gebhart/patrepeval huggingface dataset:
Design, Synthesis, and Biological Evaluation of Potent Thiazine- and Thiazepine-Based Matrix Metalloproteinase Inhibitors (1999)

The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC(50)'s against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.
The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide (2013)

Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT(H)17) cells and memory T(H)1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.
Solution Processed Aluminum Paper for Flexible Electronics (2012)

As an alternative to vacuum deposition, preparation of highly conductive papers with aluminum (Al) features is successfully achieved by the solution process consisting of Al precursor ink (AlH(3){O(C(4)H(9))(2)}) and low temperature stamping process performed at 110 °C without any serious hydroxylation and oxidation problems. Al features formed on several kinds of paper substrates (calendar, magazine, and inkjet printing paper substrates) are less than ~60 nm thick, and their electrical conductivities were found to be as good as thermally evaporated Al film or even better (≤2 Ω/□). Strong adhesion of Al features to paper substrates and their excellent flexibility are also experimentally confirmed by TEM observation and mechanical tests, such as tape and bending tests. The solution processed Al features on paper substrates show different electrical and mechanical performance depending on the paper type, and inkjet printing paper is found to be the best substrate with high and stable electrical and mechanical properties. The Al conductive papers produced by the solution process may be applicable in disposal paper electronics.
Re-using biological devices: a model-aided analysis of interconnected transcriptional cascades designed from the bottom-up (2017)

Superior descriptive and predictive capabilities were achieved considering resource limitation modelling, but further efforts are needed to improve the accuracy of models for biological engineering.
Aβ Oligomers Induce Neuronal Cell Cycle Events in Alzheimer's Disease (2008)

Neurons subject to degeneration in Alzheimer's disease (AD) exhibit evidence of re-entry into a mitotic cell cycle even before the development of substantial AD brain pathology. In efforts to identify the initiating factors underlying these cell cycle events (CCEs), we have characterized the appearance of the neuronal CCEs in the genomic-based R1.40 transgenic mouse model of AD. Notably, R1.40 mice exhibit neuronal CCEs in a reproducible temporal and spatial pattern that recapitulates the neuronal vulnerability seen in human AD. Neuronal CCEs first appear at 6 months in the frontal cortex layers II/III. This is 6-8 months before detectable amyloid beta (Abeta) deposition, suggesting that specific amyloid precursor protein (APP) processing products are responsible for the induction of neuronal CCEs. Furthermore, a reduction in the levels of Abeta (achieved by shifting the genetic background from C57BL/6 to the DBA/2 mouse strain) dramatically delays the appearance of neuronal CCEs. More significantly, elimination of beta-secretase activity blocks the appearance of CCEs, providing direct genetic evidence that the amyloidogenic processing of APP is required for the induction of CCEs. Finally, in vitro preparations of oligomeric, but not monomeric, Abeta induce DNA synthesis in dissociated cortical neurons, and this response is blocked by antioligomer specific antibodies. Together, our data suggest that low molecular weight aggregates of Abeta induce neuronal cell cycle re-entry in mouse models of Alzheimer's disease.
Myocardial injury is decreased by late remote ischaemic preconditioning and aggravated by tramadol in patients undergoing cardiac surgery: a randomised controlled trial☆ (2010)

The purpose of this study was to test, whether the late phase of remote ischaemic preconditioning (L-RIPC) improves myocardial protection in coronary artery bypass grafting (CABG) with cold-crystalloid cardioplegia and whether preoperative tramadol modifies myocardial ischaemia-reperfusion injury using the same group of patients in a single-blinded randomized controlled study. One hundred and one adult patients were randomly assigned to either the L-RIPC, control or tramadol group. L-RIPC consisted of three five-minute cycles of upper limb ischaemia and three five-minute pauses using blood pressure cuff inflation 18 hours prior to the operation. Patients in the tramadol group received 200 mg tramadol retard at 19:00 hours, the day before the operation and at 06:00 hours. Serum troponin I levels were measured at eight, 16 and 24 hours after surgery. Myocardial samples for inducible and endothelial nitric oxide synthases (iNOS, eNOS) estimation were drawn twice: before and after cannulation for cardiopulmonary bypass from the auricle of the right atrium. We found that L-RIPC can reduce injury beyond the myocardial protection provided by cold-crystalloid cardioplegia, and tramadol worsened myocardial injury after CABG. Expressions of iNOS were increased in the control (significantly) and L-RIPC groups and dampened in the tramadol group.
MECHANICAL PROPERTIES OF TWO‐PHASE DISPERSE AGAR/GELATIN MIXED GELS (2000)

ABSTRACT Agar/gelatin mixed gels with the same composition but with a different two‐phase disperse structure were prepared and their mechanical properties compared. The agar/gelatin mixture was first kept at temperature above the gelling temperature of gelatin but below that of agar and stirred for the selected period, before cooling it below the gelling temperature of gelatin. For the low rupture stress system the agar concentration was 0.7% (w/w), while the gelatin concentration was 4.5% (w/w) to achieve the same rupture stress as the agar gel. The mixing temperatures selected were 20 and 37C. For the high rupture stress system, the agar and gelatin concentration was 2.8 and 10.4% (w/w), respectively, to achieve the same rupture stress. The mixing temperatures selected were 37 and 40C. The both mixed gels prepared by this method consisted of a dispersed phase of agar and a continuous phase of gelatin. The rupture stress of the mixed gels decreased as the content of the dispersed phase increased. The rupture stress had a tendency to be lower as the size of the dispersed particles increased. These results suggest that the interface between the dispersed phase and the continuous phase plays an important role as Griffith's crack, with the rupture of mixed gels occurring from that place.
The Systemic Amyloidoses (1997)

Amyloidosis is not a single disease but a term for diseases that share a common feature: the extracellular deposition of pathologic insoluble fibrillar proteins in organs and tissues. In the mid-19th century, Virchow adopted the botanical term “amyloid,” meaning starch or cellulose, to describe abnormal extracellular material seen in the liver at autopsy.1 Subsequently, amyloid was found to stain with Congo red, appearing red microscopically in normal light but apple green when viewed in polarized light.2,3 Almost a century after Virchow's observations, the fibrillar nature of amyloid was described with the use of electron microscopy and the characteristic beta-pleated–sheet . . .
SopD2 is a Novel Type III Secreted Effector of Salmonella typhimurium That Targets Late Endocytic Compartments Upon Delivery Into Host Cells (2003)

Salmonella typhimuriumis a facultative intracellular pathogen that utilizes two type III secretion systems to deliver virulence proteins into host cells. These proteins, termed effectors, alter host cell function to allow invasion into and intracellular survival/replication within a vacuolar compartment. Here we describe SopD2, a novel member of the Salmonella translocated effector (STE) family, which share a conserved N-terminal type III secretion signal. Disruption of the sopD2 gene prolonged the survival of mice infected with a lethal dose of Salmonella typhimurium, demonstrating a significant role for this effector in pathogenesis. Expression of sopD2 was induced inside host cells and was dependent on functional ssrA/B and phoP/Q, two component regulatory systems. HA-tagged SopD2 was delivered into HeLa cells in a SPI-2-dependent manner and associated with both the Salmonella-containing vacuole and with swollen endosomes elsewhere in the cell. Subcellular fractionation confirmed that SopD2 was membrane associated in host cells, while the closely related effector SopD was localized to the cytosol. A SopD2 fusion to GFP associated with small tubular structures and large vesicles containing late endocytic markers, including Rab7. Surprisingly, expression of N-terminal amino acids 1-150 of SopD2 fused to GFP was sufficient to mediate both binding to late endosomes/lysosomes and swelling of these compartments. These findings demonstrate that the N-terminus of SopD2 is a bifunctional domain required for both type III secretion out of Salmonella as well as late endosome/lysosome targeting following translocation into host cells.
Production of Good Manufacturing Practice Grade Equine Adiposederived Mesenchymal Stem Cells for Therapeutic Use (2013)

Mesenchymal stem cells (MSC) are currently being evaluated in equine clinical studies for their potential to treat various disorders and injuries. Studies have shown that both autologous and allogeneic stem cells appear to be safe. However, an efficient cell expansion method that is reliable and cost-effective is warranted to provide off-the-shelf clinical grade stem cells. Our study aimed to determine optimum culture conditions for efficient large-scale stem cell expansion. We produced cGMP standard equine adipose derived mesenchymal stem cells on a large scale. Five different medium combinations-Dulbecco's modified Eagle's medium-knockout (DMEM-KO), alpha modified minimum essential medium (-MEM), 50:50 DMEM-KO/-MEM, 75:25 DMEM-KO/-MEM and 25:75 DMEM-KO/-MEM-at seeding densities of 1000, 2000, 3000, 4000 and 5000 cells/cm 2 , were used to determine the optimum culture conditions for large-scale production. Growth kinetics, immunophenotypes, karyotypes, morphology, trilineage differentiation, T-cell proliferation, virus positivity, pre-clinical toxicity and expression of pluripotency markers were analysed. Among the medium combinations and seeding densities tested, 25:75 DMEM-KO/-MEM at a seeding density of 5000 cells/cm 2 was found to be optimum for large-scale expansion. This medium combination gave a significantly higher cell yield than the other medium combinations, while preserving their stem cell characteristics and differentiation potential. The results indicated that the adoption of an appropriate culture system significantly improved cell yield, thus enabling the production of sufficient cells for therapeutic application in a cost-effective manner. The results also showed that the method of large-scale expansion requires minimal manipulation of cells, and it could be expanded ex vivo within two passages while retaining the characteristics of true stem cells.
Rheology and Dynamic Light Scattering of Silk Fibroin Solution Extracted from the Middle Division ofBombyx moriSilkworm (2002)

Dynamic light scattering (DLS) and rheological measurements were performed on aqueous silk fibroin solutions extracted from the middle division of Bombyx mori silkworm over a wide range of polymer concentration C from 0.08 to 27.5 wt %. DLS results obtained in the dilute region of C less than 1 wt % are consistent with a model that an elementary unit is a large protein complex consisting of silk fibroin and P25 with a 6:1 molar ratio. Rheological measurements in the dilute C region reveal that those units (or clusters) with the hydrodynamic radius of about 100 nm form a network extending over the whole sample volume with small pseudoplateau modulus mainly by ionic bonding between COO(-) ions of the fibroin molecules and divalent metallic ions such as Ca(2+) or Mg(2+) ions present in the sample and also that, after a yield stress is reached, steady plastic flow is induced with viscosity much lower than the zero-shear viscosity estimated from creep and creep recovery measurements by 4-6 orders of magnitude. Angular frequency omega dependencies of the storage and the loss shear moduli, G'(omega) and G' '(omega), measured in the linear viscoelastic region, indicate that all solutions possess the pseudoplateau modulus in the low omega region and samples become highly viscoleastic for C greater, similar 4.2 wt %. Above C = 11.2 wt % another plateau appears at the high omega end accompanied by a distinct maximum of G' ' in the intermediate omega region. The relaxation motion with tau = 0.5 s corresponding to the maximum of G' ' is one of characteristic properties of the fibroin solutions in the high C region. Thermorheological behaviors of the solution with C = 27.5 wt % show that the network structure formed in the MM part of the silk gland is susceptible to temperature and a more stable homogeneous network is realized by raising the temperature up to T = 65 degrees C.
Legume lectins — a large family of homologous proteins (1990)

More than 70 lectins from leguminous plants belonging to different suborders and tribes have been isolated, mostly from seeds, and characterized to varying degrees. Although they differ in their carbohydrate specificities, they resemble each other in their physicochemical properties. They usually consist of two or four subunits (25-30 kDa), each with one carbohydrate binding site. Interaction with carbohydrates requires tightly bound Ca2+ and Mn2+ (or another transition metal). The primary sequences of more than 15 legume lectins have been established by chemical or molecular genetic techniques. They exhibit remarkable homologies, with a significant number of invariant amino acid residues, among them most of those involved in metal binding. The 3-dimensional structures of the legume lectins are similar, too, and are characterized by a high content of beta-sheets and a lack of alpha-helix. The location of the metal and carbohydrate binding sites, established unequivocally in concanavalin A by high resolution X-ray crystallography, appears to be the same in the other legume lectins. Several of the lectin genes have been cloned and expressed in heterologous systems. This opens the way for the application of molecular genetics to the investigation of the atomic structure of the carbohydrate binding sites of the lectins, and of the relationship between their structure and biological activity. The new approaches may also provide information on the mechanisms that control gene expression in plants and on the role of lectins in nature.
Effect of 2',3'-didehydro-3'-deoxythymidine in an in vitro hollow-fiber pharmacodynamic model system correlates with results of dose-ranging clinical studies (1994)

We sought to validate an in vitro system which could predict the minimal effect dose of antiretroviral agents. Mixtures of uninfected CEM cells and CEM cells chronically infected with human immunodeficiency virus (HIV) type 1 MN were exposed to 2',3'-didehydro-3'-deoxythymidine (D4T) in vitro in a hollow-fiber model which simulates the plasma concentration-time profile of D4T in patients. Drug concentration was adjusted to simulate continuous intravenous infusion, or an intravenous bolus administered twice daily. The effect of the dosing regimen was measured with viral infectivity, p24 antigen, and reverse transcriptase or PCR for unintegrated HIV DNA. Dose deescalation studies on a twice-daily dosing schedule predicted a minimum effect dose of 0.5 mg/kg of body weight per day which correlated with the results of a clinical trial. Antiviral effect was demonstrated to be independent of schedule for every 12-h dosing versus continuous infusion. Finally, at or near the minimal effect dose, efficacy appeared to depend on the viral load. The ability of this in vitro pharmacodynamic model to assess the response of HIV-infected cells to different doses and schedules of antiviral agents may be useful in the design of optimal dosing regimens for clinical trials but requires validation with other types of antiretroviral agents.
Precursor convertases in the secretory pathway, cytosol and extracellular milieu (2002)

Precursor proteins that transit through the secretory pathway often require processing at specific sites in order to release their bioactive entities. The most prevalent limited proteolysis occurs at single or paired basic residues, and is achieved by one or more of the seven subtilisin-like proprotein convertases (PCs); Furin, PC1, PC2, PACE4 (paired basic amino acid converting enzyme 4), PC4, PC5 and PC7. Other types of cleavages occur at hydophobic residues, some of which are performed by subtilisin/kexin-like isozyme-1 (SKI-1), which is also known as site-1 protease. Together, the PCs and SKI-1 regulate the activity of a large variety of cellular proteins, including growth factors, neuropeptides, receptors, enzymes and even toxins and glycoproteins from infectious retroviruses. These processing events are exquisitely regulated by multiple zymogen-activation steps, as well as by specific subcellular localization signals. The above mentioned convertases are implicated in a number of pathologies such as cancer, neurodegenerative diseases, endocrine disorders and inflammation. Recently, it was recognized that the metalloendopeptidase N-arginine dibasic convertase (NRDc; nardilysin), which cleaves at the N-terminus side of basic residues in dibasic pairs, is localized both in the cytosol and at the cell surface or in the extracellular milieu. While NRDc binds heparin-binding epidermal growth factor (HB-EGF) at the cell surface and potentiates its physiological effect, HB-EGF potently inhibits the NRDc's activity. NRDc could represent the equivalent of the PCs in the cytosol or the extracellular space.
Texel Shading (2016)

We have developed a texture space shading system built on modern graphics hardware. It begins with a conventional rasterization stage, but records texel accesses as shading work rather than running a shade per pixel. Shading is performed by a separate compute stage, storing the results in a texture. As a baseline, the texels correspond to those required for mipmapped texturing. A final stage collects data from the texture. Storing results in a texture allows for reuse across frames. We also show how adapting shade rate to less than once per pixel further increases performance. We vary shading load to show when these techniques provide a performance win, with up to 4.1x speedup in our experiments at shading times less than 4 ms.
Signal transduction via the histidyl‐aspartyl phosphorelay (1997)

The histidyl-aspartyl phosphorelay, formerly described as the two-component system, is the predominant mode of signal transduction in bacteria. Adaptation to environmental changes occurs through a sensor histidine protein kinase and a response regulator. The histidine protein kinase is usually a transmembrane receptor and the response regulator is a cytoplasmic protein. Together the histidyl-aspartyl phosphorelay proteins mediate reversible phosphorylation events that control downstream effectors. Following autophosphorylation at a conserved histidine residue, the histidine kinase serves as a phospho-donor for the response regulator. Once phosphorylated, the response regulator mediates changes in gene expression or cellular locomotion. The EnvZ-OmpR phosphorelay system in Escherichia coli, which monitors external osmolarity and responds by differentially modulating the expression of the OmpF and OmpC major outer membrane porins, will be described as a model system. While histidine kinases were thought to be present only in prokaryotes, they have recently been identified in eukaryotic systems. Here, we review the unique and conserved features of this growing family of signal transducers.
High Mobility Group Box Protein 1: An Endogenous Signal for Dendritic Cell Maturation and Th1 Polarization (2004)

High mobility group box protein 1 (HMGB1), a DNA binding nuclear and cytosolic protein, is a proinflammatory cytokine released by monocytes and macrophages. This study addressed the hypothesis that HMGB1 is an immunostimulatory signal that induces dendritic cell (DC) maturation. We show that HMGB1, via its B box domain, induced phenotypic maturation of DCs, as evidenced by increased CD83, CD54, CD80, CD40, CD58, and MHC class II expression and decreased CD206 expression. The B box caused increased secretion of the proinflammatory cytokines IL-12, IL-6, IL-1alpha, IL-8, TNF-alpha, and RANTES. B box up-regulated CD83 expression as well as IL-6 secretion via a p38 MAPK-dependent pathway. In the MLR, B box-activated DCs acted as potent stimulators of allogeneic T cells, and the magnitude of the response was equivalent to DCs activated by exposure to LPS, nonmethylated CpG oligonucleotides, or CD40L. Furthermore, B box induced secretion of IL-12 from DCs as well as IL-2 and IFN-gamma secretion from allogeneic T cells, suggesting a Th1 bias. HMGB1 released by necrotic cells may be a signal of tissue or cellular injury that, when sensed by DCs, induces and/or enhances an immune reaction.
Re: Use of Specialized Bone Screws for Intermaxillary Fixation (2001)

Schneider, Andrew M. MD; David, Lisa R. MD; DeFranzo, Anthony J. MD; Marks, Malcolm W. MD; Molnar, Joseph A. MD,PhD; Argenta, Louis C. MD Author Information