gebhart/patrepeval huggingface dataset:
Structural Alterations of the “Address” Moiety of NAN Leading to the Discovery of a Novel Opioid Receptor Modulator with Reduced hERG Toxicity (2022)

The search for selective opioid ligands with desired pharmacological potency and improved safety profile has always been an area of interest. Our previous effort yielded a potent opioid modulator, NAN, a 6α-<i>N</i>-7'-indolyl-substituted naltrexamine derivative, which exhibited promising pharmacological activities both in vitro and in vivo. However, significant human ether-a-go-go-related gene (hERG) liability limited its further development. Therefore, a systematic structural modification on NAN was conducted in order to alleviate hERG toxicity while preserving pharmacological properties, which led to the discovery of 2'-methylindolyl derivative compound <b>21</b>. Compared to NAN, compound <b>21</b> manifested overall improved pharmacological profiles. Follow-up hERG channel inhibition evaluation revealed a seven-fold decreased potency of compound <b>21</b> compared to NAN. Furthermore, several fundamental drug-like property evaluations suggested a reasonable ADME profile of <b>21</b>. Collectively, compound <b>21</b> appeared to be a promising opioid modulator for further development as a novel therapeutic agent toward opioid use disorder treatments.
Chromophoric self-assembled nonlinear optical multilayer materials. Synthesis, properties, and structural interconversions of assemblies with rodlike alkynyl chromophores (1993)

The communication describes an approach to the synthesis of thin-film second-order nonlinear optical (NLO) materials in which self-assembled chromophore-containing multilayer structures are built up on clean glass or quartz surfaces in the repeating reaction sequence p-Cl<sub>3</sub>Si(CH<sub>2</sub>)<sub>2</sub>C<sub>6</sub>H<sub>4</sub>CH<sub>2</sub>Cl (coupling layer), 4-[N,N-bis(3-hydroxypropyl)amino]phenylethynyl-4′-pyridine (chromophore layer), Cl<sub>3</sub>SiOSiCl<sub>2</sub>OSiCl<sub>3</sub> (capping layer). The multilayer structures have been characterized by optical and X-ray photoelectron spectroscopy, advancing contact angle measurements, and polarized second harmonic generation (SHG) properties. It is found that the initially formed coupling-chromophore monolayer exhibits a rather weak SHG response which increases substantially upon capping with the Si reagent. The proposed structural reorganization of the chromophore dipoles (β<sub>zzz</sub> direction) to an average orientation more coincident with the surface normal is supported by optical spectroscopy. The square root of the SH intensity scales linearly with the number of chromophore layers up to nine layers. For a single coupling-chromophore layer, [formula omitted] esu at ℏω = 1.17 eV.
A Constitutive Effector Region on the C-terminal Side of Switch I of the Ras Protein (1995)

The "switch I" region (Asp30-Asp38) of the Ras protein takes remarkably different conformations between the GDP- and GTP-bound forms and coincides with the so-called "effector region." As for a region on the C-terminal side of switch I, the V45E and G48C mutants of Ras failed to promote neurite outgrowth of PC12 cells (Fujita-Yoshigaki, J., Shirouzu, M., Koide, H., Nishimura, S., and Yokoyama, S. (1991) FEBS Lett. 294, 187-190). In the present study, we performed alanine-scanning mutagenesis within the region Lys42-Ile55 of Ras and found that the K42A, I46A, G48A, E49A, and L53A mutations significantly reduced the neurite-inducing activity. This is an effector region by definition, but its conformation is known to be unaffected by GDP-->GTP exchange. So, this region is referred to as a "constitutive" effector (Ec) region, distinguished from switch I, a "switch" effector (Es) region. The Ec region mutants exhibiting no neurite-inducing activity were found to be correlatably unable to activate mitogen-activated protein (MAP) kinase in PC12 cells. Therefore, the Ec region is essential for the MAP kinase activation in PC12 cells, whereas mutations in this region only negligibly affect the binding of Ras to Raf-1 (Shirouzu, M., Koide, H., Fujita-Yoshigaki, J., Oshio, H., Toyama, Y., Yamasaki, K., Fuhrman, S. A., Villafranca, E., Kaziro, Y., and Yokoyama, S. (1994) Oncogene 9, 2153-2157).
Deep Learning-Assisted Detection of PUE and Jamming Attacks in Cognitive Radio Systems (2020)

Cognitive radio (CR)-based internet of things systems can be considered as an efficient solution for futuristic smart technologies. However, CRs are naturally vulnerable to two major security threats; primary user emulation (PUE) and jamming attacks. Machine learning has been recently applied to the detection of these attacks. Still, the need for feature extraction required by machine learning techniques restrains the full exploitation of raw data. To alleviate this need, this paper proposes one-dimensional deep learning as a framework for identifying such attacks. Simulations show the ability of the proposed algorithm to detect these attacks with high performance.
Exploiting Model Organisms for Disease Intervention (2006)

Model organisms provide highly relevant and convenient platforms for characterizing novel protein functions and elucidating complex biological systems, including defining the roles of these proteins and systems in disease processes. This chapter describes various practical uses of model organisms (yeast, fly, worm, fish, and mouse) that contribute to the identification and validation of human therapeutic targets as well as impact on early drug development.
Supplementary Methods, Supplementary Figures 1-4, Supplementary Tables 1-6 from Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer (2023)

&lt;p&gt;Figure S1. Summary of HRD testing in PrECOG and combined cisplatin cohorts; Figure S2. Distribution of HRD scores in PrECOG and combined cisplatin cohorts; Figure S3. Performance of HRD in predicting response in PrECOG and combined cisplatin cohorts; Figure S4. Logistic regression models to predict response in PrECOG and combined cisplatin cohorts; Table S1. Study cohorts for threshold training set; Table S2. Summary statistics of HRD scores in BRCA1/2 deficient samples by tissue in training; Table S3. Patient clinical and demographic data; Table S4. HRD score and association with therapy response in entire cohorts; Table S5. Univariate associations between clinical variables and RCB 0/1 or HR deficiency status; Table S6. Analysis of RCB 0/1 and pCR in combined PrECOG 0105 and Cisplatin Trials cohorts (logistic regression models adjusted for cohort)&lt;/p&gt;
Ultra-thin film SOI/CMOS with selective-epi source/drain for low series resistance, high drive current (2002)

A self-aligned selective epitaxial technique is used to overcome the high source/drain resistance problem in ultra-thin film SOI/CMOS devices. Very low series resistances, comparable to those for bulk CMOS devices, are demonstrated with this selective-epi source/drain.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
174 Comparison of the mechanical performance of polymeric and metallic scaffolds – testing and modelling (2017)

<h3></h3> Percutaneous coronary intervention is a standard procedure to resolve blockages within artery, which involves the implantation of stents to maintain vessel patency. Currently, bioresorbable scaffolds (BRSs) are in the process of replacing the metallic permanent predecessor (drug eluting stents) commonly used in stenting. BRSs are commonly made of poly (L) Lactide (PLLA), an aliphatic polyester which is biodegradable and biocompatible with a wide range of medical applications. The performance of these scaffolds is not well defined in comparison to their metallic counterparts. The aim of this project is to assess the mechanical performance of PLLA scaffolds (Figure 1), with a direct comparison to that of metallic stents. This will be achieved through mechanical testing of structural rings at different load rates and ranges. Scaffolds will also be characterised using nano/micro indentation. The results will be used to support computational work for predicting the behaviour of both stents during crimping and expansion (Figure 2). Figure 3, Nanoindentation data on BRS. Figure 4, AFM data on BRS. Preliminary work indicates that it is possible to assess the local mechanical properties of a stent by atomic force microscopy and nano-indentation through evaluation of the unloading curves (figures 3 and 4). Further work would incorporate assessing the performance of the polymer scaffolds at different degradation time points to ascertain that vessel patency is achieved before complete degradation of BRSs. Results obtained here will help gain a better understanding of local and global mechanical properties of BRSs and enable further research and development of the scaffolds. <h3>Acknowledgement</h3> This work was supported by a grant from the British Heart Foundation (BHF).
Vascular Endothelial Growth Factor Family and Its Receptors (2008)

The vascular endothelial growth factors (VEGFs) are key regulators of blood and lymphatic vessel development during embryogenesis and in promoting new vascular growth during physiological and pathological processes in the adult. The VEGF family of ligands in mammals includes VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF). These ligands bind to and activate three receptor tyrosine kinases, designated VEGFR-1, VEGFR-2, and VEGFR-3. VEGF ligands bind to these receptors with overlapping ligand-receptor specificities, and activation may be further modulated through interaction with coreceptors such as the neuropilins (NRP-1 and NRP-2), integrins, or Vascular endothelial-cadherin (VE-cadherin). Ligand activation of VEGFRs triggers a network of distinct downstream-signaling pathways in a cell-type-specific manner that promotes vascular permeability, endothelial cell growth, migration, and survival. VEGF is an important survival factor for hematopoietic stem cells (HSCs) and stimulates the mobilization of endothelial progenitor cells (EPC) from the bone marrow to distant sites of neovascularization. A large body of experimental evidence has established VEGF as an essential molecule in promoting angiogenesis during tumor growth. These findings have led to the development of therapeutic agents that selectively target various VEGF ligands and their receptors. This chapter reviews the biology of VEGF and its receptors, emphasizing their important role for cancerous growth.
Assessment of Lung Water Distribution by Nuclear Magnetic Resonance: A New Method for Quantifying and Monitoring Experimental Lung Injury (1988)

We have developed a new analytical method that uses nuclear magnetic resonance (NMR) imaging data to quantify lung water content and distribution. This new method generates a distribution of lung water density in which the fraction of voxels corresponding to a given water density is plotted on the vertical axis as a function of water density on the horizontal axis, thereby complementing the spatial information provided by the NMR image. We obtained reproducible lung water distribution data at comparable lung volumes in normal excised lungs and in intact living rats. In normal excised unperfused rat lungs, the distribution varied with the degree of inflation, but the changes were small compared with those associated with lung edema. The lung water density distribution changed markedly after induction of lung edema by intrabronchial saline instillation, intravenous oleic acid injection, and rapid intravenous saline infusion. Lung water density distribution data were well correlated (correlation coefficient = 0.948 for the excised lungs and 0.823 for the intact living rats) with gravimetric lung water measurements. The new analytical method is noninvasive, provides easily repeatable measurements, and is as sensitive as the gravimetric technique to lung water changes.
MOVPE growth for photodiodes in 2.5 µm region with InGaAs/GaAsSb type‐II quantum wells (2013)

Abstract Low dark current photodiodes (PDs) in the short wavelength infrared (SWIR) region over 1.7 µm are expected to be used for many applications. InGaAs/GaAsSb type‐II quantum well (QW) structures are considered to be attractive material systems for realizing low dark current PDs, owing to lattice‐matching to InP substrates. In this report, we describe the successful operation of pin‐PDs with InGaAs/GaAsSb QWs with InP capping layers grown by metal‐organic vapor phase epitaxy (MOVPE). Distinct X‐ray diffraction satellite peaks and emissions from type‐II transition were observed. Electrical and optical characteristics of pin‐PDs, such as dependence of responsivity on the number of QWs, were investigated. Dark current was 9.0 µA/cm 2 at 233 K and an external quantum efficiency (EQE) of 48% was obtained. These results indicate that it is possible to reduce the dark current of InGaAs/GaAsSb type‐II PDs by using the InP capping layers grown by MOVPE. (© 2013 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Safety, feasibility and toxicity profile of a new immunotherapy protocol for metastatic melanoma patients using in vivo salmonella typhimurium vaccination and treatment. (2007)

A17 A major obstacle for the development of effective immunotherapy is the ability of tumours to escape the immune system. The possibility to kill tumour cells because they are recognized as infected rather than as malignant, could help to overcome immune-escape mechanisms. Here we report a conceptually new approach of cancer immunotherapy based on in vivo infection of tumours and killing of infected tumour cells. Attenuated but still invasive Salmonella typhimurium (ST) can be successfully exploited to invade melanoma cells that can present antigenic determinants of bacterial origin and become targets for anti-ST specific T cells. Therefore, tumour cells are killed because they are recognized as infected. Preclinical studies on tumour-bearing mice showed that intratumoral ST-infection is able to induce the recruitment of anti-ST specific T-cells elicitated during the vaccination step unto the tumour site for recognition of ST-infected tumour cells. Tumour infection when coupled to anti-ST vaccination leads to 50-100% tumour free mice with a better outcome on larger tumours. This effect is mediated by both CD4 and CD8 T cells as neutralization of these cell types in vivo diminishes the antitumor effect. Invasive ST also exert an indirect toxic effect on tumour cells through the recruitment of inflammatory cells and the cross-presentation of tumour antigens, which allow induction of tumour-specific immune response. This is effective in retarding the growth of untreated established distant tumours and in protecting the mice from subsequent tumour challenges.  Since may 2006, 8 patients affected by not operable stage III or IV M1a metastatic melanoma where enrolled in the trial, in order to stimuli an autologous immune response using Vivotif® vaccine and ST (Ty21a) as a therapeutic agent. Two steps were foreseen: oral vaccination with Ty21a and intratumoral treatment with Ty21a. Two metastasis were treated and 1 observed in order to evaluate the indirect effect of vaccination. Planned accrual sample size is 43 patients.  Among the 8 enrolled patients, 1 could not be vaccinated due to the evidence of hepatic metastasis during stadiation, 1 had a rapid worsening of the performance status during vaccination while 2 did not develop adequate anti-ST vaccination titre. Of the remaining 4 patients, only 1 completed the first cycle obtaining a local response, while the other 3 interrupted the treatment due to progressive disease, important hypersensitivity reaction and a worsening of the hepatic function indexes. At injection, all the patients developed a variable degrease of lumbar pain, nausea/vomiting, shivering, fever, hypotension easily controlled by treatment with antihistaminics, antipyretics, antiemetics without the use of cortisones.  Treated metastases showed all the signs of local inflammation and objective dimensional stabilization or reduction, but systemic disease seem not to be affected by the immunologic treatment.
Candida Colonization and Subsequent Infections in Critically III Surgical Patients (1994)

The intensity of Candida colonization assessed by systematic screening helps predicting subsequent infections with identical strains in critically ill patients. Accurately identifying high-risk patients with Candida colonization offers opportunity for intervention strategies.
Pd@Fe2O3 Superparticles with Enhanced Peroxidase Activity by Solution Phase Epitaxial Growth (2016)

Compared to conventional deposition techniques for the epitaxial growth of metal oxide structures on a bulk metal substrate, wet-chemical synthesis based on a dispersible template offers advantages such as low cost, high throughput, and the capability to prepare metal/metal oxide nanostructures with controllable size and morphology. However, the synthesis of such organized multicomponent architectures is difficult because the size and morphology of the components are dictated by the interplay of interfacial strain and facet-specific reactivity. Here we show that solution-processable two-dimensional Pd nanotetrahedra and nanoplates can be used to direct the epitaxial growth of γ-Fe2O3 nanorods. The interfacial strain at the Pd−γ-Fe2O3 interface is minimized by the formation of an FexPd “buffer phase” facilitating the growth of the nanorods. The γ-Fe2O3 nanorods show a (111) orientation on the Pd(111) surface. Importantly, the Pd@γ-Fe2O3 hybrid nanomaterials exhibit enhanced peroxidase activity compared to that of isolated Fe2O3 nanorods with comparable surface area because of a synergistic effect for the charge separation and electron transport. The metal-templated epitaxial growth of nanostructures via wet-chemical reactions appears to be a promising strategy for the facile and high-yield synthesis of novel functional materials.
Development of a Dual-Frequency VECSEL for a compact CPT clock (2020)

International audience
New Insights on Dynamic Voltage Scaling of Multiphase Synchronous Buck Converter: A Comprehensive Design Consideration (2013)

This paper comprehensively investigates the power-related issues and introduces new control schemes in dynamic voltage scaling (DVS), which is now used in modern multi-core processor and multiprocessor system-on-chip to reduce operational voltage under light load conditions. With the aggressive motivation to boost dynamic power efficiency, the design specification of voltage transition (dv/dt) for the DVS is pushing the physical limitation of the multiphase converter design and the component stress. In this paper, the operation modes and modes transition during dynamic voltage transition are illustrated. Critical dead-times of driver IC design and system dynamics are first studied and then optimized. The excessive stress on the control MOSFET which increases the reliability concern is captured in boost mode operation. Feasible solutions are also proposed and verified by both simulation and experimental results. CdV/dt compensation for removing the adaptive voltage positioning effect and a novel nonlinear control scheme for smooth transition are proposed for dealing with fast-voltage positioning. Optimum phase number control during dynamic voltage transition is also proposed and triggered by voltage identification delta to further reduce the dynamic loss. For experimental verification, a 200 W, six-phase synchronous buck converter is implemented with the proposed schemes.
Synthesis and Antihypoxic Activity of γ‐L‐Glutamylhistamine and Its Derivatives. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Metal-bound halogen atoms in crystal engineering (2013)

In this viewpoint article we discuss an early contribution from Brammer and Orpen et al., which highlights the very rich supramolecular behaviour of halogen atoms. Their findings appear even more timely when viewed in light of the recently proposed IUPAC definition of the halogen bond.
High-resolution absolute position detection using a multiple grating. (1996)

To control electro-mechanical engines, high-resolution linear and rotary encoders are needed. Interferometric methods (grating interferometers) promise a resolution of a few nanometers, but have an ambiguity range of some microns. Incremental encoders increase the absolute measurement range by counting the signal periods starting from a defined initial point. In many applications, however, it is not possible to move to this initial point, so that absolute encoders have to be used. Absolute encoders generally have a scale with two or more tracks placed next to each other. Therefore, they use a two-dimensional grating structure to measure a one-dimensional position. We present a new method, which uses a one-dimensional structure to determine the position in one dimension. It is based on a grating with a large grating period up to some millimeters, having the same diffraction efficiency in several predefined diffraction orders (multiple grating). By combining the phase signals of the different diffraction orders, it is possible to establish the position in an absolute range of the grating period with a resolution like incremental grating interferometers. The principal functionality was demonstrated by applying the multiple grating in a heterodyne grating interferometer. The heterodyne frequency was generated by a frequency modulated laser in an unbalanced interferometer. In experimental measurements an absolute range of 8 mm was obtained while achieving a resolution of 10 nm.
The effects of propofol or sevoflurane on free radical production after tourniquet induced ischaemia-reperfusion injury during knee arthroplasty. (2007)

We studied the effects of anesthesia with propofol or sevoflurane on the production of free oxygen radicals during total knee arthroplasty performed with the use of an ischemic tourniquet by measuring the levels of malondialdehyde (MDA).We studied two groups of patients (20 patients in each group) who underwent total knee arthroplasty. To maintain anesthesia we delivered 66% nitrous oxide plus sevoflurane or propofol. Blood samples for the determination of the MDA levels were drawn before the application of the ischemic tourniquet and 5 and 30 minutes after its release.There were no differences between groups in regard to age, weight and duration of the tourniquet application. MDA levels decreased significantly in the propofol group 30 minutes after the release of the tourniquet (1.7 micromol litre(-1) vs 1.57 micromol litre(-1), Friedman's ANOVA, P = 0.007). In contrast, there was a small rise of the MDA levels in the sevoflurane group (1.82 micromol litre(-1) vs 1.96 micromol litre(-1), Friedman's ANOVA, P = 0.007).Propofol may have anti-oxidant properties in orthopaedic surgery requiring tourniquet application, but sevoflurane needs further study.