki-Ras protein can be modified in vitro by farnesylation or geranylgeranylation. However, a previous analysis of Ki-Ras prenylation in vivo found only farnesylated Ki-Ras. In this report it is shown that under normal conditions, Ki-Ras is farnesylated in vivo and when cells are treated with the farnesyl transferase inhibitors B956 or B957, farnesylation is inhibited and Ki-Ras becomes geranylgeranylated in a dose dependent manner. These results have strong implications in the design of anticancer drugs based on inhibition of prenylation.
Association of cell surface heparan sulfate proteoglycans of Schwann cells with extracellular matrix proteins (1990)

The terminal differentiation of Schwann cells is dependent on contact with basement membrane. The present study was undertaken to investigate the role of cell surface heparan sulfate proteoglycans (HSPGs) in mediating Schwann cell responses to extracellular matrix contact. Phosphatidylinositol-specific phospholipase C-releasable cell surface HSPGs purified from cultures of neonatal rat Schwann cells were subjected to affinity chromatography on immobilized laminin and fibronectin. Binding of the HSPG to both affinity matrices was observed. The strength of the association, however, was sensitive to the ionic strength of the buffer. In 0.1 M Tris-HCl, HSPG binding was essentially irreversible whereas in physiological ionic strength buffer (e.g. 0.142 M NaCl, 10 mM Tris), weaker binding was detected as a delay in elution of the HSPG from the affinity columns. Further studies of HSPG-laminin binding suggested that the binding was mediated by the glycosaminoglycan chains of the proteoglycans. Results of equilibrium gel filtration chromatography provided additional evidence for a reversible association of the HSPG and laminin with a Kd of approximately 1 x 10(-6) M. When Schwann cells were plated on plastic dishes coated with laminin, the cells attached and extended long slender processes. Inclusion of heparin, but not chondroitin sulfate, in the assay medium resulted in partial inhibition of process extension, but at concentrations of heparin which were higher than that needed to disrupt laminin-HSPG association in vitro. Addition of anti-integrin receptor antibodies resulted in more extensive inhibition of laminin-dependent process extension. Anti-integrin antibodies plus heparin essentially totally inhibited laminin-dependent process extension. These results demonstrate that cell surface HSPGs are capable of reversible association with extracellular matrix molecules and suggest that HSPG-laminin interactions play a role in laminin-dependent Schwann cell spreading.
Stimulation of Host NKT Cells by Synthetic Glycolipid Regulates Acute Graft-versus-Host Disease by Inducing Th2 Polarization of Donor T Cells (2005)

NKT cells are a unique immunoregulatory T cell population that produces large amounts of cytokines. We have investigated whether stimulation of host NKT cells could modulate acute graft-vs-host disease (GVHD) in mice. Injection of the synthetic NKT cell ligand alpha-galactosylceramide (alpha-GalCer) to recipient mice on day 0 following allogeneic bone marrow transplantation promoted Th2 polarization of donor T cells and a dramatic reduction of serum TNF-alpha, a critical mediator of GVHD. A single injection of alpha-GalCer to recipient mice significantly reduced morbidity and mortality of GVHD. However, the same treatment was unable to confer protection against GVHD in NKT cell-deficient CD1d knockout (CD1d(-/-)) or IL-4(-/-) recipient mice or when STAT6(-/-) mice were used as donors, indicating the critical role of host NKT cells, host production of IL-4, and Th2 cytokine responses mediated by donor T cells on the protective effects of alpha-GalCer against GVHD. Thus, stimulation of host NKT cells through administration of NKT ligand can regulate acute GVHD by inducing Th2 polarization of donor T cells via STAT6-dependent mechanisms and might represent a novel strategy for prevention of acute GVHD.
Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes (2008)

Cell number is an important determinant of adipose tissue mass, and the coordinated proliferation and differentiation of preadipocytes into mature lipid-laden adipocytes underpins the increased adipose tissue mass associated with obesity. Despite this, the molecular cues governing such adipose tissue expansion are poorly understood. We previously reported that fibroblast growth factor-1 (FGF-1) promotes both proliferation and differentiation of human preadipocytes and that the major adipogenic effect of FGF-1 occurs during proliferation, priming the cells for adipose conversion. In the current study, we examined whether this effect was linked to the mitogenic action of FGF-1 by investigating the mitogenic and adipogenic potential of other growth factors, platelet-derived growth factor (PDGF; AA and BB) and vascular endothelial growth factor. Although PDGF-AA and PDGF-BB showed comparable mitogenic potential to FGF-1, only FGF-1 treatment resulted in priming and subsequent differentiation. Pharmacological inhibition of FGF receptor (FGFR) tyrosine kinase activity, using the FGFR-specific inhibitors PD-173074 and SU-5402, revealed an obligate requirement for FGFR activity in these processes. A combination of biochemical and genetic approaches revealed an important role for FGFR1. Knock down of FGFR1 expression by small-interfering RNA reduced FGF-1-stimulated signaling events, proliferation, and priming. Together these data highlight the unique nature of the role of FGF-1 during the earliest stages of adipogenesis and establish a role for FGFR1 in human adipogenesis, identifying FGFR1 as a potential therapeutic target to reduce obesity.
The Use of Antibody Engineering to Create Novel Drugs that Target N-methyl-D-Aspartate Receptors (2001)

According to a recent World Health Organization survey, there are over four hundred million people worldwide suffering from mental and neurological disorders; schizophrenia affects some forty-five million people, and unipolar major depression ranked fifth in major causes of disability and death. Clearly it is of the utmost importance to develop new, effective, and safe neuro-pharmaceuticals with this increasing "global burden of disease". To this end, we have developed a strategy of generating monoclonal antibodies that act as modulators of the cell-surface central nervous system receptor-ion channel complexes. In this review we will focus on the generation and characterization of a monoclonal antibody that acts as a partial agonist to the N-methyl-D-aspartate receptor. The creation of peptide mimetics, derived from this monoclonal antibody, that may be useful as cognitive enhancers and protect neurons hypoxic and ischemic insults caused by stroke, will also be discussed.
Aptamer in Bioanalytical Applications (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTAptamer in Bioanalytical ApplicationsAnton B. Iliuk, Lianghai Hu, and W. Andy Tao*View Author Information Department of Biochemistry and Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United StatesE-mail: [email protected]Cite this: Anal. Chem. 2011, 83, 12, 4440–4452Publication Date (Web):April 27, 2011Publication History Published online5 May 2011Published inissue 15 June 2011https://pubs.acs.org/doi/10.1021/ac201057whttps://doi.org/10.1021/ac201057wreview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views16254Altmetric-Citations661LEARN 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 SUBJECTS:Biotechnology,Cancer,Cells,Genetics,Peptides and proteins Get e-Alerts
Enantioselective Construction of Tetrasubstituted Stereogenic Carbons through Brønsted Base Catalyzed Michael Reactions: α′-Hydroxy Enones as Key Enoate Equivalent (2014)

Catalytic and asymmetric Michael reactions constitute very powerful tools for the construction of new C-C bonds in synthesis, but most of the reports claiming high selectivity are limited to some specific combinations of nucleophile/electrophile compound types, and only few successful methods deal with the generation of all-carbon quaternary stereocenters. A contribution to solve this gap is presented here based on chiral bifunctional Brønsted base (BB) catalysis and the use of α'-oxy enones as enabling Michael acceptors with ambivalent H-bond acceptor/donor character, a yet unreported design element for bidentate enoate equivalents. It is found that the Michael addition of a range of enolizable carbonyl compounds that have previously demonstrated challenging (i.e., α-substituted 2-oxindoles, cyanoesters, oxazolones, thiazolones, and azlactones) to α'-oxy enones can afford the corresponding tetrasubstituted carbon stereocenters in high diastereo- and enantioselectivity in the presence of standard BB catalysts. Experiments show that the α'-oxy ketone moiety plays a key role in the above realizations, as parallel reactions under identical conditions but using the parent α,β-unsaturated ketones or esters instead proceed sluggish and/or with poor stereoselectivity. A series of trivial chemical manipulations of the ketol moiety in adducts can produce the corresponding carboxy, aldehyde, and ketone compounds under very mild conditions, giving access to a variety of enantioenriched densely functionalized building blocks containing a fully substituted carbon stereocenter. A computational investigation to rationalize the mode of substrate activation and the reaction stereochemistry is also provided, and the proposed models are compared with related systems in the literature.
The role of eosinophils and neutrophils in inflammation (2000)

The eosinophil is well recognized as a central effector cell in the inflamed asthmatic airway. Eosinophils release toxic basic proteins and lipid mediators such as cysteinyl-leukotrienes that cause bronchial epithelial damage and airflow obstruction. Eosinophil-selective cytokines and chemokines including interleukin (IL)-5, eotaxin and RANTES may represent targets for novel asthma therapies. In contrast, the role of the neutrophil in asthma remains relatively obscure. Recent evidence from the ENFUMOSA project and elsewhere suggests that neutrophils not only contribute to acute asthma exacerbations, but also are present in high numbers in the airways of patients with chronic severe asthma. Production by neutrophils of lipid mediators, reactive oxygen intermediates (ROI) and proteases such as elastase, may contribute to airflow obstruction, epithelial damage and remodelling. Leukotriene B4 and cytokines such as IL-8, granulocyte-macrophage colony stimulating factor (GM-CSF), and tumour necrosis factor (TNF)alpha chemoattract neutrophils and reduce neutrophil apoptosis, and selective agents directed against these may prevent neutrophil influx and accumulation. Airway neutrophilia remains apparent in severe asthma patients even after treatment with high doses of corticosteroids. In vitro, corticosteroids paradoxically enhance neutrophil survival by reducing apoptosis, so corticosteroid therapy may exacerbate neutrophil activity in vivo. Both corticosteroids and cytokines may suppress neutrophil apoptosis by upregulating endogenous synthesis of leukotriene (LT)B4. Specific blockade of LTB4 synthesis or LTB4 receptors may induce neutrophil apoptosis and combat the unwanted effects of high-dose steroids on neutrophil survival. Phagocytosis of apoptotic neutrophils stimulates important signals that down-regulate pro-inflammatory cytokine production by macrophages, allowing resolution and repair processes to prevail.
Tumor-specific Th17-polarized cells eradicate large established melanoma (2008)

CD4+ T cells can differentiate into multiple effector subsets, but the potential roles of these subsets in anti-tumor immunity have not been fully explored. Seeking to study the impact of CD4+ T cell polarization on tumor rejection in a model mimicking human disease, we generated a new MHC class II-restricted, T-cell receptor (TCR) transgenic mouse model in which CD4+ T cells recognize a novel epitope in tyrosinase-related protein 1 (TRP-1), an antigen expressed by normal melanocytes and B16 murine melanoma. Cells could be robustly polarized into Th0, Th1, and Th17 subtypes in vitro, as evidenced by cytokine, chemokine, and adhesion molecule profiles and by surface markers, suggesting the potential for differential effector function in vivo. Contrary to the current view that Th1 cells are most important in tumor rejection, we found that Th17-polarized cells better mediated destruction of advanced B16 melanoma. Their therapeutic effect was critically dependent on interferon-gamma (IFN-gamma) production, whereas depletion of interleukin (IL)-17A and IL-23 had little impact. Taken together, these data indicate that the appropriate in vitro polarization of effector CD4+ T cells is decisive for successful tumor eradication. This principle should be considered in designing clinical trials involving adoptive transfer-based immunotherapy of human malignancies.
Peripherally acting &mu;-opioid receptor antagonists as treatment options for constipation in noncancer pain patients on chronic opioid therapy (2017)

Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain. Other treatment options include fixed-dose combination products of oxycodone analgesic together with naloxone.
SYNTHESIS OF CHLORINATED 2-(3-BENZOFURANYL)PHENOLS (1966)

not available