gebhart/patrepeval huggingface dataset:
Aspects of the transport and delivery of antisense oligonucleotides. (2000)

This article will examine recent developments concerning the cellular uptake and subcellular trafficking of antisense oligonucleotides. It will also examine the merits of various delivery strategies for oligonucleotides. The use of conjugates of oligonucleotides with 'cell penetrating peptides' as a promising delivery technology will be emphasized.
Efficiency of Emission Control Measures on Particulate Matter-Related Health Impacts and Economic Cost during the 2014 Asia-Pacific Economic Cooperation Meeting in Beijing (2016)

<i>Background</i>: The Asia-Pacific Economic Cooperation (APEC) meeting was held from 5 November to 11 November 2014 in Beijing, and comprehensive emission control measures were implemented. The efficiency of these measures on particulate matter-related health impacts and economic cost need to be evaluated. <i>Methods</i>: The influences of emission control measures during APEC on particulate matter were evaluated, and health economic effects were assessed. <i>Results</i>: Average concentrations of PM<sub>2.5</sub> and PM<sub>10</sub> during APEC were reduced by 57.0%, and 50.6% respectively, compared with pre-APEC period. However, the concentrations of particulate matter rebounded after APEC. Compared with the pre-APEC and post-APEC periods, the estimated number of deaths caused by non-accidental, cardiovascular and respiratory diseases that could be attributed to PM<sub>2.5</sub> and PM<sub>10</sub> during the APEC were the lowest. The economic cost associated with mortality caused by PM<sub>2.5</sub> and PM<sub>10</sub> during the APEC were reduced by (61.3% and 66.6%) and (50.3% and 60.8%) respectively, compared with pre-APEC and post-APEC. <i>Conclusions</i>: The emission control measures were effective in improving short term air quality and reducing health risks and medical expenses during 2014 APEC, but more efforts is needed for long term and continuous air quality improvement and health protection.
Pancreatic tumor pathogenesis reflects the causative genetic lesion. (1991)

Transgenic mice in which c-myc expression is targeted to pancreatic acinar cells develop mixed acinar/ductal pancreatic adenocarcinomas between 2 and 7 months of age. This contrasts with the effect on pancreas of the simian virus 40 tumor antigen or activated ras, which in adult mice causes lesions composed exclusively of acinar-like cells. Furthermore, during an early stage of myc-induced pathology, transformed acinar-derived cells appear within islets, suggesting that islet hormones may influence the progression of these exocrine pancreatic tumors. These findings demonstrate that the initial oncogenic alteration can influence the pattern of subsequent tumor pathogenesis and, given that human exocrine pancreatic tumors are predominantly ductal adenocarcinomas, support the suggestion that transformed acinar cells may contribute to the genesis of this serious disease in man.
Selective adsorption and patterning of Si nanoparticles fabricated by laser ablation on functionalized self-assembled monolayer (2001)

We demonstrate an in situ selective adsorption of Si nanoparticles fabricated by laser ablation on a functionalized self-assembled monolayer (SAM). Si nanoparticles adsorbed on –CH3 terminated a SAM while Si particles did not adsorb on –NH2, –F, –OH, and –COOH, terminated SAMs. The end group of a SAM solely determines the selectivity against Si nanoparticle adsorption. We utilized the screening ability of functionalized SAMs to pattern Si nanoparticles onto desired locations on a Si substrate.
Identification of a Mitochondrial Na+/H+Exchanger (1998)

The electroneutral exchange of protons for Na+ and K+ across the mitochondrial inner membrane contributes to organellar volume and Ca2+ homeostasis. The molecular nature of these transporters remains unknown. In this report, we characterize a novel gene (YDR456w; renamed NHA2) in Saccharomyces cerevisiae whose deduced protein sequence is homologous to members of the mammalian Na+/H+ exchanger gene family. Fluorescence microscopy showed that a Nha2-green fluorescent protein chimera colocalizes with 4',6-diamidino-2-phenylindole staining of mitochondrial DNA. To assess the function of Nha2, we deleted the NHA2 gene by homologous disruption and found that benzamil-inhibitable, acid-activated 22Na+ uptake into mitochondria was abolished in the mutant strain. It also showed retarded growth on nonfermentable carbon sources and severely reduced survival during the stationary phase of the cell cycle compared with the parental strain, consistent with a defect in aerobic metabolism. Sequence comparisons revealed that Nha2 has highest identity to a putative Na+/H+ exchanger homologue (KIAA0267; renamed NHE6) in humans. Northern blot analysis demonstrated that NHE6 is ubiquitously expressed but is most abundant in mitochondrion-rich tissues such as brain, skeletal muscle, and heart. Fluorescence microscopy showed that a NHE6-green fluorescent protein chimera also accumulates in mitochondria of transfected HeLa cells. These data indicate that NHA2 and NHE6 encode homologous Na+/H+ exchangers and suggest they may be important for mitochondrial function in lower and higher eukaryotes, respectively.
Long-term Effects of a Lifestyle Intervention on Weight and Cardiovascular Risk Factors in Individuals With Type 2 Diabetes Mellitus (2010)

clinicaltrials.gov Identifier: NCT00017953.
The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF-kappa B and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain. (1995)

The Epstein-Barr virus (EBV) encoded latent membrane protein, LMP1, is oncogenic in rodent fibroblasts and is an essential effector protein in EBV-induced growth-transformation of human B lymphocytes. Previous structure-function studies with LMP1 have relied largely on rodent fibroblast transformation as a functional readout, with apparently conflicting results. We have now analysed several LMP1 mutants in various human cell types, including B cells, T cells and epithelial cells, using two independent functional assays; (i) activation of NF-kappa B, and (ii) induction of two cell surface activation markers, CD54 and CD40. The results suggest that the cytosolic N-terminus is not essential for LMP1 function in any cell type studied. The third and fourth transmembrane helices and the intracytosolic loops are dispensable for activation of NF-kappa B, but they do influence the induction of CD54 and CD40. The major effector domain appears to be the cytosolic C-terminus in which were identified two 'C-terminal activating regions', CTAR-1 (residues 194-232) and CTAR-2 (residues 351-386). Whilst the exact results depended upon the host cell line, CTAR-2 was generally more important for activation of NF-kappa B, and both CTAR-1 and CTAR-2 were required for optimal induction of CD54 and CD40. Analysis of NF-kappa B activation by LMP1 in Rat-1 fibroblasts indicated that many mutations that were functional in human cells were poorly tolerated in the rodent cells; a result that is in broad agreement with published Rat-1 transformation data.
Current concepts in intravitreal drug therapy for diabetic retinopathy (2010)

Diabetic retinopathy (DR) is a major cause of preventable blindness in the developed countries. Despite the advances in understanding and management of DR, it remains a challenging condition to manage. The standard of care for patients with DR include strict metabolic control of hyperglycemia, blood pressure control, normalization of serum lipids, prompt retinal laser photocoagulation and vitrectomy. For patients who respond poorly and who progressively lose vision in spite of the standard of care, intravitreal administration of steroids or/and anti-vascular endothelial growth factor (anti-VEGF) drugs appear to be a promising second-line of therapy. This review discusses the current concepts and the role of these novel therapeutic approaches in the management of DR.
Ease of retrieval as information: Another look at the availability heuristic. (1991)

Experienced ease of recall was found to qualify the implications of recalled content. Ss who had to recall 12 examples of assertive (unassertive) behaviors, which was difficult, rated themselves as less assertive (less unassertive) than subjects who had to recall 6 examples, which was easy In fact, Ss reported higher assertiveness after recalling 12 unassertive rather than 12 assertive behaviors. Thus, self-assessments only reflected the implications of recaUed content if recall was easy The impact of ease of recall was eliminated when its informational value was discredited by a misattribution manipulation. The informative functions of subjective experiences are discussed.
MADS-box genes of maize: frequent targets of selection during domestication (2010)

MADS-box genes encode transcription factors that are key regulators of plant inflorescence and flower development. We examined DNA sequence variation in 32 maize MADS-box genes and 32 randomly chosen maize loci and investigated their involvement in maize domestication and improvement. Using neutrality tests and a test based on coalescent simulation of a bottleneck model, we identified eight MADS-box genes as putative targets of the artificial selection associated with domestication. According to neutrality tests, one additional MADS-box gene appears to have been under selection during modern agricultural improvement of maize. For random loci, two genes were indicated as targets of selection during domestication and four additional genes were indicated to be candidate-selected loci for maize improvement. These results suggest that MADS-box genes were more frequent targets of selection during domestication than genes chosen at random from the genome.
From the Laboratory to the Clinic: A Retrospective on Fully Synthetic Carbohydrate-Based Anticancer Vaccines (2000)

This review provides an account of our explorations into oligosaccharide and glycoconjugate construction for the creation and evaluation of vaccines based on carbohydrate-centered tumor antigens. Our starting point was the known tendency of transformed cells to express selective carbohydrate motifs in the form of glycoproteins or glycolipids. Anticancer vaccines derived from carbohydrate-based antigens could be effective targets for immune recognition and attack. Obtaining significant quantities of such structures from natural sources is, however, extremely difficult. With the total synthesis of tumor-associated carbohydrate antigens accomplished, we began to evaluate at the clinical level whether the human immune system can respond to such fully synthetic antigens in a focused and useful way. Toward this goal, we have merged the resources of chemistry and immunology in an attack on the problem. The synthesis and immunoconjugation of various tumor-associated carbohydrate antigens and the results of such constructs in mice vaccinations will be described. For fashioning an effective vaccine, conjugation to a suitable immunogenic carrier was necessary and conjugates of KLH (keyhole limpet cyanin) have consistently demonstrated the relevant immunogenicity. Preclinical and clinical studies with synthetic conjugate carbohydrate vaccines show induction of IgM- and IgG-antibody responses. Another approach to anticancer vaccines involves the use of clustered glycopeptides as targets for immune attack. Initial attention has been directed to mucin related O-linked glycopeptides. Synthetic trimeric clusters of glycoepitopes derived from the Tn-, TF- and Lewis(y)-antigens, appropriately bioconjugated, have been demonstrated to be immunogenic. The hope is that patients immunized in an adjuvant manner with synthetic carbohydrate vaccines would produce antibodies reactive with cancer cells and that the production of such antibodies would mitigate against tumor spread, thereby enabling a more favorable survival and "quality of life" prognosis.
Moving belt interface with spray deposition for liquid chromatography/mass spectrometry (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMoving belt interface with spray deposition for liquid chromatography/mass spectrometryM. J. Hayes, E. P. Lankmayer, Paul. Vouros, B. L. Karger, and J. M. McGuireCite this: Anal. Chem. 1983, 55, 11, 1745–1752Publication Date (Print):September 1, 1983Publication History Published online1 May 2002Published inissue 1 September 1983https://pubs.acs.org/doi/10.1021/ac00261a024https://doi.org/10.1021/ac00261a024research-articleACS PublicationsRequest reuse permissionsArticle Views132Altmetric-Citations84LEARN 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
Multi-cell-line micro flow cytometers with buried SU-8/SOG optical waveguides (2003)

This paper reports a micro flow cytometer integrated with an innovative buried optical waveguide on soda-lime glass substrates. A novel optical waveguide using SU8/SOG (spin-on-glass) double-layer structure was demonstrated. The light guiding efficiency was improved due to smoother channel surface and larger difference of refractive index between SU-8 and organic-based SOG. Instead of using complicated optical alignment system, detection light source was coupled into the waveguide by directly inserting an etched optical fiber. A very high coupling efficiency could be achieved by this approach. In this study, the performance of the waveguides and insertion losses of the chip were measured. Results showed that the optical loss was less than 15 dB for a 40-mm long waveguide. The buried optical waveguide provides a built-in detection source for cell counting. Preliminary results indicated that a multi-cell-line flow cytometer with built-in detection system could be realized.
Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes (2012)

Transition metal-catalyzed transfers of carbenes, nitrenes, and oxenes are powerful methods for functionalizing C=C and C-H bonds. Nature has evolved a diverse toolbox for oxene transfers, as exemplified by the myriad monooxygenation reactions catalyzed by cytochrome P450 enzymes. The isoelectronic carbene transfer to olefins, a widely used C-C bond-forming reaction in organic synthesis, has no biological counterpart. Here we report engineered variants of cytochrome P450(BM3) that catalyze highly diastereo- and enantioselective cyclopropanation of styrenes from diazoester reagents via putative carbene transfer. This work highlights the capacity to adapt existing enzymes for the catalysis of synthetically important reactions not previously observed in nature.
Dynamic clustering procedures for bibliographic data (1981)

Clustering is an important tool for efficient retrieval of documents in bibliographic database systems. It can be also used to find research trend from a set of research papers. This paper discusses new clustering procedures called dynamic ones which seem to be suitable for bibliographic data handling. These procedures are developed to solve the following problems.(1) Depending on the characteristics of data, several different clustering procedures are required to obtain good results.(2) Large clusters are tend to be generated.Dynamic clustering procedures are difined to be procedures which change parameter values according to the characteristics of data. Similarity values and threshold values are dynamically modified to handle the above problems. Furthermore, to treat the latter problem data duplication is considered.
Using IPsec to Protect Mobile IPv6 Signaling Between Mobile Nodes and Home Agents (2004)

community, and requests discussion and suggestions for improvements.
Impaired Drug Absorption Due to High Stomach pH: A Review of Strategies for Mitigation of Such Effect To Enable Pharmaceutical Product Development (2013)

Published reports have clearly shown that weakly basic drugs which have low solubility at high pH could have impaired absorption in patients with high gastric pH thus leading to reduced and variable bioavailability. Since such reduction in exposure can lead to significant loss of efficacy, it is imperative to (1) understand the behavior of the compound as a function of stomach pH to inform of any risk of bioavailability loss in clinical studies and (2) develop a robust formulation which can provide adequate exposure in achlorhydric patients. In this review paper, we provide an overview of the factors that can cause high gastric pH in human, discuss clinical and preclinical pharmacokinetic data for weak bases under conditions of normal and high gastric pH, and give examples of formulation strategies to minimize or mitigate the reduced absorption of weakly basic drugs under high gastric pH conditions. It should be noted that the ability to overcome pH sensitivity issues is highly compound dependent and there are no obvious and general solutions to overcome such effect. Further, we discuss, along with several examples, the use of biopharmaceutical tools such as in vitro dissolution, absorption modeling, and gastric pH modified animal models to assess absorption risk of weak bases in high gastric pH and also the use of these tools to enable development of formulations to mitigate such effects.
Human acute myeloid leukaemia cells express adhesion proteins and bind to bone marrow fibroblast monolayers and extracellular matrix proteins. (1993)

Adhesion protein expression by acute myeloid leukaemia (AML) cells may affect bone marrow stromal localization and determine exposure of leukaemic cells to stromal derived myeloid growth factors. We have analysed the surface expression by myeloid leukaemic cells of proteins with known adhesive function and the ability of AML cells to adhere to bone marrow fibroblasts and the extracellular matrix proteins fibronectin and laminin. Cells from all six patients tested adhered to bone marrow fibroblast monolayers (mean binding 28.8 +/- 12.8%) and to purified fibronectin in five cases studied (mean binding 33.8 +/- 15.3%). Cells from four patients with AML also adhered to laminin (mean binding 20.9 +/- 4.0%). AML cells from the majority of patients with leukaemia at diagnosis or relapse expressed the ligand pair LFA-1 and ICAM-1, the CD2 ligand LFA-3, alpha and beta chains of the integrins VLA-4, VLA-5 and VLA-6, and the hyaluronate receptor CD44. Antibodies to CD11a, CD18, VLA-4 alpha, and VLA-5 alpha failed to inhibit binding of AML cells to bone marrow fibroblasts but anti-VLA-5 alpha antibodies inhibited AML cell binding to fibronectin by approximately 50%. The ability of AML cells to adhere to bone marrow fibroblasts and extracellular matrix proteins such as fibronectin and laminin may to help explain the capacity of AML cells to persist in the marrow during periods of apparent complete remission and to subsequently proliferate under the influence of locally secreted myeloid growth factors.
Low density lipoprotein receptor-related protein is necessary for the internalization of both tissue-type plasminogen activator-inhibitor complexes and free tissue-type plasminogen activator. (1994)

Tissue-type plasminogen activator (t-PA) is used as a thrombolytic agent in treatment of myocardial infarction. However, large doses of this agent must be administered in treatment to maintain a thrombolytic state because t-PA is cleared rapidly from circulation. We designed specific ligands to distinguish between two major mechanisms by which t-PA is taken into cells and degraded. One of these mechanisms involves internalization of complexes between t-PA and its cognate inhibitor plasminogen activator inhibitor type-1 (PAI-1); the other mechanism is independent of PAI-1. Using specific inhibitors for low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP), we show that the degradation by hepatocytes of both free t-PA and t-PA.PAI-1 complexes involve the receptor LRP. We demonstrate that fibroblasts degrade both free t-PA (PAI-1-independent) and t-PA complexed with its specific inhibitor PAI-1 (PAI-1-dependent), whereas genetically altered fibroblasts that do not express LRP neither internalize nor degrade these ligands. We also show that a PAI-1-independent, t-PA ligand can inhibit the degradation of both free t-PA and t-PA.PAI-1 complexes. We propose LRP is the receptor for both PAI-1-independent and PAI-1-dependent t-PA ligands.
New β-Alanine Derivatives Are Orally Available Glucagon Receptor Antagonists (2007)

A weak human glucagon receptor antagonist with an IC50 of 7 microM was initially found by screening of libraries originally targeted to mimic the binding of the glucagon-like peptide (GLP-1) hormone to its receptor. Optimization of this hit for binding affinity for the glucagon receptor led to ligands with affinity in the nanomolar range. In addition to receptor binding, optimization efforts were made to stabilize the molecules against fast metabolic turnover. A potent antagonist of the human human glucagon receptor was obtained that had 17% oral availability in rats with a plasma half-life of 90 min. The major metabolites of this lead were identified and used to further optimize this series with respect to pharmacokinetic properties. This final optimization led to a potent glucagon antagonist that was orally available in rats and dogs and was efficacious in lowering blood glucose levels in a diabetic animal model.
SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer (2012)

An association between lymph node metastasis and poor prognosis in breast cancer was observed decades ago. However, the mechanisms by which tumor cells infiltrate the lymphatic system are not completely understood. Recently, it has been proposed that the lymphatic system has an active role in metastatic dissemination and that tumor-secreted growth factors stimulate lymphangiogenesis. We therefore investigated whether SIX1, a homeodomain-containing transcription factor previously associated in breast cancer with lymph node positivity, was involved in lymphangiogenesis and lymphatic metastasis. In a model in which human breast cancer cells were injected into immune-compromised mice, we found that SIX1 expression promoted peritumoral and intratumoral lymphangiogenesis, lymphatic invasion, and distant metastasis of breast cancer cells. SIX1 induced transcription of the prolymphangiogenic factor VEGF-C, and this was required for lymphangiogenesis and lymphatic metastasis. Using a mouse mammary carcinoma model, we found that VEGF-C was not sufficient to mediate all the metastatic effects of SIX1, indicating that SIX1 acts through additional, VEGF-C-independent pathways. Finally, we verified the clinical significance of this prometastatic SIX1/VEGF-C axis by demonstrating coexpression of SIX1 and VEGF-C in human breast cancer. These data define a critical role for SIX1 in lymphatic dissemination of breast cancer cells, providing a direct mechanistic explanation for how VEGF-C expression is upregulated in breast cancer, resulting in lymphangiogenesis and metastasis.
Breast cancer risk associated with proliferative breast disease and atypical hyperplasia (1993)

AH is a reliable marker of increased breast cancer risk among women undergoing breast biopsy.