gebhart/patrepeval huggingface dataset:
Adipose triglyceride lipase is regulated by CAMKK2-AMPK signaling and drives advanced prostate cancer (2022)

Summary Lipid metabolism plays a central role in prostate cancer. To date, the major focus on prostate cancer lipid metabolism has centered on de novo lipogenesis and lipid uptake with little consideration for how cancer cells access these lipids once they are created or taken up and stored. Patient-derived phosphoproteomics identified adipose triglyceride lipase (ATGL), a previously suspected tumor suppressor, as a CAMKK2-AMPK signaling target that, conversely, promotes castration-resistant prostate cancer (CRPC) progression. Phosphorylation of ATGL increased its lipase activity, cancer cell proliferation, migration, and invasion. Shotgun lipidomics and mass spectrometry imaging demonstrated ATGL’s profound regulation of lipid metabolism in vitro and in vivo , remodeling membrane composition. Inhibition of ATGL induced metabolic plasticity, causing a glycolytic shift that could be exploited therapeutically by co-targeting both metabolic pathways. Together, these data nominate ATGL and intracellular lipolysis as potential therapeutic targets for the treatment of CRPC and provide insights for future combination therapies.
Schwann Cells Are Key Regulators of Corneal Epithelial Renewal (2023)

Limbal SCs are required for innervation-dependent corneal epithelial renewal.
Fluorescent cellular indicators are extruded by the multidrug resistance protein. (1993)

In this report we show that NIH-3T3 mouse fibroblasts stably expressing the human multidrug transporter (MDR1 or P-glycoprotein), in contrast to the control NIH-3T3 cells, actively extrude the hydrophobic acetoxymethyl ester (AM) derivatives used for cellular loading of various fluorescent calcium and pH indicators. This dye extrusion is blocked by competing substrates and inhibitors of the multidrug transporters, e.g. by verapamil, vincristine, sodium orthovanadate, oligomycin, and a monoclonal anti-MDR1 antibody. The hydrophilic free acid forms of the indicators are not exported by MDR1. We also demonstrate that in isolated cell membranes the MDR1-ATPase, similar to that by known substrates of the transporter, is stimulated by the AM derivatives of fluorescent dyes whereas the free acid forms of the dyes are without effect. Since (i) the AM derivatives of the fluorescent indicators rapidly permeate the cell membrane and are readily cleaved by high activity and large capacity cytoplasmic esterases and (ii) the free acid forms are not substrates for export by MDR1, the observations above suggest that dye extrusion by MDR1 may occur without a cytoplasmic appearance of the AM compounds. These data also call attention to the possible interaction of widely used hydrophobic fluorescent indicators with MDR1 and offer an efficient detection of MDR1-expressing tumor cells as well as a screening method for examining drug interactions with the multidrug transporter.
<title>Adaptive wavefront control using a nonlinear Zernike filter</title> (2000)

A conventional Zernike filter measures wavefront phase by superimposing the aberrated input beam with a phase-shifted version of its zero-order spectral component. The Fourier- domain phase-shifting is performed by a fixed phase-shifting dot on a glass slide in the focal plane of a Fourier- transforming lens. Using an optically-controlled phase spatial light modulator (SLM) instead of the fixed phase-shifting dot, we have simulated and experimentally demonstrated a nonlinear Zernike filter robust to wavefront tilt misalignments. In the experiments, a liquid-crystal light valve (LCLV) was used as the phase SLM. The terminology 'nonlinear' Zernike filter refers to the nonlinear filtering that takes place in the Fourier domain due to the phase change for field spectral components being proportional to the spectral component intensities. Because the Zernike filer output intensity is directly related to input wavefront phase, a parallel, distributed feedback system can replace the wavefront reconstruction calculations normally required in adaptive- optic phase correction systems. Applications include high- resolution phase distortion suppression for atmospheric turbulence, optical phase microscopy, and compensation of aberrations in optical system components. A factor of eight improvement in Strehl ratio was obtained experimentally, and simulation results suggest that even better performance could be obtained by replacing the LCLV with a more sophisticated optically-controlled phase SLM.
Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status (2019)

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (>20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive tumors. By contrast, in HPV-negative tumors, NSD1 and COL1A11 were found to be more frequently mutated in heavy smokers, while CASP8 was more frequently altered in never smokers. HPV-negative patients with NSD1 mutations experienced significantly improved overall survival compared with NSD1 WT patients. This improved prognosis was validated in an independent cohort of 77 oral cavity cancer patients and a meta-analysis that included 2 additional data sets (688 total patients, hazard ratio for death 0.44, 95% CI, 0.30-0.65). NSD1 mutations are more common in HPV-negative heavy smokers, define a cohort with favorable prognosis, and may represent a clinically useful biomarker to guide treatment deintensification for HPV-negative patients.
Bile Acid Conjugation on Solid Nanoparticles Enhances ASBT‐Mediated Endocytosis and Chylomicron Pathway but Weakens the Transcytosis by Inducing Transport Flow in a Cellular Negative Feedback Loop (2022)

Bile acid-modified nanoparticles provide a convenient strategy to improve oral bioavailability of poorly permeable drugs by exploiting specific interactions with bile acid transporters. However, the underlying mechanisms are unknown, especially considering the different absorption sites of free bile acids (ileum) and digested fat molecules from bile acid-emulsified fat droplets (duodenum). Here, glycocholic acid (GCA)-conjugated polystyrene nanoparticles (GCPNs) are synthesized and their transport in Caco-2 cell models is studied. GCA conjugation enhances the uptake by interactions with apical sodium-dependent bile acid transporter (ASBT). A new pathway correlated with both ASBT and chylomicron pathways is identified. Meanwhile, the higher uptake of GCPNs does not lead to higher transcytosis to the same degree compared with unmodified nanoparticles (CPNs). The pharmacological and genomics study confirm that GCA conjugation changes the endocytosis mechanisms and downregulates the cellular response to the transport at gene levels, which works as a negative feedback loop and explains the higher cellular retention of GCPNs. These findings offer a solid foundation in the bile acid-based nanomedicine design, with utilizing advantages of the ASBT-mediated uptake, as well as inspiration to take comprehensive consideration of the cellular response with more developed technologies.
The Effect of Rate of Distraction Osteogenesis on Structure and Function of Anterior Digastric Muscle Fibers (2005)

The authors hypothesized that distraction at a rate of 3 mm/day, compared with mandibular distraction at a rate of 1 mm/day, would produce a maladaptive response in adjacent muscles of mastication. The authors further hypothesized that the maladaptive response would manifest at the single fiber level by means of increased sarcomeric heterogeneity, decreased maximum force output, and increased susceptibility to stretch-induced injury. In an ovine model, distraction osteogenesis of the right hemimandible was performed at either 1 mm/day for 21 days (n = 2) or 3 mm/day for 7 days (n = 2) to achieve a total distraction distance of 21 mm. The left hemimandibles served as controls. After a consolidation period of 2 days, the anterior digastric muscles were harvested; in six randomly selected single fibers from each muscle, maximum calcium-activated force (Po) was measured at optimal sarcomere length. The amount of damage to the sarcomeres in each fiber was assessed microscopically. To test susceptibility to contraction-induced injury, each fiber was given an activated stretch of 20 percent. Compared with control fibers and fibers distracted at 1 mm/day, maximum tetanic force (Po) was significantly lower in fibers distracted at 3 mm/day. Compared with control fibers, specific Po (Po/cross-sectional area) was lower in fibers distracted at 3 mm/day. The number of sarcomeres appearing damaged in fibers distracted at 3 mm/day was significantly higher than in control fibers or in fibers distracted at 1 mm/day. A greater deficit in Po was observed after a single activated stretch in fibers distracted at 3 mm/day than in control fibers or in fibers distracted at 1 mm/day. The authors conclude that distraction of the anterior digastric muscle in sheep at 3 mm/day produces a maladaptive response in the muscle fibers but a rate of 1 mm/day is tolerated by the muscle fibers. These data are consistent with the hypothesis that distraction of skeletal muscle at high rates results in increased heterogeneity of sarcomere lengths and that this increase in heterogeneity is the most likely potential mechanism resulting in whole muscle force deficits and in increased susceptibility to stretch-induced injury in distracted muscles.
N-Benzylbenzamides: A Novel Merged Scaffold for Orally Available Dual Soluble Epoxide Hydrolase/Peroxisome Proliferator-Activated Receptor γ Modulators (2015)

Metabolic syndrome (MetS) is a multifactorial disease cluster that consists of dyslipidemia, cardiovascular disease, type 2 diabetes mellitus, and obesity. MetS patients are strongly exposed to polypharmacy; however, the number of pharmacological compounds required for MetS treatment can be reduced by the application of multitarget compounds. This study describes the design of dual-target ligands that target soluble epoxide hydrolase (sEH) and the peroxisome proliferator-activated receptor type γ (PPARγ). Simultaneous modulation of sEH and PPARγ can improve diabetic conditions and hypertension at once. N-Benzylbenzamide derivatives were determined to fit a merged sEH/PPARγ pharmacophore, and structure-activity relationship studies were performed on both targets, resulting in a submicromolar (sEH IC50 = 0.3 μM/PPARγ EC50 = 0.3 μM) modulator 14c. In vitro and in vivo evaluations revealed good ADME properties qualifying 14c as a pharmacological tool compound for long-term animal models of MetS.
Multifunctional Core–Shell Particle Electrodes for Application in Fluidized Bed Reactors (2022)

Fluidized particle electrodes are well-suited for a wide range of electrochemical reactions due to their large specific surface area and their tolerance toward suspended solid contaminants and gas bubbles. For effective electrode performance, particles require (i) high conductivity, (ii) efficient interparticle contact, and (iii) chemical inertness toward a broad range of reagents and solvents. In particular, sufficient interparticle contact remains a critical challenge. Magnetic stabilization of the fluidized bed provides a potential solution but requires the use of magnetic electrode materials. However, the synthesis of electrode particles with high magnetic susceptibility remains an ongoing challenge. Herein, electrojetting of magnetite/poly(methyl methacrylate) suspensions into a graphite powder bed is demonstrated to be a facile and effective route toward magnetically stabilizable electrode particles. Energy-dispersive X-ray spectroscopy and Raman spectroscopy confirmed the composition and core–shell structure of the particles. Characterization of their magnetic and electric properties showed an exceptionally high saturation magnetization of 11.1 A·m2/kg and a conductivity of 28 S/m. Further, scanning electron microscopy revealed an average diameter of approximately 200 μm, large surface areas, and spherical shapes, three prerequisites for homogeneous fluidization. Compared to previously reported fluidized bed electrodes, electrodes comprised of these novel core/shell particles showed 2-fold increases in current densities and conversion rates. These results underline the potential of the electrohydrodynamic jetting process for the design and synthesis of novel, tailor-made core–shell particles as key components of fluidized bed electrodes for electrochemical reactions.
Green preparation of reduced graphene oxide for sensing and energy storage applications (2014)

Preparation of graphene from chemical reduction of graphene oxide (GO) is recognized as one of the most promising methods for large-scale and low-cost production of graphene-based materials. This study reports a new, green, and efficient reducing agent (caffeic acid/CA) for GO reduction. The CA-reduced GO (CA-rGO) shows a high C/O ratio (7.15) that is among the best rGOs prepared with green reducing reagents. Electronic gas sensors and supercapacitors have been fabricated with the CA-rGO and show good performance, which demonstrates the potential of CA-rGO for sensing and energy storage applications.
Compensated LTCC broadside coupler design with branch lines (2008)

Abstract A compensation technique to generate enhanced return loss and directivity is proposed by using additional branch lines for a broadside coupler. The branch lines at all ports are added to reduce the port impedance, resulting in improvement of impedance matching for the tight coupled broadside coupler. The measured results of the proposed low‐temperature cofired ceramic (LTCC) coupler show more than 4 dB enhancements of return loss and isolation, compared with those of the conventional one. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 3134–3136, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23930
On directly mapping relational databases to RDF and OWL (2012)

Mapping relational databases to RDF is a fundamental problem for the development of the Semantic Web. We present a solution, inspired by draft methods defined by the W3C where relational databases are directly mapped to RDF and OWL. Given a relational database schema and its integrity constraints, this direct mapping produces an OWL ontology, which, provides the basis for generating RDF instances. The semantics of this mapping is defined using Datalog. Two fundamental properties are information preservation and query preservation. We prove that our mapping satisfies both conditions, even for relational databases that contain null values. We also consider two desirable properties: monotonicity and semantics preservation. We prove that our mapping is monotone and also prove that no monotone mapping, including ours, is semantic preserving. We realize that monotonicity is an obstacle for semantic preservation and thus present a non-monotone direct mapping that is semantics preserving.
Measurement of the inclusive $$ \mathrm{t}\overline{\mathrm{t}} $$ production cross section in proton-proton collisions at $$ \sqrt{s} $$ = 5.02 TeV (2022)

A bstract The top quark pair production cross section is measured in proton-proton collisions at a center-of-mass energy of 5.02 TeV. The data were collected in a special LHC low-energy and low-intensity run in 2017, and correspond to an integrated luminosity of 302 pb − 1 . The measurement is performed using events with one electron and one muon of opposite charge, and at least two jets. The measured cross section is 60 . 7 ± 5 . 0 (stat) ± 2 . 8 (syst) ± 1 . 1 (lumi) pb. A combination with the result in the single lepton + jets channel, based on data collected in 2015 at the same center-of-mass energy and corresponding to an integrated luminosity of 27.4 pb − 1 , is then performed. The resulting measured value is 63 . 0 ± 4 . 1 (stat) ± 3 . 0 (syst+lumi) pb, in agreement with the standard model prediction of $$ {66.8}_{-3.1}^{+2.9} $$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msubsup> <mml:mn>66.8</mml:mn> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>3.1</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>2.9</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> pb.
Functional comparison of pacifiers using finite element analysis (2022)

Pacifiers interact with the palate differently based on their fit (i.e., design and size) regardless of whether they are labeled conventional or orthodontic. Finite element analysis is an effective tool for evaluating how a pacifier's design affects functional mechanics and for providing guidance on biometric sizing.
Growth Hormone (GH) Binding and Effects of GH Analogs in Transgenic Mice (1994)

Overexpression of human (h) or bovine (b) growth hormone (GH) in transgenic mice is associated with marked (2- to 12-fold) and significant increase in hepatic binding of GH and prolactin (PRL). This is due to an increase in the number of GH and PRL receptors (GHR, PRLR) per mg of microsomal protein without changes in binding affinity. Comparison of results obtained in transgenic animals expressing bGH with a mouse metallothionein (MT) or a rat phosphoenolpyruvate carboxykinase (PEPCK) promoter suggests that effects of bGH on hepatic GHR and PRLR do not require GH overexpression during fetal life and, within the dose range tested, the effects on PRLR are not dose dependent. The increase in hepatic GHR was accompanied by significant increases in plasma GH-binding protein (GHBP) and in mean residence time of injected GH. Thus, life-long elevation of peripheral GH levels alters the availability of both free GH and GHR. Site-directed in vitro mutagenesis was used to produce hGH and bGH analogs mutated within one of the sites involved in binding to GHR and PRLR. Mutating hGH to produce amino acid identity with bGH at Position 11, 18 (within Helix 1), 57, or 60 (within the loop between Helix 1 and 2) did not affect binding to GHR in vitro, or somatotropic activity in transgenic mice in vivo but reduced lactogenic activity in Nb2 cells by 22%-45%. Mutations of bGH designed to produce amino acid identity with hGH at one to four of the corresponding positions in the bGH molecule did not interfere with binding to GHR or somatotropic activity in vivo, and failed to produce significant binding to PRLR but resulted in alterations in the effects on the hypothalamic and anterior pituitary function in transgenic mice. Apparently region(s) outside the domains examined are essential for lactogenic activity of hGH, and different portions of the GH molecule are responsible for its diverse actions in vivo.
Dental Procedures as Risk Factors for Prosthetic Hip or Knee Infection: A Hospital-Based Prospective (2010)

not administered antibiotic prophylaxis (adjusted odds ratio [OR], 0.8; 95% confidence interval [CI], 0.4‐1.6), compared with the risk for patients not undergoing a dental procedure (adjusted OR, 0.6; 95% CI, 0.4‐1.1) respectively. Antibiotic prophylaxis in high-risk or low-risk dental procedures did not decrease the risk of subsequent total hip or knee infection (adjusted OR, 0.9 [95% CI, 0.5‐1.6] and 1.2 [95% CI, 0.7‐2.2], respectively). Conclusions. Dental procedures were not risk factors for subsequent total hip or knee infection. The use of antibiotic prophylaxis prior to dental procedures did not decrease the risk of subsequent total hip or knee infection.
Mullite+CAS Bond Coat for Environmental Barrier Coatings for Si-Based Ceramics (2002)

Current environmental barrier coatings (EBCs) for silicon-based ceramics consist of a bond coat and a top coat. Mullite bond coat modified by adding low CTE glass ceramics, such as BSAS (xBaO.1xSrO.Al2O3.2SiO2) or CAS (CaO.Al2O3.2SiO2), was developed in the NASA Enabling Propulsion Materials (EPM) Program. EBCs based on mullite+CAS bond coat were characterized using high steam thermal cycling test and high steam isothermal thermogravemitry (TGA) at 1225 C - 13,000 C. The Mullite+CAS bond coat showed far superior durability compared to mullite bond coat, due to enhanced crack resistance. A BSAS top coat provided further improved durability compared to EBCs with a yttria-stabilized zirconia (YSZ) top coat. Still further improvement in the durability was achieved by adding a silicon bond coat between the mullite and the substrate. However, the silicon/mullite+CAS/BSAS EBC showed inferior long-term durability compared to the current state-of-the art EBC (silicon/mullite+BSAS/BSAS EBC), presumably due to the higher CAS-silica chemical reactivity.
Accelerated Testing of SiC Power Devices under High-Field Operating Conditions (2020)

Power metal-oxide-semiconductor field-effect transistors (MOSFETs) experience conditions of high field during normal operation. During switching conditions, unexpected transient events may occur which force devices into avalanche or short circuit conditions. Moreover, silicon carbide devices typically experience higher fields in the gate oxide and drift regions than comparable Si devices due to channel and drift property differences. A summary of SiC MOSFET reliability and ruggedness test results are reported here. Reliability tests under high field conditions: positive-bias and negative-bias temperature instability (PBTI, NBTI) to examine threshold stability; time-dependent dielectric breakdown (TDDB) for gate oxide lifetime extrapolation; high-temperature reverse bias (HTRB); and HTRB testing under high neutron flux to determine terrestrial neutron single-event burnout (SEB) rates. High-power ruggedness evaluation is presented for SiC MOSFETs under forced avalanche conditions (unclamped inductive switching (UIS)) and under short-circuit operation to bound device safe operating areas. Overall results demonstrate the intrinsic reliability of SiC MOSFETs.
Solid-Phase Strategies for the Assembly of Template-Based Protein Mimetics1 (1999)

The template concept for overcoming the protein folding problem in protein de novo design has recently been extended for mimicking essential structural and functional features of proteins. Due to progress in synthetic methodologies, template-assembled constructs now become accessible for efficient solid-phase strategies, as exemplified for three prototype protein mimetics. As a key step, regioselectively addressable functional template molecules are prepared by convergent methods and immobilized on solid support (2b in Figure 1). Up to four orthogonal amino protecting groups, i.e., Fmoc, Alloc, Dde, and pNZ, allow for the step-by-step synthesis of protein surface mimetic 3, template-assembled synthetic protein (TASP) 4, and the convergent synthesis of receptor mimetic 5 in good overall yield. The elaborated protocols extend today's potential of solid-phase peptide synthesis for the construction of molecules of high structural complexity and open the way to template-based protein mimetics by combinatorial techniques.
A Synthesis of Trisubstituted Alkenes by a Ru‐Catalyzed Addition. (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
ChemInform Abstract: 3‐(1,2,5,6‐Tetrahydropyrid‐4‐yl)pyrrolo(3,2‐b)pyrid‐5‐one: A Potent and Selective Serotonin (5‐HT1B) Agonist and Rotationally Restricted Phenolic Analogue of 5‐Methoxy‐3‐(1,2,5,6‐tetrahydropyrid‐4‐yl)indole. (1991)

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.