gebhart/patrepeval huggingface dataset:
Rationally designed Gla-domainless FXa as TFPI bait in hemophilia (2022)

Abstract Gla-domainless factor Xa (GD-FXa) was proposed as a trap to the endogenous anticoagulant Tissue Factor Pathway Inhibitor (TFPI) to restore thrombin generation in hemophilia. Using computational chemistry and experimental approaches, we previously showed that S195A GD-FXa also binds TFPI and restores ex vivo coagulation in hemophilia plasmas. To design a GD-FXa variant with improved anti-TFPI activity and identify suitable sites for mutagenesis, we performed molecular dynamics simulations. The calculations identified residues R150 FXa and K96 FXa as cold-spots of interaction between GD-FXa and the K2 domain of TFPI. In the three-dimensional model, both residues are facing TFPI hydrophobic residues and are thus potential candidates for mutagenesis into hydrophobic residues to favor an improved protein-protein interaction. Catalytically inactive GD-FXa variants containing the S195A mutation and additional mutations as K96Y, R150I, R150G and R150F were produced to experimentally confirm these computational hypotheses. Among these mutants, the R150F FXA showed increased affinity for TFPI as theoretically predicted, and was also more effective than S195A GD-FXa in restoring coagulation in FVIII deficient plasmas. Moreover, the R150 mutants lost interaction with antithrombin, which is favorable to extend their half-life.
MauveDB (2006)

Real-world data --- especially when generated by distributed measurement infrastructures such as sensor networks --- tends to be incomplete, imprecise, and erroneous, making it impossible to present it to users or feed it directly into applications. The traditional approach to dealing with this problem is to first process the data using statistical or probabilistic models that can provide more robust interpretations of the data. Current database systems, however, do not provide adequate support for applying models to such data, especially when those models need to be frequently updated as new data arrives in the system. Hence, most scientists and engineers who depend on models for managing their data do not use database systems for archival or querying at all; at best, databases serve as a persistent raw data store.In this paper we define a new abstraction called model-based views and present the architecture of MauveDB, the system we are building to support such views. Just as traditional database views provide logical data independence, model-based views provide independence from the details of the underlying data generating mechanism and hide the irregularities of the data by using models to present a consistent view to the users. MauveDB supports a declarative language for defining model-based views, allows declarative querying over such views using SQL, and supports several different materialization strategies and techniques to efficiently maintain them in the face of frequent updates. We have implemented a prototype system that currently supports views based on regression and interpolation, using the Apache Derby open source DBMS, and we present results that show the utility and performance benefits that can be obtained by supporting several different types of model-based views in a database system.
Control of tacky deposits on paper machines – A review (2006)

SUMMARY: Wood-derived pitch and tacky materials of synthetic origin in recovered fiber streams often cause serious deposit problems on papermaking equipment. Ideally such materials would be completely removed in processes such as screening, cleaning, washing, or flotation de-inking. In practice, tacky materials that remain in the fiber furnish can build up within paper machine headboxes, forming fabrics, press sections, and dryer sections, reducing production efficiency. Product quality is likely to suffer, especially if deposited material ends up in the sheet. This review considers a variety of chemical additives that papermakers have used to combat deposit problems. The premise of this article is that knowledge of the chemistry and colloidal behavior of existing deposit-control agents can guide us in the selection, usage practices, and further development of strategies for the control of tacky deposits, especially in the case of pitch, adhesive-based stickies, and wax-like deposits.
What Kinds of Trade Liberalization Agreements Do People in Developing Countries Want? (2018)

One of the most striking developments in the global economy in the past decades is the rapid proliferation of preferential trade agreements (PTAs), with many of them concluded among or with participation of developing countries. On the presumption that current popular debates on trade policy are not so much about whether citizens want free trade but rather what kinds of trade liberalization they want, we examine individual trade policy preferences with regard to PTAs that can vary in content along several dimensions. To that end we carried out conjoint choice experiments embedded in representative surveys in three developing countries that differ strongly in income levels, political system, and trade liberalization history: Costa Rica, Nicaragua, and Vietnam. We conceptualize trade policy preferences as preferences over the scale and scope of trade liberalization, environmental and labor standards, and labor market access (migration). Two main findings emerge. First, non-economic considerations, such as sympathy/antipathy toward particular countries and environmental and labor rights concerns influence citizens’ preferences at least as much as factors based on standard economic logic. Second, preferences over particular facets (attributes) of trade liberalization, that is PTA content, are surprisingly consistent across countries, despite strong differences in macro-economic and political context.
Positive phase error from parallel conductance in tetrapolar bio-impedance measurements and its compensation (2010)

Abstract Bioimpedance measurements are of great use and can provide considerable insight into biological processes. However, there are a number of possible sources of measurement error that must be considered. The most dominant source of error is found in bipolar measurements where electrode polarisation effects are superimposed on the true impedance of the sample. Even with the tetrapolar approach that is commonly used to circumvent this issue, other errors can persist. Here we characterise the positive phase and rise in impedance magnitude with frequency that can result from the presence of any parallel conductive pathways in the measurement set-up. It is shown that fitting experimental data to an equivalent electrical circuit model allows for more accurate determination of the true sample impedance as validated through finite element modelling (FEM) of the measurement chamber. Finally, the equivalent circuit model is used to extract dispersion information from cell cultures to characterise their growth.
High Efficiency Diesel Engine with Low Heat Loss Combustion Concept - Toyota’s Inline 4-Cylinder 2.8-Liter ESTEC 1GD-FTV Engine - (2016)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;A highly efficient new 2.8-liter inline 4-cylinder diesel engine has been developed in response to growing demand for diesel engines and to help save energy while providing high-torque performance. Engine efficiency was improved by reducing cooling loss based on an innovative combustion concept applied across the whole engine. Cooling loss was reduced by restricting in-cylinder gas flows and improving combustion chamber insulation. To prevent the restricted gas flows from affecting emissions, a new combustion chamber shape was developed that increased air utilization in the cylinder through optimizing the in-cylinder fuel distribution. Combustion chamber insulation was improved by a new insulation coat that changes the wall surface temperature in accordance with the gas temperature. This reduces cooling loss and avoids the trade-off effect of intake air heating. To adopt this combustion concept while improving power/ performance, it was necessary to adjust the characteristics of the intake and exhaust ports to emphasize high flows. This was achieved by adopting new intake ports with separated functions, optimizing the diameter and layout of the intake valve, and increasing the overall efficiency of the intake/exhaust system. Since optimizing the ports shapes required greater design freedom, a new cylinder head gasket with high sealing performance was developed, and a 92 mm-diameter bore was adopted with only four head bolts. By adopting this combustion concept across the whole engine, and incorporating various friction reduction technologies, the new engine reduces CO&lt;sub&gt;2&lt;/sub&gt; emissions by approximately 15% compared to the previous model and achieves a maximum thermal efficiency of approximately 44%.&lt;/div&gt;&lt;/div&gt;
Dynamic Ordering Transitions of Liquid Crystals Driven by Interfacial Complexes Formed between Polyanions and Amphiphilic Polyamines (2008)

We report the design of an amphiphilic polyamine (polymer 1) based on poly(2-alkenyl azlactone) that strongly couples the formation of polyelectrolyte complexes at aqueous/liquid crystal (LC) interfaces to ordering transitions in the LC. We demonstrate that the addition of a strong anionic polyelectrolyte to aqueous solutions in contact with polymer 1-laden LC interfaces (prepared by Langmuir-Schaefer transfer of monolayers of polymer 1 onto micrometer-thick films of nematic LC) triggers ordering transitions in the LCs. We further demonstrate that changes in the ordering of the LCs (i) are driven by electrostatic interactions between the polyelectrolytes, (ii) involve multivalent interactions between the polyelectrolytes, and (iii) are triggered by reorganization of the hydrophobic side chains of amphiphilic polymer 1 upon formation of the interfacial complexes. The results presented in this paper lead us to conclude that ordering transitions in LCs can be used to provide insights into the structure and dynamics of interfacial complexes formed between polyelectrolytes.
Reassembly and co-crystallization of a family 9 processive endoglucanase from its component parts: structural and functional significance of the intermodular linker (2015)

Non-cellulosomal processive endoglucanase 9I (Cel9I) from Clostridium thermocellum is a modular protein, consisting of a family-9 glycoside hydrolase (GH9) catalytic module and two family-3 carbohydrate-binding modules (CBM3c and CBM3b), separated by linker regions. GH9 does not show cellulase activity when expressed without CBM3c and CBM3b and the presence of the CBM3c was previously shown to be essential for endoglucanase activity. Physical reassociation of independently expressed GH9 and CBM3c modules (containing linker sequences) restored 60-70% of the intact Cel9I endocellulase activity. However, the mechanism responsible for recovery of activity remained unclear. In this work we independently expressed recombinant GH9 and CBM3c with and without their interconnecting linker in Escherichia coli. We crystallized and determined the molecular structure of the GH9/linker-CBM3c heterodimer at a resolution of 1.68 Å to understand the functional and structural importance of the mutual spatial orientation of the modules and the role of the interconnecting linker during their re-association. Enzyme activity assays and isothermal titration calorimetry were performed to study and compare the effect of the linker on the re-association. The results indicated that reassembly of the modules could also occur without the linker, albeit with only very low recovery of endoglucanase activity. We propose that the linker regions in the GH9/CBM3c endoglucanases are important for spatial organization and fixation of the modules into functional enzymes.
ChemInform Abstract: Controlled Reduction of Tertiary Amides to the Corresponding Aldehydes or Amines Using Dialkylboranes. (1997)

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.
MEDI0382, a GLP-1/Glucagon Receptor Dual Agonist, in Patients with Type 2 Diabetes—A Multiple-Ascending-Dose Study (2018)

MEDI0382 is a GLP-1/glucagon receptor dual agonist under development for the treatment of type 2 diabetes mellitus (T2DM). This double-blind study (NCT02548585) evaluated MEDI0382 in T2DM patients with BMI 27-40 kg/m2. Subjects (n = 61) were randomized to once-daily subcutaneous MEDI0382 or placebo (PBO) at different dosing levels and uptitration schedules (100 μg [C1], 150 μg [C2], 200 μg [C3], and 300 μg (2 uptitration schedules, C4 and C5). Marked reduction in fasting and postprandial glucose was achieved with a ∼40% decrease in glucose AUC0-4h after mixed-meal testing across all cohorts (P ≤ 0.0102) (Figure 1A). Weight loss was observed at all dose levels and reached statistical significance (P = 0.024) at 300 μg (C4) (Figure 1B). Ambulatory systolic blood pressure decreased nonsignificantly from baseline in the 300-μg cohort (C4, -4.9 vs. -6.5 mmHg; C5, -9.1 vs. -5.0 mmHg). Similar to other marketed GLP-1 analogs, MEDI0382 increased pulse rate vs. PBO (C4, 8.4 vs. -2.4 BPM, P = 0.0039; C5, 5.8 vs. 0.2 BPM, P = 0.0796). Treatment-related adverse events occurred more often with MEDI0382 vs. PBO (86% [36/42] vs. 47% [9/19]); most events were mild or moderate in severity. In conclusion, MEDI0382 administered for up to 22 days showed a marked reduction in both fasting and postprandial glucose with weight reduction and an acceptable tolerability profile. Disclosure D. Robertson: Employee; Self; MedImmune. Employee; Spouse/Partner; GlaxoSmithKline plc. M.W. Stumvoll: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Foundation. M.G. Posch: None. T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research &amp; Development, MedImmune, Merck Sharp &amp; Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi. L. Plum-Moerschel: None. G. Klein: None. L. Tsai: Employee; Self; MedImmune. M. Petrone: Employee; Self; MedImmune. Stock/Shareholder; Self; MedImmune. B. Hirshberg: Employee; Self; AstraZeneca, MedImmune. C. Rondinone: Employee; Self; MedImmune. Stock/Shareholder; Self; AstraZeneca, F. Hoffmann-La Roche Ltd., Abbott, AbbVie Inc. V.E. Parker: Employee; Self; MedImmune. Stock/Shareholder; Self; Accenture. Employee; Self; AstraZeneca. L. Jermutus: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. P. Ambery: Employee; Self; MedImmune. Stock/Shareholder; Self; AstraZeneca.
Cardiovascular actions of vasopressin: baroreflex modulation in the conscious rat (1986)

Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were recorded during graded infusions of arginine vasopressin (AVP), angiotensin II (ANG II), and phenylephrine (PE) in conscious, unrestrained, sinoaortic-denervated (SAD) and normal rats. Base-line MAP, CO, and TPR values before infusion were not different between groups. HR values were significantly higher in SAD rats. Dose-response curves indicated that there was a similar enhancement in pressor sensitivity to AVP, ANG II, and PE in the absence of the baroreceptors. Pressor responses to AVP were buffered by offsetting decreases of CO. Similar elevations in MAP evoked a 50% greater reduction in CO with AVP, and HR decreased 1.5 times as much with AVP than with ANG II or PE. The dose of AVP required to raise MAP by 25 mmHg in control rats resulted in similar falls of CO in SAD rats, whereas HR responses to AVP were attenuated significantly in SAD rats. We conclude that baroreceptor buffering of AVP-induced pressor responses is due principally to reflex reduction of TPR. Furthermore, CO suppression was not baroreflex-mediated, whereas bradycardia was reflex dependent. Finally, in rats, AVP does not appear to interact with the baroreceptor reflexes in a manner unique from other vasoconstrictor agents to buffer MAP.
Common Decomposition Pathways of 1-Epoxy-3-butene and 2-Butenal on Pd(111) (2008)

High resolution electron energy loss spectroscopy (HREELS) and temperature programmed desorption (TPD) were employed to study the decomposition of 1-epoxy-3-butene (EpB) and 2-butenal (crotonaldehyde, CrHO) on Pd(111). HREELS investigations indicate that both EpB and CrHO decompose through a common surface aldehyde intermediate that is distinct from molecular CrHO. The surface aldehyde intermediate decomposes to yield the gas phase decarbonylation products CO and propylene, as well as H2. Comparison with previous studies suggests that Pd is unique compared to previously studied surfaces in its reactivity with EpB and CrHO.
Retrieving the instantaneous frequency from images by wavelet ridges (2004)

Instantaneous frequency (IF) is very important in signal communications and methods, such as Hilbert transform and more recently wavelet ridges, have been developed to extract them. The importance of IF for 2D images has often been ignored. For example, in moire interferometry, IF can directly provide strain contours, which usually is the desired parameter in experimental mechanics. In this paper, the method of wavelet ridges is first extended from a 1D signal to 2D images with carrier fringes. In cases where the carrier fringes is not available, the phase shift approach is proposed, to extract the instantaneous frequency (IF) using wavelet ridges. Both methodologies are introduced and applied to real fringe patterns.
Climacteric symptoms in healthy middle-aged women. (1994)

The incidence of climacteric symptoms was determined in 247 healthy premenopausal women in a community setting. These volunteers had been recruited to a longitudinal study of bone density. Of these subjects, 46 ceased to menstruate during the study, and in this subgroup symptoms were compared before and after cessation of menstruation. Only hot flushes increased after cessation of menstruation in the longitudinal study and showed age correlation in the cross-sectional study. Hot flushes thus emerged as a true menopausal symptom. Although evidence for this is weaker, cold sweats and suffocation seem likely to be genuinely menopausal. Breast discomfort and the four mood symptoms of irritability, excitability, depression and poor concentration improved after cessation of menstruation, and this study gives no support for their being part of the menopausal syndrome; it suggests that these symptoms are more likely to be related to menstruation than to the menopause.
A self-consistent model for high repetition rate copper vapor lasers (1981)

A computer model for a high repetition rate copper vapor laser is described. Equations for the discharge pulse, laser pulse, and interpulse afterglow period are simultaneously integrated over many discharge cycles until a consistent solution is obtained. In this way, consistent initial conditions are obtained and many scaling characteristics of the copper laser are successfully reproduced. This is a major improvement over models which consider only a single-laser pulse. By modeling both an ideal and real laser, and comparing the results to experimental data, we have determined that the peak-elctron temperature and the initial density of metastable copper are the factors which dominate the performance of the laser. Processes which effect these two quantities are therefore the most important in describing the laser.
A novel proteomic mass spectrometry-based approach to reveal functionally heterogeneous tumor clones in breast cancer metastases and identify clone-specific drug targets. (2020)

e13063 Background: Breast cancer mortality is expected to rise by almost 30% by 2030 worldwide, mainly due to the occurrence of distant metastases. The development of drugs specifically targeted at tumor drivers has not yet curbed resistance to treatment, which prevents metastases curability. There is a need for new molecular approaches to tackle metastases complex biology, particularly tumor heterogeneity, a main determinant of resistance. The aim of this study was to use a proteomic mass spectrometry-based approach to reveal functionally heterogeneous’ tumor subpopulations in breast cancer metastases, and identify clone specific drug targets. Methods: Metastasis biopsies (n = 21) were collected retrospectively from patients with advanced breast cancer treated at Oscar Lambret Cancer Center (Lille, France). Tumor heterogeneity was analyzed directly on FFPE tissue sections using MALDI mass spectrometry imaging (MSI) on a RapifleX Tissuetyper. Unsupervised spatial segmentation was performed to reveal tumor subpopulations with distinct proteomic profiles within each metastasis. The full proteomic characterization of these tumor clones was further performed with spatially resolved proteomic mass spectrometry. Results: MSI revealed that breast cancer metastases contained 2 to 5 functionally distinct tumor clones (proteomic clones). Although the clone profiles within a metastasis were correlated, unsupervised hierarchical clustering showed a clear distinction between them and specific proteomic signatures. Enrichment analysis showed that differentially expressed proteins were involved in a variety of biological processes or pathways including regulation of histone acetylation, extracellular matrix degradation, DNA repair, NOTCH pathway, estrogen-responsive target genes or exocytosis. The evolution of the proteomic clones profile during disease progression was also determined by comparison of paired biopsies. To identify the candidate treatments best fitted to metastasis heterogeneity, the specific proteomic signatures of the clones were matched against a druggable genome database. It was possible to unveil candidate drug targets personalized to each metastasis functional clone. Conclusions: MALDI mass spectrometry imaging combined with spatially resolved proteomics has the potential to tackle breast cancer metastases heterogeneity, and identify candidate drug targets specific to functional clones to personalize treatments.
Hydrolysis of Ammonia-pretreated Sugar Cane Bagasse with Cellulase, β-Glucosidase, and Hemicellulase Preparations (2007)

Sugar cane bagasse consists of hemicellulose (24%) and cellulose (38%), and bioconversion of both fractions to ethanol should be considered for a viable process. We have evaluated the hydrolysis of pretreated bagasse with combinations of cellulase, β-glucosidase, and hemicellulase. Ground bagasse was pretreated either by the AFEX process (2NH3: 1 biomass, 100 °C, 30 min) or with NH4OH (0.5 g NH4OH of a 28% [v/v] per gram dry biomass; 160 °C, 60 min), and composition analysis showed that the glucan and xylan fractions remained largely intact. The enzyme activities of four commercial xylanase preparations and supernatants of four laboratory-grown fungi were determined and evaluated for their ability to boost xylan hydrolysis when added to cellulase and β-glucosidase (10 filter paper units [FPU]: 20 cellobiase units [CBU]/g glucan). At 1% glucan loading, the commercial enzyme preparations (added at 10% or 50% levels of total protein in the enzyme preparations) boosted xylan and glucan hydrolysis in both pretreated bagasse samples. Xylanase addition at 10% protein level also improved hydrolysis of xylan and glucan fractions up to 10% glucan loading (28% solids loading). Significant xylanase activity in enzyme cocktails appears to be required for improving hydrolysis of both glucan and xylan fractions of ammonia pretreated sugar cane bagasse.