gebhart/patrepeval huggingface dataset:
Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity. (1993)

Mechanisms of T cell-mediated cytotoxicity remain poorly defined at the molecular level. To investigate some of these mechanisms, we used as target cells, on the one hand, thymocytes from lpr and gld mouse mutants, and on the other hand, L1210 cells transfected or not with the apoptosis-inducing Fas molecule. These independent mutant or transfectant-based approaches both led to the conclusion that Fas was involved in the Ca(2+)-independent component of cytotoxicity mediated by at least two sources of T cells, namely nonantigen-specific in vitro activated hybridoma cells, and antigen-specific in vivo raised peritoneal exudate lymphocytes. Thus, in these cases, T cell-mediated cytotoxicity involved transduction via Fas of the target cell death signal.
Cloning of the immunological repertoire in Escherichia coli for generation of monoclonal catalytic antibodies: construction of a heavy chain variable region-specific cDNA library. (1989)

Efficient generation of catalytic antibodies is uniquely dependent on the exact nature of the binding interactions in the antigen-antibody complex. Current methods for generation of monoclonal antibodies do not efficiently survey the immunological repertoire and, therefore, they limit the number of catalysts that can be obtained. We are exploring methods to clone and express the immunological repertoire in Escherichia coli. As the essential first step, we present here a method for the establishment of a highly diverse heavy chain variable region library. Consequently, it should now be possible to express and recombine the heavy and light chain variable region fragments to generate a large array of functional combining portions of the antibody molecule. This technology may provide an alternative to the hybridoma methodology for accessing the monoclonal antibody specificity of the immune system.
Anatomically Based Modelling of the Human Skull and Jaw (2005)

We present here an anatomically based model of the human masticatory system that provides a framework for simulating the complex chewing process. The initial motivation for creating this model was the desire to have a computational model of the human jaw that can be used to simulate the action of simple bites, and to calculate the stresses and forces on the teeth that are involved. The model created also provides a platform that can be used to investigate other features of the masticatory system. To construct this global model, individual models of the bones of the skull and jaw were created from generic data sets. Geometric models of the muscles of mastication were also created and attached to the appropriate bones. To complete this initial model, representations of the crowns of the teeth were created and a basic model of the temporomandibular joint (TMJ) was included. The finite element method was used to solve for the stresses and strains created by the loading conditions during a clenching simulation involving the mandible bone. The model presented here is also discussed in relation to a model of the entire musculo-skeletal system being developed as part of the Physiome Project.
A Simplified Severity Scale for Age-Related Macular Degeneration (2005)

This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.
Acetyl- l -carnitine fed to old rats partially restores mitochondrial function and ambulatory activity (1998)

Mitochondrial function and ambulatory activity were monitored after feeding old rats acetyl-L-carnitine (ALCAR). Young (3-5 mo) and old (22-28 mo) rats were given a 1.5% (wt/vol) solution of ALCAR in their drinking water for 1 mo, were sacrificed, and their liver parenchymal cells were isolated. ALCAR supplementation significantly reverses the age-associated decline of mitochondrial membrane potential, as assessed by rhodamine 123 staining. Cardiolipin, which declines significantly with age, is also restored. ALCAR increases cellular oxygen consumption, which declines with age, to the level of young rats. However, the oxidant production per oxygen consumed, as measured by 2',7'-dichlorofluorescin fluorescence levels, is approximately 30% higher than in untreated old rats. Cellular glutathione and ascorbate levels were nearly 30% and 50% lower, respectively, in cells from ALCAR-supplemented old rats than in untreated old rats, further indicating that ALCAR supplementation might increase oxidative stress. Ambulatory activity in young and old rats was quantified as a general measure of metabolic activity. Ambulatory activity, defined as mean total distance traveled, in old rats is almost 3-fold lower than in young animals. ALCAR supplementation increases ambulatory activity significantly in both young and old rats, with the increase being larger in old rats. Thus, ALCAR supplementation to old rats markedly reverses the age-associated decline in many indices of mitochondrial function and general metabolic activity, but may increase oxidative stress.
Telomerase in Yeast (1995)

The ribonucleoprotein enzyme telomerase synthesizes telomeric DNA by copying an internal RNA template sequence. The telomerase activities of the yeasts Saccharomyces castellii and Saccharomyces cerevisiae--with regular and irregular telomeric sequences, respectively--have now been identified and characterized. The S. cerevisiae activity required the telomerase RNA gene TLC1 but not the EST1 gene, both of which are required for normal telomere maintenance in vivo. This activity exhibited low processivity and produced no regularly repeated products. An inherently high stalling frequency of the S. cerevisiae telomerase may account for its in vitro properties and for the irregular telomeric sequences of this yeast.
Evidence that glutamic acid 167 is an active-site residue of Shiga-like toxin I. (1988)

Escherichia coli Shiga-like toxin I, a close relative of Shiga toxin and a distant relative of the ricin family of plant toxins, inhibits eukaryotic protein synthesis by catalyzing the depurination of adenosine 4324 in 28S rRNA. By comparing the crystallographic structure of ricin with amino acids conserved between the Shiga and ricin toxin families, we identified seven potential active-site residues of Shiga-like toxin I. The structural gene encoding Shiga-like toxin I A chain (Slt-IA), the enzymatically active subunit, was engineered for high expression in E. coli. Oligonucleotide-directed mutagenesis of the gene for Slt-IA was used to change glutamic acid 167 to aspartic acid. As measured by an in vitro assay for inhibition of protein synthesis, the specific activity of mutant Slt-IA was decreased by a factor of 1000 compared to wild-type Slt-IA. Immunoblots showed that mutant and wild-type Slt-IA were synthesized as full-length proteins and were processed correctly by signal peptidase. Both proteins were equally susceptible to trypsin digestion, suggesting that the amino acid substitution did not produce a major alteration in Slt-IA conformation. We conclude that glutamic acid 167 is critical for activity of the Shiga-like toxin I A chain and may be located at the active site.
Amphiphilic liquid‐crystalline networks — phase behavior and alignment by mechanical fields (1995)

Abstract A cross‐linked polysiloxane carrying non‐ionic amphiphilic side‐groups attached with their hydrophobic end to the polymer backbone is synthesized. The amphiphilic groups are selectively deuterated at the α‐position of the hydrophobic alkyl chains. The phase behavior with water is studied by deuterium nuclear magnetic resonance spectroscopy. A lamellar phase (L a ) is observed on the low‐water‐concentration side of the liquid‐crystalline regime. The domains of the L a ‐phase can be aligned macroscopically by uniaxial compression of the sample.
Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas (2009)

Plasmonic nanomaterials have the opportunity to considerably improve the specificity of cancer ablation by i.v. homing to tumors and acting as antennas for accepting externally applied energy. Here, we describe an integrated approach to improved plasmonic therapy composed of multimodal nanomaterial optimization and computational irradiation protocol development. We synthesized polyethylene glycol (PEG)-protected gold nanorods (NR) that exhibit superior spectral bandwidth, photothermal heat generation per gram of gold, and circulation half-life in vivo (t(1/2), approximately 17 hours) compared with the prototypical tunable plasmonic particles, gold nanoshells, as well as approximately 2-fold higher X-ray absorption than a clinical iodine contrast agent. After intratumoral or i.v. administration, we fuse PEG-NR biodistribution data derived via noninvasive X-ray computed tomography or ex vivo spectrometry, respectively, with four-dimensional computational heat transport modeling to predict photothermal heating during irradiation. In computationally driven pilot therapeutic studies, we show that a single i.v. injection of PEG-NRs enabled destruction of all irradiated human xenograft tumors in mice. These studies highlight the potential of integrating computational therapy design with nanotherapeutic development for ultraselective tumor ablation.
White cell‐reduced platelet concentrates prepared by in‐line filtration of platelet‐rich plasma (1995)

Prestorage filtration of PRP and the preparation of filtered platelets do not result in any significant beneficial or adverse effect on subsequent platelet quality. With the large-capacity filter, consistent WBC reduction and good platelet yields are achieved.
Three-dimensional static parametric modelling of phasic colonic contractions for the purpose of microprocessor-controlled functional stimulation (2001)

The study aimed at creating an integrated electromechanical model of invoked phasic contractions in canine colon during direct high frequency voltage stimulation. The model utilized data obtained from two large anaesthetized dogs that underwent laparotomy and serosal implantation of two circumferential electrode pairs into a distal segment of the left colon. The strength distribution of the stimulating electric field was analysed over a cylindrical mesh-surface grid modelling the interrogated colonic segment. Recordings of the stimulating current were utilized to model smooth muscle depolarization using linearized macroscopic tissue conductivity. The invoked contractile stress was related to the stimulating electric field strength using an exponential sigmoid function. Artificially produced occlusion of the lumen was derived for a pair of 5mm electrodes positioned on a cylindrical mesh-surface of 2 cm diameter and 15 cm length. The model simulated contractions invoked by stimuli of different amplitude (up to 12 V) with 98.6% accuracy of approximation. Macroscopic tissue conductivity was modelled as a combination of two first-order exponential terms involving a 3ms time constant. Real-time simulation of the current drawn by the smooth muscle during 10 V/50Hz bipolar voltage stimulation was performed. The integrated electromechanical model facilitates the quantification of microprocessor-controlled phasic colonic contractions.
Treatment of thrombosed hemodialysis access grafts: Arrow-Trerotola percutaneous thrombolytic device versus pulse-spray thrombolysis. Arrow-Trerotola Percutaneous Thrombolytic Device Clinical Trial. (1998)

The PTD is safe and effective for treating thrombosed hemodialysis access grafts. The technical and long-term success rates are similar to those of PSPMT; procedure times are shorter.
Structure and Function Studies of Factor XIIIa by x-ray Crystallography (1996)

The three-dimensional structures of several forms of the factor XIII A subunit have been determined using single crystal x-ray diffraction methods. Our crystallographic studies have provided the first detailed structural view of the factor XIII A subunit and information that is useful for understanding transglutaminase function. We have identified a conserved Cys314-His373-Asp396 catalytic triad of residues in the active site of the molecule and a number of other conserved residues that may play important roles as well. The calcium and strontium structures have revealed several conserved acidic residues (Asp438, Glu485, and Glu490) involved in ion binding. We have also been able to use our crystal structures as scaffolds to model the possible structural effects of missense mutations that have been identified in factor XIII-deficient patients.
Stereoselective Synthesis of Novel Chimerical Amino Acids via a Photochemical Key Step (1999)

The synthesis of novel chimerical amino acid derivatives 6-8 bearing the 6-azatricyclo[3.3.1.03,7]nonane (methanotropane)skeleton is described. Starting with one chirality centre in L-4-oxoprolines 2 we succeeded in the fully stereoselective introduction of four new chirality centres. The key step of our synthetic route is a photochemical cyclization of phenyl ketones, whose stereoselectivity has been explained by the different stability of the triplet biradical conformers.
The Anti-inflammatory Properties of Cocoa Flavanols (2006)

Signs of chronic or acute inflammation have been demonstrated in most cardiovascular diseases of multifactorial pathogenesis, including atherosclerosis and chronic heart failure. The triggers and mechanisms leading to inflammation may vary between clinical conditions but they share many common mediators, including specific patterns of eicosanoid and cytokine production. Certain cocoa-based products can be rich in a subclass of flavonoids known as flavanols, some of which have been found in model systems to possess potential anti-inflammatory activity relevant to cardiovascular health. Indeed, experimental evidence demonstrates that some cocoa-derived flavanols can reduce the production and effect of pro-inflammatory mediators either directly or by acting on signaling pathways. However, it should be noted that the evidence for any beneficial effects of cocoa flavanols in providing a meaningful anti-inflammatory action has been gathered predominantly from in vitro experiments. Therefore, additional research in well-designed human clinical experiments, using cocoa properly characterized in terms of flavanol content, would be a welcome addition to the evidence base to determine unambiguously if this benefit does indeed exist. If so, then flavanol-rich cocoa could be a potential candidate for the treatment, or possibly prevention, of the broad array of chronic diseases that are linked to dysfunctional inflammatory responses.
Electrically Driven Varifocal Silicon Metalens (2018)

Optical metasurfaces have shown to be a powerful approach to planar optical elements, enabling an unprecedented control over light phase and amplitude. At that stage, where a wide variety of static functionalities have been accomplished, most efforts are being directed toward achieving reconfigurable optical elements. Here, we present our approach to an electrically controlled varifocal metalens operating in the visible frequency range. It relies on dynamically controlling the refractive index environment of a silicon metalens by means of an electric resistor embedded into a thermo-optical polymer. We demonstrate precise and continuous tuneability of the focal length and achieve focal length variation larger than the Rayleigh length for voltage as small as 12 V. The system time-response is of the order of 100 ms, with the potential to be reduced with further integration. Finally, the imaging capability of our varifocal metalens is successfully validated in an optical microscopy setting. Compared to conventional bulky reconfigurable lenses, the presented technology is a lightweight and compact solution, offering new opportunities for miniaturized smart imaging devices.
CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. (1990)

Budding in the yeast Saccharomyces cerevisiae involves a polarized deposition of new cell surface material that is associated with a highly asymmetric disposition of the actin cytoskeleton. Mutants defective in gene CDC24, which are unable to bud or establish cell polarity, have been of great interest with regard to both the mechanisms of cellular morphogenesis and the mechanisms that coordinate cell-cycle events. To gain further insights into these problems, we sought additional mutants with defects in budding. We report here that temperature-sensitive mutants defective in genes CDC42 and CDC43, like cdc24 mutants, fail to bud but continue growth at restrictive temperature, and thus arrest as large unbudded cells. Nearly all of the arrested cells appear to begin nuclear cycles (as judged by the occurrence of DNA replication and the formation and elongation of mitotic spindles), and many go on to complete nuclear division, supporting the hypothesis that the events associated with budding and those of the nuclear cycle represent two independent pathways within the cell cycle. The arrested mutant cells display delocalized cell-surface deposition associated with a loss of asymmetry of the actin cytoskeleton. CDC42 maps distal to the rDNA on chromosome XII and CDC43 maps near lys5 on chromosome VII.
Size-Tunable, Bright, and Stable PbS Quantum Dots: A Surface Chemistry Study (2011)

PbS Qdots are synthesized using PbCl2 and elemental sulfur as precursors. The available size range is significantly expanded using tri-n-octylphosphine (TOP), enabling the synthesis of monodisperse suspensions of Qdots with a mean size varying between 3 and 10 nm. The ligand composition and dynamics are investigated with nuclear magnetic resonance (NMR) spectroscopy. We show that the Qdots are passivated solely by highly dynamic OlAm ligands, even when TOP is employed during synthesis. In this respect, TOP is a compound strongly modifying the Qdot synthesis, without affecting the final Qdot surface chemistry. Next, the OlAm ligands are exchanged for oleic acid (OlAc). NMR data show that the OlAc ligands are tightly bound to the Qdot surface, with a coverage of 3.0±0.4 nm(-2). In addition, we demonstrate that they are bound as oleate ions. Combining this with the inorganic Qdot composition, we observe that charge-neutral Qdots are obtained when taking into account the charge of the stoichiometric PbS Qdot core, the surface excess of Pb ions, the surface-adsorbed Cl ions and the oleate ligands. The Qdot suspensions are stable under atmospheric conditions, showing no changes in the NMR and absorbance spectra for several weeks. Finally, we determine the photoluminescence quantum yield (PL QY) for OlAc-capped PbS Qdots, synthesized either with or without TOP. In both cases, they are highly luminescent, with PL QY values varying between 20 and 90%, depending on the Qdot size.
Identification of Residues Contributing to A2 Domain-dependent Structural Stability in Factor VIII and Factor VIIIa (2008)

Factor VIII circulates as a heterodimer composed of heavy (A1A2B domains) and light (A3C1C2 domains) chains, whereas the contiguous A1A2 domains are separate subunits in the active cofactor, factor VIIIa. Whereas the A1 subunit maintains a stable interaction with the A3C1C2 subunit, the A2 subunit is weakly associated in factor VIIIa and its dissociation accounts for the labile activity of the cofactor. In examining the ceruloplasmin-based factor VIII A domain model, potential hydrogen bonding based upon spatial separations of <2.8A were found between side chains of 14 A2 domain residues and 7 and 9 residues in the A1 and A3 domains, respectively. These residues were individually replaced with Ala, except Tyr residues were replaced with Phe, and proteins stably expressed to examine the contribution of each residue to protein stability. Factor VIII stability at 55 degrees C and factor VIIIa activity were monitored using factor Xa generation assays. Fourteen of 30 factor VIII mutants showed >2-fold increases in either or both decay rates compared with wild type; whereas, 7 mutants showed >2-fold increased rates in factor VIIIa decay compared with factor VIII decay. These results suggested that multiple residues at the A1-A2 and A2-A3 domain interfaces contribute to stabilizing the protein. Furthermore, these data discriminate residues that stabilize interactions in the procofactor from those in the cofactor, where hydrogen bonding in the latter appears to contribute more significantly to stability. This observation is consistent with an altered conformation involving new inter-subunit interactions involving A2 domain following procofactor activation.
Quantitative DNA analysis of low-level hepatitis B viremia in two patients with serologically negative chronic hepatitis B (1999)

Low-level viremia due to hepatitis B virus (HBV) was demonstrated in the sera of two patients diagnosed previously as having non-B, non-C chronic hepatitis. Both patients had a "silent" HBV infection, because they were negative for both hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody. The TaqMan chemistry polymerase chain reaction (PCR) amplified the HBV DNA, enabling quantitation of the virus in their sera. Their serum HBV DNA concentrations were low: the amount of each HBV S or X gene amplified showed there were approximately 10(3) copies/ml and HBV DNA was detected occasionally during clinical follow-up. Positive HBsAg staining in liver tissues was demonstrated by an immunoperoxidase technique. Vertical transmission of silent HBV from one patient to her daughter was confirmed. Direct nucleotide sequencing of the amplified HBV X region revealed several mutations, suggesting reduced viral replication. One patient had a T-to-C mutation at the extreme 5'-terminus of the direct repeat 2 region and the other exhibited a coexisting X region with a 155-nucleotide deletion. These findings suggest that HBV replication is suppressed considerably in patients with silent hepatitis B.
Regional Delivery of an Adenovirus Vector Containing the Escherichia coli Cytosine Deaminase Gene to Provide Local Activation of 5-Fluorocytosine to Suppress the Growth of Colon Carcinoma Metastatic to Liver (1996)

To evaluate the hypothesis that regional delivery of an adenovirus vector containing the Escherichia coli cytosine deaminase gene (AdCMV.CD) together with systemic 5-FC could suppress the growth of metastatic colon cancer in the liver, the AdCMV.CD vector was injected 0.8-1 cm from the site of a human colon cancer tumor in the livers of nude mice. The growth of the human colon cancer cells was quantified by dot blot analysis of genomic DNA extracted from tumor-bearing liver, hybridized with a human-specific Alu probe. The combination of regional AdCMV.CD plus systemic 5-fluorocytosine (5-FC) suppressed the growth of the metastatic tumors over the 21 days of evaluation following vector administration. Histologic evaluation showed necrosis at the site of the tumor in the livers of mice treated with AdCMV.CD/5-FC, but not in control groups. Evaluation of the potential toxicity of AdCMV.CD plus 5-FC on the normal liver showed only mild, self-limited dose-related inflammation, with no deaths. These data suggest that the regional administration of AdCMV.CD together with systemic 5-FC may be a safe and effective strategy to suppress the growth of metastases of colorectal carcinoma in the liver.