gebhart/patrepeval huggingface dataset:
Development of Ehrlichia canis, Causative Agent of Canine Ehrlichiosis, in the Tick Rhipicephalus sanguineus and Its Differentiation from a Symbiotic Rickettsia (1976)

Certain aspects of the development of Ehrlichia canis, causative agent of canine ehrlichiosis (tropical canine pancytopenia) in Rhipicephalus sanguineus ticks were studied. It was found that partial feeding of nymphs infected as larvae with E canis was a desirable, if not necessary, preliminary treatment for successful infection of dogs with ground-up ticks. It remains unclear whether feeding increased the number or altered the virulence of ehrlichiae within tick tissues. Ehrlichia canis organisms were detected by immunofluorescent microscopy in the midgut and hemocytes and by electron microscopy in the midgut and salivary glands of partially engorged adult ticks which had been infected as larvae and nymphs. Organisms were not observed in the ovary. Intracytoplasmic inclusions contained 1 to 80 elementary bodies, each provided with 2 distinct membranes. Infection of the midgut and salivary gland was confirmed by injecting homogenates of these tissues into susceptible dogs. Staining of gut smears of partially engorged adult ticks by fluorescein-conjugated anti-E canis antibody was found to be a reliable indicator of the infection.
Worldwide Epidemiology of Neutralizing Antibodies to Adeno‐Associated Viruses (2009)

Recombinant adeno-associated viruses (AAVs) have unique gene-transfer properties that speak to their potential as carriers for gene therapy or vaccine applications. However, the presence of neutralizing antibodies to AAV as a result of previous exposure can significantly limit effective gene transfer. In this study, we obtained 888 human serum samples from healthy volunteers in 10 countries around the world. Samples were assayed for neutralizing antibodies to AAV1, AAV2, AAV7, and AAV8, as well as to a novel, structurally distinct AAV vector, rh32.33, in an in vitro transduction inhibition assay. Our data revealed that neutralizing antibodies to AAV2 were the most prevalent antibodies in all regions, followed by antibodies to AAV1. The seroprevalences of antibodies to AAV7 and to AAV8 were lower than that for antibodies to AAV1, and neutralization of AAVrh32.33 was only rarely detected. Our data also indicate a strong linkage of seroreactivity between apparently distinct serotypes that has not been predicted previously in animal models.
Polymeric Delivery Systems (1993)

Examples of successful applications of controlled release are mentioned and commonly used concepts are defined. The chapter describes how polymers are used in devices and how their properties affect device performance. Processes of wide applicability including those covered in succeeding chapters are summarized.
Isoform-specific knockdown and expression of adaptor protein ShcA using small interfering RNA (2002)

Many eukaryotic genes are expressed as multiple isoforms through the differential utilization of transcription/translation initiation sites or alternative splicing. The conventional approach for studying individual isoforms in a clean background (i.e. without the influence of other isoforms) has been to express them in cells or whole organisms in which the target gene has been deleted; this is time-consuming. Recently an efficient post-transcriptional gene-silencing method has been reported that employs a small interfering double-stranded RNA (siRNA). On the basis of this method we report a rapid alternative approach for isoform-specific gene expression. We show how the adaptor protein ShcA can be suppressed and expressed in an isoform-specific manner in a human cell line. ShcA exists in three isoforms, namely p66, p52 and p46, which differ only in their N-terminal regions and are derived from two different transcripts, namely p66 and p52/p46 mRNAs. An siRNA with a sequence shared by the two transcripts suppressed all of them. However, another siRNA whose sequence was present only in p66 mRNA suppressed only the p66 isoform, suggesting that the siRNA signal did not propagate to other regions of the target mRNA. The expression of individual isoforms was achieved by first down-regulating all isoforms by the common siRNA and then transfecting with an expression vector for each isoform that harboured silent mutations at the site corresponding to the siRNA. This allowed functional analysis of individual ShcA isoforms and may be more generally applicable for studying genes encoding multiple proteins.
An Analysis of the Relationships Among Obesity, Plasma Insulin, and Hepatic Lipogenic Enzymes in "Viable Yellow Obese" Mice (Avy/a) (1976)

<P>Abstract copyright UK Data Service and data collection copyright owner.</P>
The disconnect between animal models of sepsis and human sepsis (2006)

Frequently used experimental models of sepsis include cecal ligation and puncture, ascending colon stent peritonitis, and the i.p. or i.v. injection of bacteria or bacterial products (such as LPS). Many of these models mimic the pathophysiology of human sepsis. However, identification of mediators in animals, the blockade of which has been protective, has not translated into clinical efficacy in septic humans. We describe the shortcomings of the animal models and reasons why effective therapy for human sepsis cannot be derived readily from promising findings in animal sepsis.
Cannabinoids. Structure-activity studies related to 1,2-dimethylheptyl derivatives (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCannabinoids. Structure-activity studies related to 1,2-dimethylheptyl derivativesBernard Loev, Paul E. Bender, Frederick Dowalo, Edward Macko, and Philip J. FowlerCite this: J. Med. Chem. 1973, 16, 11, 1200–1206Publication Date (Print):November 1, 1973Publication History Published online1 May 2002Published inissue 1 November 1973https://pubs.acs.org/doi/10.1021/jm00269a002https://doi.org/10.1021/jm00269a002research-articleACS PublicationsRequest reuse permissionsArticle Views267Altmetric-Citations47LEARN 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
Effect of different bioformulations of Paecilomyces lilacinus against root-knot nematode (Meloidogyne incognita) infecting tomato (Solanum esculentum) (2011)

Biocontrol potential of the parasitic fungus Paecilomyces lilacinus (Pl-181) strain was isolated from the egg masses of the nematode affected tomato (Solanum esculentum L.; syn Lycopersium esculentum Mill.) crops was evaluated for the management of root-knot nematode (Meloidogyne incognita Chitwood). The fungal isolate grown on starch rich grains was tested for an ideal formulation with different natural and synthetic inert carrier material. Keeping in view the parameters like colony count, shelf-life coupled with easy dispersibility out of Attapulgite-based clay dust powder + peat powder, heavy loam soil powder + peat powder, talc fine powder + peat powder, kaolin light powder + peat powder, boric acid powder + peat powder, bentonite powder + peat powder and Paecilomyces lilacinus + alone were tried separately. Attapulgite-based clay dust powder + peat powder + Acacia gum powder showed best performance in respect to all the three parameters and also suppressed M. incognita population to a greater extent.
Determination of Oxalic Acid in Biological Material (1970)

Abstract The properties of oxalic acid are reviewed, together with the use that may be made of these in various methods of oxalate analysis, which are critically compared. Information is given on the oxalate content of biological fluids, urinary calculi, tissues, and foods.
Evolution versus Design: Template-Directed Self-Assembly of Peptides to Artificial Proteins (TASP) (2000)

Protein design and mimicry combines elements of synthetic organic chemistry with structural and functional aspects of biological relevance in a unique way. Due to progress in this interdisciplinary research field, access to molecules featuring some essential properties of native proteins appears to be within reach, enabling the complex mechanisms in molecular recognition processes to be deciphered. Since its introduction by the authors, the template approach in protein de novo design (Template Assembled Synthetic Proteins, TASP) has experienced a broad conceptual diversification. Starting from today's state-of-the-art in protein design, we present here some ongoing work in the Lausanne laboratories focusing on the use of regioselectively addressable templates and TASP scaffolds for addressing fundamental questions in peptide assembly, protein folding and mimicry. It is shown that the developed concepts can ideally reconcile evolutionary and rational design principles for creating molecules of biological and therapeutic interest.
Validation of Diacyl Glycerolacyltransferase I as a Novel Target for the Treatment of Obesity and Dyslipidemia Using a Potent and Selective Small Molecule Inhibitor (2008)

A highly potent and selective DGAT-1 inhibitor was identified and used in rodent models of obesity and postprandial chylomicron excursion to validate DGAT-1 inhibition as a novel approach for the treatment of metabolic diseases. Specifically, compound 4a conferred weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depleted serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice.
Drawing Small Cations into Highly Charged Porous Nanocontainers Reveals “Water” Assembly and Related Interaction Problems (2003)

Containing nanowater droplets: A series of polyoxometalate capsules containing shells of water molecules is described. The surfaces of the capsules are covered with nanoscale pores, which when open permit entry to the cavities within (see structure, four of the 20 nanoscale pores are visible, and one of the six encapsulated Na+ ions is shown in violet). Variation of the cluster properties, such as charge and the nature of the internal surface, greatly influences the encapsulated species.
满足21世纪作战要求的新一代战舰——SC—21武器库式舰艇 (1997)

SC-21是美国为满足21世纪作战要求近期开发的新型导弹舰艇。它能装有500个多种导弹共用的垂直发射装置,贮存上千枚类型不同的导弹,采用双层船体和自动化损管装置,以增强受到冲击后的生存力,运用隐身技术减少雷达反射面积和被导弹攻击的面积,采用作战自动化以减少对舰员的要求。本文概述了SC-21舰艇的开发规划,提出了使命要求,分析了技术优势,描述了采用建模与仿真技术测试各种SC-21设计概念有效性的综合计划。
Lipase YS-Catalyzed Enantioselective Transesterification of Alcohols of Bicarbocyclic Compounds (1993)

Abstract Lipase YS-catalyzed enantioselective acylations of (1RS, 2RS, 4RS, 5RS)-bicyclo[2.2.1]heptane-2,5-diol, (1RS, 2SR, 4RS, 5SR)-bicyclo[2.2.2]octane-2,5-diol, (1RS, 2RS, 4RS, 5RS)-bicyclo[2.2.2]octane-2,5-diol, and (1RS, 2SR, 5RS, 6SR)-bicyclo[3.3.1]nonane-2,6-diol with aryl acetates such as phenyl acetate, 1-naphthyl acetate, and 2-naphthyl acetate gave the monoacetates and the diols in optically active forms. The optical purities of (+)-(2R, 5R)-2-acetoxybicyclo[2.2.1]heptan-5-ol, (−)-(1S, 2R, 4S, 5R)-2-acetoxybicyclo[2.2.2]octan-5-ol, and (+)-(2R, 6R)-2-acetoxybicyclo[3.3.1]nonan-6-ol obtained using phenyl acetate were higher than those of the monoacetates which have been resolved by PLE-catalyzed hydrolysis of the corresponding racemic diacetates. Enzymic acylations of the diols using phenyl esters such as phenyl propanoate, phenyl butanoate, and phenyl octanoate as acylating agents gave the corresponding monoesters, which showed nearly the same enantiomeric excess value as the acetates. A simple model for predicting which enantiomer of racemic alcohols is acylated preferentially by lipase YS-catalyzed enantioselective transesterification is proposed on the basis of the results obtained here.
Abstract 3578: New Angiochem-modified doxorubicin with increased brain penetration and efficacy against brain tumors (2010)

Abstract The blood-brain barrier (BBB) is mainly formed by brain capillary endothelial cells which are closely sealed by tight junctions and express high levels of active efflux transport proteins, including P-glycoprotein (Pgp). As a result, the overwhelming majority of small molecules, proteins and peptides do not cross the BBB. Angiochem's engineered peptide compounds (EPiC) provides a non-invasive and flexible platform for small and large molecules to treat brain diseases. Based on these properties, we have created a portfolio of new drug entities composed of siRNA, peptides and mAbs, the most advanced of which is ANG1005 formed by chemical conjugation of our peptide to three molecules of paclitaxel. ANG1005 demonstrated safety and efficacy in two phase ½ clinical trials for the treatment of primary and secondary brain tumors in humans. In the present study, we have investigated the brain uptake of a new chemical entity formed by conjugation of the peptide Angiopep-2 (An2) with 3 molecules of the anti-cancer drug doxorubicin. Despite the clinical effectiveness of doxorubicin in the treatment of many malignant tumors, clinical trials involving systemic administration have demonstrated very limited efficacy in the treatment of gliomas. This limited efficacy can be explained by the poor penetration of the drug thru the BBB and by the effect of the multidrug resistance pump, P-gp. Here, we show by mice in-situ brain perfusion that the ANG-doxorubicin (ANG1007) is transported very efficiently across the BBB. The transport rate is higher than that of unconjugated doxorubicin by at least 10-fold. In vitro, ANG1007 inhibits cancer cell proliferation, with highly cytotoxic activities against various tumor cell lines. In addition, brain perfusion studies performed with P-gp knock-out mice showed that ANG1007 bypasses the drug efflux pump P-gp at the BBB. Furthermore, ANG1007 inhibits growth of glioblastoma s.c. tumors and increases survival of mice implanted with brain tumors. In conclusion, these data confirm that conjugation of chemotherapeutic drugs such as doxorubicin to the peptide Angiopep-2 significantly enhances their entry into the brain and further validate the use of Angiochem's technology for new brain tumor therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3578.
Prognostic significance of Focal Adhesion Kinase (FAK) in node-negative breast cancer. (2015)

552 Background: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase playing an important role as a key mediator for signal transduction. We examined the subtype specific prognostic significance of FAK in node-negative breast cancer. Methods: Using microarray based gene-expression data, we analysed the prognostic significance of FAK (208820_at). The subtype specific prognostic role of FAK was analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of FAK for metastasis-free survival (MFS) was examined in the whole cohort of patients as well as in different molecular subtypes: luminal A (ER+/HER2-/aurora kinase A [AURKA]low, luminal B (ER+/HER2-/AURKAhigh), basal-like (ER-/HER2-), and HER2+. Results: Prognostic significance of FAK was seen in the whole cohort of patients (HR 1.48, 95% CI 1.16-1.87, P = 0.001). Considering the different molecular subtypes, the prognostic effect was most pronounced in luminal B carcinomas (HR 1.67, 95% CI 1.07-2.62, P = 0.0233). FAK expression was neither significantly associated with MFS in luminal A (HR 1.69, 95% CI 0.96-2.98, P = 0.0692), basal-like (HR 0.98, 95% CI 0.64-1.50, P = 0.9400) nor HER2+ (HR 1.63, 95% CI 0.49-5.46, P = 0.8512) carcinomas of the breast. Conclusions: A higher expression of FAK was associated with worse MFS in node-negative breast cancer. The prognostic significance was confined to luminal B carcinomas.
Tamibarotene (2007)

Tamibarotene is a new synthetic retinoid drug recently approved for relapsed or refractory acute promyelocytic leukemia (APL) in Japan. It is a specific agonist for retinoic acid receptor alpha/beta. Compared to all-trans retinoic acid (ATRA), a natural retinoid indicated for a first-line treatment of APL, tamibarotene is chemically more stable and several times more potent as an inducer of differentiation in promyelocytic leukemia cells. In contrast to ATRA, whose plasma concentration declines considerably during daily administration, tamibarotene sustains plasma level probably due to a lower affinity for cellular retinoic acid binding protein. Furthermore, adverse side effects were milder than those of ATRA in clinical trials. Clinical trials held in Japan showed that tamibarotene had efficacy in APL patients who had relapsed from ATRA-induced complete remission. Recently, better understanding of the various mechanisms of action of retinoids has stimulated great interest in its potential use for treatment of various diseases. Tamibarotene is being investigated for treatment of multiple myeloma and Crohn's disease in clinical trials. This review focuses on tamibarotene's mechanisms of action, chemical properties, pharmacokinetics and its use in APL as well as its potential use in various disorders.
Formation of Ru nanocrystals by plasma enhanced atomic layer deposition for nonvolatile memory applications (2006)

The formation of Ru nanocrystals is demonstrated on a SiO2 substrate by plasma enhanced atomic layer deposition using diethylcyclopentadienyl ruthenium and NH3 plasma. The island growth of Ru was observed at the initial stages of the film formation up to a nominal thickness of 11.1nm. A maximum Ru nanocrystal spatial density of 9.7×1011∕cm2 was achieved with an average size of 3.5nm and standard deviation of the size of 20%. Electron charging/discharging effect in the Ru nanocrystals is demonstrated by measuring the flatband voltage shift in the capacitance-voltage measurement of metal-oxide-semiconductor memory capacitor structure.
Randomised double‐blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non‐elective Caesarean section* (2008)

In a randomised, double-blinded study, we compared boluses of phenylephrine 100 microg with ephedrine 10 mg for treating hypotension (systolic blood pressure < 100 mmHg) in 204 patients having non-elective Caesarean section under spinal anaesthesia. Umbilical arterial (UA) and venous (UV) pH and base excess were similar between groups. In the ephedrine group, UA lactate concentration was higher (median 2.6 [interquartile range 2.3-3.3] vs 2.4 [1.9-3.0] mmolxl(-1), p = 0.002) and UV lactate concentration was higher (2.5 [2.2-3.2] vs 2.3 [1.9-2.8] mmolxl(-1), p = 0.016) and more patients had nausea or vomiting (12.7% vs 3.9%, p = 0.02). Clinical neonatal outcome was similar. Of the protocol-compliant patients (n = 148), UA Po(2) and UV Po(2) were lower in the phenylephrine group although oxygen content was similar. We conclude that phenylephrine and ephedrine are both suitable vasopressors for use in non-elective Caesarean sections.
Characteristics of lift-off fabricated AlGaAs/InGaAs single-strained-quantum-well structures on glass and silicon substrates (1988)

A technique involving the liftoff of thin (/approx/1 /mu/m) III-V structures grown on GaAs substrates and subsequent bonding to glass or SiO/sub 2/-covered Si substrates has been investigated. AlGaAs/InGaAs/GaAs single-strained-quantum-well structures have been grown by molecular beam epitaxy and characterized before and after lift-off and bonding to foreign substrates. X-ray diffraction measurements were performed to determine the strain state of the films over a wide temperature range after bonding. Low-temperature photoluminescence measurements on 125/angstrom/-well undoped structures show that the narrow linewidths observed in the as-grown samples (/approx/4 MeV) are not broadened by the lift-off and bonding process. Room- and low-temperature dc measurements made on modulation-doped field-effect transistors show that electronic transport properties are not adversely affected by this process. 8 refs., 6 figs.
The Continuum of Dental Caries—Evidence for a Dynamic Disease Process (2004)

The eventual outcome of dental caries is determined by the dynamic balance between pathological factors that lead to demineralization and protective factors that lead to remineralization. Pathological factors include acidogenic bacteria, inhibition of salivary function, and frequency of ingestion of fermentable carbohydrates. Protective factors include salivary flow, numerous salivary components, antibacterials (both natural and applied), fluoride from extrinsic sources, and selected dietary components. Intervention in the caries process can occur at any stage, either naturally or by the insertion of some procedure or treatment. Dental caries covers the continuum from the first atomic level of demineralization, through the initial enamel or root lesion, through dentinal involvement, to eventual cavitation. The dynamic balance between demineralization and remineralization determines the end result. The disease is reversible, if detected early enough. Since demineralization can be quantified at early stages, before frank cavitation, intervention methods can be tested by short-term clinical trials.
Hydrophilic Camptothecin Analogs That Form Extremely Stable Cleavable Complexes with DNA and Topoisomerase I (2004)

Camptothecin (CPT) analogs that form more stable ternary complexes with DNA and topoisomerase I (termed cleavable complexes) show greater activity in their ability to inhibit tumor cell line growth in preclinical studies. Based on our earlier work, we hypothesized that analogs bearing hydrogen bonding moieties at the 7- through 10-position of CPT would result in more stable cleavable complexes. Consequently, we synthesized analogs with 7-mono-, 7-di-, and 7-trihydroxymethylaminomethyl groups. These analogs showed increasing cleavable complex stability as the number of hydroxyl groups was increased. The 7-trihydroxymethylaminomethyl analog of 10,11-methylenedioxycamptothecin (THMAM-MD) showed remarkable ternary complex stability with a half-life of 116 minutes. This is an order of magnitude more stable than any previously examined analog. Our in vitro analysis demonstrated that these analogs were all potent topoisomerase I poisons and could inhibit tumor cell growth in culture. We studied the effects of THMAM-MD in vivo in severe combined immunodeficient mice bearing HT-29 colon cancer and MiaPaCa-2 pancreatic cancer tumors. The THMAM-MD analog showed excellent, persisting activity in inhibiting tumor growth with both lines. Taken together, our results suggest that CPTs with hydrophilic, hydrogen-bonding groups at the 7-position hold the promise of excellent clinical activity.
Complement and the Kidney (2003)

The C system contains three activation pathways along with regulators poised at key points throughout. All three pathways can participate in innate immunity because of the discriminatory capacity of the key proteins C1q, mannose-binding lectin (MBL) [3][1] and factor H for microorganisms. C also