gebhart/patrepeval huggingface dataset:
The Kaleidoscope of Microglial Phenotypes (2018)

Gene expression analyses of microglia, the tissue-resident macrophages of the central nervous system (CNS), led to the identification of homeostatic as well as neurological disease-specific gene signatures of microglial phenotypes. Upon alterations in the neural microenvironment, either caused by local insults from within the CNS (during neurodegenerative diseases) or by macroenvironmental incidents, such as social stress, microglia can switch phenotypes-generally referred to as "microglial activation." The interplay between the microenvironment and its influence on microglial phenotypes, regulated by (epi)genetic mechanisms, can be imagined as the different colorful crystal formations (microglial phenotypes) that change upon rotation (microenvironmental changes) of a kaleidoscope. In this review, we will discuss microglial phenotypes in relation to neurodevelopment, homeostasis, <i>in vitro</i> conditions, aging, and neurodegenerative diseases based on transcriptome studies. By overlaying these disease-specific microglial signatures, recent publications have identified a specific set of genes that is differentially expressed in all investigated diseases, called a microglial core gene signature with multiple diseases. We will conclude this review with a discussion about the complexity of this microglial core gene signature associated with multiple diseases.
pH-Responsive Nanoparticles for Drug Delivery (2010)

First-generation nanoparticles (NPs) have been clinically translated as pharmaceutical drug delivery carriers for their ability to improve on drug tolerability, circulation half-life, and efficacy. Toward the development of the next-generation NPs, researchers have designed novel multifunctional platforms for sustained release, molecular targeting, and environmental responsiveness. This review focuses on environmentally responsive mechanisms used in NP designs, and highlights the use of pH-responsive NPs in drug delivery. Different organs, tissues, and subcellular compartments, as well as their pathophysiological states, can be characterized by their pH levels and gradients. When exposed to these pH stimuli, pH-responsive NPs respond with physicochemical changes to their material structure and surface characteristics. These include swelling, dissociating or surface charge switching, in a manner that favors drug release at the target site over surrounding tissues. The novel developments described here may revise the classical outlook that NPs are passive delivery vehicles, in favor of responsive, sensing vehicles that use environmental cues to achieve maximal drug potency.
A review of sex determination and searches for sex-specific markers in sturgeon (2010)

The availability of monosex populations of caviar-producing female sturgeon would considerably enhance the economic viability of domestic caviar production systems. However, it is not possible to distinguish males from females by morphological characters at larval, juvenile and even adult stages. The mechanism of sex determination in sturgeons is poorly understood, and to date no sex-specific markers in sturgeon have been reported. This review concentrates on the methodologies used to elucidate the mode of sex determination in sturgeon species and provides information on the molecular tools used to determine genetic sex markers.
Secure Multicast with Source Authentication for the Internet of Things (2014)

Sakernas Internet är ett snabbt växande område av avancerad teknik och forskning. Dess säkerhet är avgörande för tillförlitligheten och tryggheten av framtida dagliga kommunikationer. DTLS protokollet är ett standardprotokoll för att garantera säkerheten för unicast kommunikation. En DTLS rekord lager tillägg för multicast i begränsade miljöer håller på att utformas för att garantera säkerheten för multicast. Däremot nuvarande förslag av DTLS baserad multicast ger inte en sådan viktig egenskap som källäkthet för de överförda uppgifterna. Dessutom är handslag lagret utformat för att bara etablera parvisa nycklar, och därmed finns det inget sätt att distribuera och hantera gruppnycklar heller. De två ovan nämnda nackdelar blir de primära målen för designen för examensarbetet. Detta examensarbete genomförs i samarbete med Philips. I examensarbetet, formulerar vi kraven för att säkerställa multicast i en begränsad miljö baserad på företagets utomhusbelysning scenariot med en centraliserad förtroende modell. Vi utvärderar olika autentiseringssystem av källor och 4 nyckelhanteringsprotokoll med avseende på de formulerade kraven. Vi väljer två autentiseringssystem och använder dem på vårt scenario. Som resultat konstruerar vi en förlängning av DTLS baserad multicast med stöd av ECDSA signaturen för källautentisering och utvecklar en prototyp implementering. Förutom det, vi bestämmer kryptografiska primitiver för TESLA systemet och anpassar det system som ska användas för den periodiska kommunikationsmodellen. Till slut, konstruerar vi en lätt och flexibel lösning för gruppnyckelhantering för att dela ut gruppnycklar och allmänna nycklar från den pålitliga myndigheten.
Whole Blood Gene Expression Testing for Coronary Artery Disease in Nondiabetic Patients: Major Adverse Cardiovascular Events and Interventions in the PREDICT Trial (2012)

The majority of first-time angiography patients are without obstructive coronary artery disease (CAD). A blood gene expression score (GES) for obstructive CAD likelihood was validated in the PREDICT study, but its relation to major adverse cardiovascular events (MACE) and revascularization was not assessed. Patients (N = 1,160) were followed up for MACE and revascularization 1 year post-index angiography and GES, with 1,116 completing follow-up. The 30-day event rate was 23% and a further 2.2% at 12 months. The GES was associated with MACE/revascularizations (p < 0.001) and added to clinical risk scores. Patients with GES >15 trended towards increased >30 days MACE/revascularization likelihood (odds ratio = 2.59, 95% confidence interval = 0.89-9.14, p = 0.082). MACE incidence overall was 1.5% (17 of 1,116) and 3 of 17 patients had GES ≤ 15. For the total low GES group (N = 396), negative predictive value was 90% for MACE/revascularization and >99% for MACE alone, identifying a group of patients without obstructive CAD and highly unlikely to suffer MACE within 12 months.
Different cis-acting DNA elements control expression of the human apolipoprotein AI gene in different cell types. (1988)

In mammals, the gene coding for apolipoprotein AI (apoAI), a protein of the plasma lipid transport system, is expressed only in the liver and the intestine. A series of plasmids containing various lengths of sequences flanking the 5' end of the human apoAI gene were constructed and assayed for transient expression after introduction into cultured human hepatoma (HepG2), colon carcinoma (Caco-2), and epithelial (HeLa) cells. The results showed that while most of these constructs are expressed in HepG2 and Caco-2 cells, none of them is expressed in HeLa cells. In addition, the results indicated that a DNA segment located between nucleotides -256 and -41 upstream from the transcription start site of this gene is necessary and sufficient for maximal levels of expression in HepG2 but not in Caco-2 cells, while a DNA segment located between nucleotides -2052 and -192 is required for maximal levels of expression in Caco-2 cells. Moreover, it was shown that the -256 to -41 DNA segment functions as a hepatoma cell-specific transcriptional enhancer with both homologous and heterologous promoters. These results indicate that different cis- and possibly trans-acting factors are involved in the establishment and subsequent regulation of expression of the apoAI gene in the mammalian liver and intestine.
The selective ablation of interleukin 2-producing cells isolated from transgenic mice. (1993)

To better understand the requirement for interleukin 2 (IL-2) in specific immune responses, we have established the use of cell ablation to selectively eliminate T cells that produce IL-2. To accomplish this we have generated transgenic mice that express the herpes simplex virus 1-thymidine kinase (HSV-TK) gene under the transcriptional control of the murine IL-2 promoter that renders IL-2-producing cells sensitive to the cytotoxic effects of the antiviral drug ganciclovir (GANC). HSV-TK activity was specifically expressed in activated T cells from transgenic mice. When CD4 T cells from transgenic mice were stimulated with the superantigen staphylococcal enterotoxin A (SEA) in the presence of GANC, proliferation and IL-2 production were almost completely inhibited and the activated CD4+V beta 3+ T cell population, eliminated. Proliferation was not restored by adding IL-2, showing that most proliferating cells are not bystander cells. In contrast, the proliferative response to concanavalin A (Con A) was only partially inhibited by treatment of CD4 T cells with GANC, although the efficiency of eliminating IL-2-producing cells was shown to be comparable with that achieved using SEA. This suggests that a portion of the proliferative response to Con A occurs via an alternative pathway not requiring IL-2 synthesis and release.
Gastrin and gastrin receptor activation: an early event in the adenoma-carcinoma sequence (2000)

This study is the first to show widespread expression of both gastrin and its receptor in colorectal polyps. Their activation occurs early in the adenoma-carcinoma sequence. Gastrin may promote progression through the adenoma-carcinoma sequence.
Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue (2013)

Limitations on the number of unique protein and DNA molecules that can be characterized microscopically in a single tissue specimen impede advances in understanding the biological basis of health and disease. Here we present a multiplexed fluorescence microscopy method (MxIF) for quantitative, single-cell, and subcellular characterization of multiple analytes in formalin-fixed paraffin-embedded tissue. Chemical inactivation of fluorescent dyes after each image acquisition round allows reuse of common dyes in iterative staining and imaging cycles. The mild inactivation chemistry is compatible with total and phosphoprotein detection, as well as DNA FISH. Accurate computational registration of sequential images is achieved by aligning nuclear counterstain-derived fiducial points. Individual cells, plasma membrane, cytoplasm, nucleus, tumor, and stromal regions are segmented to achieve cellular and subcellular quantification of multiplexed targets. In a comparison of pathologist scoring of diaminobenzidine staining of serial sections and automated MxIF scoring of a single section, human epidermal growth factor receptor 2, estrogen receptor, p53, and androgen receptor staining by diaminobenzidine and MxIF methods yielded similar results. Single-cell staining patterns of 61 protein antigens by MxIF in 747 colorectal cancer subjects reveals extensive tumor heterogeneity, and cluster analysis of divergent signaling through ERK1/2, S6 kinase 1, and 4E binding protein 1 provides insights into the spatial organization of mechanistic target of rapamycin and MAPK signal transduction. Our results suggest MxIF should be broadly applicable to problems in the fields of basic biological research, drug discovery and development, and clinical diagnostics.
Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals (2015)

Being a transient carrier of genetic information, mRNA could be a versatile, flexible, and safe means for protein therapies. While recent findings highlight the enormous therapeutic potential of mRNA, evidence that mRNA-based protein therapies are feasible beyond small animals such as mice is still lacking. Previous studies imply that mRNA therapeutics require chemical nucleoside modifications to obtain sufficient protein expression and avoid activation of the innate immune system. Here we show that chemically unmodified mRNA can achieve those goals as well by applying sequence-engineered molecules. Using erythropoietin (EPO) driven production of red blood cells as the biological model, engineered Epo mRNA elicited meaningful physiological responses from mice to nonhuman primates. Even in pigs of about 20 kg in weight, a single adequate dose of engineered mRNA encapsulated in lipid nanoparticles (LNPs) induced high systemic Epo levels and strong physiological effects. Our results demonstrate that sequence-engineered mRNA has the potential to revolutionize human protein therapies.
Increased in vitro and in vivo gene transfer by adenovirus vectors containing chimeric fiber proteins (1997)

Alteration of the natural tropism of adenovirus (Ad) will permit gene transfer into specific cell types and thereby greatly broaden the scope of target diseases that can be treated by using Ad. We have constructed two Ad vectors which contain modifications to the Ad fiber coat protein that redirect virus binding to either alpha(v) integrin [AdZ.F(RGD)] or heparan sulfate [AdZ.F(pK7)] cellular receptors. These vectors were constructed by a novel method involving E4 rescue of an E4-deficient Ad with a transfer vector containing both the E4 region and the modified fiber gene. AdZ.F(RGD) increased gene delivery to endothelial and smooth muscle cells expressing alpha(v) integrins. Likewise, AdZ.F(pK7) increased transduction 5- to 500-fold in multiple cell types lacking high levels of Ad fiber receptor, including macrophage, endothelial, smooth muscle, fibroblast, and T cells. In addition, AdZ.F(pK7) significantly increased gene transfer in vivo to vascular smooth muscle cells of the porcine iliac artery following balloon angioplasty. These vectors may therefore be useful in gene therapy for vascular restenosis or for targeting endothelial cells in tumors. Although binding to the fiber receptor still occurs with these vectors, they demonstrate the feasibility of tissue-specific receptor targeting in cells which express low levels of Ad fiber receptor.
Effects of activin A on the activities of the mouse peritoneal macrophages. (2005)

Activin A is a kind of pre-inflammatory factor that belongs to the transforming growth factor-beta (TGF-beta) superfamily. To investigate the effect and mechanism of activin A on the activities of mouse macrophages, the secretion of NO in the supernatant of cultured mouse peritoneal macrophages was examined by NO assay kit, and the expression of iNOS, ActRIIA and ARIP2 mRNA in mouse peritoneal macrophages was analyzed by RT-PCR. The results showed that activin A stimulated the secretion of NO and the expression of iNOS mRNA in non-activated mouse macrophages in a time- and dose-dependent manner. In contrast, activin A in the same concentration inhibited the secretion of NO in LPS-activated mouse macrophages in a dose-dependent manner. ActRIIA was highly expressed on macrophages, and activin A upregulated the ActRIIA mRNA expression in macrophages. Anti-ActRIIA antibody can block the secretion of NO from the macrophages stimulated by activin A. Furthermore, RT-PCR analysis revealed that activin A enhanced the ARIP2 mRNA expression in macrophages. These results indicated that Activin A may be a weak activator compared with LPS to mouse macrophages, and activin A may modulate the secretion of NO through ActRIIA-ARIP2 signal pathway in mouse macrophages.
DSH-MRAM: Differential Spin Hall MRAM for On-Chip Memories (2013)

A new device structure for spin-transfer torque-based magnetic random access memory (STT-MRAM) is proposed for on-chip memory applications. Our device structure exploits spin Hall effect to create a differential memory cell that exhibits fast and energy-efficient write operation. In addition, because of inherently differential device structure, fast and reliable read operation can be performed. Our simulation study shows 10× improvement in write energy over the standard 1T1R in-plane STT-MRAM memory cell, and 1.6× faster read operation compared with single-ended sensing (as in standard 1T1R STT-MRAMs). The bit-cell characteristics are promising for high performance on-chip memory applications.
Vancomycin-ResistantStaphylococcus aureus,Michigan, USA, 2007 (2009)

Vancomycin-resistant Staphylococcus aureus (VRSA) infections, which are always methicillin-resistant, are a rare but serious public health concern. We examined 2 cases in Michigan in 2007. Both patients had underlying illnesses. Isolates were vanA-positive. VRSA was neither transmitted to or from another known VRSA patient nor transmitted from patients to identified contacts.
Dielectric behavior of carbon black filled polymer composites (1986)

Abstract This paper reports results on the dielectric properties of carbon black filled crosslinked polyethylene composites. These systems are shown to follow percolative type models. The dielectric constant increases slowly, with carbon black concentration, up to roughly the percolation concentration and then increases rapidly over the whole concentration ranges studied. The dissipation factor‐concentration curves are bell‐shaped with maximum values at approximately the percolation concentration. The dielectric properties of these systems are discussed in terms of interfacial Maxwell‐Wagner polarization effects.
Recombinant Squalene Synthase. A Mechanism for the Rearrangement of Presqualene Diphosphate to Squalene (2002)

Squalene synthase (SQase) catalyzes the condensation of two molecules of farnesyl diphosphate (FPP) to form presqualene diphosphate (PSPP) and the subsequent rearrangement and NADPH-dependent reduction of PSPP to squalene (SQ). These reactions are the first committed steps in cholesterol biosynthesis. When recombinant SQase was incubated with FPP in the presence of dihydroNADPH (NADPH3, an unreactive analogue lacking the 5,6-double bond in the nicotinamide ring), three products were formed: dehydrosqualene (DSQ), a C30 analogue of phytoene; 10(S)-hydroxysqualene (HSQ), a hydroxy analogue of squalene; and rillingol (ROH), a cyclopropylcarbinyl alcohol formed by addition of water to the tertiary cyclopropylcarbinyl cation previously proposed as an intermediate in the rearrangement of PSPP to SQ (Poulter, C. D. Acc. Chem. Res. 1990, 23, 70-77). The structure and absolute stereochemistry of the tertiary cyclopropylcarbinyl alcohol were established by synthesis using two independent routes. Isolation of ROH from the enzyme-catalyzed reaction provides strong evidence for a cyclopropylcarbinyl-cyclopropylcarbinyl rearrangement in the biosynthesis of squalene. By comparing the SQase-catalyzed solvolysis of PSPP in the absence of NADPH3 to the reaction in the presence of NADPH3, it is apparent that the binding of the cofactor analogue substantially enhances the ability of SQase to control the regio- and stereochemistry of the rearrangements of PSPP.
New Family of Weakly Coordinating Anions (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNew Family of Weakly Coordinating AnionsRobert E. LaPointe, Gordon R. Roof, Khalil A. Abboud, and Jerzy KlosinView Author Information The Dow Chemical Company, Catalysis Laboratory Midland, Michigan 48674 Department of Chemistry, University of Florida Gainesville, Florida 32611 Cite this: J. Am. Chem. Soc. 2000, 122, 39, 9560–9561Publication Date (Web):September 16, 2000Publication History Received21 July 2000Published online16 September 2000Published inissue 1 October 2000https://pubs.acs.org/doi/10.1021/ja002664ehttps://doi.org/10.1021/ja002664erapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views2235Altmetric-Citations120LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (3)»Supporting Information Supporting Information SUBJECTS:Anions,Cations,Imidazoles,Olefin polymerization,Salts Get e-Alerts
Optic Nerve Restoration (2007)

Neural regeneration and repair in the central nervous system are currently hot topics in neuroscience. For many years there has been a hope that neurodegenerative diseases which are resistant to current therapies may be treated by the selective replacement of cells. Yet it is only recently that we have started to acquire the knowledge, tools, and techniques that may translate such optimism into new therapies. In this article, we will consider the potential to restore function to the damaged optic nerve. We will consider the technical issues involved and suggest a strategy for research progress.
Competitive binding of Pu and Am with bone mineral and novel chelating agents (2003)

Effective direct removal of actinides such as Pu and Am from bone in vivo has not been accomplished to date, even with the strong chelating agents CaNa3DTPA or ZnNa3DTPA. This study, using an established in vitro system, compared removal of Pu and Am bound to bone mineral by ZnNa3DTPA and 10 chelating agents designed specifically to sequester actinides, including Pu and Am. Ligands tested were tetra, hexa, and octadentate, with linear or branched backbones containing sulfocatechol [CAM(S)], hydroxycatechol [CAM(C)], hydroxipyridinone (1,2-HOPO, Me-3,2-HOPO), or hydroxamate functional groups. The wide range of Pu and Am removal exhibited by the test ligands generally agreed with their metal coordination and chemical properties. The most effective agents for Pu (100 microM concentration, 24-48 h contact) are all octadentate as follows: 3,4,3-LICAM(S) (54% unbound); 3,4,3-LICAM(C) (6.2%); 3,4,3-LI(1,2-HOPO) (3.8%); H(2,2)-(Me-3,2-HOPO) (2.2%) and DFO-(1,2-HOPO) (1.8%). The other ligands removed less than 1% of the bound Pu; and ZnNa3DTPA removed only 0.086%. The most effective ligands for Am removal (100 microM, 24-48 h contact) are as follows: octadentate H(2,2)-(Me-3,2-HOPO) (21% unbound); 3,4,3-LI(1,2-HOPO) (14.5%) and 3,4,3-LICAM(C) (5.9%); hexadentate TREN-(Me-3,2-HOPO) and TREN-(1,2-HOPO) (9.6%); and tetradentate 5-LIO(Me-3,2-HOPO) (5.2%). Am removal by ZnNa3DTPA was about 1.4%. Among the ligands presently considered for possible human use, only 3,4,3-LI(1,2-HOPO) removed potentially useful amounts of both Pu and Am from bone mineral.
Transfer of Biologically Derived Nanometer-Scale Patterns to Smooth Substrates (1992)

Atomic force microscopy has been used to measure the surface profile of a periodic array of 10-nanometer (nm)-diameter holes fabricated by fast-atom beam milling of a smooth graphite surface in which a 3.5-nm-thick titanium oxide screen was used as a mask. The nanostructured titanium oxide mask was itself derived from a protein crystal template. Pattern transfer from the biological crystal to the metal oxide film and finally to the graphite substrate was accomplished entirely by parallel processing.