gebhart/patrepeval huggingface dataset:
Pomegranate Phenolics from the Peels, Arils, and Flowers Are Antiatherogenic: Studiesin Vivoin Atherosclerotic Apolipoprotein E-Deficient (E0) Mice andin Vitroin Cultured Macrophages and Lipoproteins (2008)

We have analyzed in vivo and in vitro the antiatherogenic properties and mechanisms of action of all pomegranate fruit parts: peels (POMxl, POMxp), arils (POMa), seeds (POMo), and flowers (POMf), in comparison to whole fruit juice (PJ). Atherosclerotic E 0 mice consumed POM extracts [200 microg of gallic acid equivalents (GAE)/mouse/day] for 3 months. Blood samples, peritoneal macrophages (MPM), and aortas were then collected. All POM extracts possess antioxidative properties in vitro. After consumption of PJ, POMxl, POMxp, POMa, or POMf by E (0) mice, the atherosclerotic lesion area was significantly decreased by 44, 38, 39, 6, or 70%, respectively, as compared to placebo-treated group, while POMo had no effect. POMf consumption reduced serum lipids, and glucose levels by 18-25%. PJ, POMxl, POMxp, POMf, or POMa consumption resulted in a significant decrement, by 53, 42, 35, 27, or 13%, respectively, in MPM total peroxides content, and increased cellular paraoxonase 2 (PON2) activity, as compared to placebo-treated mice. The uptake rates of oxidized-LDL by E (0)-MPM were significantly reduced by approximately 15% after consumption of PJ, POMxl, or POMxp. Similar results were obtained on using J774A.1 macrophage cell line. Finally, pomegranate phenolics (punicalagin, punicalin, gallic acid, and ellagic acid), as well as pomegranate unique complexed sugars, could mimic the antiatherogenic effects of pomegranate extracts. We conclude that attenuation of atherosclerosis development by some of the POM extracts and, in particular, POMf, could be related to the combined beneficial effects on serum lipids levels and on macrophage atherogenic properties.
Readily Available Tissue-Engineered Vascular Grafts (2011)

Autologous or synthetic vascular grafts are used routinely for providing access in hemodialysis or for arterial bypass in patients with cardiovascular disease. However, some patients either lack suitable autologous tissue or cannot receive synthetic grafts. Such patients could benefit from a vascular graft produced by tissue engineering. Here, we engineer vascular grafts using human allogeneic or canine smooth muscle cells grown on a tubular polyglycolic acid scaffold. Cellular material was removed with detergents to render the grafts nonimmunogenic. Mechanical properties of the human vascular grafts were similar to native human blood vessels, and the grafts could withstand long-term storage at 4 °C. Human engineered grafts were tested in a baboon model of arteriovenous access for hemodialysis. Canine grafts were tested in a dog model of peripheral and coronary artery bypass. Grafts demonstrated excellent patency and resisted dilatation, calcification, and intimal hyperplasia. Such tissue-engineered vascular grafts may provide a readily available option for patients without suitable autologous tissue or for those who are not candidates for synthetic grafts.
The CRISPR System—Keeping Zebrafish Gene Targeting Fresh (2013)

We are entering a new era in our ability to modify and edit the genomes of model organisms. Zinc finger nucleases (ZFNs) opened the door to the first custom nuclease-targeted genome engineering in the late 1990s. However, ZFNs remained out of reach for most research labs because of the difficulty of production, high costs, and modest efficacy in many applications. Transcription activator-like effector nucleases (TALENs) were built upon a DNA binding system discovered in a group of plant bacterial pathogens and broadened custom nuclease technology, showing significant improvements in both targeting flexibility and efficiency. Perhaps most importantly, TALENs are open source and easy to produce, providing zebrafish laboratories around the world with affordable tools that can be made in-house rapidly, at low cost, and with reliably high activity. Now a new system for targeted genome engineering derived from the CRISPR/Cas system in eubacteria and archaea promises to simplify this process further. Together, these tools will help overcome many of the bottlenecks that have constrained gene targeting in zebrafish, paving the way for advanced genome engineering applications in this model teleost.
Development of Inhalational Agents for Oncologic Use (2001)

Because regional chemotherapy has been useful in treatment and palliation of many cancer types, the concept of delivering drugs by inhalation for the treatment of cancers in the lung is attractive. Much higher local drug exposure can be achieved with total doses considerably lower than those required for systemic administration, resulting in lower exposure of nonrespiratory tract tissues to potentially toxic drugs. Regional delivery of chemotherapy to the respiratory tract has been shown to have activity in preclinical and clinical studies. Technical improvements in delivery methods have now made it possible to conduct trials of inhalational agents, both to treat cancers affecting the respiratory tract and to deliver other drugs used in cancer patients. This review discusses the rationale of drug delivery by the inhalational route, its technical challenges, preclinical and clinical experiences, limitations, and promise.
Functional cDNA clones of the human respiratory syncytial (RS) virus N, P, and L proteins support replication of RS virus genomic RNA analogs and define minimal trans-acting requirements for RNA replication (1995)

The RNA-dependent RNA polymerase of human respiratory syncytial (RS) virus was expressed in a functional form from a cDNA clone. Coexpression of the viral polymerase (L) protein, phosphoprotein (P), and nucleocapsid (N) protein allowed us to develop a system for expression and recovery of replicable RS virus RNA entirely from cDNA clones. cDNA clones of the N, P, and L genes were constructed in pGEM-based expression plasmids and shown to direct expression of the appropriate polypeptides. Two types of RS virus genomic RNA analogs were expressed from an intracellular transcription plasmid that directed the synthesis of RNAs with defined 5' and 3' ends. One analog included the authentic 5' and 3' termini of the genome, and the second contained the authentic 5' terminus and its complement at the 3' terminus as found in copyback defective interfering RNAs of other negative-strand RNA viruses. Both types of genomic analogs were encapsidated and replicated in cells expressing the RS virus N, P, and L proteins. Omission of any of the three viral proteins abrogated replication, thereby defining the N, P, and L proteins as the minimal trans-acting proteins required for RNA replication. This system has the advantages that expression occurs at a level sufficient to allow direct biochemical analysis of the products of RNA replication and that neither the use of reporter genes nor wild-type RS helper virus is required. These features allow analysis of both cis- and trans-acting factors involved in the control of replication of RS virus RNA.
Course trajectories of unipolar depressive disorders identified by latent class growth analysis (2011)

MDD, Dysth and DD did not adequately match empirically derived course trajectories for unipolar depression. For the future classification of unipolar depression, it may be wise to retain the larger, heterogeneous category of unipolar depression, adopting cross-cutting dimensions of severity and duration to further characterize patients.
Epitope Mapping Protocols (2009)

Given the versatile utility of the determinination of epitopes, beneficial to a wide variety of scientists from immunologists to structural biologists to biotechnologists, the need for a thorough, sta
Testosterone treatment for men with chronic heart failure (2004)

<b>Objective.</b> To examine the impact of implementation of the Accreditation Council for Pharmacy Education9s (ACPE9s) Standards 2007 on pharmacy students’ preparation for their first advanced pharmacy practice experience (APPE). <b>Design.</b> The doctor of pharmacy (PharmD) curriculum was altered to include introductory pharmacy practice experiences (IPPE), second-year therapeutics, classroom integration of practice experiences, more biomedical sciences, an electronic portfolio system, life-long learning exercises, and additional content based on Appendix B of Standards 2007. Curricular outcomes and the assessment plan also were revised based on Standards 2007. <b>Assessment.</b> To evaluate the impact of these changes to the curriculum, faculty members rated 9 behaviors of students observed during the third week of their first APPE and compared their scores with those of students who were evaluated in 2004 before the curriculum had been revised. Students completing the revised curriculum performed all 9 behaviors more often and had a better average score than students evaluated in 2004. <b>Conclusion.</b> Curricular revisions implemented to address ACPE Standards 2007 were associated with positive clinical behaviors in students beginning their experiential education.
Antisense oligodeoxynucleotides to the cystic fibrosis transmembrane conductance regulator inhibit cAMP-activated but not calcium-activated chloride currents. (1992)

Phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR) by cAMP-dependent protein kinase leads to chloride flux in epithelial cells. Is CFTR also required for the calcium-dependent activation of chloride channels? We used antisense oligodeoxynucleotides to CFTR to reduce the expression of CFTR in colonic and tracheal epithelial cells. The antisense oligomers were a pair of adjacent 18-mers complementary to nucleotides 1-18 and 19-36 of CFTR mRNA. Sense and misantisense oligomers served as controls. A 48-h antisense treatment reduced the expression of CFTR protein as assayed by immunoprecipitation and autoradiography to 26% of the level in sense-treated T84 cells. Whole-cell patch clamp revealed that a 48-h antisense treatment of T84 and 56FHTE-8o- fetal tracheal epithelial cells reduced the cAMP-activated chloride current to approximately 10% of that in sense-treated cells. The half-life of functional CFTR is less than 24 h in these cells. In contrast, the calcium-activated chloride current was not affected by antisense treatment. Hence, the cAMP and calcium pathways are separate. CFTR is required for the cAMP pathway but not for the calcium pathway.
Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity (2008)

These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.
EGF activates ErbB-2 and stimulates phosphatidylinositol 3-kinase in human airway smooth muscle cells (1999)

The epidermal growth factor (EGF)-receptor (EGFR) family includes four homologous transmembrane receptor protein tyrosine kinases, EGFR, ErbB-2, ErbB-3, and ErbB-4. This receptor family plays a pivotal role in regulating cell proliferation, differentiation, and transformation. Ligand-induced activation of these receptors results in formation of homo- and heterodimers, which undergo transphosphorylation and transactivation. The aim of this study was to characterize the role of EGFR family members in signaling EGF-induced human airway smooth muscle (HASM) cell proliferation. Here, we show that EGF stimulates activation of EGFR and transactivation of ErbB-2 in quiescent HASM cells. Phosphatidylinositol (PI) 3-kinase, a critical signaling enzyme that modulates HASM cell growth, is preferentially associated with ErbB-2, and EGF-stimulated transactivation of ErbB-2 induces PI 3-kinase activation. ErbB-3 and ErbB-4 are present in HASM cells; however, EGF has no effect on their activation. Betacellulin, a ligand for EGFR, ErbB-3, and ErbB-4, induced DNA synthesis of HASM cells and stimulated signaling through the activation of EGFR and ErbB-2 but not of ErbB-3 and ErbB-4. Heregulin, a specific ligand for ErbB-3 and ErbB-4, did not effect DNA synthesis and did not activate its specific receptors. These data suggest that EGF imparts signals that involve activation of ErbB-2 and are associated with ErbB-2 PI 3-kinase activation. Despite the mRNA and protein expression of all members of the EGFR family, ligand-stimulated signaling induced activation of EGFR and ErbB-2 but not of ErbB-3 and ErbB-4.
Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell (2009)

Otoferlin has been proposed to be the Ca(2+) sensor in hair cell exocytosis, compensating for the classical synaptic fusion proteins synaptotagmin-1 and synaptotagmin-2. In the present study, yeast two-hybrid assays reveal myosin VI as a novel otoferlin binding partner. Co-immunoprecipitation assay and co-expression suggest an interaction of both proteins within the basolateral part of inner hair cells (IHCs). Comparison of otoferlin mutants and myosin VI mutant mice indicates non-complementary and complementary roles of myosin VI and otoferlin for synaptic maturation: (i) IHCs from otoferlin mutant mice exhibited a decoupling of CtBP2/RIBEYE and Ca(V)1.3 and severe reduction of exocytosis. (ii) Myosin VI mutant IHCs failed to transport BK channels to the membrane of the apical cell regions, and the exocytotic Ca(2+) efficiency did not mature. (iii) Otoferlin and myosin VI mutant IHCs showed a reduced basolateral synaptic surface area and altered active zone topography. Membrane infoldings in otoferlin mutant IHCs indicated disturbed transport of endocytotic membranes and link the above morphological changes to a complementary role of otoferlin and myosin VI in transport of intracellular compartments to the basolateral IHC membrane.
High-Affinity Peptide-Based Collagen Targeting Using Synthetic Phage Mimics: From Phage Display to Dendrimer Display (2009)

Peptides derived from phage display typically show significantly weaker binding than their respective high affinity phage, which can bind to protein surfaces in a multivalent fashion. Here we show that mimicking key aspects of the multivalent architecture of the phage on an AB(5) dendritic wedge can enhance the affinity of a phage-display derived collagen binding peptide 100-fold (K(d) = 550 nM), allowing direct visualization of collagen architectures in native tissues with a higher specificity than that of the native collagen binding protein CNA35. The dendrimer display approach introduced here represents a well-defined, highly versatile platform for the affinity enhancement of phage display-derived peptides that is likely to be broadly applicable.
Analysis of T-cell-receptor ?-chain-gene usage in peripheral-blood and tumor-infiltrating lymphocytes from human non-small-cell lung carcinomas (1999)

Non-small-cell lung cancers (NSCLC) are often infiltrated by T lymphocytes. It is postulated that the presence of tumor-infiltrating lymphocytes (TIL) reflects a local host immune response against autologous tumors. To identify the nature of NSCLC TIL, we have characterized the molecular structure of the TCRbeta chain expressed by infiltrating T cells and paired PBL from 9 untreated patients (4 LLC, 3 ADC and 2 SCC). For this purpose, we have used a high-resolution PCR-based method that determines CDR3 size patterns in TCRVbeta sub-families in fresh tumors and their corresponding autologous PBL samples. Oligoclonality in T-cell populations was observed in 3 (Hor, Bla and Pub) out of 9 tumor biopsies analyzed. In contrast, the TCR repertoire of the 6 following patients as well as of all the autologous PBL was diverse, with virtually all Vbeta specificities expressed. Among the 3 tumors with dominant T-cell clonotypes, relative expansion of some T-cell sub-populations was observed. One patient (Hor) with significant TCRVbeta21 expansion in tumor compared with autologous PBL, showed over-expression of a particular TCRVbeta chain with unique Vbeta21-D-Jbeta2.7 junctional region not detected in autologous PBL. TCRVbeta21/Jbeta2.7 expansion was also observed in IL-2-stimulated TIL cell lines and was confirmed by sequencing analysis of the V-D-J junctional region. These results strengthen the view that local antigen-driven selection may occur, and support the hypothesis that anti-tumor immune response may take place in some NSCLC.
Scanning Electron Microscopy of Nanoscale Chemical Patterns (2007)

A series of nanoscale chemical patterning methods based on soft and hybrid nanolithographies have been characterized using scanning electron microscopy with corroborating evidence from scanning tunneling microscopy and lateral force microscopy. We demonstrate and discuss the unique advantages of the scanning electron microscope as an analytical tool to image chemical patterns of molecules highly diluted within a host self-assembled monolayer and to distinguish regions of differential mass coverage in patterned self-assembled monolayers. We show that the relative contrast of self-assembled monolayer patterns in scanning electron micrographs depends on the operating primary electron beam voltage, monolayer composition, and monolayer order, suggesting that secondary electron emission and scattering can be used to elucidate chemical patterns.
Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS) (2011)

Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the human inflammatory demyelinating disease, multiple sclerosis (MS). EAE is a complex condition in which the interaction between a variety of immunopathological and neuropathological mechanisms leads to an approximation of the key pathological features of MS: inflammation, demyelination, axonal loss and gliosis. The counter-regulatory mechanisms of resolution of inflammation and remyelination also occur in EAE, which, therefore can also serve as a model for these processes. Moreover, EAE is often used as a model of cell-mediated organ-specific autoimmune conditions in general. EAE has a complex neuropharmacology, and many of the drugs that are in current or imminent use in MS have been developed, tested or validated on the basis of EAE studies. There is great heterogeneity in the susceptibility to the induction, the method of induction and the response to various immunological or neuropharmacological interventions, many of which are reviewed here. This makes EAE a very versatile system to use in translational neuro- and immunopharmacology, but the model needs to be tailored to the scientific question being asked. While creating difficulties and underscoring the inherent weaknesses of this model of MS in straightforward translation from EAE to the human disease, this variability also creates an opportunity to explore multiple facets of the immune and neural mechanisms of immune-mediated neuroinflammation and demyelination as well as intrinsic protective mechanisms. This allows the eventual development and preclinical testing of a wide range of potential therapeutic interventions.
[The expression technology of chimeric and humanized antibodies]. (2002)

Since the discovery of monoclonal antibody(MoAb) in 1975, MoAbs have held great promise for the treatment of human disease such as cancer, viral infection, and autoimmune disorders. The most important limitations in murine MoAb have been the immune response against murine immunoglobulins and insufficient activation of human effector function. The emergence of antibodies as an attractive therapy is the result of the evolution of MoAb technology over the past 25 years. These problems have been overcome using genetic engineering techniques to produce chimeric mouse-human, CDR-grafted, and fully human antibodies. New strategies to develop chimeric, humanized, and completely human antibodies are discussed in this review.
Correlation of 16S Ribosomal DNA Signature Sequences with Temperature-Dependent Growth Rates of Mesophilic and Psychrotolerant Strains of the Bacillus cereus Group (1999)

Sequences of the 16S ribosomal DNA (rDNA) from psychrotolerant and mesophilic strains of the Bacillus cereus group revealed signatures which were specific for these two thermal groups of bacteria. Further analysis of the genomic DNA from a wide range of food and soil isolates showed that B. cereus group strains have between 6 and 10 copies of 16S rDNA. Moreover, a number of these environmental strains have both rDNA operons with psychrotolerant signatures and rDNA operons with mesophilic signatures. The ability of these isolates to grow at low temperatures correlates with the prevalence of rDNA operons with psychrotolerant signatures, indicating specific nucleotides within the 16S rRNA to play a role in psychrotolerance.
High-content screening identifies kinase inhibitors that overcome venetoclax resistance in activated CLL cells (2016)

Novel agents such as the Bcl-2 inhibitor venetoclax (ABT-199) are changing treatment paradigms for chronic lymphocytic leukemia (CLL) but important problems remain. Although some patients exhibit deep and durable responses to venetoclax as a single agent, other patients harbor subpopulations of resistant leukemia cells that mediate disease recurrence. One hypothesis for the origin of resistance to venetoclax is by kinase-mediated survival signals encountered in proliferation centers that may be unique for individual patients. An in vitro microenvironment model was developed with primary CLL cells that could be incorporated into an automated high-content microscopy-based screen of kinase inhibitors (KIs) to identify agents that may improve venetoclax therapy in a personalized manner. Marked interpatient variability was noted for which KIs were effective; nevertheless, sunitinib was identified as the most common clinically available KI effective in overcoming venetoclax resistance. Examination of the underlying mechanisms indicated that venetoclax resistance may be induced by microenvironmental signals that upregulate antiapoptotic Bcl-xl, Mcl-1, and A1, which can be counteracted more efficiently by sunitinib than by ibrutinib or idelalisib. Although patient-specific drug responses are common, for many patients, combination therapy with sunitinib may significantly improve the therapeutic efficacy of venetoclax.
The genome of Trypanosoma cruzi contains a constitutively expressed, tandemly arranged multicopy gene homologous to a major heat shock protein. (1987)

cDNA libraries have been constructed in the plasmid vector pUC18 with mRNA isolated from both epimastigotes and trypomastigotes of the Peru strain of Trypanosoma cruzi. Pools of randomly selected clones were analyzed by hybridization-selection-translation. Translation products were immunoprecipitated either with normal human sera or with sera from patients with Chagas' disease (chagasic sera), and the immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With this approach, a cDNA clone (pEC5) was identified which encodes a portion of an 85,000-Mr polypeptide. A genomic clone was subsequently isolated (FG1) by using oligonucleotide probes derived from the DNA sequence of this cDNA clone. A portion of this clone was isolated and sequenced, and the coding region for the protein was identified. Computer analysis of the predicted protein sequence indicates that this protein is closely related to the 83,000-Mr heat shock protein (hsp83) of Drosophila melanogaster, the hsp90 of Saccharomyces cerevisiae, and the hsp90 of chicken. This gene is tandemly organized in the T. cruzi genome as a cluster of 6 to 10 copies.