gebhart/patrepeval huggingface dataset:
Intermittent vs Continuous Levodopa Administration in Patients With Advanced Parkinson Disease (2005)

This study confirms that a continuous levodopa infusion is associated with reduced motor complications compared with the standard oral formulation of the drug in patients with advanced PD. Pharmacokinetic studies demonstrate that reduced motor complications are associated with avoiding low plasma levodopa trough levels and are not adversely affected by relatively high plasma levodopa concentrations. We propose that if levodopa/carbidopa could be administered orally in a manner that mirrors the pharmacokinetic pattern of the infusion, it might lead to a similar reduction in motor complications.
Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I (2008)

4F is an anti-inflammatory, apolipoprotein A-I (apoA-I)-mimetic peptide that is active in vivo at nanomolar concentrations in the presence of a large molar excess of apoA-I. Physiologic concentrations ( approximately 35 microM) of human apoA-I did not inhibit the production of LDL-induced monocyte chemotactic activity by human aortic endothelial cell cultures, but adding nanomolar concentrations of 4F in the presence of approximately 35 microM apoA-I significantly reduced this inflammatory response. We analyzed lipid binding by surface plasmon resonance. The anti-inflammatory 4F peptide bound oxidized lipids with much higher affinity than did apoA-I. Initially, we examined the binding of PAPC (1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine) and observed that its oxidized products bound 4F with an affinity that was approximately 4-6 orders of magnitude higher than that of apoA-I. This high binding affinity was confirmed in studies with defined lipids and phospholipids. 3F-2 and 3F(14) are also amphipathic alpha-helical octadecapeptides, but 3F-2 inhibits atherosclerosis in mice and 3F(14) does not. Like 4F, 3F-2 also bound oxidized phospholipids with very high affinity, whereas 3F(14) resembled apoA-I. The extraordinary ability of 4F to bind pro-inflammatory oxidized lipids probably accounts for its remarkable anti-inflammatory properties.
JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model (2006)

Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia associated with a poor prognosis. However, there are relatively few insights into the genetic etiology of AMKL. We developed a screening assay for mutations that cause AMKL, based on the hypothesis that constitutive activation of STAT5 would be a biochemical indicator of mutation in an upstream effector tyrosine kinase. We screened human AMKL cell lines for constitutive STAT5 activation, and then used an approach combining mass spectrometry identification of tyrosine phosphorylated proteins and growth inhibition in the presence of selective small molecule tyrosine kinase inhibitors that would inform DNA sequence analysis of candidate tyrosine kinases. Using this strategy, we identified a new JAK2T875N mutation in the AMKL cell line CHRF-288-11. JAK2T875N is a constitutively activated tyrosine kinase that activates downstream effectors including STAT5 in hematopoietic cells in vitro. In a murine transplant model, JAK2T875N induced a myeloproliferative disease characterized by features of AMKL, including megakaryocytic hyperplasia in the spleen; impaired megakaryocyte polyploidization; and increased reticulin fibrosis of the bone marrow and spleen. These findings provide new insights into pathways and therapeutic targets that contribute to the pathogenesis of AMKL.
Induction of Glutathione S-Transferases in Arabidopsis by Herbicide Safeners (2002)

Herbicide safeners increase herbicide tolerance in cereals but not in dicotyledenous crops. The reason(s) for this difference in safening is unknown. However, safener-induced protection in cereals is associated with increased expression of herbicide detoxifying enzymes, including glutathione S-transferases (GSTs). Treatment of Arabidopsis seedlings growing in liquid medium with various safeners similarly resulted in enhanced GST activities toward a range of xenobiotics with benoxacor, fenclorim, and fluxofenim being the most effective. Safeners also increased the tripeptide glutathione content of Arabidopsis seedlings. However, treatment of Arabidopsis plants with safeners had no effect on the tolerance of seedlings to chloroacetanilide herbicides. Each safener produced a distinct profile of enhanced GST activity toward different substrates suggesting a differential induction of distinct isoenzymes. This was confirmed by analysis of affinity-purified GST subunits by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. AtGSTU19, a tau class GST, was identified as a dominant polypeptide in all samples. When AtGSTU19 was expressed in Escherichia coli, the recombinant enzyme was highly active toward 1-chloro-2,4-dinitrobenzene, as well as chloroacetanilide herbicides. Immunoblot analysis confirmed that AtGSTU19 was induced in response to several safeners. Differential induction of tau GSTs, as well as members of the phi and theta classes by safeners, was demonstrated by RNA-blot analysis. These results indicate that, although Arabidopsis may not be protected from herbicide injury by safeners, at least one component of their detoxification systems is responsive to these compounds.
A novel variant of human Grb7 is associated with invasive esophageal carcinoma. (1998)

The cDNAs of a putative growth factor-bound (Grb) 7 signal transduction molecule and Grb7V novel splice variant were isolated from an invasive human esophageal carcinoma. Although both Grb7 isoforms share homology with the Mig-10 cell migration gene, the Grb7V isoform lacks 88 base pairs in the C terminus; the resultant frame shift leads to substitution of an SH2 domain with a short hydrophobic sequence. The wild-type Grb7 protein, but not the Grb7V isoform, is rapidly tyrosyl phosphorylated in response to EGF stimulation in esophageal carcinoma cells. Analysis of human esophageal tumor tissues and regional lymph nodes with metastases revealed that Grb7V was expressed in 40% of Grb7-positive esophageal carcinomas. More importantly, Grb7V expression was enhanced after metastatic spread to lymph nodes as compared to the original tumor tissues. Finally, transfection of an antisense Grb7 RNA expression construct lowered endogenous Grb7 protein levels and suppressed the invasive phenotype exhibited by esophageal carcinoma cells. These findings suggest that Grb7 isoforms are involved in cell invasion and metastatic progression of human esophageal carcinomas.
Integrated Review of the Association of Cytokines With Fibromyalgia and Fibromyalgia Core Symptoms (2009)

Fibromyalgia (FMS) is a chronic widespread pain (CWP) and fatigue syndrome that affects three to six million adults in the United States. Core symptoms of FMS include pain, fatigue, and mood and sleep disturbances. To date, consensus has not been reached among researchers regarding the pathogenesis of FMS nor the specific role of cytokine activation on the neuroendocrine-immune response patterns in persons with FMS. The purpose of this article is to describe and synthesize the results of research studies focused on the relationship between cytokines and FMS and among cytokines and core symptoms of FMS. There is some support in the literature for relationships among FMS symptoms and cytokines; however, there are discrepant findings related to whether proinflammatory and anti-inflammatory cytokines are elevated or reduced in persons with FMS and whether their levels correlate with the core symptoms of this disorder. Although the use of cytokine biomarkers must be considered exploratory at this time due to the lack of consistent empirical findings, biobehavioral research focused on understanding the relationship of FMS with cytokines may lead to a better understanding of this complex syndrome. This knowledge may ultimately contribute to the development of interventions for symptom management that address not only the symptom manifestation but also a biological mediator of symptoms.
Case 16.16 (2014)

82-year-old woman with drug-resistant hypertension and a blood pressure discrepancy between upper and lower extremities MIP image from 3D CE MRA of the thoracic aorta (Figure 16.16.1) shows an irregular filling defect in the distal thoracic aorta, which causes significant narrowing of the aorta. Coronal oblique reformatted image from the 3D CE MRA (...
Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials (2015)

These results provide physicians and health care regulatory agencies with RCT-based evidence on efficacy and acceptability of currently available breast cancer CPAs; at the same time, we pinpoint how much work still remains to be done before pharmacological primary prevention becomes a routine option to reduce the burden of this disease.
Ehrlichia ewingii,a Newly Recognized Agent of Human Ehrlichiosis (1999)

These findings provide evidence of E. ewingii infection in humans. The associated disease may be clinically indistinguishable from infection caused by E. chaffeensis or the agent of human granulocytic ehrlichiosis.
Tolerance and safety of cangrelor, a novel purin receptor antagonist, used as a platelet aggregation inhibitor in the acute coronary syndrome (2000)

Tolerance and safety of cangrelor, a novel purin receptor antagonist, used as a platelet aggregation inhibitor in the acute coronary syndrome
Core-Directed Protein Design. II. Rescue of a Multiply Mutated and Destabilized Variant of Ubiquitin (1999)

We have applied the method described in the preceding paper [Finucane, M. D., et al. (1999) Biochemistry 38, 11604-11612], namely, stability-based selection using phage display, to explore the sequence requirements for packing in the hydrophobic core of ubiquitin. In contrast to the parent protein, which was a structurally compromised mutant, the selected variants could be overexpressed and purified in yields for structural studies. In particular, CD and NMR measurements showed that the selectants folded correctly to stable native-like structures. These points demonstrate the utility of our core-directed method for stabilizing and redesigning proteins. In addition and in contrast to foregoing studies on other proteins, which suggest that hydrophobic cores permit substitutions provided that hydrophobicity and core volumes are generally conserved, we find that the core of ubiquitin is surprisingly intolerant of amino acid substitutions; variants that survived our selection showed a clear consensus for the wild-type sequence. It is probable that our results differed from those from other groups for two reasons. First, ubiquitin may be unusual in that it has strict sequence requirements for its structure and stability. We discuss this result in light of sequence conservation in the eukaryotic ubiquitins and proteins of the ubiquitin structural superfamily. Second, our mutants were selected solely on the basis of stability, in contrast to the other studies that rely on function-based selection. The latter may lead to proteins that are more plastic and tolerant of substitutions.
Genetically Engineered Resistance to Fusarium Head Blight in Wheat by Expression of Arabidopsis NPR1 (2006)

Fusarium head blight (FHB) is a devastating disease of wheat and barley which causes extensive losses worldwide. Monogenic, gene-for-gene resistance to FHB has not been reported. The best source of resistance to FHB is a complex, quantitative trait derived from the wheat cv. Sumai 3. Here, we show that the Arabidopsis thaliana NPR1 gene (AtNPR1), which regulates the activation of systemic acquired resistance, when expressed in the FHB-susceptible wheat cv. Bobwhite, confers a heritable, type II resistance to FHB caused by Fusarium graminearum. The heightened FHB resistance in the transgenic AtNPRI -expressing wheat is associated with the faster activation of defense response when challenged by the fungus. PR1 expression is induced rapidly to a high level in the fungus-challenged spikes of the AtNPR1-expressing wheat. Furthermore, benzothiadiazole, a functional analog of salicylic acid, induced PR1 expression faster and to a higher level in the AtNPR1-expressing wheat than in the nontransgenic plants. We suggest that FHB resistance in the AtNPR1-expressing wheat is a result of these plants being more responsive to an endogenous activator of plant defense. Our results demonstrate that NPR1 is an effective candidate for controlling FHB.
Evolutionary optimised ontogenetic neural networks with incremental problem complexity during development (2002)

In order to optimise unconstrained, large neural network structures with evolutionary algorithms, indirect encodings have been proposed. However, if the evolutionary process is combined with network learning, which is sensible both with respect to technical applications in dynamical environments and to the biological paragon, a way has to be found to combine learning with the evolutionary optimisation of such large structures. Utilising the development of neural systems during ontogeny seems a logical starting point for the realization of a step by step learning in networks. Furthermore, the combination of network growth during the developmental phase with an incremental problem complexity might allow the optimisation of large network structures together with learning. The author proposes a model to simulate such a combined approach and applies it to the problem of time series modelling. By introducing several measures for the transfer of information from one developmental step to the next, we will be able to quantitatively analyse the behaviour of the proposed model.
Statistical Image Reconstruction for Muon Tomography Using a Gaussian Scale Mixture Model (2009)

Muon tomography is a novel imaging technique that uses background cosmic radiation to inspect vehicles or cargo containers for detecting the transportation or smuggling of heavy nuclear materials. Empirically, muon scattering data are modeled as zero-mean Gaussian random variables with variance being a function of the atom number and density of the scattering material. However, a single Gaussian distribution cannot model the tail of the true distribution and hence results in noisy reconstructed images. In this paper, we propose a Gaussian scale mixture (GSM) to approximate the true distribution of muon data. The GSM follows the true distribution more closely than a single Gaussian model. We have derived a maximum <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">a</i> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">posteriori</i> (MAP) reconstruction algorithm based on the GSM likelihood. Localization receiver operating characteristics (LROC) studies were performed using computer simulated data to evaluate the new algorithm. The results show that the use of GSM improves the detection performance significantly over that of the traditional Gaussian likelihood.
Ni(III)/(IV) Bis(dicarbollide) as a Fast, Noncorrosive Redox Shuttle for Dye-Sensitized Solar Cells (2010)

Nickel bis(dicarbollide) is used as a fast, one-electron outer sphere redox couple in dye-sensitized solar cells. Device performances with this anionic shuttle are investigated with different electrolyte concentrations and additives, using only 0.030 M of the Ni(III) bis(dicarbollide) to efficiently regenerate the ruthenium dye. Atomic layer deposition of Al(2)O(3) on the nanoparticulate TiO(2) photoanodes is further used to improve device performances, increasing current densities almost 2-fold and attaining power conversion efficiencies approximately 10x greater than its metallocene analogue, ferrocene/ferrocenium. Open-circuit voltage decay is used to probe the kinetics of the Ni(III)/(IV) bis(dicarbollide) redox couple, and electron interception is found to be approximately 10(3)x slower than ferrocene/ferrocenium, explaining the large discrepancy in open-circuit voltage potentials between these two redox shuttles.
Site-Specific Organization of Gold Nanoparticles by Biomolecular Templating (2001)

The synthesis of planar arrays of metal nanoparticles is an important goal in nanotechnology. As shown in the picture, superlattices of gold nanoparticles are readily assembled by biomolecular templating using bacterial S-layer membranes. Only nanoparticles of certain size and charge are organized in regular patterns, suggesting that arrays with controlled interparticle spacings should be possible by this method.
An electrically evoked slow potential of the frog's retina. I. Properties of response (1975)

1. Brief pulses of electrical current passed through the frog's eye cup from sclera to vitreous (inward current) evoked large, vitreous positive slow potentials of retinal origin. Brief pulses of outward current evoke no response. 2. This electrically evoked retinal response (EERG) increased sharply in amplitude as the strength of the stimulus was increased. 3. Strength-duration curves showed that the stimulating pulse was integrated with a time constant ranging from 14 to 36 ms. The time constant was a function of the amplitude chosen as a criterion. 4. The EERG was abolished by chemical agents which abolish the PII component of the ERG (KCl, NH3, aspartate). 5. The waveform of the EERG returned to the base line with exactly the same time course as the PII component of the ERG, both when the PII was evoked by flashes of light and when it was evoked by flashes of darkness. 6. These results can be explained in terms of the hypothesis that electrical stimuli act on the synaptic terminals of the photoreceptor cells.
Interleukin 1 releases histamine from human basophils and mast cells in vitro. (1987)

Interleukin (IL 1) preparations from five different sources (human monocyte, LPS-stimulated, purified IL 1 from two different laboratories) and human recombinant IL 1 (HrIL 1) were shown to be capable of directly inducing histamine (HA) release from human basophils (10 to 50% of total cellular HA, depending on the source of IL 1). The release was not due to the medium, pyrogens, or other contaminants. Il 1-induced HA release was dose dependent between 1 to 100 U/ml of IL 1 and 1 to 15 ng/ml of HrIL 1 and was rapid, with a peak release at 15 min. HA release induced by IL 1 was blocked completely by preexposure of cells to IL 1 but was not affected by prechallenge with anti-IgE. Also, preincubation of IL 1 with anti-IL 1 antibody abolished the HA-releasing activity. IL 1-induced HA release was also observed in preparations of human adenoidal mast cells. Our data indicate that it is unlikely that the HA release induced by IL 1 is due to a contamination with HA-releasing factor. This effect of IL 1 provides a mechanism for non-IgE-related local HA release and raises the possibility of a link between cellular immunity and immediate hypersensitivity of potential importance for the pathology of immuno/inflammatory diseases.
Identification of human gene functional regions based on oligonucleotide composition. (1993)

Accurate recognition of coding and intron regions within large regions of uncharacterized genomic DNA is an unsolved problem. A data base of more than 4,240,791 bp coding and 7,790,682 bp noncoding human sequences was extracted from GenBank to develop a function for locating coding regions in anonymous sequences. Several coding measures based on oligonucleotide preferences were tested on a control set that including 1/3 of all extracted sequences. An accuracy of separation of coding/noncoding regions is 87% for 9 bp oligonucleotides on 54 bp windows and 91% on 108 bp windows, respectively. For separation of coding/intron regions the accuracy is 89-90% for 8 bp oligonucleotides on 54 bp windows and up to 95% on 108 bp windows. Using the information about preferences of octanucleotides in protein coding and intron regions and significant triplet frequencies as a function of position near splice junctions, a joint splice site prediction scheme was developed. The accuracy of the joint scheme for predicting splice site positions on the test set was about 96-97%, which exceeds the accuracy of the previously reported splice site selection method based on a more complex artificial neural network approach. A model of splicing using poly-G(C) rich exon flanking sequences is suggested. A remarkable difference of oligonucleotide composition 5'- and 3'- gene regions is displayed and applied in a gene structure predictive system.
Team-based access control (TMAC) (1997)

In this paper, we introduce the notion of TeaM-based Access Control (TMAC) as an approach to applying rolebased access control in collaborative environments. Our focus is on collaborative activity that is best accomplished through organized teams. Thus, central to the TMAC approach is the notion of a "team" as an abstraction that encapsulates a collection of users in specific roles with the objective of accomplishing a specific task or goal. We were led to the idea of TMAC when our investigations revealed two interesting requirements for certain collaborative environments. The first was the need for a hybrid access control model that incorporated the advantages of broad, role-based permissions across object types, yet required fine-grained, identity-based control on individual users in certain roles and to individual object instances. The second was a need to distinguish the passive concept of permission assignment from the active concept of context-based permission activation. It remains to be seen whether these requirements should lead to yet another variation of one or more models of RBAC, or whether such requirements and TMAC concepts should form another access control model layered on top of RBAC. It is hoped the RBAC workshop will help researchers advance discussions on this issue.
Direkte Aminierung von sekundären Alkoholen mit Ammoniak (2010)

Wasserstoff-„Shuttling“ vom Alkohol auf einen Katalysator und von dort auf das Imin ermöglichte die erste direkte Umsetzung sekundärer Alkohole mit Ammoniak zu primären Aminen. Unter Verwendung einfacher Ruthenium-Phosphan-Katalysatoren wurden Ausbeuten bis 99 % erzielt. R1, R2 = Alkyl, Aryl, Alkenyl; M=[Ru3(CO)12]; L=Phosphanligand. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.