The deprivation of certitude, legitimacy and hope: foreign national prisoners and the pains of imprisonment

At the end of March 2015 there were 10,481 foreign nationals (defined as non-UK passport holders) held in prisons in England and Wales, representing 12 per cent of the overall prison population. The latest published figures from December 2014 also indicated that there were a further 394 immigration detainees also being held in various prisons, rather than Immigration Removal Centres, across England and Wales. Although Sykes’s deprivation model with its associated ‘pains of imprisonment’ has been exhaustively explored by penologists, this article argues that there are a new range of ‘pains’ uniquely faced by foreign national prisoners in England and Wales who come under the scrutiny of the Home Office’s Immigration Service. Drawing on quasi-ethnographic fieldwork in a Specialist Foreign National Prison, this article discusses the new pains relating to a lack of certitude, legitimacy and hope with regard to both their carceral and post-carceral lives

MRP3: a molecular target for human glioblastoma multiforme immunotherapy.

<p>Abstract</p> <p>Background</p> <p>Glioblastoma multiforme (GBM) is refractory to conventional therapies. To overcome the problem of heterogeneity, more brain tumor markers are required for prognosis and targeted therapy. We have identified and validated a promising molecular therapeutic target that is expressed by GBM: human multidrug-resistance protein 3 (MRP3).</p> <p>Methods</p> <p>We investigated MRP3 by genetic and immunohistochemical (IHC) analysis of human gliomas to determine the incidence, distribution, and localization of MRP3 antigens in GBM and their potential correlation with survival. To determine MRP3 mRNA transcript and protein expression levels, we performed quantitative RT-PCR, raising MRP3-specific antibodies, and IHC analysis with biopsies of newly diagnosed GBM patients. We used univariate and multivariate analyses to assess the correlation of RNA expression and IHC of MRP3 with patient survival, with and without adjustment for age, extent of resection, and KPS.</p> <p>Results</p> <p>Real-time PCR results from 67 GBM biopsies indicated that 59/67 (88%) samples highly expressed <it>MRP3 </it>mRNA transcripts, in contrast with minimal expression in normal brain samples. Rabbit polyvalent and murine monoclonal antibodies generated against an extracellular span of MRP3 protein demonstrated reactivity with defined <it>MRP3</it>-expressing cell lines and GBM patient biopsies by Western blotting and FACS analyses, the latter establishing cell surface MRP3 protein expression. IHC evaluation of 46 GBM biopsy samples with anti-MRP3 IgG revealed MRP3 in a primarily membranous and cytoplasmic pattern in 42 (91%) of the 46 samples. Relative RNA expression was a strong predictor of survival for newly diagnosed GBM patients. Hazard of death for GBM patients with high levels of <it>MRP3 </it>RNA expression was 2.71 (95% CI: 1.54-4.80) times that of patients with low/moderate levels (p = 0.002).</p> <p>Conclusions</p> <p>Human GBMs overexpress MRP3 at both mRNA and protein levels, and elevated MRP3 mRNA levels in GBM biopsy samples correlated with a higher risk of death. These data suggest that the tumor-associated antigen MRP3 has potential use for prognosis and as a target for malignant glioma immunotherapy.</p

The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs

Drug transporters are recognized as key players in the processes of drug absorption, distribution, metabolism, and elimination. The localization of uptake and efflux transporters in organs responsible for drug biotransformation and excretion gives transporter proteins a unique gatekeeper function in controlling drug access to metabolizing enzymes and excretory pathways. This review seeks to discuss the influence intestinal and hepatic drug transporters have on pharmacokinetic parameters, including bioavailability, exposure, clearance, volume of distribution, and half-life, for orally dosed drugs. This review also describes in detail the Biopharmaceutics Drug Disposition Classification System (BDDCS) and explains how many of the effects drug transporters exert on oral drug pharmacokinetic parameters can be predicted by this classification scheme

Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

Measurement of the mass difference m(D-s(+))-m(D+) at CDF II

We present a measurement of the mass difference m(D-s(+))-m(D+), where both the D-s(+) and D+ are reconstructed in the phipi(+) decay channel. This measurement uses 11.6 pb(-1) of data collected by CDF II using the new displaced-track trigger. The mass difference is found to be m(D-s(+))-m(D+)=99.41+/-0.38(stat)+/-0.21(syst) MeV/c(2)

Evaluation of Methods for the Analysis of Untreated and Processed Lignocellulosic Biomasses

The overall efficiency of the transformation of lignocellulosic materials to usable products as chemicals and fuels must be governed by adequate analysis of products before and after treatments. Using some promising technologies, lignocelluloses which are biomasses from marine plant and trees, grains, food and non-food crops, and woodbased can give products as fuel alcohol and other chemicals. Various methods of transformation from feedstock to valuable end products are discussed in the scientific literature. Therefore, yields must justify methods used for biomass transformations. As a result, adequate compositional analysis of these processing stages is needed. In this chapter, standard common methods such as gravimetric, chromatography, spectroscopic and their variations for analysis on both untreated and treated lignocelluloses are highlighted. The ease of the use and challenges with recommendations to their applicability to quantifying lignocelluloses fractionations for reproducibility and to be representative are discussed. With biomass technology, virtually all and even more products that can be produced from fossil energy can also be produced from biomass energy. Adequate analysis is therefore necessary

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate