gebhart/patrepeval huggingface dataset:
Antibiotic penetration of and bactericidal activity within endothelial cells (1994)

It has been observed that the number of cases of infective endocarditis arising in patients who have no previous identifiable cardiac abnormalities is increasing, suggesting that direct bacterial interactions with endothelium may occur. Furthermore, the prolonged natural history of endocarditis, need for lengthy therapy, and frequency of relapse suggest that intracellular bacteria that may be protected from antimicrobial action and host responses exist. Using high-performance liquid chromatography, we investigated the penetration of seven antibiotics used to treat Staphylococcus aureus infections into cultured human umbilical vein endothelial cells and the effect of these antibiotics on the intracellular killing of two strains of the organism. In general, endothelial cell penetration of lipophilic drugs, such as minocycline, ciprofloxacin, and rifampin, exceeded that of hydrophilic drugs, represented by nafcillin, cefazolin, cefuroxime, and vancomycin. Bacterial killing paralleled the intracellular penetration of all the antibiotics except rifampin, which concentrated well inside cells but had poor killing activity. However, when combined with the other antibiotics, rifampin potentiated their killing activity against intracellular S. aureus.
Managing diagnostic procedures in idiopathic pulmonary fibrosis (2013)

Idiopathic pulmonary fibrosis (IPF), the most prevalent of the idiopathic interstitial pneumonias, is associated with a poor prognosis. An accurate diagnosis of IPF is essential for its optimal management. The 2011 American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) recommendations on the diagnosis and management of IPF were developed from a systematic review of the published literature. High-resolution computed tomography (HRCT) scanning has a central role in the IPF diagnostic pathway, with formal designation of criteria for an HRCT pattern of usual interstitial pneumonia. In the correct clinical context, a usual interstitial pneumonia pattern on HRCT is indicative of a definite diagnosis of IPF and negates the need for a surgical lung biopsy. However, although the 2011 ATS/ERS/JRS/ALAT statement is a major advance, the application of the guideline recommendations by clinicians has identified limitations that should be addressed in future statements. Key problems include: 1) HRCT misdiagnosis, particularly by less experienced radiologists; 2) lack of management recommendations for the highly prevalent clinical scenarios of "probable" or "possible" IPF; 3) ongoing confusion concerning the diagnostic role of bronchoalveolar lavage; and 4) the lack of integration of clinical data in the designation of the diagnostic likelihood of IPF, including the treated course of disease. These issues become evident as the recommendations are applied and highlight the need for continued guideline adjustments.
Developing tightly-coupled data mining applications on a relational database system (1996)

We present a methodology for tightly coupling data mining applications to database systems to build high-performance applications, without requiring any change to the database software. Introduction Most of the current data mining applications have a loose connection with databases. A majority of them treat database simply as a container from which data is extracted to populate main memory data structures before the main execution begins. This approach limits the amount of data the application can handle effectively. The more database-aware applications use looselycoupled SQL to fetch data records as needed by the mining algorithm. The front-end of the application is implemented in a host programming language, with embedded SQL statements in it. The application uses a SQL select statement to retrieve the set of records of interest from the database. A loop in the application program copies records in the result set one-byone from the database address space to the application address...
Attenuation of Ischemia/Reperfusion Injury in Rats by a Caspase Inhibitor (1998)

ZVAD-fmk was effective in reducing myocardial reperfusion injury, which could at least be partially attributed to the attenuation of cardiomyocyte apoptosis.
Crystal Structure of Human BPI and Two Bound Phospholipids at 2.4 Angstrom Resolution (1997)

Bactericidal/permeability-increasing protein (BPI), a potent antimicrobial protein of 456 residues, binds to and neutralizes lipopolysaccharides from the outer membrane of Gram-negative bacteria. At a resolution of 2.4 angstroms, the crystal structure of human BPI shows a boomerang-shaped molecule formed by two similar domains. Two apolar pockets on the concave surface of the boomerang each bind a molecule of phosphatidylcholine, primarily by interacting with their acyl chains; this suggests that the pockets may also bind the acyl chains of lipopolysaccharide. As a model for the related plasma lipid transfer proteins, BPI illuminates a mechanism of lipid transfer for this protein family.
Discovery and Structural Modification of 1-Phenyl-3-(1-phenylethyl)urea Derivatives as Inhibitors of Complement (2012)

A series of 1-phenyl-3-(1-phenylethyl)urea derivatives were identified as novel and potent complement inhibitors through structural modification of the original compound from high-throughput screening. Various analogues (7 and 13-15) were synthesized and identified as complement inhibitors, with the introduction of a five- or six-carbon chain (7c, 7d, 7k, 7l, and 7o) greatly improving their activity. Optimized compound 7l has an excellent inhibition activity with IC50 values as low as 13 nM. We demonstrated that the compound 7l inhibited C9 deposition through the classical, the lectin, and the alternative pathways but had no influence on C3 and C4 depositions.
Loss of neutral endopeptidase activity contributes to neutrophil activation and cardiac dysfunction during chronic hypomagnesemia: Protection by substance P receptor blockade. (2011)

NEP activity regulates neutrophil •O(2) (-) formation by controlling SP bioavailability. When oxidative inactivation of NEP is prevented by SP receptor blockade, partial protection is afforded against cardiac contractile dysfunction.
Fruit and vegetable exports from the Mediterranean area to the EEC (1979)

The paper reviews trade patterns and volumes of the major fruit and vegetable exporters among developing Mediterranean countries and the major EEC importing countries, with due consideration of seasonality of production. By setting the array of EEC import market regulations against the seasonality of the EEC domestic production and the EEC's Common Agricultural Policy, some implications for future trade prospects are developed. Finally, with this background, projections through 1985 of domestic supply and demand for 36 different fruits and vegetables are made, and from these trade and international prices are then projected.
Both Coding Exons Of The c-mycGene Contribute to Its Posttranscriptional Regulation in the Quiescent Liver and Regenerating Liver and after Protein Synthesis Inhibition (1995)

In vivo, the steady-state level of c-myc mRNA is mainly controlled by posttranscriptional mechanisms. Using a panel of transgenic mice in which various versions of the human c-myc proto-oncogene were under the control of major histocompatibility complex H-2Kb class I regulatory sequences, we have shown that the 5' and the 3' noncoding sequences are dispensable for obtaining a regulated expression of the transgene in adult quiescent tissues, at the start of liver regeneration, and after inhibition of protein synthesis. These results indicated that the coding sequences were sufficient to ensure a regulated c-myc expression. In the present study, we have pursued this analysis with transgenes containing one or the other of the two c-myc coding exons either alone or in association with the c-myc 3' untranslated region. We demonstrate that each of the exons contains determinants which control c-myc mRNA expression. Moreover, we show that in the liver, c-myc exon 2 sequences are able to down-regulate an otherwise stable H-2K mRNA when embedded within it and to induce its transient accumulation after cycloheximide treatment and soon after liver ablation. Finally, the use of transgenes with different coding capacities has allowed us to postulate that the primary mRNA sequence itself and not c-Myc peptides is an important component of c-myc posttranscriptional regulation.
Physical design of a fourth-generation POWER GHz microprocessor (2002)

The fourth-generation POWER processor chip contains 170M transistors and includes 2 microprocessor cores, shared L2, directory for an off-chip L3, and all logic needed to interconnect multiple chips to form an SMP. It is implemented in a 0.18 /spl mu/m SOI technology, with 7 layers of Cu interconnect, and functions in systems at 1.1 GHz, and dissipates 115 W at 1.5 V.
Elevated cell‐associated levels of interleukin 1β and interleukin 6 in inflamed mucosa of inflammatory bowel disease (1996)

The aim of this study was to investigate the involvement of the monocyte-derived cytokines interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in idiopathic inflammatory bowel disease. Endoscopic biopsies of normal and inflamed intestinal mucosa were obtained from patients with ulcerative colitis (n = 11) and with Crohn's disease (n = 10). Intestinal mucosal cells were isolated by collagenase digestion. Cell viability, morphology and CD14 expression were determined. To measure cell-associated cytokine levels, cells were lysed and analysed for IL-1beta and TNF-alpha in specific radioimmunoassays and for IL-6 using a biological assay. Compared with mucosal cells from control patients without inflammatory bowel disease the inflamed intestine in ulcerative colitis and Crohn's disease displayed markedly enhanced levels of IL-1beta (median 245 pg 10(-6) cells, range 30-1275) and IL-6 (median 22 U 10(-6) cells, range 1-298). Non-inflamed mucosa in patients with ulcerative colitis and Crohn's disease did not show elevated levels of IL-1beta (median 50 pg 10(-6) cells, range 33-90) or IL-6 (mean below detection limit of assay, i.e. 1 U 10(-6) cells). In contrast, no clear cut difference between inflamed and non-inflamed mucosa could be detected for TNF-alpha. High tissue levels of IL-6 were associated with a high endoscopic grade of local inflammation. These results suggest that the monocyte-derived cytokines IL-1beta and IL-6 are mediators of inflammation in inflammatory bowel disease.
A Scalable Cross-Platform Infrastructure for Application Performance Tuning Using Hardware Counters (2000)

The purpose of the PAPI project is to specify a standard API for accessing hardware performance counters available on most modern microprocessors. These counters exist as a small set of registers that count “events”, which are occurrences of specific signals and states related to the processor's function. Monitoring these events facilitates correlation between the structure of source/object code and the efficiency of the mapping of that code to the underlying architecture. This correlation has a variety of uses in performance analysis and tuning. The PAPI project has proposed a standard set of hardware events and a standard cross-platform library interface to the underlying counter hardware. The PAPI library has been or is in the process of being implemented on all major HPC platforms. The PAPI project is developing end-user tools for dynamically selecting and displaying hardware counter performance data. PAPI support is also being incorporated into a number of third-party tools.
Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network (2019)

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYCamplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in METmRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
Surface Morphology in Selective Laser Melting of Metal Powders (2011)

Abstract Selective Laser Melting (SLM) is a powder-based additive manufacturing capable to produce parts layer-by-layer from a 3D CAD model. Currently there is a growing interest in industry for applying this technology for generating objects with high geometrical complexity. To introduce SLM process into industry for manufacturing real components, high mechanical properties of final product must be achieved. Properties of the manufactured parts depend strongly on each single laser-melted track and each single layer, as well as the strength of the connections between them. In this study, effects of the processing parameters such as hatch distance on surface morphology are analyzed.
Load modeling and calibration techniques for power system studies (2011)

Load modeling is one of the most uncertain areas in power system simulations. Having an accurate load model is important for power system planning and operation. Here, a review of load modeling and calibration techniques is given. This paper is not comprehensive, but covers some of the techniques commonly found in the literature. The advantages and disadvantages of each technique are outlined.
Generalized multi-ethnic face age-estimation (2009)

Age estimation from digital pictures of the face is a very promising research field that is now receiving wide attention. As with any good research problem, face age-estimation is wrought with many challenging interactions that cannot easily be separated out. In general, aging patterns are well understood for all humans, however, these patterns become confounded by intrinsic factors of genetics, gender differences, and ethnic deviations and, equally as important, extrinsic factors of the environment and behavior choices (i.e. sun exposure, drugs, cigarettes, etc). This novel work focuses on the development of a generalized multi-ethnic age-estimation technique — the first of its kind. In addition to the novelty of this approach, the system's overall performance measure (MAE) is “on par” with algorithms that are tuned for a specific ethnic group. Further, the proposed system performance proves to be far more stable across age than the best published results.
Synthesis and Structure-Activity Relationships of Novel Retinoid X Receptor-Selective Retinoids (1994)

Two series of potent retinoid X receptor (RXR)-selective compounds were designed and synthesized based upon recent observation that (E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1- propenyl]benzoic acid (TTNBP) binds and transactivates only the retinoic acid receptor (RAR) subtypes whereas (E)-4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydro-2-naphthalenyl)-1-propenyl]benzoic acid (3-methyl TTNPB) binds and transactivates both the RAR and RXR subfamilies. Addition of functional groups such as methyl, chloro, bromo, or ethyl to the 3 position of the tetrahydronaphthalene moiety of 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid (5a) and 4-[1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid (6a) results in compounds which elicit potent and selective activation of the RXR class. Such RXR-selective compounds offer pharmacological tools for elucidating the biological role of the individual retinoid receptors with which they interact. Activation profiles in cotransfection and competitive binding assays as well as molecular modeling calculations demonstrate critical structural determinants that confer selectivity for members of the RXR subfamily. The most potent compound of these series, 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl]ben zoi c acid (6b), is the first RXR-selective retinoid (designated as LGD1069) to enter clinical trials for cancer indications.
Polarity and Specific Sequence Requirements of Peroxisome Proliferator-activated Receptor (PPAR)/Retinoid X Receptor Heterodimer Binding to DNA (1997)

The malic enzyme (ME) gene is a target for both thyroid hormone receptors and peroxisome proliferator-activated receptors (PPAR). Within the ME promoter, two direct repeat (DR)-1-like elements, MEp and MEd, have been identified as putative PPAR response elements (PPRE). We demonstrate that only MEp and not MEd is able to bind PPAR/retinoid X receptor (RXR) heterodimers and mediate peroxisome proliferator signaling. Taking advantage of the close sequence resemblance of MEp and MEd, we have identified crucial determinants of a PPRE. Using reciprocal mutation analyses of these two elements, we show the preference for adenine as the spacing nucleotide between the two half-sites of the PPRE and demonstrate the importance of the two first bases flanking the core DR1 in 5'. This latter feature of the PPRE lead us to consider the polarity of the PPAR/RXR heterodimer bound to its cognate element. We demonstrate that, in contrast to the polarity of RXR/TR and RXR/RAR bound to DR4 and DR5 elements respectively, PPAR binds to the 5' extended half-site of the response element, while RXR occupies the 3' half-site. Consistent with this polarity is our finding that formation and binding of the PPAR/RXR heterodimer requires an intact hinge T region in RXR while its integrity is not required for binding of the RXR/TR heterodimer to a DR4.
Enhanced miniaturized Wilkinson power divider (2003)

An enhancement technique for miniaturized Wilkinson power divider is proposed in this paper. The design uses capacitance loading at the input and output ports of the device to achieve size reduction. Broadband characteristics are obtained through the addition of a compensation capacitor between the two output ports. The 11 GHz enhanced Wilkinson power divider is fabricated using a planar microstrip process on GaAs substrate. The occupied area of the device is 0.28 mm /spl times/ 0.76 mm. The measured bandwidth for which the input return loss is better than 15 dB is 60.8 % with an insertion loss on this bandwidth not greater than 0.43 dB and a phase deviation less than 0.12/spl deg/.
B lymphocyte migration to the bone marrow of humans is not random (1999)

This research is a result of analysing a total of 20 independently isolated immunoglobulin gene sequences from a defined population of mature B cells found in the bone marrow of five healthy adults. Each individual exhibited at least two identical gene sequences in our sample. Each variable immunoglobulin sequence is the product of the recombination of three gene segments, V, D and J genes. All sequences sampled contained a specific V gene, V5-51. Comparing the particular J and D genes expressed together with V5-51 as well as the junctional modifications between these genes established the relatedness of the sequences. The likelihood of finding at least two out of k identical gene sequences, if they occur randomly, is found and compared to the experimentally determined sequences. We conclude that it is unlikely that the B cells containing the related sequences found in the bone marrow is by chance. This suggests that this particular population of B cells migrate to the bone marrow in a co-ordinated fashion. Copyright © 1999 John Wiley & Sons, Ltd.
Effect of ion assisted deposition on optical scatter and surface microstructure of thin films (1985)

Ion bombardment of a film during deposition has pronounced effects on the electrical, mechanical, and optical properties of the film. One important optical property is the optical scatter characteristic of the film. This is determined by the film surface and volume microstructure, and thus can be used as a convenient diagnostic technique to examine film morphology. We have examined these effects for metal (Cu and Mo) and dielectric (SiO2 and TiO2) films. We observe, for example, a significant reduction in optical scatter due to surface structure of period &amp;lt;3 μm in the case of films deposited with simultaneous ion bombardment. Other experimental data and a simple model to explain this possible smoothing effect are presented.
The impact of microcarrier culture optimization on the glycosylation profile of a monoclonal antibody (2013)

Microcarriers are widely used for the large-scale culture of attachment-dependent cells with increased cell densities and, ultimately, higher product yield. In these processes, the specific culture conditions can affect the quality of the product, which is closely related to its glycosylation pattern. Furthermore, the lack of studies in the area reinforces the need to better understand the effects of microcarrier culture in product glycosylation. Consequently, in this work, the glycosylation profile of a monoclonal antibody (mAb) produced by adherent CHO-K1 cells grown in Cytodex 3 was evaluated under different conditions, and compared to that obtained of typical adherent cultures. It was found that microcarrier cultures result in a glycosylation profile with different characteristics from T-flask cultures, with a general increase in galactosylation and decrease in fucosylation levels, both with a potentially positive impact on mAb activity. Sialylation also varied but without a general tendency. This study then showed that the specific culture conditions used in microcarrier culture influence the mAb glycan profile, and each functional element (galactose, core fucose, sialic acid) is independently affected by these conditions. In particular, great reductions of fucosylation (from 79 to 55%) were obtained when using half volume at inoculation, and notable decreases in sialylation (from 23 to 2%) and glycoform heterogeneity (from 20 to 11 glycoforms) were observed for shake flask culture, potentially associated with the improved cell densities achieved in these culture vessels.
CD40 Ligand-Dependent T Cell Activation: Requirement of B7-CD28 Signaling Through CD40 (1996)

The role of CD40 ligand (CD40L) in the primary activation of T cells is not clear. The cellular and humoral immune responses to adenoviral vectors in a murine model of liver-directed gene transfer were studied to define the mechanisms responsible for CD40L-dependent T cell priming. CD40L-deficient mice did not develop effective cytotoxic T cells to transduced hepatocytes, and T cell-dependent B cell responses were absent. Full reconstitution of cellular and humoral immunity was achieved in CD40L-deficient mice by administration of an activating antibody to CD40 that increased expression of B7.2 on spleen cells. Wild-type mice could be made nonresponsive to vector by administration of antibodies to B7. Thus, CD40L-dependent activation of T cells occurs through signaling of CD40 in the antigen-presenting cell to enhance requisite costimulatory pathways that include B7.
Low-Dose Otelixizumab Anti-CD3 Monoclonal Antibody DEFEND-1 Study: Results of the Randomized Phase III Study in Recent-Onset Human Type 1 Diabetes (2014)

Otelixizumab was well tolerated in patients with recent-onset type 1 diabetes at a total dose of 3.1 mg, but did not achieve preservation of levels of C-peptide or other markers of metabolic control.