gebhart/patrepeval huggingface dataset:
Modulation of Th2 Responses by Peptide Analogues in a Murine Model of Allergic Asthma: Amelioration or Deterioration of the Disease Process Depends on the Th1 or Th2 Skewing Characteristics of the Therapeutic Peptide (2000)

Allergen-specific CD4+ Th2 cells play an important role in the immunological processes of allergic asthma. Previously we have shown that, by using the immunodominant epitope OVA323-339, peptide immunotherapy in a murine model of OVA induced allergic asthma, stimulated OVA-specific Th2 cells, and deteriorated airway hyperresponsiveness and eosinophilia. In the present study, we defined four modulatory peptide analogues of OVA323-339 with comparable MHC class II binding affinity. These peptide analogues were used for immunotherapy by s.c. injection in OVA-sensitized mice before OVA challenge. Compared with vehicle-treated mice, treatment with the Th2-skewing wild-type peptide and a Th2-skewing partial agonistic peptide (335N-A) dramatically increased airway eosinophilia upon OVA challenge. In contrast, treatment with a Th1-skewing peptide analogue (336E-A) resulted in a significant decrease in airway eosinophilia and OVA-specific IL-4 and IL-5 production. Our data show for the first time that a Th1-skewing peptide analogue of a dominant allergen epitope can modulate allergen-specific Th2 effector cells in an allergic response in vivo. Furthermore, these data suggest that the use of Th1-skewing peptides instead of wild-type peptide may improve peptide immunotherapy and may contribute to the development of a successful and safe immunotherapy for allergic patients.
High-voltage devices for 0.5-μm standard CMOS technology (2000)

The feasibility of the smart voltage extension (SVX) technique featuring complementary high-voltage devices without any modifications of the process steps of an 0.5-μm standard CMOS technology is discussed here. This letter focuses on the optimization of the breakdown voltage of the HVNMOS as well as the possible implementation of the HVPMOS. Different high-voltage options with increasing process modification steps are discussed as a function of the required high-voltage capabilities.
Automating the Administration of Heterogeneous LANs (1996)

The areas of machine configuration and software package installation and maintenance have been frequent areas of work in recent years. This paper describes a hybrid system developed to address both problems and more. The resulting system is designed to reduce the complexity of the administration of a large network of computers down to that of the administration of a few heterogeneous systems.

In particular, this system allows machines to be maintained without ever having to manually change files on their disks. Systems can also be upgraded, installed from scratch, or recovered with a minimum of effort. The system described is designed to be extremely general and applicable to virtually all versions of UNIX and UNIX-like operating systems.
Practical New Silyloxy-Based Alkyne Metathesis Catalysts with Optimized Activity and Selectivity Profiles (2010)

Triphenylsilanolate ligands were found to impart excellent reactivity and outstanding functional group tolerance on molybdenum alkylidyne complexes, which catalyze alkyne metathesis reactions of all sorts. The active species either can be obtained in high yield by adaptation of the established synthesis routes leading to Schrock alkylidynes or can be generated in situ from the molybdenum nitride complex 11, which itself is readily accessible in large quantity from inexpensive sodium molybdate. Complexation of the active silanolate complexes 12 and 24 with 1,10-phenanthroline affords complexes 15 and 25, respectively, which are stable in air for extended periods of time. Although these phenathroline adducts are per se unreactive vis-a-vis alkynes, catalytic activity is conveniently restored upon exposure to MnCl(2). Therefore, the practitioner has the choice of different alkyne metathesis (pre)catalysts, which are easy to handle yet broadly applicable and exceedingly tolerant. A host of representative inter- as well as intramolecular alkyne metathesis reactions, including applications to a considerable number of bioactive and, in part, labile natural products, shows the remarkable scope of these new tools. Moreover, it was found that the addition of molecular sieves (5 A >or= 4 A >> 3 A) to the reaction mixture significantly improves the chemical yields while simultaneously increasing the reaction rates. This benefit is ascribed to effective binding of 2-butyne, which is released as the common byproduct in reactions of alkynes bearing a methyl end-cap. Thus, alkyne metatheses can now be performed at ambient temperature with neither the need to apply vacuum to drive the conversion nor recourse to tailor-made substrates. The structures of representative examples of this new generation of alkyne metathesis catalysts in the solid state were determined by X-ray analysis.
Packaging Cell Lines for Generating Replication-Defective and Gutted Adenoviral Vectors (2003)

Gene transfer using adenovirus (Ad) can be a highly efficient method for transducing cells and tissues. Wild-type Ad has a 36-kb double-stranded linear genome that encodes numerous overlapping open reading frames (). Because wild-type Ad is infectious to humans, vectors used in the laboratory generally contain a deletion of one or more genes to limit their growth and replication on nonpermissive cells. One drawback to Ad vectors is that infection of a target cell results in transfer not only of the desired transgene of interest, but also of the Ad genes. Expression of these other genes can be toxic, or in vivo, can elicit a potent host-immune response against transduced cells. Consequently, methods have been developed by many labs to engineer Ad vectors that display greatly reduced expression of viral genes except in specifically generated packaging cell lines designed for propagation of the vectors. In general, two types of alterations are made to the Ad genome. In the first, individual genes, or combinations thereof, are deleted from the Ad genome and placed into a packaging cell line under control of a constitutive or inducible promoter. In the second method, all viral genes are removed from the Ad vector, and vector growth is regulated by coinfection with a helper virus. The fully deleted, or gutted, Ad vectors must then be purified away from helper virus prior to use. Both of these strategies can also be combined, whereby one uses a multiply deleted Ad vector in a specialized complementing cell line as a helper virus to grow gutted vectors.
AN IMAGE PROCESSING SYSTEM FOR DRIVER ASSISTANCE / INSTITUT FHUR NEUROINFORMATIK) (1998)

In this paper, the authors describe a system which extracts the important information from an image taken by a CCD camera that is installed at the rear view mirror of a vehicle. The approach involves a sequential and parallel sensors and information processing. By integration in the sequential branch and fusion in the parallel branch, the tasks of object detection, tracking, and classification take place. The result of this approach is the integrative coupling of different algorithms providing partly redundant information.
The Serine Protease Domain of Hepatitis C Viral NS3 Activates RNA Helicase Activity by Promoting the Binding of RNA Substrate (2007)

Nonstructural (NS) protein 3 is a DEXH/D-box motor protein that is an essential component of the hepatitis C viral (HCV) replicative complex. The full-length NS3 protein contains two functional modules, both of which are essential in the life cycle of HCV: a serine protease domain at the N terminus and an ATPase/helicase domain (NS3hel) at the C terminus. Truncated NS3hel constructs have been studied extensively; the ATPase, nucleic acid binding, and helicase activities have been examined and NS3hel has been used as a target in the development of antivirals. However, a comprehensive comparison of NS3 and NS3hel activities has not been performed, so it remains unclear whether the protease domain plays a vital role in NS3 helicase function. Given that many DEXH/D-box proteins are activated upon interaction with cofactor proteins, it is important to establish if the protease domain acts as the cofactor for stimulating NS3 helicase function. Here we show that the protease domain greatly enhances both the direct and functional binding of RNA to NS3. Whereas electrostatics plays an important role in this process, there is a specific allosteric contribution from the interaction interface between NS3hel and the protease domain. Most importantly, we establish that the protease domain is required for RNA unwinding by NS3. Our results suggest that, in addition to its role in cleavage of host and viral proteins, the NS3 protease domain is essential for the process of viral RNA replication and, given its electrostatic contribution to RNA binding, it may also assist in packaging of the viral RNA.
The detection of linkage disequilibrium in molecular sequence data. (1995)

Studies of genetic variation in natural populations at the sequence level usually show that most polymorphic sites are very asymmetrical in allele frequencies, with the rarer allele at a site near fixation. When the rarer allele at a site is present only a few times in the sample, say below five representatives, it becomes very difficult to detect linkage disequilibrium between sites from tests of association. This is a consequence of the numerical properties of even the most powerful test of association, Fisher's exact test. Sites with fewer than five representatives in the sample should be excluded from association tests, but this generally leaves few site pairs eligible for testing. A test for overall linkage disequilibrium, based on the sign of the observed linkage disequilibria, is derived which can use all the data. It is shown that more power can be achieved by increasing the length of sequence determined than by increasing the number of genomes sampled for the same total work.
Biglycan Deficiency Causes Spontaneous Aortic Dissection and Rupture in Mice (2007)

The spontaneous death of biglycan-deficient male mice from aortic rupture implicates biglycan as essential for the structural and functional integrity of the aortic wall and suggests a potential role of biglycan gene defects in the pathogenesis of aortic dissection and rupture in humans.
Base-free cationic zirconium benzyl complexes as highly active polymerization catalysts (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBase-free cationic zirconium benzyl complexes as highly active polymerization catalystsManfred Bochmann and Simon J. LancasterCite this: Organometallics 1993, 12, 3, 633–640Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/om00027a012https://doi.org/10.1021/om00027a012research-articleACS PublicationsRequest reuse permissionsArticle Views576Altmetric-Citations172LEARN 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
Cytotoxic Effect of Curcumin on Malaria Parasite Plasmodium falciparum : Inhibition of Histone Acetylation and Generation of Reactive Oxygen Species (2006)

The emergence of multidrug-resistant parasites is a major concern for malaria control, and development of novel drugs is a high priority. Curcumin, a natural polyphenolic compound, possesses diverse pharmacological properties. Among its antiprotozoan activities, curcumin was potent against both chloroquine-sensitive and -resistant Plasmodium falciparum strains. Consistent with findings in mammalian cell lines, curcumin's prooxidant activity promoted the production in P. falciparum of reactive oxygen species (ROS), whose cytotoxic effect could be antagonized by coincubation with antioxidants and ROS scavengers. Curcumin treatment also resulted in damage of both mitochondrial and nuclear DNA, probably due to the elevation of intracellular ROS. Furthermore, we have demonstrated that curcumin inhibited the histone acetyltransferase (HAT) activity of the recombinant P. falciparum general control nonderepressed 5 (PfGCN5) in vitro and reduced nuclear HAT activity of the parasite in culture. Curcumin-induced hypoacetylation of histone H3 at K9 and K14, but not H4 at K5, K8, K12, and K16, suggested that curcumin caused specific inhibition of the PfGCN5 HAT. Taken together, these results indicated that at least the generation of ROS and down-regulation of PfGCN5 HAT activity accounted for curcumin's cytotoxicity for malaria parasites.
Angiotensin-(1-7) Dilates Canine Coronary Arteries Through Kinins and Nitric Oxide (1996)

Angiotensin-(1-7) [Ang-(1-7)] was recently recognized to have novel biological functions that are distinct from those of Ang II. In these studies, we determined the vasoactive effects of Ang-(1-7) together with the endothelium-dependent mediator(s) of these responses in canine coronary arteries. Isometric tension was measured in intact canine coronary artery rings suspended in organ chambers perfused with 95% O2/5% CO2 at 37 degrees C. Ang-(1-7) caused significant concentration-dependent vascular relaxation (2.73 +/- 0.58 micromol/L, EC50) of rings precontracted with the thromboxane A2 analogue U46,619. Pretreatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (1 mol/L) abolished the vasodilator response to Ang-(1-7), whereas treatment with the cyclooxygenase inhibitor indomethacin (10 micromol/L) was without effect. The vasodilator response produced by Ang-(1-7) was blocked by 75% with the bradykinin B2 receptor antagonist Hoe 140 (1 micromol/L) or by 80% with the nonselective Ang II antagonist [Sar1,Thr8]-Ang II (1 micromol/L). In contrast, the selective AT1 or AT2 Ang II antagonists CV 11974 (1 micromol/L), and PD 123319 (1 micromol/L), respectively, were ineffective in inhibiting the Ang-(1-7)-elicited vasodilation. Furthermore, pretreatment of the coronary rings with 2 micromol/L Ang-(1-7) markedly potentiated the bradykinin response. These results suggest that Ang-(1-7) elicits coronary vasodilation that is specifically mediated by the endothelium-dependent release of nitric oxide. These responses involve a B2 bradykinin receptor and a non-AT1, non-AT2, angiotensin receptor. These data suggest that increases in circulating levels of Ang-(1-7) accompanying long-term administration of converting enzyme inhibitors or Ang II receptor blockers may contribute to the cardioprotective actions of these drugs.
αβ T Cell Receptor-positive Cells and Interferon-γ, but not Inducible Nitric Oxide Synthase, Are Critical for Granuloma Necrosis in a Mouse Model of Mycobacteria-induced Pulmonary Immunopathology (2001)

The immunological basis of tuberculin-induced necrosis, known for more than a century as "Koch's phenomenon," remains poorly understood. Aerosol infection in mice with the highly virulent Mycobacterium avium strain TMC724 causes progressive pulmonary pathology strongly resembling caseating necrosis in human patients with tuberculosis. To identify the cellular and molecular mediators causing this pathology, we infected C57BL/6 mice and mice selectively deficient in recombinase activating gene (RAG)-1, alphabeta T cell receptor (TCR), gammadelta TCR, CD4, CD8, beta2-microglobulin, interferon (IFN)-gamma, interleukin (IL)-10, IL-12p35, IL-12p35/p40, or iNOS with M. avium by aerosol and compared bacterial multiplication, histopathology, and respiratory physiology in these mice. The bacterial load in the lung was similarly high in all mouse groups. Pulmonary compliance, as a surrogate marker for granulomatous infiltrations in the lung, deteriorated to a similar extent in all groups of mice, except in alphabeta TCR-knockout (KO) and IL-12-KO mice in which compliance was higher, and in IFN-gamma and inducible nitric oxide synthase-KO mice in which compliance was reduced faster. Progressive caseation of pulmonary granulomas never occurred in alphabeta TCR-KO, IL-12-KO, and IFN-gamma-KO mice and was reduced in CD4-KO mice. In summary, alphabeta TCR(+) cells and IFN-gamma are essential for the development of mycobacteria-induced pulmonary caseous necrosis. In contrast, high mycobacterial load and extensive granulomatous infiltration per se are not sufficient to cause caseation, nor is granuloma necrosis linked to the induction of nitric oxide.
Botulinum A and the light chain of tetanus toxins inhibit distinct stages of Mg · ATP‐dependent catecholamine exocytosis from permeabilised chromaffin cells (1994)

Susceptibilities of Mg · ATP‐independent and Mg · ATP‐requiring components of catecholamine secretion from digitonin‐permeabilised chromaffin cells to inhibition by Clostridial botulinum type A and tetanus toxins were investigated. These toxins are Zn 2+ ‐dependent proteases which specifically cleave the 25‐kDa synaptosomal‐associated protein (SNAP‐25) and vesicle‐associated membrane protein (VAMP) II, respectively. When applied to permeabilised chromaffin cells they rapidly inhibited secretion in the presence of Mg · ATP but the catecholamine released in the absence of Mg · ATP, thought to represent fusion of primed granules, was not perturbed. The toxins can exert their effects per se in the absence of the nucleotide complex; therefore, Mg · ATP‐requiring steps of secretion are implicated as roles for their targets. Primed release was lost rapidly after permeabili‐sation of the cells but could be maintained by including Mg · ATP during the incubation before stimulating release with Ca 2+ . This ability of Mg · ATP to maintain primed release was only partially inhibited by botulinum neurotoxin A whereas it was abolished by tetanus toxin, consistent with the distinct substrates for these toxins. This study reveals a component of release within which these proteins are either resistant to cleavage by these toxins or in such a position that degradation can no longer prevent granule fusion. Differences in the steps of release at which these toxins can affect inhibition are also revealed.
The Growing Literature of Asian American Religions: A Review of the Field, with Special Attention to Three New Books (2000)

Many Petals of the Lotus: Five Asian Buddhist Communities in Toronto. By Janet McLellan. Toronto: University of Toronto Press, 1999.
Bordetella pertussis adenylate cyclase toxin. Structural and functional independence of the catalytic and hemolytic activities. (1992)

The Bordetella pertussis calmodulin-dependent adenylate cyclase (CyaA) is a 1706-residue-long toxin, endowed with hemolytic activity. We have constructed B. pertussis mutant strains producing modified CyaAs devoid of adenylate cyclase activity. Our results show that such modified CyaAs display hemolytic activity identical to the wild-type toxin, thus demonstrating that the hemolytic activity is independent of the adenylate cyclase activity. Furthermore, B. pertussis and Escherichia coli strains producing CyaA lacking the catalytic domain (residues 1-373) were constructed. The truncated protein exhibits hemolytic activity comparable to the wild-type toxin, thus establishing that the carboxyl-terminal 1332 residues alone are endowed with hemolytic activity. Together, these findings show that adenylate cyclase and hemolytic activities are located in two distinct regions of the molecule (respectively, approximately amino acids 1-400 and 401-1706) and that the two regions of CyaA are functionally independent.
A Recombinant Avian Infectious Bronchitis Virus Expressing a Heterologous Spike Gene Belonging to the 4/91 Serotype (2011)

We have shown previously that replacement of the spike (S) gene of the apathogenic IBV strain Beau-R with that from the pathogenic strain of the same serotype, M41, resulted in an apathogenic virus, BeauR-M41(S), that conferred protection against challenge with M41. We have constructed a recombinant IBV, BeauR-4/91(S), with the genetic backbone of Beau-R but expressing the spike protein of the pathogenic IBV strain 4/91(UK), which belongs to a different serogroup as Beaudette or M41. Similar to our previous findings with BeauR-M41(S), clinical signs observations showed that the S gene of the pathogenic 4/91 virus did not confer pathogenicity to the rIBV BeauR-4/91(S). Furthermore, protection studies showed there was homologous protection; BeauR-4/91(S) conferred protection against challenge with wild type 4/91 virus as shown by the absence of clinical signs, IBV RNA assessed by qRT-PCR and the fact that no virus was isolated from tracheas removed from birds primarily infected with BeauR-4/91(S) and challenged with IBV 4/91(UK). A degree of heterologous protection against M41 challenge was observed, albeit at a lower level.Our results confirm and extend our previous findings and conclusions that swapping of the ectodomain of the S protein is a precise and effective way of generating genetically defined candidate IBV vaccines.
Enhancement of E. coli acyl-CoA synthetase FadD activity on medium chain fatty acids (2015)

FadD catalyses the first step in E. coli beta-oxidation, the activation of free fatty acids into acyl-CoA thioesters. This activation makes fatty acids competent for catabolism and reduction into derivatives like alcohols and alkanes. Alcohols and alkanes derived from medium chain fatty acids (MCFAs, 6-12 carbons) are potential biofuels; however, FadD has low activity on MCFAs. Herein, we generate mutations in fadD that enhance its acyl-CoA synthetase activity on MCFAs. Homology modeling reveals that these mutations cluster on a face of FadD from which the co-product, AMP, is expected to exit. Using FadD homology models, we design additional FadD mutations that enhance E. coli growth rate on octanoate and provide evidence for a model wherein FadD activity on octanoate can be enhanced by aiding product exit. These studies provide FadD mutants useful for producing MCFA derivatives and a rationale to alter the substrate specificity of adenylating enzymes.