gebhart/patrepeval huggingface dataset:
Amplified microgravimetric quartz-crystal-microbalance analyses of oligonucleotide complexes: a route to a Tay–Sachs biosensor device (1998)

A. Bardea, A. Dagan, I. Ben-Dov, I. Willner, A. Bardea, I. Ben-Dov and B. Amit, Chem. Commun., 1998, 839 DOI: 10.1039/A800215K
Identifying Environmental Chemicals Causing Mutations and Cancer (1979)

Damage to DNA appears to be the major cause of most cancer and genetic birth defects and may contribute to aging and heart disease as well. The agents that cause this damage must be identified. Many of these agents are natural chemicals present in the human diet as complex mixtures. The tens of thousands of man-made chemicals that have been introduced into the environment in the last few decades must also be tested for their ability to damage DNA. Existing animal tests and human epidemiology alone are inadequate for this task because of time, expense, and the difficulty of dealing with complex mixtures, Newly developed short-term tests, most of them assaying for mutagenicity, are discussed as key tools in identifying environmental mutagens and carcinogens.
CRISPR-Cas guides the future of genetic engineering (2018)

The diversity, modularity, and efficacy of CRISPR-Cas systems are driving a biotechnological revolution. RNA-guided Cas enzymes have been adopted as tools to manipulate the genomes of cultured cells, animals, and plants, accelerating the pace of fundamental research and enabling clinical and agricultural breakthroughs. We describe the basic mechanisms that set the CRISPR-Cas toolkit apart from other programmable gene-editing technologies, highlighting the diverse and naturally evolved systems now functionalized as biotechnologies. We discuss the rapidly evolving landscape of CRISPR-Cas applications, from gene editing to transcriptional regulation, imaging, and diagnostics. Continuing functional dissection and an expanding landscape of applications position CRISPR-Cas tools at the cutting edge of nucleic acid manipulation that is rewriting biology.
Proxy Chaining and Policy Implementation in Roaming (1999)

This document describes how proxy chaining and policy implementation can be supported in roaming systems. The mechanisms described in this document are in current use.
Short and Efficient Total Synthesis of Luotonin A and 22-Hydroxyacuminatine Using A Common Cascade Strategy (2007)

Total syntheses of 22-hydroxyacuminatine and luotonin A were achieved in direct fashion and high overall yields (16% in eight steps and 47% in five steps, respectively). A mild cascade methodology was successfully applied in both syntheses as a common strategy. The new approach presents the advantages of short routes, high overall yields, use of stable intermediates, and ease of operations.
Simvastatin Reduces Expression of Cytokines Interleukin-6, Interleukin-8, and Monocyte Chemoattractant Protein-1 in Circulating Monocytes From Hypercholesterolemic Patients (2002)

Our data show that simvastatin is anti-inflammatory through the downregulation of cytokines in the endothelium and leukocytes. These effects may explain some of the clinical benefits of these drugs in the treatment of atherosclerosis.
Pterostilbene, a New Agonist for the Peroxisome Proliferator-Activated Receptor α-Isoform, Lowers Plasma Lipoproteins and Cholesterol in Hypercholesterolemic Hamsters (2005)

Resveratrol, a stilbenoid antioxidant found in grapes, wine, peanuts and other berries, has been reported to have hypolipidemic properties. We investigated whether resveratrol and its three analogues (pterostilbene, piceatannol, and resveratrol trimethyl ether) would activate the peroxisome proliferator-activated receptor alpha (PPARalpha) isoform. This nuclear receptor is proposed to mediate the activity of lipid-lowering drugs such as the fibrates. The four stilbenes were evaluated at 1, 10, 100, and 300 microM along with ciprofibrate (positive control), for the activation of endogenous PPARalpha in H4IIEC3 cells. Cells were transfected with a peroxisome proliferator response element-AB (rat fatty acyl CoA beta-oxidase response element)-luciferase gene reporter construct. Pterostilbene demonstrated the highest induction of PPARalpha showing 8- and 14-fold increases in luciferase activity at 100 and 300 microM, respectively, relative to the control. The maximal luciferase activity responses to pterostilbene were higher than those obtained with the hypolipidemic drug, ciprofibrate (33910 and 19460 relative luciferase units, respectively), at 100 microM. Hypercholesterolemic hamsters fed with pterostilbene at 25 ppm of the diet showed 29% lower plasma low density lipoprotein (LDL) cholesterol, 7% higher plasma high density lipoprotein (HDL) cholesterol, and 14% lower plasma glucose as compared to the control group. The LDL/HDL ratio was also statistically significantly lower for pterostilbene, as compared to results for the control animals, at this diet concentration. Results from in vitro studies showed that pterostilbene acts as a PPARalpha agonist and may be a more effective PPARalpha agonist and hypolipidemic agent than resveratrol. In vivo studies demonstrate that pterostilbene possesses lipid and glucose lowering effects.
Functional analysis of the AUG- and CUG-initiated forms of the c-Myc protein. (1994)

Activation of the c-myc proto-oncogene by chromosomal translocation or proviral insertion frequently results in the separation of the c-myc coding region from its normal regulatory elements. Such rearrangements are often accompanied by loss or mutation of c-myc exon 1 sequences. These genetic alterations do not affect synthesis of the major c-myc protein, p64, which is initiated from the first AUG codon in exon 2. However they can result in mutation or loss of the CUG codon located in exon 1 that normally serves as an alternative translational initiation codon for synthesis of an N-terminally extended form of c-Myc (p67). It has been hypothesized that p67 is a functionally distinct form of c-Myc whose specific loss during c-myc rearrangements confers a selective growth advantage. Here we describe experiments designed to test the functional properties of the two c-Myc protein forms. We introduced mutations within the translational initiation codons of a normal human c-myc cDNA that alter the pattern of Myc protein synthesis (p64 vs. p67). The functions of each of these proteins were experimentally addressed using co-transformation and transcriptional activation assays. Both the p64 and p67 c-Myc proteins were independently able to collaborate with bcr-abl in the transformation of Rat-1 fibroblasts. In addition, both the exon 1- and exon 2-initiated forms of the c-Myc protein stimulated transcription of a Myc/Max-responsive reporter construct to a similar level. Given the apparent absence of functional differences between p64 and p67, we conclude that the basis for c-Myc oncogenic activation lies primarily in the overall deregulation of its expression and not in alterations in the protein. The existence of the CUG translational initiator may reflect a mechanism for the continued synthesis of c-Myc protein under conditions where AUG initiation is inhibited.
Mapping High-Fidelity Volume Rendering for Medical Imaging to CPU, GPU and Many-Core Architectures (2009)

Medical volumetric imaging requires high fidelity, high performance rendering algorithms. We motivate and analyze new volumetric rendering algorithms that are suited to modern parallel processing architectures. First, we describe the three major categories of volume rendering algorithms and confirm through an imaging scientist-guided evaluation that ray-casting is the most acceptable. We describe a thread- and data-parallel implementation of ray-casting that makes it amenable to key architectural trends of three modern commodity parallel architectures: multi-core, GPU, and an upcoming many-core Intel architecture code-named Larrabee. We achieve more than an order of magnitude performance improvement on a number of large 3D medical datasets. We further describe a data compression scheme that significantly reduces data-transfer overhead. This allows our approach to scale well to large numbers of Larrabee cores.
Enhancing natural killer cell-mediated lysis of lymphoma cells by combining therapeutic antibodies with CD20-specific immunoligands engaging NKG2D or NKp30 (2015)

Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated through the IgG Fc receptor FcγRIIIa represents a major effector function of many therapeutic antibodies. In an attempt to further enhance natural killer (NK) cell-mediated ADCC, we combined therapeutic antibodies against CD20 and CD38 with recombinant immunoligands against the stimulatory NK cell receptors NKG2D or NKp30. These immunoligands, respectively designated as ULBP2:7D8 and B7-H6:7D8, contained the CD20 scFv 7D8 as a targeting moiety and a cognate ligand for either NKG2D or NKp30 (i.e. ULBP2 and B7-H6, respectively). Both the immunoligands synergistically augmented ADCC in combination with the CD20 antibody rituximab and the CD38 antibody daratumumab. Combinations with ULBP2:7D8 resulted in higher cytotoxicity compared to combinations with B7-H6:7D8, suggesting that coligation of FcγRIIIa with NKG2D triggered NK cells more efficiently than with NKp30. Addition of B7-H6:7D8 to ULBP2:7D8 and rituximab in a triple combination did not further increase the extent of tumor cell lysis. Importantly, immunoligand-mediated enhancement of ADCC was also observed for tumor cells and autologous NK cells from patients with hematologic malignancies, in which, again, ULBP2:7D8 was particularly active. In summary, co-targeting of NKG2D was more effective in promoting rituximab or daratumumab-mediated ADCC by NK cells than co-ligation of NKp30. The observed increase in the ADCC activity of these therapeutic antibodies suggests promise for a 'dual-dual-targeting' approach in which tumor cell surface antigens are targeted in concert with two distinct activating NK cell receptors (i.e. FcγRIIIa and NKG2D or B7-H6).
Continuous Wave Operation of a Mid-Infrared Semiconductor Laser at Room Temperature (2002)

Continuous wave operation of quantum cascade lasers is reported up to a temperature of 312 kelvin. The devices were fabricated as buried heterostructure lasers with high-reflection coatings on both laser facets, resulting in continuous wave operation with optical output power ranging from 17 milliwatts at 292 kelvin to 3 milliwatts at 312 kelvin, at an emission wavelength of 9.1 micrometers. The results demonstrate the potential of quantum cascade lasers as continuous wave mid-infrared light sources for high-resolution spectroscopy, chemical sensing applications, and free-space optical communication systems.
NLRP3 Plays a Critical Role in the Development of Experimental Autoimmune Encephalomyelitis by Mediating Th1 and Th17 Responses (2010)

The interplay between innate and adaptive immunity is important in multiple sclerosis (MS). The inflammasome complex, which activates caspase-1 to process pro-IL-1beta and pro-IL-18, is rapidly emerging as a pivotal regulator of innate immunity, with nucleotide-binding domain, leucine-rich repeat containing protein family, pyrin domain containing 3 (NLRP3) (cryopyrin or NALP3) as a prominent player. Although the role of NLRP3 in host response to pathogen associated molecular patterns and danger associated molecular patterns is well documented, its role in autoimmune diseases is less well studied. To investigate the role of NLRP3 protein in MS, we used a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Nlrp3 expression was elevated in the spinal cords during EAE, and Nlrp3(-/-) mice had a dramatically delayed course and reduced severity of disease. This was accompanied by a significant reduction of the inflammatory infiltrate including macrophages, dendritic cells, CD4, and CD8(+) T cells in the spinal cords of the Nlrp3(-/-) mice, whereas microglial accumulation remained the same. Nlrp3(-/-) mice also displayed improved histology in the spinal cords with reduced destruction of myelin and astrogliosis. Nlrp3(-/-) mice with EAE produced less IL-18, and the disease course was similar to Il18(-/-) mice. Furthermore, Nlrp3(-/-) and Il18(-/-) mice had similarly reduced IFN-gamma and IL-17 production. Thus, NLRP3 plays a critical role in the induction of the EAE, likely through effects on capase-1-dependent cytokines which then influence Th1 and Th17.
Inhibitory effects of deferoxamine on UVB-induced AP-1 transactivation (1999)

Production of reactive oxygen species (ROS) by iron can contribute directly to DNA and protein damage and may contribute to cell signaling and proliferation. We have examined the effects of the iron(III) chelator deferroxamine (DFO) and iron (FeCl(3)) on UVB (290-320 nm)-induced activator protein 1 (AP-1) signaling. The ability of DFO to inhibit UVB-induced AP-1 transactivation was tested in a human keratinocyte cell line stably transfected with a luciferase reporter driven by a single AP-1 element. DFO treatment 24 h prior to UVB irradiation reduced UVB-induced AP-1 transactivation by approximately 80%, with the effect of DFO diminishing as pre-treatment time was shortened. Treatment with FeCl(3) a minimum of 6 h prior to UVB potentiated the UVB induction of AP-1 transactivation by 2-3-fold. DFO was able to ablate both the UVB induction of AP-1 transactivation as well as the potentiation by FeCl(3). The antioxidants Trolox and N-acetyl cysteine were both able to inhibit UVB-induced AP-1 transactivation and Trolox was able to inhibit the potentiation of UVB-induced AP-1 by FeCl(3). These results indicate that UVB-induced AP-1 activation may be in part due to oxidant effects of UVB and intercellular iron.
General syntheses of 2',3'-dideoxynucleosides and 2',3'-didehydro-2',3'-dideoxynucleosides (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGeneral syntheses of 2',3'-dideoxynucleosides and 2',3'-didehydro-2',3'-dideoxynucleosidesC. K. Chu, V. S. Bhadti, B. Doboszewski, Z. P. Gu, Y. Kosugi, K. C. Pullaiah, and P. Van RoeyCite this: J. Org. Chem. 1989, 54, 9, 2217–2225Publication Date (Print):April 28, 1989Publication History Published online1 May 2002Published inissue 28 April 1989https://pubs.acs.org/doi/10.1021/jo00270a036https://doi.org/10.1021/jo00270a036research-articleACS PublicationsRequest reuse permissionsArticle Views1405Altmetric-Citations121LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Signaling Pathways Downstream of Pattern-Recognition Receptors and Their Cross Talk (2007)

Pattern-recognition receptors (PRRs) initiate innate immunity through pathogen recognition. Serum PRRs opsonize pathogens for enhanced phagocytic clearance. Toll-like receptors (TLRs) initiate common NF-kappaB/AP-1 and distinct IRF3/7 pathways to coordinate innate immunity and to initiate adaptive immunity against diverse pathogens. Cytoplasmic caspase-recruiting domain (CARD) helicases, such as RIG-I/MDA5, mediate antiviral immunity by inducing the production of type I interferons via the adaptor IPS-1, whereas nucleotide-binding oligomerization domain (NOD)-like receptors mediate mainly antibacterial immunity by activating NF-kappaB or inflammasomes. Dectin-1 is important for antifungal immunity, promoting phagocytosis and activating NF-kappaB. Potentially harmful TLR signaling pathways can be negatively regulated by negative feedback mechanisms and also by anti-inflammatory factors such as TGFbeta, interleukin (IL)-10, and steroids. Many combinations of TLR-TLR and TLR-NOD modulate inflammatory responses. TLRs and NALP3 interplay to produce mature IL-1beta. Thus signaling pathways downstream of PRRs and their cross talk control immune responses in effective manners.
Structure of the CCR5 Chemokine Receptor–HIV Entry Inhibitor Maraviroc Complex (2013)

The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.
Stereoselective synthesis of alcohols. 8. Diastereoselective synthesis of .beta.-methylhomoallyl alcohols via crotylboronates (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective synthesis of alcohols. 8. Diastereoselective synthesis of .beta.-methylhomoallyl alcohols via crotylboronatesReinhard W. Hoffmann and Hans Joachim ZeissCite this: J. Org. Chem. 1981, 46, 7, 1309–1314Publication Date (Print):March 1, 1981Publication History Published online1 May 2002Published inissue 1 March 1981https://pubs.acs.org/doi/10.1021/jo00320a015https://doi.org/10.1021/jo00320a015research-articleACS PublicationsRequest reuse permissionsArticle Views2149Altmetric-Citations179LEARN 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
Allison engine ATS program technical review (1995)

Gas turbines in industrial and utility applications can help meet future national and worldwide power generation requirements. Implementation of the ATS Program will also keep U.S. manufacturers on the cutting edge of turbine technology for power generation applications and enhance the nation`s economic competitiveness. Allison`s ATS addresses the program goals in the following manner: (1) Efficiency - The turbine selected for the ATS uses Allison`s latest single crystal alloys incorporating the most efficient component cooling technology Allison has developed. These features allow the turbine to operate at a rotor inlet temperature (RIT) of 1427{degrees}C (2600{degrees}F). The compression system for this engine has an overall pressure ratio of more than 20:1 and is based on technology previously demonstrated at Allison. The engine that uses these components will demonstrate a thermal efficiency that is 18% better than the best in class today. (2) Environment - The combustion system selected for this engine incorporates a catalytically stabilized, lean premix system with ceramic components requiring no significant wall cooling. This system will achieve acceptance in severe nonattainment areas, producing less than 8 ppm for oxides of nitrogen (NOx), with acceptable carbon monoxide (CO) and unburned hydrocarbon (UHC). (3) Fuel Flexibility - Allison has production engines in commercial service that are operating on biomass fuels. Previous DOE-funded programs have allowed Allison to develop and demonstrate coal-fueled gas turbine technology. (4) Cost of Power - The busbar cost of energy for the Allison ATS ranges from 23.6 to 27.6% lower than the current state of the art for systems meeting ATS environmental requirements. (5) Reliability, Availability, and Maintainability - The Allison ATS will be designed to have high reliability and low maintenance costs. Critical components will be designed using Allison`s latest life analysis methods.
Interleukin-1 receptor antagonist suppresses Langerhans cell activity and promotes ocular immune privilege. (1998)

IL-1 mediates mechanisms of immunity in corneal inflammation that subvert the normal eye's immune privileged state. However, its antagonism with topical administration of IL-1ra preserves ocular immune privilege and ACAID through suppression of LC function.
[Torasemide is the effective loop diuretic for long-term therapy of arterial hypertension]. (2011)

Torasemide is a loop diuretic and has been used for the treatment of both acute and chronic congestive heart failure (CHF) and arterial hypertension (AH). Torasemide is similar to other loop diuretics in terms of its mechanism of diuretic action. It has higher bioavailability (&gt;80%) and a longer elimination half-life (3 to 4 hours) than furosemide. In the treatment of CHF torasemide (5 to 20 mg/day) has been shown to be an effective diuretic. Non-diuretic dosages (2.5 to 5 mg/day) of torasemide have been used to treat essential AH, both as monotherapy and in combination with other antihypertensive agents. When used in these dosages, torasemide lowers diastolic blood pressure to below 90mm Hg in 70 to 80% of patients. Antihypertensive efficacy of torasemide is similar to that of thiazides and related compounds. Thus low-dose torasemide constitutes an alternative to thiazides in the treatment of essential AH.