Modelagem de proteínas por homologia

Modeling methods to derive 3D-structure of proteins have been recently developed. Protein homology-modeling, also known as comparative protein modeling, is nowadays the most accurate protein modeling method. This technique can produce useful models for about an order of magnitude more protein sequences than there have been structures determined by experiment in the same amount of time. All current protein homology-modeling methods consist of four sequential steps: fold assignment and template selection, template-target alignment, model building, and model evaluation. In this paper we discuss in some detail the protein-homology paradigm, its predictive power and its limitations.

Heat transfer inside internal combustion engine: modelling and comparison with experimental data

The paper is devoted to study specific aspects of heat transfer in the combustion chamber of compression ignited reciprocating internal combustion engines and possibility to directly measure the heat flux by means of Gradient Heat Flux Sensors (GHFS). A one – dimensional single zone model proposed by Kyung Tae Yun et al. and implemented with the aid of Matlab, was used to obtain approximate picture of heat flux behavior in the combustion chamber with relation to the crank angle. The model’s numerical output was compared to the experimental results. The experiment was accomplished by A. Mityakov at four stroke diesel engine Indenor XL4D. Local heat fluxes on the surface of cylinder head were measured with fast – response, high – sensitive GHFS. The comparison of numerical data with experimental results has revealed a small deviation in obtained heat flux values throughout the cycle and different behavior of heat flux curve after Top Dead Center.

Heat flux measurement inside internal combustion engine with gradient heat flux sensor.

This master’s thesis is devoted to study different heat flux measurement techniques such as differential temperature sensors, semi-infinite surface temperature methods, calorimetric sensors and gradient heat flux sensors. The possibility to use Gradient Heat Flux Sensors (GHFS) to measure heat flux in the combustion chamber of compression ignited reciprocating internal combustion engines was considered in more detail. A. Mityakov conducted an experiment, where Gradient Heat Flux Sensor was placed in four stroke diesel engine Indenor XL4D to measure heat flux in the combustion chamber. The results which were obtained from the experiment were compared with model’s numerical output. This model (a one – dimensional single zone model) was implemented with help of MathCAD and the result of this implementation is graph of heat flux in combustion chamber in relation to the crank angle. The values of heat flux throughout the cycle obtained with aid of heat flux sensor and theoretically were sufficiently similar, but not identical. Such deviation is rather common for this type of experiment.

Sedimentology and micromorphology of drumlin sediments at Chimney Bluffs State Park, New York, United States of America

The drumlin sediments at Chimney Bluffs, New York appear to represent a block-inmatrix style glacial melange. This melange comprises sand stringers, lenses and intraclasts juxtaposed in an apparently massive diamicton. Thin section examination of these glacigenic deposits has revealed microstructures indicative of autokinetic subglacial defonnation which are consistent with a deformable bed origin for the diamicton. These features include banding and. necking of matrix grains, oriented plasma fabrics and the formation of pressure shadows at the long axis ends of elongate clasts. Preservation of primary stratification within the sand intraclasts appears to suggest that these features were pre-existing up-ice deposits that were frozen, entrained, then deposited as part of a defonning till layer beneath an advancing ice sheet. Multi-directional micro-shearing within the sand blocks is thought to reflect the frozen nature of the sand units in such a high strain environment. It is also contended that dewatering of the sediment pile leading to the eventual immobilisation of the defonning till layer was responsible for opening sub-horizontal fissures within the diamicton. These features were subsequently infilled with mass flow poorly sorted sands and silts which were subjected to ductile defonnation during the waning stages of an actively deforming till layer. Microstructures indicative of the dewatering processes in the sand units include patches of fine-grained particles within a coarser-grained matrix and the presence of concentrated zones of translocated clays. However, these units were probably confined within an impermeable diamicton casing that prevented massive pore water influxes from the deforming till layer~ Hence, these microstructures probably reflect localised dewatering of the sand intraclasts. A layered subglacial shear zone model is proposed for the various features exhibited by the drumlin sediments. The complexity of these structures is explained in terms of ii superposing deformation styles in response to changing pore water pressures. Constructional glaciotectonics, as implied by the occurrence of sub-horizontal fissuring, is suggested as the mechanism for the stacking of the sand intraclast units within the diamicton. The usefulness of micromorphology in complimenting the traditional sedimentology of glacigenic deposits is emphasised by the current study. An otherwise massive diamicton was shown to contain microstructures indicative of the very high strain rates expected in a complexly deforming till layer. . It is quite obvious from this investigation that the classification of diamictons needs to be re-examined for evidence of microstructures that could lead to the re-interpretation of diamicton forming processes. RESUME Le pacquet de sediments drumlinaire de Chimney Bluffs, New York, represent un "bloc-en-matrice" genre de melange glaciale. Des structures microscopique comprennent l'evidence pour la defonnation intrinseque attribuee a l'origine lit non resistant du drumlin. PreselVation des structures primaires au coeur des blocs arenaces suggere que ceux sont des depots preexistant qui furent geles, entraines et par la suite sedimentes au milieu d'une couche de debris sous-glaciaires en voie de deformation. Des failles microscopiques a l'interieur des blocs arenaces appuient aussi l'idee d'un bloc cohesif (c'est-a-dire gele) au centre d'un till non resistant. Des implications significatives s'emergent de cette etude pour les conditions sous-glaciaire et les processus de la formation des drumlin.

Uncovering Financial Markets Beliefs About Inflation Targets

This paper exploits the term structure of interest rates to develop testable economic restrictions on the joint process of long-term interest rates and inflation when the latter is subject to a targeting policy by the Central Bank. Two competing models that econometrically describe agents’ inferences about inflation targets are developed and shown to generate distinct predictions on the behavior of interest rates. In an empirical application to the Canadian inflation target zone, results indicate that agents perceive the band to be substantially narrower than officially announced and asymmetric around the stated mid-point. The latter result (i) suggests that the monetary authority attaches different weights to positive and negative deviations from the central target, and (ii) challenges on empirical grounds the assumption, frequently made in the literature, that the policy maker’s loss function is symmetric (usually a quadratic function) around a desired inflation value.

Evaluation of modern and mid-Holocene seasonal precipitation of the Mediterranean and northern Africa in the CMIP5 simulations

We analyse the spatial expression of seasonal climates of the Mediterranean and northern Africa in pre-industrial (piControl) and mid-Holocene (midHolocene, 6 yr BP) simulations from the fifth phase of the Coupled Model Intercomparison Project (CMIP5). Modern observations show four distinct precipitation regimes characterized by differences in the seasonal distribution and total amount of precipitation: an equatorial band characterized by a double peak in rainfall, the monsoon zone characterized by summer rainfall, the desert characterized by low seasonality and total precipitation, and the Mediterranean zone characterized by summer drought. Most models correctly simulate the position of the Mediterranean and the equatorial climates in the piControl simulations, but overestimate the extent of monsoon influence and underestimate the extent of desert. However, most models fail to reproduce the amount of precipitation in each zone. Model biases in the simulated magnitude of precipitation are unrelated to whether the models reproduce the correct spatial patterns of each regime. In the midHolocene, the models simulate a reduction in winter rainfall in the equatorial zone, and a northward expansion of the monsoon with a significant increase in summer and autumn rainfall. Precipitation is slightly increased in the desert, mainly in summer and autumn, with northward expansion of the monsoon. Changes in the Mediterranean are small, although there is an increase in spring precipitation consistent with palaeo-observations of increased growing-season rainfall. Comparison with reconstructions shows most models underestimate the mid-Holocene changes in annual precipitation, except in the equatorial zone. Biases in the piControl have only a limited influence on midHolocene anomalies in ocean–atmosphere models; carbon-cycle models show no relationship between piControl bias and midHolocene anomalies. Biases in the prediction of the midHolocene monsoon expansion are unrelated to how well the models simulate changes in Mediterranean climate.

CHEMICAL EVOLUTION OF THE GALACTIC BULGE: SINGLE AND DOUBLE INFALL MODELS

Recent work, has produced a wealth of data concerning the chemical evolution of the Galactic bulge, both for stars and nebulae. Present theoretical models generally adopt it limited range of such constraints, frequenfly using it single chemical element (usually iron), which is not enough to describe it unambiguously. In this work, we take into account contraints involving,9 Many chemical elements as possible, basically obtained from bulge nebulae and stars. Our main goal is to show that different scenarios can describe, at least partially the abundance distribution and several dishuice-independent correlations for these objects . Three classes of models were developed. The first is it one-zone, single-infall model, the. Second is it one-zone, double-infall model and the third is a multizone, double-infall model. We show that a one-zone model with it single infall episode is able to reproduce some of the observational data, but the best results tire achieved using it multizone, double-infall model.

Giant first-forbidden resonances

Recent experimental data on first-forbidden charge-exchange resonances are discussed in the framework of a schematic model. We also evaluate the screening of the weak coupling constants induced by both the giant resonances and the Δ-isobar. It is shown that the last effect does not depend on the multipolarity of the one-particle moment. Due to the same reason, the fraction of the reaction strength pushed up into the Δ-resonance region is always the same regardless of the quantum numbers carried by the excitation. Simple expressions are derived for the dependence of the excitation energies of the first-forbidden giant resonances on the mass number and isospin of the target. The model reproduces consistently both the Gamow-Teller and the first-forbidden resonances. © 1983.

Dependência estrutural da capacidade de rotação plástic em vigas de concreto armado

Summary In this work the structural dependence of plastic rotation capacity in RC beams is evaluated using the Finite Element Method. The objective is to achieve a better understanding of the non-linear behavior of reinforced concrete members and perform extensive parameter studies, using a rational model developed by Bigaj [1] to analyze the phenomenon of plastic rotation capacity in reinforced concrete members. It is assumed that only bending failure is relevant due to sufficient member resistance against shear and torsion. The paper begins with the physical and theoretical background of the phenomenon of plastic hinge development in RC structures. Special emphasis is laid on the issue of structural dependence of deformation capacity of plastic hinges in RC members. Member size dependence and influence of properties of construction materials were emphasized as well. The essential components of the Bigajs model for calculating the plastic rotation capacity are discussed. The behaviour of the plastic hinge is analysed taking into account the strain localisation in the damage zones of the hinge region. The Fictitious Crack Model (FCM) and the Compressive Damage Zone Model (CDZ) are adopted in a Fracture Mechanics approach to model the behaviour of concrete in tension and compression, respectively. The approach is implemented in FEMOOP, a FEM in-house solver under development, and applied to evaluate ductility in 2D beams. The models were generated with GiD, a pre-processor and post-processor developed by CIMNE, and analyzed with the capabilities implemented in FEMOOP. © Universitat Politècnica de Catalunya, Barcelona, España 2010.

BCL2A1a Over-Expression in Murine Hematopoietic Stem and Progenitor Cells Decreases Apoptosis and Results in Hematopoietic Transformation

We previously reported the development of a lethal myeloid sarcoma in a non-human primate model utilizing retroviral vectors to genetically modify hematopoietic stem and progenitor cells. This leukemia was characterized by insertion of the vector provirus into the BCL2A1 gene, with resultant BCL2A1 over-expression. There is little information on the role of this anti-apoptotic member of the BCL2 family in hematopoiesis or leukemia induction. Therefore we studied the impact of Bcl2a1a lentiviral over-expression on murine hematopoietic stem and progenitor cells. We demonstrated the anti-apoptotic function of this protein in hematopoietic cells, but did not detect any impact of Bcl2a1a on in vitro cell growth or cell cycle kinetics. In vivo, we showed a higher propensity of HSCs over-expressing Bcl2a1a to engraft and contribute to hematopoiesis. Mice over-expressing Bcl2a1a in the hematologic compartment eventually developed an aggressive malignant disease characterized as a leukemia/lymphoma of B-cell origin. Secondary transplants carried out to investigate the primitive origin of the disease revealed the leukemia was transplantable. Thus, Bcl2a1 should be considered as a protooncogene with a potential role in both lymphoid and myeloid leukemogenesis, and a concerning site for insertional activation by integrating retroviral vectors utilized in hematopoietic stem cell gene therapy.

Decreasing the number of false positives in sequence classification

Abstract Background A large number of probabilistic models used in sequence analysis assign non-zero probability values to most input sequences. To decide when a given probability is sufficient the most common way is bayesian binary classification, where the probability of the model characterizing the sequence family of interest is compared to that of an alternative probability model. We can use as alternative model a null model. This is the scoring technique used by sequence analysis tools such as HMMER, SAM and INFERNAL. The most prevalent null models are position-independent residue distributions that include: the uniform distribution, genomic distribution, family-specific distribution and the target sequence distribution. This paper presents a study to evaluate the impact of the choice of a null model in the final result of classifications. In particular, we are interested in minimizing the number of false predictions in a classification. This is a crucial issue to reduce costs of biological validation. Results For all the tests, the target null model presented the lowest number of false positives, when using random sequences as a test. The study was performed in DNA sequences using GC content as the measure of content bias, but the results should be valid also for protein sequences. To broaden the application of the results, the study was performed using randomly generated sequences. Previous studies were performed on aminoacid sequences, using only one probabilistic model (HMM) and on a specific benchmark, and lack more general conclusions about the performance of null models. Finally, a benchmark test with P. falciparum confirmed these results. Conclusions Of the evaluated models the best suited for classification are the uniform model and the target model. However, the use of the uniform model presents a GC bias that can cause more false positives for candidate sequences with extreme compositional bias, a characteristic not described in previous studies. In these cases the target model is more dependable for biological validation due to its higher specificity.

Sonographic visualization and ultrasound-guided block of the third occipital nerve: prospective for a new method to diagnose C2-C3 zygapophysial joint pain

BACKGROUND: Chronic neck pain after whiplash injury is caused by cervical zygapophysial joints in 50% of patients. Diagnostic blocks of nerves supplying the joints are performed using fluoroscopy. The authors' hypothesis was that the third occipital nerve can be visualized and blocked with use of an ultrasound-guided technique. METHODS: In 14 volunteers, the authors placed a needle ultrasound-guided to the third occipital nerve on both sides of the neck. They punctured caudal and perpendicular to the 14-MHz transducer. In 11 volunteers, 0.9 ml of either local anesthetic or normal saline was applied in a randomized, double-blind, crossover manner. Anesthesia was controlled in the corresponding skin area by pinprick and cold testing. The position of the needle was controlled by fluoroscopy. RESULTS: The third occipital nerve could be visualized in all subjects and showed a median diameter of 2.0 mm. Anesthesia was missing after local anesthetic in only one case. There was neither anesthesia nor hyposensitivity after any of the saline injections. The C2-C3 joint, in a transversal plane visualized as a convex density, was identified correctly by ultrasound in 27 of 28 cases, and 23 needles were placed correctly into the target zone. CONCLUSIONS: The third occipital nerve can be visualized and blocked with use of an ultrasound-guided technique. The needles were positioned accurately in 82% of cases as confirmed by fluoroscopy; the nerve was blocked in 90% of cases. Because ultrasound is the only available technique today to visualize this nerve, it seems to be a promising new method for block guidance instead of fluoroscopy.

Acute respiratory syndrome after inhalation of waterproofing sprays: a posteriori exposure-response assessment in 102 cases

Waterproofing agents are widely used to protect leather and textiles in both domestic and occupational activities. An outbreak of acute respiratory syndrome following exposure to waterproofing sprays occurred during the winter 2002-2003 in Switzerland. About 180 cases were reported by the Swiss Toxicological Information Centre between October 2002 and March 2003, whereas fewer than 10 cases per year had been recorded previously. The reported cases involved three brands of sprays containing a common waterproofing mixture, that had undergone a formulation change in the months preceding the outbreak. A retrospective analysis was undertaken in collaboration with the Swiss Toxicological Information Centre and the Swiss Registries for Interstitial and Orphan Lung Diseases to clarify the circumstances and possible causes of the observed health effects. Individual exposure data were generated with questionnaires and experimental emission measurements. The collected data was used to conduct numeric simulation for 102 cases of exposure. A classical two-zone model was used to assess the aerosol dispersion in the near- and far-field during spraying. The resulting assessed dose and exposure levels obtained were spread on large scales, of several orders of magnitude. No dose-response relationship was found between exposure indicators and health effects indicators (perceived severity and clinical indicators). Weak relationships were found between unspecific inflammatory response indicators (leukocytes, C-reactive protein) and the maximal exposure concentration. The results obtained disclose a high interindividual response variability and suggest that some indirect mechanism(s) predominates in the respiratory disease occurrence. Furthermore, no threshold could be found to define a safe level of exposure. These findings suggest that the improvement of environmental exposure conditions during spraying alone does not constitute a sufficient measure to prevent future outbreaks of waterproofing spray toxicity. More efficient preventive measures are needed prior to the marketing and distribution of new waterproofing agents.

International Money and Finance

We discuss the effectiveness of pegged exchange rate regimes from an historical perspective, drawing conclusions for their effectiveness today. Starting with the classical gold standard period, we point out that a succession of pegged regimes have ended in failure; except for the first, which was ended by the outbreak of World War I, all of the others we discuss have been ended by adverse economic developments for which the regimes themselves were partly responsible. Prior to World War II the main problem was a shortage of monetary gold that we argue is implicated as a cause of the Great Depression. After World War II, more particularly from the late-1960s, the main problem has been a surfeit of the main international reserve asset, the US dollar. This has led to generalized inflation in the 1970s and into the 1980s. Today, excessive dollar international base money creation is again a problem that could have serious consequences for world economic stability.

Stable carbon and oxygen isotope ratios of carbonates of ODP Site 103-639

A Tithonian sequence of shallow-water limestones, intercalated with siliciclastics and overlain by dolomite, was recovered during drilling at ODP Site 639 on the edge of a tilted fault block. The carbonates were strongly affected by fracturing, dolomitization, dedolomitization, and compaction. The chronology and nature of the fractures, fracture infilling, and diagenesis of the host rock are established and correlated for both the limestone and the dolomite. A first phase of dolomitization affected limestone that was already, at least partially, indurated. In the limestone unit, fractures were filled by calcite and dolomite; most of the dolomite was recrystallized into calcite, except for the upper part. In the dolomitic unit, the first-formed dolomite was progressively recrystallized into saddle dolomite, as fractures were simultaneously activated. The dolomitic textures become less magnesian (the molar ratio mMg/mCa goes from 1.04-0.98 to 0.80), and the d18O (PDB) ranges from -10 per mil to -8 per mil. The varying pores and fissures are either cemented by a calcic saddle dolomite (mMg/mCa ranging from 0.95 to 0.80) or filled with diverse internal sediments of detrital calcic dolomite, consisting of detrital dolomite silt (d18O from -9 per mil to -7 per mil) and laminated yellow filling (with different d18O values that range from -4 per mil to +3 per mil). These internal sediments clearly contain elements of the host rock and fragments of saddle crystals. They are covered by marls with calpionellids of early Valanginian age, which permits dating of most of the diagenetic phases as pre-Valanginian. The dolomitization appears to be related to fracturing resulting from extensional tectonics; it is also partially related to an erosional episode. Two models of dolomitization can be proposed from the petrographic characteristics and isotopic data. Early replacement of aragonite bioclasts by sparite, dissolution linked to dolomitization, and negative d18O values of dolomite suggest a freshwater influence and 'mixing zone' model. On the other hand, the significant presence of saddle dolomite and repeated negative d18O values suggest a temperature effect; because we can dismiss deep burial, hydrothermal formation of dolomite would be the most probable model. For both of these hypotheses, the vadose filling of cavities and fractures by silt suggests emersion, and the different, and even positive, d18O values of the last-formed yellow internal sediment could suggest dolomitization of the top of the sequence under saline to hypersaline conditions. Fracturing resulting in the reopening of porosity and the draining of dolomitizing fluids was linked to extensional tectonics prior to the tilting of the block. These features indicate an earlier beginning to the rifting of the Iberian margin than previously known. Dolomitization, emersion, and erosion correspond to eustatic sea-level lowering at the Berriasian/Valanginian boundary. Diagenesis, rather than sedimentation, seems to mark this global event and to provide a record of the regional tectonic history.