Insights into the role of hydration in protein structure and stability obtained through hydrostatic pressure studies

A thorough understanding of protein structure and stability requires that we elucidate the molecular basis for the effects of both temperature and pressure on protein conformational transitions. While temperature effects are relatively well understood and the change in heat capacity upon unfolding has been reasonably well parameterized, the state of understanding of pressure effects is much less advanced. Ultimately, a quantitative parameterization of the volume changes (at the basis of pressure effects) accompanying protein conformational transitions will be required. The present report introduces a qualitative hypothesis based on available model compound data for the molecular basis of volume change upon protein unfolding and its dependence on temperature.

Design structure matrix ja sen hyödyntäminen ohjelmistotuotannossa

Työn tarkoituksena on selvittää, miten DSM ja siihen liittyvät analyysit toimivat. Työssä selvitetään myös, miten DSM:a voidaan hyödyntää tuotekehityksessä ja ohjelmistotuotannon kohtaamissa ongelmissa. DSM-neliömatriisiin sijoitetaan tarkasteltavan kohteen osat riveihin ja kolumneihin identtisessä järjestyksessä. Matriisin soluihin merkitään osien väliset riippuvuudet, joilla selvitetään kunkin osan lähettämä ja vastaanottama data suhteessa muihin osiin. DSM-analyysissa osien järjestystä muutetaan suoritus- tai toteutusjärjestyksen mukaisesti parhaaseen järjestykseen. Osat ryhmitellään moduuleihin, jolloin esimerkiksi tuotekehitys ohjautuu automaattisesti modulaarisuuteen. Tuotekehitysprojekteihin DSM on kompaktin muodon, yksinkertaisuuden ja automaattisen järjestelyn ansiosta erinomainen työkalu, jolla voidaan mallintaa käytännössä mitä tahansa, mikä voidaan jakaa toisistaan riippuviin osiin. DSM voi vähentää projektien suunnitteluun vaadittua työmäärää ja avustaa realististen budjettien ja aikataulujen luontia suurissa projekteissa.

Effect of exercise training and carvedilol treatment on cardiac function and structure in mice with sympathetic hyperactivity-induced heart failure

The present investigation was undertaken to study the effect of β-blockers and exercise training on cardiac structure and function, respectively, as well as overall functional capacity in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CArKO). α2A/α2CArKO and their wild-type controls were studied for 2 months, from 3 to 5 months of age. Mice were randomly assigned to control (N = 45), carvedilol-treated (N = 29) or exercise-trained (N = 33) groups. Eight weeks of carvedilol treatment (38 mg/kg per day by gavage) or exercise training (swimming sessions of 60 min, 5 days/week) were performed. Exercise capacity was estimated using a graded treadmill protocol and HR was measured by tail cuff. Fractional shortening was evaluated by echocardiography. Cardiac structure and gastrocnemius capillary density were evaluated by light microscopy. At 3 months of age, no significant difference in fractional shortening or exercise capacity was observed between wild-type and α2A/α2CArKO mice. At 5 months of age, all α2A/α2CArKO mice displayed exercise intolerance and baseline tachycardia associated with reduced fractional shortening and gastrocnemius capillary rarefaction. In addition, α2A/ α2CArKO mice presented cardiac myocyte hypertrophy and ventricular fibrosis. Exercise training and carvedilol similarly improved fractional shortening in α2A/α2CArKO mice. The effect of exercise training was mainly associated with improved exercise tolerance and increased gastrocnemius capillary density while β-blocker therapy reduced cardiac myocyte dimension and ventricular collagen to wild-type control levels. Taken together, these data provide direct evidence for the respective beneficial effects of exercise training and carvedilol in α2A/α2CArKO mice preventing cardiac dysfunction. The different mechanisms associated with beneficial effects of exercise training and carvedilol suggest future studies associating both therapies.

Computed tomography assessment of lung structure in patients undergoing cardiac surgery with cardiopulmonary bypass

Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated postoperative pulmonary alterations and their impact on blood oxygenation. Eighteen non-hypoxemic patients (15 men and 3 women) with normal cardiac function scheduled for CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at admission to the intensive care unit, and 12, 24, and 48 h after surgery. Pre- and postoperative volumetric thoracic CT scans were acquired under apnea conditions after a spontaneous expiration. Data were analyzed by the paired Student t-test and one-way repeated measures analysis of variance. Mean age was 63 ± 9 years. The PaO2/FiO2 ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially improving 12 h after surgery. Compared to preoperative CT, there was a 31% postoperative reduction in pulmonary gas volume (P < 0.001) while tissue volume increased by 19% (P < 0.001). Non-aerated lung increased by 253 ± 97 g (P < 0.001), from 3 to 27%, after surgery and poorly aerated lung by 72 ± 68 g (P < 0.001), from 24 to 27%, while normally aerated lung was reduced by 147 ± 119 g (P < 0.001), from 72 to 46%. No correlations (Pearson) were observed between PaO2/FiO2 ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. The data show that lung structure is profoundly modified after CABG with CPB. Taken together, multiple changes occurring in the lungs contribute to postoperative hypoxemia rather than atelectasis alone.

Fusion of Data from Quadcopter’s Inertial Measurement Unit Using Complementary Filter

A quadcopter is a helicopter with four rotors, which is mechanically simple device, but requires complex electrical control for each motor. Control system needs accurate information about quadcopter’s attitude in order to achieve stable flight. The goal of this bachelor’s thesis was to research how this information could be obtained. Literature review revealed that most of the quadcopters, whose source-code is available, use a complementary filter or some derivative of it to fuse data from a gyroscope, an accelerometer and often also a magnetometer. These sensors combined are called an Inertial Measurement Unit. This thesis focuses on calculating angles from each sensor’s data and fusing these with a complementary filter. On the basis of literature review and measurements using a quadcopter, the proposed filter provides sufficiently accurate attitude data for flight control system. However, a simple complementary filter has one significant drawback – it works reliably only when the quadcopter is hovering or moving at a constant speed. The reason is that an accelerometer can’t be used to measure angles accurately if linear acceleration is present. This problem can be fixed using some derivative of a complementary filter like an adaptive complementary filter or a Kalman filter, which are not covered in this thesis.

From protein structure to function with bioinformatics

It has long been known that amino acids are the building blocks for proteins and govern their folding into specific three-dimensional structures. However, the details of this process are still unknown and represent one of the main problems in structural bioinformatics, which is a highly active research area with the focus on the prediction of three-dimensional structure and its relationship to protein function. The protein structure prediction procedure encompasses several different steps from searches and analyses of sequences and structures, through sequence alignment to the creation of the structural model. Careful evaluation and analysis ultimately results in a hypothetical structure, which can be used to study biological phenomena in, for example, research at the molecular level, biotechnology and especially in drug discovery and development. In this thesis, the structures of five proteins were modeled with templatebased methods, which use proteins with known structures (templates) to model related or structurally similar proteins. The resulting models were an important asset for the interpretation and explanation of biological phenomena, such as amino acids and interaction networks that are essential for the function and/or ligand specificity of the studied proteins. The five proteins represent different case studies with their own challenges like varying template availability, which resulted in a different structure prediction process. This thesis presents the techniques and considerations, which should be taken into account in the modeling procedure to overcome limitations and produce a hypothetical and reliable three-dimensional structure. As each project shows, the reliability is highly dependent on the extensive incorporation of experimental data or known literature and, although experimental verification of in silico results is always desirable to increase the reliability, the presented projects show that also the experimental studies can greatly benefit from structural models. With the help of in silico studies, the experiments can be targeted and precisely designed, thereby saving both money and time. As the programs used in structural bioinformatics are constantly improved and the range of templates increases through structural genomics efforts, the mutual benefits between in silico and experimental studies become even more prominent. Hence, reliable models for protein three-dimensional structures achieved through careful planning and thoughtful executions are, and will continue to be, valuable and indispensable sources for structural information to be combined with functional data.

Institutional environment in North Korea: market structure and overcoming institutional voids

Tutkimus sai innoituksensa, kun tutkija huomasi tarpeen liiketaloudelliselle, ajantasaiselle ja realistiselle tutkimukselle Pohjois-Korean markkinoista, joka kuvailisi markkinoiden olemassaolevia ja puuttuvia rakenteita sekä tutkisi mahdollisuuksia ylittää puuttuvat rakenteet. Institutionaalinen teoria valittiin sopivaksi viitekehykseksi kuvailla ja tutkia markkinarakennetta. Tutkimuskysymys muotoiltiin seuraavasti: “Miten ulkomaiset yritykset voivat reagoida puuttuviin markkinarakenteisiin Pohjois-Koreassa?”. Tutkimuskysymys jaettiin kolmeen osakysymykseen: (1) Millainen on Pohjois-Korean markkinoiden institutionaalinen ympäristö? (2) Mitkä ovat merkittävimmät puuttuvat markkinarakenteet Pohjois-Koreassa? (3) Mitä mahdollisuuksia ulkomaisilla yrityksillä voisi olla reagoida puuttuviin markkinarakenteisiin? Tutkimus toteutettiin kvalitatiivisena, koska tutkimuskysymys on deskriptiivinen. Aineisto kerättiin asiantuntijahaastattelun ja kvalitatiivisen sisällönanalyysin keinoin. Primääriaineiston muodostavat 2 asiantuntijahaastattelua ja sekundääriaineiston muodostavat 95 artikkelia, jotka kerättiin 40 lähteestä. Aineisto analysoitiin kvalitatiivisen sisällönanalyysin keinoin. Aineisto koodattiin, luokiteltiin ja esitettiin kokonaisuuksina luokittelurungon avulla, joka laadittiin tutkimusta varten muodostetun teoreettisen viitekehyksen mukaan. Tulokset ja johtopäätökset voidaan tiivistää seuraavasti. (1) Pohjois-Korean markkinan instituutioihin vaikuttaa kaksoisrakenne, jossa muodollinen, sosialistinen rakenne ja epämuodollinen, markkinalähtöinen rakenne toimivat päällekkäin. (2) Puuttuvia rakenteita on sekä markkinan kontekstissa että markkinatasolla. Puutteet ovat osittain seurausta vanhojen rakenteiden korvaantumisesta uusilla, jotka eivät ole institutionalisoituneet. (3) Yritykset voivat käyttää samoja mahdollisuuuksia reagoida puuttuviin markkinarakenteisiin Pohjois-Koreassa, joita kehittyvien markkinoiden yhteydessä on esitetty. Sen tulkittiin vähentävän käsitystä, jonka mukaan Pohjois-Korean markkina on liian erikoinen yritystoiminnalle. (4) Kasvava keskiluokka sekä yrittäjyyden ja naisten yhä merkittävämpi rooli liike-elämässä aiheuttavat alhaalta ylöspäin suuntautuvaa kehitystä markkinoilla. Nämä ovat merkkejä viimeaikaisesta kehityksestä, jotka eivät ole saaneet laajaa huomiota länsimaisessa mediassa. Se korostaa tarvetta liiketaloudelliselle, ajantasaiselle jatkotutkimukselle Pohjois-Korean markkinoista.

Institutional environment in North Korea: market structure and overcoming institutional voids

The research was sparked by an exchange in South Korea, as the author identified a gap in research that provides economic, up to date and realistic information about the North Korean market in English language. A need for a research was identified that would describe the market’s existing and missing market structures and explore possibilities to overcome the missing market structures. Institutional theory was chosen as a suitable framework to describe and explore the market. The research question was formulated as follows: “How can foreign companies overcome institutional voids in the North Korean market?”. To answer the research question, it was divided into three sub-questions as follows: (1) What is the institutional environment in North Korea like? (2) What are the major institutional voids in the North Korean market? (3) What possibilities do foreign companies have to overcome institutional voids? The research is qualitative by nature due to the descriptive and exploratory nature of the research question. Data collection consisted of expert interview and content analysis, resulting in primary data of two interviews and secondary data of 95 articles from 40 different sources. The data was analyzed with the systematical technique of content analysis. The data was coded, classified and presented as concepts with the help of a classification system that was build following the theoretical framework adapted for this study. The findings can be summarized as follows. (1) The market institutions are characterized by an overlapping dual system of formal, socialist structures and informal, market-oriented structures. (2) Institutional voids prevail on both the market’s contextual and on the market level. They are partly result of old institutions being replaced by new institutions that lack institutionalization. (3) Identified possibilities to overcome institutional voids correspond with possibilities drawn from previous research. This decreases the image of North Korea as an impossibly unique market to operate in. (4) Emerging middle class, rapidly growing entrepreneurial activities and women’s increasing role in business drive a down-to-up change in the market. This signals the recent development of the market, yet has been overlooked in the Western media. Thus there is a need for further economic, up to date research concerning North Korea.

Extracting Ramachandran torsional angle distributions from 2D NMR data using Tikhonov regularization /

Solid state nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for studying structural and dynamical properties of disordered and partially ordered materials, such as glasses, polymers, liquid crystals, and biological materials. In particular, twodimensional( 2D) NMR methods such as ^^C-^^C correlation spectroscopy under the magicangle- spinning (MAS) conditions have been used to measure structural constraints on the secondary structure of proteins and polypeptides. Amyloid fibrils implicated in a broad class of diseases such as Alzheimer's are known to contain a particular repeating structural motif, called a /5-sheet. However, the details of such structures are poorly understood, primarily because the structural constraints extracted from the 2D NMR data in the form of the so-called Ramachandran (backbone torsion) angle distributions, g{^,'4)), are strongly model-dependent. Inverse theory methods are used to extract Ramachandran angle distributions from a set of 2D MAS and constant-time double-quantum-filtered dipolar recoupling (CTDQFD) data. This is a vastly underdetermined problem, and the stability of the inverse mapping is problematic. Tikhonov regularization is a well-known method of improving the stability of the inverse; in this work it is extended to use a new regularization functional based on the Laplacian rather than on the norm of the function itself. In this way, one makes use of the inherently two-dimensional nature of the underlying Ramachandran maps. In addition, a modification of the existing numerical procedure is performed, as appropriate for an underdetermined inverse problem. Stability of the algorithm with respect to the signal-to-noise (S/N) ratio is examined using a simulated data set. The results show excellent convergence to the true angle distribution function g{(j),ii) for the S/N ratio above 100.

Solid state NMR chemical shifts as an alternative to diffraction data in the determination of SIC polytypic structures

Silicon carbide, which has many polytypic modifications of a very simple and very symmetric structure, is an excellent model system for exploring, the relationship between chemical shift, long-range dipolar shielding, and crystal structure in network solids. A simple McConnell equation treatment of bond anisotropy effects in a poly type predicts chemical shifts for silicon and carbon sites which agree well with the experiment, provided that contributions from bonds up to 100 A are included in the calculation. The calculated chemical shifts depend on three factors: the layer stacking sequence, electrical centre of gravity, and the spacings between silicon and carbon layers. The assignment of peaks to lattice sites is proved possible for three polytypes (6H, 15R, and 3C). The fact that the calculated chemical shifts are very sensitive to layer spacings provides us a potential way to detennine and refine a crystal structure. In this work, the layer spacings of 6H SiC have been calculated and are within X-ray standard deviations. Under this premise, the layer spacings of 15R have been detennined. 29Si and 13C single crystal nmr studies of 6H SiC polytype indicate that all silicons and carbons are magnetically anisotropic. The relationship between a magnetic shielding tensor component and layer spacings has been derived. The comparisons between experimental and semi-empirical chemical shielding tensor components indicate that the paramagnetic shielding of silicon should be included in the single crystal chemical shift calculation.

The crystal and molecular structure of bis (pyridoxamine) copper (II) dinitrate monohydrate

The crystal structure of Cu(PM)2(N03hoH20 (where PM is pyridoxamine, CSHI2N202) has been determined from three dimensional x-ray diffraction data. The crystals are triclinic, space group pI, a = 14.248 (2), b = 8.568 (1), c = 9.319 (1) 1, a = 94.08 (1), e = 89.73 (1), y~~ 99.18 (1)°, z = 2, jl(MoK) = 10.90 em-I, Po = 1.61 g/cm3 and Pc = 1.61 g/em3• The structure a was solved by Patterson techniques from data collected on a Picker 4-circle diffractometer to 26max = 45°. All atoms, including hydrogens, have been located. Anisotropic thermal parameters have been refined for all nonhydrogen atoms. For the 2390 independent reflections with F ? 3cr(F) , R = 0.0408. The results presented here provide the first detailed structural information of a metal complex with PM itself. The copper atoms are located on centres of symmetry and each is chela ted by two PM zwitterions through the amino groups and phenolate oxygen atoms. The zwitterionic form found in this structure involves the loss of a proton from the phenolate group and protonation of the pyridine ring nitrogen atoms. The two independent Cu(PM)2 moieties are symmetrically bridged by a single oxygen atom from one of the nitrate groups. The second nitrate group is not coordinated to the copper atoms but is central to an extensive hydrogen bonding network involving the water molecule and uncoordinated functional groups of PM.

The effectiveness of explicit strategy instruction on the top level structure of a text

Thesis (M.Ed.)-- Brock University, 1995.

The relationship between stem-form, stand-closure and site -conditions : the influence of environmental conditions on tree allometry and forest structure in west-central Alberta

Changes in the configuration of a tree stern result insignificant differences in its total volume and in the proportion of that volume that is merchantable timber. Tree allometry, as represented by stem-fo~, is the result of the vertical force of gravity and the horizontal force of wind. The effect of wind force is demonstrated in the relationship between stem-form, standclosure and site-conditions. An increase in wind force on the individual tree due to a decrease in stand density should produce a more tapered tree. The density of the stand is determined by the conditions that the trees are growing under. The ability of the tree to respond to increased wind force may also be a function of these conditions . This stem-form/stand-closure/site-conditions relationship was examined using a pre-existing database from westcentral Alberta. This database consisted of environmental, vegetation, soils and timber data covering a wide range of sites. There were 653 sample trees with 82 variables that formed the basis of the analysis. There were eight tree species consisting of Pinus contorta, Picea mariana, Picea engelmannii x glauca, Abies lasiocarpa, Larix laricina, Populus tremuloides, Betula papyrifera and Populus balsamifera plus a comprehensive all-species data set. As the actual conformation of the stern is very individual, stem-fo~was represented by the diameter at breast height to total height r~tio. The four stand-closure variables, crown closure, total basal area, total volume and total number of stems were reduced to total basal area and total number of stems utilizing a bivariate correlation matrix by species. Site-conditions were subdivided into macro, meso and micro variables and reduced in number 3 using cross-tabulations, bivariate correlation and principal components analysis as screening tools. The stem-fo~/stand-closure relationship was examined using bivariate correlation coefficients for stem-fo~ with total number of stems and stem-fo~ with total basal area. The stem-fo~/site-conditions and the stand-closure/site- conditions relationships were examined using multiple correlation coefficients. The stem-form/stand-closure/site-conditions relationship was examined using multiple correlation coefficients in separate analyses for both total number of stems and total basal area. An increase in stand-closure produced a decrease in stem-form for both total number of stems and total basal area for most species. There was a significant relationship between stem-form and site-conditions and between stand-closure and site-conditions for both total number of stems and total basal area for most species. There was a significant relationship between the stemform and site-conditions, including the stand-closure, for most species; total number of stems was involved independently of the site-conditions in the prediction of stem-form and total basal area was not. Larix laricina and Betula papyrifera were the exceptions to the trends observed with most species. The influence of both stand-closure (total number of stems in particular) and site-conditions (elevation in particular) suggest that forest management practices should include these- ecological parameters in determining appropriate restocking levels.

Feature Selection and Classification Using Age Layered Population Structure Genetic Programming

The curse of dimensionality is a major problem in the fields of machine learning, data mining and knowledge discovery. Exhaustive search for the most optimal subset of relevant features from a high dimensional dataset is NP hard. Sub–optimal population based stochastic algorithms such as GP and GA are good choices for searching through large search spaces, and are usually more feasible than exhaustive and deterministic search algorithms. On the other hand, population based stochastic algorithms often suffer from premature convergence on mediocre sub–optimal solutions. The Age Layered Population Structure (ALPS) is a novel metaheuristic for overcoming the problem of premature convergence in evolutionary algorithms, and for improving search in the fitness landscape. The ALPS paradigm uses an age–measure to control breeding and competition between individuals in the population. This thesis uses a modification of the ALPS GP strategy called Feature Selection ALPS (FSALPS) for feature subset selection and classification of varied supervised learning tasks. FSALPS uses a novel frequency count system to rank features in the GP population based on evolved feature frequencies. The ranked features are translated into probabilities, which are used to control evolutionary processes such as terminal–symbol selection for the construction of GP trees/sub-trees. The FSALPS metaheuristic continuously refines the feature subset selection process whiles simultaneously evolving efficient classifiers through a non–converging evolutionary process that favors selection of features with high discrimination of class labels. We investigated and compared the performance of canonical GP, ALPS and FSALPS on high–dimensional benchmark classification datasets, including a hyperspectral image. Using Tukey’s HSD ANOVA test at a 95% confidence interval, ALPS and FSALPS dominated canonical GP in evolving smaller but efficient trees with less bloat expressions. FSALPS significantly outperformed canonical GP and ALPS and some reported feature selection strategies in related literature on dimensionality reduction.

Feature Selection and Classification Using Age Layered Population Structure Genetic Programming

The curse of dimensionality is a major problem in the fields of machine learning, data mining and knowledge discovery. Exhaustive search for the most optimal subset of relevant features from a high dimensional dataset is NP hard. Sub–optimal population based stochastic algorithms such as GP and GA are good choices for searching through large search spaces, and are usually more feasible than exhaustive and determinis- tic search algorithms. On the other hand, population based stochastic algorithms often suffer from premature convergence on mediocre sub–optimal solutions. The Age Layered Population Structure (ALPS) is a novel meta–heuristic for overcoming the problem of premature convergence in evolutionary algorithms, and for improving search in the fitness landscape. The ALPS paradigm uses an age–measure to control breeding and competition between individuals in the population. This thesis uses a modification of the ALPS GP strategy called Feature Selection ALPS (FSALPS) for feature subset selection and classification of varied supervised learning tasks. FSALPS uses a novel frequency count system to rank features in the GP population based on evolved feature frequencies. The ranked features are translated into probabilities, which are used to control evolutionary processes such as terminal–symbol selection for the construction of GP trees/sub-trees. The FSALPS meta–heuristic continuously refines the feature subset selection process whiles simultaneously evolving efficient classifiers through a non–converging evolutionary process that favors selection of features with high discrimination of class labels. We investigated and compared the performance of canonical GP, ALPS and FSALPS on high–dimensional benchmark classification datasets, including a hyperspectral image. Using Tukey’s HSD ANOVA test at a 95% confidence interval, ALPS and FSALPS dominated canonical GP in evolving smaller but efficient trees with less bloat expressions. FSALPS significantly outperformed canonical GP and ALPS and some reported feature selection strategies in related literature on dimensionality reduction.