gebhart/patrepeval huggingface dataset:
ENGINEERING IMAGING: USING PARTICLE IMAGE VELOCIMETRY TO SEE PHYSIOLOGY IN A NEW LIGHT (2009)

1. Despite the array of sophisticated imaging techniques available for biological applications, none of the standard biomedical techniques adequately provides the capability to measure motion and flow. Those techniques currently in use are particularly lacking in spatial and temporal resolution. 2. Herein, we introduce the technique of particle image velocimetry. This technique is a well-established tool in engineering research and industry. Particle image velocimetry is continuing to develop and has an increasing number of variants. 3. Three case studies are presented: (i) the use of microparticle image velocimetry to study flow generated by high-frequency oscillatory ventilation in a human airway model; (ii) the use of stereoparticle image velocimetry to study stirred cell and tissue culture devices; and (iii) a three-dimensional X-ray particle image velocimetry technique used to measure flow in an in vitro vascular flow model. 4. The case studies highlight the vast potential of applying the engineering technique of particle image velocimetry and its many variants to current research problems in physiology.
LRP1 Controls Intracellular Cholesterol Storage and Fatty Acid Synthesis through Modulation of Wnt Signaling (2008)

The low-density lipoprotein receptor-related protein LRP1 is a cell surface receptor with functions in diverse physiological pathways, including lipid metabolism. Here we show that LRP1-deficient fibroblasts accumulate high levels of intracellular cholesterol and cholesteryl-ester when stimulated for adipocyte differentiation. We demonstrate that LRP1 stimulates a canonical Wnt5a signaling pathway that prevents cholesterol accumulation. Moreover, we show that LRP1 is required for lipolysis and stimulates fatty acid synthesis independently of the noradrenergic pathway, through inhibition of GSK3beta and its previously unknown target acetyl-CoA carboxylase (ACC). As a result of ACC inhibition, mature LRP1-deficient adipocytes of adult mice are hypotrophic, and lower uptake of fatty acids into adipose tissue leads to their redistribution to the liver. These results establish LRP1 as a novel integrator of adipogenic differentiation and fat storage signals.
Synergistic effect of a novel antiandrogen, VN/124-1, and signal transduction inhibitors in prostate cancer progression to hormone independence in vitro (2008)

This study was carried out to determine the mechanisms associated with loss of androgen dependency and disease progression in prostate cancer. We investigated the role of the androgen receptor and its relationship to other signal transduction proteins. A hormone-refractory prostate cancer cell line [high-passage LNCaP (HP-LNCaP)] was established in vitro. Cells were treated with inhibitors of mammalian target of rapamycin and tyrosine kinase receptors. Expression of these proteins and the androgen receptor were measured by Western immunoblotting. Analysis of the model and various treatments was also assessed through proliferation assays, luciferase activation assays, binding assays, and ELISA. Our novel antiandrogen, VN/124-1, effectively inhibited proliferation of hormone-resistant prostate cancer cell lines (HP-LNCaP), which were no longer sensitive to bicalutamide and had increased expression of the androgen receptor. Treatment with everolimus or gefitinib resulted in an increase in protein expression and activation of the androgen receptor. Conversely, inhibition of the androgen receptor resulted in increased expression of IGFR1beta, pHER2, pmTOR, and pAkt. The addition of bicalutamide to everolimus or gefitinib inhibited cell proliferation in HP-LNCaP cells. However, the addition of VN/124-1 has proven to be superior to bicalutamide, and the combination was synergistic (P<0.05) compared with either agent alone. This study suggests that compensatory cross-talk between the androgen receptor and various signaling pathways may account for decreased sensitivity to androgen receptor antagonists and the progression to hormone-resistant prostate cancer. Furthermore, these findings suggest that inhibition of both pathways may provide effective control in hormone-resistant prostate cancer and restore sensitivity to androgen antagonists in hormone-refractory patients.
The Ability of Two Listeria monocytogenes Vaccines Targeting Human Papillomavirus-16 E7 to Induce an Antitumor Response Correlates with Myeloid Dendritic Cell Function (2004)

Previous work from our laboratory has shown that Lm-LLO-E7 induces complete regression of approximately 75% of established TC-1 tumors, whereas Lm-E7 only slows the growth of such tumors. In this study, we examine the effects of Lm-LLO-E7 vs Lm-E7 on APCs. We hypothesize that the difference in antitumor efficacy of the two vaccines is due to the ability of each of these vectors to render immature dendritic cells (DCs) effective APCs in terms of MHC class II or costimulatory molecule expression. We also examine the ability of these vectors to stimulate cytokine production by DCs. Both vectors induced IL-12 and TNF-alpha, but only Lm-LLO-E7 induced IL-2 production by DCs. Lm-LLO-E7 also induced significantly higher levels of MHC class II molecules, CD40, and B7 costimulatory molecules (CD86, B7-H1, and B7-DC) on DCs than Lm-E7. Interestingly, a shift of CD11c(+) cells from CD86(low) to CD86(high) is observed post-Lm-LLO-E7 infection. A similar shift is also observed for B7-H1 and B7-DC molecules. Moreover, Lm-LLO-E7, but not Lm-E7-pulsed DCs, stimulate naive T cell proliferation. These results indicate that Lm-LLO-E7 is more effective than Lm-E7 at inducing DC maturation. This effect is independent of the E7 Ag, because Lm-LLO-NP, and a mixture of Lm-LLO-NP and Lm-E7 induce the same changes in DC phenotype as Lm-LLO-E7. Taken together, the changes in DC expression correlate well with the differences in antitumor efficacy between these two vaccines.
Polysaccharide A from the Capsule of Bacteroides fragilis Induces Clonal CD4+ T Cell Expansion (2014)

For 3 decades, the view of MHCII-dependent antigen presentation has been completely dominated by peptide antigens despite our 2004 discovery in which MHCII was shown to present processed fragments of zwitterionic capsular polysaccharides to T cells. Published findings further demonstrate that polysaccharide A (PSA) from the capsule of Bacteroides fragilis is a potent activator of CD4(+) T cells and that these T cells have important biological functions, especially in the maintenance of immunological homeostasis. However, little is known about the nature of T cell recognition of the polysaccharide-MHCII complex or the phenotype of the resulting activated cells. Here, we use next-generation sequencing of the αβT cell receptor of CD4(+) T cells from mice stimulated with PSA in comparison with protein antigen simulation and non-immunized controls and found that PSA immunization induced clonal expansion of a small subset of suppressive CD4(+)CD45RB(low) effector/memory T cells. Moreover, the sequences of the complementarity-determining region 3 (CDR3) loop from top clones indicate a lack of specific variable β and joining region use and average CDR3 loop length. There was also a preference for a zwitterionic motif within the CDR3 loop sequences, aligning well with the known requirement for a similar motif within PSA to enable T cell activation. These data support a model in which PSA, and possibly other T cell-dependent polysaccharide antigens, elicits a clonal and therefore specific CD4(+) T cell response often characterized by pairing dual-charged CDR3 loop sequences with dual-charged PSA.
Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement. (1986)

Human complement receptor type 2 (CR2) is the B-lymphocyte receptor both for the C3d fragment of the third component of complement and for the Epstein-Barr virus. Amino acid sequence analysis of tryptic peptides of CR2 revealed a strong degree of homology with the human C3b/C4b receptor, CR1. This homology suggested that CR1 gene sequences could be used to detect the CR2 sequences at conditions of low-stringency hybridization. Upon screening a human tonsillar cDNA library with CR1 cDNA sequences, two clones were identified that hybridized at low, but not at high, stringency. Redundant oligonucleotides specific for CR2 sequences were synthesized and used to establish that the two cDNA clones weakly hybridizing with the CR1 cDNA contained CR2 sequences. One of these CR2 cDNA clones hybridized to oligonucleotides derived from two distinct CR2 tryptic peptides, whereas the other, smaller cDNA clone hybridized to oligonucleotides derived from only one of the CR2 peptides. Nucleotide sequence analysis of the CR2 cDNA confirmed that the site of oligonucleotide hybridization was identical to that predicted from the peptide sequence, including flanking sequences not included within the oligonucleotide probes. The CR2-specific cDNA sequences identified a poly(A)+ RNA species of 5 kilobases in RNA extracted from human B cells but did not hybridize to any RNA obtained from the CR2-negative T-cell line HSB-2, thus confirming the appropriate size and tissue-specific distribution for the CR2 mRNA. The striking peptide sequence homology between CR2 and CR1 and the cross-hybridization of the CR2 cDNA with the CR1-specific sequences allow the placement of CR2 in a recently defined gene family of C3- and C4-binding proteins consisting of CR1, C4-binding protein, factor H, and now, CR2.
Evidence for dual functionality of the operon plnABCD in the regulation of bacteriocin production in Lactobacillus plantarum (2001)

The regulatory operon (plnABCD) involved in bacteriocin production in Lactobacillus plantarum C11 encodes four different proteins: a cationic prepeptide (PlnA); a histidine protein kinase (PlnB); and two highly homologous response regulators (PlnC and PlnD; over 75% sequence similarity). The mature product of PlnA, plantaricin A, serves as an extracellular pheromone that induces bacteriocin production. The exact roles of plnBCD in bacteriocin production have not been established experimentally. A reporter system containing the gusA gene fused with the plnA promoter was used to study plnABCD. We demonstrated that the plnABCD operon codes for an autoregulatory unit capable of activating its own promoter. Deletion analyses, performed in a heterologous expression host to define the roles of the individual genes, confirmed that both the inducer gene (plnA) and the kinase gene (plnB) are required for autoactivation. Apparently, the latter gene encodes a protein that serves as a receptor for the pheromone peptide. It was also demonstrated conclusively that the two regulators PlnC and PlnD, which have been shown previously to bind specifically to the DNA regulatory repeats of the plnA promoter, possess differential activities on the plnA promoter, with PlnC being much more active than PlnD. The functions of the response regulators were investigated further in the bacteriocin producer strain C11 in order to reveal their roles in bacteriocin production. Surprisingly, the two response regulators display totally opposite functions: although overexpression of plnC activated transcription and bacteriocin production, the overexpression of plnD repressed both processes, thus strongly suggesting that PlnD plays a role in the downregulation of bacteriocin synthesis. To our knowledge, this is the first evidence for a protein involved directly in negative regulation of bacteriocin production, and also it was shown for the first time that two highly homologous response regulators, with opposite functions, are encoded by genes located on the same operon.
Recent Advances in the Synthesis and Functions of Reconfigurable Interlocked DNA Nanostructures (2016)

Interlocked circular DNA nanostructures, e.g., catenanes or rotaxanes, provide functional materials within the area of DNA nanotechnology. Specifically, the triggered reversible reconfiguration of the catenane or rotaxane structures provides a means to yield new DNA switches and to use them as dynamic scaffolds for controlling chemical functions and positioning functional cargoes. The synthesis of two-ring catenanes and their switchable reconfiguration by pH, metal ions, or fuel/anti-fuel stimuli are presented, and the functions of these systems, as pendulum or rotor devices or as switchable catalysts, are described. Also, the synthesis of three-, five-, and seven-ring catenanes is presented, and their switchable reconfiguration using fuel/anti-fuel strands is addressed. Implementation of the dynamically reconfigured catenane structures for the programmed organization of Au nanoparticle (NP) assemblies, which allows the plasmonic control of the fluorescence properties of Au NP/fluorophore loads associated with the scaffold, and for the operation of logic gates is discussed. Interlocked DNA rotaxanes and their different synthetic approaches are presented, and their switchable reconfiguration by means of fuel/anti-fuel strands or photonic stimuli is described. Specifically, the use of the rotaxane as a scaffold to organize Au NP assemblies, and the control of the fluorescence properties with Au NP/fluorophore hybrids loaded on the rotaxane scaffold, are introduced. The future prospectives and challenges in the field of interlocked DNA nanostructures and the possible applications are discussed.
Cardiovascular disease and nutrient antioxidants: Role of low‐density lipoprotein oxidation (1995)

Increasing evidence indicates that oxidative modification of low-density lipoprotein (LDL) is causally related to atherosclerosis. Oxidatively modified LDL (oxLDL), in contrast to native LDL, is taken up avidly by macrophages, leading to formation of lipid-laden foam cells. Foam cells are pathognomonic of the atherosclerotic fatty streak. Modified LDL may also promote atherosclerosis by many other mechanisms, such as recruitment and retention of monocyte-macrophages, T-lymphocytes, and smooth muscle cells in the arterial intima, and cytotoxicity toward endothelial cells and macrophage-derived foam cells. The "oxidation hypothesis of atherosclerosis" is supported by a number of in vivo findings, such as the presence of oxLDL in atherosclerotic lesions, and increased titers of autoantibodies against modified LDL in patients with atherosclerosis. As a corollary of the oxidation hypothesis of atherosclerosis, antioxidants that can inhibit LDL oxidation may act as antiatherogens. This conception is supported by animal studies showing that antioxidants such as probucol, butylated hydroxytoluene, and alpha-tocopherol can slow the progression of atherosclerosis. Epidemiological and clinical data indicate a protective role of dietary antioxidants against cardiovascular disease, including vitamin E, beta-carotene, and vitamin C. Likewise, basic research studies on LDL oxidation have demonstrated a protective role for antioxidants, present either in the aqueous environment of LDL or associated with the lipoprotein itself. More studies are needed to establish the effectiveness and determine the required doses of specific antioxidants to prevent and possibly treat cardiovascular disease.
A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. (1998)

Chronic macrophage-mediated inflammation is central to atherosclerosis. A role of the monocyte chemotactic and activating C-C chemokine JE/monocyte chemotactic protein-1 has been proposed. However, the human C-X-C chemokines growth-regulated oncogene (GROalpha) and IL-8, and their shared receptor, CXCR-2, also can be expressed at sites of chronic inflammation. Because we detected CXCR-2 in the intima of human atherosclerotic lesions, we examined the role of leukocyte CXCR-2 expression in affecting lesion cellularity. Atherosclerosis-susceptible LDL receptor-deficient mice were irradiated, successfully repopulated with bone marrow cells that either lacked or expressed mIL-8RH (the homologue of CXCR-2), and fed an atherogenic diet for 16 wk. In recipients of mIL-8RH+/+ marrow, mIL-8RH colocalized with densely accumulated intimal MOMA-2 positive macrophages. In contrast, lesions in recipients of mIL-8RH-/- marrow lacked mIL-8RH, had little intimal MOMA-2 staining, and were less extensive. The mIL-8RH ligand KC/GROalpha was detected in the intima of all aortic atherosclerotic lesions. Thus, the capacity of leukocytes to express mIL-8RH, and associated intralesional expression of its ligands such as KC/GROalpha, mediated the intimal accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice.
Structure and Design of Potent and Selective Cathepsin K Inhibitors (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTStructure and Design of Potent and Selective Cathepsin K InhibitorsDennis S. Yamashita, Ward W. Smith, Baoguang Zhao, Cheryl A. Janson, Thaddeus A. Tomaszek, Mary J. Bossard, Mark A. Levy, Hye-Ja Oh, Thomas J. Carr, Scott K. Thompson, Carl F. Ijames, Steven A. Carr, Michael McQueney, Karla J. D'Alessio, Bernard Y. Amegadzie, Charles R. Hanning, Sherin Abdel-Meguid, Renee L. DesJarlais, John G. Gleason, and Daniel F. VeberView Author Information Departments of Medicinal Chemistry, Macromolecular Sciences, Molecular Recognition, Structural and Physical Chemistry, Protein Biochemistry, and Gene Expression Sciences SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd. King of Prussia, Pennsylvania 19406 Cite this: J. Am. Chem. Soc. 1997, 119, 46, 11351–11352Publication Date (Web):November 19, 1997Publication History Received3 July 1997Published online19 November 1997Published inissue 1 November 1997https://pubs.acs.org/doi/10.1021/ja972204uhttps://doi.org/10.1021/ja972204urapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views902Altmetric-Citations98LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Chemical structure,Inhibitors,Ketones,Monomers,Peptides and proteins Get e-Alerts
Signaling of transforming growth factor‐β family members through Smad proteins (2000)

Smads are pivotal intracellular nuclear effectors of transforming growth factor-beta (TGF-beta) family members. Ligand-induced activation of TGF-beta family receptors with intrinsic serine/threonine kinase activity trigger phosphorylation of receptor-regulated Smads (R-Smads), whereas Smad2 and Smad3 are phosphorylated by TGF-beta, and activin type I receptors, Smad1, Smad5 and Smad8, act downstream of BMP type I receptors. Activated R-Smads form heteromeric complexes with common-partner Smads (Co-Smads), e.g. Smad4, which translocate efficiently to the nucleus, where they regulate, in co-operation with other transcription factors, coactivators and corepressors, the transcription of target genes. Inhibitory Smads act in most cases in an opposite manner from R- and Co-Smads. Like other components in the TGF-beta family signaling cascade, Smad activity is intricately regulated. The multifunctional and context dependency of TGF-beta family responses are reflected in the function of Smads as signal integrators. Certain Smads are somatically mutated at high frequency in particular types of human cancers. Gene ablation of Smads in the mouse has revealed their critical roles during embryonic development. Here we review the latest advances in our understanding of the Smad mechanism of action and their in vivo functions.
Growth of GaN free from cracks on a (111)Si substrate by selective metalorganic vapor-phase epitaxy (2002)

The selective metalorganic vapor-phase epitaxy of wurtzite GaN was performed on a (111) silicon substrate using SiO2 grid mask pattern. Within window regions of (0.2–0.5) mm×(0.2–0.5) mm, GaN films free from cracks were achieved. The full width at half maximum of the (0004) X-ray rocking curve was as narrow as 388 arcs and that of the band edge emission was 18.6 meV at 77 K. The band edge emission peak energy was redshifted. The redshift is reduced slightly in a sample grown on small windows. This suggests that the biaxial strain due to the thermal expansion coefficient mismatch is partly relaxed on small windows.
Hole blocking in carbon nanotube–polymer composite organic light-emitting diodes based on poly (m-phenylene vinylene-co-2, 5-dioctoxy-p-phenylene vinylene) (2000)

In order to investigate the role of carbon nanotubes in a polymer matrix, organic light-emitting diodes were fabricated from a polymer composite composed of poly (m-phenylene vinylene-co-2,5-dioctoxy-p-phenylene) (PmPV) and dispersed single-wall carbon nanotubes (SWNTs). Tris-(8-hydroxyquinolinolato) aluminum (Alq3) doped by Nile Red was used as an emissive material between the polymer composite and cathode. The device fabricated without SWNTs dispersed in the PmPV shows a dominant emission near red at 600 nm, which is in the range of the characteristic emission of Nile Red-doped Alq3, with a small amount of green emission from the PmPV. However, the devices fabricated with the polymer composite show an increase in the oscillator strength of the green emission with a dominant emission peak near 500 nm, the characteristic emission of PmPV. This was observed for SWNT concentrations up to 0.1 wt %. The shift in the emission indicates that the SWNTs in the PmPV matrix act as a hole-blocking material that results in a shifting of the recombination region from the Nile Red-doped Alq3 layer to the PmPV composite layer.