gebhart/patrepeval huggingface dataset:
Selective Immunolesioning of the Basal Forebrain Cholinergic System Disrupts Short‐term Memory in Rats (1996)

Selective depletion of nerve growth factor receptor-bearing neurons in the basal forebrain cholinergic system nuclei by the immunotoxin 192 IgG-saporin offers a new and highly useful tool for the study of the role of the forebrain cholinergic system in cognitive functions. In the present study, we have tested the effects of 192 IpG-saporin in an operant delayed matching-to-position task which has previously been used to discriminate between delay-dependent learning impairments and delay-independent disturbances of non-mnemonic processes. Rats were first trained to criterion performance and then received intraventricular injections of 5 microg of 192 IgG-saporin 4 weeks prior to a second testing session. Rats with 192 IgG-saporin lesions displayed a significant delay-dependent decline in performance compared to normal controls, indicating a deficit in short-term memory. Administration of the muscarinic blocker scopolamine (0.5 mg/kg, i.p.) produced more pronounced impairment in the performance of the normal control rats across all delays, and induced further impairment also in animals with 192 IgG-saporin lesions. These effects were not observed following control injections of methyl scopolamine, suggesting that the impairment induced by scopolamine was due to the blockade of central muscarinic receptors. No improvement in performance was observed in either group following systemic treatment with the muscarinic cholinergic agonist arecoline (1.00 mg/kg). Biochemical and morphological analyses confirmed the selective and severe (>90-95%) depletion of cholinergic neurons throughout the septal-diagonal band area and the nucleus basalis region by the intraventricular 192 IgG-saporin treatment. Although the immunotoxin was observed to produce additional damage to the cerebellar Purkinje cells, no gross motor abnormalities were observed that could contribute to the effects on accuracy in the task used here. In conclusion, the results show that selective combined lesions of the basal forebrain cholinergic neurons in the septal-diagonal band area and nucleus basalis produce long-lasting impairments in short-term memory, thus providing further support for a role of this system in cognitive functions.
Maternal glucocorticoid exposure alters tight junction protein expression in the brain of fetal sheep (2009)

We examined the expression of tight junction (TJ) proteins in the cerebral cortex, cerebellum, and spinal cord of fetuses after maternal treatment with single and multiple courses of dexamethasone. Ewes received either single courses of four 6-mg dexamethasone or placebo injections every 12 h for 48 h between 104 and 107 days or the same treatment once a week between 76-78 and 104-107 days of gestation. TJ protein expression was determined by Western immunoblot analysis on tissue harvested at 105-108 days of gestation. Blood-brain barrier permeability has been previously quantified with the blood-to-brain transfer constant (K(i)) with alpha-aminoisobutyric acid (39). After a single course of dexamethasone, claudin-5 increased (P < 0.05) in the cerebral cortex, occludin and claudin-1 increased in the cerebellum, and occludin increased in the spinal cord. After multiple dexamethasone courses, occludin and zonula occludens (ZO)-1 increased in the cerebral cortex, and occludin and claudin-1 increased in the cerebellum. Junctional adhesion molecule-A and ZO-2 expressions did not change. Linear regression comparing K(i) to TJ proteins showed inverse correlations with claudin-1 and claudin-5 in the cerebral cortex after a single course and ZO-2 in the spinal cord after multiple courses and direct correlations with ZO-1 in the cerebellum and spinal cord after multiple courses. We conclude that maternal glucocorticoid treatment increases the expression of specific TJ proteins in vivo, patterns of TJ protein expression vary after exposure to single and multiple glucocorticoid courses, and decreases in blood-brain barrier permeability are associated with increases in claudin-1, claudin-5, and ZO-2 expression and decreases in ZO-1 expression. In utero glucocorticoid exposure alters the molecular composition of the barrier and affects fetal blood-brain barrier function.
High-Level Production of Human Leptin by Fed-Batch Cultivation of Recombinant Escherichia coli and Its Purification (1999)

Human leptin is a 16-kDa (146-amino-acid) protein that is secreted from adipocytes and influences body weight homeostasis. In order to obtain high-level production of leptin, the human obese gene coding for leptin was expressed in Escherichia coli BL21(DE3) under the strong inducible T7 promoter. The recombinant leptin was produced as inclusion bodies in E. coli, and the recombinant leptin content was as high as 54% of the total protein content. For production of recombinant human leptin in large amounts, pH-stat fed-batch cultures were grown. Expression of leptin was induced at three different cell optical densities at 600 nm (OD600), 30, 90, and 140. When cells were induced at an OD600 of 90, the amount of leptin produced was 9.7 g/liter (37% of the total protein). After simple purification steps consisting of inclusion body isolation, denaturation and refolding, and anion-exchange chromatography, 144.9 mg of leptin that was more than 90% pure was obtained from a 50-ml culture, and the recovery yield was 41.1%.
neu Antigen-Negative Variants Can Be Generated after neu-Specific Antibody Therapy in neu Transgenic Mice (2004)

Prolonged administration of HER-2/neu-specific monoclonal antibody therapy is now widely used for the treatment of HER-2/neu-overexpressing tumors in advanced-stage breast cancer patients. Monoclonal antibody therapy has the potential to promote reduced tumor expression of HER-2/neu by receptor down-modulation and/or the generation of antigen-negative variants. Loss of antigen by either mechanism could potentially impact subsequent therapeutic strategies targeting HER-2/neu. In this study, the effects of chronic neu-specific monoclonal antibody therapy on tumor growth and neu protein expression were examined in a murine model of neu-overexpressing breast cancer. Treatment of neu-overexpressing tumors with neu-specific antibody, in vitro or in vivo, resulted in significant tumor growth inhibition. When neu antibody was used to treat neu-overexpressing tumor cells both in vitro and in vivo in tumor-bearing mice, neu receptor expression was not diminished after cessation of therapy. However, in the setting of clinically undetectable disease in a fraction of animals, antigen-negative variants were generated. An understanding of the effects of monoclonal antibodies on target antigen expression is critical for the future design and testing of novel HER-2/neu-targeted therapies administered in combination with or after HER-2/neu-specific monoclonal antibody therapy.
An Early Study on the Mechanisms that Allow Tissue-Engineered Vascular Grafts to Resist Intimal Hyperplasia (2011)

Intimal hyperplasia is one of the prominent failure mechanisms for arteriovenous fistulas and arteriovenous access grafts. Human tissue-engineered vascular grafts (TEVGs) were implanted as arteriovenous grafts in a novel baboon model. Ultrasound was used to monitor flow rates and vascular diameters throughout the study. Intimal hyperplasia in the outflow vein of TEVGs was assessed at the anastomosis and at juxta-anastomotic regions via histological analysis, and was compared to intimal hyperplasia with polytetrafluoroethylene (PTFE) grafts in the baboon model and in literature reports from other animal models. Less venous intimal hyperplasia was observed in histological sections with arteriovenous TEVGs than with arteriovenous PTFE grafts. TEVGs were associated with a mild, noninflammatory intimal hyperplasia. The extent of intimal tissue that formed with TEVG placement correlated with the rate of blood flow through tissue engineered vascular grafts at 2 weeks postimplant. Outflow vein dilatation was observed with increased flow rate. Both mid-graft flow rates and outflow vein diameters reached a plateau by week 4, which suggested that venous remodeling and intimal hyperplasia largely occurred within the first 4 weeks of implant in the baboon model. Given their compliant and noninflammatory nature, TEVGs appear resistant to triggers for venous intimal hyperplasia that are common for PTFE arteriovenous grafts, including (1) abundant proinflammatory macrophage populations that are associated with PTFE grafts and (2) compliance mismatch between PTFE grafts and the outflow vein. Our findings suggest that arteriovenous TEVGs develop only a mild form of venous intimal hyperplasia, which results from the typical hemodynamic changes that are associated with arteriovenous settings.
Absence of the Complement Anaphylatoxin C3a Receptor Suppresses Th2 Effector Functions in a Murine Model of Pulmonary Allergy (2002)

Asthma is a chronic inflammatory disease of the lung resulting in airway obstruction. The airway inflammation of asthma is strongly linked to Th2 lymphocytes and their cytokines, particularly IL-4, IL-5, and IL-13, which regulate airway hyperresponsiveness, eosinophil activation, mucus production, and IgE secretion. Historically, complement was not thought to contribute to the pathogenesis of asthma. However, our previous reports have demonstrated that complement contributes to bronchial hyperreactivity, recruitment of airway eosinophils, IL-4 production, and IgE responses in a mouse model of pulmonary allergy. To define the complement activation fragments that mediate these effects, we assessed the role of the complement anaphylatoxin C3a in a mouse model of pulmonary allergy by challenging C3aR-deficient mice intranasally with a mixed Ag preparation of Aspergillus fumigatus cell culture filtrate and OVA. Analysis by plethysmography after challenge revealed an attenuation in airway hyperresponsiveness in C3aR-deficient mice relative to wild-type mice. C3aR-deficient mice also had an 88% decrease in airway eosinophils and a 59% reduction in lung IL-4-producing cells. Consistent with the reduced numbers of IL-4-producing cells, C3aR-deficient mice had diminished bronchoalveolar lavage levels of the Th2 cytokines, IL-5 and IL-13. C3aR knockout mice also exhibited decreases in IgE titers as well as reduced mucus production. Collectively, these data highlight the importance of complement activation, the C3a anaphylatoxin, and its receptor during Th2 development in this experimental model and implicate these molecules as possible therapeutic targets in diseases such as asthma.
Ability to Predict Metastasis Based On Pathology Findings and Alterations in Nuclear Structure Of Normal-Appearing and Cancer Peripheral Zone Epithelium in the Prostate (2004)

Alterations in cancer or normal-appearing nuclei adjacent to peripheral zone cancer areas can predict PCa progression and/or death. The QNG-NN and QNG-CA solutions could be combined with pathology variables to improve the prediction of distant metastasis.
The Viability of Autologous Fat Grafts Harvested With the LipiVage System (2008)

This study evaluates the viability of adipose aspirates harvested with the LipiVage system (Genesis Biosystems Inc, Lewisville, TX), a newly developed fat harvesting device, and determines a potentially preferred method for possible large-quantity fat graft harvesting. Adipose aspirates were harvested with the LipiVage system from the abdomen of 16 female patients (group 1, n = 8) according to the instruction by the manufacturer and with conventional liposuction (group 2, n = 8). Samples from conventional liposuction were spun at 50 g for 10 minutes and the resulting middle layer of fat was collected. All fat graft samples were evaluated with trypan blue vital staining for viable adipocyte count, glycerol-3-phosphatase dehydrogenase (G3PDH) assay for intracellular enzyme activity, and histology. In this study, group 1 had significantly higher viable adipocyte count than group 2 had (3.7 +/- 0.64 versus 2.37 +/- 0.56 x 10(6) /mL, P = 0.0021). G3PDH assay showed a marked increase of intracellular enzyme activity in group 1 compared with in group 2 (0.61 +/- 0.10 versus 0.34 +/- 0.13 U/mL, P = 0.00045). Histology revealed normal structures of fragmental fatty tissues in both groups. While adipose aspirates by both modalities maintain normal structure, the LipiVage system yields a greater number of viable adipocytes and sustains a higher level of intracellular enzyme activity within fat grafts and can potentially be a preferred method of choice for large-quantity fat graft harvesting.
Use of Radiolabeled Antibodies to Carcinoembryonic Antigen for the Detection and Localization of Diverse Cancers by External Photoscanning (1978)

To determine whether tumors containing carcinoembryonic antigen could be detected by administration of a radiolabeled, affinity-purified, goat lgG having 70 per cent immunoreactivity against carcinoembryonic antigen, 18 patients with a history of cancer of diverse histopathology received an average total dose of 1.0 mCi of 131l-labeled lgG. Total-body photoscans were performed with a gamma scintillation camera at various intervals after administration of the radioactive antibody. Ordinary photoscans proved difficult to interpret because of blood-pool background radioactivity, thus necessitating the computer subtraction of radioactive blood-pool agents from the antibody's 131l activity. Tumor location could be demonstrated at 48 hours after injection in almost all cases studied. The scans were negative in patients without demonstrable tumors or with tumors apparently devoid of carcinoembryonic antigen. Circulating antigen levels of up to 350 ng per milliliter did not prevent successful tumor imaging after injection of the radioantibody.
FDA Regulation of Stem Cell–Based Products (2009)

Cell self-renewal and the capacity to differentiate into multiple cell types (pluripotency) are biological attributes casting stem cells as attractive candidates for development of therapies targeting indications that involve functional restoration of damaged tissues. In the United States, clinical trials designed to demonstrate the safety and effectiveness of stem cell-based products are regulated by the U.S. Food and Drug Administration (FDA). To ensure that subjects enrolled in a clinical study involving stem cell-based products are not exposed to significant and unreasonable risk, the FDA reviews medical and scientific information that encompasses delineation of product-specific characteristics and preclinical testing to determine whether there is sufficient safety assurance to permit initiation of human clinical studies.
Kinetic Model for FGF, FGFR, and Proteoglycan Signal Transduction Complex Assembly (2004)

The current working model for fibroblast growth factor receptor (FGFR) dimerization and activation requires the assembly of a ternary complex of fibroblast growth factor (FGF), FGFR, and heparin or heparan sulfate proteoglycan (HSPG) on the plasma membrane. The recent FGF2-FGFR1-heparin crystal structure provides a detailed but static view of the FGF-FGFR-heparin complex. However, the kinetics of ternary complex assembly has yet to be investigated. Here, we characterize FGF2, FGFR1, and heparin interactions using surface plasmon resonance (SPR). Binding constants for binary FGF2/FGFR1 (KD = 62 nM), FGF2/heparin (KD = 39 nM), and FGFR1/heparin (KD = 3.2 microM) interactions correlate to the magnitude of binding interface observed in the FGF2-FGFR1-heparin crystal structure. Interestingly, comparison of sensorgrams of sequential injections of FGF2 and FGFR1 and equimolar FGF2-FGFR1 injections onto a heparin neoproteoglycan surface demonstrates that FGF2 dramatically enhances the association of FGFR1 with heparin and leads us to propose a model for the stepwise assembly of a ternary FGF-FGFR-HSPG complex. The weak binding affinity of the FGFR1-heparin interaction suggests that in this model, FGFR and HSPG are unbound in the absence of FGF ligand. The availability of FGF results in formation of initial FGF-HSPG complexes, which promotes the rapid binding of FGFR and creates a ternary complex capable of undergoing dimerization and subsequent FGFR activation. In contrast, alternative models for the kinetic assembly of a ternary complex in which binary FGF-FGFR or FGFR-HSPG complexes are intermediates do not conform well with the experimental data.
Genome-Wide Association Studies in Alzheimer Disease (2008)

The genetics of Alzheimer disease (AD) to date support an age-dependent dichotomous model whereby earlier age of disease onset (< 60 years) is explained by 3 fully penetrant genes (APP [NCBI Entrez gene 351], PSEN1 [NCBI Entrez gene 5663], and PSEN2 [NCBI Entrez gene 5664]), whereas later age of disease onset (> or = 65 years) representing most cases of AD has yet to be explained by a purely genetic model. The APOE gene (NCBI Entrez gene 348) is the strongest genetic risk factor for later onset, although it is neither sufficient nor necessary to explain all occurrences of disease. Numerous putative genetic risk alleles and genetic variants have been reported. Although all have relevance to biological mechanisms that may be associated with AD pathogenesis, they await replication in large representative populations. Genome-wide association studies have emerged as an increasingly effective tool for identifying genetic contributions to complex diseases and represent the next frontier for furthering our understanding of the underlying etiologic, biological, and pathologic mechanisms associated with chronic complex disorders. There have already been success stories for diseases such as macular degeneration and diabetes mellitus. Whether this will hold true for a genetically complex and heterogeneous disease such as AD is not known, although early reports are encouraging. This review considers recent publications from studies that have successfully applied genome-wide association methods to investigations of AD by taking advantage of the currently available high-throughput arrays, bioinformatics, and software advances. The inherent strengths, limitations, and challenges associated with study design issues in the context of AD are presented herein.
2,4-Diaminopyrimidines. Cyclization of 6-(phenacylthio) and related derivatives to thieno[2,3-d]pyrimidines and thiazolo[3,2-c]pyrimidines (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2,4-Diaminopyrimidines. Cyclization of 6-(phenacylthio) and related derivatives to thieno[2,3-d]pyrimidines and thiazolo[3,2-c]pyrimidinesBarbara RothCite this: J. Med. Chem. 1969, 12, 2, 227–232Publication Date (Print):March 1, 1969Publication History Published online1 May 2002Published inissue 1 March 1969https://doi.org/10.1021/jm00302a008RIGHTS & PERMISSIONSArticle Views136Altmetric-Citations19LEARN 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 InReddit PDF (707 KB) Get e-Alertsclose Get e-Alerts
Electrical properties of AlGaN∕GaN heterostructures grown on vicinal sapphire (0001) substrates by molecular beam epitaxy (2006)

Electrical properties of AlGaN∕GaN heterostructures grown on vicinal sapphire (0001) substrates by molecular beam epitaxy (MBE) are investigated. It is found that electrical properties of the two-dimensional electron gas (2DEG) in the heterostructures grown on 2.0°-off vicinal substrates are superior to those grown on the 0.5°-off vicinal substrates. Anisotropic phenomenon of the 2DEG mobility in the heterostructures grown on 2.0°-off substrates is demonstrated, which strongly relates to the macrostep structures on the surface. The 2DEG mobility as high as 2018cm2∕Vs is obtained at the room temperature from the authors’ all-MBE-grown sample measured in the direction parallel to the macrostep. It is suggested that the direction effect should be taken into account when designing the device structure.
Optical interconnection networks in data centers: recent trends and future challenges (2013)

Warehouse-scale data center operators need much-higher-bandwidth intra-data center networks (DCNs) to sustain the increase of network traffic due to cloud computing and other emerging web applications. Current DCNs based on commodity switches require excessive amounts of power to face this traffic increase. Optical intra-DCN interconnection networks have recently emerged as a promising solution that can provide higher throughput while consuming less power. This article provides an update on recent developments in the field of ultra-highcapacity optical interconnects for intra-DCN communication. Several recently proposed architectures and technologies are examined and compared, while future trends and research challenges are outlined.
Aliovalent titanium substitution in layered mixed Li Ni–Mn–Co oxides for lithium battery applications (2011)

Improved electrochemical characteristics are observed for Li[Ni1/3Co1/3−yTiyMn1/3]O2 cathodes, compared to the baseline material, with up to 15% increased discharge capacity.
Biological Activities of Lipid A Complexed with Bovine‐Serum Albumin (1972)

Lipid A preparations from the lipopolysaccharides of four Salmonella minnesota R mutants and one Escherichia coli 0100 R mutant were assayed as soluble complexes with bovine serum albumin for lethality in mice, pyrogenicity in rabbits and complement inactivation. Although generally less active than endotoxic lipopolysaccharides, these lipid · albumin complexes nevertheless exhibited strong biological activity. These results indicate that lipid A contains the endotoxic principle of bacterial lipopolysaccharides.