gebhart/patrepeval huggingface dataset:
DNA Methylation Modulates Nociceptive Sensitization after Incision (2015)

DNA methylation is a key epigenetic mechanism controlling DNA accessibility and gene expression. Blockade of DNA methylation can significantly affect pain behaviors implicated in neuropathic and inflammatory pain. However, the role of DNA methylation with regard to postoperative pain has not yet been explored. In this study we sought to investigate the role of DNA methylation in modulating incisional pain and identify possible targets under DNA methylation and contributing to incisional pain. DNA methyltranferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine significantly reduced incision-induced mechanical allodynia and thermal sensitivity. Aza-2'-deoxycytidine also reduced hindpaw swelling after incision, suggesting an anti-inflammatory effect. Global DNA methylation and DNMT3b expression were increased in skin after incision, but none of DNMT1, DNMT3a or DNMT3b was altered in spinal cord or DRG. The expression of proopiomelanocortin Pomc encoding β-endorphin and Oprm1 encoding the mu-opioid receptor were upregulated peripherally after incision; moreover, Oprm1 expression was further increased under DNMT inhibitor treatment. Finally, local peripheral injection of the opioid receptor antagonist naloxone significantly exacerbated incision-induced mechanical hypersensitivity. These results suggest that DNA methylation is functionally relevant to incisional nociceptive sensitization, and that mu-opioid receptor signaling might be one methylation regulated pathway controlling sensitization after incision.
Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor mediates cellular uptake of pro-urokinase. (1993)

The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) is a large cell surface receptor consisting of a 515-kDa heavy chain and an 85-kDa light chain proteolytically derived from a 600-kDa precursor. Previous work has shown that LRP is responsible for mediating the internalization of urinary-type plasminogen activator (uPA) complexed to plasminogen activator inhibitor type I (PAI-1) (Nykjaer et al., 1992; Herz et al., 1992). The current study indicates that pro-urokinase (pro-uPA) and two chain urokinase (tc-uPA) bind directly to purified LRP, and that LRP mediates their internalization and degradation in Hep G2 cells. In vitro binding assays demonstrated that pro-uPA and tc-uPA bind to purified LRP with affinities (Kd = 45 and 60 nM, respectively) that are approximately 15 to 20-fold weaker than the affinity of uPA.PAI-1 complex for LRP (Kd = 3 nM). Competitive binding experiments revealed that pro-uPA and tc-uPA completely inhibit binding of uPA.PAI-1 complexes to purified LRP. The binding of 125I-pro-uPA to LRP is blocked by the 39-kDa receptor-associated protein, but not by an amino-terminal fragment of uPA, which is known to block binding of uPA to the urokinase receptor. 125I-Pro-uPA can be internalized and degraded by Hep G2 cells independent of PAI-1. Both the internalization and degradation are completely blocked by receptor-associated protein or affinity-purified LRP antibodies, indicating that LRP is mediating this process. These processes are also blocked by the amino-terminal fragment, which suggests that the favored pathway for uPA metabolism is initial binding to the urokinase receptor, followed by ligand transfer to LRP, then internalization leading to degradation.
Skeletal Muscle Fibrosis in the mdx/utrn+/- Mouse Validates Its Suitability as a Murine Model of Duchenne Muscular Dystrophy (2015)

Various therapeutic approaches have been studied for the treatment of Duchenne muscular dystrophy (DMD), but none of these approaches have led to significant long-term effects in patients. One reason for this observed inefficacy may be the use of inappropriate animal models for the testing of therapeutic agents. The mdx mouse is the most widely used murine model of DMD, yet it does not model the fibrotic progression observed in patients. Other murine models of DMD are available that lack one or both alleles of utrophin, a functional analog of dystrophin. The aim of this study was to compare fibrosis and myofiber damage in the mdx, mdx/utrn+/- and double knockout (dko) mouse models. We used Masson's trichrome stain and percentage of centrally-nucleated myofibers as indicators of fibrosis and myofiber regeneration, respectively, to assess disease progression in diaphragm and gastrocnemius muscles harvested from young and aged wild-type, mdx, mdx/utrn+/- and dko mice. Our results indicated that eight week-old gastrocnemius muscles of both mdx/utrn+/- and dko hind limb developed fibrosis whereas age-matched mdx gastrocnemius muscle did not (p = 0.002). The amount of collagen found in the mdx/utrn+/- diaphragm was significantly higher than that found in the corresponding diaphragm muscles of wild-type animals, but not of mdx animals (p = 0.0003). Aged mdx/utrn+/- mice developed fibrosis in both diaphragm and gastrocnemius muscles compared to wild-type controls (p = 0.003). Mdx diaphragm was fibrotic in aged mice as well (p = 0.0235), whereas the gastrocnemius muscle in these animals was not fibrotic. We did not measure a significant difference in collagen staining between wild-type and mdx gastrocnemius muscles. The results of this study support previous reports that the moderately-affected mdx/utrn+/- mouse is a better model of DMD, and we show here that this difference is apparent by 2 months of age.
Complementary Roles for Fibrin(ogen), Thrombospondin and vWF in Mediating Shear-dependent Aggregation of Platelets Stimulated at Threshold Thrombin Concentrations (2001)

We have evaluated the relative contribution of the adhesive ligands, von Willebrand factor (vWF), fibrinogen (Fg) and thrombospondin (TSP), all surface-expressed on washed platelets (WP) activated with a threshold thrombin concentration (approximately 0.04 U/ml), to platelet microaggregation (PA) at shear rates (G) from 300-2000 s(-1). In suspensions of thrombin-activated WP sheared immediately (tau0), all three ligands were required for optimal aggregation at all G, as shown by a 50-70% inhibition of capture efficiencies of PA (measured from initial rates of PA), by antibodies (Abs) directed against each protein. This aggregation involved both GPIb and GPIIbIIIa, as indicated by approximately 80% and 100% inhibition by Ab 6D1 and Ab 10E5, respectively. For WP preexposed to thrombin for 10 min to ensure maximal surface expression of secreted ligands and activated GPIIbIIIa (tau0), vWF was predominantly required at all G (63-75% inhibition by anti-vWF Ab), together with TSP (35-50% inhibition by anti-TSP Ab). Under these conditions, Fg was extensively converted to fibrin, so that fibrin, rather than Fg, could participate in microaggregation, with GPIb less required than GPIIbIIIa as indicated by a 30-60% inhibition by Ab 6D1 as compared to 100% inhibition by Ab 10E5. Our results show that interactions between multiple ligands and receptors favour microaggregation depending on shear and thrombin activation conditions.
Estimation of Respiration Rate from Three-Dimensional Acceleration Data Based on Body Sensor Network (2011)

Respiratory monitoring is widely used in clinical and healthcare practice to detect abnormal cardiopulmonary function during ordinary and routine activities. There are several approaches to estimate respiratory rate, including accelerometer(s) worn on the torso that are capable of sensing the inclination changes due to breathing. In this article, we present an adaptive band-pass filtering method combined with principal component analysis to derive the respiratory rate from three-dimensional acceleration data, using a body sensor network platform previously developed by us. In situ experiments with 12 subjects indicated that our method was capable of offering dynamic respiration rate estimation during various body activities such as sitting, walking, running, and sleeping. The experimental studies also suggested that our frequency spectrum-based method was more robust, resilient to motion artifact, and therefore outperformed those algorithms primarily based on spatial acceleration information.
SEMICONDUCTOR NANOWIRES AND NANOTUBES (2004)

▪ Abstract Semiconductor nanowires and nanotubes exhibit novel electronic and optical properties owing to their unique structural one-dimensionality and possible quantum confinement effects in two dimensions. With a broad selection of compositions and band structures, these one-dimensional semiconductor nanostructures are considered to be the critical components in a wide range of potential nanoscale device applications. To fully exploit these one-dimensional nanostructures, current research has focused on rational synthetic control of one-dimensional nanoscale building blocks, novel properties characterization and device fabrication based on nanowire building blocks, and integration of nanowire elements into complex functional architectures. Significant progress has been made in a few short years. This review highlights the recent advances in the field, using work from this laboratory for illustration. The understanding of general nanocrystal growth mechanisms serves as the foundation for the rational synthesis of semiconductor heterostructures in one dimension. Availability of these high-quality semiconductor nanostructures allows systematic structural-property correlation investigations, particularly of a size- and dimensionality-controlled nature. Novel properties including nanowire microcavity lasing, phonon transport, interfacial stability and chemical sensing are surveyed.
Steric effects in some cycloaddition reactions (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteric effects in some cycloaddition reactionsC. K. Bradsher, T. G. Wallis, I. J. Westerman, and N. A. PorterCite this: J. Am. Chem. Soc. 1977, 99, 8, 2588–2591Publication Date (Print):April 1, 1977Publication History Published online1 May 2002Published inissue 1 April 1977https://pubs.acs.org/doi/10.1021/ja00450a030https://doi.org/10.1021/ja00450a030research-articleACS PublicationsRequest reuse permissionsArticle Views119Altmetric-Citations12LEARN 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
Mechanical loading, cartilage degradation, and arthritis (2010)

Joint tissues are exquisitely sensitive to their mechanical environment, and mechanical loading may be the most important external factor regulating the development and long-term maintenance of joint tissues. Moderate mechanical loading maintains the integrity of articular cartilage; however, both disuse and overuse can result in cartilage degradation. The irreversible destruction of cartilage is the hallmark of osteoarthritis and rheumatoid arthritis. In these instances of cartilage breakdown, inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor-alpha stimulate the production of matrix metalloproteinases (MMPs) and aggrecanases (ADAMTSs), enzymes that can degrade components of the cartilage extracellular matrix. In order to prevent cartilage destruction, tremendous effort has been expended to design inhibitors of MMP/ADAMTS activity and/or synthesis. To date, however, no effective clinical inhibitors exist. Accumulating evidence suggests that physiologic joint loading helps maintain cartilage integrity; however, the mechanisms by which these mechanical stimuli regulate joint homeostasis are still being elucidated. Identifying mechanosensitive chondroprotective pathways may reveal novel targets or therapeutic strategies in preventing cartilage destruction in joint disease.
ADSORPTION AND REACTION AT ELECTROCHEMICAL INTERFACES AS PROBED BY SURFACE-ENHANCED RAMAN SPECTROSCOPY (2004)

Over the past three decades, surface-enhanced Raman spectroscopy (SERS) has gone through a tortuous pathway to develop into a powerful surface diagnostic technique for in situ investigation of surface adsorption and reactions on electrodes. This review presents the recent progress achieved mainly in our laboratory on the improvement of detection sensitivities as well as spectral, temporal, and spatial resolutions. Various surface roughening procedures for electrodes of different metals coupled with maximum use of a high-sensitivity confocal Raman microscope enable us to obtain good-quality SER spectra on the electrode surfaces made from net Pt, Ni, Co, Fe, Pd, Rh, Ru, and their alloys that were traditionally considered to be non-SERS active. A novel technique called potential-averaged SERS (PASERS) has been developed for the quantitative study of electrochemical sorption. Applications are exemplified on extensively studied areas such as coadsorption, electrocatalysis, corrosion, and fuel cells, and several advantages of in situ electrochemical SERS are demonstrated. Finally, further developments in this field are briefly discussed with emphasis on the emerging methodology.
A tissue-specific nuclear factor binds to multiple sites in the human insulin-gene enhancer (1989)

Sequence-specific binding of proteins from an insulin-secreting cell line (RINm-5F) to the human insulin-gene 5' region were examined by gel-retardation and methylation-interference analysis. Specific binding of a nuclear factor to sites between nucleotides -210 to -217 and -77 to -84 was detected. The same binding activity was shown at an upstream site (-313 to -320) with low affinity. Studies using mutated binding-site probes delineated a sequence 5'-C(T/C)CTAATG-3' for high-affinity interactions. This binding activity was also present in another insulin-producing cell line (HIT.T15), but not in extracts from cell lines that did not express the insulin gene (HeLa, HL60). Cross-species comparisons show that this sequence element is highly conserved and may thus play an important role in the cell-specific regulation of insulin-gene transcription.
Protection scheme for secure MPEG-2 streaming (2005)

We propose a protection scheme for MPEG-2 streaming media. To protect MPEG-2 media more effectively and securely, an encryption process should be considered on encoding phase of uncompressed stream and also a streaming server should be designed to support the protection scheme. However this way cannot support existing streaming systems and requires pre-processing such as demultiplexing and decoding. Our approach is to design a protection scheme independent to the streaming server. So, we propose an encryption method which can be applied to compressed MPEG-2 transport stream (TS). Proposed scheme can protect attacks over networks since streaming server streams pre-encrypted content and enables the client to decrypt the streamed data and playback in real time. Even though streamed content is stored in local system users who do not have available rights cannot use the encrypted content.
Current Knowledge of Type-Specific M Antigens of Group A Streptococci (1962)

Summary It is established that M protein is the cellular component of group A streptococci responsible for the production of type-specific antibodies, which are the basis of type-specific immunity in man. Strains freshly isolated from acute infections, so far as is known at present, always contain M antigen. Although many cultures containing M protein are avirulent for mice, all highly mouse-virulent group A strains contain M antigen. The amount of M protein in some cultures can be increased by serial mouse passage, and the virulence of such strains is usually increased at the same time. It is possible that the hyaluronic acid capsule in addition to M protein may be a factor in virulence, but its importance has not been clearly defined. M protein probably enhances virulence by impeding phagocytosis, and the capsule may contribute to virulence by a mechanism not yet fully elucidated. So far no completely purified preparations of M protein have been obtained, but progress in this direction is being made. Once this is achieved, it may be possible to define the properties of this important antigen more accurately.
Acute hypertension activates mitogen-activated protein kinases in arterial wall. (1996)

Mitogen-activated protein (MAP) kinases are rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in transmitting transmembrane signals required for cell growth and differentiation. Herein we provide evidence that two distinct classes of MAP kinases, the extracellular signal-regulated kinases (ERK) and the c-Jun NH2-terminal kinases (JNK), are transiently activated in rat arteries (aorta, carotid and femoral arteries) in response to an acute elevation in blood pressure induced by either restraint or administration of hypertensive agents (i.e., phenylephrine and angiotensin II). Kinase activation is followed by an increase in c-fos and c-jun gene expression and enhanced activating protein 1 (AP-1) DNA-binding activity. Activation of ERK and JNK could contribute to smooth muscle cell hypertrophy/hyperplasia during arterial remodeling due to frequent and/or persistent elevations in blood pressure.
Dynamic Study of Blood–Brain Barrier Closure after its Disruption using Ultrasound: A Quantitative Analysis (2012)

Delivery of therapeutic or diagnostic agents to the brain is majorly hindered by the blood-brain barrier (BBB). Recently, many studies have demonstrated local and transient disruption of the BBB using low power ultrasound sonication combined with intravascular microbubbles. However, BBB opening and closure mechanisms are poorly understood, especially the maximum gap that may be safely generated between endothelial cells and the duration of opening of the BBB. Here, we studied BBB opening and closure under magnetic resonance (MR) guidance in a rat model. First, MR contrast agents (CA) of different hydrodynamic diameters (1 to 65 nm) were employed to estimate the largest molecular size permissible across the cerebral tissues. Second, to estimate the duration of the BBB opening, the CA were injected at various times post-BBB disruption (12 minutes to 24 hours). A T(1) mapping strategy was developed to assess CA concentration at the ultrasound (US) focal point. Based on our experimental data and BBB closure modeling, a calibration curve was obtained to compute the half closure time as a function of CA hydrodynamic diameter. These findings and the model provide an invaluable basis for optimal design and delivery of nanoparticles to the brain.
Minimal Model-Based Insulin Sensitivity Has Greater Heritability and a Different Genetic Basis Than Homeostasis Model Assessment or Fasting Insulin (2003)

Insulin resistance is an important risk factor for development of type 2 diabetes as well as other chronic conditions, including hypertension, cardiovascular disease, and colon cancer. To find genes for insulin resistance it is necessary to assess insulin action in large populations. We have previously measured insulin action in a large cohort of subjects (Insulin Resistance and Atherosclerosis Study [IRAS] Family Study) using the minimal model approach. In this study, we compare sensitivity from the minimal model (insulin sensitivity index [S(I)]) with the measure of insulin resistance emanating from the homeostasis model assessment (HOMA) approach. The former measure emerges from the glycemic response to endogenous and exogenous insulin; the latter is based solely on fasting measures of glucose and insulin. A total of 112 pedigrees were represented, including 1,362 individuals with full phenotypic assessment. Heritability of S(I) was significantly greater than that for HOMA (0.310 vs. 0.163) and for fasting insulin (0.171), adjusted for age, sex, ethnicity, and BMI. In addition, correlation between S(I) and either HOMA or fasting insulin was only approximately 50% accounted for by genetic factors, with the remainder accounted for by environment. Thus S(I), a direct measure of insulin sensitivity, is determined more by genetic factors rather than measures such as HOMA, which reflect fasting insulin.
1,25-dihydroxyvitamin D3 dissolved in lipiodol produces a sustained antiproliferative effect in the human hepatoblastoma cell line HepG2. (2000)

The steroid hormone 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has potential to be used as an anti-tumor agent, but its clinical application has been restricted by the strong systemic calcemic activity. Regional administration of the drug dissolved in lipiodol, might be a way of selectively delivering high concentrations of the drug to lipiodol avid tumor cells without causing systemic side effects. In acute (1 day treatment) and chronic (5 days treatment) experiments, efficacy of the drug dissolved in ethanol (control) or lipiodol and subsequently diluted in the culture medium was tested in vitro against the hepatoblastoma cell line HepG2. Using [3H]thymidine incorporation and cell count, antiproliferative effects of 1,25-(OH)2D3 dissolved in the two different solvents was compared. Microscopic examination of cells exposed to the lipiodol containing media revealed intra-cellular presence of the oil in abundance. Chronic treatment of cells with either formulation of 1,25-(OH)2D3 resulted in profound inhibition of cell proliferation. However, exposure of cells to 1,25-(OH)2D3 in lipiodol was followed by significantly greater and lasting inhibition of cell proliferation in both acute and chronic studies. These results indicate that, 1,25-(OH)2D3 dissolved in lipiodol probably acts as a sustained release drug depot formulation, in which case it could have some potential for the regional treatment of liver tumors.
Genetic diversity of the endemic gourmet mushroom Thelephora ganbajun from south-western China (2008)

The ectomycorrhizal fungus Thelephora ganbajun is an endemic gourmet mushroom in Yunnan province, south-western China. However, despite its widespread consumer appeal, nutritional value and potential ecological role in natural forests, very little is known about its genetics, diversity and ecology. In this study, we investigated DNA sequence variation at the internal transcribed spacer (ITS) regions among 156 specimens collected from 23 sites of nine regions in Yunnan Province. Our analysis identified a total of 34 ITS haplotypes and these haplotypes were clustered into five distinct phylogenetic groups. The evolutionary divergences among these clades are similar to or greater than many known sister species pairs within the genus Thelephora and the closely related genus Tomentella. Among the 34 ITS haplotypes, 22 were represented by one specimen each and the remaining 12 were each shared by two or more specimens. The most common haplotype contained 68 specimens distributed in 21 of the 23 sites, a result consistent with gene flow among geographical populations. However, analysis of molecular variance (AMOVA) revealed low but significant genetic differentiation among local and regional populations. Interestingly, the Mantel test identified that the extent of genetic differentiation was not significantly correlated with geographical distance. Our study revealed significant genetic divergence within Th. ganbajun and limited but detectable gene flow among geographical populations of this endemic ectomycorrhizal gourmet mushroom.