gebhart/patrepeval huggingface dataset:
Ultrastructural Studies of the Cells Forming Amyloid Fibers in Classical Plaques (1989)

Three-dimensional reconstruction and ultrastructural studies of classical plaques from the cortex of patients with Alzheimer's disease showed that microglial cells of the plaques are the amyloid-forming cells. The amyloid star of the single plaque represents the product of five or six microglial cells covering about 80% of the amyloid star surface. The amyloid fibers appear to be formed within altered cisterns of the endoplasmic reticulum. Distended cisterns form channels filled with amyloid fibers. Numerous vesicles derived from the Golgi apparatus appear to be attached to or fused with the amyloid-filled channels. Reconstruction of the amyloid star and the microglia cell pole that forms the amyloid star reveals three different zones of distribution of cytoplasmic organelles and amyloid deposits. The peripheral zone comprises channels filled with loosely packed amyloid fibers arranged in a parallel manner. The transient zone consists of a mixture of fusing amyloid channels and products of disintegration of cytoplasmic pockets, dense bodies and fragments of cellular membranes. The core of the amyloid star is composed of condensed, densely packed amyloid fibers that are free of cellular debris. Formation of the three zones supports the idea that the microglia/macrophages are not phagocytes but instead are the cells manufacturing the amyloid fibers.
Binding of N-linked bovine fetuin glycopeptides to isolated rabbit hepatocytes: Gal/GalNAc hepatic lectin discrimination between Gal.beta.(1,4)GlcNAc and Gal.beta.(1,3)GlcNAc in a triantennary structure (1986)

Glycopeptides were isolated from bovine fetuin after digestion with Pronase, aminopeptidase M, and carboxypeptidase Y. The glycopeptides were derivatized with tert-butyloxycarbonyltyrosine and separated on the basis of peptide by using reverse-phase high-performance liquid chromatography. Using 400-MHz 1H NMR, the asialotriantennary oligosaccharides at each of the three N-linked glycosylation sites were found to be combinations of the following two structures in which the third branch is either Gal beta(1,4)GlcNAc or Gal beta(1,3)GlcNAc: (formula; see text) The asialotriantennary glycopeptides containing all beta(1,4)-lactosamine as the branches were designated Gal beta(1,4)GlcNAc-TRI while triantennary glycopeptides containing beta(1,3)-lactosamine as branch III were termed Gal beta(1,3)GlcNAc-TRI. The Gal beta(1,3)GlcNAc unit was localized predominantly to the branch III arm on the basis of a downfield shift (-0.027 ppm) in the H-1 and upfield shift (0.01 ppm) in the NAc methyl signals from the branch III GlcNAc resulting from Gal beta(1,3) instead of Gal beta(1,4) substitution. Revised assignments are proposed for the H-1's of Gal residues 6 (delta 4.464) and 8 (delta 4.471) [Vliegenthart, J. F. G., Dorland, L., & van Halbeek, H. (1983) Adv. Carbohydr. Chem. Biochem. 41, 209-373] in a Gal beta(1,4)GlcNAc-TRI. The proportion of Gal beta(1,3)GlcNAc-TRI glycopeptides from the Asn-Asp, Asn-Gly, and Asn-Cys sites was found to be 40%, 60%, and 20%, respectively. Analysis of the binding of these glycopeptides, containing from 20% to 60% Gal beta(1,3)GlcNAc as branch III, to rabbit hepatocytes revealed that the greater the proportion of Gal beta(1,3)GlcNAc, the lower the affinity of the mixture. The Kd for Gal beta(1,4)GlcNAc-TRI was found to be between 3.6 and 5.4 nM (P = 0.10) with a mean of 4.4 nM from binding data analyzed by using the LIGAND program [Munson, P. J., & Rodbard, D. (1980) Anal. Biochem. 107, 220-239] and computer simulations of the binding of two ligands as a mixture to one receptor site. The Kd of Gal beta(1,3)GlcNAc-TRI oligosaccharide, prepared by hydrazinolysis, was found to be 305 nM from inhibition studies.
Synthesis of thymidine oligonucleotides by phosphite triester intermediates (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of thymidine oligonucleotides by phosphite triester intermediatesRobert L. Letsinger and Willie B. LunsfordCite this: J. Am. Chem. Soc. 1976, 98, 12, 3655–3661Publication Date (Print):June 1, 1976Publication History Published online1 May 2002Published inissue 1 June 1976https://pubs.acs.org/doi/10.1021/ja00428a045https://doi.org/10.1021/ja00428a045research-articleACS PublicationsRequest reuse permissionsArticle Views1282Altmetric-Citations222LEARN 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
Decarboxylative Claisen Rearrangement Reactions of Allylic Tosylmalonate Esters (2005)

[reaction: see text] Two different combinations of silylating agent and base are used for one-pot [3,3]-sigmatropic rearrangement-decarboxylation reactions of tosylmalonic mono(allylic) esters under mild conditions, providing the products of formal regiospecific allylation of methyl tosylacetate at the more substituted allylic terminus.
Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes. (1989)

We have localized transforming growth factor-beta (TGF-beta) in many cells and tissues with immunohistochemical methods, using two polyclonal antisera raised to different synthetic preparations of a peptide corresponding to the amino-terminal 30 amino acids of TGF-beta 1. These two antibodies give distinct staining patterns; the staining by anti-CC(1-30) is intracellular. This differential staining pattern is consistently observed in several systems, including cultured tumor cells; mouse embryonic, neonatal, and adult tissues; bovine fibropapillomas; and human colon carcinomas. The extracellular staining by anti-CC(1-30) partially resembles that seen with an antibody to fibronectin, suggesting that extracellular TGF-beta may be bound to matrix proteins. The intracellular staining by anti-LC(1-30) is similar to that seen with two other antibodies raised to peptides corresponding to either amino acids 266-278 of the TGF-beta 1 precursor sequence or to amino acids 50-75 of mature TGF-beta 1, suggesting that anti-LC(1-30) stains sites of TGF-beta synthesis. Results from RIA and ELISAs indicate that anti-LC(1-30) and anti-CC(1-30) recognize different epitopes of this peptide and of TGF-beta 1 itself.
Production of Chiral and other Valuable Compounds from Microbial Polyesters (2002)

Abstract Introduction Historical Outline ( R )‐Hydroxycarboxylic Acids Production of ( R )‐3‐Hydroxycarboxylic Acid Chemical Depolymerization Biological Depolymerization Applications of ( R )‐Hydroxycarboxylic Acids Chiral Starting Material for the Synthesis of Valuable Compounds Dioxanones Lactones, Cyclic Oligomers and Dendrimer Outlook and Perspectives Patents Acknowledgments
Advances in understanding fragile X syndrome and related disorders (2011)

The gene defect underlying fragile X syndrome was discovered back in 1991. Since then, there has been enormous progress in our understanding of the molecular basis of the disease. Excitingly, our insights have now reached a next phase in which therapy specifically targeting the underlying molecular defect becomes feasible.
Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340. (1999)

Synthetic matrix metalloproteinase (MMP) inhibitors have activity against a variety of tumors in preclinical models but have not been studied in gliomas. We determined the effect of AG3340, a novel synthetic MMP inhibitor with Ki values against gelatinases in the low picomolar range, on the growth of a human malignant glioma cell line (U87) in SCID-NOD mice. Mice were injected s.c. with U87 cells. Tumors were allowed to grow to a size of approximately 0.5 x 0.5 cm (after about 3 weeks), and the mice were randomized to receive either: (a) 100 mg/kg AG3340 in vehicle; or (b) vehicle control (0.5% carboxymethyl cellulose, 0.1% pluronic F68), both given daily i.p. Tumor area was measured twice weekly, and animals were sacrificed when moribund, or earlier if premorbid histology was examined. In vivo inhibition of tumor growth was profound, with AG3340 decreasing tumor size by 78% compared with controls after 31 days (when controls were sacrificed; P < 0.01, Wilcoxon test). Control animals survived 31 days after the i.p. injections began, and AG3340 mice survived 71 days, representing a >2-fold increase in survival associated with tumor growth delay. Histological examination found that AG3340-treated tumors were smaller, had lower rates of proliferation, and significantly less invasion than control-treated tumors. Hepatic or pulmonary metastases were not seen in either group. In a separate experiment, the tumors were smaller and sampled after a shorter duration of treatment; the changes in proliferation were more marked and occurred earlier than differences in tumor invasion between the two groups. Furthermore, in vitro cell growth was not inhibited at AG3340 concentrations of <1 mM. AG3340 plasma concentrations in vivo, 1 h after administration, ranged from 67 to 365 nM. Thus, AG3340 produced a profound inhibition of glioma tumor growth and invasion. AG3340 markedly increased survival in this in vivo glioma model. Treatment with AG3340 may be potentially useful in patients with malignant gliomas.
Brain‐derived neurotrophic factor induces a rapid dephosphorylation of tau protein through a PI‐3Kinase signalling mechanism (2005)

The microtubule-associated protein tau is essential for microtubule stabilization in neuronal axons. Hyperphosphorylation and intracellular fibrillar formation of tau protein is a pathology found in Alzheimer's disease (AD) brains, and in a variety of neurodegenerative disorders referred to as 'taupathies'. In the present study, we investigated how brain-derived neurotrophic factor (BDNF), an extracellular factor that is down-regulated in AD brains, affects tau phosphorylation. BDNF stimulation of neuronally differentiated P19 mouse embryonic carcinoma cells resulted in a rapid decrease in tau phosphorylation, at phosphorylation sites recognized by Tau 1, AT 8, AT 180 and p 262-Tau antibodies. K 252 a, a tyrosine receptor kinase (Trk) inhibitor, attenuated this dephosphorylation event, suggesting that BNDF activation of TrkB is responsible for the tau dephosphorylation. In addition, BDNF had no affect on tau phosphorylation in the presence of wortmannin, a PI-3 Kinase inhibitor, or lithium, a GSK 3 beta inhibitor, suggesting that these two kinases are part of the signaling transduction cascade leading from TrkB receptor activation to tau dephosphorylation. These results suggest a link between a correlate of AD, decrease in BDNF levels and an AD pathology, tau hyperphosphorylation.
Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily (1999)

The crystal structure of intercellular adhesion molecule-2 (ICAM-2) revealed significant differences in the presentation of the critical acidic residue important for integrin binding between I and non-I-domain integrin ligands. Based on this crystal structure, we mutagenized ICAM-2 to localize the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1). The integrin binding site runs diagonally across the GFC beta-sheet and includes residues on the CD edge of the beta-sandwich. The site is oblong and runs along a flat ridge on the upper half of domain 1, which is proposed to dock to a groove in the I domain of LFA-1, with the critical Glu-37 residue ligating the Mg2+ in the I domain. Previous mutagenesis of ICAM-1 and ICAM-3, interpreted in light of the recently determined ICAM-1 and ICAM-2 structures, suggests similar binding sites. By contrast, major differences are seen with vascular cell adhesion molecule-1 (VCAM-1), which binds alpha4 integrins that lack an I domain. The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1.
Reduction to Normal of Plasma Glucose in Juvenile Diabetes by Subcutaneous Administration of Insulin with a Portable Infusion Pump (1979)

To improve plasma glucose control, we administered insulin via the subcutaneous route in seven ambulatory patients with juvenile diabetes (12 to 17 years of age), using a portable infusion pump at a basal rate with pulse-dose increments before meals. After two to four days, the mean plasma glucose (+/- 1 S.E.) of 94 +/- 5 mg per deciliter was markedly lower than when insulin was given by conventional methods in the patients' usual dose (243 +/- 28, P less than 0.01) or in a total dose equivalent to that administered with the pump (150 +/- 15, P less than 0.01). Maximal fluctuations in plasma glucose were also 50 to 150 mg per deciliter below those observed with conventional treatment (P less than 0.001). Glycosuria was eliminated in six of seven patients during pump treatment. None of the subjects had hypoglycemia. These results demonstrate that plasma glucose can be lowered to normal in ambulatory patients with brittle juvenile diabetes using a portable, subcutaneous insulin infusion system for two to four days. The feasibility and value of the long-term application of this technic need exploration.
Multiple Stress Memorization In Advanced SOI CMOS Technologies (2007)

Two distinct stress memorization phenomena in advanced SOI CMOS are reported in this work. Both require a capping layer and anneal, but can be categorized as techniques 1) requiring an amorphized source/drain region and low temperature anneal, and 2) requiring a high temperature anneal, independent of the crystalline state of the Si. Both improve NMOS drive current, and the resulting improvements are additive to >27% NMOS IDSAT improvement. The first phenomenon is previously unreported. It has been identified to be localized in the source/drains, and yields more improvement with multiple offset implantation prior to capping and annealing.
Demonstrating a Continuous Set of Two-qubit Gates for Near-term Quantum Algorithms (2020)

Quantum algorithms offer a dramatic speedup for computational problems in material science and chemistry. However, any near-term realizations of these algorithms will need to be optimized to fit within the finite resources offered by existing noisy hardware. Here, taking advantage of the adjustable coupling of gmon qubits, we demonstrate a continuous two-qubit gate set that can provide a threefold reduction in circuit depth as compared to a standard decomposition. We implement two gate families: an imaginary swap-like (iSWAP-like) gate to attain an arbitrary swap angle, θ, and a controlled-phase gate that generates an arbitrary conditional phase, ϕ. Using one of each of these gates, we can perform an arbitrary two-qubit gate within the excitation-preserving subspace allowing for a complete implementation of the so-called Fermionic simulation (fSim) gate set. We benchmark the fidelity of the iSWAP-like and controlled-phase gate families as well as 525 other fSim gates spread evenly across the entire fSim(θ,ϕ) parameter space, achieving a purity-limited average two-qubit Pauli error of 3.8×10^{-3} per fSim gate.
Electrocardiogram‐Synchronized Rotational Speed Change Mode in Rotary Pumps Could Improve Pulsatility (2011)

Continuous-flow left ventricular assist devices (LVADs) have greatly improved the prognosis of patients with end-stage heart failure, even if continuous flow is different from physiological flow in that it has less pulsatility. A novel pump controller of continuous-flow LVADs has been developed, which can change its rotational speed (RS) in synchronization with the native cardiac cycle, and we speculated that pulsatile mode, which increases RS just in the systolic phase, can create more pulsatility than the current system with constant RS does. The purpose of the present study is to evaluate the effect of this pulsatile mode of continuous-flow LVADs on pulsatility in in vivo settings. Experiments were performed on eight adult goats (61.7 ± 7.5 kg). A centrifugal pump, EVAHEART (Sun Medical Technology Research Corporation, Nagano, Japan), was installed by the apex drainage and the descending aortic perfusion. A pacing lead for the detection of ventricular electrocardiogram was sutured on the anterior wall of the right ventricle. In the present study, we compared pulse pressure or other parameters in the following three conditions, including Circuit-Clamp (i.e., no pump support), Continuous mode (constant RS), and Pulsatile mode (increase RS in systole). Assist rate was calculated by dividing pump flow (PF) by the sum of PF and ascending aortic flow (AoF). In continuous and pulsatile modes, these assist rates were adjusted around 80-90%. The following three parameters were used to evaluate pulsatility, including pulse pressure, dp/dt of aortic pressure (AoP), and energy equivalent pulse pressure (EEP = (∫PF*AoP dt)/(∫PF dt), mm Hg). The percent difference between EEP and mean AoP is used as an indicator of pulsatility, and normally it is around 10% of mean AoP in physiological pulse. Both pulse pressure and mean dp/dt max were decreased in continuous mode compared with clamp condition, while those were regained by pulsatile mode nearly to clamp condition (pulse pressure, clamp/continuous/pulsatile, 25.0 ± 7.6/11.7 ± 6.4/22.6 ± 9.8 mm Hg, mean dp/dt max, 481.9 ± 207.6/75.6 ± 36.2/351.1 ± 137.8 mm Hg/s, respectively). In clamp condition, %EEP was 10% higher than mean AoP (P = 0.0078), while in continuous mode, %EEP was nearly equivalent to mean AoP (N.S.). In pulsatile mode, %EEP was 9% higher than mean AoP (P = 0.038). Our newly developed pulsatile mode of continuous-flow LVADs can produce pulsatility comparable to physiological pulsatile flow. Further investigation on the effect of this novel drive mode on organ perfusion is currently ongoing.
Inactivation of klotho function induces hyperphosphatemia even in presence of high serum fibroblast growth factor 23 levels in a genetically engineered hypophosphatemic ( Hyp ) mouse model (2009)

Hyp mice possess a mutation that inactivates the phosphate-regulating gene, which is homologous to the endopeptidases of the X-chromosome (PHEX). The mutation is associated with severe hypophosphatemia due to excessive urinary phosphate wasting. Such urinary phosphate wasting in Hyp mice is associated with an increased serum accumulation of fibroblast growth factor (FGF) 23. We wanted to determine the biological significance of increased serum FGF23 levels and concomitant hypophosphatemia in Hyp mice and to evaluate whether FGF23 activity could be modified by manipulating klotho (a cofactor of FGF23 signaling). We generated Hyp and klotho double-mutant mice (Hyp/klotho(-/-)). Severe hypophosphatemia of Hyp mice was reversed to hyperphosphatemia in Hyp/klotho(-/-) double mutants, despite the fact that the double mutants showed significantly increased serum levels of FGF23. Hyperphosphatemia in Hyp/klotho(-/-) mice was associated with increased renal expression of sodium/phosphate cotransporter 2a (NaPi2a) protein. Exogenous injection of bioactive parathyroid hormone 1-34 down-regulated renal expression of NaPi2a and consequently reduced serum levels of phosphate in Hyp/klotho(-/-) mice. Moreover, in contrast to the Hyp mice, the Hyp/klotho(-/-) mice showed significantly higher serum levels of 1,25-dihydroxyvitamin D and developed extensive calcification in soft tissues and vascular walls. Furthermore, compared with the Hyp mice, Hyp/klotho(-/-) mice were smaller in size, showed features of generalized tissue atrophy, and generally died by 15-20 wk of age. Our in vivo studies provide genetic evidence for a pathological role of increased FGF23 activities in regulating abnormal phosphate homeostasis in Hyp mice. Moreover, these results suggest that even when serum levels of FGF23 are significantly high, in the absence of klotho, FGF23 is unable to regulate systemic phosphate homeostasis. Our in vivo observations have significant clinical implications in diseases associated with increased FGF23 activity and suggest that the functions of FGF23 can be therapeutically modulated by manipulating the effects of klotho.
Expression of a class II major histocompatibility complex (MHC) heterodimer in a lipid-linked form with enhanced peptide/soluble MHC complex formation at low pH. (1991)

A murine class II major histocompatibility complex (MHC) heterodimer, Ek, expressed as a glycan-phosphatidyl inositol-anchored chimera on Chinese Hamster Ovary cells, can present peptides, but not processed antigen to T cells. This chimeric MHC requires a 100-times higher peptide concentration to achieve a two- to four-times lower level of T cell stimulation. Cleavage with phosphatidylinositol-specific phospholipase C and purification result in large quantities of heterodimer in a water-soluble form. Plates coated with this material and then incubated with peptide can efficiently stimulate the appropriate T cell hybridomas. This stimulation is significantly enhanced when peptides are preincubated with the plate-bound MHC molecules in a pH range (5.0-5.5) similar to that of late endosomes. More than half of the soluble Ek molecules can form a specific complex with cytochrome c peptides in this pH range. This suggests that class II MHC molecules undergo distinct conformational changes in endosomal compartments that render them more capable of forming functional complexes with peptide antigens, irrespective of other cell components.