gebhart/patrepeval huggingface dataset:
An Enzyme Module System for in situ Regeneration of Deoxythymidine 5′‐Diphosphate (dTDP)‐Activated Deoxy Sugars (2007)

Abstract A highly flexible enzyme module system (EMS) was developed which allows for the first time the in situ regeneration of deoxythymidine 5′‐diphosphate (dTDP)‐activated deoxy sugars and furthermore enables us to produce novel sorangiosides in a combinatorial biocatalytic approach using three enzyme modules. The SuSy module with the recombinant plant enzyme sucrose synthase (SuSy) and the deoxy sugar module consisting of the enzymes RmlB (4,6‐dehydratase), RmlC (3,5‐epimerase) and RmlD (4‐ketoreductase) from the biosynthetic pathway of dTDP‐β‐ L ‐rhamnose were combined with the glycosyltransferase module containing the promiscuous recombinant glycosyltransferase SorF from Sorangium cellulosum So ce12. Kinetic data and the catalytic efficiency were determined for the donor substrates of SorF: dTDP‐α‐ D ‐glucose, dTDP‐β‐ L ‐rhamnose, uridine diphosphate (UDP)‐α‐ D ‐glucose (Glc), and dTDP‐6‐deoxy‐4‐keto‐α‐ D ‐glucose. The synthesis of glucosyl‐sorangioside with in situ regeneration of dTDP‐Glc was accomplished by combination of SuSy and SorF. The potential of the EMS is demonstrated by combining SuSy, RmlB, RmlC, RmlD with SorF in one‐pot for the in situ regeneration of dTDP‐activated (deoxy) sugars. The HPLC/MS analysis revealed the formation of rhamnosyl‐sorangioside and glucosyl‐sorangioside, demonstrating the in situ regeneration of dTDP‐β‐ L ‐rhamnose and dTDP‐α‐ D ‐glucose and a cycle number for dTDP higher than 9. Furthermore, NADH (reduced form of nicotinamdie adenine dinucleotide) regeneration with formate dehydrogenase in the reduction step catalyzed by the 4‐ketoreductase RmlD could be integrated in the one‐pot synthesis yielding similar conversion rates and cycle numbers. In summary, we have established the first in situ regeneration cycle for dTDP‐activated (deoxy) sugars by a highly flexible EMS which allows simple exchange of enzymes in the deoxy sugar module and exchange of glycosyltransferases as well as aglycones in the glycosyltransferase module to synthesize new hybrid glycosylated natural products in one‐pot.
The Combination Of JAK Inhibitor, Ruxolitinib, and PIM Inhibitor, LGH447, In Preclinical Models Of Myeloproliferative Neoplasia (2013)

Abstract Background The JAK-STAT pathway is an important signaling pathway downstream of multiple cytokine and growth factor receptors. It has been implicated in the pathogenesis of multiple human diseases. The genetic aberration of JAK2V617F and the associated activation of STAT in myeloproliferative neoplasia (MPN) is one example of the involvement of this pathway in human cancer. Activated JAKs phosphorylate STAT proteins, which then dimerize and translocate to the nucleus. Inside the nucleus, activated STATs modulate the expression of target genes, including PIM1. PIM kinases are involved in the regulation of cell cycle and proliferation. Recent studies have suggested that PIM1 is one of the key signature genes for STAT5 activation. Based on the biological rationale, we set out to test the combination of the JAK inhibitor, ruxolitinib, and the PIM inhibitor, LGH447, in MPN preclinical models. Methods and Results The combination of ruxolitinib and LGH447 was tested in vitro against MPN cell lines harboring JAK2V617F mutations. In vitro synergy was observed with the combination of ruxolitinib and LGH447 in UKE-1 and SET2 models. Pharmacodynamic analysis indicates potent modulation of PIM1/2 and pSTAT3/5 by LGH447 and ruxolitinib, respectively. Both agents inhibited pERK and pS6 in UKE-1. The combination achieved greater suppression on these two signaling pathways. In addition, the combination further inhibited pBAD and MCL-1 expression, with the corresponding increase of cleaved PARP. This combination was further tested in a mouse MPN model with BA/F3 cells harboring EPOR-JAK2V617F. Ruxolitinib monotherapy down-modulated overall disease burden and reduced spleen weight. It also inhibited pSTAT5 and pMEK in this model. LGH447 monotherapy had a more modest effect on MPN disease burden. The combination of ruxolitinib and LGH447 resulted in much greater reduction of overall disease burden and spleen weight than either agent alone (Figure). The combination also normalized hemoglobin levels and red blood cell counts in this model. Summary This finding suggests potential benefit with the combination of ruxolitinib and LGH447 in MPN. By targeting two critical signaling molecules in the JAK/STAT axis, this combination may achieve greater target modulation across key oncogenic pathways, such as MAPK and TOR. This may enable us to achieve greater benefit against MPN in the clinic. Disclosures: Saci: Novartis: Employment, Equity Ownership. Pinzon-Ortiz:Novartis Institutes for BioMedical Research, Inc.: Employment. Wang:Novartis: Employment. Rong:Novartis: Employment. Growney:Novartis: Employment, Equity Ownership. Squier:Novartis Pharmaceuticals Corp.: Employment. Radimerski:Novartis Pharma AG: Employment, Equity Ownership. Vanasse:Novartis Institutes of BioMedical Research: Employment. Caponigro:Novartis: Employment, Equity Ownership. Garcia:Novartis: Employment, Equity Ownership. Cao:Novartis: Employment, Equity Ownership.
Saposin C: Neuronal Effect and CNS Delivery by Liposomes (2005)

A bstract : Saposin C is one of four small lipid‐binding proteins that derive from a single precursor protein, named prosaposin (PSAP). PSAP has several neuronal effects, including neurite outgrowth stimulation, neuron preservation, and nerve regeneration enhancement. A minimal domain required for PSAP's neurotrophic function is located in the amino‐terminal half of saposin C. Genetic defects of the PSAP gene in humans and mice lead to a complex lysosomal storage disease. The skin fibroblasts from PSAP‐ and saposin C‐deficient patients have a massive accumulation of multivesicular bodies (MVBs). Incorporation of exogenous saposin C‐containing liposomes into the cultured PSAP−/− cells reduced the accumulated MVBs to normal levels. Internalized saposin C was localized to late endosomes and lysosomes. MVBs are crucial for maintaining the cellular homeostasis required for neuronal development and growth. PSAP−/− mice have a short life span (30 days) and central nervous system (CNS) neuronal degeneration. Similar to PSAP−/− fibroblasts, excessive MVBs accumulated in CNS neurons and brain tissues of PSAP‐null mice. Cultured cortical and hippocampal neurons from PSAP−/− mice had poor survival and displayed a neurite degenerative pattern. Delivery of saposin C ex vivo into cultured neurons and in vivo into brain neuronal cells in mice across the blood‐brain barrier was accomplished with intravenously administered dioleoylphosphatidylserine (DOPS) liposomes. These studies may yield a new therapeutic approach for neuron protection, preservation, and regeneration.
Synthesis of Terpolymers with Homogeneous Composition by Free Radical Copolymerization of Maleic Anhydride, Perfluorooctyl and Butyl or Dodecyl Methacrylates: Application of the Continuous Flow Monomer Addition Technique (2017)

Terpolymers of homogeneous composition were prepared by free radical copolymerization of butyl or dodecyl methacrylate, 1<i>H</i>,1<i>H</i>,2<i>H</i>,2<i>H</i>-perfluorodecyl methacrylate and maleic anhydride using the continuous monomer addition technique. The copolymerization reactions were performed at 65 °C in the presence of azobisisobutyronitrile as an initiator in a mixture of methyl ethyl ketone and 1,3-bis (trifluoromethyl)benzene. The monomers and initiator are added to the reaction mixture with the same rate they are consumed in 5- and 10-fold excess compared to the initial monomer stock. The obtained terpolymers with molecular weights <i>M</i><sub>n</sub> = 50,000⁻70,000 are of uniform composition, close to the composition determined in low conversion experiments, proving the principle of the chosen concept. The kinetic data necessary for the design of the continuous addition experiment were obtained from binary copolymerization experiments at low monomer conversion (to avoid compositional drift). In addition, the so-called terpolymerization parameter was determined from ternary copolymerization experiments.
Recent Advances in Hearing Aids (1953)

The experience gained in fitting a large number of impaired persons with hearing aids is presented, showing illustrative ranges of impairment between 30 and 100 decibels fitted with three progressively-powered hearing aids. General features of such hearing aids are discussed, showing circuits and arrangements for peak clipping and automatic gain control. The microphone and air and bone receivers are described, considering features developed for providing optimum reliability in service such as moisture proofing, and design arrangements providing miniaturization concomitant with ruggedness.
28‐2: A Novel Local Dimming algorithm with HDR for VR system based on GPU (2019)

As the screen of VR is very close to human eye and the optical lens has amplification effect, VR needs high PPI to meet people's visual requirements. High PPI panel with side‐emitting LED backlight is difficult to realize high contrast ratio(CR). Local Dimming based on direct‐illumination LED can not only save backlight power consumption but also improve the CR of the VR system. The point spread function(PSF) of LED plays an important role in Local Dimming technology. However traditional PSF always adopts approximate calculation method with low accuracy, which causes luminance distortion. In this paper, a method of PSF measurement and data processing was proposed. It can describe the spread strength and range of one single block LED actually. One improved LCD compensation algorithm was demonstrated in this paper. The light leakage characteristic of liquid crystal was considered. It can keep the hue consistent. The proposed Local Dimming method has low distortion and high dynamic contrast range. This paper also presents a method for implementing Local Dimming algorithm by GPU, which can display Local Dimming effect in real time of VR system with high frame rate.
Only strongly enhanced residual FDG uptake in early response PET (Deauville 5 or qPET ≥ 2) is prognostic in pediatric Hodgkin lymphoma: Results of the GPOH‐HD2002 trial (2018)

Only strongly enhanced residual FDG uptake in early response PET (vDS 5 or qPET ≥ 2, respectively) seems to be markedly prognostic in PHL when treatment according to the GPOH-HD-2002 protocol is given.
On Identifying Magnocellular and Parvocellular Responses on the Basis of Contrast-Response Functions (2010)

It has been proposed that magnocellular and parvocellular sensitivity in schizophrenic individuals can be assessed using steady-state visually evoked potentials (VEPs) to either low-contrast stimuli or stimuli whose contrast is modulated around a high contrast "pedestal" (Green MF, Butler PD, Chen Y, et al. Schizophr Bull. 2009;35:163-181). This suggestion faces 2 difficulties: (1) To use low-contrast stimuli to activate the magnocellular system is inconsistent with lesion studies that have shown that under many conditions, the parvocellular system responds to the lowest contrasts and (2) To rely on contrast-response relationships to identify magnocellular and parvocellular responses is difficult because other neurons exist in the visual system that have contrast-response relationships similar to those of magnocellular and parvocellular cells.
Measurement of acceleration in femtosecond laser-plasmas (1998)

Accelerations up to 4×1019 m/s2 are measured in femtosecond laser-produced plasmas at intensities of 1018 W/cm2 using the Frequency Resolved Optical Gating (FROG) technique. A high density plasma is formed by focusing an ultrashort unchirped laser pulse on a plane carbon target and part of the reflected pulse is eventually detected by a FROG autocorrelator. Radiation pressure and thermal pressure accelerate the plasma which causes a chirp in the reflected laser pulse. The retrieved phase and amplitude information reveal that the plasma motion is dominated by the large light pressure which pushes the plasma into the target. This is supported by theoretical estimates and by the results of independently measured time integrated spectra of the reflected pulse.
From the President: Doing Science by the Numbers (2006)

Society as a whole seems fascinated with attempts to quantify things. The emphasis (some would say overemphasis) on testing as a measure of both student success and quality of schools is one example.
9-Amino-1,2,3,4-Tetrahydroacridine Is a Potent Inhibitor of Histamine N-Methyltransferase. (1991)

The effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on histamine N-methyltransferase (HMT), an enzyme catalyzing the methylation of histamine to form tele-methylhistamine in the brain, was studied in vitro using a partially purified enzyme preparation from bovine brain and in vivo in the mouse brain. THA inhibited the HMT activity in competitive and non-competitive mixed type manners with respect to histamine. The Ki and Ki' values were 75 nM and 1.2 microM, respectively. The IC50 values for THA, 9-aminoacridine and physostigmine in the inhibition of HMT determined at fixed concentrations of histamine (20 microM) and S-adenosylmethionine (50 microM) were 0.2, 0.37 and 20 microM, respectively. Neostigmine exhibited only 15% inhibition even at a concentration of 100 microM. THA (2-10 mg/kg, s.c.) dose-dependently inhibited HMT in the mouse brain. The inhibition of HMT by THA (10 mg/kg) was marked at 30 and 60 min after treatment, but disappeared by 120 min after. THA (10 mg/kg) significantly increased the histamine level and decreased the tele-methylhistamine level in the mouse brain. These results indicate that THA is a potent inhibitor of HMT.
Induction of Twins in Cattle with Bilateral and Unilateral Embryo Transfer (1979)

One embryo was transferred to each uterine horn (bilateral transfer) of 21 Hereford cows and 21 Hereford heifers 5 days after estrus. Seventeen Hereford cows and 18 Hereford heifers were bred at estrus and received an additional embryo 5 days later transferred to the uterine horn contralateral to the corpus luteum (unilateral transfer). Pregnancy rates at 45 days from bilateral and unilateral transfers (cows and heifers combined) were 76% and 60%, respectively; twinning rates in pregnant recipients were 72% and 70%, respectively. Pregnancy rates at 45 days for cows and heifers (unilateral and bilateral transfers combined) were 71% and 67%, respectively. Twinning rates in these two parity groups were 75% and 67%, respectively. A lower pregnancy and twinning rate in the unilateral heifer group than in the other groups, presumably due to low fertility at AI, affected the pregnancy and twinning rates for unilateral transfers and for heifers. Birth weights were lower for twins than singles regardless of whether they were born to cows (P<.001) or heifers (P<.01). Twins produced by heifers were smaller at birth than twins produced by cows (P<.05), but the difference in the birth weight for singles from cows and singles from heifers was not significant. A shorter gestation period for twins than singles was observed in heifers (P<.01), but not in cows. The incidences of dystocia requiring assistance for dams producing twins and singles were 20% and 21%, respectively. The incidence of retained placenta was 14% for dams that produced twins and none for dams producing singles. Palpation per rectum either early (45days) or late (180 to 200 days) in pregnancy was shown to be effective for diagnosing twin pregnancy.
Eigenrays in 3D heterogeneous anisotropic media, Part I: Kinematics (2020)

ABSTRACT We present a new ray bending approach, referred to as the Eigenray method, for solving two‐point boundary‐value kinematic and dynamic ray tracing problems in 3D smooth heterogeneous general anisotropic elastic media. The proposed Eigenray method is aimed to provide reliable stationary ray path solutions and their dynamic characteristics, in cases where conventional initial‐value ray shooting methods, followed by numerical convergence techniques, become challenging. The kinematic ray bending solution corresponds to the vanishing first traveltime variation, leading to a stationary path between two fixed endpoints (Fermat's principle), and is governed by the nonlinear second‐order Euler–Lagrange equation. The solution is based on a finite‐element approach, applying the weak formulation that reduces the Euler–Lagrange second‐order ordinary differential equation to the first‐order weighted‐residual nonlinear algebraic equation set. For the kinematic finite‐element problem, the degrees of freedom are discretized nodal locations and directions along the ray trajectory, where the values between the nodes are accurately and naturally defined with the Hermite polynomial interpolation. The target function to be minimized includes two essential penalty (constraint) terms, related to the distribution of the nodes along the path and to the normalization of the ray direction. We distinguish between two target functions triggered by the two possible types of stationary rays: a minimum traveltime and a saddle‐point solution (due to caustics). The minimization process involves the computation of the global (all‐node) traveltime gradient vector and the traveltime Hessian matrix. The traveltime Hessian is used for the minimization process, analysing the type of the stationary ray, and for computing the geometric spreading of the entire resolved stationary ray path. The latter, however, is not a replacement for the dynamic ray tracing solution, since it does not deliver the geometric spreading for intermediate points along the ray, nor the analysis of caustics. Finally, we demonstrate the efficiency and accuracy of the proposed method along three canonical examples.
A low-voltage CMOS filter for hearing aids using dynamic gate biasing (2002)

In this paper we discuss the design of a low-voltage (1.5 V), continuous-time, biquadratic CMOS filter based on dynamic gate biasing (DGB), We begin by discussing the filter's structure and its tuning mechanism. The filter uses transconductance-C cells and implements low-pass, bandpass and high-pass transfer functions. The transconductances are tuned using the gate voltages of MOSFETs operating in the triode region. We review the principle of DGB, and discuss the design of the charge pump based on the filter's performance and tunability requirements. Circuit details of the filter elements and the charge pump are presented along with SPICE simulation results of the overall filter.
STUDYING INTERCLUSTER GALAXY FILAMENTS THROUGH STACKING gmBCG GALAXY CLUSTER PAIRS (2013)

We present a method to study the photometric properties of galaxies in filaments by stacking the galaxy populations between pairs of galaxy clusters. Using Sloan Digital Sky Survey data, this method can detect the inter-cluster filament galaxy overdensity with a significance of $\sim 5 \sigma$ out to $z=0.40$. Using this approach, we study the $g-r$ color and luminosity distribution of filament galaxies as a function of redshift. Consistent with expectation, filament galaxies are bimodal in their color distribution and contain a larger blue galaxy population than clusters. Filament galaxies are also generally fainter than cluster galaxies. More interestingly, the observed filament population seems to show redshift evolution at $0.12<z<0.40$: the blue galaxy fraction has a trend to increase at higher redshift: a filament "Butcher Oemler Effect". We test the dependence of the observed filament density on the richness of the cluster pair: richer clusters are connected by higher density filaments. We also test the spatial dependence of filament galaxy overdensity: this quantity decreases when moving away from the inter-cluster axis between a cluster pair. This method provides an economical way to probe the photometric properties of filament galaxies and should prove useful for upcoming projects like the Dark Energy Survey.
Neuroanatomical Mechanism for the Influence of Emotional Distracter On Working Memory Maintenance in Patients with Schizophrenia Using Functional Mri (2015)

The purpose of this study was to assess the influence of non-emotional and emotional distracters on working memory maintenance in schizophrenic patients and to demonstrate the associated brain areas. 16 schizophrenic patients and 16 healthy controls underwent 3.0T fMRI during a face recognition task with non-emotional (novel face pictures) and emotional (fear-provoking pictures) distracters. The paradigm consisted of 20 trials with the sequence “encoding – maintenance – distracter – retrieval”. As the encoding, three different human faces sequentially appear once on a quartile coordinate. Subjects were instructed to look at the distracters and maintain the memory for the encoded faces. In the retrieval, participants were presented either the previously encoded face or a new face, asked whether they recognize the face. We compared the accuracy and the brain activation maps by SPM 8. The accuracies were lower in schizophrenic patients than controls with non-emotional (52.6% and 65.4%, respectively, p<0.05) and emotional (53.3% and 65.6%, respectively, p<0.05) distracter. For non-emotional distracter, schizophrenic patients showed significantly increased activation in superior frontal gyrus, dorsolateral prefrontal gyrus, ventrolateral prefrontal gyrus (VLPFG), superior parietal gyrus (SPG), inferior parietal gyrus, anterior cingulate gyrus, and fusiform gyrus (FG) (p<0.001). And for emotional distracter, patients showed increased in VLPFC, SPG, FG, hippocampus, parahippocampal gyrus, amygdale, superior and middle temporal gyrus, middle and inferior occipital gyrus (p<0.001). There was significant difference of neuroanatomy associated with the effects of non-emotional and emotional distracters in schizophrenia. Working memory of schizophrenic patients was significantly influenced by emotional distracters.
A proton induced conformational change in metal complexes with potential hydrogen bonding triplet motifs (2002)

Biguanide-like bidentate ligands in a variety of transition metal complexes of different geometries exhibit conformational changes upon protonation/deprotonation that alter their capacity to recognise complementary hydrogen bonding motifs.
Nonideal multicomponent distillation: Use of bifurcation theory for design (1991)

Abstract A method for the design of distillation systems for nonideal multicomponent mixtures is described, offering an alternative to extensive performance simulations. The basis is an analysis of the pinches or “fixed points” in the model equations and the results are widely applicable because approximations such as constant volatilities and ideal solutions are unnecessary. Tangent pinches are represented naturally as turning points in the diagram of pinch composition vs. reflux ratio, giving a basis for designs that alleviate the effects of tangent pinches in certain nonideal mixtures. An efficient computational approach for design is demonstrated in examples for homogeneous liquid mixtures, containing as many as four components, with and without azeotropic behavior. The results are in excellent agreement with detailed performance simulations.