320 research outputs found

    State Obligations Regarding Domestic Violence: The European Court of Human Rights, Due Diligence, And International Legal Minimums of Protection

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    Over the last two decades, international human rights instruments, decisions, and dedicated advocates have advanced the understanding of domestic violence. Once considered a private act committed with widespread impunity, domestic violence is now viewed as a human rights violation that states have a responsibility to address. This article will trace the history of this progression and the emergence of a due diligence standard to assess a state\u27s response to domestic violence. The first half of the article will examine the recognition of the due diligence standard as a rule of customary international law with increasingly defined state obligations. The second half of the article will analyze the evolution of the due diligence standard within the European Court of Human Rights (ECHR) and the application of the standard in two landmark cases, and Both cases held national governments responsible for failing to exercise due diligence to adequately protect individuals from domestic violence. The decisions in these cases not only affirm the use of the due diligence standard as a tool for assessment, but also they begin to clarify the practical obligations of protecting victims from domestic violence as well as preventing, investigating, and prosecuting such violence. In particular, the ECHR highlights the need for enforceable measures of protection and a legislative framework that enables criminal prosecutions of domestic violence in the public interest. Furthermore, the article will analyze the decision in and the Court\u27s recognition that a State\u27s to exercise due diligence to protect women against domestic violence is gender-based discrimination, violating women\u27s right to equal protection of the law

    Use of an Oriented Transmembrane Protein to Probe the Assembly of a Supported Phospholipid Bilayer

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    Planar-supported phopholipid bilayers formed by te adsorpton of vesicles are increasingly used in the investigation of lipK-ependent reactis. We have studied the way in which these bilayers are forned with phopholipid vesicles coaining the btranembrane protein Tssue Factor (TF). TF complexed with te senne protease, factor Vlla, is the primary initiator of bklod coagulation by way of activation of the zymogen factor X. TF has been shown to orient randomly on the inner and outer leaflets of vesicles. We used proteolytic digestion to produce vesicles in which the exracellular domain of TF is located on the inner leaflet These vesicles show no cofactor activity for factor Vila as a result of the inability of the extacellular domain of TF to bind Vila. After freeze/thawing, 50% of the cofactor activity was regained, indicating reorientation of the sequestered, inner leaflet TF. Adsorpion of these vesicles to the inner surface of glass microcapillaries results in a continuous phospholpid bilayer. The microcapillaries were perftsed with a solution of factors Vlla and X, and the effluent was monitored for factor Xa production, a sensifive measure of the activity of the TF-Vlla complex. For coatings produced with the digested vesicles, minimal TF-Vlla acfivity was observed, showing that the supported bilayer preserves the oientation of the leaflets in the vesicles, i.e., the outer leaflet of the vesicles forms the outer leaflet of the supported bilayer

    Coexistent gout and systemic lupus erythematosus

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    No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37755/1/1780240719_ftp.pd

    Enhancement of Radiation Effect on Cancer Cells by Gold-pHLIP

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    Previous research has shown that gold nanoparticles can increase the effectiveness of radiation on cancer cells. Improved radiation effectiveness would allow lower radiation doses given to patients, reducing adverse effects; alternatively, it would provide more cancer killing at current radiation doses. Damage from radiation and gold nanoparticles depends in part on the Auger effect, which is very localized; thus, it is important to place the gold nanoparticles on or in the cancer cells. In this work, we use the pH-sensitive, tumor-targeting agent, pH Low-Insertion Peptide (pHLIP), to tether 1.4-nm gold nanoparticles to cancer cells. We find that the conjugation of pHLIP to gold nanoparticles increases gold uptake in cells compared with gold nanoparticles without pHLIP, with the nanoparticles distributed mostly on the cellular membranes. We further find that gold nanoparticles conjugated to pHLIP produce a statistically significant decrease in cell survival with radiation compared with cells without gold nanoparticles and cells with gold alone. In the context of our previous findings demonstrating efficient pHLIP-mediated delivery of gold nanoparticles to tumors, the obtained results serve as a foundation for further preclinical evaluation of dose enhancement

    Environments of the Four Tryptophans in the Extracellular Domain of Human Tissue Factor: Comparison of Results from Absorption and Fluorescence Difference Spectra of Tryptophan Replacement Mutants with the Crystal Structure of the Wild-Type Protein

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    The local environments of the four tryptophan residues of the extracellular domain of human tissue factor (sTF) were assessed from difference absorption and fluorescence spectra. The difference spectra were derived by subtracting spectra from single Trp-to-Phe or Trp-to-Tyr replacement mutants from the corresponding spectrum of the wild-type protein. Each of the mutants was capable of enhancing the proteolytic activity of factor Vila showing that the mutations did not introduce major structural changes, although the mutants were more susceptible to denaturation by guanidinium chloride. The difference spectra indicate that the Trp residues are buried to different extents within the protein matrix. This evaluation was compared with the x-ray crystal structure of sTF. There is excellent agreement between predictions from the difference spectra and the environments of the Trp residues observed in the x-ray crystal structure, demonstrating that difference absorption and particularly fluorescence spectra derived from functional single-Trp replacement mutants can be used to obtain information about the local environments of individual Trp residues in multi-tryptophan proteins
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