59 research outputs found
From Collapse to Freezing in Random Heteropolymers
We consider a two-letter self-avoiding (square) lattice heteropolymer model
of N_H (out ofN) attracting sites. At zero temperature, permanent links are
formed leading to collapse structures for any fraction rho_H=N_H/N. The average
chain size scales as R = N^{1/d}F(rho_H) (d is space dimension). As rho_H -->
0, F(rho_H) ~ rho_H^z with z={1/d-nu}=-1/4 for d=2. Moreover, for 0 < rho_H <
1, entropy approaches zero as N --> infty (being finite for a homopolymer). An
abrupt decrease in entropy occurs at the phase boundary between the swollen (R
~ N^nu) and collapsed region. Scaling arguments predict different regimes
depending on the ensemble of crosslinks. Some implications to the protein
folding problem are discussed.Comment: 4 pages, Revtex, figs upon request. New interpretation and emphasis.
Submitted to Europhys.Let
No Evidence of a Drug-Drug Interaction Between Letermovir (MK-8228) and Mycophenolate Mofetil
Introduction:
Letermovir (MK-8228) is a potent, oncedaily inhibitor of the cytomegalovirus (CMV) terminase complex that is being developed for the prophylaxis of CMV infection in transplant patients. This study evaluated the pharmacokinetic interactions, safety, and tolerability of letermovir when coadministered in healthy subjects with mycophenolate mofetil (MMF), which is the morpholinoethyl ester prodrug of mycophenolic acid (MPA).
Methods:
This was an open-label trial in 14 healthy female subjects that explored the pharmacokinetic parameters of a single 1 g oral dose of MMF administered alone on Day 1 and coadministered on Day 12 with 480 mg oral once-daily letermovir given on Day 5 and from Day 8 continued through Day 16. Letermovir PK was assessed at single dose (Day 5) and at steady state on Day 12 (with MMF) and Day 16 (alone following MMF washout).
Results:
Coadministration of 480 mg qd letermovir at steady state with a single dose of 1 g of MMF had no effect on the pharmacokinetics of MPA. The MPA AUC0-inf and Cmax geometric mean ratios (GMRs) [90% confidence interval] for the comparison (MMF with letermovir/ MMF alone) were 1.08 [0.96, 1.21] and 0.96 [0.81, 1.13], respectively. Coadministration of a single dose of 1 g MMF with 480 mg qd letermovir at steady state had no clinically meaningful effect on the pharmacokinetics of letermovir, with AUC0-24 and Cmax GMR of 1.18 [1.04, 1.32] and 1.11 [0.93, 1.34], respectively. The letermovir geometric mean accumulation ratio (Day 16/Day 5) and 95% CI were 1.13 [0.90, 1.42] for AUC0-24 and 1.01 [ 0.79, 1.28] f or Cmax, indicating that accumulation of letermovir when administered as daily doses is minimal. All related AEs were reported as mild in severity and resolved.
Conclusions:
Multiple-dose administration of 480 mg letermovir daily with a single dose of 1 g MMF was generally well tolerated by the healthy subjects in this study. Coadministration of letermovir and MMF had no clinically meaningful effect on the PK of letermovir or MPA. Letermovir and MMF may be coadministered without dose adjustment
Analysis of benzo[a]pyrene metabolites formed by rat hepatic microsomes using high pressure liquid chromatography: optimization of the method
A simple and sensitive method was developed to separate the carcinogenic polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), and six of its oxidation metabolites generated by rat hepatic microsomes enriched with cytochrome P450 (CYP) 1A1, by high pressure liquid chromatography (HPLC). The HPLC method, using an acetonitrile/water gradient as mobile phase and UV detection, provided appropriate separation and detection of both mono- and di-hydroxylated metabolites of BaP as well as BaP diones formed by rat hepatic microsomes and the parental BaP. In this enzymatic system, 3-hydroxy BaP, 9-hydroxy BaP, BaP-4,5-dihydrodiol, BaP-7,8-dihydrodiol, BaP-9,10-dihydrodiol and BaP-dione were generated. Among them the mono-hydroxylated BaP metabolite, 3-hydroxy BaP followed by di-hydroxylated BaP products, BaP-7,8-dihydrodiol and BaP-9,10-dihydrodiol, predominated, while BaP-dione was a minor metabolite. This HPLC method will be useful for further defining the roles of the CYP1A1 enzyme with both in vitro and in vivo models in understanding its real role in activation and detoxification of BaP
Sights and insights: Vocational outdoor students’ learning
Outdoor leader and adventure sport education in the United Kingdom has been characterized by an over-emphasis on technical skills at the expense of equally important, but often marginalized intra- and inter-personal skills necessary for contemporary outdoor employment. This study examined the lived experience of vocational outdoor students in order, firstly, to identify what was learned about the workplace through using reflective practice and, secondly, what was learned about reflective practice through this experience. The study used a purposive sample of students (n=15) who were invited to maintain reflective journals during summer work experience, and this was followed up with semi-structured interviews. Manual Interpretative Phenomenological Analysis (IPA) revealed that in the workplace setting students used reflective practice to understand and develop technical proficiency, support awareness of the value of theory, and acted as a platform to express emergent concepts of ‘professionalism’. Lessons about reflective practice emphasized its value in social settings, acknowledging different ways of reflection, and understanding and managing professional life beyond graduation
Children, civilianhood, and humanitarian securitization
In this paper, the influence of the construction of children as civilians over the processes of securitization in the US intervention in Somalia is examined. This is done through an analysis of the US print news media coverage of that event. The study employs two key theoretical frameworks: the first is the social understanding of civilianhood; and the second is the Copenhagen School’s theory of securitization. The work concludes that a failure to unpack the value of referent objects of security diminishes the insights that securitization theory can offer. The grammar of securitizing moves cannot be fully comprehended in instances of militarized humanitarian interventions, in particular, without this kind of analysis. Children as suffering civilians draw considerable attention from the world’s media and thus an investigation of their role in securitization can be highly informative
Mapping genes for fatness and growth on pig chromosome 13: a search in the region close to the pig PIT1 gene
Exercise therapy and cognitive behavioural therapy to improve fatigue, daily activity performance and quality of life in Postpoliomyelitis Syndrome: the protocol of the FACTS-2-PPS trial
Contains fulltext :
88661.pdf (publisher's version ) (Open Access)BACKGROUND: Postpoliomyelitis Syndrome (PPS) is a complex of late onset neuromuscular symptoms with new or increased muscle weakness and muscle fatigability as key symptoms. Main clinical complaints are severe fatigue, deterioration in functional abilities and health related quality of life. Rehabilitation management is the mainstay of treatment. Two different therapeutic interventions may be prescribed (1) exercise therapy or (2) cognitive behavioural therapy (CBT). However, the evidence on the effectiveness of both interventions is limited. The primary aim of the FACTS-2-PPS trial is to study the efficacy of exercise therapy and CBT for reducing fatigue and improving activities and quality of life in patients with PPS. Additionally, the working mechanisms, patients' and therapists' expectations of and experiences with both interventions and cost-effectiveness will be evaluated. METHODS/DESIGN: A multi-centre, single-blinded, randomized controlled trial will be conducted. A sample of 81 severely fatigued patients with PPS will be recruited from 3 different university hospitals and their affiliate rehabilitation centres. Patients will be randomized to one of three groups i.e. (1) exercise therapy + usual care, (2) CBT + usual care, (3) usual care. At baseline, immediately post-intervention and at 3- and 6-months follow-up, fatigue, activities, quality of life and secondary outcomes will be assessed. Costs will be based on a cost questionnaire, and statistical analyses on GEE (generalized estimated equations). Analysis will also consider mechanisms of change during therapy. A responsive evaluation will be conducted to monitor the implementation process and to investigate the perspectives of patients and therapists on both interventions. DISCUSSION: A major strength of the FACTS-2-PPS study is the use of a mixed methods design in which a responsive and economic evaluation runs parallel to the trial. The results of this study will generate new evidence for the rehabilitation treatment of persons with PPS. TRIAL REGISTRATION: Dutch Trial Register NTR1371
Perceived consequences of ageing with late effects of polio and strategies for managing daily life: a qualitative study
Towards an atomic level understanding of niobia based catalysts and catalysis by combining the science of catalysis with surface science
Cobalt Fischer−Tropsch Catalysts Using Nickel Promoter as a Rhenium Substitute to Suppress Deactivation
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