gebhart/patrepeval huggingface dataset:
A generic virus detection agent on the Internet (2002)

The dissemination of software has never been so easy since the Internet became widely available. This ease of access to free software has also pushed the wide spread of viruses to a new plateau. We present VICEd, a system for generic virus detection over the Internet. VICEd is based on a virus detection methodology which is a combination of software emulation and knowledge base. It detects viruses using their behaviour instead of pattern matching. It is thus more effective against unknown or mutated viruses than scanners. This methodology is interesting in its own right. VICEd is a member of a group of system management agents currently under development at the National Taiwan University.
Controlling a Single Protein in a Nanopore through Electrostatic Traps (2008)

Protein-protein pore interaction is a fundamental and ubiquitous process in biology and medical biotechnology. Here, we employed high-resolution time-resolved single-channel electrical recording along with protein engineering to examine a protein-protein pore interaction at single-molecule resolution. The pore was formed by Staphylococcus aureus alpha-hemolysin (alphaHL) protein and contained electrostatic traps formed by rings of seven aspartic acid residues placed at two different positions within the pore lumen. The protein analytes were positively charged presequences (pb2) of varying length fused to the small ribonuclease barnase (Ba). The presence of the electrostatic traps greatly enhanced the interaction of the pb2-Ba protein with the alphaHL protein pore. This study demonstrates the high sensitivity of the nanopore technique to an array of factors that govern the protein-protein pore interaction, including the length of the pb2 presequence, the position of the electrostatic traps within the pore lumen, the ionic strength of the aqueous phase, and the transmembrane potential. Alterations in the functional properties of the pb2-Ba protein and the alphaHL protein pore and systematic changes of the experimental parameters revealed the balance between forces driving the pb2-Ba protein into the pore and forces driving it out.
Ago-Allosteric Modulation and Other Types of Allostery in Dimeric 7TM Receptors (2006)

Conventionally, an allosteric modulator is neutral in respect of efficacy and binds to a receptor site distant from the orthosteric site of the endogenous agonist. However, recently compounds being ago-allosteric modulators have been described i.e., compounds acting both as agonists on their own and as enhancers for the endogenous agonists in both increasing agonist potency and providing additive efficacy-superagonism. The additive efficacy can also be observed with agonists, which are neutral or even negative modulators of the potency of the endogenous ligand. Based on the prevailing dimeric concept for 7TM receptors, it is proposed that the ago-allosteric modulators bind in the orthosteric binding site, but-importantly-in the "other" or allosteric protomer of the dimer. Hereby, they can act both as additive co-agonists, and through intermolecular cooperative effects between the protomers, they may influence the potency of the endogenous agonist. It is of interest that at least some endogenous agonists can only occupy one protomer of a dimeric 7TM receptor complex at a time and thereby they leave the orthosteric binding site in the allosteric protomer free, potentially for binding of exogenous, allosteric modulators. If the allosteric modulator is an agonist, it is an ago-allosteric modulator; if it is neutral, it is a classical enhancer. Molecular mapping in hetero-dimeric class-C receptors, where the endogenous agonist clearly binds only in one protomer, supports the notion that allosteric modulators can act through binding in the "other" protomer. It is suggested that for the in vivo, clinical setting a positive ago-allosteric modulator should be the preferred agonist drug.
Soluble Form of P-Selectin in Plasma Is Elevated in Acute Lung Injury (1995)

A number of adhesion molecules on neutrophils and the pulmonary capillary endothelium mediate the neutrophil accumulation in the lungs at the onset of adult respiratory distress syndrome or acute lung injury (ALI). P-selectin, located on both vascular endothelial cells and platelets, has been shown to be one of these neutrophil-endothelial cell adhesion molecules. In this study, we measured the soluble form of P-selectin in plasma (PPS) from 19 patients (surviving, 11; deceased, 8) with ALI due to various causes and assessed the clinical significance of this measurement. Twelve healthy subjects and 29 patients with other pulmonary diseases, including idiopathic pulmonary fibrosis (IPF) (n = 8), sarcoidosis (n = 5), pneumonia (n = 8), and sepsis without ALI (n = 8) were also studied for comparison. PPS in patients with ALI (474.5 +/- 366.8 ng/ml, mean +/- SD) were significantly higher than those in control subjects (98.8 +/- 39.7, p < 0.01) and in patients with IPF (210.4 +/- 76.6, p < 0.05), sarcoidosis (135.2 +/- 71.5, p < 0.05), pneumonia (225.3 +/- 81.0, p < 0.05), and sepsis without ALI (271.8 +/- 46.5, p < 0.05). There was no significant difference in PPS levels between seven patients with and 12 patients without multiple organ failure. Lung injury scores correlated significantly with the PPS level (r = 0.605, p < 0.05). PPS levels of deceased patients with ALI (841.0 +/- 252.4) were significantly higher than those of surviving patients with ALI (208.0 +/- 109.2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Real-time Monitoring of the Interactions of Transforming Growth Factor-β (TGF-β) Isoforms with Latency-associated Protein and the Ectodomains of the TGF-β Type II and III Receptors Reveals Different Kinetic Models and Stoichiometries of Binding (2001)

Mature transforming growth factor-beta (TGF-beta) is proteolytically derived from the C terminus of a precursor protein. Latency-associated protein (LAP), the N-terminal remnant of the TGF-beta precursor, is able to bind and neutralize TGF-beta. Mature TGF-beta exerts its activity by binding and complexing members of two subfamilies of receptors, the type I and II receptors. In addition to these signaling receptors, TGF-beta can also interact with an accessory receptor termed the type III receptor. Using a surface plasmon resonance-based biosensor (BIAcore), we determined the mechanisms of interaction of four binding proteins (LAP, the type II and III receptor ectodomains (EDs), and a type II receptor ED/Fc chimera) with three TGF-beta isoforms, and we quantified their related kinetic parameters. Using global fitting based on a numerical integration data analysis method, we demonstrated that LAP and the type II receptor/Fc chimera interacted with the TGF-beta isoforms with a 1:1 stoichiometry. In contrast, the type II ED interactions with TGF-beta were best fit by a kinetic model assuming the presence of two independent binding sites on the ligand molecule. We also showed that the type III ED bound two TGF-beta molecules. Further experiments revealed that LAP was able to block the interactions of TGF-beta with the two EDs, but that the two EDs did not compete or cooperate with each other. Together, these results strongly support the existence of a cell-surface complex consisting of one type III receptor, two TGF-beta molecules, and four type II receptors, prior to the recruitment of the type I receptor for signal transduction. Additionally, our results indicate that the apparent dissociation rate constants are more predictive of the neutralizing potency of these TGF-beta-binding proteins (LAP, the type II and III receptor EDs, and the type II receptor/Fc chimera) than the apparent equilibrium constants.
Canine parvovirus-like particles, a novel nanomaterial for tumor targeting (2006)

Specific targeting of tumor cells is an important goal for the design of nanotherapeutics for the treatment of cancer. Recently, viruses have been explored as nano-containers for specific targeting applications, however these systems typically require modification of the virus surface using chemical or genetic means to achieve tumor-specific delivery. Interestingly, there exists a subset of viruses with natural affinity for receptors on tumor cells that could be exploited for nanotechnology applications. For example, the canine parvovirus (CPV) utilizes transferrin receptors (TfRs) for binding and cell entry into canine as well as human cells. TfRs are over-expressed by a variety of tumor cells and are widely being investigated for tumor-targeted drug delivery. We explored whether the natural tropism of CPV to TfRs could be harnessed for targeting tumor cells. Towards this goal, CPV virus-like particles (VLPs) produced by expression of the CPV-VP2 capsid protein in a baculovirus expression system were examined for attachment of small molecules and delivery to tumor cells. Structural modeling suggested that six lysines per VP2 subunit are presumably addressable for bioconjugation on the CPV capsid exterior. Between 45 and 100 of the possible 360 lysines/particle could be routinely derivatized with dye molecules depending on the conjugation conditions. Dye conjugation also demonstrated that the CPV-VLPs could withstand conditions for chemical modification on lysines. Attachment of fluorescent dyes neither impaired binding to the TfRs nor affected internalization of the 26 nm-sized VLPs into several human tumor cell lines. CPV-VLPs therefore exhibit highly favorable characteristics for development as a novel nanomaterial for tumor targeting.
Cast-in-Place Cellulose Fiber-Reinforced Cement Paste, Mortar, and Concrete (2005)

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Agmatine inhibits matrix metalloproteinase-9 via endothelial nitric oxide synthase in cerebral endothelial cells (2007)

Our study supports that the down-regulation of MMP-9 by agmatine runs parallel to the up-regulation of eNOS and the maintenance of functional NO release.
52.4L Transmissive One‐Side‐Emission OLED Panel using Alignment‐Free Cathode Patterning (2015)

We propose a new technique to fabricate a transmissive one‐side‐emission OLED panel with alignment‐free cathode patterning. This technique can reduce the non‐luminescent and non‐transparent area and result in the enlargement of luminescent area. The luminance of the fabricated panel was improved 1.28 times and high transmittance was kept.
Localization of an Fc-binding reactivity to the constant region of human IgG4. Implications for the pathogenesis of rheumatoid arthritis (1995)

The majority of plasma cells in rheumatoid arthritis (RA) synovium produce rheumatoid factors (RF). IgG RF predominate in the immune complexes found in RA synovial fluid and have been implicated in the pathogenesis of RA. IgG4 RF are a major component of IgG RF produced in serum and synovium of RA patients, even though this subclass comprises only 4% of the serum IgG. We produced an IgG4 mAb, hRF-1, with RF reactivity from the synovial tissue of a patient with RA. mAb hRF-1 had binding specificity for mammalian IgG similar to Staphylococcus aureus protein A, which is characteristic of RF from patients with RA. To determine the molecular basis of this particular RF reactivity, the heavy and light chain genes of mAb hRF-1 were amplified by PCR, cloned, and ligated into the pSG5 plasmid for expression in COS-7 cells. Chain recombination experiments localized the Fc-binding reactivity to the hRF-1 heavy chain. Using a series of chimeric Ab sequences, the Fc-binding reactivity was mapped to the constant region of IgG4 rather than the variable region involved in classic RF reactivity. Multiple domains, including Hinge, CH2, and CH3 of the IgG4 constant region were required for Fc binding. Our studies demonstrate an example of RF-like Fc-binding reactivity that is conferred by the gamma-4 constant region rather than the classic Ag binding site and suggest that increased production of IgG4 may contribute to the pathogenesis of RA.
Inhibition of the Inflammasome Complex Reduces the Inflammatory Response after Thromboembolic Stroke in Mice (2008)

Inflammation is a major contributor to the pathogenesis of cerebral ischemia and stroke. In the peripheral immune response, caspase-1 activation involves the formation of a macromolecular complex termed the inflammasome. We determined whether nucleotide-binding, leucine-rich repeat, pyrin domain containing 1 (NLRP1), molecular platform consisting of capase-1, apoptosis-associated speck-like protein containing a caspase-activating recruitment domain (ASC), and NLRP1, is expressed in the normal and postischemic brain. Mice underwent thromboembolic stroke to investigate the formation of the inflammasome and subsequent activation of downstream inflammatory responses. Western blot analysis showed expression and activation of interleukin (IL) IL-1beta and IL-18 at 24 h after stroke. Size-exclusion chromatography and coimmunoprecipitation analysis showed protein association between NLRP1, ASC, caspase-1, and the X-linked inhibitor of apoptosis protein (XIAP). After ischemia, immunohistochemical analysis revealed inflammasome proteins in neurons, astrocytes, and microglia/macrophages. The potential of the inflammasome as an antiinflammatory target was showed by interference of inflammasome activation resulting in reduced cytokine levels in mice treated after ischemia with a neutralizing antibody against NLRP1. These findings show that the inflammasome complex forms after focal brain ischemia and may be a novel therapeutic target for reducing the detrimental consequences of postischemic inflammation.
Correspondence between high affinity 125I‐neurotensin binding sites and dopaminergic neurons in the rat substantia nigra and ventral tegmental area: A combined radioautographic and immunohistochemical light microscopic study (1989)

Several lines of anatomical, biochemical, and pharmacological evidence have suggested that specific high affinity neurotensin binding sites are associated with dopamine-containing neurons in the rat ventral tegmentum. In the present study we confirmed and quantified the extent of this association by combining monoiodinated neurotensin radioautography and tyrosine hydroxylase immunohistochemistry on adjacent 5-10 microns-thick midbrain sections. We found that 95-100% tyrosine hydroxylase-immunoreactive neurons detected in all subdivisions of the substantia nigra (pars compacta, pars lateralis, and pars reticulata) exhibited intense 125I-neurotensin labeling in adjacent light microscopic radioautographs. Tyrosine hydroxylase-positive dendrites radiating downward from compacta neurons were also heavily labeled throughout the pars reticulata. In the paranigral subdivision of the ventral tegmental area, silver grains were evenly distributed over neuropil and perikarya and therefore could not be readily attributed to any given tyrosine hydroxylase-positive element. In contrast, within the parabrachial pigmentous subdivision of the ventral tegmental area, 80-90% of the tyrosine hydroxylase-immunoreactive somata and proximal processes were clearly in register with 125I-neurotensin labeled cells. Finally, all tightly packed TH-positive neurons in the interfascicular nucleus showed intense 125I-neurotensin labeling. The vast majority of the neurotensin binding sites observed in the ventral midbrain tegmentum were of the high affinity, physiologically active receptor type since levocabastine, a selective blocker of the low affinity neurotensin binding component, had minimal effect on the binding density in any of the midbrain regions examined. The present results demonstrate an extensive overlap between specific, high affinity neurotensin binding sites and dopamine perikarya and dendrites in the rat ventral tegmentum, and thereby provide a direct anatomical substrate for observed neurotensin-dopamine interactions in the mesocorticolimbic and nigrostriatal projection systems.
Alcoholic hepatitis: A comprehensive review of pathogenesis and treatment (2014)

Alcoholic hepatitis (AH) is an acute hepatic inflammation associated with significant morbidity and mortality. Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism, inflammation and innate immunity. Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH; such as Child-Turcotte-Pugh score, the Maddrey discriminant function, the Lille Model, the model for end stage liver disease scores, and the Glasgow alcoholic hepatitis score. At present, Corticosteroids or pentoxifylline are the current pharmacologic treatment options; though the outcomes from the therapies are poor. Liver transplantation as the treatment of alcoholic hepatitis remains controversial, and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option. Because of the limitations in the therapeutic options, it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.
Single Domain Antibodies for the Detection of Ricin Using Silicon Photonic Microring Resonator Arrays (2012)

Ricin is a lethal protein toxin derived from the castor bean plant. Given its notorious history as a biowarfare agent and homicidal weapon, ricin has been classified as a category B bioterrorism agent. Current ricin detection methods based on immunoassays lack the required sensitivity and specificity for many homeland security surveillance applications. Importantly, many conventional antibody-based methodologies are unable to distinguish ricin from RCA 120, a nontoxic protein also found in the castor bean plant. Single domain antibodies (sdAbs), which are recombinantly derived from immunized llamas, are known to have high affinities for ricin A or B chains and low cross-reactivity with RCA 120. Herein, we demonstrate the use of silicon photonic microring resonators for antibody affinity profiling and one-step ricin detection at concentrations down to 300 pM using a 15 min, label-free assay format. These sdAbs were also simultaneously compared with a commercial anti-RCA IgG antibody in a multicapture agent, single target immunoassay using arrays of microrings, which allowed direct comparison of sensitivity and specificity. A selected sdAb was also found to exhibit outstanding specificity against another biotoxin, saporin, which has mechanism of action similar to ricin. Given the rapidity, scalability, and multiplexing capability of this silicon-based technology, this work represents a step toward using microring resonator arrays for the sensitive and specific detection of biowarfare agents.
RNA sequence and secondary structure requiresments for rho-dependent transcription termination (1985)

The interaction of E. coli termination factor rho with the nascent RNA transcript appears to be a central feature of the rho-dependent transcription termination process. Based on in vitro studies of the rho-dependent termination of the transcript initiated at the PR promoter of bacteriophage lambda, and on earlier studies, Morgan, Bear and von Hippel (J. Biol. Chem. 258, 9565-9574, 1983) proposed a model defining the features of a potential binding site for rho protein on transcripts subject to rho-dependent termination. This model suggested that an effective rho binding site on a nascent RNA transcript should be: (i) greater than 70-80 nucleotide residues in length; (ii) essentially unencumbered with stable secondary structure; (iii) relatively sequence non-specific; and (iv) located within a few hundred nucleotide residues upstream of the potential rho-dependent terminus. In this paper we examine the sequences and secondary structures of several transcripts that exhibit rho-dependent termination to test this hypothesis further. Unstructured regions of approximately the expected size and location were found on all the transcripts examined. Though several short specific sequence elements were found to occur in a very similar arrangement on the lambda PR- and lambda PL-initiated transcripts of lambda phage, no such elements of sequence regularity were found on any of the other rho-dependent transcripts. The results of the sequence comparisons reported here strongly support the generality of the "unstructured binding site" hypothesis for rho-dependent termination.
Development of an Automated Multiple Material Stereolithography Machine (2006)

An automated Multiple Material Stereolithography (MMSL) machine was developed by integrating components of a 3D Systems 250/50 stereolithography (SL) machine in a separate stand-alone system and adapting them to function with additional components required for MMSL operation. We previously reported retrofitting a 250/50 SL machine with multiple vats to accommodate multiple material fabrication for building a wide variety of multi-material models (Wicker et al., 2004). In the MMSL retrofit, spatial constraints limited the multiple vats located circumferentially on a vertical rotating vat carousel to cross-sectional areas of approximately 4.5-inches by 4.5-inches. The limited build size of the retrofitted 250/50 motivated the full development of a new system with multiple material build capabilities comparable to the build envelope of the original 250/50 machine. The new MMSL machine required fabrication of a large system frame, incorporating various 250/50 components and software, and adding a variety of new components and software. By using many existing components and software, the previous engineering development of 3D Systems could be directly applied to this new technology. Components that were transferred from an existing 250/50 to the MMSL machine included the complete optical system (including the optics plate with laser, mirrors, beam expander, scanning mirrors, and focusing lens), the rim assembly (including the laser beam profilers), the associated controllers (computer system, scanning mirror controller, power supply-vat controller) and the wiring harness. In addition to the new frame, the MMSL machine required the development of a new rotating vat carousel system, platform assembly, multi-pump filling/leveling system, and a custom LabVIEW® control system to provide automated control over the MMSL process. The overall operation of the MMSL system was managed using the LabVIEW® program, which also included controlling a new vat leveling system and new linear and rotational stages, while the 3D Systems software (Buildstation 4.0) was retained for controlling the laser scanning process. As a demonstration of MMSL technology, simple multi material parts were fabricated with vertically and horizontally oriented interfaces. The fully functional MMSL system offers enormous potential for fabricating a wide variety of multiple material functional devices.
Facile Epoxidation of Alumina-Supported Electrophilic Alkenes and Montmorillonite-Supported Electrophilic Alkenes with Sodium Hypochlorite (1987)

Alkenes gem-substituted by two electron-withdrawing substituents, dispersed on alumina or montmorillonite, are conveniently epoxided by sodium hypochlorite. A mixture of aldehyde and methylcyanoacetate or malononitrile, treated with alumina and sodium hypochlorite gives the corresponding epoxide in good yield.