gebhart/patrepeval huggingface dataset:
Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3‐month formulation in patients with schizophrenia: A phase‐1, single‐dose, randomized, open‐label study (2015)

This multicenter, randomized, open-label, parallel-group, phase-1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, aged 18-65 years) were enrolled in 1 of 4 separately conducted panels (A to D). Each panel had 2 single-dose treatment periods (period 1, 1 mg intramuscular paliperidone immediate release [IR]; period 2, intramuscular PP3M 75-525 mg eq) separated by a washout of 7-21 days. Overall, 245 of 308 (79.5%) PP3M-dosed patients completed the study. Because the PK studies of panels A and C were compromised by incomplete injection in some patients, PK data from only panels B and D are presented. Safety data from all panels are presented. Peak paliperidone plasma concentration was achieved between 23 and 34 days, and apparent half-life was ∼2-4 months. Mean plasma AUC∞ and Cmax of paliperidone appeared to be dose-proportional. Relative bioavailability in comparison with paliperidone was ∼100% independent of the dose and injection site. Headache and nasopharyngitis were the most common (>7%) treatment-emergent adverse events. Overall, safety and tolerability were similar to those of the 1-month formulation. Results support a once-every-3-months dosing interval in patients with schizophrenia or schizoaffective disorder.
In vitro assessment of antioxidant, antimicrobial, cytotoxic, anti-inflammatory, and antidiabetic activities of Campanula retrorsa crude extracts (2018)

International audience
Interleukin-19 protects mice from innate-mediated colonic inflammation (2009)

The finding that IL-19 drives pathogenic innate immune responses in the colon suggests that the selective targeting of IL-19 may be an effective therapeutic approach in the treatment of human IBD.
Nonlinear Stochastic Regularization to Characterize Tissue Residue Function in Bolus-Tracking MRI: Assessment and Comparison With SVD, Block-Circulant SVD, and Tikhonov (2009)

An accurate characterization of tissue residue function R(t) in bolus-tracking magnetic resonance imaging is of crucial importance to quantify cerebral hemodynamics. R(t) estimation requires to solve a deconvolution problem. The most popular deconvolution method is singular value decomposition (SVD). However, SVD is known to bear some limitations, e.g., R(t) profiles exhibit nonphysiological oscillations and take on negative values. In addition, SVD estimates are biased in presence of bolus delay and dispersion. Recently, other deconvolution methods have been proposed, in particular block-circulant SVD (cSVD) and Tikhonov regularization (TIKH). Here we propose a new method based on nonlinear stochastic regularization (NSR). NSR is tested on simulated data and compared with SVD, cSVD, and TIKH in presence and absence of bolus dispersion. A clinical case in one patient has also been considered. NSR is shown to perform better than SVD, cSVD, and TIKH in reconstructing both the peak and the residue function, in particular when bolus dispersion is considered. In addition, differently from SVD, cSVD, and TIKH, NSR always provides positive and smooth R(t).
Advances in epigenetic therapeutics with focus on solid tumors (2021)

Epigenetic ("above genetics") modifications can alter the gene expression without altering the DNA sequence. Aberrant epigenetic regulations in cancer include DNA methylation, histone methylation, histone acetylation, non-coding RNA, and mRNA methylation. Epigenetic-targeted agents have demonstrated clinical activities in hematological malignancies and therapeutic potential in solid tumors. In this review, we describe mechanisms of various epigenetic modifications, discuss the Food and Drug Administration-approved epigenetic agents, and focus on the current clinical investigations of novel epigenetic monotherapies and combination therapies in solid tumors.
Micro-CT analysis of tissue engineering scaffold architectures (2008)

Achalasia is associated with eNOS4a4a, iNOS22GA, and nNOS29TT genotypes. This may suggest that polymorphisms of eNOS, iNOS, and nNOS genes are risk factors for achalasia.
FOXA1 and PR predict ipsilateral event risk and identify a group with strong radiation response in ductal carcinoma in situ (DCIS) (2015)

FOXA1 and PR predict ipsilateral event risk and identify a group with strong radiation response in ductal carcinoma in situ (DCIS)
Control of cell fate and excitability at the neural electrode interface: Genetic reprogramming and optical induction (2017)

The development of implantable microelectrode arrays (MEAs) to deliver therapy by recording or stimulating electrical pulses in neural tissue has created a renaissance in the treatment of neurological disorders and the study of the brain. However, following implantation, a reactive tissue response causes a shift in the cellular constituency interfaced by devices: neuronal signal sources are displaced by encapsulating glial cells. We are developing novel applications of genetic engineering to control the identity of cells interfaced by implanted electrodes and restore neuron-device communication. We are pursuing two strategies to redefine the connection between specific electrode sites and individual subtypes of neurons: (1) the use of replication-deficient viral vectors to reprogram the identity of glia encapsulating the device toward neurons of specific identities, drawing from recent advances in cellular reprogramming, and (2) the use of optical induction of proneural genes to alter cell fate at the interface of implanted optoelectrode probes. Our data indicate successful conversion of non-spiking glia to functional neurons via the overexpression of fate-specifying genes (Ascl1, Dlx2) as well as the use of an optical induction system to drive proneural gene expression. The endgoal is a fully-integrated abiotic-biotic interface capable of “tapping into” the electrical signals generated by specified brain circuitry.
A new generation of Bt maize for control of fall armyworm (Spodoptera frugiperda) (2021)

The expression of Cry1B.868 and Cry1Da_7 in MON 95379 consistently protected maize plants against larval feeding by FAW and represents an alternative to manage trait resistance issues in South America. © 2021 Bayer Crop Science-US. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Statin Initiation: Guideline Concordance and Characteristics of New Users in Quebec, Canada (2020)

Statins are widely prescribed for the prevention of cardiovascular (CV) events. Our objective was to describe the characteristics of patients newly prescribed a statin by general practitioners and assess the concordance of prescribing with national guidelines. Patients who were 18 years or older, French-speaking, available for the 2-year study duration, and had no history of statin use were recruited. Biological parameters were measured, and medical history, sociodemographic characteristics, and health behaviours were recorded using structured questionnaires. Patients’ eligibility for a statin was assessed using the Canadian Cardiovascular Society’s dyslipidemia guidelines. Of the 1631 new statin-users enrolled, 47.6% were women. The mean age for all patients was 57.4 years. According to the Canadian guidelines, 50.6% of patients were considered at high risk for a CV event or had a statin-indicated condition. Moderate and low-risk patients represented 26.7 and 22.7% of patients, respectively.
ChemInform Abstract: General and Stereospecific Route to 9‐Substituted, 8,9‐Disubstituted, and 9,10‐Disubstituted Analogues of Benzolactam‐V8. (2000)

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.
Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement (2013)

Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)-a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.
An in Vivo Model for Elucidation of the Mechanism of Tumor Necrosis Factor-α (TNF-α)-Induced Insulin Resistance: Evidence for Differential Regulation of Insulin Signaling by TNF-α (1998)

Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce insulin resistance in cultured cells as well as in animal models. The aim of this study was to map the in vivo mechanism whereby TNF-alpha contributes to the pathogenesis of impaired insulin signaling, using obese and lean Zucker rats in which TNF-alpha activity was inhibited through adenovirus-mediated gene transfer. We employed a replication-incompetent adenovirus-5 (Ad5) vector to endogenously express a TNF inhibitor (TNFi) gene, which encodes a chimeric protein consisting of the extracellular domain of the human 55-kDa TNF receptor joined to a mouse IgG heavy chain. Control animals consisted of rats infected with the same titer of adenovirus carrying the lac-z complementary DNA, encoding for beta-galactosidase. There was a significant reduction in plasma insulin and free fatty acid levels in TNFi obese rats 2 days following Ad5 administration. The peripheral insulin sensitivity index was 50% greater, whereas hepatic glucose output was completely suppressed during hyperinsulinemic glucose clamps in TNFi obese animals, with no differences observed between the two lean groups. The improvement in peripheral and hepatic sensitivity to insulin seen in the obese animals was independent of insulin receptor (IR) number and insulin binding affinity for IR. However, TNF-alpha neutralization led to a 2.5-fold increase in tyrosine phosphorylation of IR in skeletal muscle, whereas this was unchanged in liver. There was also a 4-fold increase in particulate protein tyrosine phosphatase activity of skeletal muscle in TNFi obese animals vs. beta-galactosidase controls, whereas protein tyrosine phosphatase activity in liver was unchanged. These results suggest that TNF-alpha is a mediator of insulin resistance in obesity and may modulate IR signaling in skeletal muscle and liver through different pathways. TNF-alpha may affect insulin action in the liver either at sites distal to the IR or indirectly, possibly because of increased provision of gluconeogenic substrates or altered counterregulation. In addition, the Ad5-mediated gene delivery system employed here provides an in vivo model that is efficient and economical for exploring mechanisms involved in TNF-alpha-induced insulin resistance in various genetic models of obesity-linked diabetes.
Normal Ribosomal Biogenesis but Shortened Protein Synthetic Response to Acute Eccentric Resistance Exercise in Old Skeletal Muscle (2019)

Anabolic resistance to feeding in aged muscle is well-characterized; however, whether old skeletal muscle is intrinsically resistant to acute mechanical loading is less clear. The aim of this study was to determine the impact of aging on muscle protein synthesis (MPS), ribosome biogenesis, and protein breakdown in skeletal muscle following a single bout of resistance exercise. Adult male F344/BN rats aged 10 (Adult) and 30 (Old) months underwent unilateral maximal eccentric contractions of the hindlimb. Precursor rRNA increased early post-exercise (6-18 h), preceding elevations in ribosomal mass at 48 h in Adult and Old; there were no age-related differences in these responses. MPS increased early post-exercise in both Adult and Old; however, at 48 h of recovery, MPS returned to baseline in Old but not Adult. This abbreviated protein synthesis response in Old was associated with decreased levels of IRS1 protein and increased BiP, CHOP and eIF2α levels. Other than these responses, anabolic signaling was similar in Adult and Old muscle in the acute recovery phase. Basal proteasome activity was lower in Old, and resistance exercise did not increase the activity of either the ATP-dependent or independent proteasome, or autophagy (Cathepsin L activity) in either Adult or Old muscle. We conclude that MPS and ribosome biogenesis in response to maximal resistance exercise in old skeletal muscle are initially intact; however, the MPS response is abbreviated in Old, which may be the result of ER stress and/or blunted exercise-induced potentiation of the MPS response to feeding.
Thermally Accelerated Life Testing for Rechargeable li-Ion Batteries (2013)

Abstract not Available.
What works in crime and policing: getting closer to the frontline (2023)

The model of the National Institute for Clinical Excellence inspired other What Works Centres in domains outside of health – including policing and crime reduction. But how was this model adapted and adopted in policing? The College of Policing, which was created as the Professional Body for Policing, and a precursor body, the National Policing Improvement Agency, have for many years promoted a ‘professionalisation agenda’ in policing through various methods, including embedding evidence-based practice into police standards and policies (Hunter et al, 2017). As part of this evidence agenda, the College established a What Works Centre for Crime Reduction in 2013. This chapter, by the centre’s director, Rachel Tuffin, tells the story of the centre and how it approaches evidence generation inside an arm’s-length body and the challenges unique to policing.
ChemInform Abstract: Condensation of Long‐Chain α‐Phosphono Carboxylates with Aldehydes. (1986)

Abstract Die Wadsworth‐I‐Iorner‐Emmons‐Kondensation der Phosphonoester (I) mit den Aldehyden (II) führt mit hoher trans‐Selektivität zu den ungesättigten Estern (III).
CK2beta gene silencing increases cell susceptibility to influenza A virus infection resulting in accelerated virus entry and higher viral protein content (2008)

This study demonstrates the role of cellular CK2beta protein in the viral biology. Our results are the first to demonstrate a functional link between siRNA-mediated inhibition of the CK2beta protein and regulation of influenza A virus replication in infected cells. Overall, the data suggest that expression and activation of CK2beta inhibits influenza virus replication by regulating the virus entry process and viral protein synthesis.
Effect of high glucose on synthesis and gene expression of collagen and fibronectin in cultured vascular smooth muscle cells (1997)

Diabetes mellitus is an important risk factor of atherosclerosis. Although the mechanism for accelerated atherosclerotic disease in diabetes mellitus is not clear, extracellular matrix formation by vascular smooth muscle cells has been accepted to play important roles during development of atherosclerosis. High glucose condition has been reported to increase the synthesis of extracellular matrix such as collagen and fibronectin in cultured mesangial cells, implicating high glucose for the development of diabetic nephropathy. We studied here the effect of high glucose on the synthesis and gene expression of collagen and fibronectin in vascular smooth muscle cells. We found that vascular smooth muscle cells grown in high glucose (25 mM) medium for 1, 2, and 3 days synthesized more collagen and noncollagen protein, as compared to the cells grown in normal glucose (5.5 mM) medium for the same periods of time. We also found that cells grown in high glucose for 1, 2, and 3 days expressed higher level of type 1 procollagen mRNA than that of the cells grown in normal glucose. There was, however, no difference in the amount of newly synthesized fibronectin between cells grown in normal and high glucose condition. These results suggest hyperglycemic condition in diabetes may accelerate the atherosclerotic process by stimu-lating vascular smooth muscle cells to produce more collagen.
Design of a MZI Micro-Opto-Mechanical Pressure Sensor for a SiN photonics platform (2016)

This paper presents the design of Micro-Opto-Mechanical Pressure Sensors (MOMPS), which can exhibit much improved sensitivity and noise performance compared to their piezoelectric and capacitive counterparts. As the output intensity variation depends on multiple design parameters, such as the radius of the membrane, the position of the waveguide, the wavelength and the phase variation due to the opto-mechanical coupling, we first derive an analytical model which allows to predict the response of the total system. We then use a Finite Element opto-mechanical model to evaluate the variation of the effective refractive index due to the modification of the optical material properties created by mechanical stress as well as to the waveguide shape deformation. Finally, the sensitivity of the device for a single loop MOMPS and for spiral loops configuration is analyzed.
ChemInform Abstract: PHOTOSTIMULATED NUCLEOPHILIC AROMATIC SUBSTITUTION FOR HALIDES WITH CARBON NUCLEOPHILES. PREPARATIVE AND MECHANISTIC ASPECTS (1981)

Abstract Die aus den Carbonylverbindungen (I), (IV), (VI) bzw. (VIII) mit KO‐tBu, NaNH 2 oder LiNH 2 in flüssigem NH 3 erzeugten Anionen gehen mit Brom‐ oder Iodbenzol eine intermolekulare Photo‐ SRNl‐Reaktion ein unter Bildung der Phenyl‐substituierten Ketone (II), (V), (VII) bzw. (IX); neben (II) entstehen auch die Ketone (III).
Root Causes of the Limited Electroluminescence Stability of Organic Light-Emitting Devices Made by Solution-Coating (2018)

Although organic electroluminescent materials have long promised the prospect of making organic light emitting devices (OLEDs) via low-cost solution-coating techniques, the electroluminescence stability of devices made by such techniques continues to be rather limited making them unsuitable for commercialization. The root causes of the lower stability of OLEDs made by solution-coating versus the more conventional vacuum-deposition remain unknown. In this work, we investigate and compare between solution-coated and vacuum-deposited materials under prolonged excitation, using the archetypical host material 4,4'-bis( N-carbazolyl)-1,1'-biphenyl as a model OLED material. Results show that solution-coated films are more susceptible to degradation by excitons in comparison to their vacuum-deposited counterparts, resulting in a faster decrease in their luminescent quantum yield. The degradation rate also depends on the choice of solvent that was used in the solution-coating process. Results also show that the decrease in quantum yield is caused by exciton-induced chemical decomposition in the material as well as some possible molecular reorganization or aggregation, both of which are induced by excitons and proceed more quickly in case of solution-coated films. The faster degradation in the solution-coated films appears to originate primarily from their different morphological makeup and not due to chemical impurities. The findings uncover what appears to be one of the fundamental root causes of the lower stability of solution-coated OLEDs in general.
Purification of ACAT Protein (2010)

Acyl‐coenyzme A:cholesterol acyltransferase (ACAT‐1) is an integral membrane protein located in the endoplasmic reticulum. It catalyzes the formation of cholestryl esters from cholesterol and long‐chain fatty acyl coenzyme A. Recently, we employed human embryonic kidney 293 (HEK293) cells to stably express the recombinant human ACAT‐1 protein bearing a six‐hisitidine tag at the N‐terminus and a Flag‐tag at the C‐terminus. The incorporation of the six–histidine and flag‐tag into the ACAT‐1 sequence allows the ACAT‐1 fusion protein to be purified using two affinity columns. This enzyme was purified by solubilizing the cell membrane with 1M of potassium chloride and 3‐[(3‐cholidopropyl)dimethylammonio]‐1‐propansulfanate (CHAPS). The lysate was then loaded onto an immobilize nickel column followed by a monoclonal Flag antibody column. The flag column allowed us to elute the fusion protein by the flag peptide. More importantly, the elution of the fusion protein using the Flag peptide is one of the most critical steps in the purification because it eliminates the use of low pH (pH 3 to pH4) elution conditions that were used in earlier purifications using ACAT monoclonal antibodies. This new purification scheme allows us to recover a larger quantity of active ACAT‐1 protein for further study of the structure and function of the human ACAT‐1 protein. Supported by NIH T34GM008411
Natural Form of Noncytolytic Flexible Human Fc as a Long-Acting Carrier of Agonistic Ligand, Erythropoietin (2011)

Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained "Y-shaped" structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUC(last)). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach.