gebhart/patrepeval huggingface dataset:
Perspective of biochemical research in the neuronal ceroid‐lipofuscinosis (1992)

The search for biochemical abnormalities in the neuronal ceroid-lipofuscinoses (NCL) or Batten disease was initiated with the discovery of normal levels of gangliosides in juvenile amaurotic idiocy. The primary goal of most biochemical studies has been to discover the unique biochemical marker for carriers and at-risk individual. Ceroid, the singular pathomorphologic trait of NCL, was isolated and shown to differ from a similar but normal product of aged cells, lipofuscin. In spite of the availability of stored product, the chemical analysis of ceroid has not elucidated the unique biochemical defect in the NCL, as has been the case for other lysosomal storage disorders. The NCL were thought to be a result of lipid peroxidation because ceroid is also found in disorders of impaired vitamin E metabolism or results from a diet deficient in the antioxidant, vitamin E. In addition, tissue analysis indicated losses of polyunsaturated fatty acids in affecteds and carriers, as well as the presence of a secondary product of lipid peroxidation, 4-hydroxynonenal, in affected and carrier NCL dogs. With the exception of a fluorescent compound isolated from retinal ceroid, studies aimed at discovering the disease-specific fluorophores of ceroid have been largely inconclusive. The discovery of elevated dolichols in urine and brain tissue of NCL patients led to another hypothesis, that the basic biochemical defect in NCL involved the metabolism of dolichols and retinoids. However, the more recent view is that dolichol metabolism is secondary to the unknown NCL lesion.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanism and energetics of green fluorescent protein chromophore synthesis revealed by trapped intermediate structures (2003)

Green fluorescent protein has revolutionized cell labeling and molecular tagging, yet the driving force and mechanism for its spontaneous fluorophore synthesis are not established. Here we discover mutations that substantially slow the rate but not the yield of this posttranslational modification, determine structures of the trapped precyclization intermediate and oxidized postcyclization states, and identify unanticipated features critical to chromophore maturation. The protein architecture contains a dramatic approximately 80 degrees bend in the central helix, which focuses distortions at G67 to promote ring formation from amino acids S65, Y66, and G67. Significantly, these distortions eliminate potential helical hydrogen bonds that would otherwise have to be broken at an energetic cost during peptide cyclization and force the G67 nitrogen and S65 carbonyl oxygen atoms within van der Waals contact in preparation for covalent bond formation. Further, we determine that under aerobic, but not anaerobic, conditions the Gly-Gly-Gly chromophore sequence cyclizes and incorporates an oxygen atom. These results lead directly to a conjugation-trapping mechanism, in which a thermodynamically unfavorable cyclization reaction is coupled to an electronic conjugation trapping step, to drive chromophore maturation. Moreover, we propose primarily electrostatic roles for the R96 and E222 side chains in chromophore formation and suggest that the T62 carbonyl oxygen is the base that initiates the dehydration reaction. Our molecular mechanism provides the basis for understanding and eventually controlling chromophore creation.
The Antiangiogenic Activity in Xenograft Models of Brivanib, a Dual Inhibitor of Vascular Endothelial Growth Factor Receptor-2 and Fibroblast Growth Factor Receptor-1 Kinases (2010)

Tumor angiogenesis is a complex and tightly regulated network mediated by various proangiogenic factors. The fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) family of growth factors, and associated tyrosine kinase receptors have a major influence in tumor growth and dissemination and may work synergistically to promote angiogenesis. Brivanib alaninate is the orally active prodrug of brivanib, a selective dual inhibitor of FGF and VEGF signaling. Here, we show that brivanib demonstrates antitumor activity in a broad range of xenograft models over multiple dose levels and that brivanib alaninate shows dose-dependent efficacy equivalent to brivanib in L2987 human tumor xenografts. Brivanib alaninate (107 mg/kg) reduced tumor cell proliferation as determined by a 76% reduction in Ki-67 staining and reduced tumor vascular density as determined by a 76% reduction in anti-CD34 endothelial cell staining. Furthermore, Matrigel plug assays in athymic mice showed that brivanib alaninate inhibited angiogenesis driven by VEGF or basic FGF alone, or combined. Dynamic contrast-enhanced magnetic resonance imaging, used to assess the effects of brivanib alaninate on tumor microcirculation, showed a marked decrease in gadopentetate dimeglumine contrast agent uptake at 107 mg/kg dose, with a reduction in area under the plasma concentration-time curve from time 0 to 60 minutes at 24 and 48 hours of 54% and 64%, respectively. These results show that brivanib alaninate is an effective antitumor agent in preclinical models across a range of doses, and that efficacy is accompanied by changes in cellular and vascular activities.
Atomic-layer-deposited aluminum oxide for the surface passivation of high-efficiency silicon solar cells (2008)

We present independently confirmed efficiencies above 20% for PERC-type solar cells with the point-contacted rear being either passivated by atomic-layer-deposited Al <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> or by stacks consisting of an ultrathin Al <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> film and a thicker PECVD-SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</inf> layer. Internal quantum efficiency measurements reveal that the effective rear surface recombination velocities of the single-layer Al <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> -passivated cells are comparable to those measured on reference cells passivated by an aluminum-annealed thermal SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> , while those of the Al <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> /SiOx-passivated cells are even lower. Very low effective rear surface recombination velocities of only 70 cm/s are reported for the Al <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> O <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> /SiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</inf> stacks, including metalized areas on the cell rear.
Magneto-Archimedes levitation and its application (2002)

A novel magnetic-separation method, which uses the magneto-Archimedes levitation technique, has been introduced and evaluated. Magneto-Archimedes levitation is an easy way to attain the levitation of feeble magnetic materials by ordinal superconducting magnets with the aid of the magnetically induced buoyancy force that comes from its surroundings. The stable levitation position in a magnetic field depends on the materials because it is determined by the difference in volume magnetic susceptibilities and densities between objects and surroundings. By using this feature, we have successfully demonstrated a novel magnetic separation technique. The samples levitated were NaCl-KCl grain mixtures and colored glass particles. When they were levitated with the magneto-Archimedes technique, the initial mixture underwent separation into each kind of the ingredient particle aggregates. In this study, conventional diamagnetic levitation and magneto-Archimedes levitation are compared, and the novel magnetic separation and its features are demonstrated.
Astaxanthin, a Carotenoid without Vitamin A Activity, Augments Antibody Responses in Cultures Including T-helper Cell Clones and Suboptimal Doses of Antigen (1995)

Astaxanthin, a carotenoid without vitamin A activity, enhances T-dependent antigen (Ag)-specific humoral immune responses. We examined carotenoid actions on T-helper (Th) cell activity in a direct manner with reconstitution experiments; spleen Th cells were replaced with Ag-specific Type 1 and Type 2 (Th1 and Th2) Th cell clones. The Ag for the Th1 and Th2 clones were pigeon cytochrome C and rabbit gamma-globulin, respectively. Astaxanthin and beta-carotene augmented the number of IgM antibody (Ab)-secreting cells when unprimed B cells were incubated with Th clones and stimulated with suboptimal doses of Ag specific for each Th clone. The number of IgG Ab-secreting cells were greater with use of in vivo primed B cells than with unprimed B cells in both Th clones. Astaxanthin but not beta-carotene augmented the number of IgG Ab-secreting cells when primed B cells and Th cell clones were stimulated with suboptimal doses of Ag specific for each Th clone. In the presence of optimal doses of Ag for each Th clone, neither carotenoid augmented the number of Ab-secreting cells. Astaxanthin and beta-carotene may enhance the actions of both Th1 and Th2 cells for humoral immune responses with suboptimal Ag challenges; certain carotenoids may help maintain Ag-mediated immune responses at optimal levels.
The effects of coronavirus on human nasal ciliated respiratory epithelium (2001)

Human coronavirus (HCoV) accounts for 15-30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6-14.0) and day 3 (9.4 Hz (95% CI 7.2-11.6)), there was a significant increase (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0-0.5)) and day 3 (1.1 (95% CI 0.5-1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.
A chimeric adenovirus vector encoding reovirus attachment protein σ1 targets cells expressing junctional adhesion molecule 1 (2004)

The utility of adenovirus (Ad) vectors for gene transduction can be limited by receptor specificity. We developed a gene-delivery vehicle in which the potent Ad5 vector was genetically reengineered to display the mucosal-targeting sigma1 protein of reovirus type 3 Dearing (T3D). A sigma1 construct containing all but a small virion-anchoring domain was fused to the N-terminal 44 aa of Ad5 fiber. This chimeric attachment protein Fibtail-T3Dsigma1 forms trimers and assembles onto Ad virions. Fibtail-T3Dsigma1 was recombined into the Ad5 genome, replacing sequences encoding wild-type fiber. The resulting vector, Ad5-T3Dsigma1, expresses Fibtail-T3Dsigma1 and infects Chinese hamster ovary cells transfected with human or mouse homologs of the reovirus receptor, junctional adhesion molecule 1 (JAM1), but not the coxsackievirus and Ad receptor. Treatment of Caco-2 intestinal epithelial cells with either JAM1-specific antibody or neuraminidase reduced transduction by Ad5-T3Dsigma1, and their combined effect decreased transduction by 95%. Ad5-T3Dsigma1 transduces primary cultures of human dendritic cells substantially more efficiently than does Ad5, and this transduction depends on expression of JAM1. These data provide strong evidence that Ad5-T3Dsigma1 can be redirected to cells expressing JAM1 and sialic acid for application as a vaccine vector.
New reactions of pyrroles. II. Preparation and reactions of pyrroleglyoxyloyl derivatives (1967)

Abstract Pyrroles treated with oxalyl chloride produced pyrroleglyoxyloyl chlorides. Unsubstituted and C‐alkyl pyrroles gave products stable only at low temperatures. N ‐Substitution or presence on the ring of an electron withdrawing group ( e.g . carbonyl) increased the stability of the glyoxyloyl chlorides considerably. Substitution occurred at the 2‐position unless both 2 and 5 positions of the pyrrole nucleus were blocked. When this was the case substitution occurred slowly at position 3.
The Measurement of Surface Tension by the Pendant Drop Technique (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Measurement of Surface Tension by the Pendant Drop TechniqueClyde E. StaufferCite this: J. Phys. Chem. 1965, 69, 6, 1933–1938Publication Date (Print):June 1, 1965Publication History Published online1 May 2002Published inissue 1 June 1965https://pubs.acs.org/doi/10.1021/j100890a024https://doi.org/10.1021/j100890a024research-articleACS PublicationsRequest reuse permissionsArticle Views6343Altmetric-Citations363LEARN 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 options Get e-Alerts
Human Tumor-Infiltrating Myeloid Cells: Phenotypic and Functional Diversity (2017)

Our current understanding of human tumor-resident myeloid cells is, for the most part, based on a large body of work in murine models or studies enumerating myeloid cells in patient tumor samples using immunohistochemistry (IHC). This has led to the establishment of the theory that, by and large, tumor-resident myeloid cells are either "protumor" M2 macrophages or myeloid-derived suppressor cells (MDSC). This concept has accelerated our understanding of myeloid cells in tumor progression and enabled the elucidation of many key regulatory mechanisms involved in cell recruitment, polarization, and activation. On the other hand, this paradigm does not embrace the complexity of the tumor-resident myeloid cell phenotype (IHC can only measure 1 or 2 markers per sample) and their possible divergent function in the hostile tumor microenvironment. Here, we examine the criteria that define human tumor-infiltrating myeloid cell subsets and provide a comprehensive and critical review of human myeloid cell nomenclature in cancer. We also highlight new evidence characterizing their contribution to cancer pathogenesis based on evidence derived from clinical studies drawing comparisons with murine studies where necessary. We then review the mechanisms in which myeloid cells are regulated by tumors in humans and how these are being targeted therapeutically.
The spatial variation of the refractive index in biological cells (1996)

With a phase microscope the phase shift of cells from type L 929 fibroblast and mitochondria from liver cells was measured. Compared to the total phase shift caused by the cell relative to vacuum (approximately 1400 nm) the single phase shift of the mitochondria (approximately 180 nm) is small. Only the nucleus and the membrane of the cell give a visibly different phase shift relative to the mean value of the cell. The Fraunhofer diffraction of the measured phase object is calculated. With a simplified scattering theory, i.e. Rayleigh-Gans Scattering, different phase objects are investigated and their differential cross section is discussed.
Activation of 5‐HT1A but not 5‐HT1B receptors attenuates an increase in extracellular dopamine derived from exogenously administered l‐DOPA in the striatum with nigrostriatal denervation (2001)

In order to determine whether L-DOPA-derived extracellular dopamine (DA) in the striatum with dopaminergic denervation is affected by activation of serotonin autoreceptors (5-HT(1A) and 5-HT(1B) receptors), we applied in vivo brain microdialysis technique to 6-hydroxydopamine-lesioned rats and examined the effects of the selective 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the selective 5-HT(1B) receptor agonist CGS-12066 A on L-DOPA-derived extracellular DA levels. Single L-DOPA injection (50 mg/kg i.p.) caused a rapid increase and a following decrease of extracellular DA, with a peak value at 100 min after L-DOPA injection. Pretreatment with both 0.3 mg/kg and 1 mg/kg 8-OH-DPAT (i.p.) significantly attenuated an increase in L-DOPA-derived extracellular DA and the times of peak DA levels were prolonged to 150 min and 225 min after L-DOPA injection, respectively. These 8-OH-DPAT-induced changes in L-DOPA-derived extracellular DA were antagonized by further pretreatment with WAY-100635, a selective 5-HT(1A) antagonist. In contrast, intrastriatal perfusion with the 5-HT(1B) agonist CGS-12066 A (10 nM and 100 nM) did not induce any changes in L-DOPA-derived extracellular DA. Thus, stimulation of 5-HT(1A) but not 5-HT(1B) receptors attenuated an increase in extracellular DA derived from exogenous L-DOPA. These results support the hypothesis that serotonergic neurons are primarily responsible for the storage and release of DA derived from exogenous L-DOPA in the absence of dopaminergic neurons.
GAD 65 and Insulin B Chain Peptide (9-23) are not Primary Autoantigens in the Type 1 Diabetes Syndrome of the BB Rat (1999)

To investigate whether GAD65 whole molecule, GAD65 p35 or insulin B chain peptide (amino acids 9-23) play an essential role in the pathogenesis of type 1 diabetes in the BioBreeding (BB) rat, we gave serial injections of GAD65, p35 or insulin B chain (9-23) to six groups of BB/Worcester rats. The individual antigens were administered either intrathymically on day 2 and intraperitoneally in MF 59-0 adjuvant 5 times during the first 5 weeks, or by intranasal instillation once neonatally and 5 days/week for the following 6 weeks. Control groups were injected with vehicle only. Age of onset of diabetes and degree of insulitis were not different between controls and antigen-treated rats. Rats that received GAD65 intrathymically and intraperitoneally developed high GAD65-antibody titers without altering diabetes development. In GAD65-treated animals, serum antibodies recognized epitopes at 3 sites on GAD65 in diabetic animals but only at 1 site in non-diabetic animals. GAD65-injected animals also showed a significant reduction of IFN-gamma mRNA expression in the thymus. This study provides evidence against the hypothesis that GAD65 and insulin B chain peptide (9-23) are primary diabetogenic autoantigens in BB rats because immunizations with these antigens and GAD65-induced immune deviation did not alter the development of diabetes.
Regulation of Microtubule Dynamics by Extracellular Signals: cAMP-dependent Protein Kinase Switches Off the Activity of Oncoprotein 18 in Intact Cells (1998)

Oncoprotein 18 (Op18, also termed p19, 19K, metablastin, stathmin, and prosolin) is a recently identified regulator of microtubule (MT) dynamics. Op18 is a target for both cell cycle and cell surface receptor-coupled kinase systems, and phosphorylation of Op18 on specific combinations of sites has been shown to switch off its MT-destabilizing activity. Here we show that induced expression of the catalytic subunit of cAMP-dependent protein kinase (PKA) results in a dramatic increase in cellular MT polymer content concomitant with phosphorylation and partial degradation of Op18. That PKA may regulate the MT system by downregulation of Op18 activity was evaluated by a genetic system allowing conditional co-expression of PKA and a series of kinase target site-deficient mutants of Op18. The results show that phosphorylation of Op18 on two specific sites, Ser-16 and Ser-63, is necessary and sufficient for PKA to switch off Op18 activity in intact cells. The regulatory importance of dual phosphorylation on Ser-16 and Ser-63 of Op18 was reproduced by in vitro assays. These results suggest a simple model where PKA phosphorylation downregulates the MT-destabilizing activity of Op18, which in turn promotes increased tubulin polymerization. Hence, the present study shows that Op18 has the potential to regulate the MT system in response to external signals such as cAMP-linked agonists.
Sleep changes produced by destruction of medial septal neurons in rats (2004)

Changes in sleep-wakefulness were studied in male Wistar rats after destruction of the medial septal neurons with NMDA. Electroencephalogram, electromyogram and electrooculogram were recorded for 24 h prior to the destruction of the medial septum, and 7, 14 and 21 days after the destruction. There was a decrease in the total amount of slow wave sleep and frequency of slow wave sleep episodes after the lesion. It also produced an increase in the duration of paradoxical sleep episodes. These findings are in contrast to the changes produced after lesion of other basal forebrain areas. The present findings suggest that the medial septum may be involved in the genesis of slow wave sleep and inhibition of the durations of paradoxical sleep episodes.