gebhart/patrepeval huggingface dataset:
CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease (2008)

Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid beta protein (Abeta) peptide "oligomers" and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established antiinflammatory properties, interferes with Abeta assembly and protects neuronal cells from the toxic effect of soluble Abeta oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk significantly reduced Abeta deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a significant dose-dependent decrease of total Abeta accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD.
A 'biogenetic like' synthesis of perloline, 6-(3,4-Dimethoxyphenyl)-5-hydroxy-5,6-dihydrobenzo[c][2,7]naphthyridin-4(3H)-one (1983)

9H-Indeno[2,1-c]pyridine-1(2H),9-dione, prepared by a new efficient route, reacts with 3,4-dimethoxy- phenyllithium to form the keto alcohol (7), which rearranges with hydrazoic acid to form 5-(3,4- dimethoxyphenyl)benz[c][2,7]naphthyridin-4(3H)-one. The N -oxide photolyses smoothly to yield dehydroperloline as the sole product.
Clusters: Link between molecules and solids (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTClusters: Link between molecules and solidsDaniel A. Jelski and Thomas F. George Cite this: J. Chem. Educ. 1988, 65, 10, 879Publication Date (Print):October 1, 1988Publication History Received3 August 2009Published online1 October 1988Published inissue 1 October 1988https://doi.org/10.1021/ed065p879RIGHTS & PERMISSIONSArticle Views123Altmetric-Citations9LEARN 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 InReddit PDF (4 MB) Get e-Alerts Get e-Alerts
Effect of purified growth factors on rabbit articular chondrocytes IN MONOLAYER CULTURE. I. DNA Synthesis (1982)

Abstract The ability of purified growth factors, insulin, ascorbate, and several other compounds to stimulate DNA synthesis by rabbit articular chondrocytes was studied in monolayer culture. Platelet‐derived growth factor (1 U/ml), pituitary fibroblast growth factor (1–100 ng/ml), and epidermal growth factor (1–50 ng/ml) were stimulatory in a basal medium supplemented with 1% heat‐inactivated fetal bovine serum. Insulin, 1–50 μg/ml, had small growth‐promoting effects but acted synergistically with platelet‐derived, pituitary fibroblast, and epidermal growth factors. Increasing concentrations of serum up to 10% enhanced the growth‐promoting action of the purified factors, but not of insulin. There were indications of cooperation between insulin and bovine serum albumin and dexamethasone. Ascorbate (0.2 m M ) reduced or had little growth‐promoting action in the basal medium. At 5 and 10% serum concentrations, however, ascorbate promoted DNA synthesis as effectively as the purified growth factors. No significant stimulatory effect was shown by transferrin, thrombin, L‐glutamine, putrescine, selenous acid, dexamethasone, 7S nerve growth factor, or multiplication‐stimulating activity.
Long-circulating liposomes. (1994)

Liposomes have been investigated for use as drug carriers, and many previous studies have demonstrated enhanced efficacy of encapsulated drugs and the reduction of the side effects of drugs so entrapped. In many cases liposomal drugs are administered via the bloodstream. The stability in the bloodstream, clearance, and biodistribution are dependent on the composition, size, and charge of the liposomes. Rigid, small-size (100-200 nm) liposomes tend to be retained in the blood without degradation. Since the conventional liposomes are trapped in the reticuloendothelial system (RES), RES targeting by means of liposomes is easily achieved. This tendency of liposomes, however, is the most serious limitation when their target is not the RES. Many attempts have been made to avoid the RES-trapping and to prolong the circulation time of liposomes with monosialoganglioside GM1, polyethyleneglycol, glucuronide derivatives, and so on. When the targets are tumor tissues, these RES-avoiding, long-circulating liposomes passively accumulate in such tissues due to extravasation through the leaky vasculature in the tumor tissues. Therefore, long-circulating liposomes are useful tools, especially for tumor imaging and therapy. In this review, we show examples and discuss the mechanism of RES avoidance by these modifiers of liposomes, with special focus on the glucuronide as a modifier.
Prediction of Human Pharmacokinetics From Preclinical Information: Comparative Accuracy of Quantitative Prediction Approaches (2009)

Quantitative prediction of human pharmacokinetics is critical in assessing the viability of drug candidates and in determining first-in-human dosing. Numerous prediction methodologies, incorporating both in vitro and preclinical in vivo data, have been developed in recent years, each with advantages and disadvantages. However, the lack of a comprehensive data set, both preclinical and clinical, has limited efforts to evaluate the optimal strategy (or strategies) that results in quantitative predictions of human pharmacokinetics. To address this issue, the authors conducted a retrospective analysis using 50 proprietary compounds for which in vitro, preclinical pharmacokinetic data and oral single-dose human pharmacokinetic data were available. Five predictive strategies, involving either allometry or use of unbound intrinsic clearance from microsomes or hepatocytes, were then compared for their ability to predict human oral clearance, half-life through predictions of systemic clearance, volume of distribution, and bioavailability. Use of a single-species scaling approach with rat, dog, or monkey was as accurate as or more accurate than using multiple-species allometry. For those compounds cleared almost exclusively by P450-mediated pathways, scaling from human liver microsomes was as predictive as single-species scaling of clearance based on data from rat, dog, or monkey. These data suggest that use of predictive methods involving either single-species in vivo data or in vitro human liver microsomes can quantitatively predict human in vivo pharmacokinetics and suggest the possibility of streamlining the predictive methodology through use of a single species or use only of human in vitro microsomal preparations.
Discovery of Cellulose as a Smart Material (2006)

The past 10 years has witnessed a renewed interest in cellulose research and application, sparked mostly by technological interests in renewable raw materials and more environmentally friendly and sustainable resources. In this paper, we further expand the current knowledge in cellulose applications and technologies by reporting our discovery of cellulose as a smart material that can be used for biomimetic sensor/actuator devices and micro-electromechanical systems. This smart cellulose is termed electroactive paper (EAPap). It can produce a large bending displacement with low actuation voltage and low power consumption. The actuation phenomenon and its characteristics are illustrated in this paper. Because cellulose EAPap is ultra-lightweight, inexpensive, and biodegradable, it is advantageous for many applications such as micro-insect robots, micro-flying objects, micro-electromechanical systems, biosensors, and flexible electrical displays.
Organization of the human cholesteryl ester transfer protein gene (1990)

The plasma cholesteryl ester transfer protein (CETP) catalyzes the transfer of phospholipids and neutral lipids between the lipoproteins. Thus, this protein may be important in modulating lipoprotein levels in the plasma. We have determined the primary structure and organization of the human CETP gene. Southern blotting of cellular DNA indicated a single copy of the CETP gene exists per haploid genome. Analysis of three overlapping genomic clones showed that the gene spans approximately 25 kbp and contains 16 exons (size range 32-250 bp). Overall, the sequence and organization of the CETP gene do not resemble those of other lipid-metabolizing enzymes or apolipoproteins. However, comparison of the CETP sequence, one exon at a time, with the sequences in the sequence databases revealed a striking identity of a pentapeptide sequence (ValLeuThrLeuAla) within the hydrophobic core of the signal sequences of human CETP, apolipoproteins A-IV and A-I, and lipoprotein lipase. This pentapeptide sequence was not found in the signal sequences of other proteins, suggesting that it may mediate a specialized function related to lipid metabolism or transport.
CD33 expression and P-glycoprotein–mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy (2007)

Gemtuzumab ozogamicin (GO) contains an anti-CD33 antibody to facilitate uptake of a toxic calicheamicin-gamma(1) derivative. While recent in vitro data demonstrated a quantitative relationship between CD33 expression and GO cytotoxicity, previous correlative studies failed to identify a significant association between CD33 expression and clinical outcome. Studying patients undergoing GO monotherapy for relapsed acute myeloid leukemia (AML), we now find that AML blasts of responders have a significantly higher mean CD33 level and lower P-glycoprotein (Pgp) activity compared with nonresponders. CD33 expression and Pgp activity are inversely correlated. While both variables are associated with outcome, Pgp remains significantly associated with outcome even after adjusting for CD33, whereas CD33 does not show such an association after adjusting for Pgp. The inverse relationship between CD33 and Pgp suggests a maturation-stage-dependent expression of both proteins, and offers the rationale for using cell differentiation-promoting agents to enhance GO-induced cytotoxicity.
Mitochondrial Oxygen Affinity, Respiratory Flux Control And Excess Capacity Of Cytochrome c Oxidase (1998)

The oxygen affinity of the enzyme system involved in mitochondrial respiration indicates, in relation to intracellular oxygen levels and interpreted with the aid of flux control analysis, a significant role of oxygen supply in limiting maximum exercise. This implies that the flux control coefficient of mitochondria is not excessively high, based on a capacity of mitochondrial oxygen consumption that is slightly higher than the capacity for oxygen supply through the respiratory cascade. Close matching of the capacities and distribution of flux control is consistent with the concept of symmorphosis. Within the respiratory chain, however, the large excess capacity of cytochrome c oxidase, COX, appears to be inconsistent with the economic design of the respiratory cascade. To address this apparent discrepancy, we used three model systems: cultured endothelial cells and mitochondria isolated from heart and liver. Intracellular oxygen gradients increase with oxygen flux, explaining part of the observed decrease in oxygen affinity with increasing metabolic rate in cells. In addition, mitochondrial oxygen affinities decrease from the resting to the active state. The oxygen affinity in the active ADP-stimulated state is higher in mitochondria from heart than in those from liver, in direct relationship to the higher excess capacity of COX in heart. This yields, in turn, a lower turnover rate of COX even at maximum flux through the respiratory chain, which is necessary to prevent a large decrease in oxygen affinity in the active state. Up-regulation of oxygen affinity provides a functional explanation of the excess capacity of COX. The concept of symmorphosis, a matching of capacities in the respiratory cascade, is therefore complemented by 'synkinetic' considerations on optimum enzyme ratios in the respiratory chain. Accordingly, enzymatic capacities are matched in terms of optimum ratios, rather than equal levels, to meet the specific kinetic and thermodynamic demands set by the low-oxygen environment in the cell.
Pharmacokinetics in the rat of a panel of immunotoxins made with abrin A chain, ricin A chain, gelonin, and momordin. (1990)

A panel of immunotoxins was constructed by chemically attaching the ribosome-inactivating proteins abrin A chain, ricin A chain, gelonin, and momordin to the monoclonal mouse IgG2a antibody Fib75 by means of a disulfide linkage. All the immunotoxins were toxic in tissue culture to the EJ human bladder carcinoma cell line expressing the antigen recognized by Fib75, inhibiting the incorporation of [3H]leucine by 50% at concentrations between 1 x 10(-10) M and 8 x 10(-10) M. The pharmacokinetics of the immunotoxins in the normal Wistar rat was determined following i.v. administration. The concentrations of intact immunotoxin in serum samples taken at various intervals after injection for up to 24 h were measured by solid-phase enzyme-linked immunosorbent assays specific for each of the four different ribosome-inactivating proteins. The Fib75 immunotoxins were cleared from the circulation with comparable, but not identical, biphasic kinetics best described by a two compartment open pharmacokinetic model. The alpha-phase half-lives of the panel, between 0.35 and 0.71 h, were similar. The beta-phase half-life of Fib75-abrin A chain, 13.3 h, was significantly longer than the beta-phase half-lives of Fib75-ricin A chain, Fib75-gelonin, and Fib75-momordin, between 7.5 and 8.6 h. Fib75-abrin A chain was found to be about 3- to 4-fold more resistant than the other immunotoxins to breakdown by reduction of the disulfide linkage between the A chain and the antibody with glutathione in vitro. This suggests that the longer serum half-life of Fib75-abrin A chain may have been due to greater stability against reduction in vivo. Analysis of serum samples obtained up to 24 h after injection of Fib75-abrin A chain revealed that the chemically intact immunotoxin present in the circulation retained full cytotoxic activity. An abrin A chain immunotoxin made with a different monoclonal mouse IgG2a antibody was also found to be more stable against reduction by glutathione in vitro than an analogous ricin A chain immunotoxin. Thus, abrin A chain may posses unique molecular properties that endow immunotoxins made with this A chain with greater stability in vivo than immunotoxins made with ricin A chain or other ribosome-inactivating proteins.
Dentin Regeneration by Dental Pulp Stem Cell Therapy with Recombinant Human Bone Morphogenetic Protein 2 (2004)

Regenerative medicine is based on stem cells, signals, and scaffolds. Dental pulp tissue has the potential to regenerate dentin in response to noxious stimuli, such as caries. The progenitor/stem cells are responsible for this regeneration. Thus, stem cell therapy has considerable promise in dentin regeneration. Culture of porcine pulp cells, as a three-dimensional pellet, promoted odontoblast differentiation compared with monolayers. The expression of dentin sialophosphoprotein (Dspp) and enamelysin/matrix metalloproteinase 20 (MMP20) mRNA confirmed the differentiation of pulp cells into odontoblasts and was stimulated by the morphogenetic signal, bone morphogenetic protein 2 (BMP2). Based on the in vitro experiments, an in vivo evaluation of pulp progenitor/stem cells in the dog was performed. The autogenous transplantation of the BMP2-treated pellet culture onto the amputated pulp stimulated reparative dentin formation. In conclusion, BMP2 can direct pulp progenitor/stem cell differentiation into odontoblasts and result in dentin formation.
A general approach to synthesis of nanoparticles with controlled morphologies and magnetic properties (2005)

We present a systematic approach to fabricate a variety of magnetic nanoparticles with desirable structure and controlled magnetic properties based on our studies of the process kinetics. The morphology of binary alloy particles is dependent on their bulk thermodynamics—for immiscible heterogeneous systems (Co–Au) core-shell structures are obtained while miscible systems (Fe–Pt) lead to alloy nanoparticles. The annealing effects on FePt nanoparticles show that the coercivity and magnetic anisotropy increase dramatically after annealing at temperatures above 650°C. Studies of Co–Au core-shell structure show that the core is magnetic, but the Au shell does not significantly affect its magnetic properties.
Optimization of noise and responsivity in CMOS active pixel sensors for detection of ultralow-light levels (1997)

In this paper, we present results of the investigation of the design and operation of CMOS active pixel sensors for detection of ultra-low light levels. We present a detailed noise model of APS pixel and signal chain. Utilizing the noise model, we have developed APS pixel designs that can achieve ultra-low noise and high responsivity. We present results from two test chips, that indicate (1) that less than 5 electrons of read noise is possible with CMOS APS by reducing the size of the pixel transistors, and (2) that high responsivity can be achieved when the fill-factor of the photodiode is reduced.
An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors (2010)

Of the affinity variant minibodies tested, the A11 minibody that ranked second in affinity was selected as the best immunoPET tracer to image PSCA-expressing xenografts. This candidate is currently under development for evaluation in a pilot clinical imaging study.
Protosappanin C from sappan lignum and absolute configuration of protosappanins. (1987)

A new dibenz [b, d] oxocin derivative, named protosappanin C (3), C16H14O6, amorphous powder, [α] 23D -39.8° (MeOH), was isolated from Sappan Lignum (the dried heart-wood of Caesalpinia sappan L. (Leguminosae)). It yielded sappanin (4) on alkaline fusion, an oxime (5), a dimethyl acetal (6) on treatment with p-toluenesulfonic acid in methanol, and protosappanin B (2) on reduction with sodium borohydride. The circular dichroism spectra of 3 and 6 indicated that their biphenyl system preferentially takes S configuration, from which R configuration was assigned to C-7 of 3. On the basis of the above chemical and spectroscopic evidence, the chemical structure of 3 was established as (7R) -7, 8-dihydro-3, 7, 10, 11-tetrahydroxy-7 (6H) -dibenz [b, d] oxocincarbaldehyde. A possible route of biosynthesis of protosappanins from sappanchalcone is discussed.
Effect of trypsin treatment on the heparin- and receptor-binding properties of human plasma low-density lipoproteins (1986)

The effect of trypsin treatment on the heparin- and receptor-binding properties of human plasma low-density lipoproteins (LDL) was examined. LDL were treated with trypsin (2% by weight) for 16 h at 37 degrees C, and the trypsinized core particles (T-LDL) were isolated by gel permeation chromatography on Sepharose CL-4B. Trypsin degraded the apolipoprotein B moiety (Mr = 550,000) of LDL into numerous peptides of Mr less than 110,000, resulting in the release of 25% +/- 5% (n = 6) of its surface-associated protein. Relative to LDL, T-LDL had an increased phospholipid/protein ratio, decreased flotation density and alpha-helical structure, and increased fluidity of the surface and core constituents. Compared to LDL, T-LDL showed a 60% decreased capacity to suppress [1-14C]acetate incorporation into cellular sterols consistent with decreased binding to the LDL receptor. In contrast, T-LDL showed an enhanced capacity to form soluble complexes with heparin in the absence and presence of 2 mM Ca2+. Between 5 and 25 mM Ca2+, both LDL and T-LDL were maximally precipitated by heparin; the stoichiometry of the insoluble complexes (uronic acid/phospholipid, w/w) was 0.054 +/- 0.004 and 0.055 +/- 0.005 (n = 18) for LDL and T-LDL, respectively. Thus, trypsin treatment significantly diminished the lipoprotein's interaction with cells but not with heparin. This finding suggests that proteolysis may decrease receptor-mediated uptake of LDL without diminishing the lipoprotein's reactivity with acellular components of the arterial wall.
Reperfusion Damage to the Bile Canaliculi in Transplanted Human Liver (1996)

In 19 patients who have undergone orthotopic liver transplantation (OLT), the trend and degree of cholestasis was statistically monitored in terms of plasma levels of L-gamma-glutamyl transferase (GGT) and total bilirubin. In addition, the ultrastructure of the bile canaliculus was examined during the entire OLT procedure, i.e., during explantation, cold ischemia, and after 60 to 90 minutes of organ reperfusion. Cholestasis was evident from the second day after surgery, with a peak after approximately 10 to 16 days. Defined, small changes in the functional state of actin filaments were noted in the bile canalicular area after prolonged ischemia. But the morphological status of the bile canaliculi changed dramatically after reperfusion. In fact, the mean area and perimeter of the canaliculi had increased significantly, and there was a marked loss in the number of bile microvilli per unit of canalicular area. The bile canaliculus appears to be one of the liver structures most susceptible to ischemia-reperfusion damage. A series of biochemical changes occurring during ischemia and after reoxygenation of the transplanted liver, especially, would provide a reason for the observed early morphological damage of the bile canaliculus, which, in turn, would explain the cholestasis of these patients in the first posttransplantation period.
Alloantigen presentation by B cells. Requirement for IL-1 and IL-6. (1988)

We have evaluated the requirements for non-activated allogeneic B cells to present alloantigen in primary MLC. We found that the generation of an MLR was dependent on the addition of exogenous IL-1 and IL-6 to the cultures; neither lymphokine by itself was capable of significantly stimulating the response. Our results suggest that the concentration of these lymphokines present in a standard MLR culture may serve to regulate the magnitude of the proliferative response. The B cells that co-stimulated with IL-1 and IL-6 were found to be contained almost exclusively within the large, low density population. Presumably, large low density B cells have attained a state in which they are particularly effective at presentation of alloantigen. Together our findings indicate that three components are required for Ag presentation in primary MLC: class II MHC-positive stimulator cells that have attained the appropriate state of differentiation and the presence of both IL-1 and IL-6.