gebhart/patrepeval huggingface dataset:
3-(4-Chloro-2-Morpholin-4-yl-Thiazol-5-yl)-8-(1-Ethylpropyl)-2,6-Dimethyl-Imidazo[1,2-<i>b</i>]Pyridazine: A Novel Brain-Penetrant, Orally Available Corticotropin-Releasing Factor Receptor 1 Antagonist with Efficacy in Animal Models of Alcoholism (2007)

We describe a novel corticotropin-releasing factor receptor 1 (CRF1) antagonist with advantageous properties for clinical development, and its in vivo activity in preclinical alcoholism models. 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP) inhibited 125I-sauvagine binding to rat pituitary membranes and cloned human CRF1 with subnanomolar affinities, with no detectable activity at the CRF2 receptor or other common drug targets. After oral administration to rats, MTIP inhibited 125I-sauvagine binding to rat cerebellar membranes ex vivo with an ED50 of approximately 1.3 mg/kg and an oral bioavailability of 91.1%. Compared with R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5-a]pyrimidine) and CP154526 (N-butyl-N-ethyl-4,9-dimethyl-7-(2,4,6-trimethylphenyl)-3,5,7-triazabicyclo[4.3.0]nona-2,4,8,10-tetraen-2-amine), MTIP had a markedly reduced volume of distribution and clearance. Neither open-field activity nor baseline exploration of an elevated plus-maze was affected by MTIP (1-10 mg/kg). In contrast, MTIP dose-dependently reversed anxiogenic effects of withdrawal from a 3 g/kg alcohol dose. Similarly, MTIP blocked excessive alcohol self-administration in Wistar rats with a history of dependence, and in a genetic model of high alcohol preference, the msP rat, at doses that had no effect in nondependent Wistar rats. Also, MTIP blocked reinstatement of stress-induced alcohol seeking both in postdependent and in genetically selected msP animals, again at doses that were ineffective in nondependent Wistar rats. Based on these findings, MTIP is a promising candidate for treatment of alcohol dependence.
A Structural and Computational Study of Synthetically Important Alkali‐Metal/Tetramethylpiperidide (TMP) Amine Solvates (2008)

Two heavy alkali-metal salts of the sterically demanding amine, 2,2,6,6-tetramethylpiperidine (TMPH), have been prepared using different methodologies. Complex 1, [((tmeda)Na(tmp))2] (TMEDA=N,N, N',N'-tetramethylethylenediamine), can be synthesized by a deprotonative route. This is achieved by reacting butylsodium with TMPH in the presence of excess TMEDA in hexane. The potassium congener [((tmeda)K(tmp))2] (2), can be prepared by treating KTMP (made using a metathesis reaction between LiTMP and potassium tert-butoxide) with an excess of TMEDA in hexane. In the solid state, 1 and 2 are essentially isostructural. They are discretely dimeric and their framework consists of a four-membered M-N-M-N ring (M=Na or K, N=TMP). Due to the high steric demand of the TMP ligand, the TMEDA molecules bind to the metal centers in an asymmetric manner. In 2, each of the coordination spheres of the metals is completed by an agostic K...CH3(TMP) interaction. DFT calculations at the B3 LYP/6-311G** level give an insight into why 1 and 2 adopt dramatically different structures from their previously reported, "open-dimeric", lithium counterpart. The theoretical work also focuses on the TMEDA-free parent amide complexes and reveals that the energy difference for the formation of [(M(tmp))x] (in which, M=Li or Na, x=3 or 4; and M=K, x=2, 3 or 4) are small.
Indexing text events in digital video databases (2002)

Like shot changes, the presence of text in digital video is an important event that can be used to index digital video and provide extremely useful semantic information about the scene content. The special characteristics of digital video compared to document images both require and allow new robust approaches to recognition of text in video. We discuss the characteristics and special challenges of text in video and present a strategy of detecting, localizing, and segmenting text from video data for the text indexing problem. Preliminary results from our approach are presented.
A Bcr/Abl-independent, Lyn-dependent Form of Imatinib Mesylate (STI-571) Resistance Is Associated with Altered Expression of Bcl-2 (2004)

The relationship between the Src kinase Lyn and Bcl-2 expression was examined in chronic myelogenous leukemia cells (K562 and LAMA84) displaying a Bcr/Abl-independent form of imatinib mesylate resistance. K562-R and LAMA-R cells that were markedly resistant to induction of mitochondrial dysfunction (e.g. loss of mitochondrial membrane potential, Bax translocation, cytochrome c, and apoptosis-inducing factor release) and apoptosis by imatinib mesylate exhibited a pronounced reduction in expression of Bcr/Abl, Bcl-x(L), and STAT5 but a striking increase in levels of activated Lyn. Whereas basal expression of Bcl-2 protein was very low in parental cells, imatinib-resistant cells displayed a marked increase in Bcl-2 mRNA and/or protein levels. Treatment of LAMA-R cells with the Src kinase inhibitor PP2 significantly reduced Lyn activation as well as Bcl-2 mRNA and protein levels. Transient or stable transfection of LAMA84 or K562 cells with a constitutively active Lyn (Y508F), but not with a kinase-dead mutant (K275D), significantly increased Bcl-2 protein expression and protected cells from lethality of imatinib mesylate. Ectopic expression of Bcl-2 protected K562 and LAMA84 cells from imatinib mesylate- and PP2-mediated lethality. Conversely, interference with Bcl-2 function by co-administration of the small molecule Bcl-2 inhibitor HA14-1 or down-regulation of Bcl-2 expression by small interfering RNA or antisense strategies significantly increased mitochondrial dysfunction and apoptosis induced by imatinib mesylate and the topoisomerase inhibitor VP-16 in LAMA-R cells. In marked contrast, these interventions had little effect in parental LAMA84 cells that display low basal levels of Bcl-2. Together, these findings indicate that activation of Lyn in leukemia cells displaying a Bcr/Abl-independent form of imatinib mesylate resistance plays a functional role in Bcl-2 up-regulation and provide a theoretical basis for the development of therapeutic strategies targeting Bcl-2 in such a setting.
Binding Energy of the Positronium Molecule (1947)

A system of two electrons and two positrons is shown to possess dynamic stability. The variational calculation performed leads to a binding energy of at least 0.11 ev for this cluster. The approximate wave function which yields this value depends on the four electron-positron distances only. Neglect of the two distances between particles of the same kind permits an essential mathematical simplification which might be of interest in other problems.
Reactions of polar dienes with <i>o</i>-quinones (1989)

The behaviour of various types of polar dienes towards halogenated ortho quinones has been investigated in a number of representative cases. As compared to the commonly used para analogues, o-quinones provide a wide range of products that indicate a keener response to the nature, number, and position of substituents on both reactants. 3-Halogenated-o-naphthoquinones 1 and 2 react smoothly with a representative vinologous ketene acetal 3, vinylketene acetals 4 and 5, and a monooxygenated diene 6 to provide variously substituted phenanthrenequinones 7–11. Only monooxygenated dienes on the other hand add to o-benzoquinones 14–16 and give convenient syntheses of the corresponding o-naphthoquinones 18–20. Keywords: cycloaddition, o-naphthoquinones, phenanthrenequinones, regiospecificity.
JES Classics: ECS Science at Its Best: Phospho-Olivine Cathodes for Lithium-Ion Batteries (2009)

Lithium ion batteries have revolutionized the portable electronics market and are being intensively pursued for hybrid electric vehicle (HEV) and plug-in hybrid electric vehicle (PHEV) applications.
Dynamic field theory of movement preparation. (2002)

A theoretical framework for understanding movement preparation is proposed. Movement parameters are represented by activation fields, distributions of activation defined over metric spaces. The fields evolve under the influence of various sources of localized input, representing information about upcoming movements. Localized patterns of activation self-stabilize through cooperative and competitive interactions within the fields. The task environment is represented by a 2nd class of fields, which preshape the movement parameter representation. The model accounts for a sizable body of empirical findings on movement initiation (continuous and graded nature of movement preparation, dependence on the metrics of the task, stimulus uncertainty effect, stimulus-response compatibility effects, Simon effect, precuing paradigm, and others) and suggests new ways of exploring the structure of motor representations.
Checklist and Distribution of Korean Vespidae Revisited (2013)

한국산 말벌과에 관한 그 간의 연구는 다수의 오류를 포함하는 과거의 정보들이 동정에 반복적으로 사용되고 있어 여러 가지 분류학적 혼란이 야기되고 있는 상황이다. 이에 본 연구에서는 그 동안의 말벌 연구들을 최종 정리하여 호리병벌아과를 제외하고 확정된 한국산 말벌과의 종 목록과 그들의 분포정보를 정리하여 제공하였다. 총 2아과 5속 30종(3아종 포함)의 말벌류와 쌍살벌류를 한반도산으로 확정하였으며, 그 중 말벌아과는 3속 18종, 쌍살벌아과는 2속 12종이다. A diverse range of taxonomic confusions are brought forth since past taxonomic information including major errors following its initial provision of some uncertain information has repeatedly been applied to Korean Vespidae in its identification. Thus, this study, which made a final summarization of research on Vespidae, provided the list of Korean Vespidae determined except for Eumeninae, with their distributional data. A total of 30 species (including 3 subspecies) belonging to 5 genera of 2 subfamilies are listed: subfamily Vespinae (3 genera/ 18 species) and subfamily Polistinae (2 genera/ 12 species).
An Historical View of the Evolution of Low-Noise Concepts and Techniques (1984)

Presenting an historical paper on a broad technical subject such as this can be a more difficult task than describing the details of a technical contribution. The former is subjective while the latter, with its logic, mathematics, and measurement data is (usually) objective. Individual points of view of historical highlights, differ, so it is important that some background on the author of such a paper be known by the reader to give him an aid in evaluating the perspective of the points of view presented.
Radio Resource Management of Composite Wireless Networks: Predictive and Reactive Approaches (2011)

Recently, the IEEE 1900.4 standard specified a policy-based radio resource management (RRM) framework in which the decision making process is distributed between network-terminal entities. The standard facilitates the optimization of radio resource usage to improve the overall composite capacity and quality of service (QoS) of heterogeneous wireless access networks within a composite wireless network (CWN). Hence, the study of different RRM techniques to maintain either a load- or QoS-balanced system through dynamic load distribution across a CWN is pivotal. In this paper, we present and evaluate three primary RRM techniques from different aspects, spanning across predictive versus reactive to model-based versus measurement-based approaches. The first technique is a measurement-based predictive approach, known as predictive load balancing (PLB), commonly employed in the network-distributed RRM framework. The second technique is a model-based predictive approach, known as predictive QoS balancing (PQB), typically implemented in the network-centralized RRM framework. The third technique is a measurement-based reactive approach, known as reactive QoS balancing (RQB), anchored in the IEEE 1900.4 network-terminal distributed RRM framework. Comprehensive performance analysis between these three techniques shows that the IEEE 1900.4-based RQB algorithm yields the best improvement in QoS fairness and aggregate end-user throughput while preserving an attractive baseline QoS property.
The PRIMA system for privilege management, authorization and enforcement in grid environments (2004)

Many grid usage scenarios depend on small, dynamic working groups for which the ability to establish transient collaboration with little or no intervention from resource administrators is a key requirement. The system developed, PRIMA, focuses on the issues of management and enforcement of fine-grained privileges. Dynamic account creation and leasing as well as expressive enforcement mechanisms facilitate highly dynamic authorization policies and least privilege access to resources. PRIMA mechanisms enable the use of finegrained access rights, reduce administrative costs to resource providers, enable ad hoc and dynamic collaboration scenarios, and can also be used to provide improved security service to long-lived grid communities while leveraging other work in the grid computing and security domains.
Effects of Al<sub>2</sub>O<sub>3</sub> nanoparticles volume fractions on microstructural and mechanical characteristics of friction stir welded nanocomposites (2020)

The objective of the present study is to investigate the effect of Al2O3 nanoparticles volume percentage on tribological, mechanical and microstructural characteristics of 6061-T6 aluminum alloy based particulate-nanocomposite (P-NCs) fabricated using friction stir welding (FSW) process. Optical microscopy (OM) and scanning electron microscopy (SEM) was employed to evaluate the (a) microstructures of the produced nanocomposites to ascertain the distribution of Al2O3 nanoparticles in the nugget zone; (b) nanocomposite depth formed on Al-alloy matrix, and (c) fractured and wear characteristics. Results reveal that the produced P-NCs had a depth of 3286 µm across the perpendicular x-section of the weld nugget zone of P-NCs. With the increase in a volume percentage of Al2O3 nanoparticles there was a tremendous increment in the microhardness up to 125 HV which is higher than as-received AA6061-T6. It was also noticed that the tensile strength and the wear resistance of produced P-NCs were significantly increased at 0.3 vol% of Al2O3 nanoparticles as compared to 0.2 and 0.4 vol%. The corresponding mechanical and wear properties results were correlated to microstructure and fractography results.
Silencing cAMP-response Element-binding Protein (CREB) Identifies CYR61 as a Tumor Suppressor Gene in Melanoma (2009)

Metastatic progression of melanoma is associated with overexpression and activity of cAMP-response element-binding protein (CREB). However, the mechanism by which CREB contributes to tumor progression and metastasis remains unclear. Here, we demonstrate that stably silencing CREB expression in two human metastatic melanoma cell lines, A375SM and C8161-c9, suppresses tumor growth and experimental metastasis. Analysis of cDNA microarrays revealed that CREB silencing leads to increased expression of cysteine-rich protein 61 (CCN1/CYR61) known to mediate adhesion, chemostasis, survival, and angiogenesis. Promoter analysis and chromatin immunoprecipitation assays demonstrated that CREB acts as a negative regulator of CCN1/CYR61 transcription by directly binding to its promoter. Re-expression of CREB in CREB-silenced cells rescued the low CCN1/CYR61 expression phenotype. CCN1/CYR61 overexpression resulted in reduced tumor growth and metastasis and inhibited the activity of matrix metalloproteinase-2. Furthermore, its overexpression decreased melanoma cell motility and invasion through Matrigel, which was abrogated by silencing CCN1/CYR61 in low metastatic melanoma cells. Moreover, a significant decrease in angiogenesis as well as an increase in apoptosis was seen in tumors overexpressing CCN1/CYR61. Our results demonstrate that CREB promotes melanoma growth and metastasis by down-regulating CCN1/CYR61 expression, which acts as a suppressor of melanoma cell motility, invasion and angiogenesis.
Nucleoside Synthesis from Furanoid Glycals (1993)

Gbstract ---Reaction of furanoid glycals with PhSCl afforded I-chlorosugars, which were used for condensation reaction with silylated uracil in the presence of SnC4.These two reactions proceeded in a highly stereoselective manner.2',3'-Dideoxynucleosides and 2'3-didehydro-2.3'-dideoxynucleosidesare known to he active compounds against HIV, which causes AIDS.'To prepare these nucleosides, we have focused on the stereoselective condensation reaction between sugars and nucleic bases, since this reaction can be used to synthesize a wide variety of structurally related compound^.^-^In the course of this study, we have clarified the effect of the phenylthio group on sugar C-2 as a stereocontrolling element.3x4The condensation reaction between 2-aphenylthio-2,3-dideoxyribose (1) and silylated pyrimidine bases in the presence of SnC14 as a catalyst afforded the anomeric mixture of nucleosides in a ratio of u : P = 1 : 9.The phenylthio group on the sugar moiety was used as a hand hold to introduce the carbon-carbon double bond of 2',3'-didehydro-2',3'-dideoxynucleosides.This method, however, has a serious disadvantage.The stereoselectivity of the phenylsulfenylation of y-lactone ' .,
Generalized isolation level definitions (2002)

Commercial databases support different isolation levels to allow programmers to trade off consistency for a potential gain in performance. The isolation levels are defined in the current ANSI standard, but the definitions are ambiguous and revised definitions proposed to correct the problem are too constrained since they allow only pessimistic (locking) implementations. This paper presents new specifications for the ANSI levels. Our specifications are portable: they apply not only to locking implementations, but also to optimistic and multi-version concurrency control schemes. Furthermore, unlike earlier definitions, our new specifications handle predicates in a correct and flexible manner at all levels.
Crossing the Melfa River (1993)

Lyme neuroborreliosis (LNB) can be a serious manifestation of Lyme borreliosis. We describe the incidence, time trends and geographic distribution of LNB in Denmark. We obtained LNB cases reported by laboratories and physicians (2015-2019) from the online platform maintained by the Statens Serum Institut (SSI) (2021b). The LNB incidence (per 100,000 persons) was calculated by dividing LNB cases by the population data (denominator) obtained from Statistics Denmark (2021). Between 2015 and 2019, laboratories reported annually 162 to 200 LNB cases, while physicians reported 48 to 68 cases. The annual LNB incidence notified by laboratories ranged from 2.8 (95% CI: 2.4‒3.3) to 3.4 (95% CI: 3.0‒4.0) per 100,000 persons for the 5 study years. The average annual LNB incidence per 100,000 persons for 5 Danish regions ranged from 2.3 to 3.3; for 11 provinces, from 1.9 to 7.6; and for 98 municipalities, from 0 to 22.1. Incidence peaks occurred in persons 5‒14 and 65‒74 years of age. Higher incidences were observed among males versus females in all age groups. LNB cases were reported throughout the year, with peaks in July to September. Notified LNB incidence in Denmark was moderate with no evidence of decline. Cases occurred across all regions but were focally concentrated among residents of some municipalities. Expanding the current surveillance system to include other manifestations of LB would be valuable to better understand geographic endemicity to inform targeted preventive measures.
Early onset prostate cancer has a significant genetic component (2020)

Prostate cancer (PCa) affects more than 190,000 men each year with ~10% of men diagnosed at ≤ 55 years, i.e., early onset (EO) PCa. Based on historical findings for other cancers, EO PCa likely reflects a stronger underlying genetic etiology.
Identification, Purification, and Characterization of Transpeptidase and Glycosyltransferase Domains of <i>Streptococcus pneumoniae</i> Penicillin-Binding Protein 1a (1998)

Resistance to beta-lactam antibiotics in Streptococcus pneumoniae is due to alteration of penicillin-binding proteins (PBPs). S. pneumoniae PBP 1a belongs to the class A high-molecular-mass PBPs, which harbor transpeptidase (TP) and glycosyltransferase (GT) activities. The GT active site represents a new potential target for the generation of novel nonpenicillin antibiotics. The 683-amino-acid extracellular region of PBP 1a (PBP 1a*) was expressed in Escherichia coli as a GST fusion protein. The GST-PBP 1a* soluble protein was purified, and its domain organization was revealed by limited proteolysis. A protease-resistant fragment spanning Ser 264 to Arg 653 exhibited a reactivity profile against both beta-lactams and substrate analogues similar to that of the parent protein. This protein fragment represents the TP domain. The GT domain (Ser 37 to Lys 263) was expressed as a recombinant GST fusion protein. Protection by moenomycin of the GT domain against trypsin degradation was interpreted as an interaction between the GT domain and the moenomycin.
Techniques for studying ion channels: an introduction (1997)

In this Introduction to the Special Issue on Ion Channels in Plants, the techniques used to study ion channels are reviewed. In particular, the basic approaches used for the electrophysiological study of ion channels are explained, from voltage clamping membranes and observing current changes over time, to the construction of current-voltage relations and the use of tail current protocols to determine channel selectivity. This is done for whole-cell and single channel records.
[Pseudohypoparathyroidism. Clinical characteristics and experience with its treatment with vitamin D 3 preparations]. (1988)

The paper is concerned with the literature data on pathogenesis and a clinical course of 2 types of PHPT. Clinicolaboratory findings show that PHPT is a polymorphous syndrome of which the most common signs are skeletal changes, low stature, the tetanoid syndrome in hypocalcemia, hyperphosphatemia, the normal or raised level of endogenous PTH, insensitivity to exogenous PTH, soft tissue and brain calcification, mental deficiency. An insufficient or paradoxical PTH reaction and an adequate CT reaction are noted after calcium drug loading. Therapy with I alpha OH D3 and I alpha, 25/OH2 D3 has demonstrated its superiority over other vitamin D forms leading to fast normalization of calcium-phosphoric metabolism and elimination of the tetanoid syndrome.
VLSI implementation of a 256*256 crossbar interconnection network (2003)

Despite the fact that a crossbar interconnection network is desirable in parallel processing systems due to its flexibility of configuration and simplicity of control, many of the crossbars developed up to this time are small in size. The paper presents the analysis of VLSI layout size and signal delay of the previous crossbar circuits. Also a circuit with better layout size and signal delay is presented in comparison. Based on the new circuit, the feasibility of the implementation is shown for a 256*256 crossbar on a 1cm/sup 2/ CMOS VLSI chip.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Ly6C supports preferential homing of central memory CD8<sup>+</sup> T cells into lymph nodes (2011)

Ly6C is a murine cell-surface antigen expressed by plasma cells, subsets of myeloid cells and many T cells, including memory T cells. We previously documented that Ly6C crosslinking induces LFA-1 clustering on naïve CD8(+) T cells. Here, we show that in vitro and in vivo differentiation of naïve CD8(+) T cells into central (Tcm) but not effector (Tem) memory T cells enhances Ly6C expression, and its crosslinking induces strong LFA-1 clustering on Tcm. Blocking Ly6C function inhibits in vivo Tcm homing to LNs as efficiently as blocking L-selectin but it does not potentiate the inhibition provided by blocking either L-selectin or LFA-1 function. Thus, Ly6C, L-selectin and LFA-1 all appear to be part of a common homing pathway. In vitro, Ly6C crosslinking enhances Tcm adherence to ICAM-1 in the presence of CCL21. In summary, Tcm homing involves Ly6C, in addition to L-selectin and LFA-1, and appears to potentiate firm adhesion of Tcm to ICAM-1 in synergy with a chemokine. We propose that Ly6C augments Tcm compartmentalization into LNs during their homing.