A yeast artificial chromosome-based map of the region of chromosome 20 containing the diabetes-susceptibility gene, MODY1, and a myeloid leukemia related gene.

We have generated a physical map of human chromosome bands 20q11.2-20q13.1, a region containing a gene involved in the development of one form of early-onset, non-insulin-dependent diabetes mellitus, MODY1, as well as a putative myeloid tumor suppressor gene. The yeast artificial chromosome contig consists of 71 clones onto which 71 markers, including 20 genes, 5 expressed sequence tags, 32 simple tandem repeat DNA polymorphisms, and 14 sequence-tagged sites have been ordered. This region spans about 18 Mb, which represents about 40% of the physical length of 20q. Using this physical map, we have refined the location of MODY1 to a 13-centimorgan interval (approximately equal to 7 Mb) between D20S169 and D20S176. The myeloid tumor suppressor gene was localized to an 18-centimorgan interval (approximately equal to 13 Mb) between RPN2 and D20S17. This physical map will facilitate the isolation of MODY1 and the myeloid tumor suppressor gene.

In vivo selection of basic region-leucine zipper proteins with altered DNA-binding specificities.

A transcription interference assay was used to generate mutant basic region-leucine zipper proteins with altered DNA-binding specificities. A library of mutants of a CCAAT/enhancer binding protein was constructed by randomizing five DNA-contacting amino acids in the basic region Asn-18, Ala-15, Val-14, Ser-11, and Arg-10. These mutants were then selected for their ability to bind mutant recognition sequences containing substitutions at the 2 and 3 positions of the wild-type sequence 5'-A5T4T3G2C1G1'C2'A3A4'T5'-3'. Mutants containing the sequence Leu-18Tyr-15Xaa-14Tyr-11Arg-10, in which four of the five contact residues are altered, were identified that recognize the palindromic sequence 5'-ATCYCGY'GAT-3' (Xaa = asparagine when Y = G; Xaa = methionine when Y = A). Moreover, in a selection against the sequence 5'-ATTACGTAAT-3', mutants were obtained containing substitutions not only in the basic region but also in the hinge region between the basic and leucine zipper regions. The mutant proteins showed high specificity in a functional transcription interference assay. A model for the interaction of these mutants with the target DNA sequences is discussed.

In vivo estimates of division and death rates of human T lymphocytes.

We present data on the decay, after radiotherapy, of naive and memory human T lymphocytes with stable chromosome damage. These data are analyzed in conjunction with existing data on the decay of naive and memory T lymphocytes with unstable chromosome damage and older data on unsorted lymphocytes. The analyses yield in vivo estimates for some life-history parameters of human T lymphocytes. Best estimates of proliferation rates have naive lymphocytes dividing once every 3.5 years and memory lymphocytes dividing once every 22 weeks. It appears that memory lymphocytes can revert to the naive phenotype, but only, on average, after 3.5 years in the memory class. The lymphocytes with stable chromosome damage decay very slowly, yielding surprisingly low estimates of their death rate. The estimated parameters are used in a simple mathematical model of the population dynamics of undamaged naive and memory lymphocytes. We use this model to illustrate that it is possible for the unprimed subset of a constantly stimulated clone to stay small, even when there is a large population of specific primed cells reverting to the unprimed state.

Patterns and Predictors of Stability and Change in Representations of Romantic Relationships in Adolescence and Young Adulthood

Research on the stability of attachment representations across the lifespan has led to two alternative perspectives: the prototype and revisionist perspectives (Fraley, 2002). The prototype perspective posits that there is a stable factor underlying fluctuations in representations and the revisionist perspective argues that there is no inherently stable factor. The current study employed a latent trait-state model to investigate these alternative models of stability and change in representations of romantic relationships in adolescence and young adulthood. The study also sought to identify individual characteristics and relationship experiences that are associated with changes in representations. In a sample of 200 participants, representations were assessed by interview and self-report over seven measurement occasions between ages 15 and 23. Results were consistent with the prototype perspective emphasizing that a stable, latent factor exerts a consistent influence over the lifespan. In addition to a stable component, representations incorporated a component that varies over time. Findings showed that this fluctuating component of representations was associated with internalizing and externalizing symptomatology as well as experiences of support and negative interaction in relationships.

A novel hybrid simulation-optimization approach for the optimal design of multicomponent distillation columns

Póster presentado en Escape 22, European Symposium on Computer Aided Process Engineering, University College London, UK, 17-20 June 2012.

Optimal synthesis of liquid-liquid multistage extractors

Presentation in the 11th European Symposium of the Working Party on Computer Aided Process Engineering, Kolding, Denmark, May 27-30, 2001.

Optimal synthesis of thermally coupled distillation sequences using a novel MILP approach

This paper introduces a novel MILP approach for the design of distillation columns sequences of zeotropic mixtures that explicitly include from conventional to fully thermally coupled sequences and divided wall columns with a single wall. The model is based on the use of two superstructure levels. In the upper level a superstructure that includes all the basic sequences of separation tasks is postulated. The lower level is an extended tree that explicitly includes different thermal states and compositions of the feed to a given separation task. In that way, it is possible to a priori optimize all the possible separation tasks involved in the superstructure. A set of logical relationships relates the feasible sequences with the optimized tasks in the extended tree resulting in a MILP to select the optimal sequence. The performance of the model in terms of robustness and computational time is illustrated with several examples.

Hybrid simulation-optimization based approach for the optimal design of single-product biotechnological processes

In this work, we present a systematic method for the optimal development of bioprocesses that relies on the combined use of simulation packages and optimization tools. One of the main advantages of our method is that it allows for the simultaneous optimization of all the individual components of a bioprocess, including the main upstream and downstream units. The design task is mathematically formulated as a mixed-integer dynamic optimization (MIDO) problem, which is solved by a decomposition method that iterates between primal and master sub-problems. The primal dynamic optimization problem optimizes the operating conditions, bioreactor kinetics and equipment sizes, whereas the master levels entails the solution of a tailored mixed-integer linear programming (MILP) model that decides on the values of the integer variables (i.e., number of equipments in parallel and topological decisions). The dynamic optimization primal sub-problems are solved via a sequential approach that integrates the process simulator SuperPro Designer® with an external NLP solver implemented in Matlab®. The capabilities of the proposed methodology are illustrated through its application to a typical fermentation process and to the production of the amino acid L-lysine.

Energy consumption in an urban wastewater treatment plant: the case of Murcia Region (Spain)

Of all the costs associated with the operation and maintenance of wastewater treatment plants (WWTPs), those associated with energy use tend to be the most significant. From this point of view, it is hence logical that energy efficiency and saving strategies should be one of the current focuses of debate amongst those involved with the management of WWTPs. The present study's objective is to determine the correlation between size and energy consumption for a WWTP. To this end, 90 WWTPs currently in service were analysed and their energetic impact quantified in terms of kWh/m3 of water treated. The results obtained demonstrate that energy consumption ratio increases as the size of WWTPs decreases, either in terms of treatment volume or population equivalent served.

Optimal Design of a Hybrid Membrane System Combining Reverse and Forward Osmosis for Seawater Desalination

In this work we study Forward Osmosis (FO) as an emerging desalination technology, and its capability to replace totally or partially Reverse Osmosis (RO) in order to reduce the great amount of energy required in the current desalination plants. For this purpose, we propose a superstructure that includes both membrane based desalination technologies, allowing the selection of only one of the technologies or a combination of both of them seeking for the optimal configuration of the network. The optimization problem is solved for a seawater desalination plant with a given fresh water production. The results obtained show that the optimal solution combines both desalination technologies to reduce not only the energy consumption but also the total cost of the desalination process in comparison with the same plant but operating only with RO.

Kyrgyzstan: Balancing on the Verge of Stability. EUCAM Policy Brief No. 19, July 2011

Following the ‘revolution’ in April 2010, the subsequent interethnic violence in June and the recent international inquiry into these events, Kyrgyzstan is not in safe waters yet. The coming period leading up to the Presidential elections will be important for the country’s stability. What is the current situation in the South of the country, which saw clashes between Kyrgyz and Uzbeks, and what are the expectations for the presidential elections? Is Kyrgyzstan on the road to democracy, and what role can external actors play?