Rethinking Justice in Massachusetts: Public Attitudes Toward Crime and Punishment

Presents results from a public opinion survey about the sharp increase in the incarcerated population in Massachusetts and about current strategies for reintegrating ex-offenders who have been released into the community

Detection of gunshot residues using mass spectrometry

In recent years, forensic scientists have become increasingly interested in the detection and interpretation of organic gunshot residues (OGSR) due to the increasing use of lead- and heavy metal-free ammunition. This has also been prompted by the identification of gunshot residue- (GSR-) like particles in environmental and occupational samples. Various techniques have been investigated for their ability to detect OGSR. Mass spectrometry (MS) coupled to a chromatographic system is a powerful tool due to its high selectivity and sensitivity. Further, modern MS instruments can detect and identify a number of explosives and additives which may require different ionization techniques. Finally, MS has been applied to the analysis of both OGSR and inorganic gunshot residue (IGSR), although the "gold standard" for analysis is scanning electron microscopy with energy dispersive X-ray microscopy (SEM-EDX). This review presents an overview of the technical attributes of currently available MS and ionization techniques and their reported applications to GSR analysis. © 2014 Regina Verena Taudte et al

Regulation of peptide import through phosphorylation of Ubr1, the ubiquitin ligase of the N-end rule pathway

Substrates of the N-end rule pathway include proteins with destabilizing N-terminal residues. These residues are recognized by E3 ubiquitin ligases called N-recognins. Ubr1 is the N-recognin of the yeast Saccharomyces cerevisiae. Extracellular amino acids or short peptides up-regulate the peptide transporter gene PTR2, thereby increasing the capacity of a cell to import peptides. Cup9 is a transcriptional repressor that down-regulates PTR2. The induction of PTR2 by peptides or amino acids involves accelerated degradation of Cup9 by the N-end rule pathway. We report here that the Ubr1 N-recognin, which conditionally targets Cup9 for degradation, is phosphorylated in vivo at multiple sites, including Ser300 and Tyr277. We also show that the type-I casein kinases Yck1 and Yck2 phosphorylate Ubr1 on Ser300, and thereby make possible (“prime”) the subsequent (presumably sequential) phosphorylations of Ubr1 on Ser296, Ser292, Thr288, and Tyr277 by Mck1, a kinase of the glycogen synthase kinase 3 (Gsk3) family. Phosphorylation of Ubr1 on Tyr277 by Mck1 is a previously undescribed example of a cascade-based tyrosine phosphorylation by a Gsk3-type kinase outside of autophosphorylation. We show that the Yck1/Yck2-mediated phosphorylation of Ubr1 on Ser300 plays a major role in the control of peptide import by the N-end rule pathway. In contrast to phosphorylation on Ser300, the subsequent (primed) phosphorylations, including the one on Tyr277, have at most minor effects on the known properties of Ubr1, including regulation of peptide import. Thus, a biological role of the rest of Ubr1 phosphorylation cascade remains to be identified

The IL-1 family in relation to psoriasis

Psoriasis is a common chronic inflammatory skin disease which can also affect the joints. Its pathogenesis is still to be fully elucidated and involves a wide range of inflammatory mediators, tissue and immune cells. At present, there is no treatment available to cure psoriasis. Although biologics have considerably improved the treatment of the most severe cases there is still a pressing clinical need to improve therapy for specific disease subtypes (e.g. pustular psoriasis) and the vast majority of patients suffering from psoriasis classified as mild to moderate. In particular, efficient and well tolerated topical approaches are lacking. This work has focused 1) on advancing our understanding of IL-36 cytokines which are recognised for their significance in pustular psoriasis, 2) on identifying endogenous disease limiting mediators such as IL-18 binding protein and how they could be manipulated in a therapeutic approach and 3) on IL-17 neutralising RNA aptamers as tools for topical therapy. Main results include the identification of biologic activity of processed and non-processed IL-36 members. N-terminal cleavage is required to increase activity of all IL-36 members. The protease responsible for IL-36RA processing was elucidated. Neutrophil proteases as well as kallikrein 7 can cleave pro-inflammatory IL-36 members. However, a second processing step seems necessary for full activation and the potentially responsible aminopeptidase remains to be identified. Secondly, it was found that human primary fibroblasts produce significant levels of IL-18BP, which controls pro-inflammatory function of IL-18. Endogenous IL-18BP can be induced by IL-27 which, when given in combination with hydrocortisone does not induce pro-inflammatory responses. Thirdly, an IL-17 specific aptamer was verified to block IL-17A activity in fibroblast and fibroblast Th17 co-cultures but not in keratinocyte cultures. Significant uptake of the RNA aptamer by keratinocytes was identified as potentially responsible for the lack of neutralising capacity

Handling Trajectory Uncertainties for Airborne Conflict Management

Airborne conflict management is an enabling capability for NASA's Distributed Air-Ground Traffic Management (DAG-TM) concept. DAGTM has the goal of significantly increasing capacity within the National Airspace System, while maintaining or improving safety. Under DAG-TM, autonomous aircraft maintain separation from each other and from managed aircraft unequipped for autonomous flight. NASA Langley Research Center has developed the Autonomous Operations Planner (AOP), an onboard decision support system that provides airborne conflict management (ACM) and strategic flight planning support for autonomous aircraft pilots. The AOP performs conflict detection, prevention, and resolution from nearby traffic aircraft and area hazards. Traffic trajectory information is assumed to be provided by Automatic Dependent Surveillance Broadcast (ADS-B). Reliable trajectory prediction is a key capability for providing effective ACM functions. Trajectory uncertainties due to environmental effects, differences in aircraft systems and performance, and unknown intent information lead to prediction errors that can adversely affect AOP performance. To accommodate these uncertainties, the AOP has been enhanced to create cross-track, vertical, and along-track buffers along the predicted trajectories of both ownship and traffic aircraft. These buffers will be structured based on prediction errors noted from previous simulations such as a recent Joint Experiment between NASA Ames and Langley Research Centers and from other outside studies. Currently defined ADS-B parameters related to navigation capability, trajectory type, and path conformance will be used to support the algorithms that generate the buffers

LA-ICP-MS/MS improves limits of detection in elemental bioimaging of gadolinium deposition originating from MRI contrast agents in skin and brain tissues

© 2018 Elsevier GmbH A novel analytical method to detect the retention of gadolinium from contrast agents for magnetic resonance imaging (MRI) in tissue samples of patients is presented. It is based on laser ablation - inductively coupled plasma - triple quadrupole - mass spectrometry (LA-ICP-MS/MS). Both Gd and P were monitored with a mass shift of +16, corresponding to mono-oxygenated species, as well as Zn, Ca, and Fe on-mass. This method resulted in a significantly reduced background and improved limits of detection not only for phosphorus, but also for gadolinium. These improvements were essential to perform elemental bioimaging with improved resolution of 5 μm x 5 μm, allowing the detection of small Gd deposits in fibrotic skin and brain tumour tissue with diameters of approximately 50 μm. Detailed analyses of these regions revealed that most Gd was accompanied with P and Ca, indicating co-precipitation

A portable explosive detector based on fluorescence quenching of pyrene deposited on coloured wax-printed μpADs

A new technique for the detection of explosives has been developed based on fluorescence quenching of pyrene on paper-based analytical devices (μPADs). Wax barriers were generated (150 °C, 5 min) using ten different colours. Magenta was found as the most suitable wax colour for the generation of the hydrophobic barriers with a nominal width of 120 μm resulting in fully functioning hydrophobic barriers. One microliter of 0.5 mg mL-1 pyrene dissolved in an 80 : 20 methanol-water solution was deposited on the hydrophobic circle (5 mm diameter) to produce the active microchip device. Under ultra-violet (UV) illumination, ten different organic explosives were detected using the μPAD, with limits of detection ranging from 100-600 ppm. A prototype of a portable battery operated instrument using a 3 W power UV light-emitting-diode (LED) (365 nm) and a photodiode sensor was also built and evaluated for the successful automatic detection of explosives and potential application for field-based screening. © 2013 The Royal Society of Chemistry