1,220 research outputs found

    Innovative Approaches to Diversion Data

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    Prosecutors across the country are collecting and using data to make decisions in their offices. At the same time, prosecutors are interested in developing and sustaining prosecutorial diversion approaches. Prosecutors can use data to assist in decision-making regarding diversion case processing choices as well as to make office policy and resource allocation decisions that, in turn, support expanded diversion programs. Data collection can help prosecutors decide if a prosecutorial diversion program will work for them, and if so, what characteristics it should have. Finally, data can help prosecutors see whether they are obtaining their intended outcomes. Prosecutors possess varying levels of data and resources for using data. Using a case study of how the Manhattan District Attorney\u27s Office, a data-heavy prosecutor\u27s office, has incorporated data into its diversion decision-making, this paper will discuss how data can be collected, analyzed, and shared in developing and overseeing a prosecutor-led diversion program to increase transparency, efficiency, effectiveness, and consistency

    Valence-bond Non-equilibrium Solvation Model for a Twisting Monomethine Cyanine

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    We propose and analyze a two-state valence-bond model of non-equilibrium solvation effects on the excited-state twisting reaction of monomethine cyanines. Suppression of this reaction is thought responsible for environment-dependent fluorescence yield enhancement in these dyes. Fluorescence is quenched because twisting is accompanied via the formation of dark twisted intramolecular charge-transfer (TICT) states. For monomethine cyanines, where the ground state is a superposition of structures with different bond and charge localization, there are two possible twisting pathways with different charge localization in the excited state. For parameters corresponding to symmetric monomethines, the model predicts two low-energy twisting channels on the excited-state surface that lead to a manifold of twisted intramolecular charge-transfer (TICT) states. For typical monomethines, twisting on the excited state surface will occur with a small barrier or no barrier. Changes in the solvation configuration can differentially stabilize TICT states in channels corresponding to different bonds, and that the position of a conical intersection between adiabatic states moves in response to solvation to stabilize either one channel or the other. There is a conical intersection seam that grows along the bottom of the excited-state potential with increasing solvent polarity. For monomethine cyanines with modest-sized terminal groups in moderately polar solution, the bottom of the excited-state potential surface is completely spanned by a conical intersection seam.Comment: To appear in the Journal of Chemical Physic

    Structure of Frequency-Interacting RNA Helicase from \u3ci\u3eNeurospora crassa\u3c/i\u3e Reveals High Flexibility in a Domain Critical for Circadian Rhythm and RNA Surveillance

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    The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact. In contrast with the earlier FRH structures, a new crystal form of FRH results in an ATP binding site that is undisturbed by crystal contacts and adopts a conformation consistent with nucleotide binding and hydrolysis. Strikingly, this new FRH structure adopts an arch domain conformation that is dramatically altered from previous structures. Comparison of the existing FRH structures reveals conserved hinge points that appear to facilitate arch motion. Regions in the arch have been previously shown to mediate a variety of protein-protein interactions critical for RNA surveillance and circadian clock functions. The conformational changes highlighted in the FRH structures provide a platform for investigating the relationship between arch dynamics and Mtr4/FRH function

    Sustained antigen release polyanhydride-based vaccine platform for immunization against bovine brucellosis

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    Brucellosis is a bacterial zoonosis and a significant source of economic loss and a major public health concern, worldwide. Bovine brucellosis, as caused primarily by Brucella abortus, is an important cause of reproductive loss in cattle. Vaccination has been the most effective way to reduce disease prevalence contributing to the success of control and eradication programs. Currently, there are no human vaccines available, and despite the success of commercial vaccines for livestock, such as B. abortus strain RB51 (RB51), there is need for development of novel and safer vaccines against brucellosis. In the current study, we report the fabrication of and immune responses to an implantable single dose polyanhydride-based, methanol-killed RB51 antigen containing delivery platform (VPEAR) in cattle. In contrast to animals vaccinated with RB51, we did not observe measurable RB51-specific IFN-Îł or IgG responses in the peripheral blood, following initial vaccination with VPEAR. However, following a subsequent booster vaccination with RB51, we observed an anamnestic response in both vaccination treatments (VPEAR and live RB51). The magnitude and kinetics of CD4+ IFN-Îł-mediated responses and circulating memory T cell subpopulations were comparable between the two vaccination treatments. Additionally, IgG titers were significantly increased in animals vaccinated with VPEAR as compared to live RB51- vaccinated animals. These data demonstrate that killed antigen may be utilized to generate and sustain memory, IFN-Îł-mediated, CD4+ T cell and humoral responses against Brucella in a natural host. To our knowledge, this novel approach to vaccination against intracellular bacteria, such as Brucella, has not been reported before

    Psychometric properties of the revised children’s anxiety and depression scale (RCADS) for autistic youth without co-occurring intellectual disability

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    Autistic youth often present with comorbid anxiety and depression yet there is a dearth of validated assessment tools. The Revised Children’s Anxiety and Depression Scale (RCADS) assesses internalizing symptoms but there is little psychometric data in autistic youth. Treatment-seeking autistic youth with anxiety or obsessive-compulsive symptoms (N = 74; age 6–14 years), and caregivers, were administered the RCADS-Parent, RCADS-Child, and assessments of internalizing, externalizing symptoms and social impairment indicative of autism. RCADS-Parent and RCADS-Child total anxiety scores demonstrated excellent internal consistency, and the six subscales demonstrated acceptable-to-good internal consistency. The RCADS-Child and Parent total anxiety scores were weakly correlated, and neither child age nor gender altered the strength of this association. Convergent validity was supported by moderate-to-strong correlations with clinician and parent-reported anxiety symptoms. Support for divergent validity was mixed. Results provide support for the RCADS-Parent and RCADS-Child as reliable, valid measures of internalizing symptoms in autistic youth

    Multi-omic detection of Mycobacterium leprae in archaeological human dental calculus

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    Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record.publishedVersio
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