gebhart/patrepeval huggingface dataset:
Discovery of Potent and Selective Sirtuin 2 (SIRT2) Inhibitors Using a Fragment-Based Approach (2014)

Sirtuin 2 (SIRT2) is one of the sirtuins, a family of NAD(+)-dependent deacetylases that act on a variety of histone and non-histone substrates. Accumulating biological functions and potential therapeutic applications have drawn interest in the discovery and development of SIRT2 inhibitors. Herein we report our discovery of novel SIRT2 inhibitors using a fragment-based approach. Inspired by the purported close binding proximity of suramin and nicotinamide, we prepared two sets of fragments, namely, the naphthylamide sulfonic acids and the naphthalene-benzamides and -nicotinamides. Biochemical evaluation of these two series provided structure-activity relationship (SAR) information, which led to the design of (5-benzamidonaphthalen-1/2-yloxy)nicotinamide derivatives. Among these inhibitors, one compound exhibited high anti-SIRT2 activity (48 nM) and excellent selectivity for SIRT2 over SIRT1 and SIRT3. In vitro, it also increased the acetylation level of α-tubulin, a well-established SIRT2 substrate, in both concentration- and time-dependent manners. Further kinetic studies revealed that this compound behaves as a competitive inhibitor against the peptide substrate and most likely as a noncompetitive inhibitor against NAD(+). Taken together, these results indicate that we have discovered a potent and selective SIRT2 inhibitor whose novel structure merits further exploration.
Fringe interpreting for aspheric surface testing. (1991)

In the usual method of fringe analysis for aspheric surface, the difference between the test surface and the reference surface is measured by the order of fringes. But, in this method, the error can't be avoided from the approximate interpretation. By simulating the error using a certain aspheric surface, it is shown that the error can't be ignored. Then, a new method is proposed which doesn't contain the error from the approximate interpretation. In this new method, fringe density which can be obtained from interference fringe's figure is introduced as a data. This new method doesn't measures the difference between test surface and reference surface, but measures the test surface directly.
Novel Carbon Dioxide Microsensor Based on Tin Oxide Nanomaterial Doped With Copper Oxide (2009)

Carbon dioxide (CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) is one of the major indicators of fire and therefore its measurement is very important for low-false-alarm fire detection and emissions monitoring. However, only a limited number of CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> sensing materials exist due to the high chemical stability of CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> . In this work, a novel CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> microsensor based on nanocrystalline tin oxide (SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ) doped with copper oxide (CuO) has been successfully demonstrated. The CuO-SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> based CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> microsensors are fabricated by means of microelectromechanical systems technology and sol-gel nanomaterial-synthesis processes. At a doping level of CuO : SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> = 1 : 8 (molar ratio), the resistance of the sensor has a linear response to CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> concentrations for the range of 1% to 4% CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> in air at 450 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">deg</sup> C. This approach has demonstrated the use of SnO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> , typically used for the detection of reducing gases, in the detection of an oxidizing gas.
Magnetoelastic effects in SrTi<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow/><mml:mrow><mml:mn>1</mml:mn><mml:mo>−</mml:mo><mml:mi>x</mml:mi></mml:mrow></mml:msub><mml:msub><mml:mi mathvariant="normal">M</mml:mi><mml:mi>x</mml:mi></mml:msub></mml:mrow></mml:math>O<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:msub><mml:mrow/><mml:mn>3</mml:mn></mml:msub></mml:math>(M = Fe, Co, or Cr) epitaxial thin films (2011)

SrTi${}_{1\ensuremath{-}x}$M${}_{x}$O${}_{3}$ films in which M = Fe, Co, or Cr and $x=0.04$--0.5 have been grown epitaxially on CeO${}_{2}$-buffered Si, SrTiO${}_{3}$, and LaAlO${}_{3}$ substrates. Films grown in vacuum containing Fe or Co typically showed a strong uniaxial magnetic anisotropy in the out-of-plane direction, a saturation moment on the order of 0.5\ensuremath{\mu}${}_{\mathrm{B}}$/Fe or Co, and a magnetization that persists to temperatures of order 1000 K. In contrast, films containing Cr showed no evidence of a spontaneous magnetic moment. The films are typically in a high in-plane compressive strain state due to epitaxial growth. The results are discussed in terms of the magnetoelastic effects from specific ionic valence states, and the magnetization versus temperature curves are fitted to a model for magnetoelastic spin ordering.
Triptycene-Based, Carboxylate-Bridged Biomimetic Diiron(II) Complexes (2013)

A triptycene-based bis(benzimidazole) ester ligand, L3, was designed to enhance the electron-donating ability of the heterocyclic nitrogen atoms relative to those of the first-generation bis(benzoxazole) analogs, L1 and L2. A convergent synthesis of L3 was designed and executed. Three-component titration experiments using UV/Vis spectroscopy revealed that the desired diiron(II) complex could be obtained with a 1:2:1 ratio of L3/Fe(OTf)[subscript 2](MeCN)[subscript 2]/external carboxylate reactants. X-ray crystallographic studies of two diiron complexes derived in this manner from L3 revealed their formulas to be [Fe[subscript 2]L3(μ-OH)(μ-O[subscript 2]CR)(OTf)2], where R = 2,6-bis(p-tolyl)phenyl (7) or triphenylmethyl (8). The structures are similar to that of a diiron complex derived from L1, [Fe[subscript 2]L1(μ-OH)(μ-O[subscript 2]CAr[superscript Tol])(OTf)[subscript 2]] (9), a notable difference being that, in 7 and 8, the geometry at iron more closely resembles square-pyramidal than trigonal-bipyramidal. Mössbauer spectroscopic analyses of 7 and 8 indicate the presence of high-spin diiron(II) cores. These results demonstrate the importance of substituting benzimidazole for benzoxazole for assembling biomimetic diiron complexes with syn disposition of two N-donor ligands, as found in O[subscript 2]-activating carboxylate-bridged diiron centers in biological systems.
Supplementary Table S2 from RLY-4008, the First Highly Selective FGFR2 Inhibitor with Activity across &lt;i&gt;FGFR2&lt;/i&gt; Alterations and Resistance Mutations (2023)

&lt;p&gt;Biochemical inhibition of FGFR by RLY-4008 and pan-FGFRi&lt;/p&gt;
Sulfur Oxyacids and Radicals in the Gas Phase. A Variable-Time Neutralization−Photoexcitation−Reionization Mass Spectrometric and Ab Initio/RRKM Study (1997)

Hydroxysulfinyl radical (1), hydrogensulfonyl radical (2), and dihydroxysulfane (6) were generated in the gas phase by collisional reduction of the corresponding cations and studied by the variable-time and photoexcitation methods of neutralization−reionization mass spectrometry and by ab initio and RRKM calculations. Radicals 1 and 2 were thermodynamically and kinetically stable. Two rotamers of 1, syn-1 and anti-1, were found computationally to be local energy minima. The computations suggested a complex potential energy surface for dissociations of 1. The minimum-energy reaction path was the rate-determining isomerization to 2 followed by fast loss of H• to form SO2. Direct H• loss from 1 was kinetically disfavored. Cleavage of the S−OH bond in 1 was highly endothermic and became kinetically significant at excitations >325 kJ mol-1. In contrast to ab initio/RRKM predictions, 1 formed by vertical reduction of hydroxysulfinyl cation (1+) dissociated mainly to OH• and SO, whereas loss of H• was less significant. Both dissociations showed microsecond kinetics as established by variable-time measurements. Photoexcitation of nondissociating 1 opened the H-loss channel, whereas collisional excitation did not change the branching ratio for the H• and OH• loss channels. The experimental results pointed to the formation of a large fraction of metastable and dissociative excited electronic states of 1 upon vertical electron transfer. Radical 2 was cogenerated with 1 by vertical reduction of a mixture of 1+ and 2+ produced by highly exothermic protonation of SO2 with H3+. Pronounced loss of H• from 2 occurred following collisional neutralization in accordance with RRKM predictions. Dihydroxysulfane (6) was stable following collisional neutralization of the cation-radical 6•+. The G2(MP2) potential energy surface predicted the isomerization to hydrogensulfinic acid (7) followed by loss of water to be the lowest-energy dissociation of 6. RRKM calculations showed the 6 → 7 isomerization to be the rate-determining step. Cation-radical 6•+ also eliminated water through unimolecular isomerization to a stable nonclassical isomer, OS•+···H2O (9). The thermochemistry of the neutral and ionic systems is discussed. The important role of excited electronic states in the formation of radicals by vertical electron transfer is emphasized.
Between Liquid and All Solid: A Prospect on Electrolyte Future in Lithium‐Ion Batteries for Electric Vehicles (2020)

Herein, three electrolyte families (liquid, polymer, and ceramic) are compared and their future perspectives in research and application are discussed. First, the transport mechanism for each family is presented, as their beneficial and taxing properties stem from the differences in these mechanisms. Following a discussion of each group, their advantages, and limitations, a clear conclusion can be drawn on the need to focus on research on solid electrolytes, which present brighter prospects in terms of significant future advances in lithium‐based battery systems. Yet, in a more realistic perspective based on current work by companies such as Samsung, Solid Power, and QuantumScape, it is our understanding that the hybridization of polymer and solid electrolytes will likely dominate practical electrolyte chemistries, at least in the near future, given that the synergetic properties of the two families are larger than their single parts. Inevitably, solid‐state electrolytes will dominate, mainly in electric vehicles and future lithium battery chemistries.
Shape deformation of the insula in alcoholics: reduction of left–right asymmetry (2007)

We have investigated shape deformation of the insula to get a viewpoint of how chronic alcohol consumption affects the perisylvian region and compared the deformity pattern between the left and right hemisphere. A landmark-based structural and surface shape analysis of the insula was performed in 20 patients with alcohol dependence and 20 controls matched for age. The shape analysis revealed that the left and right insula follow distinct shape deformation patterns, which resulted in the reduction of left-right asymmetry. The shape deformity was most prominent in the central part of both insula. Our findings indicate that the right and left hemisphere are both affected but shows distinct patterns of deformation in alcohol dependence.
Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders (2012)

Neuromyelitis optica (NMO) has been described as a disease clinically characterised by severe optic neuritis (ON) and transverse myelitis (TM). Other features of NMO include female preponderance, longitudinally extensive spinal cord lesions (>3 vertebral segments), and absence of oligoclonal IgG bands . In spite of these differences from multiple sclerosis (MS), the relationship between NMO and MS has long been controversial. However, since the discovery of NMO-IgG or aquaporin-4 (AQP4) antibody (AQP4-antibody), an NMO-specific autoantibody to AQP4, the dominant water channel in the central nervous system densely expressed on end-feet of astrocytes, unique clinical features, MRI and other laboratory findings in NMO have been clarified further. AQP4-antibody is now the most important laboratory finding for the diagnosis of NMO. Apart from NMO, some patients with recurrent ON or recurrent longitudinally extensive myelitis alone are also often positive for AQP4-antibody. Moreover, studies of AQP4-antibody-positive patients have revealed that brain lesions are not uncommon in NMO, and some patterns appear to be unique to NMO. Thus, the spectrum of NMO is wider than mere ON and TM. Pathological analyses of autopsied cases strongly suggest that unlike MS, astrocytic damage is the primary pathology in NMO, and experimental studies confirm the pathogenicity of AQP4-antibody. Importantly, therapeutic outcomes of some immunological treatments are different between NMO and MS, making early differential diagnosis of these two disorders crucial. We provide an overview of the epidemiology, clinical and neuroimaging features, immunopathology and therapy of NMO and NMO spectrum disorders.
Significantly Enhanced Hydrogen Storage in Metal−Organic Frameworks via Spillover (2005)

The utilization of hydrogen in fuel-cell powered vehicles is limited by the lack of a safe and effective system for hydrogen storage. At the present time, there is no viable storage technology capable of meeting the DOE targets. Porous metal-organic frameworks (MOFs) are novel and potential candidates for hydrogen storage. Until now it is still not possible to achieve any significant hydrogen storage capacity in MOFs at ambient temperature. Here, we report, for the first time, significant amounts of hydrogen storage in MOF-5 and IRMOF-8 at ambient temperature by using a very simple technique via hydrogen dissociation and spillover. Thus, hydrogen uptakes for MOF-5 and IRMOF-8 can be enhanced by a factor of 3.3 and 3.1, respectively (to nearly 2 wt % at 10 MPa and 298 K). Furthermore, the isotherms are totally reversible. These findings suggest that our technique is suitable for hydrogen storage in a variety of MOF materials because of their similar structures as MOF-5 and IRMOF-8.
Exploring new frontiers in x-ray quantum limited portal imaging using active matrix flat-panel imagers (AMFPIs) (2003)

In recent years, indirect detection active matrix flat-panel imagers (AMFPIs) have become the gold standard in radiotherapy imaging. The excellent imaging performance of AMFPI-based electronic portal imaging devices (EPIDs) can be attributed to their ability to perform x-ray quantum limited imaging under radiotherapy conditions. However, all current commercial (AMFPI and non-AMFPI) EPIDs use only approximately 1% to 2% of the incident radiation. In this work, strategies to significantly improve the overall performance of indirect detection AMFPI-based EPIDs through novel designs, are presented. Specifically, the focus of this work is on thick, structured scintillators, which achieve high x-ray detection efficiency while simultaneously maintaining spatial resolution. Fundamental signal and noise measurements using prototype, small area, structured scintillators are reported. In addition, theoretical calculations were performed in order to estimate the signal and noise properties of various structured scintillator configurations. Results from theory and experiments were used to estimate the frequency-dependent detective quantum efficiency (DQE). Results suggest that these designs could yield DQE values that are significantly higher than those for current commercial EPID technologies.
Evaluating the SDN control traffic in large ISP networks (2015)

Scalability of Software Defined Networking (SDN) approach is one of the key issues that many network operators are willing to address and understand. Indeed, the promised programmability and flexibility of a SDN network is paid with a non-negligible control traffic exchanged between the network nodes and the SDN controllers. We consider a network controlled by a real OpenFlow-enabled controller, i.e. OpenDaylight. We evaluate analytically the number of OpenFlow messages for installing a new traffic flow, assuming the default reactive forwarding application available in OpenDaylight. We apply these results to the specific case of a large ISP network, comprising a backbone interconnecting many POPs. By evaluating exactly the amount of generated control traffic, we are able to assess the scalability of the reactive forwarding application in a practical relevant scenario for ISPs.
Editor's evaluation: Inhibitory IL-10-producing CD4+ T cells are T-bet-dependent and facilitate cytomegalovirus persistence via coexpression of arginase-1 (2022)

The results presented here indicate that IL-10-producing CD4+ T cells express genes associated with chronically activated TH1-like cells, undergo clonal expansion, and inhibit antiviral T cell responses via the secretion of arginase-1, facilitating viral persistence in mice infected with MCMV.
Development of a repressible mycobacterial promoter system based on two transcriptional repressors (2010)

Tightly regulated gene expression systems represent invaluable tools for studying gene function and for the validation of drug targets in bacteria. While several regulated bacterial promoters have been characterized, few of them have been successfully used in mycobacteria. In this article we describe the development of a novel repressible promoter system effective in both fast- and slow-growing mycobacteria based on two chromosomally encoded repressors, dependent on tetracycline (TetR) and pristinamycin (Pip), respectively. This uniqueness results in high versatility and stringency. Using this method we were able to obtain an ftsZ conditional mutant in Mycobacterium smegmatis and a fadD32 conditional mutant in Mycobacterium tuberculosis, confirming their essentiality for bacterial growth in vitro. This repressible promoter system could also be exploited to regulate gene expression during M. tuberculosis intracellular growth.
Synthesis, thermal, and mechanical characterization of liquid-crystalline polyhydroxyethers (1997)

High molecular weight liquid-crystalline polyhydroxyethers, containing functional hydroxy groups, were synthesized from an aromatic diol and the diglycidylether of an aromatic diol. The polymers showed a liquid-crystalline melt when about 70% or more of the aromatic units in the chain were biphenyl units. Tensile modulus values varied from 3 GPa for as-cast films to 6 GPa for drawn films. These polymers are potentially suitable candidates to reinforce common thermoplastics by reactive blending. For this purpose polyhydroxyethers have been prepared, having a liquid-crystalline melt in the processing range of PET, viz. 260–290°C. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 1971–1978, 1997
Horizontal slot waveguide channel for enhanced Raman scattering (2013)

Herein we characterize and experimentally demonstrate a new type of a horizontal slot waveguide structure for remarkably enhanced Raman scattering detection in nanometer-scale void channels. As the measurement sensitivity is one of the key limiting factors in nanofluidic detection, it is essential to search advanced solutions for such detection. Combining an all dielectric resonance waveguide grating and a surface enhanced Raman scattering (SERS) substrate in a close proximity it is possible to create high electromagnetic field energy hot zones within an adjustable slot region. This results in a strong enhancement in Raman scattering. We show the theoretical principles and demonstrate, with rhodamine 6G molecules, an approximately 20-fold enhancement compared to a conventional SERS substrate within the corresponding slot arrangement. We foresee potential applications for the proposed approach in the fields of medical, biological and chemical sensing, where the high detection sensitivity is essential due to integration with nanofluidic devices.
Identification and Rationalization of Kinetic Folding Intermediates for a Low-Density Lipoprotein Receptor Ligand-Binding Module (2018)

Many mutations that cause familial hypercholesterolemia localize to ligand-binding domain 5 (LA5) of the low-density lipoprotein receptor, motivating investigation of the folding and misfolding of this small, disulfide-rich, calcium-binding domain. LA5 folding is known to involve non-native disulfide isomers, yet these folding intermediates have not been structurally characterized. To provide insight into these intermediates, we used nuclear magnetic resonance (NMR) to follow LA5 folding in real time. We demonstrate that misfolded or partially folded disulfide intermediates are indistinguishable from the unfolded state when focusing on the backbone NMR signals, which provide information on the formation of only the final, native state. However, <sup>13</sup>C labeling of cysteine side chains differentiated transient intermediates from the unfolded and native states and reported on disulfide bond formation in real time. The cysteine pairings in a dominant intermediate were identified using <sup>13</sup>C-edited three-dimensional NMR, and coarse-grained molecular dynamics simulations were used to investigate the preference of this disulfide set over other non-native arrangements. The transient population of LA5 species with particular non-native cysteine connectitivies during folding supports the conclusion that cysteine pairing is not random and that there is a bias toward certain structural ensembles during the folding process, even prior to the binding of calcium.
The antioxidant properties of thioctic acid: Characterization by cyclic voltammetry (1997)

Thioctic acid (TA) level and its antioxidant capacity were monitored by cyclic voltammetry (CV), in solution and in human plasma. A linear correlation between the anodic wave current Ia at 900 mV and [TA] was obtained. This indicates that TA, commonly found in human plasma, is an antioxidant component characterized by a potential E1/2 = 900 mV and constitute, at least in part, the second anodic wave of the CV tracing. When plasma from diabetic patients was analyzed by CV, those patients under treatment with TA showed higher Ia than others not taking the drug. When the patients under treatment with TA were divided into groups according to the severity of their nephropathy, or according to the severity of their total complication count, Ia levels representing TA were significantly higher in those patients with more severe complications.
Quetiapine for Bipolar Depressive Episode in Obsessive-Compulsive Disorder Patients Maintained on Selective Serotonin Reuptake Inhibitor Treatment (2021)

The revealed beneficial effect of quetiapine addition for acute episode of BP-D in OCD patients maintained on selective serotonin reuptake inhibitor treatment merits further controlled investigation.