gebhart/patrepeval huggingface dataset:
3-(4-Chloro-2-Morpholin-4-yl-Thiazol-5-yl)-8-(1-Ethylpropyl)-2,6-Dimethyl-Imidazo[1,2-b]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.
VE-cadherin expression allows identification of a new class of hematopoietic stem cells within human embryonic liver (2010)

Edification of the human hematopoietic system during development is characterized by the production of waves of hematopoietic cells separated in time, formed in distinct embryonic sites (ie, yolk sac, truncal arteries including the aorta, and placenta). The embryonic liver is a major hematopoietic organ wherein hematopoietic stem cells (HSCs) expand, and the future, adult-type, hematopoietic cell hierarchy becomes established. We report herein the identification of a new, transient, and rare cell population in the human embryonic liver, which coexpresses VE-cadherin, an endothelial marker, CD45, a pan-hematopoietic marker, and CD34, a common endothelial and hematopoietic marker. This population displays an outstanding self-renewal, proliferation, and differentiation potential, as detected by in vitro and in vivo hematopoietic assays compared with its VE-cadherin negative counterpart. Based on VE-cadherin expression, our data demonstrate the existence of 2 phenotypically and functionally separable populations of multipotent HSCs in the human embryo, the VE-cadherin(+) one being more primitive than the VE-cadherin(-) one, and shed a new light on the hierarchical organization of the embryonic liver HSC compartment.
XML linking (1999)

article Free Access Share on XML linking Author: Steven J. DeRose Brown University, Brown University Scholarly Technology Group Brown University, Brown University Scholarly Technology GroupView Profile Authors Info & Claims ACM Computing SurveysVolume 31Issue 4esDec. 1999 pp 21–eshttps://doi.org/10.1145/345966.346015Published:01 December 1999Publication History 18citation1,256DownloadsMetricsTotal Citations18Total Downloads1,256Last 12 Months17Last 6 weeks4 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Effects of heterologous platelet-rich plasma gel on standardized dermal wound healing in rabbits (2015)

Heterologous platelet-rich plasma gel promoted dermal wound healing in rabbits with no adverse effects.
Identification of GSK461364, a novel small molecule polo-like kinase 1 inhibitor for the treatment of cancer (2007)

4171 Polo-like kinase 1 (Plk1) plays an important role in the entry to, progression through, and exit from mitosis. The multiple roles Plk1 plays in mitosis make it an intriguing target to inhibit to disrupt the cell cycle and treat cancer. This presentation will highlight the lead optimization studies and elucidation of the structure-activity relationship leading to the identification of a novel thiophene amide Plk1 inhibitor. It will include the synthesis of a Plk-selective inhibitor, in addition to optimization of potency and developability characteristics through several iterations of structural changes, culminating in the identification of the clinical candidate. These efforts led to the development of GSK461364, an extremely potent Plk1 inhibitor (IC 50 ~3 nM) with greater than 100-fold selectivity across a panel of 47 other kinases. It also potently inhibits the proliferation of many tumor cell lines in vitro , shows in vivo activity in tumor xenograft mouse models, and has appropriate physical and pharmacokinetic characteristics to support further evaluation as an anticancer agent.
Effect of extra N-terminal residues on the stability and folding of human lysozyme expressed in Pichia pastoris (2000)

A human lysozyme expression system by Pichia pastoris was constructed with the expression vector of pPIC9, which contains the alpha-factor signal peptide known for high secretion efficiency. P. pastoris expressed the human lysozyme at about 300 mg/l broth, but four extra residues (Glu(-4)-Ala(-3)-Glu(-2)-Ala(-1)-) were added at the N-terminus of the expressed protein (EAEA-lysozyme). To determine the effect of the four extra residues on the stability, structures and folding of the protein, calorimetry, X-ray crystal analysis and GuHCl denaturation experiments were performed. The calorimetric studies showed that the EAEA-lysozyme was destabilized by 9.6 kJ/mol at pH 2.7 compared with the wild-type protein, mainly caused by the substantial decrease in the enthalpy change (DeltaH). On the basis of structural information on the EAEA-lysozyme, thermodynamic analyses show that (1) the addition of the four residues slightly affected the conformation in other parts far from the N-terminus, (2) the large decrease in the enthalpy change due to the conformational changes would be almost compensated by the decrease in the entropy change and (3) the decrease in the Gibbs energy change between the EAEA and wild-type human lysozymes could be explained by the summation of each Gibbs energy change contributing to the stabilizing factors concerning the extra residues.
Inheritance in Nicotiana Tabacum (1924)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
ON THE TRANSDUCING PHAGES IN GLUTAMIC ACID-PRODUCING BACTERIA (1976)

Transducing phages were sought among temperate phages harbored by coryneform and glutamic acid-producing bacteria. By using a nonlysogenic subline of Brevibacterium flavum strain 2247, as the phage indicator, twenty-four temperate phages were isolated from strains of coryneform and unidentified glutamic acid-producing bacteria. Phage CP-119 transduced various markers at frequencies of around 10-7, and the addition of 4mM cAMP to recipient cultures stimulated the transduction. Phage CP-123 transduced the trp marker at a frequency of approximately 10-6 when 1.2M MgCl2 was added to the reaction mixture. Characteristics of these transducing phages and of the lysogeny states of glutamic acid-producing bacteria were discussed.
Reagents for the crosslinking of proteins by equilibrium transfer alkylation (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReagents for the crosslinking of proteins by equilibrium transfer alkylationSumita Mitra and Richard G. LawtonCite this: J. Am. Chem. Soc. 1979, 101, 11, 3097–3110Publication Date (Print):May 1, 1979Publication History Published online1 May 2002Published inissue 1 May 1979https://pubs.acs.org/doi/10.1021/ja00505a043https://doi.org/10.1021/ja00505a043research-articleACS PublicationsRequest reuse permissionsArticle Views472Altmetric-Citations43LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Establishment of a micro-particle bombardment transformation system for Dunaliella salina. (2005)

In this study, we chronicle the establishment of a novel transformation system for the unicellular marine green alga, Dunaliella salina. We introduced the CaMV35S promoter-GUS construct into D. salina with a PDS1000/He micro-particle bombardment system. Forty eight h after transformation, via histochemical staining, we observed the transient expression of GUS in D. salina cells which had been bombarded under rupture-disc pressures of 450 psi and 900 psi. We observed no GUS activity in either the negative or the blank controls. Our findings indicated that the micro-particle bombardment method constituted a feasible approach to the genetic transformation of D. salina. We also conducted tests of the cells' sensitivity to seven antibiotics and one herbicide, and our results suggested that 20 microg/ml of Basta could inhibit cell growth completely. The bar gene, which encodes for phosphinothricin acetyltransferase and confers herbicide tolerance, was introduced into the cells via the above established method. The results of PCR and PCR-Southern blot analyses indicated that the gene was successfully integrated into the genome of the transformants.
New Architectures for Designed Catalysts: Selective Oxidation using AgAu Nanoparticles on Colloid‐Templated Silica (2017)

A highly modular synthesis of designed catalysts with controlled bimetallic nanoparticle size and composition and a well-defined structural hierarchy is demonstrated. Exemplary catalysts-bimetallic dilute Ag-in-Au nanoparticles partially embedded in a porous SiO<sub>2</sub> matrix (SiO<sub>2</sub> -Ag<sub>x</sub> Au<sub>y</sub> )-were synthesized by the decoration of polymeric colloids with the bimetallic nanoparticles followed by assembly into a colloidal crystal backfilled with the matrix precursor and subsequent removal of the polymeric template. This work reports that these new catalyst architectures are significantly better than nanoporous dilute AgAu alloy catalysts (nanoporous Ag<sub>3</sub> Au<sub>97</sub> ) while retaining a clear predictive relationship between their surface reactivity with that of single-crystal Au surfaces. This paves the way for broadening the range of new catalyst architectures required for translating the designed principles developed under controlled conditions to designed catalysts under operating conditions for highly selective coupling of alcohols to form esters. Excellent catalytic performance of the porous SiO<sub>2</sub> -Ag<sub>x</sub> Au<sub>y</sub> structure for selective oxidation of both methanol and ethanol to produce esters with high conversion efficiency, selectivity, and stability was demonstrated, illustrating the ability to translate design principles developed for support-free materials to the colloid-templated structures. The synthetic methodology reported is customizable for the design of a wide range of robust catalytic systems inspired by design principles derived from model studies. Fine control over the composition, morphology, size, distribution, and availability of the supported nanoparticles was demonstrated.
Design, modeling and fabrication of a constant flow pneumatic micropump (2007)

This paper characterizes a bi-directional pneumatic diaphragm micropump and presents a model for performance of an integrated fluidic capacitor. The fluidic capacitor is used to convert pulsatile flow into a nearly continuous flow stream. The pump was fabricated in acrylic using a CNC mill. The stroke volume of the pump is ~1 µL. The pump is self-priming, bubble tolerant and insensitive to changes in head pressure and pneumatic pressure within its operating range. The pump achieves a maximum flow rate of 5 mL min−1 against zero head pressure. With pneumatic pressure set to 40 kPa, the pump can provide flow at 2.6 mL min−1 against a head pressure of 25 kPa. A nonlinear model for the capacitor was developed and compared with experimental results. The ratio of the time constant of the capacitor to the cycle time of the pump is shown to be an accurate indicator of capacitor performance and a useful design tool.
Sensor Fault Detection Using Noise Analysis (1999)

The feasibility of sensor fault detection using noise analysis is evaluated. The noise powers at various frequency bands present in the sensor output are calculated using power spectrum density estimation and compared with historically established noise pattern to identify any abnormalities. The method is applicable to systems for which the noise is stationary under normal operating conditions. Principal component analysis (PCA) is used to reduce the space of secondary variables derived from the power spectrum. T2 statistics is used to detect deviations from the norm. We take advantage of the low-pass filtering characteristics exhibited by most process plants and closed-loop control systems, which allows the noise power at higher frequency bands to be used in the fault detection. The algorithm does not require a process model because it focuses on characterization of each individual sensor and the measurement it generates. Experimental studies with two kinds of garden variety sensors (off the shelf temperature and pressure sensors) are used to validate the feasibility of the proposed approach.
Fundamental and applied experimental investigations of corrosion of steel by LBE under controlled conditions: kinetics, chemistry, morphology, and surface preparation: quarterly report (January 2005-April 2005) (2004)

This project has four components: The fabrication of a materials test apparatus with unique capabilities, Comparative studies of steel corrosion under gas phase conditions comparable to the Lead Bismuth Eutectic (LBE) oxygen control conditions, Isotope labeling studies, and Collaborative efforts with other workers in the field. \nSummary of accomplishments: Started occupation of the High Temperature Materials Experimental Facility. Presented a paper at the meeting of the American Chemical Society in San Diego in March 13-17. Currently reviving the ion beam for implantation experiments. Currently analyzing 38 steel samples from the DELTA loop from LANL.
Short-Term Load Forecasting of Transformer Using Artificial Neural Networks (2005)

신경회로망을 이용한 변압기의 단기 부하예측 알고리즘을 제안한다. 변압기에 대한 단기부하예측은 그 필요성에도 불구하고 연구자들에게 많은 관심을 받지 못했다. 제안된 알고리즘은 입력값으로 예측일 이전의 변압기 최대부하와 해당지역의 최고온도, 최저온도 그리고 예측일의 최고온도, 최저온도로 구성하고 적절한 학습케이스를 선택하여 신경회로망의 학습을 통해 배전용 변압기의 단기부하예측을 수행하였다. 제안된 방법은 서울 남현동의 배전용 변압기를 샘플로 추출하여 예측하였다. 예측결과 배전용 변압기의 부하예측에 대한 정확도의 우수성을 확인했다. 제안된 알고리즘은 배전용 변압기의 과부하에 의한 사고 예방에 도움을 줄 것이다.
Benchmarking iron dextran sensitivity: reactions requiring resuscitative medication in incident and prevalent patients (2005)

The incidence of reactions to iron dextran requiring resuscitative medications, per exposure or per patient, is approximately 0.035%. Reactions of this severity occur after either the test dose or first dose of iron dextran.
Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large US registry study (2019)

The Pigmented Lesion Assay (PLA, sensitivity 91-95%, specificity 69-91%, negative predictive value ?99%) is a commercially available, non-invasive gene expression test that helps dermatologists guide pigmented lesion management decisions and rule out melanoma. Earlier studies have demonstrated high clinical utility and no missed melanomas in a 3-6-month follow-up period. We undertook the current investigations to provide 12-month follow-up data on PLA(-) tests, and to further confirm utility. A 12-month chart review follow-up of 734 pigmented lesions that had negative PLA results from 5 US dermatology centers was performed. Thirteen of these lesions (1.8%) were biopsied in the follow-up period and submitted for histopathologic review. None of the lesions biopsied had a histopathologic diagnosis of melanoma. The test's utility was studied further in a registry (N=1575, 40 US dermatology offices, 62 participating providers), which demonstrated that 99.9% of PLA(-) lesions were clinically monitored, thereby avoiding a surgical procedure, and 96.5% of all PLA(+) lesions were appropriately biopsied, most commonly with a tangential shave. This long-term follow-up study confirms the PLA's high negative predictive value and high utility in helping guide the management of pigmented lesions to avoid unnecessary surgical procedures.
High-Copy Expression Vector Based on Amplification-Promoting Sequences (1994)

We describe a new vector system that allows efficient expression of heterologous proteins in transformed mouse L fibroblasts. This is due to its persistence at high copy numbers, achieved by a 370-bp amplification promoting element (muNTS1) derived from the nontranscribed spacer of murine rDNA. Copy number determination showed that this sequence mediates a 40- to 800-fold amplification of the vector DNA in transfected L cells. High copy number was accompanied by increased expression levels of the reporter gene secreted alkaline phosphatase (SEAP). Analyzing the structural organization of multicopy plasmid DNA in mouse L cells revealed that plasmid DNA is integrated as reiterated head-to-tail concatamers into the chromosomal DNA. The vector described here can be used as a versatile high-copy expression system for heterologous proteins overcoming any limitation to enzyme-deficient cell lines.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation (1998)

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.
Electroporation enhances c-myc antisense oligodeoxynucleotide efficacy (1993)

Obtaining high transfection efficiencies and achieving appropriate intracellular concentrations and localization are two of the most important barriers to the implementation of gene targeted therapy. The efficiency of endogenous uptake of oligodeoxynucleotides (ODNs) varies from cell type to cell type and may be a limiting factor of antisense efficacy. The use of electroporation to obtain high intracellular concentrations of a synthetic ODN in essentially 100% of viable cells is described. It is also shown that the transfected ODNs initially localize to the nucleus and remain there for at least 48 hours. The cellular trafficking of electroporated ODNs is shown to be an energy dependent process. Targeting of the c-myc proto-oncogene of U937 cells by electroporation of phosphorothioate-modified ODNs results in rapid and specific suppression of this gene at ODN concentrations much lower than would otherwise be required. This technique appears to be applicable to a variety of cell types and may represent a powerful new investigate tool as well as a promising approach to the ex vivo treatment of hematologic disorders.