gebhart/patrepeval huggingface dataset:
The role of leukotrienes in allergic diseases (2014)

Leukotrienes (LTs), both LTB4 and the cysteinyl LTs (CysLTs) LTC4, LTD4 and LTE4, are implicated in a wide variety of inflammatory disorders. These lipid mediators are generated from arachidonic acid via multistep enzymatic reactions through which arachidonic acid is liberated from membrane phospholipids through the action of phospholipase A2. LTB4 and CysLTs exert their biological effects by binding to cognate receptors, which belong to the G protein-coupled receptor superfamily. LTB4 is widely considered to be a potent chemoattractant for most subsets of leukocytes, whereas CysLTs are potent bronchoconstrictors that have effects on airway remodeling. LTs play a central role in the pathogenesis of asthma and many other inflammatory diseases. This review will provide an update on the synthesis, biological function, and relevance of LTs to the pathobiology of allergic diseases, and examine the current and future therapeutic prospects of LT modifiers.
Silkworm expression system as a platform technology in life science (2009)

Many recombinant proteins have been successfully produced in silkworm larvae or pupae and used for academic and industrial purposes. Several recombinant proteins produced by silkworms have already been commercialized. However, construction of a recombinant baculovirus containing a gene of interest requires tedious and troublesome steps and takes a long time (3-6 months). The recent development of a bacmid, Escherichia coli and Bombyx mori shuttle vector, has eliminated the conventional tedious procedures required to identify and isolate recombinant viruses. Several technical improvements, including a cysteine protease or chitinase deletion bacmid and chaperone-assisted expression and coexpression, have led to significantly increased protein yields and reduced costs for large-scale production. Terminal N-acetyl glucosamine and galactose residues were found in the N-glycan structures produced by silkworms, which are different from those generated by insect cells. Genomic elucidation of silkworm has opened a new chapter in utilization of silkworm. Transgenic silkworm technology provides a stable production of recombinant protein. Baculovirus surface display expression is one of the low-cost approaches toward silkworm larvae-derived recombinant subunit vaccines. The expression of pharmaceutically relevant proteins, including cell/viral surface proteins, membrane proteins, and guanine nucleotide-binding protein (G protein) coupled receptors, using silkworm larvae or cocoons has become very attractive. Silkworm biotechnology is an innovative and easy approach to achieve high protein expression levels and is a very promising platform technology in the field of life science. Like the "Silkroad," we expect that the "Bioroad" from Asia to Europe will be established by the silkworm expression system.
An overview of statistical learning theory (1999)

Statistical learning theory was introduced in the late 1960's. Until the 1990's it was a purely theoretical analysis of the problem of function estimation from a given collection of data. In the middle of the 1990's new types of learning algorithms (called support vector machines) based on the developed theory were proposed. This made statistical learning theory not only a tool for the theoretical analysis but also a tool for creating practical algorithms for estimating multidimensional functions. This article presents a very general overview of statistical learning theory including both theoretical and algorithmic aspects of the theory. The goal of this overview is to demonstrate how the abstract learning theory established conditions for generalization which are more general than those discussed in classical statistical paradigms and how the understanding of these conditions inspired new algorithmic approaches to function estimation problems. A more detailed overview of the theory (without proofs) can be found in Vapnik (1995). In Vapnik (1998) one can find detailed description of the theory (including proofs).
Comprehensive Algorithm for Quantitative Real-Time Polymerase Chain Reaction (2005)

Quantitative real-time polymerase chain reactions (qRT-PCR) have become the method of choice for rapid, sensitive, quantitative comparison of RNA transcript abundance. Useful data from this method depend on fitting data to theoretical curves that allow computation of mRNA levels. Calculating accurate mRNA levels requires important parameters such as reaction efficiency and the fractional cycle number at threshold (CT) to be used; however, many algorithms currently in use estimate these important parameters. Here we describe an objective method for quantifying qRT-PCR results using calculations based on the kinetics of individual PCR reactions without the need of the standard curve, independent of any assumptions or subjective judgments which allow direct calculation of efficiency and CT. We use a four-parameter logistic model to fit the raw fluorescence data as a function of PCR cycles to identify the exponential phase of the reaction. Next, we use a three-parameter simple exponent model to fit the exponential phase using an iterative nonlinear regression algorithm. Within the exponential portion of the curve, our technique automatically identifies candidate regression values using the P-value of regression and then uses a weighted average to compute a final efficiency for quantification. For CT determination, we chose the first positive second derivative maximum from the logistic model. This algorithm provides an objective and noise-resistant method for quantification of qRT-PCR results that is independent of the specific equipment used to perform PCR reactions.
Plasma dopa concentrations and the “on‐off” effect after chronic treatment of Parkinson's disease (1974)

Plasma concentrations 01 dopa were measured during “on” (mobile and dyskinetic) and “off” (akinetic and/or tremulous) episodes in 10 patients who had been treated chronically with levodopa for Parkinson9s disease. Dopa levels were higher during “on” than “off” spells (1.29 ± 1.08 versus 0.62 ± 0.59 mcg per milliliter; p &lt; 0.01). A diet containing less than 10 gm per day of protein resulted in higher plasma dopa levels (2.05 ± 1.00 versus 1.20 ± 0.92 mcg per milliliter; p &lt;0.001). The “on-off” effect was greatly relieved by low protein diets in 3 of 1 1 patients, possibly because of decreased competition for absorption by dietary amino acids. These results suggest that extracerebral metabolism of levodopa may be important in the “on-off” effect.
Effects of the phenethanolamine clenbuterol on protein and lipid metabolism in growing rats (1989)

Zusammenfassung Einfluß des Phenylethanolamins Clenbuterol auf den Protein‐ und Fettstoffwechsel wachsender Ratten Es wurden Untersuchungen an weiblichen Wistar‐Ratten von unterschiedlicher Lebendmasse mit der Referenzsubstanz Clenbuterol durchgeführt, um die ernährungsphysiologische Attraktivität der β‐Agonisten zu beurteilen und um Erkenntnisse über ihren Wirkmechanismus zu gewinnen. Die stimulierenden Effekte von Clenbuterol (25 ppm in der Diät) auf den Zuwachs und die N‐Retention stiegen mit der Lebendmasse zu Behandlungsbeginn. Die ernährungsphysiologische Wirkung der β‐Agonisten scheint also bei hohem Körperfettgehalt und entsprechend geringem Proteinretentionsvermögen am ausgeprägtesten zu sein. Den Eingriff der Substanz in den intermediären Protein‐ und Fettstoffwechsel belegen direkte und indirekte Parameter. Ein gesteigerter Proteinansatz wurde im Stoffwechselversuch (N‐Bilanz) sowie durch die vergleichende Schlachtkörperanalyse nachgewiesen. Der Körperproteingehalt war tendenziell erhöht, die Serumharnstoffkonzentration nach 24 h Fasten signifikant angestiegen. Der Körperfettgehalt und der tägliche Fettansatz wurden dagegen stark reduziert, wie die Schlachtkörperanalyse und die Sektion des perirenalen Fettgewebes zeigten. Entsprechend waren die Blutspiegel an unveresterten Fettsäuren im Fastenzustand erniedrigt. Nach 14‐tägiger Verabreichung von Clenbuterol mit dem Futter (25 ppm) waren die Serumkonzentrationen an Glucose, unveresterten Fettsäuren und insbesondere an Insulin im Vergleich zur unbehandelten Kontrolle deutlich reduziert. Es wird vermutet, daß geringe Insulinspiegel, verbunden mit einer verminderten Insulinsensivität der Fettzellen (Insulinresistenz), zumindest teilweise für die antilipogenen Effekte der β‐Agonisten verantwortlich sind. Die Messung einiger relevanter NADPH‐abhängiger lipogener Enzyme (MDH, G‐6PDH, 6‐PGDH) konnte in dieser Arbeit eine Lipogenesehemmung durch Clenbuterol nicht bestätigen.
Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double‐blind, placebo‐controlled, dose‐ranging study to evaluate efficacy and safety (2007)

Lubiprostone improved SBM rates in a dose-dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk-to-benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.
Inhibition of Platelet-derived Growth Factor-induced Cell Growth Signaling by a Short Interfering RNA for EWS-Fli1 via Down-regulation of Phospholipase D2 in Ewing Sarcoma Cells (2005)

EWS-Fli1, a fusion gene resulting from a chromosomal translocation t(11;22, q24;q12) and found in Ewing sarcoma and primitive neuroectodermal tumors, encodes a transcriptional activator and promotes cellular transformation. However, the precise biological functions of its products remain unknown. To investigate the role of EWS-Fli1 in cell growth signaling, we transfected Ewing sarcoma TC-135 cells with short interfering RNAs for EWS-Fli1. EWS-Fli1 knockdown reduced cell growth and platelet-derived growth factor (PDGF)-BB-induced activation of the growth signaling enzymes. Interestingly, phospholipase D2 (but not the PDGF-BB receptor) showed marked down-regulation in the EWS-Fli1-knocked down TC-135 cells compared with the control cells. In Ewing sarcoma TC-135 cells, the PDGF-BB-induced phosphorylation of growth signaling involving extracellular signal-regulated kinase, Akt, p70S6K, and the expression of cyclin D3 were markedly inhibited by transfection with short interfering RNA phospholipase (PL)-D2. The PDGF-BB-induced activation of growth signaling was also suppressed by 1-butanol, which prevents the production of phosphatidic acid by phospholipase D (but not by t-butyl alcohol), thereby implicating PLD2 in PDGF-BB-mediated signaling in TC-135 cells. These results suggest that EWS-Fli1 may play a role in the regulation of tumor proliferation-signaling enzymes via PLD2 expression in Ewing sarcoma cells.
Towards the selection of phosphorothioate aptamers (2000)

The high affinity of a given nucleic acid for a protein ligand can be used to isolate specific inhibitors of enzymes involved in pathological situations. The latter property is the basis of the SELEX (systematic evolution of ligands by exponential enrichment) technique. Recently, several potent nucleic acids inhibitors of HIV-1 replication have been isolated using the SELEX approach. However, phosphodiester oligodeoxynucleotides (PO-ODNs) were not used as antiviral agents because of their sensitivity to nucleases. Our goal in this work was to explore the possibility of selecting, from a fully substituted phosphorothioate library, oligonucleotides having both a strong affinity for HIV-1 reverse transcriptase (RT) and nuclease resistance. HIV-1 RT initiates in vivo reverse transcription from the 3' end of a host tRNALys. Although phosphorothioate ODNs (PS-ODNs) have been claimed to bind unspecifically to proteins, we have shown previously that an ODN corresponding to the acceptor stem of tRNALys was able to inhibit specifically HIV-1 replication in HIV-1 infected cells, without showing cytotoxicity up to 10 microM. As the SELEX strategy requires 'in vitro' transcription and reverse transcription of the selected DNA, we have assayed the available PS precursors as a model system by using PS-dNTPs and rNTPs. We have also developed an experimental procedure to optimize the incorporation of four PS-dNTPs during the PCR step of the SELEX approach. In the course of this work, we have showed that the PS-dGTP is a strong inhibitor of thermostable DNA polymerases as well as of HIV-1 RT.
Silica Sol-Gel Encapsulation of Pancreatic Islets (1998)

We developed a biocomposite material containing silica ceramic. The sol-gel technology in which ceramic materials are polymerized from liquid solutions at room temperature and physiologic pH can be used to produce ceramics that have a determined pore size and that contain living organisms or cells. Capsules were stable to extreme acid and base conditions as well as to trypsin in vitro for 6 months. We used insulin-secreting murine islet cells as the first mammalian material for encapsulation. Two approaches to generating successful encapsulation of islets were used: drop-tower sphere generation and emulsion. Sphere diameters of less than 1 mm were associated with positive insulin secretory capacity as documented by a static batch incubation technique. Average pore sizes were 161 A for drop-tower spheres and 105 A for emulsion spheres. Capsules allowed the passage of insulin and cytokines but not the passage of antibody. Implantation of encapsulated islets did not result in fibrosis of the capsule in vivo, and retrieval of capsules after 1 month in vivo documented continued insulin secretory capacity. Further in vivo experiments documented increased survival of transplant recipients despite failure to achieve normoglycemia in all but a few cases. Silica sol-gel encapsulation provides a potentially useful alternative for encapsulation of cells for transplantation or drug delivery, and further work is warranted to develop this potentially useful approach for the treatment of diabetes mellitus.
Shape Memory Effect of Bacterial Poly[(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)] (2005)

Abstract Summary: A bacterial poly[(3‐hydroxybutyrate)‐ co ‐(3‐hydroxyvalerate)] biosynthesized by Pseudomonas sp. HJ‐2 was found to be a shape memory polymer. Permanent shapes were set by annealing at room temperature the samples that had been pre‐treated above 95 °C in specified shapes. The temporary shapes were set by stretching and holding the elongated samples. Thermal shrinkage began at 45 °C and stopped at 75 °C to recover to their permanent shapes. Apparently, the orientation induced the formation of hard segments that were responsible for setting the temporary shapes. The shape memory effect of this polymer was explained based on the DSC and XRD results at different phases. The recovery of a coil shape upon heating a strip of HJ‐2 PHB35V, demonstrating the polymers shape memory effect. magnified image The recovery of a coil shape upon heating a strip of HJ‐2 PHB35V, demonstrating the polymers shape memory effect.
Intracerebroventricular enzyme infusion corrects central nervous system pathology and dysfunction in a mouse model of metachromatic leukodystrophy (2011)

Arylsulfatase A (ASA) catalyzes the desulfation of sulfatide, a major lipid component of myelin. Inherited functional deficiencies of ASA cause the lysosomal storage disease (LSD) metachromatic leukodystrophy (MLD), which is characterized by intralysosomal accumulation of sulfatide, progressive neurological symptoms and early death. Enzyme replacement therapy (ERT) using intravenous injection of active enzyme is a treatment option for many LSDs as exogenous lysosomal enzymes are delivered to lysosomes of patient's cells via receptor-mediated endocytosis. Efficient treatment of MLD and other LSDs with central nervous system (CNS) involvement is, however, hampered by the blood-brain barrier (BBB), which limits transfer of therapeutic enzymes from the circulation to the brain parenchyma. To bypass the BBB, we infused recombinant human ASA (rhASA) by implanted miniature pumps into the cerebrospinal fluid (CSF) of a conventional and a novel, genetically aggravated ASA knockout mouse model of MLD. rhASA continuously delivered to the lateral ventricle for 4 weeks penetrated the brain parenchyma and was targeted to the lysosomes of brain cells. Histological analysis revealed complete reversal of lysosomal storage in the infused hemisphere. rhASA concentrations and sulfatide clearance declined with increasing distance from the infusion site. Correction of the ataxic gait indicated reversal of central nervous system dysfunctions. The profound histopathological and functional improvements, the requirement of low enzyme doses and the absence of immunological side effects suggest intracerebroventricular ERT to be a promising treatment option for MLD and other LSDs with prevailing CNS disease.
Effect of hypoxia on the transcription pattern of subunit isoforms and the kinetics of cytochrome c oxidase in cortical astrocytes and cerebellar neurons (2006)

Brain energy metabolism essentially depends on the availability of oxygen representing the energetic substrate for cytochrome c oxidase (COX). The catalytic activity of mammalian COX is regulated by binding of ATP to the N-terminus of subunit IV. This causes an allosteric inhibition of the enzyme at a high energy level and thus plays an important role in adjusting energy production to cellular energy requirements. We have studied COX activity in cortical astrocytes and cerebellar granule cells after normoxia and hypoxia treatment. Differences in the kinetic behaviour of COX from these two brain cell types can be addressed to a differential, but cell type-specific, expression of the COX subunit IV-2 isoform. Besides COX isoform IV-1, which is ubiquitously transcribed in all mammalian tissues, we also detected low levels of COX isoform IV-2 in cerebellar neurons, but not in cortical astrocytes. Under conditions of oxygen deprivation, transcription of COX IV-2 is induced in astrocytes and further up-regulated in cerebellar granule cells. Elevated transcription levels of the COX IV-2 isoform are accompanied by an abolition of the allosteric inhibition of COX by ATP. We conclude that the presence of the COX isoform IV-2 suppresses the sensitivity of COX to its allosteric regulator ATP and overrules the regulation of COX by the cellular energy level. This suggests a pivotal role of COX as an oxygen sensor for brain function.
Platelet rich plasma injection grafts for musculoskeletal injuries: a review (2008)

In Europe and the United States, there is an increasing prevalence of the use of autologous blood products to facilitate healing in a variety of applications. Recently, we have learned more about specific growth factors, which play a crucial role in the healing process. With that knowledge there is abundant enthusiasm in the application of concentrated platelets, which release a supra-maximal quantity of these growth factors to stimulate recovery in non-healing injuries. For 20 years, the application of autologous PRP has been safely used and documented in many fields including; orthopedics, sports medicine, dentistry, ENT, neurosurgery, ophthalmology, urology, wound healing, cosmetic, cardiothoracic, and maxillofacial surgery. This article introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality. In summary, PRP provides a promising alternative to surgery by promoting safe and natural healing. However, there are few controlled trials, and mostly anecdotal or case reports. Additionally the sample sizes are frequently small, limiting the generalization of the findings. Recently, there is emerging literature on the beneficial effects of PRP for chronic non-healing tendon injuries including lateral epicondylitis and plantar fasciitis and cartilage degeneration (Mishra and Pavelko, The American Journal of Sports Medicine 10(10):1-5, 2006; Barrett and Erredge, Podiatry Today 17:37-42, 2004). However, as clinical use increases, more controlled studies are needed to further understand this treatment.
ATRIAL NATRIURETIC HORMONES ORIGINATING FROM THE N‐TERMINUS OF THE ATRIAL NATRIURETIC FACTOR PROHORMONE (1995)

1. Four peptide hormones consisting of amino acids 1-30 (Long Acting Sodium Stimulator), 31-67 (Vessel Dilator), 79-98 (Kaliuretic Stimulator) and 99-126 (atrial Natriuretic Factor [ANF]) originate from the same 126 amino acid ANF prohormone. 2. Each of these four peptide hormones circulates as a distinct peptide with vessel dilator and long acting sodium stimulator circulating at 10- to 24-fold higher concentrations than ANF while kaliuretic stimulator circulates at a three-fold higher concentration than ANF. 3. Each of these peptide hormones is released with an increase in central volume causing stretch of the atrium of the heart and with rapid heart beats greater than 125 beats/min. 4. Each of these peptide hormones lowers blood pressure, causes a diuresis and enhances sodium and/or potassium excretion. 5. In disease states which retain sodium and water such as congestive heart failure (CHF), each of these atrial peptides increases in the circulation proportionately to the severity of sodium retention, but of the radioimmunoassays to each of these hormones only the vessel dilator radioimmunoassay differentiates between mild (class I) CHF and healthy individuals.
Collaboration using multiple PDAs connected to a PC (1998)

The Pebbles research project is investigating how the functionality and the user interface can be spread across all of the computing and input / output devices that one or more users have available. In this way, the hand-held devices can be used to augment the other computers rather than just being a replacement when other computers are not available. As part of this research, we are looking at how multiple people can use their hand-helds to share control of a main computer running either legacy applications, or custom multi-person applications. We are also looking at how information and control can be fluidly moved between the main screen and the individual hand-held screens.
Ascertaining how much compliance is enough with outpatient antibiotic regimens. (1992)

Compliance with outpatient antibiotic regimens can now be measured by electronically monitoring the time history of dosing. This new approach reveals that many patients comply only partially with prescribed regimens in randomized, controlled, outpatient trials. Omitted or delayed doses and early cessation of dosing are commonly observed. Partial compliance converts a fixed-dose trial into a set of natural experiments in dose ranging, presenting a variety of patterns of dose timing that can be correlated with clinical outcomes for an estimate of minimum compliance needed for satisfactory outcome. Reliable measures indicate little difference in compliance between once- and twice-daily regimens, but considerably higher rates of omitted doses with three-times-daily or four-times-daily dosing. A key practical issue is to ensure continuity of drug action in the face of the most common compliance errors. Continuity of action is more likely when the prescribed interval between doses is considerably shorter, preferably half or less, than the drug's duration of action, allowing doses occasionally to be delayed or omitted without a gap in drug action. Thus, a twice-daily regimen may be expected to maintain crucial continuity of drug action better than a once-daily regimen, even if a few more doses are missed. Errors to avoid in compliance with outpatient antibiotic regimens are prolonged intervals between doses and early cessation of treatment.
Degradation of peptides to diketopiperazines: application of Pyrolysis–gas chromatography to sequence determination in actinomycins (1971)

Pyrolysis–gas chromatography of peptides permits identification of diketopiperazines derived from adjacent amino-acid pairs; utilization of this technique for obtaining sequence information is illustrated by its application to four actinomycins.
Identification of rat lung-specific microRNAs by microRNA microarray: valuable discoveries for the facilitation of lung research (2007)

The identified lung-specific miRNAs from this work will facilitate functional studies of miRNAs during normal physiological and pathophysiological processes of the lung.