167 research outputs found
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Health Coverage Expansion in California: What Can Consumers Afford to Spend?
Analyzes Californians' current spending on insurance premiums and out-of-pocket expenditures to assess whether proposals to make obtaining health insurance mandatory include sufficient measures to make it affordable for low- and middle-income families
Spontaneous Chelation-Driven Reduction of the Neptunyl Cation in Aqueous Solution.
Octadentate hydroxypyridinone (HOPO) and catecholamide (CAM) siderophore analogues are known to be efficacious chelators of the actinide cations, and these ligands are also capable of facilitating both activation and reduction of actinyl species. Utilizing X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopies, as well as cyclic voltammetry measurements, herein, we elucidate chelation-based mechanisms for driving reactivity and initiating redox processes in a family of neptunyl-HOPO and CAM complexes. Based on the selected chelator, the ability to control the oxidation state of neptunium and the speed of reduction and concurrent oxo group activation was demonstrated. Most notably, reduction kinetics for the NpV O2 +/ /NpIV redox couple upon chelation by the ligands 3,4,3-LI(1,2-HOPO) and 3,4,3-LI(CAM)2 (1,2-HOPO)2 was observed to be faster than ever reported, and in fact quicker than we could measure using either X-ray absorption spectroscopy or electrochemical techniques
Controlling Dimensionality Via A Dual Ligand Strategy In Ln-thiophene-2,5-dicarboxylic Acid-terpyridine Coordination Polymers
Coordenação de Aperfeiçoamento de Pessoal de NÃvel Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Eleven new lanthanide (Ln = Nd-Lu)-thiophene-2,5-dicarboxylic acid (25-TDC)-2,2':6',2 ''-terpyridine (terpy) coordination polymers (1-11) which employ a dual ligand strategy have been synthesized hydrothermally and structurally characterized by single crystal and powder X-ray diffraction. Two additional members of the series (12 and 13) were made with Ce3+ and Pr3+ and characterized via powder X-ray diffraction only. The series is comprised of three similar structures wherein differences due to the lanthanide contraction manifest in Ln(3+) coordination number as well as the number of bound and solvent water molecules within the crystal lattice. Structure type I (Ce3+-Sm3+) contains two nine-coordinate Ln(3+) metal centers each with a bound water molecule. Structure type II (Eu3+-Ho3+) features a nine and an eight coordinate Ln(3+) metal along with one bound and one solvent water molecule. Structure type III (Er3+-Lu3+) includes two eight-coordinate Ln(3+) metal centers with both water molecules residing in the lattice. Assembly into supramolecular 3D networks via p-p interactions is observed for all three structure types, whereas structure types II and III also feature hydrogen-bonding interactions via the well-known C-H center dot center dot center dot O and O-H center dot center dot center dot O synthons. Visible and near-IR luminescence studies were performed on compounds 1, 2, 10, and 13 at room temperature. As a result characteristic near-IR luminescent bands of Pr3+, Nd3+, Sm3+, and Yb3+ as well as visible bands of Sm3+ were observed.44361584315854Material Science of Actinides, an Energy Frontier Research Center - U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-SC0001089]George Washington UniversityCoordenação de Aperfeiçoamento de Pessoal de NÃvel Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de NÃvel Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CAPES [4671120]FAPESP [2009/54066-7
The Mechanism of Membrane Targeting of Human Sphingosine Kinase 1
Sphingosine 1-phosphate is a bioactive sphingolipid that regu- lates cell growth and suppresses programmed cell death. The bio- synthesis of sphingosine 1-phosphate is catalyzed by sphingosine kinase (SK) but the mechanism by which the subcellular localization and activity of SK is regulated in response to various stimuli is not fully understood. To elucidate the origin and structural determi- nant of the specific subcellular localization of SK, we performed biophysical and cell studies of human SK1 (hSK1) and selected mutants. In vitro measurements showed that hSK1 selectively bound phosphatidylserine over other anionic phospholipids and strongly preferred the plasma membrane-mimicking membrane to other cellular membrane mimetics. Mutational analysis indicates that conserved Thr54 and Asn89 in the putative membrane-binding surface are essential for lipid selectivity and membrane targeting both in vitro and in the cell. Also, phosphorylation of Ser225 enhances the membrane affinity and plasma membrane selectivity of hSK1, presumably by modulating the interaction of Thr54 and Asn89 with the membrane. Collectively, these studies suggest that the specific plasma membrane localization and activation of SK1 is mediated largely by specific lipid-protein interactions
The Grizzly, October 9, 1981
False Alarms Plague Campus • Task Force Attempts to Answer Concerns in the Evening School • Breaking of Tradition, Speeding Up of Progress • Sadat is Dead: What Happens Now? • Letters to the Editor • Books Sought by Ursinus Friends • Pi Nu Epsilon Banquet • Sid Quinn, Barbara Blatt • Transplanted Texan: A Funny Thing Happened to Me at the Forum • Making Love is Fact of Life • Kinky Culture at the Spectrum • LeKites Elected Class of \u2785 President • Second Semi-annual Photo Exhibit Presented Tomorrow • Oktoberfest Comes to Ritter • Business Law Dropped from Day School Curriculum By Request of the Econ Department • 20 hrs. Limitation Causes Uproar • USGA Notes • Cross Country Leaves \u27Em Talking • Hockey Suffers First Loss of Season • Dickinson Latest Victim to Ursinus Defense • Soccer Shuts Out Hopkinshttps://digitalcommons.ursinus.edu/grizzlynews/1063/thumbnail.jp
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Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.
Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine
A COMPARATIVE MAPPING OF ENZYMES INVOLVED IN HEXOSEMONOPHOSPHATE SHUNT AND CITRIC ACID CYCLE IN THE BRAIN *
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66082/1/j.1471-4159.1963.tb05042.x.pd
The Batten Disease Palmitoyl Protein Thioesterase 1 Gene Regulates Neural Specification and Axon Connectivity during Drosophila Embryonic Development
Palmitoyl Protein Thioesterase 1 (PPT1) is an essential lysosomal protein in the mammalian nervous system whereby defects result in a fatal pediatric disease called Infantile Neuronal Ceroids Lipofuscinosis (INCL). Flies bearing mutations in the Drosophila ortholog Ppt1 exhibit phenotypes similar to the human disease: accumulation of autofluorescence deposits and shortened adult lifespan. Since INCL patients die as young children, early developmental neural defects due to the loss of PPT1 are postulated but have yet to be elucidated. Here we show that Drosophila Ppt1 is required during embryonic neural development. Ppt1 embryos display numerous neural defects ranging from abnormal cell fate specification in a number of identified precursor lineages in the CNS, missing and disorganized neurons, faulty motoneuronal axon trajectory, and discontinuous, misaligned, and incorrect midline crossings of the longitudinal axon bundles of the ventral nerve cord. Defects in the PNS include a decreased number of sensory neurons, disorganized chordotonal neural clusters, and abnormally shaped neurons with aberrant dendritic projections. These results indicate that Ppt1 is essential for proper neuronal cell fates and organization; and to establish the local environment for proper axon guidance and fasciculation. Ppt1 function is well conserved from humans to flies; thus the INCL pathologies may be due, in part, to the accumulation of various embryonic neural defects similar to that of Drosophila. These findings may be relevant for understanding the developmental origin of neural deficiencies in INCL
Cellular Bases of Barbiturate and Phenytoin Anticonvulsant Drug Action
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65509/1/j.1528-1157.1982.tb06093.x.pd
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