Optimal control strategies for tuberculosis treatment: a case study in Angola

We apply optimal control theory to a tuberculosis model given by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions. Numerical simulations are given using data from Angola.Comment: This is a preprint of a paper whose final and definite form will appear in the international journal Numerical Algebra, Control and Optimization (NACO). Paper accepted for publication 15-March-201

Signal Conditioning for Cryogenic Thermometry in the LHC

Temperature measurement is a key issue in the LHC, as it will be used to regulate the cooling of the superconducting magnets. The compromise between available cooling power and the coil superconducting characteristics leads to a restricted temperature control band, around 1.9 K. An absolute accuracy DeltaT < 10 mK below 2.2 K, and DeltaT < 5 K above 25 K, is necessary. For resistive thermometers covering the full temperature range, and having a negative dR/dT sensitivity, this is typically equivalent to a relative accuracy DeltaR/R of 3 10**-3 over 3 resistance decades. Also, to limit the thermometer's self-heating, the sensing current must be limited to few muA. Furthermore, the radiation levels next to the accelerator are expected to degrade significantly the performance of conventional analogue electronics. As these stringent requirements are not met by commercial conditioners, three different architectures have been developed at CERN. The first compresses the input dynamic range using a logarithmic transfer function; the second partitions the input range into three linear regions; the third converts resistance linearly into the frequency of a square wave. They fulfil the above specifications and provide industrial robustness in terms of thermal drift, galvanic protection, and compact packaging, while optimising cost-to-performance ratio. This paper describes the principles of their design, compares their characteristics and shows results of field tests. Future developmens include ASIC versions, Fieldbus interfacing, and radiation tolerant re-design

SUMOylation inhibits FOXM1 activity and delays mitotic transition

The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response

Low energy magnetic excitations of the Mn_{12}-acetate spin cluster observed by neutron scattering

We performed high resolution diffraction and inelastic neutron scattering measurements of Mn_{12}-acetate. Using a very high energy resolution, we could separate the energy levels corresponding to the splitting of the lowest S multiplet. Data were analyzed within a single spin model (S=10 ground state), using a spin Hamiltonian with parameters up to 4^{th} order. The non regular spacing of the transition energies unambiguously shows the presence of high order terms in the anisotropy (D= -0.457(2) cm^{-1}, B_4^0 = -2.33(4) 10^{-5}cm^{-1}). The relative intensity of the lowest energy peaks is very sensitive to the small transverse term, supposed to be mainly responsible for quantum tunneling. This allows an accurate determination of this term in zero magnetic field (B_4^4 = \pm 3.0(5) 10^{-5} cm^{-1}). The neutron results are discussed in view of recent experiments and theories.Comment: 4 pages ? 3 figures, submitted to Physical Review Lette

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast

Protein disulphide isomerase-assisted functionalization of keratin-based matrices

In living systems, protein disulphide isomerase (PDI, EC 5.3.4.1) regulates the formation of new disulphide bonds in proteins (oxidase activity) and catalyzes the rearrangement of non-native disulphide bonds (isomerase activity), leading proteins towards their native configuration. In this study, PDI was used to attach cysteine-containing compounds (CCCs) onto hair, to enhance compound migration within hair fibre and to trigger protein release. A fluorescent (5(6)-TAMRA)-labelled keratin peptide was incorporated into hair by using PDI. Similarly, PDI promoted the grafting of a cysteine-functionalized dye onto wool, as suggested by matrix-assisted laser desorption and ionization time-of-flight results. These reactions were thought to involve oxidation of disulphide bonds between CCCs and wool or hair cysteine residues, catalyzed by the oxidized PDI active site. On the other hand, PDI was demonstrated to enhance the migration of a disulphide bondfunctionalized dye within the keratin matrix and trigger the release of RNase A from wool fibres’ surface. These observations may indicate that an isomerisation reaction occurred, catalyzed by the reduced PDI active site, to achieve the thiol-disulphide exchange, i.e. the rearrangement of disulphide bonds between CCCs and keratin. The present communication aims to highlight promising biotechnological applications of PDI, derived from its almost unique properties within the isomerase family.We thank to FCT "Fundacao para a Ciencia e Tecnologia" (scholarship SFRH/BD/38363/2007) for providing Margarida Fernandes the grant for PhD studies

NMR investigations of the interaction between the azo-dye sunset yellow and Fluorophenol

The interaction of small molecules with larger noncovalent assemblies is important across a wide range of disciplines. Here, we apply two complementary NMR spectroscopic methods to investigate the interaction of various fluorophenol isomers with sunset yellow. This latter molecule is known to form noncovalent aggregates in isotropic solution, and form liquid crystals at high concentrations. We utilize the unique fluorine-19 nucleus of the fluorophenol as a reporter of the interactions via changes in both the observed chemical shift and diffusion coefficients. The data are interpreted in terms of the indefinite self-association model and simple modifications for the incorporation of a second species into an assembly. A change in association mode is tentatively assigned whereby the fluorophenol binds end-on with the sunset yellow aggregates at low concentration and inserts into the stacks at higher concentrations

Game theory of mind

This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution

Understanding caretakers' dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate

BACKGROUND: Malaria kills. A single rectal dose of artesunate before referral can reduce mortality and prevent permanent disability. However, the success of this intervention depends on caretakers' adherence to referral advice for follow-up care. This paper explores the dilemma facing caretakers when they are in the process of deciding whether or not to transit their child to a health facility after pre-referral treatment with rectal artesunate. METHODS: Four focus group discussions were held in each of three purposively selected villages in Mtwara rural district of Tanzania. Data were analysed manually using latent qualitative content analysis. RESULTS: The theme "Caretakers dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate" depicts the challenge they face. Caretakers' understanding of the rationale for going to hospital after treatment--when and why they should adhere--influenced adherence. Caretakers, whose children did not improve, usually adhered to referral advice. If a child had noticeably improved with pre-referral treatment however, caretakers weighed whether they should proceed to the facility, balancing the child's improved condition against other competing priorities, difficulties in reaching the health facilities, and the perceived quality of care at the health facility. Some misinterpretation were found regarding the urgency and rationale for adherence among some caretakers of children who improved which were attributed to be possibly due to their prior understanding. CONCLUSION: Some caretakers did not adhere when their children improved and some who adhered did so without understanding why they should proceed to the facility. Successful implementation of the rectal artesunate strategy depends upon effective communication regarding referral to clinic