gebhart/patrepeval huggingface dataset:
Corticotropin-Releasing Hormone Contributes to the Peripheral Inflammatory Response in Experimental Autoimmune Encephalomyelitis (2005)

Peripheral corticotropin-releasing hormone (CRH) is thought to have proinflammatory effects. We used the model of experimental autoimmune encephalomyelitis (EAE) to study the role of CRH in an immune-mediated disease. We showed that CRH-deficient mice are resistant to EAE, with a decrease in clinical score as well as decreased cellular infiltration in the CNS. Furthermore, Ag-specific responses of primed T cells as well as anti-CD3/anti-CD28 TCR costimulation were decreased in crh(-/-) mice with decreased production of Th1 cytokines and increased production of Th2 cytokines. Wild-type mice treated in vivo with a CRH antagonist showed a decrease in IFN-gamma production by primed T cells in vitro. This effect of CRH is independent of its ability to increase corticosterone production, because adrenalectomized wild-type mice had similar disease course and severity as control mice. We found that IkappaBalpha phosphorylation induced by TCR cross-linking was decreased in crh(-/-) T cells. We conclude that peripheral CRH exerts a proinflammatory effect in EAE with a selective increase in Th1-type responses. These findings have implications for the treatment of Th1-mediated diseases such as multiple sclerosis.
Fiber optic intensity-modulated sensors: a review in biomechanics (2012)

Fiber optic sensors have a set of properties that make them very attractive in biomechanics. However, they remain unknown to many who work in the field. Some possible causes are scarce information, few research groups using them in a routine basis, and even fewer companies offering turnkey and affordable solutions. Nevertheless, as optical fibers revolutionize the way of carrying data in telecommunications, a similar trend is detectable in the world of sensing. The present review aims to describe the most relevant contributions of fiber sensing in biomechanics since their introduction, from 1960s to the present, focusing on intensity-based configurations. An effort has been made to identify key researchers, research and development (R&D) groups and main applications.
Phase I and Imaging Trial of Indium 111-Labeled Anti-Epidermal Growth Factor Receptor Monoclonal Antibody 225 in Patients With Squamous Cell Lung Carcinoma (1991)

Murine monoclonal antibody (MAb) 225 (IgG1) against the epidermal growth factor (EGF) receptor competitively blocks EGF binding and inhibits EGF-induced activation of receptor tyrosine kinase and cell proliferation. The effect of MAb 225 was studied in a phase I trial in patients with inoperable squamous cell carcinoma of the lung, which invariably expresses high levels of EGF receptors. Groups of three patients received total doses of MAb 225 ranging from 1 mg to 300 mg. Except at the lowest dose, each infusion included 4 mg of indium 111 (111In)-labeled MAb 225. No toxicity was observed. Tumors were imaged in all patients who received doses of 20 mg or greater. Presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater. Single-photon-emission-computed tomography could be carried out at the 120-mg and 300-mg doses and significantly improved tumor visualization. All patients produced anti-murine antibodies. We conclude that treatment with an MAb that inhibits EGF receptor function is safe at the doses and schedule studied. 111In-labeled MAb images squamous cell lung carcinoma; tumor uptake of the labeled MAb is dose dependent. Further studies are warranted to explore the potential therapeutic efficacy of anti-EGF receptor MAbs and other agents that act in a comparable manner.
Plasma Aluminum Concentrations in Pediatric Patients Receiving Long‐Term Parenteral Nutrition (2014)

Pediatric patients receiving long-term PN for IF in Canada are at risk for Al toxicity.
Kinetics of conventional carbon coated-Li3V2(PO4)3 and nanocomposite Li3V2(PO4)3/graphene as cathode materials for lithium ion batteries (2012)

Recently, improvement on cycling stability and rate performance were reported when the electrode materials were supported by graphene. In this work, we report the approaches for fabricating a nano-structure Li3V2(PO4)3/carbon with conventional carbon-coating and Li3V2(PO4)3/graphene with graphene sheets supporting the composite. The crystal structure and morphology, the lithium diffusion behavior and high rates capacities of pure LVP, composites of LVP with conventional carbon and graphene sheets are studied in detail. The conventional carbon or some LVP particles are separately aggregated without effectively compounding with each other, but there is a more efficient carbon coating by graphene because the LVP nanoparticles are grown on or are enwrapped into a 2D network of graphene layers. Minor graphene contained in the Li3V2(PO4)3/graphene nanocomposite can result in a reduction of crystal size, a large surface area, an increase in conductivity (three orders of magnitude), and great improvement in the rate performance and cycling stability. We proposed an effective carbon coating (ECC) model of microstructure of LVP nanoparticles compounded with carbon or graphene to discuss the key roles of graphene on the great improvement of electrochemical performance. It should offer a new idea in the design and synthesis of battery electrodes based on carbon-coated technology.
Formation of columnar arrangements in copper(II) complexes of derivatives (1998)

The synthesis and mesomorphic properties of a homologous series of 2-(3′,4′,5′-trialkoxyphenyl)azomethinopyridines and their copper(II) complexes are reported. Liquid crystalline properties of the copper(II) complexes were studied by DSC analysis and polarized optical microscopy. The results indicated that copper complexes with six sidechains (3) exhibited columnar phases, whereas copper(II) complexes with two or four sidechains (1 and 2) formed only crystalline phases. The structures of the mesophases for copper(II) complexes 3 were characterized and confirmed as disordered hexagonal columnar phases (Col hd ) by powder X-ray diffraction. Relatively high clearing points and the short range of mesophase temperature for the copper complexes were attributed to a relatively strong interaction of pyridyl core-core groups within the columns. The EPR spectra measured at various temperatures were also examined.
Oxidation, Lipoxygenase, and Atherogenesis (1994)

Mounting evidence suggests that oxidative processes contribute to the pathogenesis of atherosclerosis and that antioxidants may represent a strategy to complement the lowering of lipids in the therapy of this disease. Although multiple molecular events have been identified in vitro and although it is tempting to ascribe multiple atherogenic properties to oxidized LDL, our understanding of this process remains incomplete. Further research is warranted in several areas. First, it will be important to selectively inhibit different aspects of the process to determine the relative contribution of various biological targets. In this regard pharmacological inhibition of 15-lipoxygenase in vivo in relevant animal models is required to address the question of the contribution of this enzyme to significant oxidative events. The lack of specific inhibitors has made this task more difficult. It will also be important to define the biologically active moiety of oxidized LDL to begin to determine the mechanisms through which it exerts its atherogenic effects. It is likely that alternate protein targets can be identified both downstream and upstream of the oxidative process. Research is only now beginning to elucidate the inflammatory mechanisms that account for the cellular response. Further research into adhesion events, cytokine profiles, and downstream effector molecules of the oxidative process are likely to identify alternate targets for therapeutic intervention.
A Family of Rab27-binding Proteins (2002)

The Rab27a GTPase regulates diverse processes involving lysosome-related organelles, including melanosome motility in melanocytes, and lytic granule release in cytotoxic T lymphocytes. Toward an understanding of Rab27a function, we searched for proteins that interact with Rab27a(GTP) using the yeast two-hybrid system and identified JFC1/Slp1, a protein of unknown function. JFC1/Slp1 and related proteins, including melanophilin, contain a conserved amino-terminal domain similar to the Rab3a-binding domain of Rabphilin-3. We used several methods to demonstrate that this conserved amino-terminal domain is a Rab27-binding domain. We show that this domain interacts directly, and in a GTP-dependent manner with Rab27a. Furthermore, overexpression of this domain in melanocytes results in perinuclear clustering of melanosomes, suggesting that this region is sufficient for interaction with, and perturbation of function of, Rab27a in a physiological context. Thus, we identified a novel family of Rab27-binding proteins. We also show that melanophilin associates with Rab27a and myosin Va on melanosomes in melanocytes, and present evidence that a domain within the carboxyl-terminal region of melanophilin interacts with the carboxyl-terminal tail of the melanocyte-specific splice isoform of myosin Va. Thus, melanophilin can associate simultaneously with activated Rab27a and myosin Va via distinct regions, and serve as a linker between these proteins.
Fetal liver stroma consists of cells in epithelial-to-mesenchymal transition (2003)

Liver becomes the predominant site of hematopoiesis by 11.5 dpc (days after coitus) in the mouse and 15 gestational weeks in humans and stays so until the end of gestation. The reason the liver is the major hematopoietic site during fetal life is not clear. In this work, we tried to define which of the fetal liver microenvironmental cell populations would be associated with the development of hematopoiesis and found that a population of cells with mixed endodermal and mesodermal features corresponded to hematopoietic-supportive fetal liver stroma. Stromal cells generated from primary cultures or stromal lines from mouse or human fetal liver in the hematopoietic florid phase expressed both mesenchymal markers (vimentin, osteopontin, collagen I, alpha smooth muscle actin, thrombospondin-1, EDa fibronectin, calponin, Stro-1 antigens, myocyte-enhancer factor 2C) and epithelial (alpha-fetoprotein, cytokeratins 8 and 18, albumin, E-cadherin, hepatocyte nuclear factor 3 alpha) markers. Such a cell population fits with the description of cells in epithelial-to-mesenchymal transition (EMT), often observed during development, including that of the liver. The hematopoietic supportive capacity of EMT cells was lost after hepatocytic maturation, induced by oncostatin M in the cell line AFT024. EMT cells were observed in the fetal liver microenvironment during the hematopoietic phase but not in nonhematopoietic liver by the end of gestation and in the adult. EMT cells represent a novel stromal cell type that may be generated from hepatic endodermal or mesenchymal stem cells or even from circulating hematopoietic stem cells (HSCs) seeding the liver rudiment.
Identification of a region of genetic variability among Bacillus anthracis strains and related species (1996)

The identification of a region of sequence variability among individual isolates of Bacillus anthracis as well as the two closely related species, Bacillus cereus and Bacillus mycoides, has made a sequence-based approach for the rapid differentiation among members of this group possible. We have identified this region of sequence divergence by comparison of arbitrarily primed (AP)-PCR "fingerprints" generated by an M13 bacteriophage-derived primer and sequencing the respective forms of the only polymorphic fragment observed. The 1,480-bp fragment derived from genomic DNA of the Sterne strain of B. anthracis contained four consecutive repeats of CAATATCAACAA. The same fragment from the Vollum strain was identical except that two of these repeats were deleted. The Ames strain of B. anthracis differed from the Sterne strain by a single-nucleotide deletion. More than 150 nucleotide differences separated B. cereus and B. mycoides from B. anthracis in pairwise comparisons. The nucleotide sequence of the variable fragment from each species contained one complete open reading frame (ORF) (designated vrrA, for variable region with repetitive sequence), encoding a potential 30-kDa protein located between the carboxy terminus of an upstream ORF (designated orf1) and the amino terminus of a downstream ORF (designated lytB). The sequence variation was primarily in vrrA, which was glutamine- and proline-rich (30% of total) and contained repetitive regions. A large proportion of the nucleotide substitutions between species were synonymous. vrrA has 35% identity with the microfilarial sheath protein shp2 of the parasitic worm Litomosoides carinii.
Histological Studies of Subcutaneous and Intraperitoneal Implants of Trypsin-Prepared Dermal Collagen Allografts in the Rat (1976)

The possibility of using allograft collagen for the permanent replacement of lost or damaged connective tissues has been examined in the rat. The cellular components of skin, which are known to be of major importance in allograft rejection, were removed by treating skin with a solution of crystalline trypsin at 15 degrees C. Non-collagenous structures were largely removed by 7 days, but the purification process continued up to 28 days without damage to the collagen fibrils. Dermal collagen allografts, which were implanted intraperitoneally or subcutaneously and biopsied 3-83 days after operation, became recellularized and revascularized without being being resorbed. In contrast to skin allografts, there was no evidence of cellular rejection of the collagen grafts, even when recipient animals had been sensitized to allogeneic skin from the same donor. Densensitization of collagen to collagenase, by treating dermal collagen with solutions of glutaraldehyde at concentrations ranging from 0.001-1.0 per cent, was also investigated in vitro and by implantation. The best results, in terms of preservation of the collagen bundle architecture and graft recellularization without persisting inflammation, were achieved with collaged pre-treated with a solution of 0.01% glutaraldehyde.
Multiclass cancer diagnosis using tumor gene expression signatures (2001)

The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is difficult or impossible because of atypical clinical presentation or histopathology. To determine whether the diagnosis of multiple common adult malignancies could be achieved purely by molecular classification, we subjected 218 tumor samples, spanning 14 common tumor types, and 90 normal tissue samples to oligonucleotide microarray gene expression analysis. The expression levels of 16,063 genes and expressed sequence tags were used to evaluate the accuracy of a multiclass classifier based on a support vector machine algorithm. Overall classification accuracy was 78%, far exceeding the accuracy of random classification (9%). Poorly differentiated cancers resulted in low-confidence predictions and could not be accurately classified according to their tissue of origin, indicating that they are molecularly distinct entities with dramatically different gene expression patterns compared with their well differentiated counterparts. Taken together, these results demonstrate the feasibility of accurate, multiclass molecular cancer classification and suggest a strategy for future clinical implementation of molecular cancer diagnostics.
Structure-activity and structure-selectivity studies on diaminoquinazolines and other inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase (1995)

Twenty-eight 2,4-diaminopteridines with alkyl and aralkyl groups at the 6- and 7-positions, five 1,3-diamino-7,8,9,10-tetrahydropyrimido [4,5-c]isoquinolines with an alkyl, alkylthio, or aryl group at the 6-position, and nine 4,6-diamino-1,2-dihydro-s-triazines with one or two alkyl groups at the 2-position and a substituted phenyl or naphthyl group at the 1-position were evaluated as inhibitors of dihydrofolate reductase enzymes from Pneumocystis carinii, Toxoplasma gondii, and rat liver. Halogen substitution at the 5- or 6-position of 2,4-diaminoquinazoline favored selective binding to the P. carinii enzyme but not the T. gondii enzyme. For example, the 50% inhibitory concentrations of 2,4-diamino-6-chloroquinazoline as an inhibitor of P. carinii, T. gondii, and rat liver dihydrofolate reductase were 3.6, 14 and 29 microM, respectively, corresponding to 12-fold selectivity for the P. carinii enzyme but only marginal selectivity for the T. gondii enzyme. Greater than fivefold selectivity for P. carinii but not T. gondii dihydrofolate reductase was also observed for the 2,4-diaminoquinazolines with 5-methyl, 5-fluoro, 5- and 6-bromo, 6-chloro, and 5-chloro-6-bromo substitution. In contrast, alkyl and aralkyl substitution at the 6- and 7-positions of 2,4-diaminopteridines was found to be a favorable feature for selective inhibition of the T. gondii enzyme and, in two cases, for both enzymes. Nine of the fifty-one compounds tested against P. carinii dihydrofolate reductase and four of the thirty compounds tested against T. gondii dihydrofolate reductase displayed fivefold or greater selectivity for the microbial enzyme versus the rat liver enzyme. The most selective against both enzymes was 2,4-diamino-6,7-bis(cyclohexylmethyl) pteridine, with a selectivity ratio 2 orders of magnitude greater than the value reported for trimetrexate and piritrexim. Since substitution at the 7-position is generally considered to be detrimental to the binding of 2,4-diaminop-teridines and related compounds to mammalian dihydrofolate reductase, the selectivity observed in this study with the 6,7-bis(cyclohexylmethyl) analog may represent a useful approach to enhancing selective inhibition of the enzyme from nonmammalian species.
Phase-resolved polarization sensitive optical coherence tomography imaging of tendon and muscle (2003)

We describe a phase-resolved polarization sensitive optical coherence tomography system that can obtain the Stokes vectors, polarization diversity intensity, and birefringence images of rat-tail tendon and muscle. The Stokes vectors were obtained by processing the analytical interference fringe signals from two perpendicular polarization-detection channels for the same reference polarization state. From the four Stokes vectors, the birefringence image, which is insensitive to orientation of the optical axis in the sample, and the polarization diversity intensity image, in which speckle noise is greatly reduced, were obtained. The birefringence changes in the rat muscle caused by freezing were investigated using phase-resolved polarization sensitive optical coherence tomography. It was found that freezing degrades birefringence in rat muscle.
Monitoring and management of structured peer-to-peer systems (2009)

The peer-to-peer paradigm shows the potential to provide the same functionality and quality like client/server based systems, but with much lower costs. In order to control the quality of peer-to-peer systems, monitoring and management mechanisms need to be applied. Both tasks are challenging in large-scale networks with autonomous, unreliable nodes. In this paper we present a monitoring and management framework for structured peer-to-peer systems. It captures the live status of a peer-to-peer network in an exhaustive statistical representation. Using principles of autonomic computing, a preset system state is approached through automated system re-configuration in the case that a quality deviation is detected. Evaluation shows that the monitoring is very precise and lightweight and that preset quality goals are reached and kept automatically.
Retinal degeneration 12 (rd12): a new, spontaneously arising mouse model for human Leber congenital amaurosis (LCA). (2005)

Mutations in the retinal pigment epithelium gene encoding RPE65 cause an early onset autosomal recessive form of human retinitis pigmentosa, known as Leber congenital amaurosis (LCA), which results in blindness or severely impaired vision in children. A naturally arising mouse Rpe65 mutation provides a good model for studying the pathology of human RPE65 mutations and the effects of retinyl ester accumulation.
Stereoselectivity of Ins(1,3,4,5)P4 recognition sites: implications for the mechanism of the Ins(1,3,4,5)P4-induced Ca2+ mobilization (1993)

Ins(1,3,4,5)P4 was able to mobilize the entire Ins(1,4,5)P3-sensitive intracellular Ca2+ store in saponin-permeabilized SH-SY5Y human neuroblastoma cells in a concentration-dependent manner, yielding an EC50 value of 2.05 +/- 0.45 microM, compared with 0.14 +/- 0.03 microM for Ins(1,4,5)P3. However, L-Ins(1,3,4,5)P4 [= D-Ins(1,3,5,6)P4] failed to cause mobilization of intracellular Ca2+ at concentrations up to 100 microM. Binding studies using pig cerebellar membranes as a source of both Ins(1,4,5)P3/Ins(1,3,4,5)P4-specific binding sites have revealed a marked contrast in their stereospecificity requirements. Ins(1,4,5)P3-receptors from pig cerebella exhibited stringent stereospecificity, L-Ins(1,4,5)P3 and L-Ins(1,3,4,5)P4 were > 1000-fold weaker, whereas Ins(1,3,4,5)P4 (IC50 762 +/- 15 nM) was only about 40-fold weaker than D-Ins(1,4,5)P3 (IC50 20.7 +/- 9.7 nM) at displacing specific [3H]Ins(1,4,5)P3 binding from an apparently homogeneous Ins(1,4,5)P3 receptor population. In contrast, the Ins(1,3,4,5)P4-binding site exhibited poor stereoselectivity. Ins(1,3,4,5)P4 produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding, with two-site analysis revealing KD values for high- and low-affinity sites of 2.1 +/- 0.5 nM and 918 +/- 161 nM respectively. L-Ins(1,3,4,5)P4 also produced a biphasic displacement of specific [32P]Ins(1,3,4,5)P4 binding which was less than 10-fold weaker than with D-Ins(1,3,4,5)P4 (IC50 values for the high- and low-affinity sites of 17.2 +/- 3.7 nM and 3010 +/- 542 nM respectively). Therefore, although L-Ins(1,3,4,5)P4 appears to be a high-affinity Ins(1,3,4,5)P4-binding-site ligand in pig cerebellum, it is a very weak agonist at the Ca(2+)-mobilizing receptors of permeabilized SH-SY5Y cells. We suggest that the ability of D-Ins(1,3,4,5)P4 to access intracellular Ca2+ stores may derive from specific interaction with the Ins(1,4,5)P3- and not the Ins(1,3,4,5)P4-receptor population.
What treatment should we use if drugs fail for OAB; and, what really works after drugs? (2010)

A list of 10 unanswered questions and research topics was compiled. Additionally, 5 top priority research topics were identified.