Development of Preventive Measures to Reduce Mortalities for Holding Live Wild-caught Flounder in Recirculating Aquaculture Systems

A substantial high-value market exists for wild-caught live summer flounder (Paralichthys dentatus). An important component of accessing this market is the ability to hold wild-caught flounder in land based recirculating aquaculture systems (RAS). A major constraint to holding summer flounder in land-based RAS is fish mortalities associated with the ectoparasite argulus spp. Very little information exists that provides a live flounder holding facility with FDA approved treatment options to prevent introduction of argulus from wild caught fish into holding systems. The project objective was to test the available FDA approved chemotherapeutics for treatment of ectoparasite infections in summer flounder. To validate treatment efficacy, 8 infected individuals were treated with bath treatments according to maximum recommended doses (250ppm formalin for 60 m; 200 ppm hydrogen peroxide for 30 m; and freshwater for 20 m) and then transferred to separate RAS to monitor for two weeks. Daily observations were made to determine if treatments were lethal to the attached argulus. Following the two week monitoring period, fish from all treatments showed no sign of a reduction in attached argulus. According to the findings of this study, there are currently no FDA approved treatments for argulus infections on summer flounder. It is recommended that a live wild flounder holding facility visually inspect all incoming fish for the presence of argulus and maintain fish in a quarantine system prior to holding in a RAS

Reachability in Biochemical Dynamical Systems by Quantitative Discrete Approximation (extended abstract)

In this paper, a novel computational technique for finite discrete approximation of continuous dynamical systems suitable for a significant class of biochemical dynamical systems is introduced. The method is parameterized in order to affect the imposed level of approximation provided that with increasing parameter value the approximation converges to the original continuous system. By employing this approximation technique, we present algorithms solving the reachability problem for biochemical dynamical systems. The presented method and algorithms are evaluated on several exemplary biological models and on a real case study.Comment: In Proceedings CompMod 2011, arXiv:1109.104

Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations

Understanding and control of structures and rates involved in protein-ligand binding are es- sential for drug design. Unfortunately, atomistic molecular dynamics (MD) simulations cannot di- rectly sample the excessively long residence and rearrangement times of tightly binding complexes. Here we exploit the recently developed multi-ensemble Markov model framework to compute full protein-peptide kinetics of the oncoprotein fragment 25−109Mdm2 and the nano-molar inhibitor peptide PMI. Using this system, we report, for the first time, direct estimates of kinetics beyond the seconds timescales using simulations of an all-atom MD model, with high accuracy and pre- cision. These results only require explicit simulations on the sub-milliseconds timescale and are tested against existing mutagenesis data and our own experimental measurements of the dissoci- ation and association rates. The full kinetic model reveals an overall downhill but rugged binding funnel with multiple pathways. The overall strong binding arises from a variety of conformations with different hydrophobic contact surfaces that interconvert on the milliseconds timescale.Funding is acknowledged by European Commission (ERC StG “pcCells” to F.N.), Deutsche Forschungsgemeinschaft (SFB 1114/C3, SFB 740/D7, and TRR 186/A12 to F.N. and SFB 1114/A4 to F.N. and T.W.). J.C. is a Wellcome Trust Senior Research Fellow (WT 095195MA). J.S. is a Marie Sklodowska-Curie Internationally outgoing fellow. M.D.C. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) studentship

Smoking characteristics of Polish immigrants in Dublin

<p>Abstract</p> <p>Background</p> <p>This study examined two main hypotheses: a) Polish immigrants' smoking estimates are greater than their Irish counterparts (b) Polish immigrants purchasing cigarettes from Poland smoke "heavier" (≥ 20 cigarettes a day) when compared to those purchasing cigarettes from Ireland. The study also set out to identify significant predictors of 'current' smoking (some days and everyday) among the Polish immigrants.</p> <p>Methods</p> <p>Dublin residents of Polish origin (n = 1,545) completed a previously validated Polish questionnaire in response to an advertisement in a local Polish lifestyle magazine over 5 weekends (July–August, 2007). The Office of Tobacco Control telephone-based monthly survey data were analyzed for the Irish population in Dublin for the same period (n = 484).</p> <p>Results</p> <p>Age-sex adjusted smoking estimates were: 47.6% (95% Confidence Interval [CI]: 47.3%; 48.0%) among the Poles and 27.8% (95% CI: 27.2%; 28.4%) among the general Irish population (p < 0.001). Of the57% of smokers (n = 345/606) who purchased cigarettes solely from Poland and the 33% (n = 198/606) who purchased only from Ireland, 42.6% (n = 147/345) and 41.4% (n = 82/198) were "heavy" smokers, respectively (p = 0.79). Employment (Odds Ratio [OR]: 2.89; 95% CI: 1.25–6.69), lower education (OR: 3.76; 95%CI: 2.46–5.74), and a longer stay in Ireland (>24 months) were significant predictors of current smoking among the Poles. An objective validation of the self-reported smoking history of a randomly selected sub-sample immigrant group, using expired carbon monoxide (CO) measurements, showed a highly significant correlation coefficient (r = 0.64) of expired CO levels with the reported number of cigarettes consumed (p < 0.0001).</p> <p>Conclusion</p> <p>Polish immigrants' smoking estimates are higher than their Irish counterparts, and particularly if employed, with only primary-level education, and are overseas >2 years.</p

CheriABI: Enforcing Valid Pointer Provenance and Minimizing Pointer Privilege in the POSIX C Run-time Environment

The CHERI architecture allows pointers to be implemented as capabilities (rather than integer virtual addresses) in a manner that is compatible with, and strengthens, the semantics of the C language. In addition to the spatial protections offered by conventional fat pointers, CHERI capabilities offer strong integrity, enforced provenance validity, and access monotonicity. The stronger guarantees of these architectural capabilities must be reconciled with the real-world behavior of operating systems, run-time environments, and applications. When the process model, user-kernel interactions, dynamic linking, and memory management are all considered, we observe that simple derivation of architectural capabilities is insufficient to describe appropriate access to memory. We bridge this conceptual gap with a notional \emph{abstract capability} that describes the accesses that should be allowed at a given point in execution, whether in the kernel or userspace. To investigate this notion at scale, we describe the first adaptation of a full C-language operating system (FreeBSD) with an enterprise database (PostgreSQL) for complete spatial and referential memory safety. We show that awareness of abstract capabilities, coupled with CHERI architectural capabilities, can provide more complete protection, strong compatibility, and acceptable performance overhead compared with the pre-CHERI baseline and software-only approaches. Our observations also have potentially significant implications for other mitigation techniques.This work was supported by the Defense Advanced Research Projects Agency (DARPA) and the Air Force Research Laboratory (AFRL), under contracts FA8750-10-C-0237 (``CTSRD'') and HR0011-18-C-0016 (``ECATS''). The views, opinions, and/or findings contained in this report are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. We also acknowledge the EPSRC REMS Programme Grant (EP/K008528/1), the ERC ELVER Advanced Grant (789108), Arm Limited, HP Enterprise, and Google, Inc. Approved for Public Release, Distribution Unlimited

PET imaging of αvβ3 integrin expression in tumours with 68Ga-labelled mono-, di- and tetrameric RGD peptides

Contains fulltext : 97195.pdf (publisher's version ) (Closed access)PURPOSE: Due to the restricted expression of alpha(v)beta(3) in tumours, alpha(v)beta(3) is considered a suitable receptor for tumour targeting. In this study the alpha(v)beta(3)-binding characteristics of (68)Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their (111)In-labelled counterparts. METHODS: A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)](2)) and a tetrameric (E{E[c(RGDfK)](2)}(2)) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with (68)Ga. In vitro alpha(v)beta(3)-binding characteristics were determined in a competitive binding assay. In vivo alpha(v)beta(3)-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. RESULTS: The IC(50) values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)](2) and DOTA-E{E[c(RGDfK)](2)}(2) were 23.9 +/- 1.22, 8.99 +/- 1.20 and 1.74 +/- 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 +/- 1.15, 3.34 +/- 1.16 and 1.80 +/- 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the (68)Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 +/- 0.30, 5.24 +/- 0.27 and 7.11 +/- 0.67%ID/g, respectively) was comparable to that of their (111)In-labelled counterparts (2.70 +/- 0.29, 5.61 +/- 0.85 and 7.32 +/- 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. CONCLUSION: The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The (68)Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of alpha(v)beta(3) expression with PET

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809