gebhart/patrepeval huggingface dataset:
Therapeutic Use of Agonists of the Nuclear Receptor PPAR&#947; in Alzheimers Disease (2007)

Alzheimer's disease (AD) is a devastating neurodegenerative disease for which there are no highly effective therapies. A novel therapeutic approach to the treatment of AD is the use of agonists of the nuclear receptor, peroxisome proliferators-activated receptor gamma (PPARgamma). PPARgamma is a ligand activated transcription factor whose best described roles are to regulate lipid metabolism and inflammation. Agonists of PPARgamma have been shown to ameliorate AD-related pathology in animal models of AD and improve cognition. A number of potential mechanisms have been advanced to account for these effects. PPARgamma agonists act as insulin sensitizers, facilitating insulin action. In addition, PPARgamma agonists have been shown to inhibit inflammatory gene expression, alter Abeta homeostasis and exhibit neuroprotective effects. Importantly, recent clinical trials of FDA approved PPARgamma agonists have been shown to improve cognition and memory in AD patients. Thus, PPARgamma agonists represent a new and potentially efficacious treatment of AD.
DNA Immunization in a Mouse Model of Latent Tuberculosis: Effect of DNA Vaccination on Reactivation of Disease and on Reinfection with a Secondary Challenge (2002)

Individuals who are latently infected with Mycobacterium tuberculosis can develop active disease via either endogenous reactivation of the latent bacilli or exogenous reinfection with a second mycobacterial strain. In this study, we investigated whether immunization with a tuberculosis DNA vaccine cocktail that induces significant protective responses in mice could prevent reactivation of disease in a murine latent-tuberculosis model. In addition, we assessed whether DNA vaccination could retard the growth of a secondary aerogenic infection with M. tuberculosis (exogenous reinfection) in latently infected mice. In the reactivation studies, administration of the DNA vaccine combination did not prevent recrudescence of the latent infection after injection of dexamethasone. Moreover, for the reinfection experiments, only a modest decrease in the growth of a secondary M. tuberculosis challenge in DNA-vaccinated animals, compared to controls, was observed 14 and 28 days after the reinfection of previously exposed mice. Interestingly, although proliferation of the secondary challenge was reduced significantly in a nonvaccinated chronic-infection group relative to the naïve controls, the number of bacilli still increased by 500-fold 1 month after the secondary challenge in mice with active tuberculosis. These results indicate that novel immunotherapeutic approaches will be required to prevent reactivation of infection or reinfection of individuals with latent tuberculosis.
DNA Methylation Analysis in the Intestinal Epithelium—Effect of Cell Separation on Gene Expression and Methylation Profile (2013)

Taken together, our data highlight the importance of considering the potential effect of cell separation on gene expression as well as DNA methylation signatures. The decision to separate tissue samples will therefore depend on study design and specific separation protocols.
UV-induced strand break damage in single stranded bromodeoxyuridine-containing DNA oligonucleotides (1998)

Aerobic UVB photolysis of single stranded bromodeoxyuridine (BrdU)-containing DNA oligonucleotides produces immediate and latent strand break products consistent with a specific BrdU base radical-mediated abstraction of the C1′ hydrogen atom from the 5′ neighbouring deoxyribose.
Anti-interleukin-5 therapy in severe asthma (2013)

Asthma is a chronic inflammatory disorder of the airways that leads to acute symptoms, exacerbations and sometimes, for a small part of the asthmatic population, fatal or near-fatal exacerbations. This as yet significant minority of individuals present with severe asthma and have persisting daily symptoms, and exacerbations despite compliance with high doses of inhaled steroids and additional treatment. For more than a decade, the pharmacological management of patients with severe asthma has focused on evaluating specific cytokines. The rationale of this approach is based on the distinguished key role played by eosinophils in the asthma inflammatory processes. Eosinophils are recruited from the circulation to airways where they cause airway damage via different mechanisms. Eosinophils are regulated in terms of their recruitment, activation, growth, differentiation and survival by interleukin (IL)-5. Abundant data from in vitro experiments, animal models and clinical trials has confirmed that IL-5 inhibition may be an effective approach for the treatment of asthma, especially severe asthma. Interfering with eosinophil function or reducing their numbers has been one of the most important goals of therapeutic monoclonal antibodies, which target cytokine receptor interactions in asthma, particularly IL-5. This review will consider new treatments options for severe asthma, particularly those targeting IL-5, that have already been evaluated in clinical trials in asthmatic patients.
Albumin microspheres for study of the reticuloendothelial system. (1972)

Summary An improved method for the preparation of HSA microspheres with an average diameter of 0.5–0.7 microns and narrow particle-size range, suitable for the study of the RES, has been described. No toxic effects towards the new drug were observed in animals. Nonradioactive HSA spheres could be stored for more than 10 months. Labeling of the spheres with 99mTc was carried out under sterile conditions immediately before use. The tagging efficiency was 65–83%, and the labeled product was stable for up to 20 hr. When injected intravenously, about 90% of the 99mTc microspheres were extracted by the liver. Blood clearance studies in dogs showed small variability in day-to-day preparations. The advantage of this new drug over the widely used 99mTc-sulfur-colloid is that it can be used for the assessment of RES functions in addition to scanning the distribution of the RES.
Phase I Clinical Study of AZD2171, an Oral Vascular Endothelial Growth Factor Signaling Inhibitor, in Patients With Advanced Solid Tumors (2007)

Once-daily oral AZD2171 at doses of 45 mg or less was generally well tolerated and was associated with encouraging antitumor activity in patients with a broad range of advanced solid tumors.
Blocking Herpes Simplex Virus 2 Glycoprotein E Immune Evasion as an Approach To Enhance Efficacy of a Trivalent Subunit Antigen Vaccine for Genital Herpes (2014)

Herpes simplex virus is the most common cause of genital ulcer disease worldwide. Infection results in emotional distress for infected individuals and their partners, is life threatening for infants exposed to herpes during childbirth, and greatly increases the risk of individuals acquiring and transmitting HIV infection. A vaccine that prevents genital herpes infection will have major public health benefits. Our vaccine approach includes strategies to prevent the virus from evading immune attack. Mice were immunized with a trivalent vaccine containing an antigen that induces antibodies to block virus entry and two antigens that induce antibodies that block immune evasion from antibody and complement. Immunized mice demonstrated no genital disease, and 32/33 (97%) animals had no evidence of infection of dorsal root ganglia, suggesting that the vaccine may prevent the establishment of latency and recurrent infections.
Functional cerebral imaging by susceptibility‐contrast NMR (1990)

In vivo measurement of cerebral physiology by dynamic contrast-enhanced NMR is demonstrated. Time-resolved images of the cerebral transit of paramagnetic contrast agent were acquired using a new ultrafast NMR imaging technique and a novel mechanism of image contrast based on microscopic changes in tissue magnetic susceptibility. Global hypercapnia in dogs was used to establish the relationship between susceptibility-induced signal change and brain blood volume, and the response of gray and white matter to this microvascular stimulus was measured.
Characteristics of LaAlO3/Si(100) deposited under various oxygen pressures (2002)

High-k dielectric LaAlO3 (LAO) thin films were deposited by laser molecular-beam epitaxy under various oxygen pressures. X-ray diffraction showed that the LAO films were amorphous. The chemical compositions and thickness of the LAO thin films were measured using Rutherford backscattering spectrometry. Al/LAO/Si metal–oxide–semiconductor capacitor structures were fabricated and measured. The leakage current density versus voltage curves showed that the leakage current of the LAO thin films decreased by increasing the oxygen pressure of the preparation. Specifically, when prepared under the active oxygen (containing atom oxygen), the leakage current of the LAO sample was lower than that prepared under the general oxygen. All of the capacitance–voltage curves have a positive shift along the voltage axis and the flatband voltage decreased with increasing oxygen pressures during the LAO thin-film preparation.
Substituted heteroaromatic anthranilic acids with antiinflammatory activity (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubstituted heteroaromatic anthranilic acids with antiinflammatory activityE. Falch, J. Weis, and T. NatvigCite this: J. Med. Chem. 1968, 11, 3, 608–611Publication Date (Print):May 1, 1968Publication History Published online1 May 2002Published inissue 1 May 1968https://doi.org/10.1021/jm00309a047RIGHTS & PERMISSIONSArticle Views97Altmetric-Citations11LEARN 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 (477 KB) Get e-Alerts Get e-Alerts
Bayesian optimisation for Intelligent Environmental Monitoring (2012)

Environmental Monitoring (EM) is typically performed using sensor networks that collect measurements in predefined static locations. The possibility of having one or more autonomous robots to perform this task increases versatility and reduces the number of necessary sensor nodes to cover the same area. However, several problems arise when making use of autonomous moving robots for EM. The main challenges are how to build an accurate spatial-temporal model while choosing locations for measuring the phenomenon. This paper addresses the problem by using Bayesian Optimisation for choosing sensing locations, and presents a new utility function that takes into account the distance travelled by a moving robot. The proposed methodology is tested in simulation and in a real environment. Compared to existing strategies, our approach exhibits slightly better accuracy in terms of RMSE error and considerably reduces the total distance travelled by the robot.
An Objective Analysis of the Pressure-Volume Curve in the Acute Respiratory Distress Syndrome (2000)

To assess the interobserver and intraobserver variability in the clinical evaluation of the quasi-static pressure-volume (P-V) curve, we analyzed 24 sets of inflation and deflation P-V curves obtained from patients with ARDS. We used a recently described sigmoidal equation to curve-fit the P-V data sets and objectively define the point of maximum compliance increase of the inflation limb (P(mci, i)) and the true inflection point of the deflation limb (P(inf,d)). These points were compared with graphic determinations of lower Pflex by seven clinicians. The graphic and curve-fitting methods were also compared for their ability to reproduce the same parameter value in data sets with reduced number of data points. The sigmoidal equation fit the P-V data with great accuracy (R(2) = 0.9992). The average of Pflex determinations was found to be correlated with P(mci,i) (R = 0.89) and P(inf,d) (R = 0.76). Individual determinations of Pflex were less correlated with the corresponding objective parameters (R = 0.67 and 0.62, respectively). Pflex + 2 cm H(2)O was a more accurate estimator of P(inf,d) (2 SD = +/-6.05 cm H(2)O) than Pflex was of P(mci,i) (2 SD = +/-8.02 cm H(2)O). There was significant interobserver variability in Pflex, with a maximum difference of 11 cm H(2)O for the same patient (SD = 1.9 cm H(2)O). Clinicians had difficulty reproducing Pflex in smaller data sets with differences as great as 17 cm H(2)O (SD = 2.8 cm H(2)O). In contrast, the curve-fitting method reproduced P(mci,i) with great accuracy in reduced data sets (maximum difference of 1.5 cm H(2)O and SD = 0.3 cm H(2)O). We conclude that Pflex rarely coincided with the point of maximum compliance increase defined by a sigmoid curve-fit with large differences in Pflex seen both among and within observers. Calculating objective parameters such as P(mci,i) or P(inf,d) from curve-fitted P-V data can minimize this large variability.
Review: Disruption of the Postsynaptic Density in Alzheimer’s Disease and Other Neurodegenerative Dementias (2010)

The most common causes of neurodegenerative dementia include Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). We believe that, in all 3, aggregates of pathogenic proteins are pathological substrates which are associated with a loss of synaptic function/plasticity. The synaptic plasticity relies on the normal integration of glutamate receptors at the postsynaptic density (PSD). The PSD organizes synaptic proteins to mediate the functional and structural plasticity of the excitatory synapse and to maintain synaptic homeostasis. Here, we will discuss the relevant disruption of the protein network at the PSD in these dementias and the accumulation of the pathological changes at the PSD years before clinical symptoms. We suggest that the functional and structural plasticity changes of the PSD may contribute to the loss of molecular homeostasis within the synapse (and contribute to early symptoms) in these dementias.
CD8+αβ+ T Cells That Lack Surface CD5 Antigen Expression Are a Major Lymphotactin (XCL1) Source in Peripheral Blood Lymphocytes (2003)

To better characterize the cellular source of lymphotactin (XCL1), we compared XCL1 expression in different lymphocyte subsets by real-time PCR. XCL1 was constitutively expressed in both PBMC and CD4(+) cells, but its expression was almost 2 log higher in CD8(+) cells. In vitro activation was associated with a substantial increase in XCL1 expression in both PBMC and CD8(+) cells, but not in CD4(+) lymphocytes. The preferential expression of XCL1 in CD8(+) cells was confirmed by measuring XCL1 production in culture supernatants, and a good correlation was found between figures obtained by real-time PCR and XCL1 contents. XCL1 expression was mostly confined to a CD3(+)CD8(+) subset not expressing CD5, where XCL1 expression equaled that shown by gammadelta(+) T cells. Compared with the CD5(+) counterpart, CD3(+)CD8(+)CD5(-) cells, which did not express CD5 following in vitro activation, showed preferential expression of the alphaalpha form of CD8 and a lower expression of molecules associated with a noncommitted/naive phenotype, such as CD62L. CD3(+)CD8(+)CD5(-) cells also expressed higher levels of the XCL1 receptor; in addition, although not differing from CD3(+)CD8(+)CD5(+) cells in terms of the expression of most alpha- and beta-chemokines, they showed higher expression of CCL3/macrophage inflammatory protein-1alpha. These data show that TCR alphabeta-expressing lymphocytes that lack CD5 expression are a major XCL1 source, and that the contribution to its synthesis by different TCR alphabeta-expressing T cell subsets, namely CD4(+) lymphocytes, is negligible. In addition, they point to the CD3(+)CD8(+)CD5(-) population as a particular T cell subset within the CD8(+) compartment, whose functional properties deserve further attention.
Development of a Microscale Implantable Neural Interface (MINI) Probe System (2005)

Cortical recording devices hold promise for providing augmented control of neuroprostheses and brain-computer interfaces in patients with severe loss of motor function due to injury or disease. This paper reports on the preliminary in vitro and in vivo results of our microscale implantable neural interface (MINI) probe system. The MINI is designed to use proven components and materials with a modular structure to facilitate ongoing improvements as new technologies become available. This device takes advantage of existing, well-characterized Michigan probe technologies and combines them to form a multichannel, multiprobe cortical assembly. To date, rat, rabbit, and non-human primate models have been implanted to test surgical techniques and in vivo functionality of the MINI. Results demonstrate the ability to form a contained hydrostatic environment surrounding the implanted probes for extended periods and the ability of this device to record electrophysiological signals with high SNRs. This is the first step in the realization of a cortically-controlled neuroprosthesis designed for human applications.
CD49f-positive cell population efficiently enriches colon cancer-initiating cells (2013)

Cancer stem cells (CSCs) also known as cancer-initiating cells (CICs) show high tumorigenic activity and high chemo- and radiation resistance. It is, therefore, important to identify CSCs reliably to develop novel curative cancer treatments. In this study, we re-evaluated CSC markers of colorectal cancer for their cellular differentiation and tumorigenic activity, with the aim to identify reliable CSC markers. The rates of change in CD44, CD133, CD166, CD24, CD49f and CXCR4 expression during sodium butyrate (NaBT)-induced cell differentiation were assessed in HT29 and Caco2 colon cancer cell lines. Expression levels of target markers were assessed in clinical CRC samples. Tumorigenic activity was assessed on isolated cell fractions identified by multicolor flow cytometric analysis. In the cell differentiation assay, the average percent change was higher in CD44 (-98.2%) and CD49f (-74.4%) compared to CD133 (-17.9%) and CD166 (-49.4%). Expression of CD24 and CXCR4 appeared random in HT29 and Caco2. Expression of CD44, CD49f, CD133 and CD166 was confirmed in all four clinical CRC samples. Limiting dilution assay of CD44- and CD133-expressing cells revealed that only the CD133⁺CD44⁺ population possessed tumorigenic activity. Tumorigenesis was not affected by CD166 expression. Highly tumorigenic cells could be enriched in samples with higher CD49f expression; CD49f⁺ cells showed high tumorigenesis, whereas CD133⁺ and CD44⁺ cells that were negative for CD49f exhibited no tumorigenic activity. Multicolor analysis revealed that CD49f⁺ cells localized in CD44⁺ and CD133⁺ cell fractions. These findings demonstrated that CD49f is an important marker for identifying colorectal CSCs and suggest that the CD49f⁺ cell fraction may be the best candidate for colorectal CSCs.
Application of active-phase plot to the kinetic analysis of lipoxygenase in reverse micelles (1992)

A new plot for explaining the complex expression of the enzymic activity in reverse micelles has been developed as an extension of the theoretical model described by our group [Bru, Sánchez-Ferrer & García-Carmona (1990) Biochem. J. 268, 679-684]. The plot describes the changes in the relative volume, amount of enzyme (mumoles), enzyme concentration (microM) and substrate concentration (microM) in the phase where the enzyme is active. To illustrate the usefulness of this plot, the complex activity of soya bean lipoxygenase in reverse micelles acting on its interfacial substrate, octadecadienoic acid, was studied. It showed the key parameters ruling the activity profiles of lipoxygenase with respect to micelle size (omega 0), micelle concentration (theta) and the substrate/surfactant molar ratio (rho), which have never been described before.
Hand-held glucose monitor and recorder (1988)

A portable blood glucose sensor is described. The instruments uses a polarographic method already widely accepted in clinical assay devices. The accuracy of the measurement and its speed and simplicity of use are achieved primarily by a specially constructed, proprietary disposable membrane that ensures a reliable electrooxidation current. The electrodes are Pt against Ag/AgCl. The surface characteristics of the chlorided electrode that give the best polargraphic response are discussed. Electronic methods for sensor signal processing and data recording are described. Patient data are read by a clinical workstation which analyzes the data and provides hard copy to assist the managing physician.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Aptamer Sensors Combined with Enzymes for Highly Sensitive Detection (2011)

Diagnostics have taken on a larger role patient care, with diagnostics for point-of-care testing (POCT) having greatly expanded during the last two decades. The expectation is that POCT will continue to grow because it can help to expand personalized therapy and theranostics, which will provide the right medicine to the right person, with the right dosage at the right time. For POCT, it will be necessary to construct miniaturized biosensors at a low cost that have high sensitivity with rapid sensing. Affinity-based techniques that are used clinical diagnostics rely on the high affinity and specificity of antibodies for highly sensitive detection of target molecules. Antibody-based diagnostic systems are well established, and enable the detection of various molecules. However, aptamers are expected to be the next-generation elements for molecular recognition. Aptamers are short strands of nucleic acids that have been designed to specifically bind to various target molecules, and have comparable affinity and specificity to antibodies. They are selected using the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technique (Tuerk & Gold, 1990), also referred to as in vitro selection or in vitro evolution. SELEX is a combinatorial chemistry technique that produces single-stranded oligonucleotides of DNA or RNA, which specifically bind to a target ligand(s). It has been two decades since the first report on aptamers became public (Ellington & Szostak, 1990; Tuerk & Gold, 1990). During these two decades, many aptamers have been reported and an aptamer has been approved as a therapeutic medicine by the US Food and Drug Administration (FDA). Aptamers have many advantages as biosensors that antibodies do not have, such as: 1. The ability to be selected by SELEX. 2. The ability to be synthesized and modified. 3. The ability to renature. 4. More stability than antibodies. 5. The ability to change conformation upon binding to target molecules. For theranostics, the first advantage is important when it is necessary to obtain affinity probes against various novel biomarkers. SELEX has many advantages, and is an excellent method to evolve aptamers so that they have an extremely high binding affinity to a variety of target ligands. We were able to successfully achieve the automatic vitro screening of aptamers, which enabled us to obtain aptamers against more than 100 proteins per month (Cox & Ellington, 2001). Aptamers can therefore be developed more rapidly than antibodies.