gebhart/patrepeval huggingface dataset:
Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis (2009)

The synthetic retinoid Fenretinide (FEN) increases insulin sensitivity in obese rodents and is in early clinical trials for treatment of insulin resistance in obese humans with hepatic steatosis (46). We aimed to determine the physiological mechanisms for the insulin-sensitizing effects of FEN. Wild-type mice were fed a high-fat diet (HFD) with or without FEN from 4-5 wk to 36-37 wk of age (preventive study) or following 22 wk of HF diet-induced obesity (12 wk intervention study). Retinol-binding protein-4 (RBP4) knockout mice were also fed the HFD with or without FEN in a preventive study. FEN had minimal effects on HFD-induced body weight gain but markedly reduced HFD-induced adiposity and hyperleptinemia in both studies. FEN-HFD mice gained epididymal fat but not subcutaneous or visceral fat mass in contrast to HFD mice without FEN. FEN did not have a measurable effect on energy expenditure, food intake, physical activity, or stool lipid content. Glucose infusion rate during hyperinsulinemic-euglycemic clamp was reduced 86% in HFD mice compared with controls and was improved 3.6-fold in FEN-HFD compared with HFD mice. FEN improved insulin action on glucose uptake and glycogen levels in muscle, insulin-stimulated suppression of hepatic glucose production, and suppression of serum FFA levels in HFD mice. Remarkably, FEN also reduced hepatic steatosis. In RBP4 knockout mice, FEN reduced the HFD-induced increase in adiposity and hyperleptinemia. In conclusion, long-term therapy with FEN partially prevents or reverses obesity, insulin resistance, and hepatic steatosis in mice on HFD. The anti-adiposity effects are independent of the RBP4 lowering effect.
Design control--the ultimate protection? (1991)

Over the last decade or so, medical device manufacturers with customers in the United States and the United Kingdom should have discovered the benefits of using quality systems in their manufacturing process. Both the American GMP Regulations (21 CFR-820)--enforced by the U.S. Food and Drug Administration (FDA)--and the U.K. Department of Health Guides to Good Manufacturing Practice based upon BS 5750: Part I (1979)--enforced through the National Health Service supply chain-- have been applied with the objective of ensuring the availability of safe and effective medical devices. This article examines the design control aspects of a quality system and asks whether the medical device industry should be suspicious of third-party assessments of confidential documentation.
Serum tumor marker CYFRA 21-1 in the diagnostics of NSCLC lung cancer. (1998)

Cytokeratins are epithelial markers whose expression is not lost during malignant transformation. The level of soluble cytokeratin fragment 19 was measured with an enzyme immunoassay method developed by Boehringer Mannheim (Enzymum-test CYFRA 21-1) in the serum of 200 male and 50 female patients with NSCLC (Non Small Cell Lung Cancer) lung cancer (120 planocellulare and 80 adenocarcinoma in males; 22 planocellulare and 28 adenocarcinoma in females). The comparative group comprised 50 young healthy males and 50 females without any clinical proof for malignancy or any other lung disease. The aim of this investigation was to find out if any possible statistical difference exists in the serum level of CYFRA 21-1 between patients with lung cancer and healthy controls, and also between different types of lung cancers. The mean value of serum CYFRA 21-1 in NSCLC (6.25 ng/ml) was significantly higher than in healthy controls (1.26 ng/ml) (p < 0.001). Sensitivity for CYFRA 21-1 (using 3.3 ng/ml, a cut-off value corresponding to a 98% specificity for healthy controls) in NSCLC was 60.5%. Positive CYFRA 21-1 levels were significantly higher in patient with carcinoma planocellulare (66.2%) than in adenocarcinoma (52.1%). CYFRA 21-1 levels were significantly different between squamous cell carcinoma (6.52 ng/ml) and adenocarcinoma (5.86 ng/ml) (p < 0.05). Our results indicate that CYFRA 21-1 may be a useful tumor marker in NSCLC, especially in carcinoma planocellulare. CYFRA 21-1 may also be useful in identification of the preoperative stages of diseases and the postoperative monitoring of NSCLC.
The paths more taken (2010)

An unsupervised clustering of the webpages on a website is a primary requirement for most wrapper induction and automated data extraction methods. Since page content can vary drastically across pages of one cluster (e.g., all product pages on amazon.com), traditional clustering methods typically use some distance function between the DOM trees representing a pair of webpages. However, without knowing which portions of the DOM tree are "important," such distance functions might discriminate between similar pages based on trivial features (e.g., differing number of reviews on two product pages), or club together distinct types of pages based on superficial features present in the DOM trees of both (e.g., matching footer/copyright), leading to poor clustering performance.
CUDA Accelerated LTL Model Checking (2009)

Recent technological developments made available various many-core hardware platforms. For example, a SIMD-like hardware architecture became easily accessible for many users who have their computers equipped with modern NVIDIA GPU cards with CUDA technology. In this paper we redesign the maximal accepting predecessors algorithm [7] for LTL model checking in terms of matrix-vector product in order to accelerate LTL model checking on many-core GPU platforms. Our experiments demonstrate that using the NVIDIA CUDA technology results in a significant speedup of verification process.
MEMS tunable VCSEL light source for ultrahigh speed 60kHz - 1MHz axial scan rate and long range centimeter class OCT imaging (2012)

This paper demonstrates new wavelength swept light source technology, MEMS tunable VCSELs, for OCT imaging. The VCSEL achieves a combination of ultrahigh sweep speeds, wide spectral tuning range, flexibility in sweep trajectory, and extremely long coherence length, which cannot be simultaneously achieved with other technologies. A second generation prototype VCSEL is optically pumped at 980nm and a low mass electrostatically tunable mirror enables high speed wavelength tuning centered at ~1310nm with ~110nm of tunable bandwidth. Record coherence length &gt;100mm enables extremely long imaging range. By changing the drive waveform, a single 1310nm VCSEL was driven to sweep at speeds from 100kHz to 1.2MHz axial scan rate with unidirectional and bidirectional high duty cycle sweeps. We demonstrate long range and high resolution 1310nm OCT imaging of the human anterior eye at 100kHz axial scan rate and imaging of biological samples at speeds of 60kHz - 1MHz. A first generation 1050nm device is shown to sweep over 100nm. The results of this study suggest that MEMS based VCSEL swept light source technology has unique performance characteristics and will be a critical technology for future ultrahigh speed and long depth range OCT imaging.
Mutants of Taq DNA polymerase resistant to PCR inhibitors allow DNA amplification from whole blood and crude soil samples (2009)

Potent PCR inhibitors in blood and soil samples can cause false negative results from PCR-based clinical and forensic tests. We show that the effect of these inhibitors is primarily upon Taq DNA polymerase, since mutational alteration of the polymerase can overcome the inhibition to the extent that no DNA purification is now required. An N-terminal deletion (Klentaq1) is some 10-100-fold inhibition resistant to whole blood compared to full-length, wild-type (w.t.) Taq, which is strongly inhibited by 0.1-1% blood. Further mutations at codon 708, both in Klentaq 1 and Taq, confer enhanced resistance to various inhibitors of PCR reactions, including whole blood, plasma, hemoglobin, lactoferrin, serum IgG, soil extracts and humic acid, as well as high concentrations of intercalating dyes. Blood PCR inhibitors can predominantly reduce the DNA extension speed of the w.t. Taq polymerase as compared to the mutant enzymes. Single-copy human genomic targets are readily amplified from whole blood or crude soil extract, without pretreatment to purify the template DNA, and the allowed increase in dye concentration overcomes fluorescence background and quenching in real-time PCR of blood.
HER2/neu expression correlates with vasculogenic mimicry in invasive breast carcinoma (2012)

Vasculogenic mimicry (VM) refers to the condition in which tumour cells mimic endothelial cells to form extracellular matrix-rich tubular channels. VM is more extensive in more aggressive tumours. The human epidermal growth factor receptor 2 (HER2) gene is amplified in 20-30% of human breast cancers and has been implicated in mediating aggressive tumour growth and metastasis. However, thus far, there have been no data on the role of HER2 in VM formation. Immunohistochemical and histochemical double-staining methods were performed to display VM in breast cancer specimens. Transfection in MCF7 cells was performed and clones were selected by G418. The three-dimensional Matrigel culture was used to evaluate VM formation in the breast cancer cell line. According to statistical analysis, VM was related to the presence of a positive nodal status and advanced clinical stage. The positive rate of VM increased with increased HER2 expression. In addition, cases with HER2 3+ expression showed significantly greater VM channel count than those in other cases. The exogenous HER2 overexpression in MCF-7 cells induced vessel-like VM structures on the Matrigel and increased the VM mediator vascular endothelial (VE) cadherin. Our data provide evidence for a clinically relevant association between HER2 and VM in human invasive breast cancer. HER2 overexpression possibly induces VM through the up-regulation of VE cadherin. Understanding the key molecular events may provide therapeutic intervention strategies for HER2+ breast cancer.
Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation (1984)

A series of monoclonal antibodies that define B cell restricted and associated antigens was utilized in an attempt to characterize tumors of B lineage and to relate these tumors to B cell differentiative stages. Antigens that were previously shown to be B cell restricted on normal B lymphocytes were similarly expressed only on B cell malignancies. In contrast, antigens that were B cell associated were also found on tumors of other lineages. Moreover, on the basis of cell surface phenotypes, tumors of B cell origin were divided into three major subgroups, which corresponded to the level of differentiation of the malignant tumor cell: pre-B cell stage (non-T acute lymphoblastic leukemia and chronic myelocytic leukemia in lymphoid blast crisis); the mid-B cell stage (chronic lymphocytic leukemia, poorly differentiated lymphomas); and secretory B cell stage (large cell lymphomas and plasma cell tumors). A hypothetical model is derived that relates the malignant B cell to its normal cellular counterpart on the basis of cell surface expression of this panel of B cell-restricted and B cell- associated antigens.
IL-1β Epitope Mapping Using Site-Directed Mutagenesis and Hydrogen−Deuterium Exchange Mass Spectrometry Analysis (2005)

Hu007, a humanized IgG1 monoclonal antibody, binds and neutralizes human, cynomolgus, and rabbit IL-1beta but only weakly binds to mouse and rat IL-1beta. Biacore experiments demonstrated that Hu007 and the type-I IL-1 receptor competed for binding to IL-1beta. Increasing salt concentrations decrease the association rate with only moderate effects on the dissociation rate, suggesting that long-range electrostatics are critical for formation of the initial complex. To understand the ligand-binding specificity of Hu007, we have mapped the critical residues involved in the recognition of IL-1beta. Selected residues in cynomolgus IL-1beta were mutated to the corresponding residues in mouse IL-1beta, and the effects of the changes on binding were evaluated by surface plasmon resonance measurements using Biacore. Specifically, substitution of F150S decreased binding affinity by 100-fold, suggesting the importance of hydrophobic interactions in stabilizing the antibody/antigen complex. Substitution of three amino acids near the N- and C-terminal regions of cIL-1beta with those found in mouse IL-1beta (V3I/S5Q/F150S) decreased the binding affinity of Hu007 to IL-1beta by about 1000-fold. Conversely, mutating the corresponding residues in mouse IL-1beta to the human sequence resulted in an increase in binding affinity of about 1000-fold. Hydrogen-deuterium exchange/mass spectrometry analysis confirmed that these regions of IL-1beta were protected from exchange because of antibody binding. The results from this study demonstrate that Hu007 binds to a region located in the open end of the beta-barrel structure of IL-1beta and blocks binding of IL-1beta to its receptor.
Proinflammatory Effects of Respiratory Syncytial Virus–Induced Epithelial HMGB1 on Human Innate Immune Cell Activation (2018)

High mobility group box 1 (HMGB1) is a multifunctional nuclear protein that translocates to the cytoplasm and is subsequently released to the extracellular space during infection and injury. Once released, it acts as a damage-associated molecular pattern and regulates immune and inflammatory responses. Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections in infants and elderly, for which no effective treatment or vaccine is currently available. This study investigated the effects of HMGB1 on cytokine secretion, as well as the involvement of NF-κB and TLR4 pathways in RSV-induced HMGB1 release in human airway epithelial cells (AECs) and its proinflammatory effects on several human primary immune cells. Purified HMGB1 was incubated with AECs (A549 and small alveolar epithelial cells) and various immune cells and measured the release of proinflammatory mediators and the activation of NF-κB and P38 MAPK. HMGB1 treatment significantly increased the phosphorylation of NF-κB and P38 MAPK but did not induce the release of cytokines/chemokines from AECs. However, addition of HMGB1 to immune cells did significantly induce the release of cytokines/chemokines and activated the NF-κB and P38 MAPK pathways. We found that activation of NF-κB accounted for RSV-induced HMGB1 secretion in AECs in a TLR4-dependent manner. These results indicated that HMGB1 secreted from AECs can facilitate the secretion of proinflammatory mediators from immune cells in a paracrine mechanism, thus promoting the inflammatory response that contributes to RSV pathogenesis. Therefore, blocking the proinflammatory function of HMGB1 may be an effective approach for developing novel therapeutics.
Towards molecular farming in the future: using plant‐cell‐suspension cultures as bioreactors (1999)

Plant-suspension cells are an in vitro system that can be used for recombinant protein production under carefully controlled certified conditions. Plant-suspension cells can be grown in shake flasks or fermenters to produce secondary metabolites, like vincristine and vinblastine, and to produce recombinant proteins after transformation. This review article focuses on discussing the generation of transformed suspension-cell lines expressing recombinant proteins, like antibodies, and recombinant-protein downstream processing and purification.
DNA: INSULATOR OR WIRE? (1997)

RETURN TO ISSUEPREVNewsNEXTDNA: INSULATOR OR WIRE?Flurry of new research, heated debate focuses on biomoleculeELIZABETH K. WILSONView Author Information C&EN West Coast News BureauCite this: Chem. Eng. News 1997, 75, 8, 33–39Publication Date (Print):February 24, 1997Publication History Published online12 November 2010Published inissue 24 February 1997https://pubs.acs.org/doi/10.1021/cen-v075n008.p033https://doi.org/10.1021/cen-v075n008.p033newsACS PublicationsCopyright © 1997 American Chemical SocietyArticle Views27Altmetric-Citations6LEARN 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 options SUBJECTS:Genetics Get e-Alerts
Optimal Asset Allocation using Adaptive Dynamic Programming (1995)

In recent years, the interest of investors has shifted to computerized asset allocation (portfolio management) to exploit the growing dynamics of the capital markets. In this paper, asset allocation is formalized as a Markovian Decision Problem which can be optimized by applying dynamic programming or reinforcement learning based algorithms. Using an artificial exchange rate, the asset allocation strategy optimized with reinforcement learning (Q-Learning) is shown to be equivalent to a policy computed by dynamic programming. The approach is then tested on the task to invest liquid capital in the German stock market. Here, neural networks are used as value function approximators. The resulting asset allocation strategy is superior to a heuristic benchmark policy. This is a further example which demonstrates the applicability of neural network based reinforcement learning to a problem setting with a high dimensional state space.
Liver transplantation: an unfinished product. (1989)

Liver transplantation has become an extraordinarily valuable and useful operation, but one that is not perfect and that has not been exploited to anything like its full potential. Better immunosuppression may become available soon as exemplified by developments with the Japanese drug, FK506. Improved preservation with the UW solution is already here. With these advantages, liver transplantation is certain to become far more widely used than at any time in the past. Examples were cited of innovative approaches using liver transplantation for the treatment of hepatic malignancies.
e-Nanoflex Sensor System: Smartphone-Based Roaming Health Monitor (2011)

The growing need and market demand for point of care (POC) systems to improve patient’s quality of life are driving the development of wireless nanotechnology based smart systems for diagnosis and treatment of various chronic and life threatening diseases. POC diagnostics for neurological, metabolic, and cardiovascular disorders require constant long term untethered monitoring of individuals. Given the uncertainty associated with location and time at which immediate diagnosis and treatment may be required, constant vigilance and monitoring are the only practical solutions. What is needed is for a remote cyber-enabled health care smart system incorporating novel ideas from nanotechnology, low power embedded systems, wireless networking, and cloud computing to fundamentally advance. To meet this goal, we present e-Nanoflex platform, which is capable of monitoring patient health wherever they may be and communicating the data in real time to a physician or a hospital. Unlike state-of-the-art systems that are either local sensor systems or rely on custom relaying devices, e-Nanoflex is a highly nonintrusive and inexpensive end-to-end cyber-physical system. Using nanostructured sensors, e-Nanoflex provides nearly invisible monitoring of physiological conditions. It relies on smartphones to filter, compress, and relay geo-tagged data. Further, it ties to a backend cloud infrastructure for data storage, data dissemination, and abnormality detection using machine learning techniques. e-Nanoflex is a complete end-to-end system for physiological sensing and geo-tagged data dissemination to hospitals and caregivers. It is intended as a basic platform that can support any nanostructure based flexible sensor to monitor a variety of conditions such as body temperature, respiration air flow, oxygen consumption, bioelectric signals, pulse oximetry, muscle activity, and neural activity. Additionally, to address the cost of manufacturing sensors, e-Nanoflex uses a low cost production technique based on roll to roll gravure printing. We show the efficacy of our platform through a case study that involves acquiring electrocardiogram signals using gold nano-electrodes fabricated on a flexible substrate.
A new crosslinker for mass spectrometric analysis of the quaternary structure of protein complexes (2001)

Mass spectrometric structural analysis of crosslinked peptides is a powerful method to elucidate the spatial arrangement of polypeptides in protein complexes. Our aim is to develop bifunctional crosslinkers that, after crosslinking protein complexes followed by proteolytic digestion, give rise to crosslinked peptides that can be readily tracked down by mass spectrometry. To this end we synthesized the crosslinker N-benzyliminodiacetoyloxysuccinimid (BID), which yields stable benzyl cation marker ions upon low-energy collision-induced dissociation (CID) tandem mass spectrometry. Sensitive detection of the marker ion upon low-energy CID is demonstrated with different BID-crosslinked peptide preparations. With BID it becomes possible to retrieve crosslinked and crosslinker-adducted peptides, without the necessity of purifying crosslinked peptides prior to identification. The basic design of this crosslinker can be varied upon, in order to meet specific crosslinking needs.
Neuromodulation for fecal incontinence: Outcome in 16 patients with definitive implant (2001)

Neuromodulation can be considered an option for fecal incontinence. However, an accurate clinical and instrumental evaluation and careful patient selection are required to optimize outcome.
Identification of anthranilate and benzoate metabolic operons of Pseudomonas fluorescens and functional characterization of their promoter regions (2006)

We have found the anthranilate and benzoate promoters to be useful for tightly controlling recombinant gene expression at both small (< 1 L) and large (20 L) fermentation scales.
Calculation of magnetic field noise from high-permeability magnetic shields and conducting objects with simple geometry (2008)

High-permeability magnetic shields generate magnetic field noise that can limit the sensitivity of modern precision measurements. We show that calculations based on the fluctuation-dissipation theorem allow quantitative evaluation of magnetic field noise, either from current or magnetization fluctuations, inside enclosures made of high-permeability materials. Explicit analytical formulas for the noise are derived for a few axially symmetric geometries, which are compared with results of numerical finite element analysis. Comparison is made between noises caused by current and magnetization fluctuations inside a high-permeability shield and also between current-fluctuation-induced noises inside magnetic and nonmagnetic conducting shells. A simple model is suggested to predict power-law decay of noise spectra beyond a quasi-static regime. Our results can be used to assess noise from existing shields and to guide design of new shields for precision measurements.