gebhart/patrepeval huggingface dataset:
Chimeric Trop2 Virus-like Particles (2011)

Trop2 is a recently discovered cell surface glycoprotein overexpressed in pancreatic cancer which could potentially be used as an immunotherapeutic target. Enveloped virus-like particles (VLPs) are highly immunogenic and versatile immune stimulatory agents which can be modified to incorporate exogenous proteins on their membrane envelope to use as cancer vaccines. In this study, we investigated the effects of murine Trop2 (mTrop2) VLP immunization in a pancreatic cancer syngeneic murine model. VLPs incorporating mTrop2 were used to immunize C57BL/6 tumor-bearing mice. Immunization with mTrop2 VLPs led to a significant reduction in tumor growth accompanied by a broad activation and tumor infiltration of CD4(+) and CD8(+) T cells as well as natural killer and natural killer T cells. VLP immunization generated mTrop2-specific cytotoxic T lymphocytes and antibodies with no measurable induction of autoimmunity. Importantly, VLP immunization decreased the population of regulatory T cells and myeloid-derived suppressor cells inside the tumor tissue resulting in decreased levels of immunosuppressive cytokines like interleukin-10 and transforming growth factor-β while promoting the activation of immature macrophages and dendritic cells. Furthermore, combination of VLP immunization with gemcitabine treatment showed an improved effect significantly increasing the survival of tumor bearing mice. Our results demonstrate that mTrop2 VLP immunization can activate broad antitumor immune responses and affect key players in the tumor microenvironment overcoming a major barrier, which has limited the efficacy of cancer vaccines. This study presents a novel immunotherapeutic approach which could potentially be used as an alternative treatment option in combination therapies to treat pancreatic cancer patients.
Large intestine (2002)

Department of Gastroenterology, Henry Ford Hospital, Detroit, Michigan, USA. Correspondence to Robert S. Bresalier, MD, Department of Gastroenterology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, Michigan 48202-2689, USA; e-mail: [email protected]
Beta 2-adrenergic receptor and angiotensin II receptor modulation of sympathetic neurotransmission in human atria. (1994)

The aim of the present study was to investigate beta-adrenergic receptor and angiotensin II (Ang II) receptor modulation of norepinephrine release in human atria. Slices of human atrial appendages were incubated with [3H]norepinephrine, superfused with Krebs-Henseleit solution, and electrically stimulated in superfusion chambers. Pretreatment of the tissue with 6-hydroxydopamine (1.2 mmol/L) before the [3H]norepinephrine incubation to destroy sympathetic nerves reduced the uptake of radioactivity and abolished the stimulation-induced (S-I) outflow of radioactivity. Furthermore, S-I outflow of radioactivity was prevented by the addition of tetrodotoxin (1 mumol/L) to and omission of extracellular Ca2+ from the superfusion solution. Separation of [3H]norepinephrine from its metabolites revealed that the S-I outflow of radioactivity was mainly composed of intact [3H]norepinephrine. Thus, the S-I outflow of radioactivity was taken as an index of norepinephrine release. Isoproterenol (0.001 to 0.1 mumol/L) dose-dependently enhanced the S-I outflow of radioactivity. The concentration-response curve of isoproterenol was shifted to the right by the selective beta 2-adrenergic receptor antagonist ICI 118551 (0.01 and 0.1 mumol/L) but not by the beta 1-adrenergic receptor-selective antagonist atenolol (0.3 and 30 mumol/L). Ang II (0.001 to 1.0 mumol/L) also dose-dependently enhanced S-I outflow of radioactivity. The facilitatory effect of Ang II was blocked by either the peptide Ang II receptor antagonist saralasin (1.0 mumol/L) or EXP 3174 (0.1 mumol/L), the in vitro active form of the nonpeptide Ang II receptor antagonist losartan. The cell-permeable cAMP analogue 8-bromo-cAMP (30 to 300 mumol/L) dose-dependently enhanced S-I outflow of radioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Successful Treatment of Experimental Allergic Encephalomyelitis (EAE) in Guinea Pigs with Homologous Myelin Basic Protein (1974)

Abstract Homologous myelin basic protein has been used successfully for treatment of experimental allergic encephalomyelitis (EAE) in NIH and strain 13 guinea pigs. Response of strain 13 guinea pigs to both induction and treatment of EAE was more consistent than response of outbred, NIH guinea pigs. Serum levels of antibasic protein antibody were related to the amount of mycobacteria used for sensitization rather than to disease severity or success of treatment.
Oligosaccharides of Human Milk (1969)

Abstract A new pentasaccharide, lacto-N-fucopentaose III has been isolated from human milk and characterized as O-β-d-Gal-(1 → 4)-[O-α-l-Fuc-(1 → 3)]-O-β-d-GlcNac-(1 → 3)-O-β-d-Gal-(1 → 4)-d-Glc. The preparation of O-β-d-GlcNAc-(1 → 3)-O-β-d-Gal-(1 → 2)-d-erythritol from lacto-N-tetraose is described.
Production Control to Reduce Starvation in a Partially Flexible Production-Inventory System (2017)

In this paper, we study production control problems in a partially flexible production-inventory system. In such a system, the upstream flexible production subsystem can make two different products, with nonnegligible setup time during changeover. The downstream inflexible production subsystem consists of two manufacturing facilities, with each dedicated to one product type only. The two production subsystems are connected by two dedicated buffers, which comprise the inventory subsystem. Using a renewal model, an optimal control policy is developed to switch products by predefined thresholds for inventory levels to minimize starvation (idle) time of downstream productions. Closed formulas are derived, and sensitivity analyses with respect to setup time change, machine reliability variation, and demand fluctuation are carried out. Finally, an application study in a door manufacturing line at an automotive assembly plant making two distinct types of doors is introduced.
Molecular cloning and expression of <i>Clostridium difficile</i> toxin A in <i>Escherichia coli</i> K 12 (1987)

Clostridium difficile toxin A was purified to homogeneity and was used to raise monospecific antiserum in rabbits. A gene bank of C. difficile DNA in Escherichia coli was constructed by cloning Sau3A-cleaved clostridial DNA fragments into the bacteriophage vector lambda EMBL3. Out of 4500 plaques screened with antitoxin A, 9 clones were positively identified. One of these clones lambda tA5 expressed a 235 kDa protein which exhibited a cytotonic effect on Chinese hamster ovary cells, and had the ability to haemagglutinate rabbit erythrocytes, both properties characteristic of toxin A. The size of the lambda tA5 insert DNA was 14.3 kb.
Alkaloids of the Bark of Aspidosperma rhombeosignatum (1979)

During investigations on the constituents of the trunk bark of A. rhombeosignatum Markgraf, among several others, two new natural indole alkaloids were isolated, limaspermidine (or 21 hydroxy–aspidospermidine) (lia) and 15, 16, 17 trimethoxy–21–oxoaspidoalbidine (III b). Both of them have previously been reported as synthetic products.
Characterization of Viral Load, Viability and Persistence of Influenza A Virus in Air and on Surfaces of Swine Production Facilities (2016)

Indirect transmission of influenza A virus (IAV) in swine is poorly understood and information is lacking on levels of environmental exposure encountered by swine and people during outbreaks of IAV in swine barns. We characterized viral load, viability and persistence of IAV in air and on surfaces during outbreaks in swine barns. IAV was detected in pigs, air and surfaces from five confirmed outbreaks with 48% (47/98) of oral fluid, 38% (32/84) of pen railing and 43% (35/82) of indoor air samples testing positive by IAV RT-PCR. IAV was isolated from air and oral fluids yielding a mixture of subtypes (H1N1, H1N2 and H3N2). Detection of IAV RNA from air was sustained during the outbreaks with maximum levels estimated between 7 and 11 days from reported onset. Our results indicate that during outbreaks of IAV in swine, aerosols and surfaces in barns contain significant levels of IAV potentially representing an exposure hazard to both swine and people.
Development of micro <scp>RNA</scp> therapeutics is coming of age (2014)

MicroRNAs (miRNAs) play key regulatory roles in diverse biological processes and are frequently dysregulated in human diseases. Thus, miRNAs have emerged as a class of promising targets for therapeutic intervention. Here, we describe the current strategies for therapeutic modulation of miRNAs and provide an update on the development of miRNA-based therapeutics for the treatment of cancer, cardiovascular disease and hepatitis C virus (HCV) infection.
Transplantation of human or rodent tumors into cyclosporine-treated mice: a feasible model for studies of tumor biology and chemotherapy. (1984)

Total growth of transplanted human or rodent tumors in the subrenal capsule of mice was much improved by treatment with cyclosporine (CSA, cyclosporin A). Tumor size increased rapidly between days 6 and 12 after implantation, CSA injected on days 1-5 or 2-8 prevented tumor regression. In contrast, immunologic regression occurred after 6 days in absence of the drug. Tumor growth was comparable in CSA-treated mice, athymic nude mice with human tumors, or normal mice with syngeneic rodent tumors. Studies with rodent tumors in syngeneic mice showed that the CSA treatments had no antitumor effect. Inflammatory infiltration was seen on days 6-12 after tumor implantation into control mice. Immunoperoxidase staining showed murine T cells to be prominent in the infiltrate. In contrast, tumors in CSA-treated mice contained minimal inflammatory infiltrate even 12 days after implantation. Allogeneic tumors in CSA-treated mice caused neovascularization, metastases, and local invasion into the kidney. cis-Diamminedichloroplatinum showed highly significant activity against human tumors in CSA-treated mice during the period 6-10 days after tumor implantation but showed no statistically significant antitumor activity 0-6 days after implantation in mice not treated with CSA. We suggest that in CSA-treated mice the subrenal capsule assay for tumor growth provides a rapid, economical model for investigations in vivo of mouse or human tumor biology, for drug screening with a standard tumor, or for determination of optimal treatment of particular human tumors.
Exploring the Role of Software Architecture in Dynamic and Fault Tolerant Pervasive Systems (2007)

Pervasive systems are rapidly growing in size, complexity, distribution, and heterogeneity. As a result, the traditional practice of developing one-off embedded applications that are often rigid and unmanageable is no longer acceptable. This is particularly evident in a growing class of mobile and dynamic pervasive systems that are highly unpredictable, and thus require flexible and adaptable software support. At the same time, many of these applications are mission critical and have stringent fault tolerance requirements. In this paper, we argue that an effective approach to developing software systems in this domain is to employ the principles of software architecture. We discuss the design and implementation of facilities we have provided in a tool-suite targeted for architecture-based development of fault tolerant pervasive systems.
Cerebral Ischemia Related to Globus Pallidus Internus Stimulation for Cervical Dystonia (2011)

The authors present this unique case of cerebral infarction as a complication of DBS. The mechanism of ischemia is unclear. However, in this case, we had performed microstimulation with high amplitude in order to determine the adverse effects. This magnitude of electrical stimulation may have led to small-vessel vasospasm, which may have induced ischemia. Although ischemia after DBS surgery is seldom reported, cerebral ischemia may be a surgical complication after DBS implantation.
Peptic Ulcer Perforation after Phenylbutazone Therapy (1954)

Two Cases of Injury to the Femoral ArteryThe following two cases are thought to be worthy of record on account of the rarity of injury to the femoral artery.
Catalytic and Molecular Properties of the Quinohemoprotein Tetrahydrofurfuryl Alcohol Dehydrogenase from <i>Ralstonia eutropha</i> Strain Bo (2001)

The quinohemoprotein tetrahydrofurfuryl alcohol dehydrogenase (THFA-DH) from Ralstonia eutropha strain Bo was investigated for its catalytic properties. The apparent k(cat)/K(m) and K(i) values for several substrates were determined using ferricyanide as an artificial electron acceptor. The highest catalytic efficiency was obtained with n-pentanol exhibiting a k(cat)/K(m) value of 788 x 10(4) M(-1) s(-1). The enzyme showed substrate inhibition kinetics for most of the alcohols and aldehydes investigated. A stereoselective oxidation of chiral alcohols with a varying enantiomeric preference was observed. Initial rate studies using ethanol and acetaldehyde as substrates revealed that a ping-pong mechanism can be assumed for in vitro catalysis of THFA-DH. The gene encoding THFA-DH from R. eutropha strain Bo (tfaA) has been cloned and sequenced. The derived amino acid sequence showed an identity of up to 67% to the sequence of various quinoprotein and quinohemoprotein dehydrogenases. A comparison of the deduced sequence with the N-terminal amino acid sequence previously determined by Edman degradation analysis suggested the presence of a signal sequence of 27 residues. The primary structure of TfaA indicated that the protein has a tertiary structure quite similar to those of other quinoprotein dehydrogenases.
Lung cancer chemoprevention: difficulties, promise and potential agents? (2012)

The manuscript presents: a) a number of promising agents which appear applicable to further Phase II prevention trials; b) approaches to defining potential preventive agents as well; c) approaches which might mitigate the side effects associated with potential agents most specifically the use of aerosols. Finally, we discuss biomarker studies both preclinical and clinical which might help support potential Phase II trials. The particular appeal to the preclinical studies is that they can be followed to a tumor endpoint. We hope that this will give the reader further background and allow one to appreciate the potential and some of the hurdles associated with lung cancer chemoprevention.
M.D.A. Freeman, ed., The State, The Law and the Family, Tavistock Publications Ltd. Sweet and Maxwell Ltd., London, 1984 pp. xi + 318 (1986)

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TrkA expression in the CNS: evidence for the existence of several novel NGF-responsive CNS neurons (1995)

NGF acts as a neurotrophic factor by binding and activating its receptor on certain neuronal populations in the CNS and PNS. TrkA is a receptor for NGF. Recent findings in vitro indicate that this NGF-activated receptor tyrosine kinase transduces the NGF signal. To further define NGF actions in the CNS, we examined trkA expression in the adult rat brain. We found that trkA mRNA and immunoreactivity (IR) coincided in specific, defined neuronal populations in the forebrain and brainstem. In addition to cholinergic neurons in the basal forebrain and neostriatum, trkA expression was found in noncholinergic neurons in (1) the paraventricular anterior and reuniens thalamic nuclei, (2) the rostral and intermediate subnuclei of the interpeduncular nucleus (IPN), (3) scattered neurons in the ventrolateral and paramedian medulla, (4) the prepositus hypoglossal nucleus, and (5) the area postrema. NGF responsiveness was demonstrated for each of these populations. In contrast to trkA, p75NGFR was found only in a minority of NGF-responsive populations. Our data provide further evidence that expression of trkA marks NGF-responsive CNS neurons and suggests novel roles for NGF in the brain.
Overexpression of the ferritin H subunit in cultured erythroid cells changes the intracellular iron distribution (1996)

To test the hypothesis that variations in H- and L-subunit composition in the ferritin shell affect intracellular iron metabolism, we established stable transfectants of mouse erythroleukemia cells overexpressing the H-ferritin subunit. Analyses were performed on individual clones of transfected cells induced to differentiate with hexamethylenbisacetamide (HMBA). The results showed that there was a reduction in the amount of hemoglobin produced, in inverse relationship with the level of H-subunit overexpression. Incorporation of [2- 14C]glycine into heme was reduced by 20% t0 30% in the clones overexpressing H-ferritin subunit compared with control clone. However, the reduction in hemoglobin production was not reversed by addition of heme precursors (delta-aminolevulinic acid or iron) or by hemin itself. A reduced accumulation of beta-globin mRNA was also observed, which could account for the impaired hemoglobin synthesis. Furthermore, synthesis of the endogenous L-ferritin subunit was greatly repressed. Gel retardation assays performed on cytoplasmic extracts of transfected cells using an iron-responsive element (IRE) as a probe revealed that in overexpressing cells, the iron-regulatory protein (IRP) had a conformation with a high RNA-binding affinity, thus leading to translational repression of the endogenous L-ferritin synthesis. These data suggest that an increased formation of H-rich isoferritins leads to a rapid chelation of the regulatory iron pool. While the mechanism underlying the reduction in beta-globin mRNA remains to be elucidated, this study provides direct evidence for the role of IRP-mediated regulation of ferritin expression in erythroid cell metabolism.
Vesicles of polymeric bilayer and monolayer membranes (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVesicles of polymeric bilayer and monolayer membranesT. Kunitake, N. Nakashima, K. Takarabe, M. Nagai, A. Tsuge, and H. YanagiCite this: J. Am. Chem. Soc. 1981, 103, 19, 5945–5947Publication Date (Print):September 1, 1981Publication History Published online1 May 2002Published inissue 1 September 1981https://pubs.acs.org/doi/10.1021/ja00409a071https://doi.org/10.1021/ja00409a071research-articleACS PublicationsRequest reuse permissionsArticle Views375Altmetric-Citations73LEARN 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
Structure and Proposed Amino-Acid Sequence of a Pepsin from Atlantic Cod (<i>Gadus morhua</i>) (1998)

The crystal structure of a pepsin from the gastric mucosa of Atlantic cod has been determined to 2.16 A resolution. Data were collected on orthorhombic crystals with cell dimensions a = 35.98, b = 75.40 and c = 108.10 A, on a FAST area-detector system. The phase problem was solved by the molecular-replacement method using porcine pepsin (PDB entry 5PEP) as a search model. The structure has been refined to a crystallographic R factor of 20.8% using all reflections between 8.0 and 2.16 A, without prior knowledge of the primary sequence. The resulting crystal structure is very similar to the porcine enzyme, consisting of two domains with predominantly beta-sheet structure in the same sequential positions as the enzyme from pig. In the course of the model building, 122 residues were substituted and two residues deleted from the starting model to give a polypeptide chain of 324 amino acids and a sequence identity of 57.7% with the pig pepsin. No carbohydrate residues were located. Sequence alignment with available aspartic proteinases, indicates that the fish enzyme seems to be more related to mammalian gastric pepsins than to the mammalian gastricsins and chymosins, lysosomal cathepsin D's and a pepsin from tuna fish. The amino-acid composition of the cod enzyme, however, is more in accordance with the cathepsin D's.
Pre-column reactions to eliminate interferents in the liquid chromatographic analysis of p-hydroxybenzoates in complex pharmaceuticals (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPre-column reactions to eliminate interferents in the liquid chromatographic analysis of p-hydroxybenzoates in complex pharmaceuticalsFrederick F. CantwellCite this: Anal. Chem. 1976, 48, 13, 1854–1859Publication Date (Print):November 1, 1976Publication History Published online1 May 2002Published inissue 1 November 1976https://pubs.acs.org/doi/10.1021/ac50007a011https://doi.org/10.1021/ac50007a011research-articleACS PublicationsRequest reuse permissionsArticle Views106Altmetric-Citations41LEARN 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
Transient Neonatal Zinc Deficiency Caused by a Heterozygous G87R Mutation in the<i>Zinc Transporter ZnT-2 (SLC30A2)</i>Gene in the Mother Highlighting the Importance of Zn<sup><b>2+</b></sup>for Normal Growth and Development (2013)

Suboptimal dietary zinc (Zn(2+)) intake is increasingly appreciated as an important public health issue. Zn(2+) is an essential mineral, and infants are particularly vulnerable to Zn(2+) deficiency, as they require large amounts of Zn(2+) for their normal growth and development. Although term infants are born with an important hepatic Zn(2+) storage, adequate Zn(2+) nutrition of infants mostly depends on breast milk or formula feeding, which contains an adequate amount of Zn(2+) to meet the infants' requirements. An exclusively breast-fed 6 months old infant suffering from Zn(2+) deficiency caused by an autosomal dominant negative G87R mutation in the Slc30a2 gene (encoding for the zinc transporter 2 (ZnT-2)) in the mother is reported. More than 20 zinc transporters characterized up to date, classified into two families (Slc30a/ZnT and Slc39a/Zip), reflect the complexity and importance of maintaining cellular Zn(2+) homeostasis and dynamics. The role of ZnTs is to reduce intracellular Zn(2+) by transporting it from the cytoplasm into various intracellular organelles and by moving Zn(2+) into extracellular space. Zips increase intracellular Zn(2+) by transporting it in the opposite direction. Thus the coordinated action of both is essential for the maintenance of Zn(2+) homeostasis in the cytoplasm, and accumulating evidence suggests that this is also true for the secretory pathway of growth hormone.