双晶晶界在高温下的热稳定性的分子动力学研究

晶界结构在高温下的热稳定性问题是一个长期争论而又未能解决的问题，其争论的焦点是：在远低于熔点的温度下，晶界结构是否发生了可观察到的无序化，即是否存在一个远低于熔点的结构转化温度。为了能澄清这一争论，本文系统地研究了晶界结构的热稳定性。为了消除相互作用势的影响和系统误差，本文首先采用Morse势和经验多体势分别对铝、铜单晶的熔化过程进行了分子动力学模拟。在平衡态下，通过计算表征结构无序化的静态结构因子、径向分布函数和单晶原子位形图，获得了铝、铜单晶的熔点，结果表明：多体势计算的铝和铜的单晶熔点更接近实验值。因此，采用经验多体势应用分子动力学方法分别模拟了铝、铜Σ3、Σ5、Σ9、Σ11、Σ19、Σ33六种对称倾侧双晶晶界晶界结构由有序向无序转化的过程，计算了平衡态下的表征结构无序化的静态结构因子、径向分布函数和晶界原子位形图并将多体势获得的铝、铜单晶熔点作为晶界结构转化温度的约化熔点，获得了铝、铜Σ3、Σ5、Σ9、Σ11、Σ19、Σ33六种对称倾侧双晶晶界结构的转化温度和熔点，结果表明：1．Σ5、Σ9、Σ11、Σ19、Σ33五种对称倾侧双晶晶界均在远低于单晶熔点温度时，晶界结构发生了可观察到的无序化，而且双晶晶界结构的转变温度相差不大，双晶晶界熔点也低于单晶熔点。2．Σ3晶界在温度远低于熔点时，其晶界结构没有发生可观察到的无序化；Σ3晶界的转化温度与单晶熔点接近。所以，可以认为Σ3晶界不存在转化温度。这是由于Σ3晶界为共格孪晶，具有较低的能量。综上所述，除Σ3共格孪晶外，在远低于熔点温度下，晶界结构发生了可观察到的无序化，即：存在一个远低于熔点的转化温度，此时其静态结构因子约为0.5左右；晶界结构的熔点均低于单晶熔点，此时其静态结构因子约为0.15左右。从全文模拟结果可以看出，静态结构因子、径向分布函数、晶界原子位形图三种方法在确定晶界的结构转化温度和熔点时，静态结构因子是最有效、最准确的定量方法。

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

Background: The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE). A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results: Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE epsilon 4 allele, increasing the risk of AD (OR = 5.96, 95% CI 2.74-12.94, p < 0.001 and OR = 6.71, 95% CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women. In MCI patients such as synergistic effect was only found between AG and APOE epsilon 4 allele (OR = 3.21 95% CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95% CI 1.69-20.42, p < 0.01). Conclusion: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon 4 allele that proves greater in women with AD.

Asymptotic scaling in the two-dimensional O(3) Nonlinear sigma model: a Monte Carlo study on parallel computers

We investigate the 2d O(3) model with the standard action by Monte Carlo simulation at couplings β up to 2.05. We measure the energy density, mass gap and susceptibility of the model, and gather high statistics on lattices of size L ≤ 1024 using the Floating Point Systems T-series vector hypercube and the Thinking Machines Corp.'s Connection Machine 2. Asymptotic scaling does not appear to set in for this action, even at β = 2.10, where the correlation length is 420. We observe a 20% difference between our estimate m/Λ^─_(Ms) = 3.52(6) at this β and the recent exact analytical result . We use the overrelaxation algorithm interleaved with Metropolis updates and show that decorrelation time scales with the correlation length and the number of overrelaxation steps per sweep. We determine its effective dynamical critical exponent to be z' = 1.079(10); thus critical slowing down is reduced significantly for this local algorithm that is vectorizable and parallelizable.

We also use the cluster Monte Carlo algorithms, which are non-local Monte Carlo update schemes which can greatly increase the efficiency of computer simulations of spin models. The major computational task in these algorithms is connected component labeling, to identify clusters of connected sites on a lattice. We have devised some new SIMD component labeling algorithms, and implemented them on the Connection Machine. We investigate their performance when applied to the cluster update of the two dimensional Ising spin model.

Finally we use a Monte Carlo Renormalization Group method to directly measure the couplings of block Hamiltonians at different blocking levels. For the usual averaging block transformation we confirm the renormalized trajectory (RT) observed by Okawa. For another improved probabilistic block transformation we find the RT, showing that it is much closer to the Standard Action. We then use this block transformation to obtain the discrete β-function of the model which we compare to the perturbative result. We do not see convergence, except when using a rescaled coupling β_E to effectively resum the series. For the latter case we see agreement for m/ Λ^─_(Ms) at , β = 2.14, 2.26, 2.38 and 2.50. To three loops m/Λ^─_(Ms) = 3.047(35) at β = 2.50, which is very close to the exact value m/ Λ^─_(Ms) = 2.943. Our last point at β = 2.62 disagrees with this estimate however.

Negative regulators of a growth factor-mediated signaling pathway in the nematode Caenorhabditis elegans

Vulval differentiation in C. elegans is mediated by an Epidermal growth factor (EGF)- EGF receptor (EGFR) signaling pathway. I have cloned unc-101, a negative regulator of vulval differentiation of the nematode C. elegans. unc-101 encodes a homolog of AP47, the medium chain of the trans-Golgi clathrin-associated protein complex. This identity was confirmed by cloning and comparing sequence of a C. elegans homolog of AP50, the medium chain of the plasma membrane clathrin-associated protein complex. I provided the first genetic evidence that the trans-Golgi clathrin-coated vesicles are involved in regulation of an EGF signaling pathway. Most of the unc-101 alleles are deletions or nonsense mutations, suggesting that these alleles severely reduce the unc-101 activity. A hybrid gene that contains parts of unc-101 and mouse AP4 7 rescued at least two phenotypes of unc-101 mutations, the Unc and the suppression of vulvaless phenotype of let-23(sy1) mutation. Therefore, the functions of AP47 are conserved between nematodes and mammals.

unc-101 mutations can cause a greater than wild-type vulval differentiation in combination with certain mutations in sli-1, another negative regulator of the vulval induction pathway. A mutation in a new gene, rok-1, causes no defect by itself, but causes a greater than wild-type vulval differentiation in the presence of a sli-1 mutation. The unc-101; rok-1; sli-1 triple mutants display a greater extent of vulval differentiation than any double mutant combinations of unc-101, rok-1 and sli-1. Therefore, rok-1 locus defines another negative regulator of the vulval induction pathway.

I analyzed a second gene encoding an AP47 homolog in C. elegans. This gene, CEAP47, encodes a protein 72% identical to both unc-101 and mammalian AP47. A hybrid gene containing parts of unc-101 and CEAP47 sequences can rescue phenotypes of unc-101 mutants, indicating that UNC- 101 and CEAP47 proteins can be redundant if expressed in the same set of cells.

El clima de aula. Un factor decisivo en el aprendizaje de lenguas

[spa] Se ha propuesto una guía didáctica para realizar en sesiones de euskera que profundice en el conocimiento mutuo entre los alumnos para que se fomente así la creación de vinculos interpersonales basados en el diálogo, la negociación y la comprensión. Todo ello supone la generación de un ambiente de aula cálido en el que todos los alumnos (gitanos y no gitanos) se sientan respetados, reconocidos y valorados, lo que garantiza el desarrollo óptimo y el acercamiento de los alumnos a la segunda lengua

Studies on the condition factor of the Sierra Leone mangrove oyster (Crassostrea tulipa)

Sierra Leone is a tropical country where water temperatures are high throughout the year. Consequently the local oysters tend to spawn the year round, with one or two spawning peaks. The condition of such tropical oysters may not be as high as those oyesters in temperate countries since the stored glycogen is regularly utilized to form gonads. A high condition factor value indicates that the oysters have accumulated glycogen and or gonads, whereas a low condition factor value indicates that the oysters have spawned and are in the process of accumulating glycogen, which may later be utilized for gonad development. In oyster culture, condition factor studies may be supported by plankton and oyster spat settlement studies in the culture area. These studies give an indication of when oyster larvae and spat settlement are at their peak values. In Sierra Leone studies of the plankton and spat settlement are undertaken every week throughout the year. Conditions factor is obtained from the ratio weight of dry (oyster) meat x 1000/internal volume. Detailed condition factor values are shown in relation to salinity at two stations. Condition factor declines with reducing salinity, which principally occurs during the rainy season. The best times to collect spat are May to June and September to October

Engineered discoidin domain from factor VIII binds αvβ3 integrin with antibody-like affinity

Alternative scaffolds are non-antibody proteins that can be engineered to bind new targets. They have found useful niches in the therapeutic space due to their smaller size and the ease with which they can be engineered to be bispecific. We sought a new scaffold that could be used for therapeutic ends and chose the C2 discoidin domain of factor VIII, which is well studied and of human origin. Using yeast surface display, we engineered the C2 domain to bind to αvβ3 integrin with a 16 nM affinity while retaining its thermal stability and monomeric nature. We obtained a crystal structure of the engineered domain at 2.1 Å resolution. We have christened this discoidin domain alternative scaffold the “discobody.”

Transcription factor occupancy in differentiating skeletal muscle

With recent advances in high-throughput sequencing, mapping of genome-wide transcription factor occupancy has become feasible. To advance the understanding of skeletal muscle differentiation specifically and transcriptional regulation in general, I determined the genome-wide occupancy map for myogenin in differentiating C2C12 myocyte cells. I then analyzed the myogenin map for underlying sequence content and the association between occupied elements and expression trajectories of adjacent genes. Having determined that myogenin primarily associates with expressed genes, I performed a similar analysis on occupancy maps of other transcription factors active during skeletal muscle differentiation, including an extensive analysis of co-occupancy. This analysis provided strong motif evidence for protein-protein interactions as the primary driving force in the formation of Myogenin / Mef2 and MyoD / AP-1 complexes at jointly-occupied sites. Finally, factor occupancy analysis was extended to include bHLH transcription factors in tissues other than skeletal muscle. The cross-tissue analysis led to the emergence of a motif structure used by bHLH TFs to encode either tissue-specific or "general" (public) access in a variety of lineages.