gebhart/patrepeval huggingface dataset:
Beta-Secretase: Structure, Function, and Evolution (2008)

The most popular current hypothesis is that Alzheimer's disease (AD) is caused by aggregates of the amyloid peptide (Abeta), which is generated by cleavage of the Abeta protein precursor (APP) by beta-secretase (BACE-1) followed by gamma-secretase. BACE-1 cleavage is limiting for the production of Abeta, making it a particularly good drug target for the generation of inhibitors that lower Abeta. A landmark discovery in AD was the identification of BACE-1 (a.k.a. Memapsin-2) as a novel class of type I transmembrane aspartic protease. Although BACE-2, a homologue of BACE-1, was quickly identified, follow up studies using knockout mice demonstrated that BACE-1 was necessary and sufficient for most neuronal Abeta generation. Despite the importance of BACE-1 as a drug target, development has been slow due to the incomplete understanding of its function and regulation and the difficulties in developing a brain penetrant drug that can specifically block its large catalytic pocket. This review summarizes the biological properties of BACE-1 and attempts to use phylogenetic perspectives to understand its function. The article also addresses the challenges in discovering a selective drug-like molecule targeting novel mechanisms of BACE-1 regulation.
Interactively visualizing procedurally encoded scalar fields (2004)

While interactive visualization of rectilinear gridded volume data sets can now be accomplished using texture mapping hardware on commodity PCs, interactive rendering and exploration of large scattered or unstructured data sets is still a challenging problem. We have developed a new approach that allows the interactive rendering and navigation of procedurally-encoded 3D scalar fields by reconstructing these fields on PC class graphics processing units. Since the radial basis functions (RBFs) we use for encoding can provide a compact representation of volumetric scalar fields, the large grid/mesh traditionally needed for rendering is no longer required and ceases to be a data transfer and computational bottleneck during rendering. Our new approach will interactively render RBF encoded data obtained from arbitrary volume data sets, including both structured volume models and unstructured scattered volume models. This procedural reconstruction of large data sets is flexible, extensible, and can take advantage of the Moore's Law cubed increase in performance of graphics hardware.
Clinicopathologic Features and Long-term Outcomes of NUT Midline Carcinoma (2012)

NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.
A Mental Health Database Creation Method with Neuroscience-Inspired Search Functions (2020)

Mental health, an essential factor for maintaining a high quality of life, is determined by one’s nutritional, physical, and psychological situations. Since mental health is influenced by multiple factors, a multidisciplinary approach is effective. Due to the complexity of this mechanism, most non-specialists have little knowledge and access to the related information. There are multiple factors that influence one’s mental health, such as nutrition, physical activities, daily habits, and personal cognitive characteristics. Because of this complexity, it can be hard for non-specialists to find and implement appropriate methods for improving their mental health. This paper presents the 2-Phase Correlation Computing method for interpreting the characteristics of each emotion/mental state, nutrients, exercises, life habits with a vector space. The vector space reflects the roles of neurotransmitters. The 2-Phase Correlation Computing extracts the information expected to be most relevant to the user’s request. In this method, expert knowledge, characteristics of emotions, and mental states are defined in the “Requests” Matrix, and each stimulus into “Nutrients”, “Exercises”, and “Life Habits” Matrixes. “Nutrients”, “Exercises”, and “Life Habits” are expressed and computed to as “Stimuli”. In short, this method introduces logos to the chaotic world of decision making in mental health.
Photophysics of Sulfur-Containing Centers on AgBr Surfaces (2002)

Silver halide microcrystals, the basic element in photographic products, are commonly reacted with labile sulfur-containing compounds to increase their photographic efficiency (speed). Such “sulfur-sensitized” AgBr microcrystals have been examined with computational and photophysical techniques. Density functional and lattice-relaxation computations have given estimates of the optical transition energies and the electron- and hole-trapping abilities of a number of small sulfur-containing clusters that may be deposited on, or buried in, an AgBr surface. These data indicate that single sulfides, whatever their structure, are not deep traps for electrons or holes. Disulfides, in general, can trap holes and certain structures; for example, a disulfide at a double-kink site can trap electrons. Computations indicate that single sulfides substituted for a halogen in the (001) surface and charge compensated with an interstitial silver ion in the surface or in the bulk do not trap electrons; neither do disulfides in the bulk. A single sulfide substituted for a bromide at a positive kink and compensated with an interstitial silver ion appears to be capable of initiating the formation of small, stable silver clusters (Agn, n ≈ 4) that become “latent image”, the centers that eventually lead to a visible photographic image. Photographic data from sulfur-sensitized AgBr microcrystals indicate that the optimum formal sulfur level is about 10 000 S atoms/μm2. Radio-frequency photoconductivity measurements show that deposited sulfur centers trap photoelectrons. The optimum and higher levels of sulfur deposited on the surface of AgBr microcrystals produce an absorption band (∼525 nm) and associated low-temperature luminescence (∼725 nm). The luminescence lifetime behavior and ODMR data clearly indicate that this sulfur-related absorption and emission is due to a donor−acceptor processes. ODMR spectra obtained by monitoring the intrinsic AgBr luminescence (590 nm) have a resonance that is assigned to a Ag2+ center. This Ag2+ species is thought to arise from a silver dimer associated with a sulfur species at the surface.
Overexpression of the LexA-regulated tisAB RNA in E. coli inhibits SOS functions; implications for regulation of the SOS response (2008)

The DNA damage induced SOS response in Escherichia coli is initiated by cleavage of the LexA repressor through activation of RecA. Here we demonstrate that overexpression of the SOS-inducible tisAB gene inhibits several SOS functions in vivo. Wild-type E. coli overexpressing tisAB showed the same UV sensitivity as a lexA mutant carrying a noncleavable version of the LexA protein unable to induce the SOS response. Immunoblotting confirmed that tisAB overexpression leads to higher levels of LexA repressor and northern experiments demonstrated delayed and reduced induction of recA mRNA. In addition, induction of prophage lambda and UV-induced filamentation was inhibited by tisAB overexpression. The tisAB gene contains antisense sequences to the SOS-inducible dinD gene (16 nt) and the uxaA gene (20 nt), the latter encoding a dehydratase essential for galacturonate catabolism. Cleavage of uxaA mRNA at the antisense sequence was dependent on tisAB RNA expression. We showed that overexpression of tisAB is less able to confer UV sensitivity to the uxaA dinD double mutant as compared to wild-type, indicating that the dinD and uxaA transcripts modulate the anti-SOS response of tisAB. These data shed new light on the complexity of SOS regulation in which the uxaA gene could link sugar metabolism to the SOS response via antisense regulation of the tisAB gene.
Closed-loop control of a woofer–tweeter adaptive optics system using wavelet-based phase reconstruction (2010)

A novel closed-loop control technique for adaptive optics (AO) systems based on a wavelet-based phase reconstruction technique and a woofer-tweeter controller is presented. The wavelet-based reconstruction technique is based on obtaining a Haar decomposition of the phase screen directly from gradient measurements and has been extended here with the use of a Poisson solver to improve performance. This method is O(N) (i.e., a linear computation cost as number of actuators increases) and is the fastest of the known O(N) reconstruction techniques. The controller configuration is based on the woofer-tweeter controller to control low- and high-spatial-frequency aberrations, respectively. The separation of the woofer and tweeter signals is done using a computationally efficient method that is based on the availability of a low-spatial-resolution reconstruction during the wavelet synthesis process. The performance of the proposed technique is evaluated using a simulated AO system and phase screens generated to reflect atmospheric turbulence with various dynamic characteristics. Results indicate that the combination of the wavelet-based phase reconstruction and woofer-tweeter controller leads to very good results with respect to speed and accuracy.
ASIC for 1-GHz wide band monobit receiver (2002)

An ASIC for a wide band (1 GHz) digital monobit receiver designed for processing two simultaneous signals will be described. The receiver consists of three major elements: (1) a nonlinear radio frequency (RF) front-end, (2) a signal sampler and formatting system (analog-to-digital converter (ADC) and demultiplexers), and (3) a monobit algorithm implemented as an ASIC for signal detection and frequency measurement. The receiver uses a two-bit ADC operating at 2.5 GHz whose outputs are collected and formatted by demultiplexers for presentation to the ASIC. The ASIC has two basic functions: (1) perform a fast Fourier transform (FFT) and (2) determine the number of signals and report their frequencies.
Energy scaling of mode-locked fiber lasers with chirally-coupled core fiber (2011)

We report a mode-locked dissipative soliton laser based on large-mode-area chirally-coupled-core Yb-doped fiber. This demonstrates scaling of a fiber oscillator to large mode area in a format that directly holds the lowest-order mode and that is also compatible with standard fiber integration. With an all-normal-dispersion cavity design, chirped pulse energies above 40 nJ are obtained with dechirped durations below 200 fs. Using a shorter fiber, dechirped durations close to 100 fs are achieved at pump-limited energies. The achievement of correct energy scaling is evidence of single-transverse-mode operation, which is confirmed by beam-quality and spectral-interference measurements.
On the microscopic origin of the frequency dependence of hole trapping in pMOSFETs (2012)

A detailed understanding of the physical mechanisms behind hole capture in pMOSFETs is essential for a number of reliability issues, including the negative bias temperature instability (NBTI), hot carrier degradation, random telegraph and 1/f noise. In order to better understand the controversial frequency dependence of NBTI, we study the frequency dependence of hole capture on individual defects by extending the time-dependent defect spectroscopy (TDDS) to the AC case. Conventionally, hole capture is explained by a first-order process using effective capture and emission time constants, τ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> and τ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">β</sub> . Our experimental data clearly reveals, however, that this assumption is incorrect under higher frequencies where modern digital applications typically operate. In particular, the frequency dependence visible in these effective capture times clearly confirms that hole capture must occur via an intermediate metastable state. Interestingly, the metastable state we have previously introduced to explain the DC-TDDS data also fully explains the AC-TDDS case.
Influence of heterogeneities on liver steatosis evaluation by Fibroscan® (CAP™): relevance of a liver guidance tool (2013)

Purpose: Controlled Attenuation Parameter (CAP) is a measure of ultrasound attenuation developed to assess steatosis on the Fibroscan®. CAP performance in clinical studies always showed satisfactory results. However, CAP is based on the hypothesis that liver parenchyma is homogeneous whereas it is not everywhere (blood vessel, nodules, etc.). The objective of here is to determine the influence of heterogeneities on CAP and show the clinical relevance of a liver guidance tool, developed to target the homogeneous parenchyma.
Nerve Stimulator-guided Injection of Autologous Stem Cells Near the Equine Left Recurrent Laryngeal Nerve (2018)

Recurrent laryngeal neuropathy (RLN) commonly affects horses and is characterized by abnormal respiratory sounds and exercise intolerance. The recurrent laryngeal nerve shows lesions of demyelination. The benefit of applying stem cells to demyelinated nerves has been demonstrated in various animal models. The aim of the study was to test the feasibility and safety of a peri-neuronal injection of autologous muscle-derived mesenchymal stem cells to the left recurrent laryngeal nerve in healthy horses by using an electrical nerve stimulator. Muscle-derived stems cell are obtained from five healthy Standardbred horses by sampling 20 mg of muscle tissue with a semi-automatic 14 G biopsy needle from the triceps muscle. Movements of the larynx are monitored via upper-airway video endoscopy. The left recurrent laryngeal nerve is approached with an insulated nerve block needle. Nerve stimulation is applied, starting at 2 mA, and the successful abduction of the left arytenoid is monitored. The stimulation intensity is reduced progressively. When a loss of the motor response is observed at 0.5 mA, 107 autologous muscle-derived stem cells are injected. Two examiners, who are blinded to the time point, score the laryngeal function of the horses prior to the treatment and at day 1, day 7, and day 28 after the injection of the cells. In a sixth horse, 1 mL of 2% lidocaine is injected to further confirm the correct positioning of the needle. This leads to a temporary paralysis of the left arytenoid cartilage. This study proves that the recurrent laryngeal nerve can be approached with the help of an electrical nerve stimulator and that the electrical stimulation of the nerve is well tolerated by the horses. No modification of the laryngeal function was observed in any of the horses after the injection of the stem cells. Further studies should be conducted to describe the effects of a peri-neuronal injection of autologous muscle-derived mesenchymal stem cells to horses suffering from RLN.
Species-Specific Differences in the Expression and Regulation of α4β7 Integrin in Various Nonhuman Primates (2015)

Among nonhuman primates, SIV-infected Asian pigtailed macaques (PM) are relatively more susceptible to infection and disease progression than SIV-infected rhesus macaques (RM). In addition, SIV-infected African natural hosts such as the sooty mangabeys (SM) are resistant to disease. The mechanisms associated with such species-related variable clinical outcomes remain ill-defined but hold the potential to provide insights into the underlying mechanisms surrounding HIV pathogenesis. Recent findings indicate that the expression of the heterodimeric gut homing integrin α4β7 can influence both susceptibility and disease progression in RM. It was reasoned that differences in the frequencies/surface densities of α4β7-expressing lymphocytes might contribute to the differences in the clinical outcome of SIV infection among NHPs. In this article, we report that CD4(+) T cells from PM constitutively express significantly higher levels of α4β7 than RM or SM. Retinoic acid, a key regulator of α4β7 expression, was paradoxically found at higher levels in the plasma of SM versus RM or PM. We also observed pairing of β7 with αE (αEβ7) on CD4(+) T cells in the peripheral blood of SM, but not PM or RM. Finally, the differential mean density of expression of α4β7 in RM versus SM versus PM was predominantly dictated by species-specific sequence differences at the level of the β7 promoters, as determined by in vitro reporter/promoter construct transfection studies. We propose that differences in the regulation and expression of α4β7 may explain, in part, the differences in susceptibility and SIV disease progression in these NHP models.
Syntheses and nonlinear absorption properties of conjugated porphyrin supramolecules (2007)

Self-assemblies consisting of acetylene-linked bisporphyrins with a 4-nitrophenylethynyl substituent and with a phenylethynyl substituent were synthesized. The Q-band of the phenylethynyl-substituted compound appears at 762 nm whereas that of the 4-nitrophenylethynyl-substituted one was red-shifted to 784 nm and intensified. This may be attributed to the participation of the nitro group in the π-electronic communication system. HOMOs and LUMOs were calculated for these compounds using an INDO/S-CI method. The effective two-photon absorption cross-section values of these self-assemblies were measured by using a nanosecond open aperture Z-scan method. The maximum effective two-photon absorption cross-section values of 4-nitrophenylethynyl- and phenylethynyl-substituted bisporphyrins were obtained as 1.2 × 10 5 GM and 8.1 × 10 4 GM , respectively, at 890 nm. A 1.5 enhancement factor was obtained by introducing nitro groups, which was similar to the value previously reported for ferrocene- and fullerene-connected supramolecular porphyrin.
Photosensitiser delivery for photodynamic therapy. Part 2: systemic carrier platforms (2008)

PS conjugates and supramolecular delivery platforms can improve PDT selectivity by exploiting cellular and physiological specificities of the targeted tissue. Overexpression of receptors in cancer and angiogenic endothelial cells allows their targeting by affinity-based moieties for the selective uptake of PS conjugates and encapsulating delivery carriers, while the abnormal tumour neovascularisation induces a specific accumulation of heavy weighted PS carriers by enhanced permeability and retention (EPR) effect. In addition, polymeric prodrug delivery platforms triggered by the acidic nature of the tumour environment or the expression of proteases can be designed. Promising results obtained with recent systemic carrier platforms will, in due course, be translated into the clinic for highly efficient and selective PDT protocols.
<i>Ab-initio</i> calculation of excited state absorption of Cr4+ in Y3Al5O12 (1999)

The Cr3+ and Cr4+ impurity states in Y3Al5O12 (YAG) crystal are studied by ab-initio supercell calculations using the density-functional theory. Calculations are carried out with Cr substitutions at the octahedral and tetrahedral Al sites including the effect of Ca co-doping. Optical transitions between various levels and to conduction band states are also calculated. A model for excited state absorption for Cr4+ in YAG is proposed.
Mouse (C57BL/KsJ) liver phosphofructokinase. Allosteric kinetics and age-related changes in the genetically diabetic state. (1981)

The regulatory kinetic properties of phosphofructokinase partially purified from the livers of C57BL/KsJ mice were studied. The fructose 6-phosphate saturation curves were highly pH dependent. At a fixed MgATP concentration (1 mM), allosteric kinetics was observed in the range of pH studied (7.3 to 8.3) and the S0.5 values for fructose 6-phosphate decreased by about 0.2 to 0.3 mM for each 0.1-unit increment in pH. Allosteric effects on the sigmoidal response to fructose 6-phosphate: activation by AMP, NH4+, and glucose 1,6-bisphosphate, inhibition by MgATP2-, and synergistic inhibition between ATP and citrate, were all present at pH 8.0 to 8.2. Comparative kinetic studies with liver phosphofructokinase isolated from both the normal (C57BL/KsJ) and the genetically diabetic (C57BL/KsJ-db) mice of 9 to 10 and 15 to 16 weeks of age showed that the enzyme from the livers of diabetic mice exhibited decreased activity at subsaturating concentrations of fructose 6-phosphate. However, phosphofructokinase isolated from the livers of normal and genetically diabetic mice of 4 to 5 weeks of age showed no difference in kinetic properties. Thus, there appears to be a correlation between the change in properties of liver phosphofructokinase and the expression of hyperglycemia and obesity in the genetically diabetic mice. The decreased activity of liver phosphofructokinase in the older diabetic animals may well be one of the causes of the increased blood glucose levels. The results are also discussed in a general context with regard to the possible role of phosphofructokinase in the regulation of hepatic gluconeogenesis.
New highly active and selective Et oligomerization catalysts based on cationic diamide zirconium complexes (2001)

Group 4 complexes based on the diamide ligand, [Me3CN(SiMe2)2NCMe3]2−, have been investigated as possible catalysts for olefin conversions. The dialkyl complexes, (Me2SiNCMe3)2ZrR2 (R = CH2Ph, Me), were converted into zwitterionic (X-ray: {Me2SiNCMe3}2Zr(η1-Bz){ηn-BzB(C6F5)3}), or cationic mono-alkyl compounds by reaction with B(C6F5)3 or borate reagents. These electrophilic species catalyzed ethylene oligomerization, affording highly linear alpha-olefins under mild conditions (C6 fraction > 99.5% 1-hexene at 50°C, 6 bar). The highest activities (290 Kg/g Zr.h) were obtained in toluene solvent using tri-iso-butylaluminium (TIBA) as scavenger. The catalyst exhibited activity decay in alkane solvent, which was countered by replacement of TIBA by more crowded trialkylaluminium scavengers or branched alkylaluminoxane scavengers. The product consisted primarily of linear alpha-olefins (LAO) with low levels of remote-branched AO's. These are formed by successive insertion of higher olefin and one or more ethylenes in a growing chain, followed by chain transfer.
Thirty years of progress in shallow water acoustics in Russia (2012)

The paper presents an overview of main results achieved in the field of shallow water acoustics in Russia. The results may be divided into two groups. The first represents development of the novel physical equipment for acoustic probing. The second group is associated with the experimental and theoretical research of sound propagation and scattering on oceanic shelf in the presence of regular and random inhomogeneities of different nature.