gebhart/patrepeval huggingface dataset:
Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity. (1992)

We have introduced a variety of amino acid substitutions into carboxyl-terminal CA1A2X sequence (C = cysteine; A = aliphatic; X = any amino acid) of the oncogenic [Val12]Ki-Ras4B protein to identify the amino acids that permit Ras processing (isoprenylation, proteolysis, and carboxyl methylation), membrane association, and transformation in cultured mammalian cells. While all substitutions were tolerated at the A1 position, substitutions at A2 and X reduced transforming activity. The A2 residue was important for both isoprenylation and AAX proteolysis, whereas the X residue dictated the extent and specificity of isoprenoid modification only. Differences were observed between Ras processing in living cells and farnesylation efficiency in a cell-free system. Finally, one farnesylated mutant did not undergo either proteolysis or carboxyl methylation but still displayed efficient membrane association (approximately 50%) and transforming activity, indicating that farnesylation alone can support Ras transforming activity. Since both farnesylation and carboxyl methylation are critical for yeast a-factor biological activity, the three CAAX-signaled modifications may have different contributions to the function of different CAAX-containing proteins.
Glypican-3 is a binding protein on the HepG2 cell surface for tissue factor pathway inhibitor (1997)

Tissue factor pathway inhibitor (TFPI) is a primary regulator of the initiation of blood coagulation. TFPI is internalized and degraded by HepG2 cells through the low-density-lipoprotein receptor-related protein (LRP) but also binds another molecule present on the cell surface at approx. 10-fold the abundance of LRP [Warshawsky, Broze and Schwartz (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 6664-6668]. When HepG2 cells are washed with heparin or dextran sulphate, a substance that binds TFPI is removed from the cell surface and can be detected in a slot-blot assay. Preincubation with trypsin destroys the reactivity of the TFPI-binding component in the slot-blot assay, suggesting that it is a protein. In addition, when the sulphation of glycosaminoglycans (GAGs) is prevented by growing the HepG2 cells in the presence of 30 mM sodium chlorate, TFPI binding is unaffected, whereas the binding of bovine lipoprotein lipase, a protein known to associate with cell-surface GAGs, falls to 50% of control levels. Dextran sulphate washes of HepG2 cells grown in sodium chlorate have an equal reactivity in slot-blot experiments to that of non-treated cells, suggesting that GAGs are not totally responsible for the binding activity observed. By using the slot blot to follow binding activity and conventional protein purification techniques, a protein species that migrates at 40 kDa after reduction was identified in the HepG2 cell wash. The binding of this protein to TFPI was confirmed with immobilized TFPI. Amino acid sequence analysis identified this protein species as a proteolytic fragment of glypican-3 (also called OCI-5), a member of the glypican family of glycosylphosphatidylinositol-anchored proteoglycans.
Synthesis of bovine growth hormone in primates by using a herpesvirus vector. (1985)

A strain of herpesvirus saimiri containing a bovine growth hormone (bGH) gene under the control of the simian virus 40 (SV40) late-region promoter was constructed. This strain, bGH-Z20, was replication competent and stably harbored the bGH gene upon serial passage. Nonpermissive marmoset T cells persistently infected with bGH-Z20 produced a 0.9-kilobase RNA which contained all of the bGH exon sequences and appeared to initiate within the SV40 promoter region. However, in permissively infected owl monkey kidney cells, RNAs containing growth hormone sequences appeared to initiate from herpesvirus saimiri promoters positioned upstream from the SV40-growth hormone gene. Persistently infected T cells in culture secreted 500 ng of bGH protein per 10(6) cells per 24 h during the several months of testing. The secreted protein was 21 kilodaltons, the size of authentic bGH. New World primates experimentally infected with bGH-Z20 produced circulating bGH and developed immunoglobulin G antibodies directed against bGH. Because herpesviruses characteristically remain latent in the infected host, these observations suggest a means for replacing gene products missing or defective in hereditary genetic disorders.
Asparagine assimilation is critical for intracellular replication and dissemination ofFrancisella (2013)

In order to develop a successful infectious cycle, intracellular bacterial pathogens must be able to adapt their metabolism to optimally utilize the nutrients available in the cellular compartments and tissues where they reside. Francisella tularensis, the agent of the zoonotic disease tularaemia, is a highly infectious bacterium for a large number of animal species. This bacterium replicates in its mammalian hosts mainly in the cytosol of infected macrophages. We report here the identification of a novel amino acid transporter of the major facilitator superfamily of secondary transporters that is required for bacterial intracellular multiplication and systemic dissemination. We show that inactivation of this transporter does not affect phagosomal escape but prevents multiplication in the cytosol of all cell types tested. Remarkably, the intracellular growth defect of the mutant was fully and specifically reversed by addition of asparagine or asparagine-containing dipeptides as well as by simultaneous addition of aspartic acid and ammonium. Importantly, bacterial virulence was also restored in vivo, in the mouse model, by asparagine supplementation. This work unravels thus, for the first time, the importance of asparagine for cytosolicmultiplication of Francisella. Amino acid transporters are likely to constitute underappreciated players in bacterial intracellular parasitism.
Dissociation of the effects of the antitumour ether lipid ET‐18‐OCH3 on cytosolic calcium and on apoptosis (1997)

1. We have compared the effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3) on the cytosolic free calcium concentration ([Ca2+]i) and on apoptosis in several normal and leukaemia cells, including human polymorphonuclear neutrophils (PMNs), U937 cells, and undifferentiated as well as dimethylsulphoxide-differentiated HL60 cells (uHL60 and dHL60, respectively). 2. ET-18-OCH3 produced apoptosis, as evidenced by DNA degradation into oligonucleosome-size fragments, in U937 and uHL60 cells, but not in dHL60 cells or PMNs. 3. ET-18-OCH3 induced an increase in [Ca2+]i mediated through the platelet-activating factor (PAF) receptor in U937, dHL60 cells and PMNs, as shown by cross-desensitization experiments and by prevention of the [Ca2+]i changes by the PAF antagonist WEB-2170. The EC50 values for the increase in [Ca2+]i induced by PAF and ET-18-OCH3 were 5 x 10(-11) and 2.5 x 10(-7) M, respectively. In uHL60 cells the effect of ET-18-OCH3 on [Ca2+]i was very small and was not affected by WEB-2170. 4. PAF did not produce apoptosis in any of the cell types tested. WEB-2170 did not prevent the apoptosis induced by ET-18-OCH3. 5. The uptake of [3H]-ET-18-OCH3 was much larger in U937 and uHL60 cells than in dHL60 cells and PMNs. 6. Our results indicate that the apoptotic effect of ET-18-OCH3 is not related to the changes in [Ca2+]i, effected by interaction with plasma membrane PAF receptors, but to other actions which are associated with the uptake of this drug into the cells.
La crisis del limón en Tucumán en el marco del desarrollo capitalista mundial (2006)

Molecular engineering enables the creation of aptamers with novel functions, but the prerequisite is a deep understanding of their structure and recognition mechanism. The cellular-mesenchymal epithelial transition factor (c-MET) is garnering significant attention due to the critical role of the c-MET/HGF signaling pathway in tumor development and invasion. This study reports a strategy for constructing novel chimeric aptamers that bind to both c-MET and other specific proteins. c-MET was identified to be the molecular target of a DNA aptamer, HF3-58, selected through cell-SELEX. The binding structure and mechanism of HF3-58 with c-MET were systematically studied, revealing the scaffold, recognition, and redundancy regions. Through molecular engineering design, the redundancy region was replaced with other aptamers possessing stem-loop structures, yielding novel chimeric aptamers with bispecificity for binding to c-MET and specific proteins. A chimeric bispecific aptamer HF-3b showed the ability to mediate the adhesion of T-cells to tumor cells, suggesting the prospective utility in tumor immunotherapy. These findings suggest that aptamer HF3-58 can serve as a molecular engineering platform for the development of diverse multifunctional ligands targeting c-MET. Moreover, comprehensive understanding of the binding mechanisms of aptamers will provide guidance for the design of functional aptamers, significantly expanding their potential applications.
Two pointer input for 3D interaction (1997)

Article Free Access Share on Two pointer input for 3D interaction Authors: Robert C. Zeleznik Brown University site of the NSF Science and Technology Center for Computer Graphics and Scientific Visualization, Providence, RI Brown University site of the NSF Science and Technology Center for Computer Graphics and Scientific Visualization, Providence, RIView Profile , Andrew S. Forsberg Brown University site of the NSF Science and Technology Center for Computer Graphics and Scientific Visualization, Providence, RI Brown University site of the NSF Science and Technology Center for Computer Graphics and Scientific Visualization, Providence, RIView Profile , Paul S. Strauss Silicon Graphics Computer Systems Silicon Graphics Computer SystemsView Profile Authors Info & Claims I3D '97: Proceedings of the 1997 symposium on Interactive 3D graphicsApril 1997 Pages 115–120https://doi.org/10.1145/253284.253316Published:30 April 1997Publication History 72citation1,514DownloadsMetricsTotal Citations72Total Downloads1,514Last 12 Months39Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
The Antibody-Antigen Reaction: A Visual Observation (1973)

Abstract Rothen and Mathot (1) and later Vroman and Adams (2) have shown that the antibody-antigen reaction will take place at a liquid-solid interface, and that the results of this interaction can be detected by the use of an ellipsometer. This optical instrument measures the adsorption and rotation of plane polarized light incident on the surface in question and has a limiting sensitivity of much less than a monolayer of adsorbed protein. I have used this technique to study the adsorption of protein from a solution onto various surfaces, such as Nb, Ta, Ni, Au, In, and Si, and further to observe the kinetics of the subsequent reaction with antibodies (Giaver, I., in preparation). These studies confirm earlier findings that the adsorption of a globular protein such as bovine serum albumin (BSA)1 and ovalbumin (OA) results in a monolayer about 30Å thick while the reaction with appropriate antibodies increases the thickness of the layer to approximately 100Å. This communication, however, reports on a very simple experiment whereby the immunologic reaction can be studied with the unaided eye without the help of an optical instrument to give a qualitative test for the presence of antibodies.
Application Sharing from Mobile Devices with a Collaborative Shared Display (2014)

With the increasing ubiquity of smartphones, tablets, and large pixel-rich displays, there are many exciting new possibilities for using these devices for collaborative work. While there already exist hardware and software that support communication and interaction between mobile devices and shared displays, application sharing in these scenarios is still limited and inflexible. We present a new method of application sharing which allows collaborators to download clips or snapshots of each other's applications. These snapshots can be used to re-launch and resume the shared application back to the state it was in when it was shared. We have built a system that supports sharing, annotating, organizing, and downloading these applications to and from a LearnSpace server. We have built an application framework which allows Android applications to be built for this system while only requiring minimal changes to the program. We also describe solutions for extending our solution to new types of collaborative displays and to other application platforms.
Pilot Plant Preparation of an αvβ3 Integrin Antagonist. Part 1. Process Research and Development of a (S)-β-Amino Acid Ester Intermediate:  Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction (2003)

Described are four process research investigations directed toward discerning a scalable, enantioselective method for preparing (S)-β-amino acid ester 3, a key intermediate to the αvβ3 integrin antagonist 1. Reported are an asymmetric Michael reaction approach, attempts to enantioselectively hydrogenate an enamine, resolution of (±)-3 via diastereomeric salt formation, and a synthetic route employing a novel, diastereoselective imino-Reformatsky reaction. This last research initiative proved successful and was employed as the enabling route to initial API supply. Process development of this enabling chemistry is reported. The technical issues researched and optimized were (1) the necessity of employing MEM-protection for high yield and diastereoselectivity in the imino-Reformatsky reaction, (2) the reaction kinetics of MEM chloride hydrolysis and the application of these data to an on-scale quench procedure, (3) the efficient formation of the (S)-phenylglycinol imine 15 in NMP and a dehydration of this product solution on-scale, employing molecular sieves, (4) a calorimetric study of the Reformatsky reaction and the application of these data, (5) the replacement of Pb(OAc)4 with NaIO4 and the use of methylamine to sequester competing oxazolidine formation, and (6) further development of the isolation and purification protocol for the ethyl ester, p-TsOH salt of (S)-3. The results and challenges associated with two campaigns in which the potential commercial process was practiced are discussed.
A Bactericidal Effect for Human Lactoferrin (1977)

Streptococcus mutans and Vibrio cholerae, but not Escherichia coli, were killed by incubation with purified human apolactoferrin. Concentrations of lactoferrin below that necessary for total inhibition resulted in a marked reduction in viable colony-forming units. This bactericidal effect was contingent upon the metal-chelating properties of the lactoferrin molecule.
The Linear-Quadratic Model and Most Other Common Radiobiological Models Result in Similar Predictions of Time-Dose Relationships (1998)

One of the fundamental tools in radiation biology is a formalism describing time-dose relationships. For example, there is a need for reliable predictions of radiotherapeutic isoeffect doses when the temporal exposure pattern is changed. The most commonly used tool is now the linear-quadratic (LQ) formalism, which describes fractionation and dose-protraction effects through a particular functional form, the generalized Lea-Catcheside time factor, G. We investigate the relationship of the LQ formalism to those describing other commonly discussed radiobiological models in terms of their predicted time-dose relationships. We show that a broad range of radiobiological models are described by formalisms in which a perturbation calculation produces the standard LQ relationship for dose fractionation/protraction, including the same generalized time factor, G. This approximate equivalence holds not only for the formalisms describing binary misrepair models, which are conceptually similar to LQ, but also for formalisms describing models embodying a very different explanation for time-dose effects, namely saturation of repair capacity. In terms of applications to radiotherapy, we show that a typical saturable repair formalism predicts practically the same dependences for protraction effects as does the LQ formalism, at clinically relevant doses per fraction. For low-dose-rate exposure, the same equivalence between predictions holds for early-responding end points such as tumor control, but less so for late-responding end points. Overall, use of the LQ formalism to predict dose-time relationships is a notably robust procedure, depending less than previously thought on knowledge of detailed biophysical mechanisms, since various conceptually different biophysical models lead, in a reasonable approximation, to the LQ relationship including the standard form of the generalized time factor, G.
The electrical properties of metal microelectrodes (1968)

The electrical properties of metal microelectrodes for single-unit recording are reviewed. An equivalent circuit is presented, the elements of which are discussed. The most important element is the electrolytic capacitor formed by the metal-electrolyte interface. Its value is about 0.2 pF/µ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at 1 kHz. The effects of exposed metallic area at the tip and platinization are described, and some consideration is given to problems peculiar to the operation of these electrodes in neural tissue.
Triacylglyceride Thermal Cracking: Pathways to Cyclic Hydrocarbons (2011)

Thermal cracking of triacylglyceride (TG) oils results in complex mixtures, containing nearly 20% cyclic hydrocarbons, which can be further processed into middle-distillate transportation fuels and byproduct chemicals. The occurrence patterns of cyclic products obtained via the thermal cracking of several TG feedstocks, such as canola and soybean oils, as well as triolein and tristearin (conducted at 430–440 °C in the absence of catalysts under vacuum), were investigated to probe possible formation mechanisms. Detailed gas chromatographic characterization furnished full molar homology/molecular size and partial isomeric profiles for cyclopentanes, cyclopentenes, cyclohexanes, cyclohexenes, aromatics, and polycyclic aromatic hydrocarbons (PAHs). It was found that the data were inconsistent with previously proposed mechanisms involving the Diels–Alder reaction as a single pathway. An alternate mechanism was proposed and supported with experimental evidence based on the intramolecular cyclization of alkenyl and alkadienyl radicals formed as a result of TG cracking. The product homology profiles corroborate the proposed mechanism and show the depletion of medium-size alkenes coupled with the accumulation of corresponding monocyclic hydrocarbons (those with the matching number of carbon atoms). Similarly, the product mixtures were depleted of long-chain alkyl-substituted monocyclic hydrocarbons because of the formation of the corresponding PAHs as long as sufficient time is available. Entropy appears to determine the type and size of cyclic hydrocarbons formed.
Transactional Support in MapReduce for Speculative Parallelism (2010)

MapReduce has emerged as a popular programming model for large-scale distributed computing. Its framework enforces strict synchronization between successive map and reduce phases and limited data-sharing within a phase. Use of keyvalue based persistent storage with MapReduce presents intriguing opportunities and challenges. These challenges relate primarily to semantic inconsistencies arising from the different fault-tolerant mechanisms employed by the execution environment and the underlying storage medium. We define formal transactional semantics for MapReduce over reliable key-value stores. With minimal performance overhead and no increase in program complexity, our solutions support broad classes of distributed applications hitherto infeasible inMapReduce. Specifically, this paper (i) motivates the use of key-value stores as the underlying storage for MapReduce, (ii) defines transactional semantics for MapReduce to address any inconsistencies, (iii) demonstrates broader application scope enabled by data sharing within and across jobs, and (iv) presents a detailed evaluation demonstrating the low overhead of our proposed semantics. 1.
A Family with Hereditary Spastic Paraparesis and Epilepsy (1997)

The association of HSP and epilepsy should no longer be assumed to be fortuitous.
XML Algebra Optimization (2002)

Mapping of XML data into and out of relational database systems, including query processing over such virtual XML views that wrap relational sources, has become a topic of critical importance recently. The Rainbow XML data management system, being developed at WPI, focuses on the processing and optimization of XQuery queries against XML views of that relational data. For this, Rainbow’s query model, XML Algebra Tree (XAT), has been designed. Because the XML formatting operators are interleaved with the computation operators, this XAT must then be optimized before being translated into SQL. For this, our computation pushdown technology splits the XAT into the XML-specific and SQL-doable operators with the later then being converted into SQL statements. However, the XAT after computation pushdown may contain unreferenced columns or unused operators. We show that these unneeded operators cannot be discovered by the relational engine after SQL generation. Leaving these operators in the tree would create unnecessarily large SQL statements that will slow down the overall execution. Our main contributions to XML query processing, described in this paper, are threefold. One, we describe the XAT algebra for modeling XQuery expressions. Two, we propose rewriting rules to optimize XQueries by cancelling operators. Three, we describe a cutting algorithm that removes unreferenced columns and operators from the XATs. We have implemented the techniques discussed in this paper in the Rainbow system. Our experimental study compares the performance of execution before and after operator cancel out and before and after cutting.
A BIST scheme using microprogram ROM for large capacity memories (2002)

A practical microprogram ROM BIST (built-in self-test) scheme suitable for LSI memories is proposed. This BIST can be used to install N-pattern and N/sup 2/-pattern test procedures, using BIST circuits with 12-word*10-b and 16-word*16-b ROMs, respectively. As a practical test procedure, a data retention test, in which BIST circuits with an 8-word*11-b ROM were used, was investigated. BIST circuit area overheads for the above three test patterns for 16-Mb DRAMs are less than 1%, 2%, and 1.5%, respectively. A testing method for the BIST circuits themselves, with no special BIST circuit overhead, is also proposed for more practical applications. The measured operational margin for a 16-Mb DRAM using the BIST showed a good agreement with that using an LSI tester.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>