gebhart/patrepeval huggingface dataset:
An expert system approach to parameterized module synthesis (1988)

An expert system that converts a description of transistor connectivity into a parameterized CMOS modules is presented. PAMS (parameterized module synthesis) was designed to augmented a standard cell environment by automatically generating special-purpose modules parameterized in terms of area, speed, and power dissipation. A frame-based approach facilitates the representation of specific parameterization-domain knowledge. Allowing parameterization differentiates PAMS from previous expert systems in this field.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes (2009)

The serine/threonine family of Pim kinases function as oncogenes and have been implicated in prostate cancer progression, particularly in hormone-refractory prostate disease, as a result of their antiapoptotic function. In this study, we used a pharmacologic inhibitor targeting the Pim family members, SGI-1776, to determine whether modulation of Pim kinase activity could alter prostate cancer cell survival and modulate chemotherapy resistance. Extensive biochemical characterization of SGI-1776 confirmed its specificity for the three isoforms of the Pim family. Treatment of prostate cancer cells with SGI-1776 resulted in a dose-dependent reduction in phosphorylation of known Pim kinase substrates that are involved in cell cycle progression and apoptosis (p21(Cip1/WAF1) and Bad). Consequently, SGI-1776 compromised overall cell viability by inducing G(1) cell cycle arrest and triggering apoptosis. Overexpression of recombinant Pim-1 markedly increased sensitivity of SGI-1776-mediated prostate cancer cell apoptosis and p21(Cip1/WAF1) phosphorylation inhibition, reinforcing the specificity of SGI-1776. An additional cytotoxic effect was observed when SGI-1776 was combined with taxane-based chemotherapy agents. SGI-1776 was able to reduce cell viability in a multidrug resistance 1 protein-based taxane-refractory prostate cancer cell line. In addition, SGI-1776 treatment was able to resensitize chemoresistant cells to taxane-based therapies by inhibiting multidrug resistance 1 activity and inducing apoptosis. These findings support the idea that inhibiting Pim kinases, in combination with a chemotherapeutic agent, could play an important role in prostate cancer treatment by targeting the clinical problem of chemoresistance.
Chlorination of water used for poultry processing (1968)

Synopsis The effect on bacterial numbers in the spin‐chillers and on the processed carcasses in a large broiler processing plant of increasing the amount of free residual chlorine by stages from 0 to 20 p.p.m. has been studied. The count at 22° C. on nutrient agar in the chillers and on the birds was lowest at the 18–20 p.p.m. level of chlorine. This effect was less at the 5–8 and 10–13 P‐P‐m. levels. Faecal streptococci, and Staphylococcus aureus on the carcasses were not significantly affected by increasing the chlorine concentration. Coli‐aerogenes numbers were significantly reduced in the spin‐chillers at the highest chlorine level. It is concluded that 18–20 p.p.m. of free chlorine in a suitable water supply is of value in broiler processing but that lower levels of chlorine may not be effective.
Mechanistic Insight into CM18-Tat11 Peptide Membrane-Perturbing Action by Whole-Cell Patch-Clamp Recording (2014)

The membrane-destabilization properties of the recently-introduced endosomolytic CM18-Tat11 hybrid peptide (KWKLFKKIGAVLKVLTTG-YGRKKRRQRRR, residues 1-7 of cecropin-A, 2-12 of melittin, and 47-57 of HIV-1 Tat protein) are investigated in CHO-K1 cells by using the whole-cell configuration of the patch-clamp technique. CM18-Tat11, CM18, and Tat11 peptides are administered to the cell membrane with a computer-controlled micro-perfusion system. CM18-Tat11 induces irreversible cell-membrane permeabilization at concentrations (≥4 µM) at which CM18 triggers transient pore formation, and Tat11 does not affect membrane integrity. We argue that the addition of the Tat11 module to CM18 is able to trigger a shift in the mechanism of membrane destabilization from "toroidal" to "carpet", promoting a detergent-like membrane disruption. Collectively, these results rationalize previous observations on CM18-Tat11 delivery properties that we believe can guide the engineering of new modular peptides tailored to specific cargo-delivery applications.
Classification and properties of 64 multiplexed microsphere sets. (1998)

We describe a practical method for the analysis of multiple analytes in a single sample. The vehicle for each separate measurement consists of a set of microspheres identifiable by characteristic fluorophores embedded in the particles. The use of robust, bench-top flow cytometers (flow microfluorimeters) for the analysis of the multiple sets of microspheres is facilitated by hardware and software, which acquire the data from the cytometer, classify the microspheres according to sets, and collate measurement information from each microsphere set in real time. This measurement system can analyze up to 64 analytes in a single sample. The advantages of multiplexed assays using flow cytometry include robust measurements, because each microsphere set is measured repeatedly. The advantage of the assay's is consistent with simultaneous measurement of many parameters as well as the speed with which the flow microfluorimeter (cytometer) makes measurements (many hundreds per second). Here, we describe the properties of the microspheres, the calibration of the cytometer, and the influence of the properties of the microspheres on the sensitivity of measurements.
A novel endogenous erythropoietin mediated pathway prevents axonal degeneration (2004)

Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy.
Windows Registry and Hiding Suspects' Secret in Registry (2008)

Windows registry, a central repository for configuration data, should be investigated for obtaining forensic evidences, since it contains lots of information that are of potential evidential value. Using some forensic tools, forensic examiners can investigate values of windows registry and get information can be forensic evidences. However, since windows registry contains huge amount of values and these values can be modified by users, suspect can hide his secret like password in registry values. In this paper, we discuss the basics of Windows XP registry and extract some registry entries related to forensic analysis. Finally, we show that some countermeasures are needed, listing up consideration items for hiding secrets in registry as suspect's viewpoint.
Voronoi binding site model of a polycyclic aromatic hydrocarbon binding protein (1990)

A three-dimensional Voronoi binding site model has been formulated from a series of competitors for the binding site on a recently isolated polycyclic aromatic hydrocarbon binding protein (PBP) from mouse liver. The PBP binds polycyclic aromatic hydrocarbons, such as benzo[a]pyrene (B[a]P), with high affinity and shows other characteristics associated with receptor-ligand complexes. Altogether, the in vitro binding constant of seven molecules were used to deduce the geometry and the energetics of a possible site model consisting of five regions: one tetrahedron-shaped finite central hydrophobic pocket, one infinite region representing access to the solvent, and three strongly repulsive regions representing the sterically forbidden walls of the pocket. The model then predicted the binding energies correctly for nine additional competitors and suggests that competition of monoaromatic (benzene) derivatives with B[a]P would be weak.
Liposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) or gemcitabine plus cisplatin in advanced cholangiocarcinoma: The AIO-NIFE-trial, an open label, randomized, multicenter phase II trial. (2018)

TPS4145 Background: Biliary tract cancer (CCC) is associated with a poor prognosis due to mostly advanced stages at diagnosis. Overall survival does not exceed 6 months and the 5-year overall survival rate is less than 5% for patients with advanced or metastatic disease. Advanced CCC shows response to chemotherapy resulting in an improved disease control, improved survival and quality of life (QoL). In the ABC-02 phase III trial, gemcitabine combined with cisplatin compared with gemcitabine alone prolonged PFS (8.0 vs. 5.0 mo) and OS (11.7 vs. 8.1 mo) and is considered as standard of care. So far this regimen has not been compared with other active combination regimen. Irinotecan in combination with 5-FU showed promising results in 1st- and 2nd-line therapy in many GI cancers. In pancreatic adenocarcinomas, the combination of liposomal irinotecan (nal-IRI) plus 5-FU/LV improves survival in a post gemcitabine-based treatment setting. Our research hypothesis is that this regimen compares well with respect to clinical endpoints with the standard of care gemcitabine plus cisplatin in patients with advanced CCC. Methods: NIFE is a randomized study for patients (to be enrolled n = 92) with locally advanced or metastatic, non-resectable, intra- or extrahepatic cholangiocarcinoma): Arm A (experimental): Nal-IRI 80 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2, on day 1, cycle q2w), Arm B (standard): Cisplatin 25 mg/m2 and Gemcitabine 1000 mg/m2 on day 1 and 8, cycle q3w. NIFE is an open label, non-comparative, multicenter, two-sided phase II study with an unconnected analysis of the results in both arms against a fixed PFS rate ( < 40% at 6months). The randomization (1:1) is eminent to achieve two comparable patient groups. Primary objective is PFS at 6 months. Key secondary objectives are 3-year OS, PFS, ORR, DCR and QoL/TUDD. There will be a retrospective surgical and radiological review. Tissue and blood sample collection will be mandatory for biomarker analyses (microdissection and exome sequencing of tumor tissue, ctDNA exome sequencing, transcriptome, miRNA-arrays). Start was in Q I/2018 in 25 centers in Germany. Clinical trial information: NCT03044587.
Glutamate: The New Frontier in Pharmacotherapy for Cocaine Addiction (2008)

Considerable research into the neurobiology of cocaine addiction has shed light on the role of glutamate. Findings from models of relapse to cocaine-seeking indicate that the glutamatergic system is critically involved, as glutamate levels in the nucleus accumbens increase during reinstatement and glutamate receptor activation is necessary for reinstatement to drug-seeking. Thus, it would seem beneficial to block the increased glutamate release, but full antagonists of ionotropic glutamate receptors produce undesirable side effects. Therefore, modulation of glutamatergic transmission would be advantageous and provide novel pharmacotherapeutic avenues. Pharmacotherapies have been developed that have the potential to modulate excessive glutamatergic transmission through ionotropic and metabotropic (mGluR) glutamate receptors. Compounds that modulate glutamatergic transmission through ionotropic glutamate receptors include the non-competitive N-methyl-D-aspartic acid antagonists, amantadine and memantine, and the partial N-methyl-D-aspartic acid agonist d-cycloserine. They have shown promise in preclinical models of cocaine addiction. The mGluR2/3 agonist LY379268 is effective in inhibiting cocaine seeking in preclinical animal models and could decrease stress-induced relapse due to its anxiolytic effects. Similarly, the mGluR1/5 antagonists, 2-methyl-6-(phenylethynyl)pyridine and 3-[2-methyl-4-thiazolyl)ethynyl]pyridine, have shown to be effective in preclinical models of cocaine addiction. The cysteine pro-drug, N-acetylcysteine, restores the inhibitory tone on presynaptic glutamate receptors and has been effective in reducing cue-induced craving and cocaine use in humans. Furthermore, anticonvulsants, such as topiramate or lamotrigine, have shown efficacy in treating cocaine dependence or reducing relapse in humans. Future pharmacotherapy may focus on manipulating signal transduction proteins and pathways, which include Homer/N-methyl-D-aspartic acid complexes, to provide effective treatment for cocaine addiction.
Reactive Immunization Suppresses Advanced Glycation and Mitigates Diabetic Nephropathy (2009)

Agents that inhibit glycation end products by reducing the carbonyl load from glycation and glycoxidation are an emerging pharmacologic approach to treat complications of diabetes. We previously demonstrated that antibodies generated to the glycoprotein keyhole limpet hemocyanin (KLH) can cross-link with reactive carbonyl residues on protein conjugates. Here, we immunized streptozotocin-induced diabetic rats with KLH to assess the capacity of the elicited antibodies to intercept carbonyl residues on glycated proteins and to mitigate glycation-related pathology. Compared with diabetic rats immunized with adjuvant alone, KLH-immunized diabetic rats had decreased levels of glycated peptides in sera and demonstrated a reduction in albuminuria, proteinuria, deposition of glycation end products in the kidney, and histologic damage. In vitro, low molecular weight glycated peptides from rat serum reacted with anti-KLH antibodies at a faster rate than normal IgG and selectively modified the lambda chains. The reaction products contained peptide sequences from type I collagen alpha chain, albumin, and LDL receptor-related protein. These adduction reactions were inhibited by free KLH and by reduction of glycated peptides with borohydride. In summary, these results suggest that inherent reactivity of Ig light chains provides a natural mechanism for the removal of cytotoxic glycation products. This reactivity can be augmented by glycoprotein-specific reactive immunization, a potential biopharmaceutical approach to glycation-related pathology.
Engineering therapeutic monoclonal antibodies (2008)

During last two decades, the chimerization and humanization of monoclonal antibodies (mAbs) have led to the approval of several for the treatment of cancer, autoimmune diseases, and transplant rejection. Additional approaches have been used to further improve their in vivo activity. These include combining them with other modalities such as chemotherapy and redesigning them for improved pharmacokinetics, effector function, and signaling activity. The latter has taken advantage of new insights emerging from an increased understanding of the cellular and molecular mechanisms that are involved in the interaction of immunoglobulin G with Fc receptors and complement as well as the negative signaling resulting from the hypercrosslinking of their target antigens. Hence, mAbs have been redesigned to include mutations in their Fc portions, thereby endowing them with enhanced or decreased effector functions and more desirable pharmacokinetic properties. Their valency has been increased to decrease their dissociation rate from cells and enhance their ability to induce apoptosis and cell cycle arrest. In this review we discuss these redesigned mAbs and current data concerning their evaluation both in vitro and in vivo.
Cellular Mechanisms that Control Pulmonary Vascular Tone during Hypoxia and Normoxia: Possible Role of Ca 2+ ATPases (1992)

We investigated cellular mechanisms that may be involved in controlling cytosol calcium and pulmonary artery pressure during hypoxia and normoxia in isolated blood-perfused ferret lungs. Alveolar hypoxia in ferret lungs causes an active increase in pulmonary vascular resistance. Hypoxic pulmonary vasoconstriction directly correlates with extracellular calcium ([Ca2+]o), and the absence of [Ca2+]o in the perfusate markedly attenuates the hypoxemia-induced pulmonary vasoconstriction. Alveolar hypoxia does not potentiate the production of thromboxane B2 (TxB2) or 6-keto-PGF1 alpha. Vanadate, a widely used inhibitor of Ca2+ATPases, increases pulmonary arterial pressure (Ppa) in the presence or absence of [Ca2+]o and without affecting the production of TxB2 or 6-keto-PGF1 alpha. Vanadate and ouabain, an inhibitor of Na+/K+ATPase, produce synergistic increases in Ppa. Amiloride, an inhibitor of Na+/Ca2+ exchange, reverses the increase in Ppa caused by ouabain, but not the increase caused by vanadate. The additional effect produced by ouabain on Ppa after near maximal vanadate effect and the ability of amiloride to reverse the pulmonary vasoconstriction caused by ouabain, but not vanadate, suggests that vanadate does not inhibit Na+/K+ATPase in ferret lungs. In addition, cyclic GMP (cGMP), which has been reported to increase the activity of Ca2+ATPases in vascular smooth muscle, was able to reverse and prevent the effect of vanadate on Ppa, but not the effect of ouabain. Inhibition of Ca2+ATPases with vanadate in ferret lungs increases pulmonary vascular resistance during both normoxia and hypoxia. The Ca2+ entry mediated by alveolar hypoxia appears to overpower the ability of Ca2+ATPases and other membrane Ca2+ transport proteins to translocate [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)
MVA: The Multimodal Virtual Assistant (2014)

Michael Johnston, John Chen, Patrick Ehlen, Hyuckchul Jung, Jay Lieske, Aarthi Reddy, Ethan Selfridge, Svetlana Stoyanchev, Brant Vasilieff, Jay Wilpon. Proceedings of the 15th Annual Meeting of the Special Interest Group on Discourse and Dialogue (SIGDIAL). 2014.
Genetic dissection ofnodalfunction in patterning the mouse embryo (2001)

Loss-of-function analysis has shown that the transforming growth factor-like signaling molecule nodal is essential for mouse mesoderm development. However, definitive proof of nodal function in other developmental processes in the mouse embryo has been lacking because the null mutation blocks gastrulation. We describe the generation and analysis of a hypomorphic nodal allele. Mouse embryos heterozygous for the hypomorphic allele and a null allele undergo gastrulation but then display abnormalities that fall into three distinct mutant phenotypic classes, which may result from expression levels falling below critical thresholds in one or more domains of nodal expression. Our analysis of each of these classes provides conclusive evidence for nodal-mediated regulation of several developmental processes in the mouse embryo, beyond its role in mesoderm formation. We find that nodal signaling is required for correct positioning of the anteroposterior axis, normal anterior and midline patterning, and the left-right asymmetric development of the heart, vasculature, lungs and stomach.
Direct estimation of motion and extended scene structure from a moving stereo rig (2002)

We investigate the relationship between the kinematics (infinitesimal motion model) of a calibrated Stereo Rig and point and line image feature measurements seen at two time instances of the rig's motion (four images in all). In particular we are interested in the byproduct of this analysis providing a direct connection between the spatio-temporal derivatives of the images at two time instances and kinematics of the 3D motion of the Rig. We establish a fundamental result showing that 3 quadruples of point-line-line-line matches (i.e., point in the reference image and lines coincident with the corresponding points in the remaining three images) are sufficient for a unique linear solution for the kinematics of the rig. In other words, the projected instantaneous motion of "one and a half" 3D lines is sufficient for recovering the kinematics of the moving rig. In particular, spatio-temporal derivatives across 3 points are sufficient for a direct estimation of the rig's motion. Consequently, we describe a new direct estimation method for motion estimation and 3D reconstruction from stereo image sequences obtained by a stereo rig moving through a rigid world. Correspondences (optic flow) are not required as spatio-temporal derivative are used instead. One can then use the images from both pairs combined, to compute a dense depth map. Finally, since the basic equations are linear, we combine the contribution coming from all pixels in the image using a Least Squares approach.
Sub-Inhibitory Concentrations of Mupirocin Strongly Inhibit Alpha-Toxin Production in High-Level Mupirocin-Resistant MRSA by Down-Regulating agr, saeRS, and sarA (2018)

Mupirocin, a topical antibiotic, has been utilized for decades to treat <i>Staphylococcus aureus</i> skin infections, as well as to decolonize patients at risk of methicillin-resistant <i>S. aureus</i> (MRSA) infection. The aims of this study were to investigate the expression of α-toxin (encoded by the <i>hla</i> gene) in ten clinical MRSA strains (MIC = 1024 μg/ml) in response to a sub-inhibitory concentration of mupirocin (1/32 minimum inhibitory concentration [MIC]) (32 μg/ml) by using α-toxin activity determination and enzyme-linked immune sorbent assay (ELISA). Subsequently, real-time polymerase chain reaction (RT-PCR) was used to examine the expression of <i>saeR</i>, <i>agrA</i>, <i>RNAIII</i>, and <i>sarA</i> genes under sub-inhibitory concentration of mupirocin in order to investigate the mechanism of action of this treatment regarding its strong inhibition of α-toxin expression. For all the strains tested, mupirocin dramatically reduced mRNA levels of α-toxin. The results indicated that α-toxin activity in mupirocin-treated groups was significantly lower than that in untreated groups. The results show that the levels of <i>agrA</i>, <i>RNAIII</i>, <i>saeR</i>, and <i>sarA</i> expression significantly decrease by 11.82- to 2.23-fold (<i>P</i> < 0.01). Moreover, we speculate that mupirocin-induced inhibition of α-toxin expression may be related to the inhibition of regulatory loci, such as <i>agr</i>, <i>sarA</i> and <i>saeRS</i>. More specifically, we found that the mechanism involves inhibiting the expression of <i>agrA</i> and <i>RNAIII</i>. In conclusion, sub-inhibitory concentrations of mupirocin strongly inhibit alpha-toxin production in high-level mupirocin-resistant MRSA by down-regulating <i>agr, saeRS</i> and <i>sarA</i>, which could potentially be developed as a supplemental treatment to control high-level mupirocin-resistant MRSA infection and reduce the risk of infection and colonization.
Elite control of HIV infection: implications for vaccine design (2008)

Although many elements of innate and adaptive immunity are associated with control of HIV infection, the specific mechanism(s) by which elite controllers achieve control remain undefined. Ongoing studies of elite controllers, including those examining host genetic polymorphisms, should facilitate the definition of an effective HIV-specific immune response and guide vaccine design.
Modifying Carbon Particles with Polypyrrole for Adsorption of Cobalt Ions as Electrocatatytic Site for Oxygen Reduction (2005)

Carbon nanoparticles modified with a polypyrrole (PPy) film, impregnated with a solution of a cobalt salt, and heat-treated under an inert atmosphere at 600−700 °C are a good electrocatalyst for the four-electron reduction of O2.