gebhart/patrepeval huggingface dataset:
Peroxisome proliferator–activated receptor (PPAR)α expression in T cells mediates gender differences in development of T cell–mediated autoimmunity (2007)

Peroxisome proliferator-activated receptor (PPAR)alpha is a nuclear receptor that mediates gender differences in lipid metabolism. PPARalpha also functions to control inflammatory responses by repressing the activity of nuclear factor kappaB (NF-kappaB) and c-jun in immune cells. Because PPARalpha is situated at the crossroads of gender and immune regulation, we hypothesized that this gene may mediate sex differences in the development of T cell-mediated autoimmune disease. We show that PPARalpha is more abundant in male as compared with female CD4(+) cells and that its expression is sensitive to androgen levels. Genetic ablation of this gene selectively removed the brake on NF-kappaB and c-jun activity in male T lymphocytes, resulting in higher production of interferon gamma and tumor necrosis factor (but not interleukin 17), and lower production of T helper (Th)2 cytokines. Upon induction of experimental autoimmune encephalomyelitis, male but not female PPARalpha(-/-) mice developed more severe clinical signs that were restricted to the acute phase of disease. These results suggest that males are less prone to develop Th1-mediated autoimmunity because they have higher T cell expression of PPARalpha.
Biosensors Based on Aligned Carbon Nanotubes Coated with Inherently Conducting Polymers (2003)

Abstract The use of multiwalled aligned carbon nanotubes provides a novel electrode platform for inherently conducting polymer based biosensors. The example used here to highlight the usefulness of such a platform is the polypyrrole based glucose oxidase system for detection of glucose. The use of these three dimensional electrodes offers advantages in that large accessible enzyme loadings can be obtained within an ultrathin layer. It has also been found that the detection of H 2 O 2 at these new electrode structures containing iron loaded nanotube tips can be achieved at low anodic potentials. The result is a sensitive and selective glucose sensor.
Enzyme Replacement Therapy for Gaucher Disease: Skeletal Responses to Macrophage-targeted Glucocerebrosidase (1995)

Prolonged treatment over 3 1/2 years with macrophage-targeted glucocerebrosidase produces objective reversal of disease in both the axial and appendicular skeleton in patients with Gaucher disease. Marked improvement occurs in marrow composition and bone mass in both children and adults.
Database and Knowledge Base Integration – A Data Mapping Method for Arden Syntax Knowledge Modules (1996)

One of the most important categories of decision-support systems in medicine are data driven systems where the inference engine is linked to a database. It is, therefore, important to find methods that facilitate the implementation of database queries referred to in the knowledge modules. A method is described for linking clinical databases to a knowledge base with Arden Syntax modules. The method is based on a query meta-database including templates for SQL queries which is maintained by a database administrator. During knowledge module authoring the medical expert refers only to a code in the query meta-database; no knowledge is needed about the database model or the naming of attributes and relations. The method uses standard tools, such as C+2 and ODBC, which makes it possible to implement the method at many platforms and to link to different clinical databases in a standardized way.
Safety and tolerability of antagonist anti‐human CD40 Mab ch5D12 in patients with moderate to severe Crohn's disease (2005)

Antagonizing CD154-CD40 interactions with ch5D12 is a promising therapeutic approach for remission induction in Crohn's disease.
A non-glycosylated, plant-produced human monoclonal antibody against anthrax protective antigen protects mice and non-human primates fromB. anthracisspore challenge (2011)

The health and economic burden of infectious diseases in general and bioterrorism in particular necessitate the development of medical countermeasures. One proven approach to reduce the disease burden and spread of pathogen is treatment with monoclonal antibodies (mAb). mAbs can prevent or reduce severity of the disease by variety of mechanisms, including neutralizing pathogen growth, limiting its spread from infected to adjacent cells, or by inhibiting biological activity of toxins, such as anthrax lethal toxin. Here, we report the production of glycosylated (pp-mAb (PA) ) and non-glycosylated (pp-mAb (PANG) ) versions of a plant-derived mAb directed against protective antigen (PA) of Bacillus anthracis in Nicotiana benthamiana plants using agroinfiltration. Both forms of the antibody were able to neutralize anthrax lethal toxin activity in vitro and protect mice against an intraperitoneal challenge with spores of B. anthracis Sterne strain. A single 180 µg intraperitoneal dose of pp-mAb (PA) or pp-mAb (PANG) provided 90% and 100% survival, respectively. When tested in non-human primates, pp-mAb (PANG) was demonstrated to be superior to pp-mAb (PA) in that it had a significantly longer terminal half-life and conferred 100% protection against a lethal dose of aerosolized anthrax spore challenge after a single 5 mg/kg intravenous dose compared to a 40% survival rate conferred by pp-mAb (PA) . This study demonstrates the potential of a plant-produced non-glycosylated antibody as a useful tool for the treatment of inhalation anthrax.
Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor. (1992)

Based on the knowledge that neutrophil elastase (NE) in cystic fibrosis (CF) epithelial lining fluid (ELF) can induce human bronchial epithelial cells to express the gene for interleukin 8 (IL-8), an 8.5-kD neutrophil chemoattractant, we have evaluated CF ELF for the presence of IL-8, and investigated the ability of aerosolized recombinant secretory leukoprotease inhibitor (rSLPI) to suppress NE, and hence IL-8, levels on the respiratory epithelial surface in CF. Enzyme-linked immunoassay revealed 21.9 +/- 4.8 nM IL-8 in CF ELF compared with none in normals. Active NE was detectable in ELF of all individuals with CF and was significantly decreased (P < 0.03) after aerosolization of rSLPI. Human bronchial epithelial cells exposed to CF ELF recovered before rSLPI therapy expressed IL-8 mRNA transcripts, but ELF recovered after rSLPI therapy induced far less bronchial epithelial cell IL-8 gene expression. Consistent with this, rSLPI aerosol therapy caused a marked reduction in CF ELF IL-8 levels (P < 0.05) and neutrophil number (P < 0.02). There was also a clear association between CF ELF active NE and IL-8 levels (r = 0.94). These data suggest that rSLPI therapy not only suppresses respiratory epithelial NE levels, but also breaks a cycle of inflammation on the CF epithelial surface.
Outer Membrane Proteins as a Carrier for Detoxified Lipooligosaccharide Conjugate Vaccines for NontypeableHaemophilus influenzae (1999)

Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media and respiratory tract infections. Outer membrane proteins (OMP) and lipooligosaccharide (LOS) are major surface antigens of NTHi and potential vaccine candidates. De-O-acylated LOS (dLOS) or oligosaccharide (OS) was coupled to total OMP to form dLOS-OMP and OS-OMP conjugates, while a dLOS-tetanus toxoid (TT) was synthesized for comparison. These conjugates were evaluated in mice and rabbits for immunogenicity. dLOS-OMP elicited a better boostable antibody response against LOS than did dLOS-TT, while OS-OMP was not immunogenic. Formulation of the conjugates with Ribi adjuvant significantly enhanced the immunogenicity of dLOS-OMP and dLOS-TT but not that of OS-OMP. In addition, rabbit antisera elicited by dLOS-OMP but not dLOS-TT (or OMP alone) demonstrated bactericidal activity against 40% of the NTHi strains tested. These results indicate that dLOS is a better derivative of LOS than OS and that OMP is a good carrier for NTHi LOS-based conjugate vaccines.
Raman spectroscopic study of glutaraldehyde-stabilized collagen and pericardium tissue (2003)

Abstract For the first time, Raman spectroscopy has been employed to investigate formation of cross-links in collagen and porcine pericardium tissue upon glutaraldehyde (GA) treatment. GA treatment causes a very high fluorescence background, which overlaps Raman bands. It has been found that short fixation time, i.e. 2 h, reduces background radiation significantly, providing new possibilities for studying changes in molecular structure of collagen upon GA modification. The observed changes in position and intensity of Raman bands allowed us to recognize different types of GA–collagen interactions. Strong spectral evidence has been found for the peptide contribution to the formation of the GA–collagen cross-links and for the formation of secondary amines via Schiff base intermediates, and pyridinium-type cross-links. The results also revealed that different hydration levels and a more complex structure of intact tissue in comparison to collagen preparation strongly influence the formation of a GA cross-linking network, e.g. ether-type bond is preferred to form in a less hydrated collagen preparation. Our results have shown that GA treatment causes an increase in water content of pericardium tissue and collagen. Keywords: RAMAN SPECTROSCOPYGLUTARALDEHYDECOLLAGENCROSS-LINKING
Structure of a Bag/Hsc70 Complex: Convergent Functional Evolution of Hsp70 Nucleotide Exchange Factors (2001)

Bag (Bcl2-associated athanogene) domains occur in a class of cofactors of the eukaryotic chaperone 70-kilodalton heat shock protein (Hsp70) family. Binding of the Bag domain to the Hsp70 adenosine triphosphatase (ATPase) domain promotes adenosine 5'-triphosphate-dependent release of substrate from Hsp70 in vitro. In a 1.9 angstrom crystal structure of a complex with the ATPase of the 70-kilodalton heat shock cognate protein (Hsc70), the Bag domain forms a three-helix bundle, inducing a conformational switch in the ATPase that is incompatible with nucleotide binding. The same switch is observed in the bacterial Hsp70 homolog DnaK upon binding of the structurally unrelated nucleotide exchange factor GrpE. Thus, functional convergence has allowed proteins with different architectures to trigger a conserved conformational shift in Hsp70 that leads to nucleotide exchange.
Molecular Aspects of Renal Handling of Aminoglycosides and Strategies for Preventing the Nephrotoxicity (2004)

Aminoglycosides such as gentamicin and amikacin are the most commonly used antibiotics worldwide in the treatment of Gram-negative bacterial infections. However, serious complications like nephrotoxicity and ototoxicity are dose-limiting factors in the use of aminoglycosides. A relatively large amount of the intravenously administered dose is accumulated in the kidney (about 10% of dose), whereas little distribution of aminoglycosides to other tissues is observed. Aminoglycosides are taken up in the epithelial cells of the renal proximal tubules and stay there for a long time, resulting in nephrotoxicity. Acidic phospholipids are considered as a binding site for aminoglycosides in the brush-border membrane of the proximal tubular cells. More recently, it has been reported that megalin, a giant endocytic receptor abundantly expressed at the apical membrane of renal proximal tubules, plays an important role in binding and endocytosis of aminoglycosides in the proximal tubular cells. The elucidation of the aminoglycoside-binding receptor would help design a strategy to prevent against aminoglycoside-induced nephrotoxicity. In this review, we summarize recent advances in the understandings of the molecular mechanisms responsible for renal accumulation of aminoglycosides, especially megalin-mediated endocytosis. In addition, approaches toward prevention of aminoglycoside-induced nephrotoxicity are discussed, based on the molecular mechanisms of the renal accumulation of aminoglycosides.
Observation of Raman G-Peak Split for Graphene Nanoribbons with Hydrogen-Terminated Zigzag Edges (2011)

Raman scattering of individual hydrogen-terminated zigzag-edged graphene nanoribbons (Z-GNRs) was studied with focus on the G-peak. In addition to the bulk graphene G-peak appearing at ∼1594 cm(-1) (G(+)), an edge-related G-peak at ∼1583 cm(-1) (G(-)) was observed for Z-GNRs. This additional Raman vibrational mode originates from the zigzag edges where localized metallic edge states are present. The relative intensity ratio G(-)/G(+) displays a strong dependence on the ribbon width (W). It increases gradually with decreasing W, and the G(+) finally vanishes at W = 5(±3) nm. Polarized Raman scattering was also employed to confirm the four-fold symmetry of the split TO modes, and the results are in good agreement with previous theoretical predictions. Our work offers the first direct experimental evidence to confirm the validity of predicted Raman scattering of GNRs.
A morphogen gradient of Wnt/β-catenin signalling regulates anteroposterior neural patterning inXenopus (2001)

Anteroposterior (AP) patterning of the vertebrate neural plate is initiated during gastrulation and is regulated by Spemann's organizer and its derivatives. The prevailing model for AP patterning predicts a caudally increasing gradient of a 'transformer' which posteriorizes anteriorly specified neural cells. However, the molecular identity of the transforming gradient has remained elusive. We show that in Xenopus embryos (1) dose-dependent Wnt signalling is both necessary and sufficient for AP patterning of the neuraxis, (2) Wnt/beta-catenin signalling occurs in a direct and long-range fashion within the ectoderm, and (3) that there is an endogenous AP gradient of Wnt/beta-catenin signalling in the presumptive neural plate of the Xenopus gastrula. Our results indicate that an activity gradient of Wnt/beta-catenin signalling acts as transforming morphogen to pattern the Xenopus central nervous system.
Basic Mechanisms of TMS (2002)

Transcranial magnetic stimulation (TMS) is now established as an important noninvasive measure for neurophysiologic investigation of the central and peripheral nervous systems in humans. Magnetic stimulation can be used for stimulating peripheral nerves with a similar mechanism of activation as for electrical stimulation. When TMS is applied to the cerebral cortex, however, some features emerge that distinguish it from transcranial electrical stimulation. One of the most important features is designated the D and I wave hypothesis, which is now widely accepted as a mechanism of TMS of the motor cortex. Transcranial electrical stimulation excites the pyramidal tract axons directly, either at the initial segment of the neuron or at proximal internodes in the subcortical white matter, giving rise to D (direct) waves, whereas TMS excites the pyramidal neurons transsynaptically, giving rise to I (indirect) waves. There are still other phenomena with mechanisms that remain to be elucidated. First, not only excitatory effects but also inhibitory effects can be elicited by TMS of the cerebral cortex (e.g., the silent period and intracortical inhibition). The inhibitory effect may also be used to investigate cerebral functions other than the motor cortex, such as the visual, sensory cortices, and the frontal eye field, from which no overt response like the motor evoked potential can be elicited. Second, there is an abundance of intraregional functional connectivities among different cortical areas that can also be revealed by TMS, or TMS in combination with neuroimaging techniques. Last, repetitive transcranial stimulation exerts a lasting effect on brain function even after the stimulation has ceased. With further investigation of the neural mechanisms of TMS, these techniques will open up new possibilities for investigating the physiologic function of the brain as well as opportunities for clinical application.
Government Executive and Policy Reform in Japan (2006)

This paper argues that institutional constraints play a crucial role in effectively executing policy reform processes. From the perspective of historical institutionalism, it explains that when institutional constraints typified by political parties, bureaucracy, and businesses, yielded strong influences on the government executive, policy reform proved to be difficult and tedious as seen in the reform process of Japan after 1993. However, as seen in the reform process of Japan during the Koizumi government, policy reform process showed positive signs of success as the same institutional constraints have exhibited deterioration and weaknesses since 2003 which made it easy for the Koizumi government to pursue what was necessary in overcoming an economic recession. In particular strong stance of Koizumi against his political party and subsequent announcement of a snap election will be an important milestone for his continuing policy reform efforts.
Reassessment of the clinical significance of native dna antibodies in systemic lupus erythematosus (1979)

Abstract To further clarify the clinical significance of nDNA antibodies in systemic lupus erythematosus, 70 patients were studied longitudinally over an average period of 3 years each. Serum hemolytic complement (CH50) and nDNA antibodies measured by antigen binding and complement fixation were assessed during episodes of clinically inactive and active disease. Only slightly more than half of episodes of active disease were associated with low CH50 and high nDNA binding, and there was a significant occurrence of high nDNA binding or low CH50 with inactive disease. In contrast, nDNA antibodies measured by complement fixation were never present in the absence of clinical disease. Complement fixing nDNA antibodies were associated mainly with episodes of renal disease, whereas all types of disease activity except those involving predominantly the central nervous system (CNS) showed some correlation with the combined parameters of low CH50 and high nDNA binding. Most episodes of CNS disease occurred without CH50 depression or high nDNA binding. Disease activity was less commonly associated with only low CH50 or high nDNA binding. However, when rash was the predominant manifestation, low CH50 alone was frequently present. The CH50 test correlated with disease activity better than the nDNA antibody binding or complement fixation tests. However, as illustrated by longitudinal studies, a combination of these assays provided the best monitoring of disease activity. Contrary to recent reports, IgG/IgM nDNA antibody ratios did not correlate with disease activity. Studies on isolated nDNA antibody populations provided evidence that differences in complement‐fixing activity were not due to class or subclass composition as previously proposed. Consideration of the above qualifications may result in more effective clinical application of the nDNA antibody test.
Expression of the temperature-inducible outer membrane proteins of yersiniae (1985)

The expression of the temperature-inducible plasmid-coded outer membrane proteins (YOPs) of Yersinia pseudotuberculosis was studied. These proteins were not recovered in the outer membrane fraction when the strain was grown in minimal medium at 37 degrees C, but they were expressed under these conditions. A strict correlation was found between Ca2+ dependency in the virulent strain, YPIII(pIB1), and ability to express YOPs. Ca2+-independent plasmid mutants or RNA-polymerase mutants harboring the virulence plasmid were unable to express YOPs, in contrast to the wild-type strain. These strains were also found to be avirulent. Sera recovered from patients or animals undergoing infection with either Y. pseudotuberculosis, Y. pestis, or Y. enterocolitica possessed antibodies directed against YOPs, indicating that they were expressed in all three pathogenic Yersinia species during infection. The YOPs of the three different species showed high immunological relatedness.
Experimental Binding Energies in Supramolecular Complexes (2016)

On the basis of many literature measurements, a critical overview is given on essential noncovalent interactions in synthetic supramolecular complexes, accompanied by analyses with selected proteins. The methods, which can be applied to derive binding increments for single noncovalent interactions, start with the evaluation of consistency and additivity with a sufficiently large number of different host-guest complexes by applying linear free energy relations. Other strategies involve the use of double mutant cycles, of molecular balances, of dynamic combinatorial libraries, and of crystal structures. Promises and limitations of these strategies are discussed. Most of the analyses stem from solution studies, but a few also from gas phase. The empirically derived interactions are then presented on the basis of selected complexes with respect to ion pairing, hydrogen bonding, electrostatic contributions, halogen bonding, π-π-stacking, dispersive forces, cation-π and anion-π interactions, and contributions from the hydrophobic effect. Cooperativity in host-guest complexes as well as in self-assembly, and entropy factors are briefly highlighted. Tables with typical values for single noncovalent free energies and polarity parameters are in the Supporting Information.
Antiepileptic Drugs in Development: Prospects for the Near Future (1994)

Among some 14 new antiepileptic drugs (AEDs), those most extensively tested in humans include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), vigabatrin (VGB), and zonisamide (ZNS). All are currently marketed in some but not all countries. Although no large, comparative studies on efficacy have been conducted, all of these new AEDs are effective in adult localization-related epilepsies, and some have activity in specific syndromes. Although these drugs all have some CNS side effects, especially when administered in combination with other AEDs, they also all have low toxicity profiles. The availability of AEDs with different mechanisms of action may facilitate rational polytherapy. FBM is not teratogenic in animals. Half-life of FBM in humans is 11-28 h. Daily FBM dosages are 15-45 mg/kg in children and 2,400-4,800 mg in adults. Side effects include insomnia and anorexia, with weight loss. FBM increases phenytoin (PHT) and valproate (VPA) concentrations, and FBM concentration may be affected by other drugs. It is available in the United States for treatment of Lennox-Gastaut syndrome and partial seizures in adults. GBP is very water soluble. Half-life of GBP in humans is 5-7 h and daily dosages range from 900 to 2,400 mg in adults. Few side effects have been observed. GBP is not metabolized by the liver and has no drug interactions. It is available in the United Kingdom and the United States. LTG has no teratogenicity in animal models. Half-life of LTG in humans depends on co-medication: with enzyme inducers it is 15-24 h, and with VPA it is approximately 60 h. LTG dosages are 100-600 mg/day in adults. LTG is available in Europe. OCBZ is rapidly metabolized to 10,11-dihydro-10-hydroxy-carbazepine (MHD), the active compound. Animal studies have shown similar efficacy but superior toxicity to carbamazepine (CBZ) in animal models. For MHD, half-life ranges from 10 to 15 h in patients. OCBZ dosages range from 300 to 1,800 mg/day. VGB is a potent, irreversible inhibitor of GABA transaminase which elevates GABA levels in the CNS. Daily dosages of 2,000-4,000 mg of VGB are needed in adults. Although intramyelinic edema has developed in rats and dogs, it has not yet presented in other mammals or humans. ZNS is a sulfonamide effective in animal models of epilepsy. Half-life of ZNS is 27-36 h. ZNS daily dosage is 400-600 mg. ZNS has been effective in some cases of Baltic myoclonic epilepsy.