gebhart/patrepeval huggingface dataset:
Tim3/Galectin-9 interactions regulate innate and adaptive immunity to Mycobacterium tuberculosis (70.6) (2012)

Abstract In vivo control of Mycobacterium tuberculosis (Mtb) reflects the balance between host-immunity and bacterial evasion strategies. Effector TH1 cells that mediate protective immunity by depriving the bacterium of its intracellular niche are regulated in many ways to prevent over-exuberant inflammation. Although Tim3 is generally recognized to down regulate TH1 responses and mediate T cell exhaustion, we recently described that its interaction with Galectin-9 (Gal9) expressed by Mtb infected macrophages (Mϕ) stimulates IL-1β secretion, which is essential for host resistance to Mtb. IL-1β signaling is both necessary for Tim3 mediated Mtb control and sufficient to directly kill Mtb in murine and human Mϕ. The molecular mechanism by which IL-1β restricts bacterial growth is not known. We report that IL-1β kills Mtb through the recruitment of other antimicrobial effector molecules. IL-1β directly augments TNF signaling through increased TNF secretion and TNFR cell surface expression. Furthermore, Tim3/Gal9 and IL-1β activates the executioner caspase-3. Thus, Tim3/Gal9, via IL-1β and downstream TNF production lead to apoptosis and restriction of intracellular Mtb growth. We propose that Tim3/Gal9 interaction acts as a bidirectional molecular rheostat that activates pathways to clear intracellular pathogens in innate immune cells while fine-tuning termination of TH1 responses to prevent immunopathology.
Diagnosis of systemic lupus erythematosus. (2003)

Systemic lupus erythematosus is a multisystem inflammatory disease that is often difficult to diagnose. Before the diagnosis can be established, four of 11 clinical and laboratory criteria must be met. Antinuclear antibody titer is the primary laboratory test used to diagnose systemic lupus erythematosus. Because of the low prevalence of the disease in primary care populations, the antinuclear antibody titer has a low predictive value in patients without typical clinical symptoms. Therefore, as specified by the American College of Rheumatology, this titer should be obtained only in patients with unexplained involvement of two or more organ systems. Patients with an antinuclear antibody titer of 1:40 and characteristic multiorgan system involvement can be diagnosed with systemic lupus erythematosus without additional testing; however, patients with an antibody titer of 1:40 who fail to meet full clinical criteria should undergo additional testing, including tests for antibody to double-stranded DNA antigen and antibody to Sm nuclear antigen. While an antinuclear antibody titer of less than 1:40 usually rules out systemic lupus erythematosus, patients with persistent, characteristic multisystem involvement may be evaluated for possible antinuclear antibody-negative disease.
The Lens and Zonules (1973)

International Ophthalmology Clinics is a valuable resource for any medical professional seeking to stay informed and up-to-date regarding developments in this dynamic specialty. Each issue of this quarterly publication presents a comprehensive review of a single topic in a new or changing area of ophthalmology. The timely, tightly focused review articles found in this publication give ophthalmologists the opportunity to benefit from the knowledge of leading experts in this rapidly changing field.
Metabolism of Δ1-Tetrahydrocannabinol by Rats Tolerant to Cannabis (1974)

Daily treatment of rats with phenobarbital, 75 mg/kg, for 5 days resulted in an induction of the metabolism of 14 C-Δ 1 -transterahydrocannabinol (THC) in vitro and in vivo. Although the K m and V max for THC metabolism by liver preparations in vitro were not altered, the rate of formation of highly polar THC metabolites was significantly increased and the final concentration of 7-hydroxy-Δ 1 -THC was decreased. Phenobarbital also significantly increased the rate of biliary excretion of THC and its metabolites and their disappearance from the blood and tissues.In one experiment, rats receiving a marihuana extract daily (providing THC, 5–10 mg/kg) failed to gain body weight during the first week of treatment, but then became tolerant to this effect. But neither the rate of THC metabolism in vitro nor the pattern of metabolites formed was influenced in the tolerant animals compared to controls. In another experiment, rats were shown to become tolerant on chronic treatment with marihuana extract, as indicated by a reduction in marihuana-induced enhancement of ethanol sleeping time. The biliary excretion, disappearance from the blood, and residual tissue levels of THC and its metabolites were not altered in the tolerant animals compared to pair-fed and ad libitum-fed controls. Therefore the mechanism of tolerance development to cannabis in the rat is more likely of CNS than of metabolic origin.
Ultrahigh Sensitivity Carbon Nanotube Agents for Photoacoustic Molecular Imaging in Living Mice (2010)

Photoacoustic imaging is an emerging modality that overcomes to a great extent the resolution and depth limitations of optical imaging while maintaining relatively high-contrast. However, since many diseases will not manifest an endogenous photoacoustic contrast, it is essential to develop exogenous photoacoustic contrast agents that can target diseased tissue(s). Here we present a novel photoacoustic contrast agent, Indocyanine Green dye-enhanced single walled carbon nanotube (SWNT-ICG). We conjugated this contrast agent with cyclic Arg-Gly-Asp (RGD) peptides to molecularly target the alpha(v)beta(3) integrins, which are associated with tumor angiogenesis. Intravenous administration of this tumor-targeted contrast agent to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. The new contrast agent gave a markedly 300 times higher photoacoustic contrast in living tissues than previously reported SWNTs, leading to subnanomolar sensitivities. Finally, we show that the new contrast agent can detect approximately 20 times fewer cancer cells than previously reported SWNTs.
2'-O-Nitro-1-.beta.-D-arabinofuranosylcytosine. A new derivative of 1-.beta.-D-arabinofuranosylcytosine that resists enzymic deamination and has antileukemic activity (1983)

To overcome the susceptibility of the anticancer drug 1-beta-D-arabinofuranosylcytosine (ara-C) to enzymatic deamination, and hence deactivation, we prepared the 2'-O-nitro-1-beta-D-arabinofuranosylcytosine (termed nitrara-C) and evaluated it for biological activity. Nitrara-C was resistant to enzymatic deamination and inhibited the proliferation of several strains of human leukemic T and B lymphoblasts grown in culture. Moreover, it substantially extended the life spans of mice with L1210 leukemia. Studies with ara-C-resistant human leukemic lymphoblasts deficient in deoxycytidine kinase activity disclosed that the inhibitory activity of the new compound depends on its phosphorylation.
Role of notch signaling in angiogenesis and breast cancer (2011)

The Notch family of transmembrane receptors consists of four members in mammals, Notchl through Notch4. Upon ligand binding, Notch receptors become activated and participate in intracellular signaling pathways that regulate cell fate decisions. Notchl-3 are expressed on numerous cell types. Because Notch4 is primarily expressed on endothelial cells, we postulated that Notch4 activation would modulate cell fate decisions in an endothelial-specific manner. Angiogenesis, the sprouting of endothelial cells from pre-existing microvessels, requires modulation of the endothelial cell phenotype. We have identified a role for Notch4 activation in the regulation of angiogenesis. Expression of activated Notch4 inhibits endothelial sprouting in vitro and angiogenesis in vivo. Activated Notch4 does not inhibit endothelial cell migration through the extracellular matrix protein fibrinogen, whereas migration through collagen is inhibited. Activated Notch4 increases endothelial cell adhesion to collagen by modulating the affinity state of cell-surface collagen receptors belonging to the pi integrin family. Specifically, activated Notch4 converts pi integrin from an inactive, non-ligand-binding state to an active, high-affinity conformation. Our findings suggest that Notch4 activation in endothelial cells inhibits angiogenesis in part by promoting pi integrin-mediated adhesion to the underlying matrix. Although Notch signaling regulates normal cellular processes, increasing evidence suggests a role for aberrant Notch signaling in cellular transformation. During tumor progression, epithelial tumor cells often acquire a mesenchymal phenotype through epithelial-tomesenchymal transition (EMT), a process that promotes invasion and dissemination of cancer cells. In human breast cancer, EMT directly correlates with downregulated expression of the adherens junction protein epithelial (E)-cadherin. Given that Notch pathway elements are expressed at sites of epithelial-mesenchymal cell-cell interactions during embryogenesis and within primary human breast tumors, we investigated whether Notch signaling would modulate E-cadherin expression in human breast cells. Our studies identify activated Notch signaling as a novel mechanism for the downregulation of E-cadherin expression in normal human breast epithelial cells. In human breast tumor xenografts lacking E-cadherin expression, we show that a soluble inhibitor of Notch signaling attenuates E-cadherin promoter methylation and induces Ecadherin re-expression. This re-induction of E-cadherin in turn inhibits p-catenin nuclear accumulation, resulting in a marked reduction in breast tumor growth and metastasis.
Hypoxia induces different genes in the lungs of rats compared with mice (2003)

Different animal species have a varying response to hypoxia. Mice develop less pulmonary artery thickening after chronic hypoxia exposure than rats. We hypothesized that the lung tissue gene expression pattern displayed in hypoxic rats would differ from that of hypoxic mice. We exposed Sprague-Dawley rats and C57BL/6 mice to both 1 and 3 wk of hypobaric hypoxia. Although both species developed pulmonary hypertension, mice showed less pulmonary vascular remodeling than rats. Microarray gene analysis demonstrated a distinct pattern of gene expression between mice and rats when exposed to hypoxic conditions. In addition, some genes appeared to be more responsive at an earlier time point of 1 wk of hypoxia. Hypoxic conditions in the rat induce genes involved in endothelial cell proliferation, repression of apoptosis, and vasodilation. Mice exposed to hypoxic conditions decrease the expression of genes involved in vasodilation and in endothelial cell proliferation. Although we cannot determine whether the differential expression of genes during chronic hypoxia is cause or consequence of the differential pulmonary vascular remodeling, we propose that a balance between over- and under-expression of a selective group of genes may be responsible for lung vascular remodeling and vascular tone control.
Outer membranes of Gram‐negative bacteria are permeable to steroid probes (1992)

The permeability of bacterial outer membranes was assayed by coupling the influx of highly hydrophobic probes, 3-oxosteroids, with their subsequent oxidation catalysed by 3-oxosteroid delta 1-dehydrogenase, expressed from a gene cloned from Pseudomonas testosteroni. In Salmonella typhimurium producing wild-type lipopolysaccharide, the permeability coefficients for uncharged steroids were 0.45 to 1 x 10(-5) cm s-1, and the diffusion appeared to occur mainly through the lipid bilayer domains of the outer membrane. These rates are one or two magnitudes lower than that expected for their diffusion through the usual biological membranes. The permeation rates were markedly increased (up to 100 times) when the lipopolysaccharide leaflet was perturbed either by adding deacylpolymyxin or by introducing mutations leading to the production of deep rough lipopolysaccharides. An amphiphilic, negatively charged probe, testosterone hemisuccinate, penetrated much more slowly than the uncharged steroids. Study of various Gram-negative species revealed that P. testosteroni, Pseudomonas acidovorans, and Acinetobacter calcoaceticus showed higher outer membrane permeability to steroid probes and higher susceptibility to hydrophobic agents such as fusidic acid, novobiocin and crystal violet relative to S. typhimurium and Escherichia coli.
A technique for controlling the alignment of silver nanowires with an electric field (2006)

Highly aligned silver nanowire arrays are synthesized under direct current electric field (DCEF) treatment by a solid state ionics method without any template at normal temperature and pressure. The degree of alignment of the synthesized nanowires increases with increase of the DCEF strength. The mechanism of the effect of the DCEF on the nanowire alignment is discussed briefly. Moreover, the alignment of the individual nanowires in a bundle is further proved by observing the polarization dependence in the experiment of the polarized reflection measurements.
Continuous Countercurrent Extraction of Hemicellulose from Pretreated Wood Residues (2001)

Two-stage dilute acid pretreatment followed by enzymatic cellulose hydrolysis is an effective method for obtaining high sugar yields from wood residues such as softwood forest thinnings. In the first-stage hydrolysis step, most of the hemicellulose is solubilized using relatively mild conditions. The soluble hemicellulosic sugars are recovered from the hydrolysate slurry by washing with water. The washed solids are then subjected to more severe hydrolysis conditions to hydrolyze approx 50% of the cellulose to glucose. The remaining cellulose can further be hydrolyzed with cellulase enzyme. Our process simulation indicates that the amount of water used in the hemicellulose recovery step has a significant impact on the cost of ethanol production. It is important to keep water usage as low as possible while maintaining relatively high recovery of soluble sugars. To achieve this objective, a proto-type pilot-scale continuous countercurrent screw extractor was evaluated for the recovery of hemicellulose from pretreated forest thinnings. Using the 274-cm (9-ft) long extractor, solubles recoveries of 98, 91, and 77% were obtained with liquid-to-insoluble solids (L/IS) ratios of 5.6, 3.4, and 2.1, respectively. An empirical equation was developed to predict the performance of the screw extractor. This equation predicts that soluble sugar recovery above 95% can be obtained with an L/IS ratio as low as 3.0.
Characterization of the cylindrical cavities of Anopore and Nuclepore membranes (1992)

The microscopic properties of the inner surface of the cavities of Anopore and Nuclepore membranes are investigated with scanning electron microscopy (SEM), nitrogen adsorption isotherms, and deuterium nuclear magnetic resonance (2H-NMR). Useful information about the cavity orientation and morphology, and internal surface area is obtained. Analysis of SEM photographs yields estimates of the surface area and the porosity of these membranes which complements the adsorption results. The orientation of liquid crystals permeated in the cavities of Anopore and Nuclepore membranes is probed with the 2H-NMR technique. It is found that the orientation of the liquid crystal molecules is governed by the confining volume and surface conditions. The 2H-NMR spectral line shape of the confined liquid crystal also provides information on the substrate morphology and roughness that is consistent with SEM and adsorption experiments.
Depletion-mode ZnO nanowire field-effect transistor (2004)

Single ZnO nanowire metal-oxide-semiconductor field-effect transistors (MOSFETs) were fabricated using nanowires grown by site selective molecular-beam epitaxy. When measured in the dark at 25°C, he depletion-mode transistors exhibit good saturation behavior, a threshold voltage of ∼−3V, and a maximum transconductance of order 0.3mS∕mm. Under ultraviolet (366nm) illumination, the drain–source current increase by approximately a factor of 5 and the maximum transconductance is ∼5mS∕mm. The channel mobility is estimated to be ∼3cm2∕Vs, which is comparable to that reported for thin film ZnO enhancement mode MOSFETs, and the on∕off ratio was ∼25 in the dark and ∼125 under UV illumination.
Suramin Is an Active Site-directed, Reversible, and Tight-binding Inhibitor of Protein-tyrosine Phosphatases (1998)

The effect of suramin, a well known antitrypanosomal drug and a novel experimental agent for the treatment of several cancers, on protein-tyrosine phosphatases (PTPases) has been examined. Suramin is a reversible and competitive PTPase inhibitor with Kis values in the low microM range, whereas the Kis for the dual specificity phosphatase VHR is at least 10-fold higher. Although suramin can also inhibit the activity of the potato acid phosphatase at a slightly higher concentration, it is 2-3 orders of magnitude less effective against the protein Ser/Thr phosphatase 1alpha and the bovine intestinal alkaline phosphatase. Suramin binds to the active site of PTPases with a binding stoichiometry of 1:1. Furthermore, when suramin is bound to the active site of PTPases, its fluorescence is enhanced approximately by 10-fold. This property has allowed the determination of the binding affinity of suramin for PTPases and several catalytically impaired mutant PTPases by fluorescence titration techniques. Thus, the active site Cys to Ser mutants bind suramin with similar affinity as the wild type, while the active site Arg to Ala mutant exhibits a 20-fold reduced affinity toward suramin. Interestingly, the general acid deficient Asp to Ala mutant PTPases display an enhanced affinity toward suramin, which is in accord with their use as improved "substrate-trapping" agents. That suramin is a high affinity PTPase inhibitor is consistent with the observation that suramin treatment of cancer cell lines leads to an increase in tyrosine phosphorylation of several cellular proteins. Given the pleiotropic effects of suramin on many enzyme systems and growth factor-receptor interactions, the exact in vivo actions of suramin require further detailed structure-activity investigation of suramin and its structural analogs.
Identification of Major Binding Proteins and Substrates for the SH2-Containing Protein Tyrosine Phosphatase SHP-1 in Macrophages (1998)

The protein tyrosine phosphatase SHP-1 is a critical regulator of macrophage biology, but its detailed mechanism of action remains largely undefined. SHP-1 associates with a 130-kDa tyrosyl-phosphorylated species (P130) in macrophages, suggesting that P130 might be an SHP-1 regulator and/or substrate. Here we show that P130 consists of two transmembrane glycoproteins, which we identify as PIR-B/p91A and the signal-regulatory protein (SIRP) family member BIT. These proteins also form separate complexes with SHP-2. BIT, but not PIR-B, is in a complex with the colony-stimulating factor 1 receptor (CSF-1R), suggesting that BIT may direct SHP-1 to the CSF-1R. BIT and PIR-B bind preferentially to substrate-trapping mutants of SHP-1 and are hyperphosphorylated in macrophages from motheaten viable mice, which express catalytically impaired forms of SHP-1, indicating that these proteins are SHP-1 substrates. However, BIT and PIR-B are hypophosphorylated in motheaten macrophages, which completely lack SHP-1 expression. These data suggest a model in which SHP-1 dephosphorylates specific sites on BIT and PIR-B while protecting other sites from dephosphorylation via its SH2 domains. Finally, BIT and PIR-B associate with two tyrosyl phosphoproteins and a tyrosine kinase activity. Tyrosyl phosphorylation of these proteins and the level of the associated kinase activity are increased in the absence of SHP-1. Our data suggest that BIT and PIR-B recruit multiple signaling molecules to receptor complexes, where they are regulated by SHP-1 and/or SHP-2.
A novel mechanism of complement-independent clearance of red cells deficient in glycosyl phosphatidylinositol–linked proteins (2003)

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by the increased sensitivity of red blood cells (RBCs) to complement, leading to intravascular hemolysis and hemoglobinuria. PNH is due to the expansion of a cell clone that has acquired a mutation in the PIGA gene. Mice with targeted Piga gene inactivation genetically mimic the human disease and have phosphatidylinositol glycan class A-negative (PIGA-) RBCs with a reduced half-life in circulation. Although PIGA-RBCs are hypersensitive to complement in vitro, their complement sensitivity in vivo is barely detectable. Here we show that the shortened survival of PIGA- RBCs is independent of complement either by using inhibitory C5 antibodies or by transfusion into C5-, C4-, C3-, or factor B-deficient mice. Splenectomy or high-dose cortisone treatment had no effect on the shorter survival of PIGA- RBCs. However, treatment with liposome-encapsulated clodronate, an agent that depletes macrophages in vivo, normalized the half-life of PIGA- RBCs. This indicates that the shortened survival of PIGA- RBCs is due to a novel pathway of PIGA- RBC clearance that is mediated by macrophages, but occurs independently of complement. Future investigations will show whether this novel pathway of PIGA- RBC destruction identified in mice may also operate in patients with PNH.
Crystal Structures, Anisotropic Growth, and Optical Properties: Controlled Synthesis of Lanthanide Orthophosphate One‐Dimensional Nanomaterials (2005)

The fundamental understanding of the relationship between crystal structure and the dynamic processes of anisotropic growth on the nanoscale, and exploration of the key factors governing the evolution of physical properties in functional nanomaterials, have become two of the most urgent and challenging issues in the fabrication and exploitation of functional nanomaterials with designed properties and the development of nanoscale devices. Herein, we show how structural and kinetic factors govern the tendency for anisotropic growth of such materials under hydrothermal conditions, and how the crystal structure and morphology influence the optical properties of Ln3+-doped nanocrystals. The synthesis of phase-pure and single-crystalline monoclinic, hexagonal, and tetragonal one-dimensional LnPO4 nanostructures of different aspect ratios by means of kinetically controlled hydrothermal growth processes is demonstrated. It is shown that the tendency for anisotropic growth under hydrothermal conditions can be enhanced simply by modifying the chemical potentials of species in the reaction solution through the use of carefully selected chelating ligands. A systematic study of the photoluminescence of various Eu3+-doped lanthanide phosphates has revealed that the optical properties of these nanophosphors are strongly dependent on their crystal structures and morphologies.