gebhart/patrepeval huggingface dataset:
Saturated and Polyunsaturated Fatty Acids Reciprocally Modulate Dendritic Cell Functions Mediated through TLR4 (2005)

Abstract TLRs provide critical signals to induce innate immune responses in APCs such as dendritic cells (DCs) that in turn link to adaptive immune responses. Results from our previous studies demonstrated that saturated fatty acids activate TLRs, whereas n-3 polyunsaturated fatty acids inhibit agonist-induced TLR activation. These results raise a significant question as to whether fatty acids differentially modulate immune responses mediated through TLR activation. The results presented in this study demonstrate that the saturated fatty acid, lauric acid, up-regulates the expression of costimulatory molecules (CD40, CD80, and CD86), MHC class II, and cytokines (IL-12p70 and IL-6) in bone marrow-derived DCs. The dominant negative mutant of TLR4 or its downstream signaling components inhibits lauric acid-induced expression of a CD86 promoter-reporter gene. In contrast, an n-3 polyunsaturated fatty acid, docosahexaenoic acid, inhibits TLR4 agonist (LPS)-induced up-regulation of the costimulatory molecules, MHC class II, and cytokine production. Similarly, DCs treated with lauric acid show increased T cell activation capacity, whereas docosahexaenoic acid inhibits T cell activation induced by LPS-treated DCs. Together, our results demonstrate that the reciprocal modulation of both innate and adaptive immune responses by saturated fatty acid and n-3 polyunsaturated fatty acid is mediated at least in part through TLRs. These results imply that TLRs are involved in sterile inflammation and immune responses induced by nonmicrobial endogenous molecules. These results shed new light in understanding how types of dietary fatty acids differentially modulate immune responses that could alter the risk of many chronic diseases.
Osteoblastic gene expression during adipogenesis in hematopoietic supporting murine bone marrow stromal cells (1993)

A growing body of data suggests that the bone marrow stroma contains a population of pluripotent cells capable of differentiating into adipocytes, osteoblasts, and lymphohematopoietic supporting cells. In this work, the murine stromal cell lines BMS2 and +/+ 2.4 have been examined as preadipocytes and adipocytes for evidence of osteoblastic gene expression. Adipocyte differentiation has been quantitated using fluorescence activated cell sorting. Within 7-10 days of adipocyte induction by treatment with glucocorticoids, indomethacin, and methylisobutylxanthine, between 40% to 50% of the cells contain lipid vacuoles and exhibit a characteristic adipocyte morphology. Based on immunocytochemistry, both the adipocytes and preadipocytes express a number of osteoblastic markers; these include alkaline phosphatase, osteopontin, collagen (I, III), bone sialoprotein II, and fibronectin. Based on biochemical assays, the level of alkaline phosphatase expression is not significantly different between preadipocyte and adipocyte cells. However, unlike rat cell lines, dexamethasone exposure causes a dose-dependent decrease in enzyme activity. The steady-state mRNA levels of the osteoblast associated genes varies during the process of adiopogenesis. The relative level of collagen I and collagen III mRNA is lower in adipocyte-induced cells when compared to the uninduced controls. Osteocalcin mRNA is detected in preadipocytes but absent in adipocytes. These data indicate that osteoblastic gene expression is detected in cells capable of undergoing adipocyte differentiation, consistent with the hypothesis that these cell lineages are interrelated.
Adenine nucleotides promote dissociation of pertussis toxin subunits. (1986)

Pertussis toxin is composed of an enzymatically active A subunit and a binding component (B oligomer). Both the holotoxin and the isolated A subunit have previously been shown to exhibit NAD glycohydrolase activity although the A subunit is more active on a molar basis than the holotoxin. We have investigated the mechanism by which ATP stimulates the activity of this toxin. Since dissociation of pertussis toxin subunits would result in increased NAD glycohydrolase activity, the ability of ATP to promote release of the A subunit from the B oligomer was examined. In the presence of the zwitterionic detergent 3-(3-cholamidopropyldimethyl)-1-ammonio)-propanesulfonate, concentrations of ATP as low as 1 microM promoted subunit dissociation. The concentration of ATP required for release of the A subunit was similar to that required for stimulation of NAD glycohydrolase activity. Both ATP and ADP promoted subunit dissociation and stimulated NAD glycohydrolase activity. In contrast, AMP and adenosine did not alter NAD glycohydrolase activity or affect subunit structure. The ability of ATP to decrease the affinity of the A subunit for the B oligomer may play a role in nucleotide stimulation of pertussis toxin activity.
Biweekly Low-dose Sequential Gemcitabine, 5-Fluorouracil, Leucovorin, And Cisplatin (Gfp): A Highly Active Novel Therapy For Metastatic Adenocarcinoma Of The Exocrine Pancreas (2003)

Phase II studies have suggested an improved response rate and acceptable toxicity profile associated with gemcitabine combinations compared to gemcitabine alone for treatment of metastatic adenocarcinoma of the pancreas. The GFP regimen (gemcitabine, 5-fluorouracil, leucovorin, and cisplatin) is based on laboratory evidence of disease-specific chemotherapy interaction. This retrospective analysis examined the outcome of 49 consecutive patients with histologically confirmed metastatic pancreatic adenocarcinoma treated between July 1998 and September 2000. Day 1 treatment consisted of gemcitabine 500 mg/m2 over 30 minutes and then leucovorin 300 mg bolus, 5-fluorouracil (5-FU) 400 mg/m2 bolus, followed by infusional 5-FU 600 mg/m2 over 8 hours. Day 2 consisted of leucovorin 300 mg bolus, 5-FU 400 mg/m2 bolus, followed by cisplatin 50-75 mg/m2 over 30 minutes and then infusional 5-FU 600 mg/m2 over 8 hours. Treatment was administered every 2 weeks. Median patient age was 61.5 years, 74% were men, and 20 patients had refractory disease (11 patients had disease progression upon gemcitabine-based therapy). Grade 3-4 toxic effects (% patients) consisted of neutropenia (30%), thrombocytopenia (14%), anemia (8%), and neutropenic fever (2%). Grade 3-4 nonhematological toxicities (% patients) consisted of neuropathy (14%), ototoxicity (8%), nephrotoxicity (6%), nausea/vomiting (14%), and mucositis (10%). The majority of dose reductions were made for neuropathy or cytopenias. Filgrastim and erythropoietin were given as needed to promote dose intensity. Eight patients attained a partial response (PR) by RECIST criteria. Fourteen had stable disease (SD). Two patients attaining PR and two attaining SD had progressive disease with prior gemcitabine-based therapy. The median time to disease progression (TTP) from GFP start was 9 weeks. For all 49 patients, the median overall survival (OS) from GFP start was 10.6 months, 12-month survival was 46%, and 24-month survival was 30%. Notably, upon disease progression, 31 patients continued to receive the GFP regimen with irinotecan 80 mg/m2 inserted on day 1 following gemcitabine, the G-FLIP regimen (gemcitabine, 5-fluorouracil, leucovorin, irinotecan, and cisplatin). Measured from G-FLIP initiation, the TTP for the 31 patients treated sequentially was 10 weeks, and for the 14 patients attaining SD or PR the TTP was 25 weeks. The median overall survival measured from GFP initiation was 11.8 months. The response rate, non-cross resistance, TTP, OS, and tolerability warrant prospective development of this novel combination. This experience also demonstrates that adding a single new drug such as irinotecan to the same first-line chemotherapy combination upon disease progression may be an important alternative for the treatment of relapsed/resistant cancer.
Highly Tolerated Amino Acid Substitutions Increase the Fidelity of Escherichia coli DNA Polymerase I (2007)

Fidelity of DNA synthesis, catalyzed by DNA polymerases, is critical for the maintenance of the integrity of the genome. Mutant polymerases with elevated accuracy (antimutators) have been observed, but these mainly involve increased exonuclease proofreading or large decreases in polymerase activity. We have determined the tolerance of DNA polymerase for amino acid substitutions in the active site and in different segments of E. coli DNA polymerase I and have determined the effects of these substitutions on the fidelity of DNA synthesis. We established a DNA polymerase I mutant library, with random substitutions throughout the polymerase domain. This random library was first selected for activity. The essentiality of DNA polymerases and their sequence and structural conservation suggests that few amino acid substitutions would be tolerated. However, we report that two-thirds of single base substitutions were tolerated without loss of activity, and plasticity often occurs at evolutionarily conserved regions. We screened 408 members of the active library for alterations in fidelity of DNA synthesis in Escherichia coli expressing the mutant polymerases and carrying a second plasmid containing a beta-lactamase reporter. Mutation frequencies varied from 1/1000- to 1000-fold greater compared with wild type. Mutations that produced an antimutator phenotype were distributed throughout the polymerase domain, with 12% clustered in the M-helix. We confirmed that a single mutation in this segment results in increased base discrimination. Thus, this work identifies the M-helix as a determinant of fidelity and suggests that polymerases can tolerate many substitutions that alter fidelity without incurring major changes in activity.
Introduction (2003)

This book explores one of the great moments of transition in modern history – the French Revolution – through the lives and experiences of the inhabitants of six villages. It joins together the problem-oriented approach of the comparative historian and the craft skills of the micro-historian to produce an unusual, authentic and above all decentred analysis of the way a generation of French country dwellers responded to the pressures threatening to alter their lives fundamentally from the 1760s onwards. The reader will judge how far this project has been successful. The practice of comparative history is usually confined to large-scale social phenomena, and it is an open question whether a genre that might be described as ‘comparative micro-history’ can – or should – exist. The research for this book commenced under no particular theoretical or methodological banner. As anyone who has worked at the grass roots will testify, the availability or non-availability of source materials tends to overshadow all other considerations. Nevertheless, it would be wrong to give the impression that the book simply evolved in a random and haphazard manner. Three guiding ambitions served to direct and structure my investigations: a desire to improve the ‘reach’ of social history in an area that historians of France think they know rather well; a desire to transcend the ubiquitous village monograph; and finally a desire to try to avoid a composite or ‘synthetic’ history of the experiences of country dwellers in which examples are culled from far and wide in order to illustrate propositions that have usually been formulated in advance.
Optical Design of InAlGaAs Low-Loss Tunnel-Junction Apertures for Long-Wavelength Vertical-Cavity Lasers (2006)

We report on the optical design of thin selectively etched InAlGaAs tunnel-junction apertures for the realization of optically efficient long-wavelength vertical-cavity surface-emitting lasers (VCSELs). These apertures were designed to introduce minimal optical loss to the structure, facilitate single-mode operation, and yield optical mode diameters that better match the injected current density profile. We then demonstrate InP-based VCSELs emitting at 1304 nm utilizing these low-loss InAlGaAs apertures, resulting in optically efficient low-loss devices with differential quantum efficiencies of up to 60%.
Jedi: extracting and synthesizing information from the Web (1998)

Jedi (Java based Extraction and Dissemination of Information) is a lightweight tool for the creation of wrappers and mediators to extract, combine, and reconcile information from several independent information sources. For wrappers it uses attributed grammars, which are evaluated with a fault-tolerant parsing strategy to cope with ambiguous grammars and irregular sources. For mediation it uses a simple generic object-model that can be extended with Java-libraries for specific models such as HTML, XML or the relational model. This paper describes the architecture of Jedi, and then focuses on Jedi's wrapper generator.
Image-Guided Transcranial Focused Ultrasound Stimulates Human Primary Somatosensory Cortex (2015)

Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.
Crystal Structure of a New Anti-hypertension Drug DDPH (1997)

1-(2, 6-Dimethylphenoxy )-2-(3, 4-dimethoxyphenylethylamiro ) propane hydrochoride(DDPH) is a new drug for anti-hypertension. The crystal of (±)DDPH belongs to the spacegroup DDPH crystallizes in the space group P212121 with The crystal structures were determined by X-ray diffraction. After structurerefinement using least-Squares methed, the final R factors of (±)DDPH and (+) DDPH are0.080 and 0.074 respectively.
Monoclonal antibody therapy of lymphoid malignancy. (1985)

Monoclonal antibodies which bind to tumour cell surface antigens have produced regressions of malignancies in an increasing number of clinical trials. The largest experience to date is in the treatment of refractory B and T lymphoid tumours using a variety of intravenously administered mouse monoclonal antibodies. Treatment with antibodies against common differentiation antigens or very specific anti-idiotype antibodies has been effective in both cases. Toxicity has been acceptably low. A number of problems which limit the application and efficacy of monoclonal antibody therapy of lymphoid malignancy have been identified. Most prominent among these are tumour heterogeneity, which allows non-antibody binding subpopulations of the tumour to escape therapy, and the patient's immunological response to the monoclonal antibody-tumour cell complex. As more experience is accumulated, solutions to these problems will be found.
Computing the Boundary of a Class of Labeled-Leaf BSP Solids (2005)

We describe an algorithm that computes the boundary of the shadow volume cast by a collection of piecewise linear polyhedra in space using BSP trees. Unlike boundary representations, representing solids in general and shadow volumes in particular using BSP trees makes it possible to implement boolean operations easily and robustly. Also, in contrast with operating in Constructive Solid Geometry or on Nef polyhedra, no neighborhood analysis is needed. 1
Sequence constraints and recognition by CTL of an HLA-B27-restricted HIV-1 gag epitope. (1995)

Previous studies on the variation of an immunodominant HLA-B27-restricted HIV-1 gag p24 epitope (KRWIIL GLNK, amino acids 263-272) have demonstrated the persistence of variants recognized by CTL. Sequence comparisons of HIV isolates showed that this region is relatively conserved and as a consequence might restrict antigenic variation. To evaluate the possibility of HIV-1 to yield infectious mutants of this epitope that lack the ability to bind to HLA-B27 or escape HLA-B27-restricted CTL recognition, single-point mutations were constructed in the infectious molecular clone of HIV-1 Lai. Changes of arginine 264, the anchor amino acid for HLA-B27, to lysine or glycine resulted in infectious HIV-1 variants. The respective synthetic peptides showed reduced ability to sensitize target cells for CTL recognition and a corresponding loss of binding affinity to HLA-B27. In contrast, mutation of glycine 269 to lysine or glutamate abrogated HIV-1 infectivity. The corresponding peptides were able to bind to HLA-B27 but were not recognized by CTL. These data show that HIV-1 tolerates some genetic variation of the HLA-B27-restricted CTL epitope in gag p24 and that single-point mutations can alter quantitatively the immunologic properties. Further, it demonstrates that the mere nonrecognition of peptides derived from quasispecies analysis of small regions might simply correspond to nonviable virus variants and cannot be taken as evidence for CTL escape mutants. Together with the previously published data on the persistence of CTL epitopes, these results suggest that CTL do not play a major role in driving HIV-1 evolution in vivo.
ChemInform Abstract: Boat Conformations. Part 4. Synthesis, NMR Spectroscopy, and Molecular Dynamics of Methyl 4,6‐O‐Benzylidene‐3‐deoxy‐3‐phthalimido‐α‐D‐altropyranoside Derivatives. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
<title>Controlling perceived depth in stereoscopic images</title> (2001)

Stereoscopic images are hard to get right, and comfortable images are often only produced after repeated trial and error. The main difficulty is controlling the stereoscopic camera parameters so that the viewer does not experience eye strain or double images from excessive perceived depth. Additionally, for head tracked displays, the perceived objects can distort as the viewer moves to look around the displayed scene. We describe a novel method for calculating stereoscopic camera parameters with the following contributions: (1) Provides the user intuitive controls related to easily measured physical values. (2) For head tracked displays; necessarily ensures that there is no depth distortion as the viewer moves. (3) Clearly separates the image capture camera/scene space from the image viewing viewer/display space. (4) Provides a transformation between these two spaces allowing precise control of the mapping of scene depth to perceived display depth. The new method is implemented as an API extension for use with OpenGL, a plug-in for 3D Studio Max and a control system for a stereoscopic digital camera. The result is stereoscopic images generated correctly at the first attempt, with precisely controlled perceived depth. A new analysis of the distortions introduced by different camera parameters was undertaken.
Joints Made by RecA Protein in the Interior of Linear Duplex DNA:Effects of Single-Stranded Ends, Length of Homology, and Dynamic State (1994)

The importance of 3' single-stranded ends in homologous recombination led us to reevaluate reactions of single strands at homologous sites in the interior of linear duplex DNA. As the length of homology increased, the yield of joints increased up to about 2 kb of homology, at which the apparent yields were the same at either 3' or 5' single-stranded ends, or away from ends, although such joints were qualitatively different. In the presence of RecA protein and ATP, joints that formed between any of these single strands and interior sequences in duplex DNA were in a dynamic state in which they constantly recycled. Consequently, their apparent yields at steady state were sensitive to conditions of reaction, such as the concentrations of DNA, salt, and ATP vs ADP, observations which rationalize conflicting reports in the literature. The dynamic state of joints in the interior of duplex DNA strengthens the conclusion [see Burnett et al. (1994)] that RecA protein dissociates joints when it cannot displace the 5' end of a strand from the recipient duplex.
Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia (2016)

Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality. We demonstrated that human memory-like NK cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary human AML blasts in vitro. Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer cell immunoglobulin-like receptor (KIR) to KIR-ligand interactions. In addition, multidimensional analyses identified distinct phenotypes of control and memory-like NK cells from the same individuals. Human memory-like NK cells xenografted into mice substantially reduced AML burden in vivo and improved overall survival. In the context of a first-in-human phase 1 clinical trial, adoptively transferred memory-like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML.
Noise reduction in spectral CT: Reducing dose and breaking the trade‐off between image noise and energy bin selection (2011)

Noise reduction can be accomplished for spectral CT by exploiting data redundancies in the energy domain. HYPR-LR is a robust method for reducing image noise in a variety of spectral CT imaging systems without losing spatial resolution or CT number accuracy. This method improves the flexibility to select energy bins in the manner that optimizes material identification and separation without paying the penalty of increased image noise or its corollary, increased patient dose.