9 research outputs found
McKithen v. Brown: Due Process and Post-Conviction DNA Testing
When the Second Circuit decided McKithen v. Brown, it joined an ever-growing list of courts faced with a difficult and pressing issue of both constitutional and criminal law: is there a federal constitutional right of post-conviction access to evidence for DNA testing? This issue, which sits at the intersection of new forensic technologies and fundamental principles of constitutional due process, has divided the courts. The Second Circuit, wary of reaching a hasty conclusion, remanded McKithenâs case to the district court for consideration. The district court for the Eastern District of New York was asked to decide whether a constitutional right of access to evidence for DNA testing exists both broadly as well as under the defendantâs circumstances. This iBrief concludes that although a due process post-conviction right of access to evidence for DNA testing may exist under some circumstances, it does not exist under current constitutional jurisprudence in McKithenâs case
Van der Waals Interactions Dominate LigandâProtein Association in a Protein Binding Site Occluded from Solvent Water
In the present study we examine the enthalpy of binding of 2-methoxy-3-isobutylpyrazine (IBMP) to the mouse major urinary protein (MUP), using a combination of isothermal titration calorimetry (ITC), NMR, X-ray crystallography, all-atom molecular dynamics simulations, and site-directed mutagenesis. Global thermodynamics data derived from ITC indicate that binding is driven by favorable enthalpic contributions, rather than a classical entropy-driven signature that might be expected given that the binding pocket of MUP-1 is very hydrophobic. The only ligandâprotein hydrogen bond is formed between the side-chain hydroxyl of Tyr120 and the ring nitrogen of the ligand in the wild-type protein. ITC measurements on the binding of IBMP to the Y120F mutant demonstrate a reduced enthalpy of binding, but nonetheless binding is still enthalpy dominated. A combination of solvent isotopic substitution ITC measurements and all-atom molecular dynamics simulations with explicit inclusion of solvent water suggests that solvation is not a major contributor to the overall binding enthalpy. Moreover, hydrogen/deuterium exchange measurements suggest that there is no significant contribution to the enthalpy of binding derived from âtighteningâ of the protein structure. Data are consistent with binding thermodynamics dominated by favorable dispersion interactions, arising from the inequality of solventâsolute dispersion interactions before complexation versus soluteâsolute dispersion interactions after complexation, by virtue of poor solvation of the binding pocket
Strong SoluteâSolute Dispersive Interactions in a ProteinâLigand Complex
The contributions of soluteâsolute dispersion interactions to binding thermodynamics have generally been thought to be small, due to the surmised equality between soluteâsolvent dispersion interactions prior to the interaction versus soluteâsolute dispersion interactions following the interaction. The thermodynamics of binding of primary alcohols to the major urinary protein (MUP-I) indicate that this general assumption is not justified. The enthalpy of binding becomes more favorable with increasing chain length, whereas the entropy of binding becomes less favorable, both parameters showing a linear dependence. Despite the hydrophobicity of the interacting species, these data show that binding is not dominated by the classical hydrophobic effect, but can be attributed to favorable ligandâprotein dispersion interactions
CuO Nanoparticle Dissolution and Toxicity to Wheat (<i>Triticum aestivum)</i> in Rhizosphere Soil
It
has been suggested, but not previously measured, that dissolution
kinetics of soluble nanoparticles such as CuO nanoparticles (NPs)
in soil affect their phytotoxicity. An added complexity is that such
dissolution is also affected by the presence of plant roots. Here,
we measured the rate of dissolution of CuO NPs in bulk soil, and in
soil in which wheat plants (<i>Triticum aestivum)</i> were
grown under two soil NP dosing conditions: (a) freshly added CuO NPs
(500 mg Cu/kg soil) and (b) CuO NPs aged for 28 d before planting.
At the end of the plant growth period (14 d), available Cu was measured
in three different soil compartments: bulk (not associated with roots),
loosely attached to roots, and rhizosphere (soil firmly attached to
roots). The labile Cu fraction increased from 17 mg/kg to 223 mg/kg
in fresh treatments and from 283 mg/kg to 305 mg/kg in aged treatments
over the growth period due to dissolution. Aging CuO NPs increased
the toxicity to <i>Triticum aestivum</i> (reduction in root
maximal length). The presence of roots in the soil had opposite and
somewhat compensatory effects on NP dissolution, as measured in rhizosphere
soil. pH increased 0.4 pH units for fresh NP treatments and 0.6 pH
units for aged NPs. This lowered CuO NP dissolution in rhizosphere
soil. Exudates from <i>T. aestivum</i> roots also increased
soluble Cu in pore water. CaCl<sub>2</sub> extractable Cu concentrations
increaed in rhizosphere soil compared to bulk soil, from 1.8 mg/kg
to 6.2 mg/kg in fresh treatment and from 3.4 mg/kg to 5.4 mg/kg
in aged treatments. Our study correlated CuO NP dissolution and
the resulting Cu ion exposure profile to phytotoxicity, and showed
that plant-induced changes in rhizosphere conditions should be considered
when measuring the dissolution of CuO NPs near roots
Persistence of copper-based nanoparticle-containing foliar sprays in Lactuca sativa (lettuce) characterized by spICP-MS
Copper oxide and hydroxide nanoparticles (Cu-NPs) are components of some commercial pesticides. When these Cu-NPs dissolve in the environment, their size distribution, efficacy, and toxicity are altered. Since acute toxicity screens typically involve pristine NPs, quantification of the transformation of their size distribution in edible leaf vegetables is necessary for
accurate consumer risk assessment. Single particle ICP-MS was used to investigate the persistence of three forms of Cu-NPs following foliar application to live lettuce (Lactuca sativa): CuO NP, Cu(OH)2 NP, and Kocide 3000Âź. A methanol-based digestion method was used to minimize Cu-NP dissolution during extraction from the leaf tissues. After dosing, the NPs associated with the leaf tissues were characterized over a 9-day period to monitor persistence. Nanoparticle counts and total copper mass concentrations remained constant, though the particle size distributions shifted down over time.Washing the leaves in tap water resulted in removal of total copper while the number of Cu-NPs remaining depended on the form applied. This work indicates
that washing of lettuce preferentially removed dissolved Cu over Cu-NPs, and that the amount of residual Cu- NPs remaining is low when applied at the recommended rates for Kocide 3000Âź.publishe
Selecting measures for the neurodevelopmental assessment of children in low- and middle-income countries
Diseases affecting millions of children in low- and middle-income countries (LMICs), such as malnutrition, micronutrient deficiency, malaria, and HIV, can lead to adverse neurodevelopmental outcomes. Thus, a key health outcome in children is neurodevelopmental status. In this paper, the neurodevelopmental screening and testing measures most commonly utilized in LMICs are reviewed, and a matrix is presented to help researchers and clinicians determine which measures may be most useful for various LMIC inquiries. The matrix is based on an Internet literature review of 114 publications for the period January 1998 to February 2016, reporting the psychometric properties of instruments tested in LMIC children. The measures are classified as screening tests or more detailed tests that include both comprehensive batteries of general development and tests of specific domains. For completeness, two experts have reviewed this paper, as well as the authors. An overview of the tests used to date is presented, including the benefits and drawbacks of each test, in order to provide researchers and developmental clinicians with a way to decide which tests may be best suited to their developmental assessment goals. Remarkable progress has been made in neurodevelopmental testing in children in LMICs over the past two decades but there remains a need for additional research in this area to develop new tests, better evaluate and adapt current tests, and assess test validity and reliability across cultures