gebhart/patrepeval huggingface dataset:
Circulating Cell-Free DNA from Colorectal Cancer Patients May Reveal High KRAS or BRAF Mutation Load (2013)

We used a novel method based on allele-specific quantitative polymerase chain reaction (Intplex) for the analysis of circulating cell.free DNA (ccfDNA) to compare total ccfDNA and KRAS- or BRAF-mutated ccfDNA concentrations in blood samples from mice xenografted with the human SW620 colorectal cancer (CRC) cell line and from patients with CRC. Intplex enables single-copy detection of variant alleles down to a sensitivity of ≥0.005 mutant to wild-type ratio. The proportion of mutant allele corresponding to the percentage of tumor-derived ccfDNA was elevated in xenografted mice with KRAS homozygous mutation and varied highly from 0.13% to 68.7% in samples from mutation-positive CRC patients (n = 38). Mutant ccfDNA alleles were quantified in the plasma of every patient at stages II/III and IV with a mean of 8.4% (median, 8.4%) and 21.8% (median, 12.4%), respectively. Twelve of 38 (31.6%) and 5 of 38 (13.2%) samples showed a mutation load higher than 25%and 50%, respectively. This suggests that an important part of ccfDNA may originate from tumor cells. In addition, we observed that tumor-derived (mutant) ccfDNA was more fragmented than ccfDNA from normal tissues. This observation suggests that the form of tumor-derived and normal ccfDNA could differ. Our approach revealed that allelic dilution is much less pronounced than previously stated, considerably facilitating the noninvasive molecular analysis of tumors.
Prostaglandin E2 Inhibits Lesion Formation in Dextran Sodium Sulphate‐Induced Colitis in Rats and Reduces the Levels of Mucosal Inflammatory Cytokines (2000)

Effects of rectally injected prostaglandin E2 (PGE2) in rats with dextran sodium sulphate (DSS)-induced colitis were investigated in terms of histopathology, local myeloperoxidase (MPO) activity, local mRNA expression of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and growth-regulated gene produced/cytokine-induced neutrophil chemoattractant (GRO/CINC)-1, and secretion of TNF-alpha and GRO/CINC-1. In animals with no PGE2 treatment, DSS-induced erosion and ulceration were particularly severe in the rectum and extended to the proximal colon. Neutrophil infiltration was characteristically present in the lesions and surrounding mucosa. MPO activity at lesion sites was increased. IL-1beta and GRO/CINC-1 mRNA expression was increased, while TNF-alpha mRNA expression was significantly decreased. GRO/CINC-1 secretion was increased but a similar elevation of TNF-alpha was not detected. In the PGE2-treated group, lesion formation was inhibited grossly and microscopically. Neutrophil infiltration and MPO activity in and around lesions were lessened. The reduction in TNF-alpha mRNA expression and secretion was not affected by PGE2. The expression of mRNA for IL-1beta and GRO/CINC-1 was reduced, as was the secretion of GRO/CINC-1. As mRNA expression and secretion of cytokines in lesions of non-PGE2-treated animals was similar to that reported in human ulcerative colitis, rectal injection of PGE2 may prove to be an effective therapy.
A ten-year review of neonatal sepsis and comparison with the previous fifty-year experience (1990)

Records have been kept prospectively in our institution since 1928 of all positive blood cultures taken from neonates. Using a modification of objective Centers for Disease Control criteria to define sepsis, we reviewed the records of all neonates with positive blood cultures for the years 1979 to 1988 inclusive and found 270 cases of sepsis. The sepsis rate for infants less than or equal to 30 days of age was 2.7 cases/1000 live births, with a mortality rate from sepsis of 15.9%. There was an increase in sepsis due to commensal species (CS) over the period (P less than 0.007). The number of infants in the nursery who developed sepsis when more than 30 days of age also increased (P less than 0.002), as did the rate of sepsis from CS in this group (P less than 0.001). Isolation of CS from the blood with fulfillment of the modified Centers for Disease Control criteria was associated with a 13.7% mortality rate, whereas isolation of CS without fulfillment was associated with a 4% rate (P less than 0.01).
Heterocyclic synthesis from o-halogeno-acids. Part III. Synthesis of 2-methylindole-4-carboxylic acid and related compounds and of some derivatives of 3-phenylisoquinolin-1(2H)-one (1976)

Condensation of 2-bromo-3-nitrobenzoic acid with acetylacetone in the presence of copper(II) acetate and ethanolic sodium ethoxide gives 2-acetylacetonyl-3-nitrobenzoic acid. Deacetylation with water–dimethyl sulphoxide at 170 °C yields 3-methyl-5-nitroisocoumarin, which is converted by catalytic hydrogenation and alkaline hydrolysis into 2-methylindole-4-carboxylic acid. Similar condensation and reduction reactions yield related compounds including dimethyl 2-methylindole-3,4-dicarboxylate. Tricyclic products are obtained by heating o-phenacylbenzoic acid with 2-amino-1-phenylethanol, ethane-1,2-diamine, and o-phenylenediamine. o-Phenacylbenzoic acid is also converted into 2-substituted 3-phenylisoquinolin-1(2H)-ones, which are cyclised to form dibenzo[a,g]-quinolizin-8-one derivatives and/or oxazolo[2,3-a]isoquinolinylium salts.
Adjust to Target in Type 2 Diabetes (2008)

Weekly basal-bolus insulin adjustments based on premeal and bedtime glucose patterns resulted in significant reductions in A1C. Having two effective approaches to delivering and adjusting rapid-acting mealtime insulin may increase physicians' and patients' willingness to advance therapy to a basal-bolus insulin regimen.
The Role of Processing Variables in the Flux Growth of Lead Zinc Niobate-Lead Titanate Relaxor Ferroelectric Single Crystals (1996)

Relaxor ferroelectric single crystals of Pb(Zn 1/3 Nb 2/3 )O 3 –PbTiO 3 (PZN-PT) are of interest as high performance transducers due to their very large piezoelectric coupling and dielectric properties. A high temperature flux solution method was used to grow (1- x )PZN-( x )PT, where x = 0.0, 0.1 and 0.15 single crystals. Processing conditions were optimized to increase the size and yield of the perovskite crystals, including variation of the flux to composition ratio, cooling rate, soak time and soak temperature. The crystals varied in size from 0.01 cm to 1.5 cm on an edge, and in color from opaque to brown due to the changes in processing conditions. The crystals were characterized by XRD, dielectric constant and dielectric loss measurements. As the content of PT increased the transition from the paraelectric to the ferroelectric phase approached first order behavior and the crystal structure transformed from rhombohedral to tetragonal. This structure transition caused the lattice constant along the c -axis to elongate as the c / a ratio increased. At room temperature, the dielectric constants for the PZN-PT compositions along the [111] or [001] axes were as great as 5000 and the dielectric losses were as low as 0.01.
mDia function is critical for the cell suicide program triggered by farnesyl transferase inhibition (2007)

Farnesyl transferase inhibitors (FTIs) exhibit limited cytotoxic effects against human cancer cells, perhaps explaining the limited efficacy of FTIs in clinical trials. Learning how these well-tolerated drugs trigger p53-independent apoptosis in mouse models of cancer might therefore benefit efforts to leverage their utility in clinic. Recent clinical findings indicate that the oncogenic Rho guanine nucleotide exchange factor AKAP13/Lbc is associated with clinical responsiveness, in support of an earlier genetic proof in mice that gain of the geranylgeranylated isoform of RhoB which blocks oncogenic Rho signaling is essential for FTI-induced apoptosis. Here we offer evidence that the RhoB effector mDia is a critical downstream player in this death program. Dominant inhibition of mDia ablated FTI-induced apoptosis but not actin reorganization or growth inhibition, the latter of which has been linked previously to interactions with a RhoB effector kinase pathway that downregulates c-Myc. In nude mice, dominant inhibition of mDia promoted tumor formation and ablated FTI antitumor efficacy. Our findings suggest that the RhoB-mDia pathway is critical for the cell death mechanism engaged by FTI. Further, they suggest that mDia may be important for Rho-dependent survival of oncogenically transformed cells, perhaps driven by AKAP13/Lbc.
Efficient finite field computations for elliptic curve cryptography (2014)

Finite field multiplication and inversion are two basic operations involved in Elliptic Cure Cryptosystem (ECC), high performance of field operations can be applied to provide efficient computation of ECC. In this thesis, two classes of fields are proposed for multipliers with much reduced time delay. A most-significant-digit first and a least-significant-digit first digit-serial Montgomery multiplications are also proposed, using novel fixed elements R(x) which are different from x m and x m-1 . Architectures of the proposed Montgomery multipliers are studied and obtained for the fields generated by the irreducible pentanomials, which are selected based on the proposed special finite fields. Complexities of the Montgomery multipliers in term of critical path delay and gate count of the architectures are investigated; the critical path delay of the proposed multipliers are found to be as good as or better than the existing works for the same class of fields. Then, implementation of the proposed multipliers (m=233) using Field Programmable Gate Array (FPGA) is provided. In addition, an FPGA implementation of an efficient normal basis inversion algorithm is also presented (m=163). The normal basis multiplication unit is implemented using a digit-level structure, and a C-code is written to generate the first coordinate of the product of two normal basis elements for all field size m.
Violence and civility in discourse: Uses of mitigation by rural Southern white men (2018)

Department of English article
Space-variant Pancharatnam–Berry phase optical elements with computer-generated subwavelength gratings (2002)

Space-variant Pancharatnam-Berry phase optical elements based on computer-generated subwavelength gratings are presented. By continuously controlling the local orientation and period of the grating we can achieve any desired phase element. We present a theoretical analysis and experimentally demonstrate a Pancharatnam-Berry phase-based diffraction grating for laser radiation at a wavelength of 10.6microm.
Patterned Superhydrophobic Surfaces:  Toward a Synthetic Mimic of the Namib Desert Beetle (2006)

The present study demonstrates a surface structure that mimics the water harvesting wing surface of the Namib Desert beetle. Hydrophilic patterns on superhydrophobic surfaces were created with water/2-propanol solutions of a polyelectrolyte to produce surfaces with extreme hydrophobic contrast. Selective deposition of multilayer films onto the hydrophilic patterns introduces different properties to the area including superhydrophilicity. Potential applications of such surfaces include water harvesting surfaces, controlled drug release coatings, open-air microchannel devices, and lab-on-chip devices.
Antigen-induced suppression of the proliferative response of T cell clones. (1988)

Proliferation of Ag-specific T cell clones can be inhibited by the addition of high concentrations of Ag at the beginning of culture. Under these conditions the cells produce lymphokines and express high affinity IL-2R but fail to divide, even after the addition of exogenous IL-2. This state results from restimulation of the cells with Ag-Ia molecule complexes approximately 20 h after initiation of culture. It can be prevented by addition of either an anti-Ia or an anti-L3T4 mAb at that time, but not by cyclosporin A, and mimicked in cultures containing low concentrations of antigen by addition at that time of high Ag concentrations or normal stimulatory concentrations of Con A. These observations suggest that restimulation of activated T cell clones 20 h after their initial stimulation prevents them from dividing.
Internet X.509 Public Key Infrastructure Certificate Management Protocols (1999)

This document describes the Internet X.
ASTOR: an autostereoscopic optical see-through augmented reality system (2005)

We present a novel autostereoscopic optical see-through system for augmented reality (AR). It uses a transparent holographic optical element (HOE) to separate the views produced by two, or more, digital projectors. It is a minimally intrusive AR system that does not require the user to wear special glasses or any other equipment, since the user would see different images depending on the point of view. The HOE itself is a thin glass plate or plastic film that can easily be incorporated into other surfaces, such as a window. The technology offers great flexibility, allowing the projectors to be placed where they are the least intrusive. ASTOR's capability of sporadic AR visualization is currently ideal for smaller physical workspaces, such as our prototype setup in an industrial environment.
In Vivo Gene Therapy of Hemophilia B: Sustained Partial Correction in Factor IX-Deficient Dogs (1993)

The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model. When the canine factor IX complementary DNA was transduced directly into the hepatocytes of affected dogs in vivo, the animals constitutively expressed low levels of canine factor IX for more than 5 months. Persistent expression of the clotting factor resulted in reductions of whole blood clotting and partial thromboplastin times of the treated animals. Thus, long-term treatment of hemophilia B patients may be feasible by direct hepatic gene therapy in vivo.
Polyethylene upcycling to long-chain alkylaromatics by tandem hydrogenolysis/aromatization (2020)

The current scale of plastics production and the accompanying waste disposal problems represent a largely untapped opportunity for chemical upcycling. Tandem catalytic conversion by platinum supported on γ-alumina converts various polyethylene grades in high yields (up to 80 weight percent) to low-molecular-weight liquid/wax products, in the absence of added solvent or molecular hydrogen, with little production of light gases. The major components are valuable long-chain alkylaromatics and alkylnaphthenes (average ~C<sub>30</sub>, dispersity Ð = 1.1). Coupling exothermic hydrogenolysis with endothermic aromatization renders the overall transformation thermodynamically accessible despite the moderate reaction temperature of 280°C. This approach demonstrates how waste polyolefins can be a viable feedstock for the generation of molecular hydrocarbon products.
Plasma‐enhanced chemical vapor deposited silicon carbide as an implantable dielectric coating (2003)

Amorphous silicon carbide (a-SiC) films, deposited by plasma-enhanced chemical vapor deposition (PECVD), have been evaluated as insulating coatings for implantable microelectrodes. The a-SiC was deposited on platinum or iridium wire for measurement of electrical leakage through the coating in phosphate-buffered saline (PBS, pH 7.4). Low leakage currents of <10(-11) A were observed over a +/-5-V bias. The electronic resistivity of a-SiC was 3 x 10(13) Omega-cm. Dissolution rates of a-SiC in PBS at 37 and 90 degrees C were determined from changes in infrared absorption band intensities and compared with those of silicon nitride formed by low-pressure chemical vapor deposition (LPCVD). Dissolution rates of LPCVD silicon nitride were 2 nm/h and 0.4 nm/day at 90 and 37 degrees C, respectively, while a-SiC had a dissolution rate of 0.1 nm/h at 90 degrees C and no measurable dissolution at 37 degrees C. Biocompatibility was assessed by implanting a-SiC-coated quartz discs in the subcutaneous space of the New Zealand White rabbit. Histological evaluation showed no chronic inflammatory response and capsule thickness was comparable to silicone or uncoated quartz controls. Amorphous SiC-coated microelectrodes were implanted in the parietal cortex for periods up to 150 days and the cortical response evaluated by histological evaluation of neuronal viability at the implant site. The a-SiC was more stable in physiological saline than LPCVD Si(3)N(4) and well tolerated in the cortex.
Green‐Emitting CePO4:Tb/LaPO4 Core–Shell Nanoparticles with 70 % Photoluminescence Quantum Yield (2003)

Quantum leap: Very high quantum yields, thought to be impossible for nanocrystalline phosphor materials, were achieved with CePO4:Tb/LaPO4 core–shell nanoparticles (see picture). Because the LaPO4 shell reduces energy losses at the particle surface, transparent colloidal solutions of these 8-nm particles are highly photoluminescent.
5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones:  Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives (1999)

Molecular modeling analysis of compounds belonging to the recently published series of dihydro-alkoxy-benzyl-oxopyrimidines (DABOs), such as S-DABOs and DATNOs, gave support to the design of new 2, 6-disubstituted benzyl-DABO derivatives as highly potent and specific inhibitors of the HIV-1 reverse transcriptase (RT). To follow up on the novel DABO derivatives, we decided to investigate the effect of electron-withdrawing substituents in the benzyl unit of the S-DABO skeleton versus their anti-HIV-1 activity. Such chemical modifications impacted the inhibitory activity, especially when two halogen units were introduced at positions 2 and 6 in the phenyl portion of the benzyl group bound to C-6 of the pyrimidine ring. Various 5-alkyl-2-(alkyl(or cycloalkyl)thio)-6-(2, 6-dichloro(or 2,6-difluoro)phenylmethyl)-3, 4-dihydropyrimidin-4(3H)-ones were then synthesized and tested as anti-HIV-1 agents in both cell-based and enzyme (recombinant reverse transcriptase, rRT) assays. Among the various mono- and disubstituted phenyl derivatives, the most potent were those containing a 6-(2,6-difluorophenylmethyl) substituent (F-DABOs), which showed EC50's ranging between 40 and 90 nM and selectivity indexes up to >/=5000. An excellent correlation was found between EC50 and IC50 values which confirmed that these compounds act as inhibitors of the HIV-1 RT. The structure-activity relationships of the newly synthesized pyrimidinones are presented herein.
GSVA: gene set variation analysis for microarray and RNA-Seq data (2013)

GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org.
Characterization of the enhanced adhesion of neutrophil leukocytes to thrombin-stimulated endothelial cells. (1990)

We have characterized the mechanisms by which thrombin enhances neutrophil leukocyte (PMN) adhesion to human endothelial cells in vitro. Thrombin rapidly and transiently increased PMN adhesion by an action on the endothelial cells. The transience of the response was due to at least two factors: desensitization of the endothelial cell responsiveness to thrombin in the continued presence of the agonist; and the lability (t1/2 less than 15 min) of the effector molecules expressed by the endothelium. Experiments with exogenous platelet-activating factor (PAF) and with PAF antagonists demonstrated that PAF production, although it may facilitate the enhanced PMN adhesion seen in response to thrombin, is not sufficient to explain the reaction. By using a variety of antibodies directed against cell surface ligands, and comparing adhesion of PMN to endothelium and to protein-coated surfaces, we deduce that several endothelial ligands not previously reported as playing a role in PMN adhesion are involved in these interactions. Of particular interest was the finding that antibodies recognizing two thrombin-regulated endothelial cell surface ligands, GMP-140 and the CD63-related Ag, both inhibited adhesion of PMN to thrombin- or LPS-pretreated endothelium. We conclude that thrombin acts to enhance PMN adhesion to endothelium at least in part by transiently altering the conformation or level of expression of these ligands.
Structure−Activity Relationships of Monomeric C2-Aryl Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Antitumor Agents (2010)

A comprehensive SAR investigation of the C2-position of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) monomer antitumor agents is reported, establishing the molecular requirements for optimal in vitro cytotoxicity and DNA-binding affinity. Both carbocyclic and heterocyclic C2-aryl substituents have been studied ranging from single aryl rings to fused ring systems, and also styryl substituents, establishing across a library of 80 analogues that C2-aryl and styryl substituents significantly enhance both DNA-binding affinity and in vitro cytotoxicity, with a correlation between the two. The optimal C2-grouping for both DNA-binding affinity and cytotoxicity was found to be the C2-quinolinyl moiety which, according to molecular modeling, is due to the overall fit of the molecule in the DNA minor groove, and potential specific contacts with functional groups in the floor and walls of the groove. This analogue (14l) was shown to delay tumor growth in a HCT-116 (bowel) human tumor xenograft model.
Replication Factor C Disengages from Proliferating Cell Nuclear Antigen (PCNA) upon Sliding Clamp Formation, and PCNA Itself Tethers DNA Polymerase δ to DNA (1998)

Replication factor C (RF-C) and proliferating cell nuclear antigen (PCNA) assemble a complex, called sliding clamp, onto DNA. The clamp in turn loads DNA polymerases (pol) delta and epsilon to form the corresponding holoenzymes, which play an essential role in replication of eukaryotic chromosomal DNA and in several DNA repair pathways. To determine the fate of RF-C after loading of PCNA onto DNA, we tagged the RF-C subunit p37 with a protein kinase A recognition motif, so that the recombinant five-subunit RF-C complex could be 32P-labeled and quantitatively detected in femtomolar amounts. Nonspecific binding of RF-C to DNA was minimized by replacing the p140 subunit with an N-terminally truncated p140 subunit lacking the previously identified nonspecific DNA binding domain. Neither of these modifications impaired the clamp loading activity of the recombinant RF-C. Using gel filtration techniques, we demonstrated that RF-C dissociated from the DNA after clamp loading or pol delta holoenzyme assembly, while PCNA or PCNA.pol delta complex remained bound to DNA. PCNA catalytically loaded onto the template-primer was sufficient by itself to tether pol delta and stimulate DNA replication. The readdition of RF-C to the isolated PCNA.DNA complex did not further stimulate pol delta DNA synthesis. We conclude that pol delta holoenzyme consists of PCNA and pol delta core and that RF-C serves only to load PCNA clamp.