gebhart/patrepeval huggingface dataset:
Expression and signaling specificity of the IFNAR chain of the type I interferon receptor complex. (1995)

The IFNAR chain of the type I interferon (IFN) receptor (IFNIR) undergoes rapid ligand-dependent tyrosine phosphorylation and acts as a species-specific transducer for type I IFN action. Using the vaccinia/T7 expression system to amplify IFNAR expression, we found that human HeLa-S3 cells transiently express high levels of cell surface IFNAR chains (approximately 250,000 chains per cell). Metabolic labeling and immunoblot analysis of transfected HeLa cells show that the IFNAR chain is initially detected as 65-kDa and 98-kDa precursors, and then as the 130-kDa mature protein. Due to variation in N-glycosylation, the apparent molecular mass of the mature IFNAR chain varies from 105 to 135 kDa in different cells. IFNIR structure was characterized in various human cell lines by analyzing 125I-labeled IFN cross-linked complexes recognized by various antibodies against IFNIR subunits and JAK protein-tyrosine kinases. Precipitation of cross-linked material from Daudi cells with anti-IFNAR antibodies showed that IFNAR was present in a 240-kDa complex. Precipitation of cross-linked material from U937 cells with anti-TYK2 sera revealed a 240-kDa complex, which apparently did not contain IFNAR and was not present in IFN-resistant HEC1B cells. The tyrosine phosphorylation and down-regulation of the IFNAR chain were induced by type I IFN in several human cell lines of diverse origins but not in HEC1B cells. However, of type I IFNs, IFN-beta uniquely induced the tyrosine phosphorylation of a 105-kDa protein associated with the IFNAR chain in two lymphoblastoid cell lines (Daudi and U266), demonstrating the specificity of transmembrane signaling for IFN-beta and IFN-alpha through the IFNAR chain.
Overcoming the Challenges of Solid Bridging and Constriction during Pd-Catalyzed C−N Bond Formation in Microreactors (2010)

We investigate the mechanisms that govern plugging in microreactors during Pd-catalyzed amination reactions. Both bridging and constriction were shown to be important mechanisms that lead to clogging in our system and greatly limited the utility of microsystems for this class of reactions. On the basis of these observations, several approaches were engineered to overcome the challenge of plugging and to enable the continuous-flow synthesis of a biarylamine. Bridging could be eliminated with acoustic irradiation while constriction was managed via fluid velocity and the prediction of growth rates.
Substrate Specificities of Escherichia coli Thioesterase I/Protease I/Lysophospholipase L1 Are Governed by Its Switch Loop Movement (2005)

Escherichia coli thioesterase I/protease I/lysophospholipase L(1) (TAP) is a multifunctional lysophospholipase and acyl-CoA thioesterase with a SGNH-hydrolase fold. The relationship between TAP's structure and its versatile substrate specificity, however, is unclear. Here, we present the crystal structure of TAP in complex with octanoic acid (TAP-OCA; OCA, a free fatty acid with eight carbon atoms, C(8)). A structural comparison of native TAP with TAP-OCA reveals a remarkable conformational change in loop(75)(-)(80), called "switch loop movement", upon OCA binding to the substrate-binding crevice of TAP. OCA binding to the substrate-binding crevice results in a continuous hydrophobic surface, which triggers switch loop movement. The switch loop movement is acyl chain length dependent, with an effect of stabilizing the Michaelis complex (MC) of TAP during catalysis, and is essential for TAP's substrate preference. The finding of a sulfate ion binding site in the TAP structures, together with previous enzyme kinetic analyses, leads us to postulate that a putative CoA binding site is essential for efficient catalysis of thioesters in TAP. We also present the crystal structure of L109P-OCA (TAP's L109P mutant in complex with OCA), in which Leu109 mutated to Pro109 abolishes switch loop movement. This result strengthens our hypothesis that the switch loop movement is induced by hydrophobic interactions.
Static analysis of programs with application to malicious core detection (1992)

The goal of this research was to develop a method of detecting malicious code (e.g., computer viruses, worms, Trojan-horses, and time/logic bombs) and security-related vulnerabilities in system programs. The Malicious Code Filter (MCF) is a programmable static analysis tool developed for this purpose. It allows system administrators and security analysts to examine a program before installation, thereby avoiding any damage a malicious program might inflict. This dissertation has addressed several issues in malicious code detection: (1) We investigated and classified malicious code. Based on this analysis, we developed the tell-tale sign approach to distinguish malicious code from benign programs. The novel idea about tell-tale signs is that they allow us to determine whether or not a program is malicious without requiring a programmer to provide a formal specification. (2) We generalized program slicing to reason about tell-tale malicious properties. Program slicing produces a bona-fide program--a subset of the original program behaving exactly the same with respect to the realization of a specified property. By combining the tell-tale sign approach with program slicing, we can examine a small subset of a large program to conclude whether or not the program is malicious. (3) We demonstrated the capabilities of the tell-tale sign approach and program slicing to detect some common UNIX vulnerabilities. (4) We determined how our approach can be defeated and developed countermeasures--the well-behavedness check. Static analysis produces inaccurate slices on a program that has pointer overflows, out-of bounds array accesses, or self-modifying code. Well-behavedness check applies flow analysis (integer-range analysis) and verification techniques (loop invariant generation, verification condition generation, and theorem proving) to identify such problematic cases.
The MCF is designed in a modular way so that it can serve as a platform for further malicious code research including dynamic analysis and testing-based detection techniques.
Molecular Evolution of Zika Virus during Its Emergence in the 20th Century (2014)

Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda in 1947. Although entomological and virologic surveillance have reported ZIKV enzootic activity in diverse countries of Africa and Asia, few human cases were reported until 2007, when a Zika fever epidemic took place in Micronesia. In the context of West Africa, the WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever at Institut Pasteur of Dakar (http://www.pasteur.fr/recherche/banques/CRORA/) reports the periodic circulation of ZIKV since 1968. Despite several reports on ZIKV, the genetic relationships among viral strains from West Africa remain poorly understood. To evaluate the viral spread and its molecular epidemiology, we investigated 37 ZIKV isolates collected from 1968 to 2002 in six localities in Senegal and Côte d'Ivoire. In addition, we included strains from six other countries. Our results suggested that these two countries in West Africa experienced at least two independent introductions of ZIKV during the 20(th) century, and that apparently these viral lineages were not restricted by mosquito vector species. Moreover, we present evidence that ZIKV has possibly undergone recombination in nature and that a loss of the N154 glycosylation site in the envelope protein was a possible adaptive response to the Aedes dalzieli vector.
Metformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic Review (2013)

Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
Design of polymeric nanoparticles for biomedical delivery applications (2012)

Polymeric nanoparticles-based therapeutics show great promise in the treatment of a wide range of diseases, due to the flexibility in which their structures can be modified, with intricate definition over their compositions, structures and properties. Advances in polymerization chemistries and the application of reactive, efficient and orthogonal chemical modification reactions have enabled the engineering of multifunctional polymeric nanoparticles with precise control over the architectures of the individual polymer components, to direct their assembly and subsequent transformations into nanoparticles of selective overall shapes, sizes, internal morphologies, external surface charges and functionalizations. In addition, incorporation of certain functionalities can modulate the responsiveness of these nanostructures to specific stimuli through the use of remote activation. Furthermore, they can be equipped with smart components to allow their delivery beyond certain biological barriers, such as skin, mucus, blood, extracellular matrix, cellular and subcellular organelles. This tutorial review highlights the importance of well-defined chemistries, with detailed ties to specific biological hurdles and opportunities, in the design of nanostructures for various biomedical delivery applications.
Iron, Infections, and Anemia of Inflammation (1997)

Iron is essential to all microorganisms. To obtain iron from the very low concentrations present in their environment, microorganisms have developed sophisticated mechanisms such as the siderophore system. As a primitive defense mechanism, humans have developed mechanisms to withhold iron from microorganisms. Iron-binding proteins such as transferrin, ferritin, and lactoferrin have a central role in human ferrokinetics. These iron-binding proteins also participate in the process of decreasing iron availability for the microorganisms. They do so by decreasing iron reutilization. Anemia of inflammation (previously called anemia of chronic disease) is seen in the setting of infectious, inflammatory, and neoplastic diseases. It results, in part, from changes in the intracellular metabolism of iron. Alterations of iron physiology seen in many clinical circumstances make excess iron available to microorganisms, thus enhancing their pathogenicity. Understanding the molecular basis of iron withholding by the human host, both in the absence of and during infection, and that of iron acquisition by microorganisms may provide us with new and innovative antimicrobial agents and vaccines.
Somnis de la raó tecnològica. A propòsit de Bodies in technology de Don Ihde (2002)

L'article preten aprofitar la lectura d'un llibre del teoric
nord-america Don Ihde per reflexionar sobre la
relacio contemporania entre tecnologia, cos i
percepcio. Totes les epoques es pensen a si
mateixes mitjancant conceptes pertanyents mes al
seu passat que al present que els incumbeix, pero
poques vegades s'ha donat una disparitat tan gran
entre la complexitat d'allo que succeeix i la simplicitat
que s'utilitza per pensar-ho com en la nostra.
El llibre d'Ihde, Bodies in technology, te la virtut de
suggerir eines per omplir aquesta bretxa, ates que
ens fa ser conscients que en l'actualitat aquestes
nocions -tecnologia, cos i percepcio- han deixat
d'esser, actuar i significar com ens fa suposar la
inercia.
Genistein, a dietary-derived inhibitor of in vitro angiogenesis. (1993)

Consumption of a plant-based diet can prevent the development and progression of chronic diseases that are associated with extensive neovascularization; however, little is known about the mechanisms. To determine whether prevention might be associated with dietary-derived angiogenesis inhibitors, we have fractionated urine of healthy human subjects consuming a plant-based diet and examined the fractions for their abilities to inhibit the proliferation of vascular endothelial cells. Using gas chromatography-mass spectrometry, we showed that one of the most potent fractions contained several isoflavonoids, which we subsequently synthesized. Of all synthetic compounds, the isoflavonoid genistein was the most potent and inhibited endothelial cell proliferation and in vitro angiogenesis at concentrations giving half-maximal inhibition of 5 and 150 microM, respectively. As we have previously demonstrated, genistein concentrations in urine of subjects consuming a plant-based diet are in the micromolar range, while those of subjects consuming a traditional Western diet are lower by a factor of > 30. The high excretion of genistein in urine of vegetarians and our present results suggest that genistein may contribute to the preventive effect of a plant-based diet on chronic diseases, including solid tumors, by inhibiting neovascularization. Thus, genistein may represent a member of a new class of dietary-derived anti-angiogenic compounds.
BACE2 is Stored in Secretory Granules of Mouse and Rat Pancreatic β Cells (2008)

BACE2 is a protease homologous to BACE1 protein, an enzyme involved in the amyloid formation of Alzheimer disease (AD). However, despite the high homology between these two proteins, the biological role of BACE2 is still controversial, even though a few studies have suggested a pathogenetic role in sporadic inclusion-body myositis and hereditary inclusion-body myopathy, which are characterized by vacuolization of muscular fibers with intracellular deposits of proteins similar to those found in the brain of AD patients. Although BACE2 has also been identified in the pancreas, its function remains unknown and its specific localization in different pancreatic cell types has not been definitively ascertained. For these reasons, the authors have investigated the cellular and subcellular localization of BACE2 in normal rodent pancreases. BACE2 immunoreactivity was found in secretory granules of beta cells, co-stored with insulin and IAPP, while it was lacking in the other endocrine and exocrine cell types. The presence of BACE2 in secretory granules of beta cells suggests that it may play a role in diabetes-associated amyloidogenesis.
A Short, Efficient Copper-Mediated Synthesis of 1α,25-Dihydroxyvitamin D2 (1α,25-Dihydroxyergocalciferol) and C-24 Analogs1,2 (1997)

Two synthetic routes to the nonnatural hormone 1α,25-dihydroxyergocalciferol [2b, 1α,25-(OH)2-D2] and analogs modified at C-24 have been developed both starting from aldehyde 7b. Key steps in route A (eight steps, ≈38% overall yield from 7b) are (1) stereoselective addition of (E)-vinyllithium reagent 8c to aldehyde 7b; and (2) SN2‘ anti-displacement of the allylic phosphate of 5e by organocuprates derived from Grignard reagents and CuCN in the presence of LiCl. Key steps in route B (eight steps from 7b, 48% overall yield) are (1) Wittig−Horner type coupling between ketone 22, which bears an allylic phosphate group on the side chain, and the ylide derived from the Lythgoe−Roche phosphine oxide to form the vitamin D triene unit; and (2) efficient SN2‘ anti-displacement of the phosphate group of 23 by the organocuprate derived from MeMgCl, CuCN, and LiCl, without affecting the labile vitamin D triene system, to give, after deprotection, 1α,25-(OH)2-D2. Route B is particularly attractive as an approach to diverse C-24 vitamin D analogs for biological screening.
Developments in Automatic Text Retrieval (1991)

Recent developments in the storage, retrieval, and manipulation of large text files are described. The text analysis problem is examined, and modern approaches leading to the identification and retrieval of selected text items in response to search requests are discussed.
Rock magnetic studies on sediments from Erlongwan maar lake, Long Gang Volcanic Field, Jilin province, NE China (2006)

Detailed rock magnetic investigations were carried out on two 23-m-long sediment cores from Erlongwan maar lake, NE China. The completely laminated sediment sequence of the lake is interrupted by 410 graded layers with thicknesses between 0.1 and 150 cm. Magnetite of PSD-size was identified as the main magnetic carrier mineral by temperature-dependent measurements of the saturation magnetization and determination of hysteresis parameters. The minerogenic components in the laminated sediments and the graded layers are nearly identical, and their rock magnetic characteristics reflect the prevailing conditions, anoxic or oxic, during deposition. The most reliable criteria for estimating the availability of oxygen is whether an increase in minerogenic influx is linked to a shift in the magnetic grain size spectrum to coarser (oxic) or finer (anoxic) grains. Comparison of different rock magnetic parameters indicative for magnetic grain size and coercitivity revealed, that the S-ratio which is known to reflect the presence of high coercive minerals, is grain size indicative in sediments with a monomineralic magnetic composition.
Deaths attributable to smallpox vaccination, 1959 to 1966, and 1968 (1970)

There were 68 deaths in the United States from complications of smallpox vaccination in the nine years 1959 to 1966, and 1968; 19 were associated with vaccinia necrosum, 36 were caused by postvaccinial encephalitis, 12 by eczema vaccinatum, and 1 by Stevens-Johnson syndrome. Of the 68 who died, 24 were infants, although only 12% of all primary vaccinations are given to this age group. All of the deaths from eczema vaccinatum were in children who were not vaccinated themselves, but acquired vaccinia from a sibling, playmate, or parent. This suggests that reduction of the number of deaths from eczema vaccinatum cannot be established by screening vaccinees alone. Reducing the number of primary vaccinations performed would lower the risks of acquiring eczema vaccinatum and postvaccinial encephalitis.
Creation of Functional Membranes Using Polyelectrolyte Multilayers and Polymer Brushes (2008)

Over the last 15 years, the layer-by-layer deposition of polyelectrolytes and the growth of polymer brushes from surfaces have become established techniques for the formation of a wide range of thin films. This article discusses the use of these techniques in creating the skin layer of nanofiltration or gas-separation membranes and in functionalizing the interior of membranes for protein adsorption or catalysis. In the case of separation membranes for nanofiltration, the minimal thickness of layer-by-layer films allows for high flux, and the wide range of available polyelectrolytes that can form these films permits the tailoring of membranes for separations such as water softening, the reduction of F (-) concentrations, and the removal of dyes from wastewater. For gas separation, polymers grown from surfaces are more attractive than layer-by-layer coatings because most polyelectrolyte films are not highly gas-selective. Cross-linked poly(ethylene glycol dimethacrylate) films grown from porous alumina exhibit CO(2)/CH(4) selectivities of around 20, and the careful selection of monomers should further improve the selectivity of similar membranes. Both layer-by-layer methods and polymer brushes can also be employed to modify the interior of membranes, and we have utilized these techniques to create catalysts, antibody arrays in membranes, and membrane absorbers for protein purification. Polymer brushes are particularly attractive because they allow the absorption of multilayers of protein to yield membranes with binding capacities as high as 150 mg protein/cm(3). Some challenges in the practical implementation of these systems, such as the economical formation of membranes using highly permeable polymeric supports, and future directions in research on membrane modification with multilayer films and polymer brushes are also discussed herein.
LC–MS Analysis of Polyclonal Human Anti-Neu5Gc Xeno-Autoantibodies Immunoglobulin G Subclass and Partial Sequence Using Multistep Intravenous Immunoglobulin Affinity Purification and Multienzymatic Digestion (2012)

Human polyclonal IgG antibodies directly against the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc) are potential biomarkers and mechanistic contributors to cancer and other diseases associated with chronic inflammation. Using a sialoglycan microarray, we screened the binding pattern of such antibodies (anti-Neu5Gc IgG) in several samples of clinically approved human IVIG (IgG). These results were used to select an appropriate sample for a multistep affinity purification of the xeno-autoantibody fraction. The sample was then analyzed via our multienzyme digestion procedure followed by nano liquid chromatography (nanoLC) coupled to linear ion trap-Fourier transform mass spectrometry (LTQ-FTMS). We used characteristic and unique peptide sequences to determine the IgG subclass distribution and thus provided direct evidence that all four IgG subclasses can be generated during a xeno-autoantibody immune response to carbohydrate Neu5Gc-antigens. Furthermore, we obtained a significant amount of sequence coverage of both the constant and variable regions. The approach described here, therefore, provides a way to characterize these clinically significant antibodies, helping to understand their origins and significance.
Raman spectroscopic detection using a two-dimensional spatial heterodyne spectrometer (2015)

Spatial heterodyne Raman spectroscopy (SHRS) is a type of method for the detection of Raman spectra and can achieve a very high spectral resolution. SHRS has no moving parts and can be built with rugged, compact packages, making it extremely suitable for planetary exploration. However, if a high spectral resolution is needed, a traditional one-dimensional spatial heterodyne spectrometer cannot achieve a broad bandpass because it is limited by the number of pixels of the detector. In order to solve this, two-dimensional (2-D) SHRS can be used to broaden the bandpass. A breadboard of 2-D SHRS has been designed and built, and some artificial and natural targets have been tested to learn about the detection ability of 2-D SHRS. The results show that 2-D SHRS can be used to detect Raman signals scattered from liquid and solid targets. When the Raman scattered signal is strong, it can even detect targets in containers. The detection of anti-Stokes Raman shift for sulfur and carbon tetrachloride has also been tried, and the results show that 2-D SHRS has the ability to detect anti-Stokes Raman shift below 500 cm−1. The research may have a general implication in chemical analysis and planetary exploration.
Overall resettlement action plan (2004)

The Chongqing Urban Management Project consists of seven components in water supply, sewage treatment, and refuse treatment and disposal in five cities of Chongqing Municipality. This resettlement action plan (RAP) is composed of a main summary report and six final RAPs related to each project component in Chongqing, Fuling, Wanzhou, and Nan Bin. The resettlement program will ensure that the production levels, income-earning capacity, and living standards of project affected persons (PAPs) can be improved, or at least restored to the level prior to that before implementation of the RAP. The following measures will be taken to safeguard the entitlements of the affected people: 1) Special care will be taken for vulnerable groups: assistance in building and moving into resettlement areas and new houses, and allocation of specific compensations. 2) Compensation to the collective for cultivation losses and land acquisition will mainly be used to increase the productive capacity of the collective. 3) Assistance will be provided to PAPs to select their new sites, build their new houses, and adjust to their new environment. 4) The implementation of both land acquisition and resettlement will be monitored and evaluated by an independent monitoring institute. Representatives of PAPs will participate in the organization of the resettlement; and the institution concerned will define appropriate procedures and provide means to redress any grievances.