gebhart/patrepeval huggingface dataset:
BAFF: a novel therapeutic target for autoimmunity. (2002)

Autoimmunity results from a break in self-tolerance involving humoral and/or cell-mediated immune mechanisms. One pathological consequence of a failure in central and/or peripheral tolerance is the generation of autoantibodies and subsequent formation of complement-fixing immune complexes that contribute to tissue damage. Prevailing pharmacological strategies for treating autoimmune diseases involve the use of broad-acting immunosuppressants that with long term use have associated toxicities. The current drive in drug development is towards therapies that target a specific biological pathway or pathogenic cell population. Recent discovery of the BAFF-mediated B-cell survival pathway provides a unique opportunity for developing focused intervention for autoreactive B-cell function.
Current and Potential Uses of Imiquimod (2005)

Imiquimod, an imidazoquinoline amine, is an immune response modifier first FDA-approved for the treatment of external genital and perianal warts in 1997. Since its appearance on the market, its antiviral and antitumor properties have been used in the treatment of a variety of dermatologic conditions. In this review article, the basic mechanism of action of imiquimod, current FDA-approved and non-FDA-approved uses of imiquimod, and key points of medication application frequency, possible adverse effects, and use in combination therapy are discussed. Common skin conditions that may be eradicated with imiquimod are emphasized.
Identification of the Novel Cycloaliphatic Brominated Flame Retardant 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane in Canadian Arctic Beluga (Delphinapterus leucas) (2007)

1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) is used primarily as an additive flame retardant. Technical grade TBECH consists of near equimolar amounts of two (of a possible four) diastereoisomers: rac-(1R,2R)-1,2-dibromo-(4S)-4-((1S)-1,2-dibromoethyl)cyclohexane ((alpha-TBECH) and rac-(1R,2R)-1,2-dibromo-(4S)-4-((1R)-1,2-dibromoethyl)cyclohexane (beta-TBECH). The two other possible isomers, gamma- and delta-TBECH, appear in the technical mixture when heated at temperatures above 120 degrees C. Careful selection of GC-capillary column length was critical in resolution of the two main diastereoisomers. Column lengths of 60 or 30 m (0.25 microm film thickness) resulted in incomplete separation of the alpha- and beta-isomers, while on a 10 m column, the isomers were baseline separated. The gamma- and delta-isomers could not be resolved on any column length in this study. Increased injector port temperature induced thermal conversion of the alpha- and beta-isomers to gamma- and delta-TBECH. Electron impact ionization (EI) was used to provide specificity because no characteristic ions in the electron capture negative ionization (ECNI) mass spectrum of TBECH were evident. In EI, the dominant ions in the mass spectrum corresponded to a concomitant loss of HBr and Br from the molecular ion; the biggest peak in this ion cluster (m/z 266.9208) was used for quantitation and the second biggest peak (m/z 264.9227) was used for confirmation. Beluga (Delphinapterus leucas) blubber extracts of animals from the Canadian Arctic (n=29) were analyzed using low resolution (LR) MS and high resolution (HR) MS run at a resolving power of 10,000. beta-TBECH was the only isomer observed in the samples and was detected in 17 samples. The LRMS technique appeared to overestimate beta-TBECH concentrations compared to HRMS, suggesting a small interference arose at the nominal mass monitored. This potential interference also led to some false positive and negative values (n=7) based on the expected ion ratio of the quantitation and confirmation ions. Observed concentrations of the beta-isomer as measured by HRMS ranged from 1.1 to 9.3 ng/g (lipid weight).
UTSA-74: A MOF-74 Isomer with Two Accessible Binding Sites per Metal Center for Highly Selective Gas Separation (2016)

A new metal-organic framework Zn2(H2O)(dobdc)·0.5(H2O) (UTSA-74, H4dobdc = 2,5-dioxido-1,4-benzenedicarboxylic acid), Zn-MOF-74/CPO-27-Zn isomer, has been synthesized and structurally characterized. It has a novel four coordinated fgl topology with one-dimensional channels of about 8.0 Å. Unlike metal sites in the well-established MOF-74 with a rod-packing structure in which each of them is in a five coordinate square pyramidal coordination geometry, there are two different Zn(2+) sites within the binuclear secondary building units in UTSA-74 in which one of them (Zn1) is in a tetrahedral while another (Zn2) in an octahedral coordination geometry. After activation, the two axial water molecules on Zn2 sites can be removed, generating UTSA-74a with two accessible gas binding sites per Zn2 ion. Accordingly, UTSA-74a takes up a moderately high and comparable amount of acetylene (145 cm(3)/cm(3)) to Zn-MOF-74. Interestingly, the accessible Zn(2+) sites in UTSA-74a are bridged by carbon dioxide molecules instead of being terminally bound in Zn-MOF-74, so UTSA-74a adsorbs a much smaller amount of carbon dioxide (90 cm(3)/cm(3)) than Zn-MOF-74 (146 cm(3)/cm(3)) at room temperature and 1 bar, leading to a superior MOF material for highly selective C2H2/CO2 separation. X-ray crystal structures, gas sorption isotherms, molecular modeling, and simulated and experimental breakthroughs comprehensively support this result.
Two-Way Ranging Algorithms Using Estimated Frequency Offsets in WPAN and WBAN (2008)

Asynchronous two-way ranging methods such as TWR and SDS-TWR have been considered for many ranging systems because these methods are useful in the absence of synchronization. To estimate the location of a mobile node, accurate ranging is essential between an anchor node and the mobile node. Ranging errors calculated with timestamps and reference frequency are derived from the difference of frequency offsets and unequal processing latency of ranging frame. In this paper, we propose to estimate frequency offsets of local nodes. The TWR and SDS-TWR based on measured timestamps and clock frequency offsets give exact relation and guarantee constant accuracy with coarse oscillators. The performance applied to low-rate UWB and high-rate UWB is evaluated according to the distribution of ranging errors.
Does Single-stranded DNA Pass through the Inner Channel of the Protein Hexamer in the Complex with the Escherichia coli DnaB Helicase? (1998)

The structure of the complex of the Escherichia coli primary replicative helicase DnaB protein with single-stranded (ss) DNA and replication fork substrates has been examined using the fluorescence energy transfer method. In these experiments, we used the DnaB protein variant, R14C, which has arginine 14 replaced by cysteine in the small 12-kDa domain of the protein using site-directed mutagenesis. The cysteine residues have been modified with a fluorescent marker which serves as a donor or an acceptor to another fluorescence label placed in different locations on the DNA substrates. Using the multiple fluorescence donor-acceptor approach, we provide evidence that, in the complex with the enzyme, ssDNA passes through the inner channel of the DnaB hexamer. This is the first evidence of the existence of such a structure of a hexameric helicase-ssDNA complex in solution. In the stationary complex with the 5' arm of the replication fork, without ATP hydrolysis, the distance between the 5' end of the arm and the 12-kDa domains of the hexamer (R = 47 A) is the same as in the complex with the isolated ssDNA oligomer (R = 47 A) having the same length as the arm of the fork. These data indicate that both ssDNA and the 5' arm of the fork bind in the same manner to the DNA binding site. Moreover, in the complex with the helicase, the length of the ssDNA is similar to the length of the ssDNA strand in the double-stranded DNA conformation. In the stationary complex, the helicase does not invade the duplex part of the fork beyond the first 2-3 base pairs. This result corroborates the quantitative thermodynamic data which showed that the duplex part of the fork does not contribute to the free energy of binding of the enzyme to the fork. Implications of these results for the mechanism of a hexameric helicase binding to DNA are discussed.
Influence of Mexiletine on the Pharmacokinetics of Theophylline in Healthy Volunteers (1991)

Preliminary reports suggest an interaction exists between theophylline and mexiletine. We conducted a two-way crossover study in 15 healthy male subjects to assess the magnitude of the pharmacokinetic interaction between mexiletine and theophylline. Twelve subjects completed 5 days of therapy on sustained-release theophylline 200 mg every 12 hours alone and 5 days of therapy with theophylline and mexiletine 150 mg every 8 hours. The two treatment periods were separated by a minimum of 7 days. On the morning of day 5 of each treatment period, blood samples for theophylline to be assayed by fluorescence immunoassay were collected over 24 hours. Mexiletine significantly increased the mean AUC, Cmax, t1/2 beta, and Cl of theophylline. Mexiletine did not affect tmax or Vd. Side effects occurred in 4 subjects during treatment with theophylline alone all of which were judged to be mild in intensity. During concomitant theophylline-mexiletine therapy, 10 subjects reported side effects of which 4 were judged to be severe, 1 moderate, and 5 mild. The magnitude of the increase in theophylline plasma concentrations induced by mexiletine as measured by AUC (0-24) was 58%, which is similar to other preliminary reports of this interaction. The authors conclude that the magnitude of the pharmacokinetic interaction between theophylline and mexiletine may be clinically significant in patients in light of the increased incidence of side effects in our healthy subjects. Theophylline dosage adjustments will be required in patients who receive concomitant mexiletine therapy.
Route Choice to Supply Chain Based on Petri Net (2006)

The route choice to supply chain is discussed, and modeling method and formalized description based on color Petri net is presented. According to model characteristic, and solution of reverse route to supply chain network is used, and capability of parallel calculation is exerted fully. It shows that the model to supply chain is calculated automatically, and total time and total cost of order channel are derived, and the objective of optimal route choice is attained
Increase in Free and Bound Abscisic Acid during Natural and Ethylene-induced Senescence of Citrus Fruit Peel (1973)

Free and bound abscisic acid and neutral growth inhibitors were detected in citrus fruit peel using two bioassays and gasliquid chromatography. None of the inhibitor components seems to be directly associated with chloroplasts or chromoplasts in citrus fruit peel.Green, nonsenescent fruits contain mostly neutral inhibitors and relatively low amounts of free and bound abscisic acid. Upon harvest and storage in ethylene, 50 microliters per liter, both free and bound abscisic acid accumulate rapidly, attaining within 24 hours a level of 1 microgram per gram. After 48 hours bound abscisic acid reaches a much higher level than free abscisic acid. Fruits allowed to senesce on the tree follow a similar course of abscisic acid accumulation, attaining finally a 10: 1 ratio of bound to free abscisic acid.
Phenylpropanoid Metabolism in Astringent and Nonastringent Persimmon (Diospyros kaki) Cultivars Determines Sensitivity to Alternaria Infection (2021)

Fruits of nonastringent persimmon cultivars, as compared to astringent ones, were more resistant to <i>Alternaria</i> infection despite having lower polyphenol content. Metabolic analysis from the pulp of nonastringent "Shinshu", as compared to the astringent "Triumph", revealed a higher concentration of salicylic, coumaric, quinic, 5-<i>o</i>-feruloyl quinic, ferulic acids, β-glucogallin, gallocatechin, catechin, and procyanidins. Selected compounds like salicylic, ferulic, and ρ-coumaric acids inhibited <i>in vitro Alternaria</i> growth, and higher activity was demonstrated for methyl ferulic and methyl ρ-coumaric acids. These compounds also reduced <i>in vivo Alternaria</i> growth and the black spot disease in stored fruits. On the other hand, methyl gallic acid was a predominant compound in the "Triumph" pulp, as compared to the "Shinshu" pulp, and it augmented <i>Alternaria</i> growth <i>in vitro</i> and <i>in vivo</i>. Our results might explain the high sensitivity of the cultivar "Triumph" to <i>Alternaria</i>. It also emphasizes that specific phenolic compounds, and not the total phenol, affect susceptibility to fungal infection.
Detection of Francisella tularensis in infected mammals and vectors using a probe-based polymerase chain reaction. (2000)

We investigated the use of a TaqMan 5' nuclease assay (5NA) directed against the Francisella tularensis outer membrane protein (Fop) gene and a polymerase chain reaction-enzyme immunoassay (PCR-EIA) directed against the tul 4 gene for detection of this organism in experimentally infected mice and in field-collected tick vectors. We also evaluated the use of specially formulated filter paper (FTA) for rapid sample preparation. The 5NA had a detection limit of 1 pg of genomic DNA (<100 colony-forming units) and could be completed within several hours. The PCR-EIA could detect 1 pg of genomic DNA and 10 attograms (ag) (22 copies) of cloned insert, but takes longer to perform. Both assays were genus-specific, and successfully detected F. tularensis in mouse tissues (5NA) and in tick extracts (PCR-EIA). The FTA paper provided inexpensive, rapid, template preparation for the tick extracts, mouse tissues, and DNA obtained from clinical specimens. These probe-based assays have the potential to provide rapid, real-time/high-throughput molecular diagnostics in field situations.
Semicircular duct and ampulla dimensions in cat, guinea pig and man (1977)

Predictions from the classic theory of semicircular canal operation, the torsion pendulum model, depend upon labyrinthine dimensions and the physical properties of the endolymph. The dimensions of the semicircular canal, duct and ampulla in cat, guinea pig and man were determined from measurements of magnified sections of decalcified temporal bones. Estimates of the effect of shrinkage were obtained from measures in fresh material and it appears shrinkage is probably only a fairly small factor. The dimensions so obtained were used to provide new estimates of the short time constant and other mechanical parameters of the torsion pendulum model in the three species.
P1‐627: AMYLOID BURDEN IMPACTS EVERYDAY FUNCTIONING INDEPENDENT OF COGNITION AND AWARENESS IN SUBJECTIVE COGNITIVE DECLINE: FINDINGS FROM THE INSIGHT PRE‐AD COHORT (2018)

With growing interest in preventative treatments in minimally symptomatic populations such as subjective cognitive decline (SCD), it becomes increasingly necessary to identify instruments able to detect the first clinical symptoms. Instruments measuring early changes in ‘instrumental activities of daily living’ (IADL) could fill this gap. With amyloid deposition as one of the earliest pathological changes in AD, we aimed to investigate the relationship between amyloid and IADL and the influence of cognition and awareness on this relationship in a SCD cohort. In this cross-sectional study, we included participants from the prospective INSIGHT pre-AD cohort (University Salpêtrière Hospital, Paris, France), who had amyloid Florbetapir PET, a neuropsychological and IADL assessment. β-Amyloid deposition was measured by the standard uptake value ratio (SUVr) in cortical regions: frontal, temporal, parietal, anterior cingulate, posterior cingulate and precuneus, using whole cerebellum and pons as reference regions. IADL was measured using the Amsterdam IADL Questionnaire, as completed by the study partner. Scoring was reversed and log-transformed to obtain a normal distribution. Global cognition (MMSE), memory (FSCRT free recall), executive functions (TMT-B and FAB) and awareness (Awareness of Cognitive Decline Index) were also assessed. The relationship between amyloid (global and local effects) and IADL was investigated using multivariable linear regression analyses, corrected for age, sex, education and APOE4 where necessary. Subsequently, we corrected for cognition and awareness. A total of 308 participants were included (Mean age=76±3.4, 63% female). Amyloid positive participants were more frequently APOE4 carriers and older (see Table 1). Global amyloid SUVr was related to IADL, and this effect remained significant after correcting for age and APOE4 (Figure 1). IADL was predominantly associated with SUVr in frontal, parietal and temporal regions (p's< .05, corrected for age and APOE4). After entering cognition and awareness, the relationship between amyloid and IADL remained significant (β=0.244, 95%CI 0.011-0.477).
<title>Observation of human tissue with phase-contrast x-ray computed tomography</title> (1999)

Human tissues obtained from cancerous kidneys fixed in formalin were observed with phase-contrast X-ray computed tomography (CT) using 17.7-keV synchrotron X-rays. By measuring the distributions of the X-ray phase shift caused by samples using an X-ray interferometer, sectional images that map the distribution of the refractive index were reconstructed. Because of the high sensitivity of phase- contrast X-ray CT, a cancerous lesion was differentiated from normal tissue and a variety of other structures were revealed without the need for staining.
Neurokinin-1 receptor antagonists as novel antidepressants: trials and tribulations (2007)

Based upon animal experiments and early clinical trials, neurokinin-1 receptor antagonists showed promise as novel antidepressants. Subsequently, however, more extensive clinical trials did not reveal evidence of efficacy in depression. The development of novel antidepressants will require a better understanding of the neural basis of antidepressant action in humans.
THE IN-STORE TRAINING CONCEPT (1973)

Looks at three approaches to in-store training of personnel.
Efficient sampling techniques for uncertainty quantification in history matching using nonlinear error models and ensemble level upscaling techniques (2009)

The Markov chain Monte Carlo (MCMC) is a rigorous sampling method to quantify uncertainty in subsurface characterization. However, the MCMC usually requires many flow and transport simulations in evaluating the posterior distribution and can be computationally expensive for fine‐scale geological models. We propose a methodology that combines coarse‐ and fine‐scale information to improve the efficiency of MCMC methods. The proposed method employs off‐line computations for modeling the relation between coarse‐ and fine‐scale error responses. This relation is modeled using nonlinear functions with prescribed error precisions which are used in efficient sampling within the MCMC framework. We propose a two‐stage MCMC where inexpensive coarse‐scale simulations are performed to determine whether or not to run the fine‐scale (resolved) simulations. The latter is determined on the basis of a statistical model developed off line. The proposed method is an extension of the approaches considered earlier where linear relations are used for modeling the response between coarse‐scale and fine‐scale models. The approach considered here does not rely on the proximity of approximate and resolved models and can employ much coarser and more inexpensive models to guide the fine‐scale simulations. Numerical results for three‐phase flow and transport demonstrate the advantages, efficiency, and utility of the method for uncertainty assessment in the history matching.
MARS-F modeling of post-disruption runaway beam loss by magnetohydrodynamic instabilities in DIII-D (2019)

A drift orbit model for relativistic test electrons has been incorporated into the MARS-F code, in order to study the runaway electron (RE) behavior in the presence of magneto-hydrodynamic perturbations computed by MARS-F. By implementing the model directly into the MARS-F curve-linear magnetic coordinates, maximal accuracy in representing the full field perturbation is preserved. The updated code is utilized to study the high current RE beam loss in a post-disruption DIII-D plasma, revealing that a fast growing, <em>n</em> = 1 (<em>n</em> is the toroidal mode number) resistive kink instability, at ~100 Gauss level, can induce significant fraction of RE loss, largely by perturbing drift orbits of REs. A 103 Gauss perturbation fully terminates the RE beam, as found in both experiment and modeling. The 3-D field induced loss increases with the perturbation amplitude but decreases with the particle energy. The loss fraction is generally not sensitive to the initial particle pitch angle. The particle velocity change, due to electric field acceleration/deceleration, small pitch angle scattering, synchrotron radiation and Bremsstrahlung, further perturbs the RE trajectory but plays a minor role in prompt RE loss within microseconds time scale. Therefore, the dominant dependencies are simply the RE energy and instability strength. For comparison, a resonant magnetic perturbation field, generated by 4 kAt <em>n</em> = 3 even parity I-coil currents in DIII-D and with the plasma response field included, is found to induce almost no loss for the same RE beam.
Advanced MRI of the Optic Nerve (2017)

Recently-developed orbit-specific MRI coils, quantitative sequences, and rapid acquisition techniques can improve our future ability to study optic nerve pathologies noninvasively. As advanced MRI becomes more proficient at characterizing the optic nerves, its role in the clinical management of patients should increase.
Oral arginine supplementation does not prevent bacterial translocation afterhemorrhagic stress in the rat (1998)

Oral arginine supplementation does not prevent bacterial translocation afterhemorrhagic stress in the rat
Nonpolarizing interference films inside a glass cube (1976)

The reflectance and transmittance of dielectric films at nonzero angle of incidence show strong polarization effects, and for many applications these effects are not wanted. Costich has recently published on the reduction of these effects in interference films. The extension of his theory to the case of a multilayer inside a glass cube is possible, but an efficient design does not result. In this paper another method using quarter-wave layers only is developed.
Effect of Escherichia coli alpha-hemolysin on human peripheral leukocyte function in vitro (1982)

To gain further evidence for the role of the Escherichia coli alpha-hemolysin in pathogenesis, its in vitro effects on human peripheral leukocyte function were studied. Leukocytes exposed to low doses of alpha-hemolysin responded with a marked chemiluminescence response, indicating activation of oxidative metabolism. This response was time and dose dependent. Pretreatment of leukocytes with doses of alpha-hemolysin at which nearly 80% of the cells survived decreased the ability of the cells to phagocytize bacteria and particles and to undergo chemotaxis. Premature activation of leukocytes and inhibition of phagocytosis and chemotaxis by alpha-hemolysin, if they occur in vivo, would greatly enhance the survival of an invading E. coli strain.