gebhart/patrepeval huggingface dataset:
Tyrosine 547 Constitutes an Essential Part of the Catalytic Mechanism of Dipeptidyl Peptidase IV (2004)

Human dipeptidyl peptidase IV (DPP-IV) is a ubiquitously expressed type II transmembrane serine protease. It cleaves the penultimate positioned prolyl bonds at the N terminus of physiologically important peptides such as the incretin hormones glucagon-like peptide 1 and glucose-dependent insulinotropic peptide. In this study, we have characterized different active site mutants. The Y547F mutant as well as the catalytic triad mutants S630A, D708A, and H740L showed less than 1% wild type activity. X-ray crystal structure analysis of the Y547F mutant revealed no overall changes compared with wild type apoDPP-IV, except the ablation of the hydroxyl group of Tyr(547) and a water molecule positioned in close proximity to Tyr(547). To elucidate further the reaction mechanism, we determined the crystal structure of DPP-IV in complex with diisopropyl fluorophosphate, mimicking the tetrahedral intermediate. The kinetic and structural findings of the tyrosine residue are discussed in relation to the catalytic mechanism of DPP-IV and to the inhibitory mechanism of the 2-cyanopyrrolidine class of potent DPP-IV inhibitors, proposing an explanation for the specificity of this class of inhibitors for the S9b family among serine proteases.
On-the-Fly Active Learning of Interpretable Bayesian Force Fields for\n Atomistic Rare Events (2019)

Machine learned force fields typically require manual construction of\ntraining sets consisting of thousands of first principles calculations, which\ncan result in low training efficiency and unpredictable errors when applied to\nstructures not represented in the training set of the model. This severely\nlimits the practical application of these models in systems with dynamics\ngoverned by important rare events, such as chemical reactions and diffusion. We\npresent an adaptive Bayesian inference method for automating the training of\ninterpretable, low-dimensional, and multi-element interatomic force fields\nusing structures drawn on the fly from molecular dynamics simulations. Within\nan active learning framework, the internal uncertainty of a Gaussian process\nregression model is used to decide whether to accept the model prediction or to\nperform a first principles calculation to augment the training set of the\nmodel. The method is applied to a range of single- and multi-element systems\nand shown to achieve a favorable balance of accuracy and computational\nefficiency, while requiring a minimal amount of ab initio training data. We\nprovide a fully open-source implementation of our method, as well as a\nprocedure to map trained models to computationally efficient tabulated force\nfields.\n
Problems and prospects for electrical signaling [VLSI] (1999)

Summary form only given, as follows. The growing gap between on-chip gates and off-chip I/O bandwidth is reaching crisis proportions, yet signaling system designers continue to use inefficient and inappropriate circuit techniques for many chip-to-chip interconnections. For example, most chip-to-chip interconnect still uses CMOS inverters as transmitters and receivers, even though it would be difficult to imagine more unfavorable components for a signaling system. Processor-to-memory and processor-to-processor communication systems are still almost universally built using physical buses, transmission lines with multiple loads attached along their length. Though logically simple and convenient, these structures impose fundamental limits on signal speed that preclude their use above about 1-2 Gbaud, exact a heavy price in power dissipation, and are very difficult to engineer. Some have suggested replacing electrical signaling with optical interconnect; however, converting between optical and electrical signals is still expensive, and in any case, electrical signaling is far from its theoretical limits. With reasonable assumptions, the wiring embedded in a typical circuit board has bisection bandwidth of order 10 s of Tbit/s. Recent advances in high-speed serial link techniques point the way to unlocking a substantial fraction of this bandwidth. In CMOS, 1-2 Gbit/s links are fairly common, experimental 4 Gb/sec links have been demonstrated, and speeds up to 20 Gbits/s appear quite feasible.
Three- versus four-coordinate phosphorus in the gas phase and in solution: Treacherous relative energies for phosphine oxide and phosphinous acid (2002)

Previous ab initio studies have consistently predicted phosphine oxide (H3PO) to be less stable than its nearly isoenergetic cis- and trans-phosphinous acid isomers (H2POH). However, complete basis set extrapolations employing the coupled-cluster series show that phosphine oxide is actually ca. 1.0 kcal/mol more stable than its acid forms in the gas phase. Incorporation of tight d functions via Dunning’s core-valence (cc-pCVXZ) or newly constructed “plus d” [cc-pV(X+d)Z] basis sets is essential for rapid convergence of core polarization effects which are evident even at the SCF level. The precision to which the phosphorus hybridization is described in the three- and four-coordinate environments ultimately determines the predicted gas-phase relative energy orderings. Focal-point analyses demonstrate that this system represents a disturbing case where use of a conventional valence quadruple-ζ quality basis set (cc-pVQZ)—even at the CCSD(T) level—fails to provide the correct relative energy ordering for simple closed-shell species which do not exhibit appreciable multireference character. Thus, we underscore the importance of using phosphorus basis sets which have the flexibility to describe core polarization adequately. In addition, Monte Carlo (MC) free-energy perturbation simulations in solution clearly demonstrate that the small energy gap significantly increases in favor of the oxide (10.0 kcal/mol) upon solvation due to stronger hydrogen bonding with the highly polar Pδ+→Oδ− bond.
Profile Mode (2016)

This document contains recommendations for terminology in mass spectrometry. Development of standard terms dates back to 1974 when the IUPAC Commission on Analytical Nomenclature issued recommendations on mass spectrometry terms and definitions. In 1978, the IUPAC Commission on Molecular Structure and Spectroscopy updated and extended the recommendations and made further recommendations regarding symbols, acronyms, and abbreviations. The IUPAC Physical Chemistry Division Commission on Molecular Structure and Spectroscopy’s Subcommittee on Mass Spectroscopy revised the recommended terms in 1991 and appended terms relating to vacuum technology. Some additional terms related to tandem mass spectrometry were added in 1993 and accelerator mass spectrometry in 1994. Owing to the rapid expansion of the field in the intervening years, particularly in mass spectrometry of biomolecules, a further revision of the recommendations has become necessary. This document contains a comprehensive revision of mass spectrometry terminology that represents the current consensus of the mass spectrometry community.
Disease correction in mucopolysaccharidosis type IIIB mice by intraparenchymal or cisternal delivery of a capsid modified AAV8 codon-optimized NAGLU vector (2022)

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive lysosomal storage disease caused by mutations in the gene that encodes the protein N-acetyl-glucosaminidase (NAGLU). Defective NAGLU activity results in aberrant retention of heparan sulfate within lysosomes leading to progressive central nervous system (CNS) degeneration. Intravenous treatment options are limited by the need to overcome the blood-brain barrier and gain successful entry into the CNS. Additionally, we have demonstrated that AAV8 provides a broader transduction area in the MPS IIIB mouse brain compared with AAV5, 9 or rh10. A triple-capsid mutant (tcm) modification of AAV8 further enhanced GFP reporter expression and distribution. Using the MPS IIIB mouse model, we performed a study using either intracranial six site or intracisterna magna injection of AAVtcm8-codon-optimized (co)-NAGLU using untreated MPS IIIB mice as controls to assess disease correction. Disease correction was evaluated based on enzyme activity, heparan sulfate storage levels, CNS lysosomal signal intensity, coordination, activity level, hearing and survival. Both histologic and enzymatic assessments show that each injection method results in supranormal levels of NAGLU expression in the brain. In this study, we have shown correction of lifespan and auditory deficits, increased CNS NAGLU activity and reduced lysosomal storage levels of heparan sulfate following AAVtcm8-coNAGLU administration and partial correction of NAGLU activity in several peripheral organs in the murine model of MPS IIIB.
ChemInform Abstract: Sulfanylation of 1,3‐Dithiane Anions by 5‐(Alkylsulfanyl)‐1‐phenyltetrazoles. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
Repurposing auranofin as an intestinal decolonizing agent for vancomycin-resistant enterococci (2018)

Multidrug-resistant enterococcal pathogens, especially vancomycin-resistant enterococci (VRE), are among the pathogens that require new antibiotic innovation. The colonization of the gut represents a major pathway by which VRE can cause infection and spread to other patients. In the current study, auranofin (FDA-approved rheumatoid arthritis drug) is evaluated for its potential use as a decolonizing agent for VRE. Auranofin was found to exert potent antimicrobial activity against a wide range of enterococcal clinical isolates with a minimum inhibitory concentration of 1 μg/mL. No resistant mutants could be developed against auranofin over the course of 14 passages. Auranofin was also found to exert potent anti-biofilm activity against VRE. Auranofin was superior to linezolid, the drug of choice for VRE infection treatment, in the in vivo mouse model. Auranofin significantly reduced the VRE burden in feces, cecum, and ileum contents after 8 days of treatment. Accordingly, this study provides valuable evidence that auranofin has significant promise as a novel gastrointestinal decolonizing agent for VRE.
Optical coherence tomography for advanced screening in the primary care office (2013)

Optical coherence tomography (OCT) has long been used as a diagnostic tool in the field of ophthalmology. The ability to observe microstructural changes in the tissues of the eye has proved very effective in diagnosing ocular disease. However, this technology has yet to be introduced into the primary care office, where indications of disease are first encountered. We have developed a portable, handheld imaging probe for use in the primary care setting and evaluated its tissue site accessibility, ability to observe diseased tissue, and screening capabilities in in vivo human patients, particularly for pathologies related to the eye, ear and skin. Various stages of diabetic retinopathy were investigated using the handheld probe and early-stage diabetic retinopathy was flagged as abnormal from the OCT images. At such early stages of disease, it is difficult to observe abnormalities with the limited tools that are currently available to primary care physicians. These results indicate that OCT shows promise to transform from being a diagnostic technology in the medical and surgical specialities to a screening technology in the primary care office and at the front-line of healthcare.
Differential Effects of Semantic and Identity Priming in Patients with Left and Right Hemisphere Lesions (1993)

Abstract Patients with single brain lesions in the anterior or posterior left and right hemispheres and a group of controls were studied in two priming experiments. The first experiment employed associative pairs (DOCTOR-NURSE) and the second employed identical pairs (NURSE-nurse). Short and long prime-target stimulus onset asynchronies (SOAs) (i.e., 250 and 1850 msec) were manipulated within block in both experiments. In the first experiment, patients with left hemisphere injury showed a deficient priming effect while patients with right hemisphere injury and controls showed a normal pattern. In contrast, all groups showed an identity priming effect in the second experiment. These results indicate that while entries in the mental lexicon are available for the groups of patients studied, the spread of activation to related concepts in this lexicon is disrupted in the left hemisphere-damaged group.
Improved gas exchange and survival after KL‐4 surfactant in newborn pigs with severe acute lung injury (2010)

In newborn pigs with severe HCl-induced ALI, treatment with KL-4 surfactant resulted in improved respiratory parameters, less dependent atelectasis, and improved short-term survival.
Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer (2020)

Rapidly proliferating tumor and immune cells need metabolic programs that support energy and biomass production. The amino acid glutamine is consumed by effector T cells and glutamine-addicted triple-negative breast cancer (TNBC) cells, suggesting that a metabolic competition for glutamine may exist within the tumor microenvironment, potentially serving as a therapeutic intervention strategy. Here, we report that there is an inverse correlation between glutamine metabolic genes and markers of T cell-mediated cytotoxicity in human basal-like breast cancer (BLBC) patient data sets, with increased glutamine metabolism and decreased T cell cytotoxicity associated with poor survival. We found that tumor cell-specific loss of glutaminase (GLS), a key enzyme for glutamine metabolism, improved antitumor T cell activation in both a spontaneous mouse TNBC model and orthotopic grafts. The glutamine transporter inhibitor V-9302 selectively blocked glutamine uptake by TNBC cells but not CD8+ T cells, driving synthesis of glutathione, a major cellular antioxidant, to improve CD8+ T cell effector function. We propose a "glutamine steal" scenario, in which cancer cells deprive tumor-infiltrating lymphocytes of needed glutamine, thus impairing antitumor immune responses. Therefore, tumor-selective targeting of glutamine metabolism may be a promising therapeutic strategy in TNBC.
In-situ microscale through-silicon via strain measurements by synchrotron x-ray microdiffraction exploring the physics behind data interpretation (2014)

In-situ microscale thermomechanical strain measurements have been performed in combination with synchrotron x-ray microdiffraction to understand the fundamental cause of failures in microelectronics devices with through-silicon vias. The physics behind the raster scan and data analysis of the measured strain distribution maps is explored utilizing the energies of indexed reflections from the measured data and applying them for beam intensity analysis and effective penetration depth determination. Moreover, a statistical analysis is performed for the beam intensity and strain distributions along the beam penetration path to account for the factors affecting peak search and strain refinement procedure.
Hydrogen effects on the thermal conductivity of delocalized vibrational modes in amorphous silicon nitride (a−SiNx:H) (2021)

Hydrogenated amorphous dielectric thin films are critical materials in a wide array of technologies. In this work, we present a thorough investigation of the thermal conductivity of hydrogenated amorphous silicon nitride $(a\text{\ensuremath{-}}{\mathrm{SiN}}_{x}:\mathrm{H})$, a ubiquitously used material in which the stoichiometry plays a direct role in its functionality and application. In particular, through chemical, vibrational, and structural analysis in tandem with thermal conductivity measurements on chemically variant silicon nitride films, we show that hydrogen incorporation into silicon nitride disrupts the bonding among silicon and nitrogen atoms, and directly impacts the thermal conductivity, leading to as much as a factor of 2.5 variation in heat transfer. This variability, driven by the change in hydrogen content, is fundamentally related to the changes in the average atomic distances, as we experimentally measure with selected-area electron diffraction and computationally show with molecular dynamics simulations. This, combined with our evidence of chemical and spatial fluctuations on the order of average atomic pair distances, leads us to conclude that the vibrational heat transport in $a\text{\ensuremath{-}}{\mathrm{SiN}}_{x}:\mathrm{H}$ is primarily dominated by diffusonlike modes. The results presented in this work combined with our extensive review of prior reports on the thermal conductivity of $a\text{\ensuremath{-}}{\mathrm{SiN}}_{x}:\mathrm{H}$ films resolves discrepancies in decades of prior literature and facilitates a more universal understanding of the vibrational heat transport processes in hydrogenated amorphous silicon nitride.
Acoustic Green Synthesis of Graphene-Gallium Nanoparticles and PEDOT:PSS Hybrid Coating for Textile To Mitigate Electromagnetic Radiation Pollution (2022)

Solid matrix-supported liquid metal nanoparticles have been drawing attention as a nanoadditive in the fabrication of electroconductive flexible and soft materials. The present work reports a facile, green, and sonochemical synthesis approach of gallium (Ga) nanoparticles embedded in reduced graphene oxide (RGO) under ambient conditions for the first time. The as-synthesized ultrasonic energy-irradiated RGO/Ga nanocomposite was studied using SEM, TEM, DSC, XRD, XPS, and solid-state NMR. Because of their electrical conductivity, RGO/Ga nanoparticles have been used as a conducting inclusion for a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) matrix and coated on cotton fabrics to develop a smart e-textile for electromagnetic (EM) radiation-shielding application. In the X-band (8.2–12.4 GHz) frequency range, the nanocomposites’ EM interference-shielding efficiency was about 34 dB. Moreover, because of the liquid metal–graphene interfaces; the fabricated materials were excellent heat conductors reporting ∼44% increment in thermal conductivity compared to a bare fabric. The coated cotton textile’s durability was tested under various conditions. The hard phase of the RGO/Ga nanoparticles is disseminated throughout the fabric, while the polymeric soft phase, that is, PEDOT:PSS macrochains, tended to interlink among the dispersed phases to construct a large spatial conducting network. Therefore, such a lightweight, flexible, and conductive e-fabric could be used not only for mitigating EM pollution but also as an alternative to commercial metallic EM wave absorbers in telecommunication, aerospace, and next-generation flexible electronics areas.
Stochastic macromodeling for hierarchical uncertainty quantification of nonlinear electronic systems (2015)

A hierarchical stochastic macromodeling approach is proposed for the efficient variability analysis of complex nonlinear electronic systems. A combination of the Transfer Function Trajectory and Polynomial Chaos methods is used to generate stochastic macromodels. In order to reduce the computational complexity of the model generation when the number of stochastic variables increases, a hierarchical system decomposition is used. Pertinent numerical results validate the proposed methodology.
A modular atomic force microscopy approach reveals a large range of hydrophobic adhesion forces among bacterial members of the leaf microbiota (2019)

Bacterial adhesion is the initial step in surface colonization and community formation. At the single-cell level, atomic force microscopy (AFM) techniques have enabled the quantification of adhesive forces between bacteria and substrata. However, conventional techniques depend on the irreversible immobilization of cells onto cantilevers, thus hampering throughput. Here, we developed a modular AFM method to reversibly immobilize functionalized beads as surface mimic and to probe adhesion of individual bacteria. We performed single-cell force spectroscopies with phylogenetically diverse leaf isolates of various size and morphology. Adhesion measurement of 28 bacterial strains revealed large differences in hydrophobic interactions of about three orders of magnitude. The highest adhesion forces of up to 50 nN were recorded for members of the Gammaproteobacteria. The hydrophobicity of the different isolates correlated positively with the retention of bacteria observed in planta and might provide a basis for successful leaf colonization and potentially disease outbreaks of pathogens.
Biventricular defibrillation with sequential shocks using patient-derived computational models (2002)

Standard transvenous defibrillation is performed with implantable cardioverter defibrillators (ICD) using a dual-current pathway. The defibrillation energy is delivered from the right ventricle (RV) electrode to the superior vena cava (SVC) electrode and the ICD metallic housing. Clinical studies of biventricular defibrillation, which uses an additional electrode, placed on the left ventricular (LV) free wall, in conjunction with sequential shocks, have reported a 50% reduction in defibrillation threshold (DFT) energy. The goal of our study is to use computational methods to examine the biventricular defibrillation fields together with their corresponding DFTs, and to compare to standard defibrillation. Thoracic models derived from 5 patients were used in this study. The computational models were created from segmented CT images. The electric field distribution during defibrillation was computed using the finite volume method. The critical mass hypothesis was used to define a successful shock and to calculate the DFT. Our simulations show that the biventricular lead system reduces the DFT by 30% in comparison to standard configuration in 3 of the models and increases DFT up to 12% in the remaining 2. These results are consistent with clinical reports and suggest that patient-specific computational models may be able to identify those patients who could benefit from biventricular defibrillation.
Engraftment of donor cells with germ-line integration of HHV6 mimics HHV6 reactivation following cord blood/haplo transplantation (2014)

To the editor:

Human herpes virus 6 (HHV-6) infection occurs in >95% of the population before the age of 2 years and remains latent in adults.[1][1] Although HHV-6 reactivation commonly occurs following cord-blood transplantation, the majority of cases are self-limiting. A minority who reactivate
Secure indoor positioning: Relay attacks and mitigation using presence sensing systems (2015)

Secure indoor positioning is critical to successful adoption of location-based services in buildings. However, positioning based on off-the-air signal measurements is prone to various security threats. In this paper, we provide an overview of security threats encountered in such indoor positioning systems, and particularly focus on the relay threat. In a relay attack, a malicious entity may gain unauthorized access by introducing a rogue relay device in a zone of interest, which is then validly positioned by the location network, and then transfer the control rights to a malicious device outside the zone. This enables the malicious entity to gain access to the application network using the rogue device. We present multiple solutions relying on a presence sensing system to deal with this attack scenario. In one solution, a localized presence sensing system is used to validate the user presence in the vicinity of the position before location-based control is allowed. In another solution, the user device is required to respond to a challenge by a physical action that may be observed and validated by the presence sensing system.