gebhart/patrepeval huggingface dataset:
Voltage-gated calcium channels in GtoPdb v.2021.2 (2021)

Calcium (Ca2+) channels are voltage-gated ion channels present in the membrane of most excitable cells. The nomenclature for Ca2+channels was proposed by [127] and approved by the NC-IUPHAR Subcommittee on Ca2+ channels [70]. Most Ca2+ channels form hetero-oligomeric complexes. The α1 subunit is pore-forming and provides the binding site(s) for practically all agonists and antagonists. The 10 cloned α1-subunits can be grouped into three families: (1) the high-voltage activated dihydropyridine-sensitive (L-type, CaV1.x) channels; (2) the high- to moderate-voltage activated dihydropyridine-insensitive (CaV2.x) channels and (3) the low-voltage-activated (T-type, CaV3.x) channels. Each α1 subunit has four homologous repeats (I-IV), each repeat having six transmembrane domains and a pore-forming region between transmembrane domains S5 and S6. Voltage-dependent gating is driven by the membrane spanning S4 segment, which contains highly conserved positive charges that respond to changes in membrane potential. All of the α1-subunit genes give rise to alternatively spliced products. At least for high-voltage activated channels, it is likely that native channels comprise co-assemblies of α1, β and α2-δ subunits. The γ subunits have not been proven to associate with channels other than the α1s skeletal muscle Cav1.1 channel. The α2-δ1 and α2-δ2 subunits bind gabapentin and pregabalin.
The Discovery of Kisqali <sup>®</sup> (Ribociclib): A <scp>CDK</scp> 4/6 Inhibitor for the Treatment of <scp>HR</scp> +/ <scp>HER</scp> 2− Advanced Breast Cancer (2021)

Kisqali (ribociclib) was first approved by the US FDA on 13 March 2017 for the treatment of hormone receptor positive (HR+)/human epidermal growth factor 2 negative (HER2−) advanced breast cancer. The CDK4/6 pathway plays a central role in controlling cell cycle progression and is dysfunctional in many human cancers. The chapter outlines key genetic data that pointed to CDK4/6 as an important oncology target and describes a multi-parallel approach to identifying chemical starting points including biochemical screening and fragment-based discovery methods. Optimization with structure-guided insight led to ribociclib, which is very highly selective for CDK4/6 against other kinases. We also describe drug combination strategy, early clinical data, and results from pivotal registration trials. CDK4/6 inhibitors in combination with endocrine treatment have emerged as the standard of care for women with HR+ metastatic breast cancer. Ribociclib achieved statistically significant overall survival improvement in two phase III trials with two distinct patient populations in HR+/HER2– advanced breast cancer.
Arylboronic Acid-Catalyzed Direct Condensation of Carboxylic Acids with Ureas (2004)

The first example of the catalytic direct condensation of carboxylic acids with ureas to give N-acylureas, N,N′-diacyl-2-imidazolidones, and poly(N,N′-diacyl-2-imidazolidone)s is described. Arylboronic acids bearing electron-withdrawing substituents are highly effective as catalysts for this condensation. Furthermore, a new and efficient one-pot procedure for the conversion of carboxylic acids and urea to nitriles via N-acylurea intermediates was accomplished by using arylboronic acid and rhenium(VII) oxo complexes as hybrid catalysts.
Characterizing organic particle impacts on inert metal surfaces: Foundations for capturing organic molecules during hypervelocity transits of Enceladus plumes (2020)

The presence and accessibility of a sub-ice-surface saline ocean at Enceladus, together with geothermal activity and a rocky core, make it a compelling location to conduct further, in-depth, astrobiological investigations to probe for organic molecules indicative of extraterrestrial life. Cryovolcanic plumes in the south polar region of Enceladus enable the use of remote in situ sampling and analysis techniques. However, efficient plume sampling and the transportation of captured organic materials to an organic analyzer present unique challenges for an Enceladus mission. A systematic study, accelerating organic ice-particle simulants into soft inert metal targets at velocities ranging 0.5-3.0 km s<sup>-1</sup>, was carried out using a light gas gun to explore the efficacy of a plume capture instrument. Capture efficiency varied for different metal targets as a function of impact velocity and particle size. Importantly, organic chemical compounds remained chemically intact in particles captured at speeds up to ~2 km s<sup>-1</sup>. Calibration plots relating the velocity, crater, and particle diameter were established to facilitate future ice-particle impact experiments where the size of individual ice particles is unknown.
[Long-term result after UPPP for OSAS by evaluation of nocturnal oxygenation]. (2000)

The nocturnal oxygenation of 45 patients with OSAS who had UPPP at our hospital were evaluated by pulse oximetry before and after surgery and at the time more than one year after UPPP. "Successful case" is defined as the case that showed more than 50% reduced oxygen desaturation index(ODI) after UPPP. Twenty seven cases including 15 severe cases(ODI > or = 40) have showed continuously successful ODI for more than one year. We could not get good result in 8 cases, which kept high ODI. Four of them are now using dental appliance. We have recognized the recurrence of sleep apnea in 10 cases that once got successful results just after UPPP. Our report strongly suggests the importance of long-term follow-up after surgery.
Knowledge-Based User Interface Design (1985)

A key problem in user interface design is delivering the design model on which a program is based in terms of the running software that users actually have to deal with. This article presents a methodology for helping programmers to explicitly state a design model and link it to the actual functions and data of the programs. Terms in the model are defined according to their relationship to a set of prebuilt abstract categories. The model so defined forms an explicit conceptual framework that enforces the consistency of the programmers' design, and provides the basis of user understanding of the program. Because the model is linked to actual program software, the connection of user understanding to the running code - the real user interface - is thus defined in terms of the explicit model. The methodology is presented in terms of techniques implemented in the Consul system, a knowledge-based environment for the design of integrated office automation software.
Role of Solubility Parameters in Understanding the Steric Stabilization of Exfoliated Two-Dimensional Nanosheets by Adsorbed Polymers (2012)

In this paper we show that graphene, hexagonal boron nitride, and molybdenum disulfide can all be exfoliated and stabilized against aggregation in solvents that cannot alone exfoliate these materials, provided that dissolved polymers are present. In each case we demonstrate this steric stabilization for a range of polymers. To understand this, we have derived an expression for the free energy of adsorption of polymer chains onto the surface of nanosheets in a solvent environment. Critically, we express all energetic interactions in terms of the Hildebrand solubility parameters of solvent, polymer, and nanosheet. This allows us to predict the dispersed nanosheet concentration to display a Gaussian peak when plotted against polymer Hildebrand parameter. This is borne out by experimental data. The model correctly (within ∼2 MPa1/2) predicts the peak to occur when polymer and solvent solubility parameters match. In addition, the model describes both the peak width and the dependence of nanosheet concentration on polymer molecular weight. Because of the wide availability of solubility parameters for solvents, polymers, and many nanomaterials, this work is of practical importance for the production of polymer–nanosheet composite dispersions. However, more importantly it extends our understanding of the conditions required for steric stabilization and provides simple rules which define the required combination of solvent and polymer to best stabilize a given type of nanomaterial or colloid.
ChemInform Abstract: Total Synthesis of Natural (+)‐Acetoxycrenulide. (1995)

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.
Prominent Bone Loss Mediated by RANKL and IL-17 Produced by CD4+ T Cells in TallyHo/JngJ Mice (2011)

Increasing evidence that decreased bone density and increased rates of bone fracture are associated with abnormal metabolic states such as hyperglycemia and insulin resistance indicates that diabetes is a risk factor for osteoporosis. In this study, we observed that TallyHo/JngJ (TH) mice, a polygenic model of type II diabetes, spontaneously developed bone deformities with osteoporotic features. Female and male TH mice significantly gained more body weight than control C57BL/6 mice upon aging. Interestingly, bone density was considerably decreased in male TH mice, which displayed hyperglycemia. The osteoblast-specific bone forming markers osteocalcin and osteoprotegerin were decreased in TH mice, whereas osteoclast-driven bone resorption markers such as IL-6 and RANKL were significantly elevated in the bone marrow and blood of TH mice. In addition, RANKL expression was prominently increased in CD4+ T cells of TH mice upon T cell receptor stimulation, which was in accordance with enhanced IL-17 production. IL-17 production in CD4+ T cells was directly promoted by treatment with leptin while IFN-γ production was not. Moreover, blockade of IFN-γ further increased RANKL expression and IL-17 production in TH-CD4+ T cells. In addition, the osteoporotic phenotype of TH mice was improved by treatment with alendronate. These results strongly indicate that increased leptin in TH mice may act in conjunction with IL-6 to preferentially stimulate IL-17 production in CD4+ T cells and induce RANKL-mediated osteoclastogenesis. Accordingly, we propose that TH mice could constitute a beneficial model for osteoporosis.
Steady-state characteristics of lateral <i>p-n</i> junction vertical-cavity surface-emitting lasers (2001)

We developed an analytical device model for lateral p-n junction vertical-cavity surface-emitting lasers (LJVCSELs) with a quantum well active region. The model takes into account the features of the carrier injection, transport, and recombination in LJVCSELs as well as the features of the photon propagation in the cavity. This model is used for the calculation and analysis of the LJVCSEL steady-state characteristics. It is shown that the localization of the injected electrons primarily near the p-n junction and the reabsorption of lateral propagating photons significantly effects the LJVCSELs performance, in particular, the LJVCSEL threshold current and power-current characteristics. The reincarnation of electrons and holes due to the reabsorption of lateral propagating photons can substantially decrease the threshold current.
Role of Substrates and Products of PI 3-kinase in Regulating Activation of Rac-Related Guanosine Triphosphatases by Vav (1998)

Mitogen stimulation of cytoskeletal changes and c-jun amino-terminal kinases is mediated by Rac small guanine nucleotide-binding proteins. Vav, a guanosine diphosphate (GDP)-guanosine triphosphate (GTP) exchange factor for Rac that stimulates the exchange of bound GDP for GTP, bound to and was directly controlled by substrates and products of phosphoinositide (PI) 3-kinase. The PI 3-kinase substrate phosphatidylinositol-4,5-bisphosphate inhibited activation of Vav by the tyrosine kinase Lck, whereas the product phosphatidylinositol-3,4,5-trisphosphate enhanced phosphorylation and activation of Vav by Lck. Control of Vav in response to mitogens by the products of PI 3-kinase suggests a mechanism for Ras-dependent activation of Rac.
Advances in translational bioinformatics facilitate revealing the landscape of complex disease mechanisms (2014)

Advances of high-throughput technologies have rapidly produced more and more data from DNAs and RNAs to proteins, especially large volumes of genome-scale data. However, connection of the genomic information to cellular functions and biological behaviours relies on the development of effective approaches at higher systems level. In particular, advances in RNA-Seq technology has helped the studies of transcriptome, RNA expressed from the genome, while systems biology on the other hand provides more comprehensive pictures, from which genes and proteins actively interact to lead to cellular behaviours and physiological phenotypes. As biological interactions mediate many biological processes that are essential for cellular function or disease development, it is important to systematically identify genomic information including genetic mutations from GWAS (genome-wide association study), differentially expressed genes, bidirectional promoters, intrinsic disordered proteins (IDP) and protein interactions to gain deep insights into the underlying mechanisms of gene regulations and networks. Furthermore, bidirectional promoters can co-regulate many biological pathways, where the roles of bidirectional promoters can be studied systematically for identifying co-regulating genes at interactive network level. Combining information from different but related studies can ultimately help revealing the landscape of molecular mechanisms underlying complex diseases such as cancer.
Deep Kinematic Models for Kinematically Feasible Vehicle Trajectory Predictions (2019)

Self-driving vehicles (SDVs) hold great potential for improving traffic safety and are poised to positively affect the quality of life of millions of people. To unlock this potential one of the critical aspects of the autonomous technology is understanding and predicting future movement of vehicles surrounding the SDV. This work presents a deep-learning-based method for kinematically feasible motion prediction of such traffic actors. Previous work did not explicitly encode vehicle kinematics and instead relied on the models to learn the constraints directly from the data, potentially resulting in kinematically infeasible, suboptimal trajectory predictions. To address this issue we propose a method that seamlessly combines ideas from the AI with physically grounded vehicle motion models. In this way we employ best of the both worlds, coupling powerful learning models with strong feasibility guarantees for their outputs. The proposed approach is general, being applicable to any type of learning method. Extensive experiments using deep convnets on real-world data strongly indicate its benefits, outperforming the existing state-of-the-art.
A high performance self-oscillating sub-harmonic mixer (SO-SHM) incorporating compact microstrip resonant cell (CMRC) for wireless sensor application (2004)

Hypersensitivity to topical hydrocortisone is becoming increasingly recognized. We present further evidence that this is mediated via a delayed-type hypersensitivity reaction. A hydrocortisone: albumin complex was able to induce a proliferative response in the peripheral blood mononuclear cells of patients allergic to hydrocortisone. Protein binding of hydrocortisone or a degradation product may be important in the development of corticosteroid allergy.
Brain acetylcholinesterase activity in FTDP-17 studied by PET (2006)

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant tauopathy. To date, 33 distinct mutations in the tau gene have been reported.1 The clinical features of the N279K tau mutation include parkinsonism, personality changes, and supranuclear gaze palsy.2 Occasionally, cognitive impairment resembling Alzheimer disease (AD) can occur in FTDP-17. In AD, acetylcholinesterase (AChE) activities are depleted in the cerebral cortex. Although impairment of the nigrostriatal dopaminergic pathway has been demonstrated in FTDP-17,3 functional imaging of the cholinergic system in FTDP-17 has not been reported. Using PET and 11C-labeled N -methylpiperidin-4-yl acetate ([11C]MP4A),4 we measured AChE activity in the brains of two patients with FTDP-17 carrying the N279K tau mutation.

### Patients and control subjects.

A 50-year-old man with congenital nystagmus began having neck and right arm rigidity and a shuffling gait at age 44. His symptoms improved with trihexyphenidyl and levodopa. During the next several years, however, he began to fall frequently and became forgetful and depressed. A half year before the PET study, he scored 17 of 30 points (cut-off …
Measurement of large serine integrase enzymatic characteristics in HEK293 cells reveals variability and influence on downstream reporter expression (2021)

Large serine integrases (LSIs) offer tremendous potential for rapid genetic engineering as well as building biological systems capable of responding to stimuli and integrating information. Currently, there is no unified metric for directly measuring the enzymatic characteristics of LSI function, which hinders evaluation of their suitability to specific applications. Here, we present an experimental protocol for recording DNA recombination in HEK293 cells in real-time through fluorophore expression and software which fits the kinetic data to a model tailored to LSI recombination dynamics. Our model captures the activity of LSIs as three parameters: expression level (K<sub>exp</sub> ), catalytic rate (k<sub>cat</sub> ), and substrate affinity (K<sub>d</sub> ). The expression level and catalytic rate for phiC31 and Bxb1 varied greatly, suggesting disparate routes to high recombination efficiencies. Moreover, the expression level and substrate affinity jointly impacted downstream reporter expression, potentially by obstructing transcriptional machinery. We validated these observations by swapping between promoters and mutating key recombinase residues and DNA recognition sites to individually modulate each parameter. Our model for identifying key LSI parameters in cellulo provides insight into selecting the optimal recombinase for various applications as well as for guiding the engineering of improved LSIs.
Multi-axis Force Sensing with Pre-stressed Resonant Composite Plates : An Alternative to Strain Gauge Force Sensors (2014)

International audience
Hepatotoxin-Induced Changes in the Adult Murine Liver Promote MYC-Induced Tumorigenesis (2008)

Our results suggest a model whereby oncogenes can remain latently activated, but exposure of the adult liver to hepatotoxins that promote hepatocyte proliferation can rapidly uncover their malignant potential.
Development of correction formula for field potential duration of human induced pluripotent stem cell-derived cardiomyocytes sheets (2017)

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used in many studies to assess proarrhythmic risks of chemical compounds. In those studies, field potential durations (FPD) of hiPSC-CMs have been corrected by clinically used Fridericia's and/or Bazett's formulae, however, the rationale for the use of these formulae has not been well established. In the present study, we developed a correction formula for experiments using hiPSC-CMs. First, we analyzed the effect of beating rate on FPD in the hiPSC-CMs sheets with electrical stimuli and a HCN channel inhibitor zatebradine. Next, we examined the relationship between the electrophysiological properties and the expression levels of ion channel genes in the cell sheets. Zatebradine slowed the beating rate and allowed to analyze FPD changes at various pacing cycle lengths. Rate-dependent change in the repolarization period was smaller in the cell sheets than that reported on the human hearts, which can be partly explained by lower gene expression level of hKCNJ2 and hKCNE1. Thus, non-linear equation for correcting FPD in the cell sheet; FPDc = FPD/RR<sup>0.22</sup> with RR given in second was obtained, which may make it feasible to assess net repolarization delay by various chemical compounds with a chronotropic action.
Improvement of respiratory compromise through abductor reinnervation and pacing in a patient with bilateral vocal fold impairment (2009)

Based on our preliminary data, PCA reinnervation and pacing offer promise for amelioration of respiratory compromise after paradoxical adduction in bilateral vocal fold impairment.
Anti-Obesity Effects of Chitosan and Psyllium Husk with L-Ascorbic acid in Guinea Pigs (2012)

The aim of this study was to investigate whether L-Ascorbic acid would facilitate the anti-obesity effects of chitosan and psyllium husk in vivo. The study was carried out with male Hartley guinea pigs for 5 weeks. The results show that chitosan itself did not influence body weight gain and food efficiency ratio (FER). However, the addition of L-Ascorbic acid to chitosan decreased these parameters; the body weight gain and FER in the chitosan-2 group (high-fat diet group with 5 % chitosan containing 0.5 % L-Ascorbic acid) was significantly (p < 0.05) lower than that in F-controls (high-fat diet group), and was similar to that in controls (normal diet group). L-Ascorbic acid enhanced significantly (p < 0.05) the increases of total fecal weight and fecal fat excretion by chitosan. The addition of L-Ascorbic acid to psyllium husk did not differ from psyllium husk alone in terms of changes in weight gain, plasma lipid levels, and fat pad weight. We found that the addition of L-Ascorbic acid to chitosan influenced the reduction in body weight gain and FER, and the increase in total fecal weight and fecal fat excretion in guinea pigs fed a high-fat diet.
A perspective on the use of light as a driving element for bio-hybrid actuation (2022)

Bio-hybrid actuators are devices based on muscle cells or tissues, designed to exploit the force generated by the biological element to execute an action or a movement. Typically, cells and tissue control are achieved electrically by using metal electrodes implanted in living elements. In this Perspective, we focus our attention on an alternative stimulation approach based on light. We highlight the potential of light stimulation in terms of performance and discuss the comparison with classical electrical stimulation. Finally, we discuss future challenges and possible applications of light-controlled actuators.
Adaptive Modulation Control for Multiple-Phase Voltage Regulators (2007)

This paper presents a new Adaptive Modulation Control (AMC) method which has proven to be very effective in achieving high bandwidth designs. AMC is a type of nonlinear control since it works only during large dynamic load transitions. Influence of AMC in both the time domain and frequency domain is analyzed. Simulation results and experimental data are included to show a very high bandwidth as well as excellent transient performance.