gebhart/patrepeval huggingface dataset:
PI3K/Akt/FOXO3a pathway contributes to thrombopoietin-induced proliferation of primary megakaryocytes in vitro and in vivo via modulation of p27Kip1 (2008)

Thrombopoietin (TPO), the primary regulator of megakaryocyte (MK) and platelet formation, modulates the activity of multiple signal transduction molecules, including those in the Jak/STAT, p42/p44 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. We previously demonstrated that PI3K and Akt are necessary for TPO-induced cell cycle progression of primary MK progenitors. However, the molecular events secondary to the activation of PI3K/Akt responsible for MK proliferation remain unclear. In this study we show that FOXO3a and its downstream target p27(Kip1) play an important role in TPO-induced proliferation of MK progenitors. We found that TPO down-modulates p27(Kip1) expression at both the mRNA and protein levels in primary MKs in a PI3K dependent fashion. UT-7/TPO, a megakaryocytic cell line, stably expressing constitutively active Akt or a dominant-negative form of FOXO3a failed to reduce p27(Kip1) expression after TPO stimulation, and fail to induce p27(Kip1) expression following TPO withdrawal. Induced expression of an active form of FOXO3a resulted in increased p27(Kip1) expression in this cell line. In addition, the number of MKs is significantly increased in bone marrow from Foxo3a-deficient mice. Taken together with the previous observation that p27(Kip1)-deficient mice also display increased numbers of MK progenitors, our findings indicate that the PI3K/Akt/FOXO3a/p27(Kip1) pathway contributes to normal TPO-induced MK proliferation.
<title>Voxel similarity measures for automated image registration</title> (1994)

We present the concept of the feature space sequence: 2D distributions of voxel features of two images generated at registration and a sequence of misregistrations. We provide an explanation of the structure seen in these images. Feature space sequences have been generated for a pair of MR image volumes identical apart from the addition of Gaussian noise to one, MR image volumes with and without Gadolinium enhancement, MR and PET-FDG image volumes and MR and CT image volumes, all of the head. The structure seen in the feature space sequences was used to devise two new measures of similarity which in turn were used to produce plots of cost versus misregistration for the 6 degrees of freedom of rigid body motion. One of these, the third order moment of the feature space histogram, was used to register the MR image volumes with and without Gadolinium enhancement. These techniques have the potential for registration accuracy to within a small fraction of a voxel or resolution element and therefore interpolation errors in image transformation can be the dominant source of error in subtracted images. We present a method for removing these errors using sinc interpolation and show how interpolation errors can be reduced by over two orders of magnitude.
Packet Radio for Library Online Catalogs (1984)

The advent of online catalogs in libraries has resulted in a problem that&#13;\ncould not have been foreseen when most library buildings were built the&#13;\nneed for wiring to transmit data between terminals and the online catalog.&#13;\nThis problem is particularly serious in older libraries, where there are&#13;\ninsufficient conduits, false ceilings are rare, and one faces the prospect of&#13;\nrunning cables through marble floors.&#13;\nInstalling such wiring can be costly. The experience of the University&#13;\nof California demonstrates that the cost of installing terminals in quantities&#13;\nof eight to ten may range from $8,000 to $12,000, not including staff&#13;\ncosts. Even if the wiring for data communications makes up only half of&#13;\nthis figure ($4000 to $6000), it is evident that the wiring can cost as much as&#13;\nor more than the terminal itself.
The archaeology of business networks: the use of archival records in case study research (2000)

Abstract The case study in the Industrial Marketing and Purchasing (IMP) tradition relies almost exclusively on in-depth interviews as the main source of data. This article discusses the use of another strategy, namely archival research. The first section of the article argues that archival research is an important but often overlooked tool in case study research. Using archival material provides longitudinal data, generates new theories about business networks and improves the validity and reliability of findings. In the second section of the article a model of archival research is presented and strategies for managing the process are discussed. Keywords: Case studyarchival researchindustrial networksmarketing theory
The cell biology of bone growth. (1994)

The field of bone cell biology is clearly of relevance to the problem of stunting in children, as in the final analysis the cells of the growing long bone are the ultimate 'regulators'. It is the alterations in the functions of these cells that manifests as a reduction in height. Normal longitudinal growth is achieved by the coordinated recruitment, proliferation, differentiation, maturation and eventual death of the cells of growth plate and bone. Cellular activity is closely regulated by endocrine factors acting directly or indirectly, with factors produced locally and stored within the bone and cartilage microenvironment having a critical role in intercellular communication. Disruption of any of these processes can lead to growth disturbances, since it only requires a defect in a single gene to have profound effects. Studies in recent years have shed light on the biochemical and molecular effects of cytokines and growth factors and have shown that these regulatory molecules may mediate the effects of certain hormones important in controlling growth. However, the complex interrelationship of these molecules is still not clear. Notwithstanding, understanding of the mechanisms involved in bone remodelling is increasing, as this area attracts much research because of the high incidence of metabolic bone disease in Western society. Although studies of adult bone remodelling are of relevance, there is a requirement for increased research directed specifically at the mechanisms of endochondral ossification and its regulation. Longitudinal bone growth is a challenge to the cell biologist, since it is an accelerated cycle of cellular division and differentiation, within which it is not easy to separate events temporally and spatially. In addition, different regulatory mechanisms are probably important at different stages of growth. Another difficulty impeding progress in this field is the lack of appropriate animal models for research. Much information has come from studies involving rodents, and species differences must always be taken into account. Larger mammals such as the growing piglet or the calf are probably more appropriate for the study of postnatal longitudinal growth in man. If the mechanisms of stunting are to be established at a cellular level, a number of approaches need to be considered. Studies need to be designed using more appropriate animal models, and conditions such as nutritional intake, immunological challenges, chronic intestinal diseases and mechanical loading need to be manipulated. Any effects on longitudinal growth may then be studied temporally and correlated with non-invasive measurements including assays of hormones, cytokines, growth factors and proteins known to regulate their activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Localization of immunogenic regions on the flagellin proteins of Campylobacter jejuni 81116 (1991)

The purpose of this study was to localize antigenic regions on the flagellin protein of Campylobacter jejuni 81116. This strain has two flagellin genes, flaA and flaB, which are 95% identical; only flaA seems to be expressed in motile C. jejuni 81116 cells. Fragments of flaA and flaB were cloned in the bacterial expression vector pEX, and the expression products were incubated with flagellin-specific antibodies. Monoclonal antibodies to broadly cross-reactive epitopes recognized fragments that are located in the termini (CF16 and CF17) and in the center (CF15) of both flagellin A and B proteins. Most of the serotype-specific monoclonal antibodies (CF1, CF2, CD3, CF4, and CF13) reacted with only the center of flagellin A in an area where flagellin A and B differ in 6 amino acid residues. The epitopes in this area were further characterized by competitive binding experiments. The charge and molecular weight microheterogeneity of flagellin, as determined by two-dimensional gel electrophoresis, were unrelated to the expression of both flagellin genes or parts thereof.
Mitochondria-Targeted Antioxidant Peptide SS31 Protects Cultured Human Lens Epithelial Cells against Oxidative Stress (2014)

SS31 was able to protect HLEB-3 cells against oxidative damage and, thus, represents a potential new treatment modality for preventing the formation of cataracts and other age-related disorders.
Circulating Monocyte-Platelet Aggregates Are a More Sensitive Marker of In Vivo Platelet Activation Than Platelet Surface P-Selectin (2001)

As demonstrated by 3 independent means (in vivo tracking of activated platelets in baboons, human coronary intervention, and human AMI), circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin.
Modulation of seizure susceptibility in the mouse by the strychnine‐insensitive glycine recognition site of the NMDA receptor/ion channel complex (1990)

1. In order to determine whether the strychnine-insensitive glycine modulatory site on the N-methyl-D-aspartate (NMDA) receptor/ion channel complex is fully activated in vivo, the ability of the selective glycine receptor agonist, D-serine, to modulate seizure susceptibility in the mouse has been examined. 2. D-Serine (10-200 micrograms per mouse, i.c.v.) dose-dependently increased the potency of NMDLA in inducing seizures in Swiss Webster mice by approximately 3 fold. L-Serine was without significant effect. 3. The potency of pentylenetetrazol in inducing seizures was also enhanced by D-, but not L-serine, although the magnitude of the shift (1.6 fold) was considerably less than for NMDLA. 4. Similar doses of D-serine were also able to block the anticonvulsant effect of the non-selective glycine receptor antagonist, kynurenic acid, against seizures induced by NMDLA, but were without effect on the anticonvulsant effect of the competitive NMDA receptor antagonist, 3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). 5. D-Serine completely antagonized the protective effect of the selective glycine receptor antagonist, 7-chlorokynurenic acid, against sound-induced seizures in DBA/2 mice, but was less effective in this model against the less selective antagonist, kynurenic acid. 6 The results indicate that in vivo, NMDA receptors are not maximally potentiated by endogenous glycine and suggest an important involvement of the glycine modulatory site on the NMDA receptor/ion channel complex in the pathophysiology of epilepsy.
Synthesis and Initial Evaluation of YM-08, a Blood-Brain Barrier Permeable Derivative of the Heat Shock Protein 70 (Hsp70) Inhibitor MKT-077, Which Reduces Tau Levels (2013)

The molecular chaperone, heat shock protein 70 (Hsp70), is an emerging drug target for treating neurodegenerative tauopathies. We recently found that one promising Hsp70 inhibitor, MKT-077, reduces tau levels in cellular models. However, MKT-077 does not penetrate the blood-brain barrier (BBB), limiting its use as either a clinical candidate or probe for exploring Hsp70 as a drug target in the central nervous system (CNS). We hypothesized that replacing the cationic pyridinium moiety in MKT-077 with a neutral pyridine might improve its clogP and enhance its BBB penetrance. To test this idea, we designed and synthesized YM-08, a neutral analogue of MKT-077. Like the parent compound, YM-08 bound to Hsp70 in vitro and reduced phosphorylated tau levels in cultured brain slices. Pharmacokinetic evaluation in CD1 mice showed that YM-08 crossed the BBB and maintained a brain/plasma (B/P) value of ∼0.25 for at least 18 h. Together, these studies suggest that YM-08 is a promising scaffold for the development of Hsp70 inhibitors suitable for use in the CNS.
Dendrimers as Encapsulating, Stabilizing, or Directing Agents for Inorganic Nanoparticles (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTDendrimers as Encapsulating, Stabilizing, or Directing Agents for Inorganic NanoparticlesLyudmila M. Bronstein*† and Zinaida B. Shifrina‡View Author Information† Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States‡ A.N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Science, Moscow, RussiaE-mail: [email protected]Cite this: Chem. Rev. 2011, 111, 9, 5301–5344Publication Date (Web):June 30, 2011Publication History Received7 March 2011Published online30 June 2011Published inissue 14 September 2011https://pubs.acs.org/doi/10.1021/cr2000724https://doi.org/10.1021/cr2000724review-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views10918Altmetric-Citations262LEARN 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 SUBJECTS:Dendrons,Encapsulation,Gold,Metal nanoparticles,Nanoparticles Get e-Alerts
Severe lung fibrosis requires an invasive fibroblast phenotype regulated by hyaluronan and CD44 (2011)

Tissue fibrosis is a major cause of morbidity, and idiopathic pulmonary fibrosis (IPF) is a terminal illness characterized by unremitting matrix deposition in the lung. The mechanisms that control progressive fibrosis are unknown. Myofibroblasts accumulate at sites of tissue remodeling and produce extracellular matrix components such as collagen and hyaluronan (HA) that ultimately compromise organ function. We found that targeted overexpression of HAS2 (HA synthase 2) by myofibroblasts produced an aggressive phenotype leading to severe lung fibrosis and death after bleomycin-induced injury. Fibroblasts isolated from transgenic mice overexpressing HAS2 showed a greater capacity to invade matrix. Conditional deletion of HAS2 in mesenchymal cells abrogated the invasive fibroblast phenotype, impeded myofibroblast accumulation, and inhibited the development of lung fibrosis. Both the invasive phenotype and the progressive fibrosis were inhibited in the absence of CD44. Treatment with a blocking antibody to CD44 reduced lung fibrosis in mice in vivo. Finally, fibroblasts isolated from patients with IPF exhibited an invasive phenotype that was also dependent on HAS2 and CD44. Understanding the mechanisms leading to an invasive fibroblast phenotype could lead to novel approaches to the treatment of disorders characterized by severe tissue fibrosis.
Improvement of symptoms of non‐allergic chronic rhinitis by local treatment with capsaicin (1991)

Sixteen adult patients suffering from severe chronic non-allergic rhinitis with nasal vasoconstrictor abuse for more than a year, received, under local anaesthesia, an intranasal spray of capsaicin (3.3 x 10(-3) mol), the pungent agent in hot pepper, once weekly for 5 weeks. The subjective intensity of their nasal obstruction, rhinorrhoea and sneezing frequency were evaluated throughout the study and the vascular effects of capsaicin on the nasal mucosa were recorded by anterior rhinomanometry and laser Doppler flowmetry. Calcitonin gene-related peptide (CGRP) is a vasodilator agent present in sensory nerves and may play a major role in the vascular component of neurogenic inflammation. Therefore, the nasal mucosa content of CGRP-like immunoreactivity (CGRP-LI) was determined by radioimmunoassay in biopsies obtained before and after the capsaicin treatment. Intra-nasal capsaicin application evoked a larger vascular response in patients with rhinitis than in controls (P less than 0.05). Both nasal vascular responses and subjective discomfort following capsaicin were markedly reduced after the fifth application (P less than 0.01). In parallel, a 50% reduction of the CGRP-LI content in the nasal biopsies was observed. All symptoms were significantly improved throughout a 6 month follow-up period. No significant side-effects occurred and weaning from nasal vasoconstrictor agents was possible. Both the subjective symptom score and objective measurements of vascular reactivity suggest that repeated intra-nasal capsaicin application could be beneficial for patients with chronic rhinitis, possibly by reducing hyperreactive nasal reflexes.
Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs (2010)

Human and mouse embryonic stem cells (ESCs) are derived from blastocyst-stage embryos but have very different biological properties, and molecular analyses suggest that the pluripotent state of human ESCs isolated so far corresponds to that of mouse-derived epiblast stem cells (EpiSCs). Here we rewire the identity of conventional human ESCs into a more immature state that extensively shares defining features with pluripotent mouse ESCs. This was achieved by ectopic induction of Oct4, Klf4, and Klf2 factors combined with LIF and inhibitors of glycogen synthase kinase 3beta (GSK3beta) and mitogen-activated protein kinase (ERK1/2) pathway. Forskolin, a protein kinase A pathway agonist which can induce Klf4 and Klf2 expression, transiently substitutes for the requirement for ectopic transgene expression. In contrast to conventional human ESCs, these epigenetically converted cells have growth properties, an X-chromosome activation state (XaXa), a gene expression profile, and a signaling pathway dependence that are highly similar to those of mouse ESCs. Finally, the same growth conditions allow the derivation of human induced pluripotent stem (iPS) cells with similar properties as mouse iPS cells. The generation of validated "naïve" human ESCs will allow the molecular dissection of a previously undefined pluripotent state in humans and may open up new opportunities for patient-specific, disease-relevant research.
Virulence or Niche Factors: What's in a Name? (2012)

The increasing interest in the human microbiota raises some interesting questions about the terminology we use to describe some of the structures and strategies employed by commensal and pathogenic microbes to compete in these complex biological ecosystems. For example, all microbes arriving in the alimentary tract face the task of surviving passage through the stomach, coping with bile, interacting with the immune system, competing with the established microbiota, and obtaining sufficient nutrients to gain a foothold in this hostile environment. It is not surprising then that many gastrointestinal microbes (both pathogens and commensals) use similar strategies to overcome the challenges associated with this particular biological niche. Given that many of these structures and strategies were discovered and characterized in pathogens and because they often play important roles in establishing and maintaining an infection, they have often been characterized as virulence factors. It would be misleading to describe the same strategies and structures found in harmless commensals as "virulence factors," since they represent a sine qua non for life in the gastrointestinal tract. It may be time to reconsider and refer to them as "niche factors," both in terms of providing scientific accuracy but also in light of the growing interest in using gut microbes as probiotics, where the distinction between virulence factors and niche factors is likely to be very important from a regulatory perspective.
Expansion Hyoidplasty: 1983 First‐Place Resident Research Award: Clinical Category* (1984)

An inspiratory, circumferential, passive collapse of the hypopharyngeal lumen is the mechanism of airway obstruction in some patients with "idiopathic" obstructive sleep apnea syndrome. While permanent tracheotomy has resolved the obstruction and reversed the associated cardiopulmonary sequelae, it is not without complications. The expansion hyoidplasty was conceived as an alternative. The hyoid bone is trisected just medial to each lesser cornu, then held in an expanded position by a permanent brace. The greater cornua with attached middle constrictor and hyoglossus are moved laterally, while the body of the hyoid with attached geniohyoid and genioglossus shifts the base of tongue anteriorly. The procedure is potentially reversible. Twenty dogs were studied before and after hyoid expansion, 10 for superior hypopharyngeal pressure-volume measurements and 10 for the closing-pressure study. Pressure-volume studies demonstrated a consistent expansion of the superior hypopharynx. Deglutition and laryngeal competence wee not grossly affected. Reexamination of four animals in the closing-pressure group 1 year postoperatively demonstrated stability of the hyoid expansion and no evidence of serious parahyoid tissue complications.
Large‐scale synthesis of hematoregulatory nonapeptide SK&F 107647 by fragment coupling (1999)

Linear and convergent routes for the large-scale preparation of the hematoregulatory nonapeptide (Glp-Glu-Asp)2-DAS-(Lys)2 (2, SK&F 107647) were investigated. A convergent approach ('3 + 2'-route employing Boc-and benzyl ester protecting groups) was selected for the preparation of multihundred-gram quantities of 2. Key steps were the preparation and the coupling of tripeptide hydrochloride (HCl.H)2-DAS-(Lys(Z)-OBn)2 (6, DAS-2,7-L,L-diaminosuberic acid) and tripeptide Glp-Glu(OBn)-Asp(OBn)-OH (26). Several coupling reagents were investigated in order to reduce the amount of epimerization of this fragment coupling. TDBTU [O-(3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl-1,1,3,3-tetrameth yluronium tetrafluoroborate] was identified as the condensation reagent of choice. Using this synthetic route > 97% pure final product in an overall yield of 35% calculated on di-Boc protected 2,7-L,L-diaminosuberic acid was prepared.
Effects of Pulsed Electromagnetic Fields on Interleukin-1β and Postoperative Pain: A Double-Blind, Placebo-Controlled, Pilot Study in Breast Reduction Patients (2010)

Pulsed electromagnetic field therapy significantly reduced postoperative pain and narcotic use in the immediate postoperative period. The reduction of IL-1 beta in the wound exudate supports a mechanism that may involve manipulation of the dynamics of endogenous IL-1 beta in the wound bed by means of a pulsed electromagnetic field effect on nitric oxide signaling, which could impact the speed and quality of wound repair.
Fast hypergraph partition (1989)

We present a new Ο(n2) heuristic for hypergraph min-cut bipartitioning, an important problem in circuit placement. Fastest previous methods for this problem are Ο(n2 log n). Our approach is based on the intersection graph G dual to the input hypergraph. Paths in G are used to construct partial bipartitions which can be completed optimally. The method is provably good and, in particular, obtains optimum results for “difficult” inputs, i.e., hypergraphs with smaller than expected minimum cutsize. Computational results for a wide range of inputs are also discussed.