gebhart/patrepeval huggingface dataset:
CGRP-Based Migraine Therapeutics: How Might They Work, Why So Safe, and What Next? (2018)

Migraine is a debilitating neurological condition that involves the neuropeptide calcitonin gene-related peptide (CGRP). An exciting development is the recent FDA approval of the first in an emerging class of CGRP-targeted drugs designed to prevent migraine. Yet despite this efficacy, there are some fundamental unanswered questions, such as <i>where</i> and <i>how</i> CGRP works in migraine. Preclinical data suggest that CGRP acts via both peripheral and central mechanisms. The relevance of peripheral sites is highlighted by the clinical efficacy of CGRP-blocking antibodies, even though they do not appreciably cross the blood-brain barrier. The most likely sites of action are within the dura and trigeminal ganglia. Furthermore, it would be foolish to ignore perivascular actions in the dura since CGRP is the most potent vasodilatory peptide. Ultimately, the consequence of blocking CGRP or its receptor is reduced peripheral neural sensitization. Underlying their efficacy is the question of <i>why</i> the antibodies have such an excellent safety profile so far. This may be due to the presence of a second CGRP receptor and vesicular release of a large bolus of peptides. Finally, despite the promise of these drugs, there are unmet gaps because they do not work for all patients; so <i>what next</i>? We can expect advances on several fronts, including CGRP receptor structures that may help development of centrally-acting antagonists, combinatorial treatments that integrate other therapies, and development of drugs that target other neuropeptides. This is truly an exciting time for CGRP and the migraine field with many more discoveries on the horizon.
Magnetic field imaging using ct technique — roi reconstruction system (1993)

Abstract This paper proposes a method to visualize the spatial distribution of the magnetic field in the region of interest (ROI), using CT technique. An experimenal system is constructed to visualize the magnetic field in ROI. In the reconstruction of the distribution in general by the CT technique, the projection data should not contain data outside the region of reconstruction. In the visualization of the magnetic field by CT techniques proposed up to the present, however, the projection data containing the magnetic field distribution outside the region of reconstruction are contained in the measurement. Consequently, the technique has been applied only to the case where the magnetic field exists only inside ROI. This paper proposes the following method. Wires for detecting the magnetic field are placed in the region of reconstruction. It is noted that the projection data obtained from the induced voltage does not contain the magnetic field distribution outside the region of reconstruction. This property is utilized in the visualization of the magnetic field distribution in the region of reconstruction. This paper describes also the principle of the fore‐mentioned methods, as well as the ROI visualization system constructed based on the principle. Using the proposed method, result of visualization is shown for magnetic field distribution produced by a permanent magnet.
Anti‐wear performance of organomolybdenum compounds as lubricant additives (2006)

Abstract A four‐ball tester was used to evaluate the anti‐wear performance of three kinds of organomolybdemun compounds in engine oils and lithium soap grease, i.e. molybdenum dialkyldithiophosphate (MoDDP), molybdenum dialkyldithiocarbamate (MoDTC), and sulphur‐ and phosphorus‐free organomolybdeum (molybdate). The results indicate that a low concentration of MoDDP does not improve the anti‐wear properties of the commercial engine oils, but a high concentration of MoDDP can obviously improve the anti‐wear properties of the engine oils. MoDTC does not improve the anti‐wear properties of the engine oils, but worsens the anti‐wear properties of the oils. Significant improvement of the anti‐wear properties is obtained with molybdate added in the four fully formulated oils. Both MoDDP and molybdate have good anti‐wear properties in the lithium soap grease, especially MoDDP with a high concentration. Copyright © 2006 John Wiley & Sons, Ltd.
Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification (2009)

Abstract Acute erythroid leukemia (AEL) is a rare type of acute myeloid leukemia (AML) for which diagnostic criteria have been refined in the 2008 World Health Organization (WHO) classification of AML. The relationship of AEL to myelodysplastic syndromes (MDSs) and to AML with myelodysplasia-related changes (AML-MRC) is not clearly defined. We conducted a retrospective, multi-institutional study of patients with AEL and compared them with patients with MDS or AML-MRC with erythroid hyperplasia (≥ 50% erythroid cells). Among a total of 124 patients with AEL, 32% had a history of MDS or chronic cytopenia, 32% had therapy-related disease, and 35% had de novo disease. Sixty-four percent of patients had unfavorable AML risk-group karyotypes. FLT3 and RAS mutations were infrequent, occurring in 6% and 2%, respectively. The median overall survival (OS) of all AEL patients was 8 months, comparable with that of patients with MDS or AML-MRC with erythroid hyperplasia. The OS was related to cytogenetic risk group, but not blast count or morphologic dysplasia. Our findings suggest that AEL is in the continuum of MDS and AML with erythroid hyperplasia, where karyotype rather than an arbitrary blast cutoff represents the most important prognostic factor.
Stem Cell Transplantation for Spinal Cord Neurodegeneration (2011)

Amyotrophic lateral sclerosis (ALS), a disorder that affects 30,000 individuals in the USA alone, is characterized by relatively rapid degeneration of upper and lower motor neurons, with death normally occurring 2-5 years following diagnosis due to respiratory paralysis. Transplantation of various classes of neural precursor cells (NPCs) is a promising therapeutic strategy for the treatment of traumatic CNS injury and neurodegeneration, including ALS, because of the ability to replace lost or dysfunctional CNS cell types, provide neuroprotection, and deliver gene factors of interest. In order to target cellular therapy to diaphragmatic dysfunction in models of ALS, NPCs can be transplanted specifically into the cervical spinal cord ventral gray matter of both SOD1G93A rats and mice. The SOD1G93A rats and mice are currently the most well-studied animal model of the disease.
Design of a Spacer Grid Using Axiomatic Design (2003)

Recently, much attention is focused on the design of fuel assemblies in the Pressurized Light Water Reactor (PWR). The spacer grid is one of the main structural components in a fuel assembly. It supports fuel rods, guides cooling water, and maintains geometry from external impact loads. In this research, a new shape of the spacer grid is designed by axiomatic approach. The Independence Axiom is utilized for the design. For the conceptual design, functional requirements (FRs) are defined and corresponding design parameters (DPs) are found to satisfy corresponding FRs in sequence. Overall configuration and shapes are determined in this process. Detailed design is carried out based on the sequence from axiomatic design. For the detailed design, the system performances are evaluated by using linear and nonlinear finite element analyses. The dimensions are determined by optimization. Some commercial codes are utilized for the analysis and design.
QTLs for shelf life in lettuce co-locate with those for leaf biophysical properties but not with those for leaf developmental traits (2007)

Developmental and biophysical leaf characteristics that influence post-harvest shelf life in lettuce, an important leafy crop, have been examined. The traits were studied using 60 informative F9 recombinant inbed lines (RILs) derived from a cross between cultivated lettuce (Lactuca sativa cv. Salinas) and wild lettuce (L. serriola acc. UC96US23). Quantitative trait loci (QTLs) for shelf life co-located most closely with those for leaf biophysical properties such as plasticity, elasticity, and breakstrength, suggesting that these are appropriate targets for molecular breeding for improved shelf life. Significant correlations were found between shelf life and leaf size, leaf weight, leaf chlorophyll content, leaf stomatal index, and epidermal cell number per leaf, indicating that these pre-harvest leaf development traits confer post-harvest properties. By studying the population in two contrasting environments in northern and southern Europe, the genotype by environment interaction effects of the QTLs relevant to leaf development and shelf life were assessed. In total, 107 QTLs, distributed on all nine linkage groups, were detected from the 29 traits. Only five QTLs were common in both environments. Several areas where many QTLs co-located (hotspots) on the genome were identified, with relatively little overlap between developmental hotspots and those relating to shelf life. However, QTLs for leaf biophysical properties (breakstrength, plasticity, and elasticity) and cell area correlated well with shelf life, confirming that the ideal ideotype lettuce should have small cells with strong cell walls. The identification of QTLs for leaf development, strength, and longevity will lead to a better understanding of processability at a genetic and cellular level, and allow the improvement of salad leaf quality through marker-assisted breeding.
Phosphorylation of double-stranded DNAs by T<sub>4</sub> polynucleotide kinase (1976)

The phosphorylation by T4 polynucleotide kinase of various double-stranded DNAs containing defined 5'-hydroxyl end group structures has been studied. Particular emphasis was placed on finding conditions that allow complete phosphorylation. The DNAs employed were homodeoxyoligonucleotides annealed on the corresponding homopolymers, DNA duplexes corresponding to parts of the genes for alanine yeast tRNA, and a suppressor tyrosine tRNA from Escherichia coli. The rate of phosphoylation of DNAs with 5'-hydroxyl groups in gaps was approximately ten times slower than for the corresponding single-stranded DNA. At low concentrations of ATP, 1 muM, incomplete phosphorylation was obtained, whereas with higher concentrations of ATP, 30 muM, complete phosphorylation was achieved. In the case of DNAs with 5'-hydroxyl groups at nicks approximately 30% phosphorylation could be detected using 30 muM ATP. A DNA containing protruding 5'-hydroxyl group ends was phosphorylated to completion using the same conditions as for single-stranded DNA, i.e., a ratio between the concentrations of ATP and 5'-hydroxyl groups of 5:1 and a concentration of ATP of approximately 1 muM. For a number of DNAs containing protruding 3'-hydroxyl group ends and one DNA containing even ends incomplete phosphorylation was found under similar conditions. For all these DNAs a plateau level was observed varying from 20 to 45% of complete phosphorylation. At 20 muM and higher ATP concentrations, the phosphorylation was complete also for these DNAs. With low concentrations of ATP a rapid production of inorganic phosphate was noted for all the latter DNAs. The apparent equilibrium constants for the forward and reverse reaction were determined for a number of different DNAs, and these data revealed that the plateau levels of phosphorylation obtained at low concentrations of ATP for DNAs with protruding 3'-hydroxyl group and even ends is not a true equilibrium resulting from the forward and reverse reaction. It is suggested that the plateau levels are due to formation of inactive enzyme-substrate and enzyme-product complexes. For all double-stranded DNAs tested, except DNAs containing protruding 5'-hydroxyl group ends, addition of KCl to the reaction mixture resulted in a drastic decrease in the rate of phosphorylation, as well as in the maximum level phosphorylated. Spermine, on the other hand, had little influence. Both of these agents have previously been shown to activate T4 polynucleotide kinase using single-stranded DNAs as substrates (Lillehaug, J.R., and Kleppe, K. (1975), Biochemistry 14, 1221). The inhibition of phosphorylation of double-stranded DNAs by salt might be the result of stabilization of the 5'-hydroxyl group regions of these DNAs.
Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq (2017)

Cellular functions are strongly dependent on surrounding cells and environmental factors. Current technologies are limited in their ability to characterize the spatial location and gene programs of cells in poorly structured and dynamic niches. We developed a method, NICHE-seq, that combines photoactivatable fluorescent reporters, two-photon microscopy, and single-cell RNA sequencing (scRNA-seq) to infer the cellular and molecular composition of niches. We applied NICHE-seq to examine the high-order assembly of immune cell networks. NICHE-seq is highly reproducible in spatial tissue reconstruction, enabling identification of rare niche-specific immune subpopulations and gene programs, including natural killer cells within infected B cell follicles and distinct myeloid states in the spleen and tumor. This study establishes NICHE-seq as a broadly applicable method for elucidating high-order spatial organization of cell types and their molecular pathways.
Calibration of mass spectrometric peptide mass fingerprint data without specific external or internal calibrants (2005)

The MST calibration algorithm is well suited to calibrate MS spectra of protein samples resulting from two-dimensional gel electrophoretic separation. The TPS based calibration algorithm might be used to correct systematic mass measurement errors observed for large MS sample supports. As compared to other methods, our combined MS spectra calibration strategy increases the peptide/protein identification rate by an additional 5-15%.
A Game-Theoretic Approach to Apprenticeship Learning (2007)

We study the problem of an apprentice learning to behave in an environment with an unknown reward function by observing the behavior of an expert. We follow on the work of Abbeel and Ng [1] who considered a framework in which the true reward function is assumed to be a linear combination of a set of known and observable features. We give a new algorithm that, like theirs, is guaranteed to learn a policy that is nearly as good as the expert’s, given enough examples. However, unlike their algorithm, we show that ours may produce a policy that is substantially better than the expert’s. Moreover, our algorithm is computationally faster, is easier to implement, and can be applied even in the absence of an expert. The method is based on a game-theoretic view of the problem, which leads naturally to a direct application of the multiplicative-weights algorithm of Freund and Schapire [2] for playing repeated matrix games. In addition to our formal presentation and analysis of the new algorithm, we sketch how the method can be applied when the transition function itself is unknown, and we provide an experimental demonstration of the algorithm on a toy video-game environment. 1
Synthesis, properties and potential applications of two-dimensional transition metal dichalcogenides (2015)

Abstract In recent years, 2-dimensional (2D) materials such as graphene and h-BN have been spotlighted, because of their unique properties and high potential applicability. Among these 2D materials, transition metal dichalcogenides (TMDs) have attracted a lot of attention due to their unusual electrical, optical, and mechanical properties. Also, TMDs have virtually unlimited potential in various fields, including electronic, optoelectronic, sensing, and energy storage applications. For these various applications, there are many methods for sample preparation, such as the mechanical, liquid exfoliation and chemical vapor deposition techniques. In this review, we introduce the properties, preparation methods and various applications of TMDs materials.
Penicillin-binding protein 1B from Escherichia coli contains a membrane association site in addition to its transmembrane anchor. (1993)

A working structural model of penicillin-binding protein 1B (PBP 1B) from Escherichia coli derived from previous data consists of a highly charged aminoterminal cytoplasmic tail, a 23-amino-acid hydrophobic transmembrane anchor, and a 758-amino-acid periplasmic domain. Using an engineered thrombin cleavage site, we have investigated the solubility properties of the periplasmic domain of PBP 1B. Twelve amino acids, comprised of the consensus thrombin cleavage site (LVPR decreases GS) and flanking glycine residues, were inserted into PBP 1B just past its putative transmembrane segment. To aid in purification, a hexa-histidine tag was also inserted at its amino terminus, and the engineered protein (PBP 1B-GT/H6) was purified and characterized. Inclusion of the thrombin cleavage site had no effect on the protein's intrinsic tryptophan fluorescence and affinity for [14C]penicillin G, indicating that the protein structure was not significantly perturbed. PBP 1B-GT/H6 was readily cleaved by thrombin at low thrombin/protein ratios to a protein with properties consistent with the removal of its cytoplasmic tail and transmembrane regions. Cleavage of the protein was dependent upon the presence of the thrombin cleavage site, and the thrombin-cleaved protein (PBP 1Bper) displayed an identical affinity for [14C] penicillin G binding as wild-type PBP 1B and uncleaved PBP 1B-GT/H6. [14C]Penicillin G-labeled PBP 1Bper eluted from a gel filtration column in the presence but not in the absence of 0.7% 3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonic acid, and PBP 1Bper was found entirely in the membrane fraction of a thrombin digest of membranes containing overproduced PBP 1B-GT/H6. To further characterize this unusual solubility behavior, purified PBP 1Bper was reconstituted into lipid vesicles, which were then floated on a sucrose gradient. Floated vesicles contained > 95% of total 125I-penicillin V binding, indicating that PBP 1Bper directly associates with lipid membranes. These results strongly suggest that the periplasmic domain of PBP 1B associates with membranes independent of its amino terminal transmembrane region.
Transient P‐cadherin expression in radiation proctitis; a model of mucosal injury and repair (2002)

Morphology at both cellular and glandular levels in the colon is dependent to an extent on cell-cell adhesion mediated by cadherin-catenin complexes. Alterations in the expression of E-cadherin, the cadherin normally present in colon, have been shown to be implicated in tissue remodelling within the gastrointestinal tract. Furthermore, it has previously been shown that P-cadherin, normally present only in stratified epithelia and placenta, is expressed in colitis and during neoplastic change in the colon. The morphological features of mucosal injury induced by pre-operative radiotherapy in the non-neoplastic rectal mucosa were studied in patients with rectal adenocarcinoma. Three characteristic phases of radiation proctitis were defined on histological grounds (acute injury, and early and late regenerative phases) essentially correlating with the time interval between radiotherapy and surgery; such features were mirrored by alterations in cadherin-catenin expression and localization in rectal crypts. On immunohistochemistry and western blotting, P-cadherin was highly expressed in the acute injury and early regenerative phases, with a decreased level of expression during late regeneration. E-cadherin and associated catenins were translocated from membrane to cytoplasm in degenerating crypts, with return of normal membranous expression in regenerating crypts. In conclusion, radiation-induced proctitis represents an in vivo model of mucosal injury and regeneration and provides a valid model in which to study events during epithelial injury and repair. Altered cadherin expression, in particular transient aberrant P-cadherin expression, is intimately associated with these processes.
Communication Via Decentralized Processing (2008)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> The problem of a nomadic terminal sending information to a remote destination via agents with lossless connections to the destination is investigated. Such a setting suits, e.g., access points of a wireless network where each access point is connected by a wire to a wireline-based network. The Gaussian codebook capacity for the case where the agents do not have any decoding ability is characterized for the Gaussian channel. This restriction is demonstrated to be severe, and allowing the nomadic transmitter to use other signaling improves the rate. For both general and degraded discrete memoryless channels, lower and upper bounds on the capacity are derived. An achievable rate with unrestricted agents, which are capable of decoding, is also given and then used to characterize the capacity for the deterministic channel. </para>
Development of Self-Issuable (Divisible and Transferable) Offline Electronic Cash (2015)

Based on anonymous tag based credentials and linear Mix-nets, this paper develops a scheme for e-cash systems that can be used in offline environments. The developed scheme makes e-cash holders anonymous while disabling them to use e-cash dishonestly. It also makes e-cash divisible and transferable. In detail, although no one except cash holders themselves can know correspondences between them and their e-cash, e-cash issuing authority can identify dishonest cash holders that had generated and/or spent e-cash illegitimately. In addition, cash holders can generate new e-cash of arbitrary values from their holding e-cash to make purchases of amounts less than original cash values. Also, cash holders can use e-cash that they had received from others as same as the one directly issued to them from the issuing authority.
Dynacortin, a Genetic Link between Equatorial Contractility and Global Shape Control Discovered by Library Complementation of a <i>Dictyostelium discoideum</i> Cytokinesis Mutant (2000)

We have developed a system for performing interaction genetics in Dictyostelium discoideum that uses a cDNA library complementation/multicopy suppression strategy. Chemically mutagenized cells were screened for cytokinesis-deficient mutants and one mutant was subjected to library complementation. Isolates of four different genes were recovered as modifiers of this strain's cytokinesis defect. These include the cleavage furrow protein cortexillin I, a novel protein we named dynacortin, an ezrin-radixin-moesin-family protein, and coronin. The cortexillin I locus and transcript were found to be disrupted in the strain, identifying it as the affected gene. Dynacortin is localized partly to the cell cortex and becomes enriched in protrusive regions, a localization pattern that is similar to coronin and partly dependent on RacE. During cytokinesis, dynacortin is found in the cortex and is somewhat enriched at the poles. Furthermore, it appears to be reduced in the cleavage furrow. The genetic interactions and the cellular distributions of the proteins suggest a hypothesis for cytokinesis in which the contraction of the medial ring is a function of spatially restricted cortexillin I and myosin II and globally distributed dynacortin, coronin, and RacE.