gebhart/patrepeval huggingface dataset:
Interactive Sankey Diagrams (2006)

We present a system that allows users to interactively explore complex flow scenarios represented as Sankey diagrams. Our system provides an overview of the flow graph and allows users to zoom in and explore details on demand. The support for quantitative flow tracing across the flow graph as well as representations at different levels of detail facilitate the understanding of complex flow situations. The energy flow in a city serves as a sample scenario for our system. Different forms of energy are distributed within the city and they are transformed into heat, electricity, or other forms of energy. These processes are visualized and interactively explored. In addition our system can be used as a planning tool for the exploration of alternative scenarios by interactively manipulating different parameters in the energy flow network.
S-Acyl-2-thioethyl Phosphoramidate Diester Derivatives as Mononucleotide Prodrugs (2003)

The synthesis and in vitro anti-HIV activity of phosphoramidate diester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing one S-pivaloyl-2-thioethyl (tBuSATE) group and various amino residues are reported. These compounds were obtained from an H-phosphonate strategy using an amidative oxidation step. Most of these derivatives appeared to inhibit HIV-1 replication, with EC(50) values at micromolar concentration in thymidine kinase-deficient (TK-) cells, revealing a less restrictive intracellular decomposition process than previously reported for other phosphoramidate prodrugs. The proposed decomposition pathway of this new series of mixed pronucleotides may successively involve an esterase and a phosphoramidase hydrolysis.
An empirical approach to protein conformation stability and flexibility (1983)

Abstract Experimental measurements of disulfide bond stability at various stages of protein folding are considered in terms of the effective concentrations of the thiol groups relative to each other; values of up to 10 7 M are observed, so that intramolecular interactions within the interior of a protein are much more stable, and provide greater stability to the folded conformation, than those on the surface or in a flexible segment. Intramolecular interactions can have substantially lower free energies than intermolecular, for solely entropic reasons; this implies that polar interactions, such as hydrogen bonds and salt bridges, can provide net stabilization to a folded conformation, in spite of the unfolded protein having intermolecular interactions with the solvent. These considerations can account for the lower free energy and enthalpy of the folded state and are useful for considering protein flexibility.
Exhaustive docking of molecular fragments with electrostatic solvation (1999)

A new method is presented for docking molecular fragments to a rigid protein with evaluation of the binding energy. Polar fragments are docked with at least one hydrogen bond with the protein while apolar fragments are positioned in the hydrophobic pockets. The electrostatic contribution to the binding energy, which consists of screened intermolecular energy and protein and fragment desolvation terms, is evaluated efficiently by a numerical approach based on the continuum dielectric approximation. The latter is also used to predetermine the hydrophobic pockets of the protein by rolling a low dielectric sphere over the protein surface and calculating the electrostatic desolvation of the protein and van der Waals interaction energy. The method was implemented in the program SEED (solvation energy for exhaustive docking). The SEED continuum electrostatic approach has been successfully validated by a comparison with finite difference solutions of the Poisson equation for more than 2,500 complexes of small molecules with thrombin and the monomer of HIV-1 aspartic proteinase. The fragments docked by SEED in the active site of thrombin reproduce the structural features of the interaction patterns between known inhibitors and thrombin. Moreover, the combinatorial connection of these fragments yields a number of compounds that are very similar to potent inhibitors of thrombin. Proteins 1999;37:88-105.
Serial Changes in the Rate of Proteoglycan Synthesis After Chemonucleolysis of Rabbit Intervertebral Discs (1999)

Doses within the therapeutic range can damage disc cells, at least in the rabbit, so that proteoglycan synthesis declined to 30% of control rates, and no significant recovery of disc height was observed.
IL-6, in Synergy with IL-7 or IL-15, Stimulates TCR-Independent Proliferation and Functional Differentiation of CD8+ T Lymphocytes (2008)

Recent reports have shown that IL-21, in synergy with IL-15, stimulates proliferation of CD8(+) T lymphocytes in the absence of signaling via the TCR. In this study, we show that IL-6, which induces phosphorylation of STAT3 similarly to IL-21, also can stimulate proliferation of CD8(+) T cells in synergy with IL-7 or IL-15. IL-6 displays a stronger synergy with IL-7 than with IL-15 to stimulate naive CD8(+) T cells. Concomitant stimulation by IL-6 or IL-21 augments phosphorylation and DNA-binding activity of STAT5 induced by IL-7 or IL-15. Like IL-21, IL-6 reduces the TCR signaling threshold required to stimulate CD8(+) T cells. Prior culture of P14 TCR transgenic CD8 T cells with IL-6 or IL-21 in the presence of IL-7 or IL-15 augments their proliferation and cytolytic activity upon subsequent stimulation by Ag. Furthermore, cytokine stimulation induces quantitatively and qualitatively distinct phenotypic changes on CD8(+) T cells compared with those induced by TCR signaling. We propose that the ability of IL-6 to induce TCR-independent activation of CD8(+) T cells in synergy with IL-7 or IL-15 may play an important role in the transition from innate to adaptive immunity.
Common Pathogenetic Mechanism for Three Tumor Types in Bilateral Acoustic Neurofibromatosis (1987)

Bilateral acoustic neurofibromatosis (BANF) is a genetic defect associated with multiple tumors of neural crest origin. Specific loss of alleles from chromosome 22 was detected with polymorphic DNA markers in two acoustic neuromas, two neurofibromas, and one meningioma from BANF patients. This indicates a common pathogenetic mechanism for all three tumor types. The two neurofibromas were among three taken from the same patient, and both showed loss of identical alleles demonstrating that the same chromosome suffered deletion in both tumors. The third neurofibroma from this patient showed no detectable loss of heterozygosity, which suggests the possibility of a more subtle mutational event that affects chromosome 22. In the two acoustic neuromas, only a portion of chromosome 22 was deleted, narrowing the possible chromosomal location of the gene that causes BANF to the region distal to the D22S9 locus in band 22q11. The identification of progressively smaller deletions on chromosome 22 in these tumor types may well provide a means to clone and characterize the defect.
Photochemical Synthesis of Gold Nanorods (2002)

Gold nanorods have been synthesized by photochemically reducing gold ions within a micellar solution. The aspect ratio of the rods can be controlled with the addition of silver ions. This process reported here is highly promising for producing uniform nanorods, and more importantly it will be useful in resolving the growth mechanism of anisotropic metal nanoparticles due to its simplicity and the relatively slow growth rate of the nanorods.
Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry (2005)

Methylation is one of the major epigenetic processes pivotal to our understanding of carcinogenesis. It is now widely accepted that there is a relationship between DNA methylation, chromatin structure, and human malignancies. DNA methylation is potentially an important clinical marker in cancer molecular diagnostics. Understanding epigenetic modifications in their biological context involves several aspects of DNA methylation analysis. These aspects include the de novo discovery of differentially methylated genes, the analysis of methylation patterns, and the determination of differences in the degree of methylation. Here we present a previously uncharacterized method for high-throughput DNA methylation analysis that utilizes MALDI-TOF mass spectrometry (MS) analysis of base-specifically cleaved amplification products. We use the IGF2/H19 region to show that a single base-specific cleavage reaction is sufficient to discover methylation sites and to determine methylation ratios within a selected target region. A combination of cleavage reactions enables the complete evaluation of all relevant aspects of DNA methylation, with most CpGs represented in multiple reactions. We successfully applied this technology under high-throughput conditions to quantitatively assess methylation differences between normal and neoplastic lung cancer tissue samples from 48 patients in 47 genes and demonstrate that the quantitative methylation results allow accurate classification of samples according to their histopathology.
Prevention of Barite Sagging While Drilling High-Pressure High-Temperature (HPHT) Wells (2018)

Abstract Barite sagging is one of the common issues while drilling high pressure-high temperature wells. This will cause variation in the mud weight in both vertical and deviated wells. Barite sagging can cause many problems such as; density variations, well-control problems, stuck pipe, downhole mud losses, and induced wellbore instability. The objective of this study is to assess the effect of adding a new copolymer to the invert emulsion drilling fluid to prevent the sagging issue. Sag test was conducted under static conditions over a wide range of temperature (200°F to 350°F). Sag test was performed using vertical and decline (45° degree) aging cell. In addition, the effect of adding the new copolymer on the rheological properties and the electrical stability of the invert emulsion drilling fluid was evaluated. The results obtained showed that adding 1 lbm/bbl of the new copolymer had no effect on drilling fluid density (14.5 ppg). The new copolymer slightly enhanced the electrical stability of the invert emulsion drilling mud. The new copolymer had a minor effect on the plastic viscosity, yield point, and gel strength. Adding 1 lbm/bbl of the copolymer prevent barite sagging at 350°F, where the sag factor was 0.55 before adding copolymer, and 0.503 after adding it. The storage modulus (G′) was increased by 40% after adding 1 lbm/bbl of the new copolymer confirming the sag test results. There was no effect of adding the new copolymer in the filtration loss and filter cake thickness. The novelty of this work is the development of a new drilling fluid formulation that can be used in drilling HPHT wells without any sag issue. This development will help the drilling engineers to safely drill deep wells and maintain the drilling fluid integrity during the drilling operation. In general, this will reduce the overall cost of the drilling operation by reducing the non-productive time in solving many issues such as well control, loss of circulation, or pipe sticking.
Flow-based evaluation of cerebral revascularization using near-infrared indocyanine green videoangiography (2014)

Indocyanine green videoangiography is reliable for evaluating flow through the EC-IC or IC-IC bypass. The type of flow observed through the graft has a direct relationship with postoperative imaging findings. Despite the possibility of competitive flow, Type III and some Type II flows through the graft indicate the need for graft evaluation and anastomosis exploration.
The Genes Coding for Enterocin EJ97 Production by Enterococcus faecalis EJ97 Are Located on a Conjugative Plasmid (2003)

Enterococcus faecalis EJ97 produces a cationic bacteriocin (enterocin EJ97) of low molecular mass (5,327.7 Da). The complete amino acid sequence of enterocin EJ97 was elucidated after automated microsequencing of oligopeptides generated by endoproteinase GluC digestion and cyanogen bromide treatment. Transfer of the 60-kb conjugative plasmid pEJ97 from the bacteriocinogenic strain E. faecalis EJ97 to E. faecalis OG1X conferred bacteriocin production and resistance on the recipient. The genetic determinants of enterocin EJ97 were located in an 11.3-kb EcoRI-BglII DNA fragment of pEJ97. This region was cloned and sequenced. It contains the ej97A structural gene plus three open reading frames (ORFs) (ej97B, ej97C, and ej97D) and three putative ORFs transcribed in the opposite direction (orfA, orfB, and orfC). The gene ej97A translated as a 44-amino-acid residue mature protein lacking a leader peptide with no homology to other bacteriocins described so far. The product of ej97B (Ej97B) shows strong homology in its C-terminal domain to the superfamily of bacterial ATP-binding cassette transporters. The products of ej97C (Ej97C) and ej97D (Ej97D) could be proteins with 71 and 64 residues, respectively, of unknown functions and with no significant similarity to known proteins. There are two additional ORFs (ORF1 and ORF6) flanking the ej97 module, which have been identified as a transposon-like structure (tnp). ORF1 shows similarities to transposase of the Lactococcus lactis element ISS1 and is up to 50% identical to IS1216. This is flanked by two 18-bp inverted repeats (IRs) that are almost identical to those of ISS1 and IS1216. ORF6 (resEJ97) shows strong homology to the resolvase of plasmid pAM373 and up to 40 to 50% homology with the recombinase of several multiresistant plasmids and transposons from Staphylococcus aureus and E. faecalis. These data suggest that EJ97 could represent a new class of bacteriocins with a novel secretion mechanism and that the whole structure could be a composite transposon. Furthermore, two additional gene clusters were found: one cluster is probably related to the region responsible for the replication of plasmid pEJ97, and the second cluster is related to the sex pheromone response. These regions showed a high homology to the corresponding regions of the conjugative plasmids pAM373, pPD1, and pAD1 of E. faecalis, suggesting that they have a common origin.
A new adaptive beamformer for optimal acoustic echo and noise cancellation with less computational load (2008)

In this paper, we investigates positive synergies of the combination of acoustic echo canceller with new adaptive beamformer (NABF) for acoustic echo and background noise cancellation. The NABF uses multichannel linear prediction error filters (LPEFs) in the sidelobe canceling path and adaptive noise estimation filters (ANEFs) in the multi-channel noise canceller. Since the AEC module is located behind the fixed beamformer of the NABF only one AEC module is required and the AEC does not feel any repercussions from the NABF. In order to illustrate the effectiveness of the proposed integrated scheme (AECNABF), it is compared to the multi-channel acoustic echo canceller (AEC-first) which provide good performance but at the expense of very high computational complexity. Simulation results show that the performance of the proposed scheme is comparable to that of AEC-first scheme with very less computational complexity.
Conformationally Defined Retinoic Acid Analogues. 4. Potential New Agents for Acute Promyelocytic and Juvenile Myelomonocytic Leukemias (1998)

We recently synthesized several conformationally constrained retinoic acid (RA) analogues [8-(2'-cyclohexen-1'-ylidene)-3, 7-dimethyl-2,4,6-octatrienoic acids with different alkyl substituents at 2' (R1) and 3' (R2) positions on the cyclohexene ring] (Muccio et al. J. Med. Chem. 1996, 39, 3625) as cancer chemopreventive agents. UAB8 (R1 = Et; R2 = iPr), which contains sufficient steric bulk at the terminal end of the polyene chain to mimic the trimethylcyclohexenyl ring of RA, displayed biological properties similar to those of RA. To explore the efficacy of this retinoid in acute promyelocytic leukemia (APL) and juvenile myelomonocytic leukemia (JMML), we evaluated UAB8 isomers in in vitro assays which measure the capacity of retinoids to inhibit aberrant myeloid colony growth from blood or bone marrow cells obtained from human JMML patients and in assays measuring the potential of retinoids to differentiate NB4 cells (an APL cell line). Both (all-E)- and (13Z)-UAB8 were 2-fold more active than RA in the NB4 cell differentiation assay; however, only (all-E)-UAB8 had comparable activity to the natural retinoids in the JMML cell assays. These results were compared to the biological effectiveness of a new retinoid, UAB30 [8-(3', 4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4, 6-octatrienoic acid], which had different nuclear receptor binding and transactivational properties than UAB8. Relative to (all-E)-RA and (all-E)-UAB8, (all-E)-UAB30 bound well to RARalpha but did not activate transcription-mediated RARalpha homodimers, even though it was effective in RARbeta- and RARgamma-mediated transactivational assays. In APL assays, this retinoid had much reduced activity and was only moderately effective in JMML assays and in cancer chemoprevention assays.
Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose and insulin, body size, and physical activity. Atherosclerosis Risk in Communities (ARIC) Study Investigators. (1994)

Abdominal adiposity, physical inactivity, and abnormal glucose metabolism are associated positively with carotid intimal-medial wall thickness, suggesting these factors contribute to atherogenesis.
Intranasal bacille Calmette–Guérin (BCG) vaccine dosage needs balancing between protection and lung pathology (2004)

SUMMARY Intranasal vaccination may offer practical benefits and better protection against respiratory infections, including tuberculosis. In this paper, we investigated the persistence of the Mycobacterium bovis-strain bacille Calmette–Guérin (BCG) Pasteur, lung granuloma formation and protection against pathogenic tuberculous challenge in mice. A pronounced BCG dose-dependent granulomatous infiltration of the lungs was observed following intranasal, but not after subcutaneous, vaccination. Corresponding doses of BCG, over a 100-fold range, imparted similar protection against H37Rv challenge when comparing the intranasal and subcutaneous vaccination routes. Interestingly, a BCG dose-dependent reduction of the H37Rv challenge infection was observed in the lungs, but not in the spleens, following both intranasal and subcutaneous vaccination. In the light of the observed concurrence between the extent of granuloma formation and the level of protection of the lungs, we conclude that intranasal vaccination leading to best protective efficacy needs to be balanced with an acceptable safety margin avoiding undue pathology in the lungs.
Power and Performance: Software Analysis and Optimization (2015)

Power and Performance: Software Analysis and Optimization is a guide to solving performance problems in modern Linux systems. Power-efficient chips are no help if the software those chips run on is inefficient. Starting with the necessary architectural background as a foundation, the book demonstrates the proper usage of performance analysis tools in order to pinpoint the cause of performance problems, and includes best practices for handling common performance issues those tools identify. Provides expert perspective from a key member of Intel's optimization team on how processors and memory
Identification of 7-Phenylaminothieno- [3,2-b]pyridine-6-carbonitriles as a New Class of Src Kinase Inhibitors (2004)

We disclose here a new class of kinase inhibitors, obtained by replacing the phenyl ring of a 3-quinolinecarbonitrile system with a thiophene ring. When suitably substituted, the resultant 7-phenylaminothieno[3,2-b]pyridine-6-carbonitrile analogues show potent inhibition of Src kinase activity.
Direct Cooperation Between Androgen Receptor and E2F1 Reveals a Common Regulation Mechanism for Androgen-Responsive Genes in Prostate Cells (2012)

We have studied the regulation of ATAD2 gene expression by androgens in prostate cells. ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. We showed that ATAD2 expression is directly regulated by AR via an AR binding sequence (ARBS) located in the distal enhancer of its regulatory region. The gene is also regulated by the E2F1 transcription factor. Using knockdown and chromatin immunoprecipitation technique approaches, we could demonstrate that AR and E2F1 functionally collaborate and physically interact between each other. From the analysis of chromatin conformation, we conclude that this cooperation results from a chromatin looping over the ATAD2 promoter region between the ARBS and E2F1 binding site in an androgen-dependent manner. Furthermore, we could show that several genes overexpressed in prostate cancer and potentially involved in several aspects of tumor development have an ARBS and an E2F1 binding site in their regulatory regions and exhibit the same mechanism of regulation by both transcription factors as ATAD2.
Learning Joint Statistical Models for Audio-Visual Fusion and Segregation (2000)

People can understand complex auditory and visual information, often using one to disambiguate the other. Automated analysis, even at a lowlevel, faces severe challenges, including the lack of accurate statistical models for the signals, and their high-dimensionality and varied sampling rates. Previous approaches [6] assumed simple parametric models for the joint distribution which, while tractable, cannot capture the complex signal relationships. We learn the joint distribution of the visual and auditory signals using a non-parametric approach. First, we project the data into a maximally informative, low-dimensional subspace, suitable for density estimation. We then model the complicated stochastic relationships between the signals using a nonparametric density estimator. These learned densities allow processing across signal modalities. We demonstrate, on synthetic and real signals, localization in video of the face that is speaking in audio, and, conversely, audio enhan...
Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells (2002)

Dendritic cells (DCs) are potent antigen-presenting cells that are able to initiate and modulate immune responses and are hence exploited as cellular vaccines for immunotherapy. Their capacity to migrate from peripheral tissues to the T-cell areas of draining lymph nodes is crucial for the priming of T lymphocytes. In this study, we investigated how the maturation of human monocyte-derived DCs (MoDCs) by several different stimuli under serum-free conditions affected their T-cell stimulatory function, cytokine secretion, and migratory behavior. Surprisingly, we found that for all maturation stimuli tested, the addition of prostaglandin E2 (PGE2) was required for effective migration of MoDCs toward the lymph node-derived chemokines CCL19 (EBI1 ligand chemokine/macrophage inflammatory protein--3beta) and CCL21 (secondary lymphoid tissue chemokine [SLC]/6Ckine). Costimulation with PGE2 enhanced the expression of the CCL19/CCL21 receptor CCR7 on the cell surface of MoDCs when they were matured with soluble CD40 ligand or proinflammatory cytokines, but did not affect CCR7 expression of polyI:C-stimulated MoDCs. The effects of PGE2 on MoDCs were mediated through increased cyclic adenosine monophosphate by 2 of the known PGE2 receptors, EP2 and EP4, which are expressed and down-regulated after PGE2 binding in these cells. In conclusion, our results suggest that signals provided by the proinflammatory mediator PGE2 are crucial for MoDCs to acquire potent T-helper cell stimulatory capacity and substantial chemotactic responsiveness to lymph node-derived chemokines. This is a new and important parameter for the preparation of MoDCs as cellular vaccines in tumor immunotherapy. (Blood. 2002;100:1354-1361)