gebhart/patrepeval huggingface dataset:
Improved Production of Adenovirus Vectors Expressing Apoptotic Transgenes (2000)

Adenovirus vectors expressing gene products that can induce apoptosis have potential utility in gene therapy applications ranging from the treatment of proliferative diseases to transplantation. However, adenovirus vectors carrying proapoptotic gene products are difficult to produce, as the apoptotic environment is not conducive to adenovirus gene expression and replication. Production of AdFasL/G, an adenovirus vector that expresses high levels of Fas ligand, was severely reduced in the 293 packaging cell line. Increased yields of AdFasL/G were achieved by inclusion of peptide-based caspase inhibitors in the growth medium. However, use of these inhibitors for large-scale production would be difficult and expensive. A screen for gene products that increase the yield of AdFasL/G in 293 cells revealed that the poxvirus serpin CrmA and the adenovirus 14.7K product were able to increase virus yields significantly. Apoptosis induced by AdFasL/G was attenuated in 293CrmA cell lines and virus titers were increased dramatically. However, serial passage of AdFasL/G on 293CrmA cells resulted in the generation of replication-competent adenovirus. To resolve this problem, the CrmA gene was introduced into AE25 cells, an E1-complementing cell line that has limited sequence identity with the vectors. AdFasL/G titers were increased 100-fold on AE25CrmA cells relative to the AE25 cells and RCA contamination was not detectable. In addition, adenovirus vectors that express FADD, caspase 8, and Fas/APO1 were produced efficiently in AE25CrmA and 293CrmA.
PET imaging of regional 18F-FDG uptake and lung function after cigarette smoke inhalation. (2007)

Substantial interanimal variability and spatial heterogeneity in lung function and (18)F-FDG uptake seem to characterize the response to smoke exposure. The highest levels of local (18)F-FDG uptake were associated with differences in V/Q matching and shunt fraction among animals. The data also suggest that preexisting heterogeneity in V/Q could have been responsible for the large interanimal variability by affecting the heterogeneity and strength of the acute response to smoke inhalation.
Role of liquid crystals in the lubrication of living joints (1993)

This investigation was devoted to the study of a natural phenomenon-low friction in living joints-and development of synthetic lubricants. The experiments conducted allowed us to establish that the known property of synovia to ensure the high antifrictional ability of joint cartilages is provided by the realization of a liquid-crystalline state of the lubricant in the friction zone that was unknown before. An idea was advanced that molecules of liquid-crystalline cholesterol compounds found in synovia are arranged with their longer axis aligned with prevailing microgroove locomotions on cartilage surfaces to make a liquid-crystalline nematic phase, thus reducing energy dissipation during relative motion of contacting cartilages and leading to the medicative effect revealed by experimentation.
Recombinant TSH-Receptor for Determination of TSH-Receptor-Antibodies (2009)

We have expressed the complete coding sequence of the human TSH-R in eucaryotic cells. Limiting dilution enabled us to select two clones, JP09 and JP26, which have formed the basis of binding and bioassays respectively, for TSH-R antibodies. Results obtained in the binding assay correlated well with those obtained in the TRAK (Henning Berlin) assay, while the bioassay was at least as sensitive as measurements made with FRTL5 or human thyroid cells. These cell lines provide a reliable source of human TSH-R which will be useful in routine diagnosis.
Irisin protects mitochondria function during pulmonary ischemia/reperfusion injury (2017)

Irisin protects against ischemia/reperfusion injury to the lung by improving mitochondrial function.
<title>Cytochrome P450s and molecular epidemiology</title> (1993)

Cytochrome P450 (P450) represent a superfamily of heme-containing monooxygenases that are found throughout the animal and plant kingdoms and in many microorganisms. A number of these enzymes are involved in biosynthetic pathways of steroid synthesis but in mammals the vast majority of P450s function to metabolize foreign chemicals or xenobiotics. In the classical phase I reactions on the latter, a membrane-bound P450 will hydroxylate a compound, usually hydrophobic in nature, and the hydroxyl group will serve as a substrate for the various transferases or phase II enzymes that attach hydrophilic substituents such as glutathione, sulfate or glucuronic acid. Some chemicals, however, are metabolically-activated by P450s to electrophiles capable of reacting with cellular macromolecules. The cellular concentrations of the chemical and P450, reactivity of the active metabolite with nucleic acid and the repairability of the resultant adducts, in addition to the nature of the cell type, likely determines whether a chemical will be toxic and kill the cell or will transform the cell. Immunocorrelative and cDNA-directed expression have been used to define the substrate specificities of numerous human P450s. Levels of expression of different human P450 forms have been measured by both in vivo and in vitro methodologies leading to the realization that a large degree of interindividual differences occur in P450 expression. Reliable procedures for measuring P450 expression in healthy and diseased subjects will lead to prospective and case- cohort studies to determine whether interindividual differences in levels of P450 are associated with susceptibility or resistance to environmentally-based disease.
Biosynthesis and Enzymatic Characterization of Human SKI-1/S1P and the Processing of Its Inhibitory Prosegment (2000)

Biochemical and enzymatic characterization of the novel human subtilase hSKI-1 was carried out in various cell lines. Within the endoplasmic reticulum of LoVo cells, proSKI-1 is converted to SKI-1 by processing of its prosegment into 26-, 24-, 14-, 10-, and 8-kDa products, some of which remain tightly associated with the enzyme. N-terminal sequencing and mass spectrometric analysis were used to map the cleavage sites of the most abundant fragments, which were confirmed by synthetic peptide processing. To characterize its in vitro enzymatic properties, we generated a secreted form of SKI-1. Our data demonstrate that SKI-1 is a Ca(2+)-dependent proteinase exhibiting optimal cleavage at pH 6.5. We present evidence that SKI-1 processes peptides mimicking the cleavage sites of the SKI-1 prosegment, pro-brain-derived neurotrophic factor, and the sterol regulatory element-binding protein SREBP-2. Among the candidate peptides encompassing sections of the SKI-1 prosegment, the RSLK(137)- and RRLL(186)-containing peptides were best cleaved by this enzyme. Mutagenesis of the latter peptide allowed us to develop an efficiently processed SKI-1 substrate and to assess the importance of several P and P' residues. Finally, we demonstrate that, in vitro, recombinant prosegments of SKI-1 inhibit its activity with apparent inhibitor constants of 100-200 nM.
Abstract 475: Relationship Between Oxidized Phospholipid Content On Apolipoprotein B-100 Particles, Statin Therapy and Atheroma Volume: Observations From The REVERSAL Study (2007)

Background: Increased levels of oxidized phospholipids on apolipoprotein B-100 particles (OxPL/apoB) are associated with angiographically defined coronary artery disease, progression of carotid atherosclerosis and predict new cardiovascular events. Interestingly, OxPL/apoB levels increase in response to low-fat diets or therapy with different statins. Furthermore, during dietary-induced atherosclerosis regression in animals, increases in plasma OxPL/apoB levels are associated with reduced OxPL content in atheromatous plaques, suggesting a flux of OxPL from the vessel wall to the lumen. Methods: In a subgroup of 220 patients from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, we measured several biomarkers of oxidized LDL (OxLDL), including OxPL/apoB and IgG and IgM apoB-100 immune complexes (apoB-IC) and OxLDL autoantibodies, at baseline and after 18 months of treatment with atorvastatin (AT) 80mg/d or pravastatin (PR) 40mg/d. Measures of total atheroma volume (TAV) and vessel remodeling with intravascular ultrasound (IVUS) were analyzed. Results: Compared to baseline values, OxPL/apoB levels increased 58.5% (P<0.0001) in response to AT and 32.7% (P<0.0001) in response to PR. In contrast, IG apoB-IC, IgM apoB-IC and IgM OxLDL autoantibodies were significantly reduced by both AT and PR (p-value: range 0.04 – 0.0001). However, no differences in OxLDL biomarkers were noted between the AT and PR groups. In the entire group, there were no correlations between TAV and vessel remodeling with any OxLDL biomarkers at baseline or 18 months. Conclusion: Statin therapy results in significant increases in OxPL/apoB and decreases in immune complexes and OxLDL autoantibodies. However, these measures do not correlate with atheroma volume or vessel wall remodeling measured by IVUS. Whether statin-induced changes in plaque characteristics, such as the lipid core, correlate with plasma OxLDL biomarkers remains to be determined.
Binding Affinity and Specificity of Neuromyelitis Optica Autoantibodies to Aquaporin-4 M1/M23 Isoforms and Orthogonal Arrays (2011)

Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for the neuroinflammatory disease neuromyelitis optica (NMO). We measured the binding of NMO autoantibodies to AQP4 in human astrocyte-derived U87MG cells expressing M1 and/or M23 AQP4, or M23 mutants that do not form orthogonal array of particles (OAPs). Binding affinity was quantified by two-color fluorescence ratio imaging of cells stained with NMO serum or a recombinant monoclonal NMO autoantibody (NMO-rAb), together with a C terminus anti-AQP4 antibody. NMO-rAb titrations showed binding with dissociation constants down to 44 ± 7 nm. Different NMO-rAbs and NMO patient sera showed a wide variation in NMO-IgG binding to M1 versus M23 AQP4. Differences in binding affinity rather than stoichiometry accounted for M1 versus M23 binding specificity, with consistently greater affinity of NMO-IgG binding to M23 than M1 AQP4. Binding and OAP measurements in cells expressing different M1:M23 ratios or AQP4 mutants indicated that the differential binding of NMO-IgG to M1 versus M23 was due to OAP assembly rather than to differences in the M1 versus M23 N termini. Purified Fab fragments of NMO-IgG showed similar patterns of AQP4 isoform binding, indicating that structural changes in the AQP4 epitope upon array assembly, and not bivalent cross-linking of whole IgG, result in the greater binding affinity to OAPs. Our study establishes a quantitative assay of NMO-IgG binding to AQP4 and indicates remarkable, OAP-dependent heterogeneity in NMO autoantibody binding specificity.
Characterization of a Salt-Independent Pectin Methylesterase Purified from Valencia Orange Peel (2002)

The pectin methylesterase (PME; EC 3.1.1.11) present in a commercial orange peel enzyme preparation was characterized to establish its identity among the multiple PME isozymes present in Valencia orange (Citrus sinensis L.) peel. We show the commercial enzyme corresponds to the major peak 2 PME previously separated by heparin-Sepharose chromatography (Cameron et al., J. Food Sci. 1998, 63, 253). Both PMEs have comparable elution profiles on cation-exchange and hydrophobic-interaction perfusion chromatography columns, molecular weights (ca. 34 kDa) and pI (pH 9.2), and biochemical properties, including a broad pH activity range and activity in the absence of added cations. An identical partial amino terminal peptide sequence was also obtained for the PMEs, which further demonstrated a structural identity with other plant PMEs. The biochemical and structural properties readily distinguish this Valencia orange PME from salt-dependent isozymes and further suggest that it is an ortholog to the salt-independent fruit-specific isozyme of tomato. This work provides a well-defined, enzymatically homogeneous, salt-independent (type 1) plant PME isozyme that is suitable for studying details of the enzyme's mode of action and for use in modifying methylester patterns for studying the structure-functional property relationships in pectin.
Changes in computer extracted features of vessel tortuosity on CT scans post-treatment in responders compared to non-responders for non-small cell lung cancer on immunotherapy. (2017)

11518 Background: Immune-checkpoint blockade treatments demonstrate promising clinical efficacy in patients with non-small cell lung cancer (NSCLC). Nivolumab is a PD-1 inhibitor that is FDA approved for treatment of patients with chemotherapy refractory advanced NSCLC. The current standard clinical approach to evaluating tumor response is sub-optimal in defining clinical benefit from immunotherapy drugs. We sought to evaluate whether computer extracted measurements of vessel tortuosity significantly and differentially change post treatment between NSCLC patients who do and do not respond to immunotherapy. Methods: A total of 50 NSCLC patients including pre- and post- treatment CT scans were included in this study. The patients were either responders or non-responders to Nivolumab. Patients who did not receive Nivolumab after 2 cycles due to lack of response or progression as per RECIST were classified as ‘non-responders’. A total of 35 tortuosity features of the vessels around the lung nodules were investigated. In the training cohort (N = 25), the features were ranked based on the degree of change between pre- and post- treatment CT. The top 4 features were used for training a Support Vector Machine (SVM) classifier to identify which patients did and did not respond to immunotherapy on a validation cohort of N = 25 patients. Results: The top features identified were the ones associated with the curvature of the vessel branches. The AUC for the SVM classifier was 0.75 for the training and 0.79 for the test set. Conclusions: Changes in specific vessel tortuosity features between baseline and post-treatment CT scans following nivolumab were different between NSCLC patients who did and did not respond. Multi-site validation of the vessel tortuosity features is needed to establish it as a predictive biomarker for NSCLC patients treated with immunotherapy.
Incidence of secondary malignancies among patients with <scp>W</scp>aldenström macroglobulinemia: An analysis of the <scp>SEER</scp> database (2015)

Patients with WM had a 49% higher risk of SMs than the general population. The selectively increased risk for hematologic SMs and certain solid SMs may be associated with transformation, therapy, and immune dysregulation.
High‐level cell‐free synthesis yields of proteins containing site‐specific non‐natural amino acids (2008)

We describe an E. coli-based cell-free system for the production of proteins with a non-natural amino acid (nnAA) incorporated site-specifically (modified protein). The mutant Methanococcus jannaschii tyrosyl-tRNA synthetase (mTyrRS) and tRNA(Tyr) pair were used as orthogonal elements. The mTyrRS experienced proteolysis and modified protein yields improved with higher synthetase addition (200-300 microg/mL). Product yields were also improved by increasing levels of total protein to 20 mg protein/mL and available vesicle surface area to 0.5 m(2)/mL. This new E. coli-based cell-free procedure produced up to 400 microg/mL of eCAT109pAz, 660 microg/mL of eDHFR10pAz, and 210 microg/mL of mDHFR31pAz with p-azido-L-phenylalanine (pAz) incorporated site-specifically at the amber nonsense codon. O-methyl-L-tyrosine and p-acetyl-L-phenylalanine were incorporated by similar protocols. The desired specificity for incorporation of the nnAA by the cell-free system was confirmed. Additionally, the modified proteins were enzymatically active and reactive for copper(I)-catalyzed (3 + 2) cycloadditions (click chemistry).
A Capillary Mixer with Adjustable Reaction Chamber Volume for Millisecond Time-Resolved Studies by Electrospray Mass Spectrometry (2003)

A novel continuous-flow apparatus for on-line kinetic studies of (bio)chemical solution-phase processes by electrospray ionization mass spectrometry (ESI-MS) is described. The device is based on two concentric capillaries. Fluid is released from the inner capillary into the intercapillary space, where it mixes with solution flowing through the outer capillary, thus initiating the reaction of interest. Gas-phase analyte ions are formed near the tip of the outer capillary by pneumatically assisted ESI. This setup allows the mixer to be placed directly within the ion source, thus providing a minimal dead volume of ~8 nL. Time-resolved data can be recorded in both "spectral" and "kinetic" modes. In the former case, the position of the inner capillary is fixed at various points, such that entire mass spectra can be recorded for selected reaction times. For experiments in kinetic mode, the mass spectrometer monitors the signal intensity at selected m/z values, while the inner capillary is continuously pulled back, thus providing intensity-time profiles for specific reactive species. A theoretical framework is developed that allows the measured kinetics to be analyzed by taking into account the effects of laminar flow within the reaction capillary. Failure to take these effects into account results in erroneous rate constants. Studies on the demetalation kinetics of chlorophyll reveal that the apparatus can reliably measure rate constants up to at least 100 s-1. This represents a substantial improvement over previous ESI-MS-based kinetic methods. Spectral mode experiments on the refolding of ubiquitin show the changing proportions of denatured and tightly folded protein subpopulations in solution. When monitored in kinetic mode, the refolding process was found to proceed with a rate constant of 5.2 s-1.
Interference cancellation and blind equalization for linear multi-user systems (2000)

Potential applications of blind channel identification and equalization in wireless communication systems have been previously explored. For multi-user systems that are irreducible and column-reduced, second order statistical methods normally can identify channel dynamics up to a unitary mixing matrix. We investigate the equalizability of desired users and the cancellation of unwanted interfering signals based on second order output statistics. We show that a desired user channel can be equalized if it has the longest memory. Furthermore, interfering user signals can be cancelled under a more related multi-user channel condition.
Measurements of the critical inclusion size for arcing and macroparticle ejection from aluminum sputtering targets (2001)

Arcing during sputtering is a significant cause of defect generation during sputter deposition of thin films. We studied the effect of dielectric inclusion size on the propensity for arcing while sputtering aluminum targets in argon at power densities ranging from 8 to near 60 W/cm2. We found that there is a critical inclusion size required for arcing to occur. The critical size for an Al2O3 inclusion in an aluminum-sputtering target in an argon plasma is 440±160 μm. Inclusions with sizes above this critical value readily induce arcing and macroparticle ejection during sputtering. Inclusions below this critical size do not cause arcing or macroparticle ejection. We also found that the inclusion critical size was not sensitive to the sputtering power density. When the inclusion size exceeds the critical value the plasma boundary over the inclusion is deformed by the charge accumulating on the dielectric inclusion and the plasma positive column diffuses toward the target leading to a bipolar arc. Inclusions below the critical size do not distort the dark space to an extent great enough to permit bipolar arc formation. Our proposed model predicts that the critical inclusion size depends upon the sheath thickness, which ranged between 300 and 600 μm for the experimental conditions used in this study.
Fast and Efficient Graph Traversal Algorithm for CPUs: Maximizing Single-Node Efficiency (2012)

Graph-based structures are being increasingly used to model data and relations among data in a number of fields. Graph-based databases are becoming more popular as a means to better represent such data. Graph traversal is a key component in graph algorithms such as reachability and graph matching. Since the scale of data stored and queried in these databases is increasing, it is important to obtain high performing implementations of graph traversal that can efficiently utilize the processing power of modern processors. In this work, we present a scalable Breadth-First Search Traversal algorithm for modern multi-socket, multi-core CPUs. Our algorithm uses lock- and atomic-free operations on a cache-resident structure for arbitrary sized graphs to filter out expensive main memory accesses, and completely and efficiently utilizes all available bandwidth resources. We propose a work distribution approach for multi-socket platforms that ensures load-balancing while keeping cross-socket communication low. We provide a detailed analytical model that accurately projects the performance of our single- and multi-socket traversal algorithms to within 5-10% of obtained performance. Our analytical model serves as a useful tool to analyze performance bottlenecks on modern CPUs. When measured on various synthetic and real-world graphs with a wide range of graph sizes, vertex degrees and graph diameters, our implementation on a dual-socket Intel <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">®</sup> Xeon <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">®</sup> X5570 (Intel microarchitecture code name Nehalem) system achieves 1.5X-13.2X performance speedup over the best reported numbers. We achieve around 1 Billion traversed edges per second on a scale-free R-MAT graph with 64M vertices and 2 Billion edges on a dual-socket Nehalem system. Our optimized algorithm is useful as a building block for efficient multi-node implementations and future exascale systems, thereby allowing them to ride the trend of increasing per-node compute and bandwidth resources.
Chemical lift‐off of GaN epitaxial films grown on c‐sapphire substrates with CrN buffer layers (2008)

Abstract GaN epitaxial films are grown on c‐plane sapphire substrates with CrN buffer. The GaN layers show high crystalline quality and smooth surface morphology without being cracked. Selective etching of CrN buffer is performed by wet etching using conventional Cr metal etchant, which results in success ful lift‐off of GaN thick layers. We confirm that the crystalline quality of GaN does not change through the etching process. These results indicate that the chemical lift‐off process using CrN buffer is promising for production of both freestanding GaN substrates and vertical‐structure devices. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Two-mode InGaSb/GaSb strained-layer superlattice infrared photodetector (1993)

An interesting two-mode photodetector was constructed using an In/sub 0.19/Ga/sub 0.81/Sb/GaSb strained-layer superlattice (SLS). Such a structure is, at the same time, of type I for heavy hole and type II for light hole. The mini-subbands of this In/sub 0.19/Ga/sub 0.81/Sb/GaSb SLS are calculated using the modified Kronig-Penney model, as a function of well width at 300 K. A ten-period In/sub 0.19/Ga/sub 0.81/Sb/GaSb SLS structure can be applied as a two-mode photodetector with near-zero and reverse bias. This phenomenon can be proved by the spectral response of the structure grown by low-pressure metalorganic chemical vapor deposition (MOCVD). The wavelengths of dominant absorption peaks are 1.92 and 1.77 mu m at near-zero and reverse bias, respectively. The experimental data are in good agreement with the theoretical deductions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>