gebhart/patrepeval huggingface dataset:
Neutrophil-mediated solubilization of the subendothelial matrix: oxidative and nonoxidative mechanisms of proteolysis used by normal and chronic granulomatous disease phagocytes. (1986)

Both normal and chronic granulomatous disease (CGD) neutrophils were able to degrade the subendothelial matrix secreted by human endothelial cells via an elastase-dependent process. In the absence of the plasma antiproteinase, alpha-1-proteinase inhibitor (alpha-1-PI), normal neutrophils protect their released elastase from inactivation by using the chlorinated oxidants hypochlorous acid and endogenous N-chloroamines to suppress the antiproteinase's activity. In contrast, CGD neutrophils were unable to generate either class of chlorinated oxidant or to inactivate the porcine pancreatic elastase inhibitory capacity of alpha-1-PI unless the cells were supplemented with exogenous hydrogen peroxide. Despite the reliance of normal neutrophils on chlorinated oxidants to inactivate alpha-1-PI, neutrophils triggered in the presence of agents that block the generation of these reactive species continued to degrade the subendothelial matrix at a suppressed but significant rate in the presence of a 50-fold excess of the antiproteinase. The continued solubilization of the matrix by normal neutrophils was not due to the incomplete inhibition of oxidant generation because triggered CGD neutrophils were also able to degrade the matrix in the presence of excess alpha-1-PI. If CGD neutrophils were stimulated in the presence of an exogenous source of H2O2 and alpha-1-PI, the proteolytic potential of the cells was identical to that observed with normal stimulated neutrophils. We conclude that normal neutrophils can enhance their ability to degrade the subendothelial matrix by oxidatively protecting elastase from inactivation by alpha-1-PI but both normal and CGD neutrophils possess non-oxidatively linked mechanisms for sequestering and using elastase to mediate proteolytic effects in the presence of native antiproteinase.
Comparison of Pathogen DNA Isolation Methods from Large Volumes of Whole Blood to Improve Molecular Diagnosis of Bloodstream Infections (2013)

For patients suffering from bloodstream infections (BSI) molecular diagnostics from whole blood holds promise to provide fast and adequate treatment. However, this approach is hampered by the need of large blood volumes. Three methods for pathogen DNA isolation from whole blood were compared, i.e. an enzymatic method (MolYsis, 1-5 ml), the novel non-enzymatic procedure (Polaris, 1-5 ml), and a method that does not entail removal of human DNA (Triton-Tris-EDTA EasyMAG, 200 µl). These methods were evaluated by processing blood spiked with 0-1000 CFU/ml of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Downstream detection was performed with real-time PCR assays. Polaris and MolYsis processing followed by real-time PCRs enabled pathogen detection at clinically relevant concentrations of 1-10 CFU/ml blood. By increasing sample volumes, concurrent lower cycle threshold (Ct) values were obtained at clinically relevant pathogen concentrations, demonstrating the benefit of using larger blood volumes. A 100% detection rate at a concentration of 10 CFU/ml for all tested pathogens was obtained with the Polaris enrichment, whereas comparatively lower detection rates were measured for MolYsis (50-67%) and EasyMAG (58-79%). For the samples with a concentration of 1 CFU/ml Polaris resulted in most optimal detection rates of 70-75% (MolYsis 17-50% and TTE-EasyMAG 20-36%). The Polaris method was more reproducible, less labour intensive, and faster (45 minutes (including Qiagen DNA extraction) vs. 2 hours (MolYsis)). In conclusion, Polaris and MolYsis enrichment followed by DNA isolation and real-time PCR enables reliable and sensitive detection of bacteria and fungi from 5 ml blood. With Polaris results are available within 3 hours, showing potential for improved BSI diagnostics.
The Anti-Selective Boron-Mediated Asymmetric Aldol Reaction of Carboxylic Esters (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTThe Anti-Selective Boron-Mediated Asymmetric Aldol Reaction of Carboxylic EstersAtsushi Abiko, Ji-Feng Liu, and Satoru MasamuneView Author Information Institute for Fundamental Research, Kao Corporation Ichikai-machi, Haga-gun, Tochigi 321-34, Japan Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139 Cite this: J. Am. Chem. Soc. 1997, 119, 10, 2586–2587Publication Date (Web):March 12, 1997Publication History Received28 October 1996Published online12 March 1997Published inissue 1 March 1997https://pubs.acs.org/doi/10.1021/ja963754fhttps://doi.org/10.1021/ja963754frapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views6150Altmetric-Citations180LEARN 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 SUBJECTS:Aldehydes,Aldol reactions,Molecular structure,Organic compounds,Selectivity Get e-Alerts
CD8+ cytolytic T cell clones derived against the Plasmodium yoelii circumsporozoite protein protect against malaria (1991)

Immunization of BALB/c mice with radiation-attenuated Plasmodium yoelii sporozoites induces cytotoxic T lymphocytes (CTL) specific for an epitope located within the amino acid sequence 277-288 of the P. yoelii circumsporozoite (CS) protein. Several CD8+ CTL clones were derived from the spleen cells of sporozoite-immunized mice, all displaying an apparently identical epitope specificity. All the clones induced high levels of cytolysis in vitro upon exposure to peptide-incubated MHC-compatible target cells. The adoptive transfer of two of these clones conferred complete protection against sporozoite challenge to naive mice. This protection is species and stage specific. Using P. yoelii specific ribosomal RNA probes to monitor the in vivo effects of the CTL clones, we found that their target was the intrahepatocytic stage of the parasite. The protective clones completely inhibited the development of the liver stages of P. yoelii. Some CTL clones were only partially inhibitory in vivo, while others failed completely to alter liver stage development and to confer any detectable degree of protection. The elucidation of the effector mechanism of this CTL mediated protection against rodent malaria should facilitate the design of an effective malaria vaccine. From a broader perspective this model may provide further insight into the mechanism(s) of CTL mediated killing of intracellular non-viral pathogens in general.
Acute and subchronic toxicity studies of kernel extract of Sclerocarya birrea in rats (2011)

Sclerocarya birrea fruits are widely eaten in developing countries especially in rural areas and serves as nutrients supplements. However, they also contain phyto-toxin which may affect the normal functioning of the body. Acute toxicity was performed by a single oral administration at a dose of 3000 mg/kg body weight. Sub chronic evaluation was done by oral feeding of the rats with the seed kernel extract daily at doses of 1000, 2000, 3000 and 4000 mg/kg body weight for 28 days. The results of acute toxicity showed no mortality and general behavior changes. The lethal dosage (LD50) was greater than 3000 mg/kg body weight. Rats fed with 1000 and 2000 mg/kg body weight of the extract showed increased body weights throughout the period of treatment but not significantly (p<0.05) different from the control group. Significant (p<0.05) reduction in the body weights were noticed in those administered with 3000 and 4000 mg/kg body weight at the 4th and all the weeks respectively. Significant (p<0.05) increased in serum total protein, albumin, bilirubin, transaminases, creatinine, urea, uric acid and electrolytes were observed in rats fed with 3000 to 4000 mg/kg body weight of the extract, suggesting liver and kidney toxicity. Therefore, the seed kernel extract of S. birrea may be relatively toxic at doses of 3000 and 4000 mg/kg body weight.
TAP‐translocated peptides specifically bind proteins in the endoplasmic reticulum, including gp96, protein disulfide isomerase and calreticulin (1997)

The endoplasmic reticulum (ER) membrane-embedded transporter associated with antigen processing (TAP) associates with peptides in the cytosol and translocates these into the ER lumen. Here, MHC class I molecules bind a subset of these peptides and the remainder is either removed or degraded, or may be retained in the ER in association with other proteins. We have visualized peptide-binding proteins in the ER using radioactive peptides with a photoreactive group. Besides TAP, two proteins were identified as gp96 and protein disulfide isomerase (PDI). Calreticulin, previously found in complex with TAP, only binds glycosylated peptides. In addition, two as yet unidentified, ER luminal glycoproteins (gp120 and gp170) were visualized. The effects of peptide size and sequence on binding to the ER-resident proteins were studied by using partially degenerated peptides with photoreactive side chains. All identified proteins were able to bind peptides within the size range of peptides translocated by TAP, from 8 to more than 20 amino acids. Whereas PDI associated with all peptides tested, gp96 and gp120 showed a clear sequence preference for non-charged amino acids at positions 2 and 9 in 9mer peptides. Thus various ER proteins, other than the MHC class I heterodimer and TAP, are able to interact with peptides albeit with a different substrate selectivity.
Regulation of Cadherin Adhesive Activity (2000)

Adhesive interactions between cells are dynamic and regulated during tissue development and homeostasis. Cadherins are major cell–cell adhesion molecules involved in the development and maintenance of all solid tissues ([Takeichi 1991][1]; [Gumbiner 1996][2]). Therefore, regulation of cadherin-
The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in promoting beta-cell fate specification in Pdx1+ pancreatic progenitor cells (2007)

Despite much progress in identifying transcriptional regulators that control the specification of the different pancreatic endocrine cell types, the spatiotemporal aspects of endocrine subtype specification have remained largely elusive. Here, we address the mechanism by which the transcription factors Nkx6.1 (Nkx6-1) and Nkx6.2 (Nkx6-2) orchestrate development of the endocrine alpha- and beta-cell lineages. Specifically, we assayed for the rescue of insulin-producing beta-cells in Nkx6.1 mutant mice upon restoring Nkx6 activity in select progenitor cell populations with different Nkx6-expressing transgenes. Beta-cell formation and maturation was restored when Nkx6.1 was expressed in multipotential Pdx1(+) pancreatic progenitors, whereas no rescue was observed upon expression in committed Ngn3(+) (Neurog3(+)) endocrine progenitors. Although not excluding additional roles downstream of Ngn3, this finding suggests a first requirement for Nkx6.1 in specifying beta-cell progenitors prior to Ngn3 activation. Surprisingly, although Nkx6.2 only compensates for Nkx6.1 in alpha-but not in beta-cell development in Nkx6.1(-/-) mice, a Pdx1-promoter-driven Nkx6.2 transgene had the same ability to rescue beta-cells as the Pdx1-Nkx6.1 transgene. This demonstrates that the distinct requirements for Nkx6.1 and Nkx6.2 in endocrine differentiation are a consequence of their divergent spatiotemporal expression domains rather than their biochemical activities and implies that both Nkx6.1 and Nkx6.2 possess alpha- and beta-cell-specifying activities.
Uptake of CO2by Roots of Xanthium Plants (1962)

1. The magnitude of CO2 uptake and fixation by Xanthium plant roots was reinvestigated in an attempt to explain unexpectedly low C14/C12 ratios of tree leaves with regard to fixation of radiocarbon of nuclear-test origin. 2. It was found that plants derive relatively insignificant amounts of carbon from CO2 via the roots, and the minute amounts that are incorporated are approximately one hundred times less than the amount lost by root respiration. 3. The results permit the conclusion that the previously noted C14/C12 ratios of the tree leaves were most likely obtained by incorporation of carbon from sources stored in the tree.
Interferon therapy for the treatment of renal cancer (1986)

Renal cell carcinoma (RCC) has remained refractory to substantive change of its natural history despite intervention with a number of therapeutic modalities. Alpha interferons leukocyte interferon alpha [HuIFN-alpha (Le)] and lymphoblastoid interferon alpha [HuIFN-alpha (Ly)] initially were shown to produce regressions of metastatic renal cancers in approximately 25% of patients. Trials with recombinant alpha interferons have demonstrated response rates similar to those observed with natural interferons and have documented that the effect is due to the interferon molecule. Responses with interferons beta and gamma also have been observed, although it is too early to estimate response rates. The interpretation of response rates with interferon is confounded by the rare spontaneous regression of RCC. Responses appear to be delayed (mean response, 3-4 months) relative to those seen in patients with tumors responsive to chemotherapy. A subset of patients with slowly progressive disease may be more likely to to respond. Other patient characteristics predictive of response have not been well characterized. Questions of optimal dose and schedule remain unresolved for both natural and recombinant interferons. Trials of interferon combinations, interferon and chemotherapeutic agents, and interferon administered with other biological-response modifiers are under way. The availability of recombinant interferons should facilitate the isolation and correlation of laboratory and clinical effects.
A maize protein associated with the G-box binding complex has homology to brain regulatory proteins. (1992)

The G-box element is a moderately conserved component of the promoter of many inducible genes, including the alcohol dehydrogenase genes of Arabidopsis and maize. We used monoclonal antibodies generated against partially purified G-box binding factor (GBF) activity to characterize maize proteins that are part of the DNA binding complex. Antibodies interacted with partially purified maize GBF complexes to produce a slower migrating complex in the gel retardation assay. Immunoprecipitation experiments suggested that the protein recognized by the antibody is not a DNA binding protein in and of itself, but rather is associated with the DNA binding complex. These monoclonal antibodies were used to isolate cDNA clones encoding a protein that we have designated GF14. Maize GF14 contains a region resembling a leucine zipper and acidic carboxy and amino termini, of which the latter can form an amphipathic alpha-helix similar to known transcriptional activators such as VP16 and GAL4. Protein gel blot analysis of cell culture extract showed that a single, major protein of approximately 30 kD is recognized by anti-GF14; the protein is also present predominantly in the kernel and root. The deduced amino acid sequence of maize GF14 is more than 80% identical to Arabidopsis GF14 and Oenothera PHP-O, and is more than 60% identical to a class of mammalian brain proteins described as both protein kinase C inhibitors and activators of tyrosine and tryptophan hydroxylases. GF14 is found in a variety of monocotyledons and dicotyledons, gymnosperms, and yeast. This suggests a deep evolutionary conservation of a potential regulatory protein associated with a core sequence found in the promoter region of many genes.
Pivoting M-tree: A Metric Access Method for Efficient Similarity Search. (2004)

In this paper pivoting M-tree (PM-tree) is introduced, a metric access method combining M-tree with the pivot-based approach.
Accelerated Production of Antigen-specific T Cells for Preclinical and Clinical Applications Using Gas-permeable Rapid Expansion Cultureware (G-Rex) (2010)

The clinical manufacture of antigen-specific cytotoxic T lymphocytes (CTLs) for adoptive immunotherapy is limited by the complexity and time required to produce large numbers with the desired function and specificity. The culture conditions required are rigorous, and in some cases only achieved in 2-cm wells in which cell growth is limited by gas exchange, nutrients, and waste accumulation. Bioreactors developed to overcome these issues tend to be complex, expensive, and not always conducive to CTL growth. We observed that antigen-specific CTLs undergo 7 to 10 divisions poststimulation. However, the expected CTL numbers were achieved only in the first week of culture. By recreating the culture conditions present during this first week-low frequency of antigen-specific T cells and high frequency of feeder cells-we were able to increase CTL expansion to expected levels that could be sustained for several weeks without affecting phenotype or function. However, the number of 24-well plates needed was excessive and cultures required frequent media changes, increasing complexity and manufacturing costs. Therefore, we evaluated novel gas-permeable culture devices (G-Rex) with a silicone membrane at the base allowing gas exchange to occur uninhibited by the depth of the medium above. This system effectively supports the expansion of CTL and actually increases output by up to 20-fold while decreasing the required technician time. Importantly, this amplified cell expansion is not because of more cell divisions but because of reduced cell death. This bioprocess optimization increased T-cell output while decreasing the complexity and cost of CTL manufacture, making cell therapy more accessible.
High Turnover Numbers with Ruthenium-Based Metathesis Catalysts (2002)

Effective turnover numbers (TON's) and turnover frequencies (TOF's) of unprecedented magnitude have been obtained for the metathesis of various substrates in the presence of ruthenium-based catalysts, without the use of an additional solvent. For the self-metathesis of 1-octene, the 2nd generation Grubbs' catalyst (IMesH2)(PCy3)(Cl)2RuCHPh (2a) (IMesH2=1,3-dimesityl-4,5-dihydroimidazol-2-ylidene) gave TON's 5 times higher than those of the 1st generation catalyst (PCy3)2(Cl)2RuCHPh (1) while maintaining a high degree of selectivity for the formation of the product 7-tetradecene. Moreover, the catalyst (IPrH2)(PCy3)(Cl)2RuCHPh (2b), bearing the extremely bulky 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene ligand (IPrH2), gave TON's 6 times higher (TON >640,000) and initial TOF's 20 times higher than those of 2a at ambient temperature. At elevated temperatures, TOF's were twice as high and initial TOF's were 6 times as high for 2b relative to 2a, and with nearly 100% selectivity. Initial TOF's exceeding 3,800 s1 could be achieved with 2b at 60 °C. Under similar conditions, comparable TON's for the self-metathesis of trans-4-decene and methyl oleate, and the ring-closing metathesis of diethyl diallylmalonate were also obtained.
Efficient Intraocular Penetration of Topical Anti–TNF-α Single-Chain Antibody (ESBA105) to Anterior and Posterior Segment without Penetration Enhancer (2009)

Topically administered ESBA105 quickly reaches therapeutic levels in the anterior and posterior segment without any need for a penetration enhancer. Drug penetration and ocular biodistribution patterns of ESBA105 applied as eye drops appear highly attractive for clinical use to treat TNF-alpha dependant diseases of the eye.
Magnetically-Guided Self-Assembly of Fibrin Matrices with Ordered Nano-Scale Structure for Tissue Engineering (2006)

The development of effective biological scaffold materials for tissue engineering and regenerative medicine applications hinges on the ability to present precise environmental cues to specific cell populations to guide their position and function. Natural extracellular matrices have an ordered nano-scale structure that can modulate cell behaviors critical for developmental control, including directional cell motility. Here we describe a method for fabricating fibrin gels with defined architecture on the nanometer scale in which magnetic forces are used to position thrombin-coated magnetic micro-beads in a defined 2-dimensional array and thereby guide the self-assembly of fibrin fibrils through catalytic cleavage of soluble fibrinogen substrate. Time-lapse and confocal microscopy confirmed that fibrin fibrils nucleate near the surface of the thrombin-coated beads and extend out in a radial direction to form these gels. When controlled magnetic fields were used to position the beads in hexagonal arrays, the fibrin nano-fibrils that polymerized from the beads oriented preferentially along the bead--bead axes in a geodesic (minimal path) pattern. These biocompatible scaffolds supported adhesion and spreading of human microvascular endothelial cells, which exhibited co-alignment of internal actin stress fibers with underlying fibrin nano-fibrils within some membrane extensions at the cell periphery. This magnetically-guided, biologically-inspired microfabrication system is unique in that large scaffolds may be formed with little starting material, and thus it may be useful for in vivo tissue engineering applications in the future.
Efficient execution of operations in a DBMS for multidimensional arrays (2002)

In the RasDaMan project a database system for management of multidimensional arrays is being built. It offers a declarative query language extending SQL-92 with operations on arrays of arbitrary base types and a C++ programming interface. Integrating arrays in the query language enables the system to process complex queries on high-volume multidimensional data in the database server close to physical data storage. Storage of arrays is done in tiles of arbitrary size. Operations on arrays are transformed into operations on tiles during query optimization and execution. These operations are then executed on tiles loaded from mass storage. This paper describes the underlying formal model for tile based operations on multidimensional arrays and its efficient implementation in C++ as part of the RasDaMan system.
A power control MAC protocol for ad hoc networks (2002)

This paper presents a power control MAC protocol based on the IEEE 802.11 standard. Several researchers have proposed a simple modification of IEEE 802.11 to incorporate power control. The main idea of these power control schemes is to use different power levels for RTS-CTS and DATA-ACK. Specifically, maximum transmit power is used for RTS-CTS, and the minimum required transmit power is used for DATA-ACK transmissions in order to save energy. However, we show that this scheme can degrade network throughput and can result in higher energy consumption than using IEEE 802.11 without power control. We propose an improved power control protocol which does not degrade throughput and yields energy saving.