Protein oligomers studied by solid-state NMR the case of the full-length nucleoid-associated protein histone-like nucleoid structuring protein

Members of the histone-like nucleoid structuring protein (H-NS) family play roles both as architectural proteins and as modulators of gene expression in Gram-negative bacteria. The H-NS protein participates in modulatory processes that respond to environmental changes in osmolarity, pH, or temperature. H-NS oligomerization is essential for its activity. Structural models of different truncated forms are available. However, high-resolution structural details of full-length H-NS and its DNA-bound state have largely remained elusive. We report on progress in characterizing the biologically active H-NS oligomers with solid-state NMR. We compared uniformly ((13)C,(15)N)-labeled ssNMR preparations of the isolated N-terminal region (H-NS 1-47) and full-length H-NS (H-NS 1-137). In both cases, we obtained ssNMR spectra of good quality and characteristic of well-folded proteins. Analysis of the results of 2D and 3D (13)C-(13)C and (15)N-(13)C correlation experiments conducted at high magnetic field led to assignments of residues located in different topological regions of the free full-length H-NS. These findings confirm that the structure of the N-terminal dimerization domain is conserved in the oligomeric full-length protein. Small changes in the dimerization interface suggested by localized chemical shift variations between solution and solid-state spectra may be relevant for DNA recoginition.

Controlling the spin of metal atoms adsorbed on oxide surfaces: Ni on regular and defective sites of the MgO(001) surface

We have analyzed the relative energy of nonmagnetic and magnetic low-lying electronic states of Ni atoms adsorbed on regular and defective sites of the MgO(001) surface. To this end cluster and periodic surface models are used within density functional theory. For Ni atoms adsorbed on oxygen vacancies at low coverage, the interaction energy between the metal and the support is much larger than on regular sites. Strong bonding results in a diamagnetic adsorbed species and the energy required to reach the high-spin state increases. Moreover, a correlation appears between the low-spin to high-spin energy difference and the interaction energy hypothesizing that it is possible to prepare the surface to tune the high-spin to low-spin energy difference. Magnetic properties of adsorbed thin films obtained upon increasing coverage are more difficult to interpret. This is because the metallic bond is readily formed and dominates over the effect of the atoms directly bound to the vacancy.

Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 30-40% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

A Large-Sized Multiwire Proportional Counter for Radiological Survey of Large Areas and Surfaces

Työn tavoitteena oli selvittää, miten eri parametrit vaikuttavat monilankaisen verrannollisuuslaskurin laskennallisiin ominaisuuksiin sekä voidaanko suurikokoista monilankaverrannollisuuslaskuria käyttää tehokkaasti suurien pintojen ? - ja ?- kontaminaation mittaamiseen. Ensin selvitettiin EU:n nykyistä clearing-käytäntöä sekä hahmoteltiin tulevia materiaalivirtoja, esiteltiin verrannollisuuslaskurin ja sen monilankamallin toimintaperiaate sekä käytettävien materiaalien ominaisuudet. Kootun teorian pohjalta selvitettiin tärkeimpien parametrien vaikutus ilmaisimen laskennallisiin ominaisuuksiin. Lopuksi suoritettiin rakenteilla olevan monilankaverrannollisuuslaskurin alustava testaus. Tulevien vuosien aikana eri puolilla maailmaa suljettavat erityyppiset ydinlaitokset luovat suuren tarpeen tehokkaiden kontaminaatiomittauslaitteistojen kehittämiselle. Tällä hetkellä mittaukset suoritetaan lähinnä noin 1 dm2 käsi-instrumentein, joten suurikokoinen, automatisoitu mittauslaitteisto sekä tehostaisi mittausprosessia suuresti sekä säästäisi runsaasti miestyötunteja. Jatkotoimenpiteiksi ehdotetaan laitteiston jatkotestausta, liikkeen ja nopeuden testausta sekä lopulta paikkaherkkyystoiminnon toteuttamisperiaatteen valintaa ja testausta.

Synthesis of triheptanoin and formulation as a solid diet for rodents

Triheptanoin-enriched diets have been successfully used in the experimental treatment of various metabolic disorders. Maximal therapeutic effect is achieved in the context of a ketogenic diet where triheptanoin oil provides 30-40% of the daily caloric intake. However, pre-clinical studies using triheptanoin-rich diets are hindered by the difficulty of administering to laboratory animals as a solid foodstuff. In the present study, we successfully synthesized triheptanoin to the highest standards of purity from glycerol and heptanoic acid, using sulfonated charcoal as a catalyst. Triheptanoin oil was then formulated as a solid, stable and palatable preparation using a ketogenic base and a combination of four commercially available formulation agents: hydrophilic fumed silica, hydrophobic fumed silica, microcrystalline cellulose, and talc. Diet compliance and safety was tested on C57Bl/6 mice over a 15-week period, comparing overall status and body weight change. Practical applications: This work provides a complete description of (i) an efficient and cost-effective synthesis of triheptanoin and (ii) its formulation as a solid, stable, and palatable ketogenic diet (triheptanoin-rich; 39% of the caloric intake) for rodents. Triheptanoin-rich diets will be helpful on pre-clinical experiments testing the therapeutic efficacy of triheptanoin in different rodent models of human diseases. In addition, using the same solidification procedure, other oils could be incorporated into rodent ketogenic diet to study their dosage and long-term effects on mammal health and development. This approach could be extremely valuable as ketogenic diet is widely used clinically for epilepsy treatment.

PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.

Recombination dynamics in ZnO nanowires: Surfaces states versus mode quality factor

In this work, we investigate the influence of finite size on the recombinations dynamics of ZnO nanowires. We demonstrate that diameter as well as lenght of nanowires determine the lifetime of the neutral donor bound excitons. Our findings suggest that while the length is mainly responsible for different mode quality factors of the cavity-like nanowires, the diameter determines the influence of surface states as alternative recombinations channels for the optical modes trapped in the nanocavity. In addition, comparing nanowires grown using different catalyst we show that the surfaces states strongly depend on each precursor characteristics.

The high-speed induction motor: calculating the effects of solid-rotor material on machine characteristics

A method for the analysis of high-speed solid-rotor induction motors in presented. The analysis is based on a new combination of the three dimensional linear method and the transfer matrix method. Both saturation and finite length effects are taken into account. The active region of the solid rotor is divided into saturated and unsaturated parts. The time dependence is assumed to be sinusoidal and phasor quantities are used in the solution. The method is applied to the calculation of smooth solid rotors manufactured of different materials. Six rotor materials are tested: three construction steels, pure iron, a cobaltiron alloy and an aluminium alloy. The results obtained by the method agree fairly well with the measurement quantities.

Allosteric conversation in the androgen receptor ligand-binding domain surfaces

Androgen receptor (AR) is a major therapeutic target that plays pivotal roles in prostate cancer (PCa) and androgen insensitivity syndromes. We previously proposed that compounds recruited to ligand-binding domain (LBD) surfaces could regulate AR activity in hormone-refractory PCa and discovered several surface modulators of AR function. Surprisingly, the most effective compounds bound preferentially to a surface of unknown function [binding function 3 (BF-3)] instead of the coactivator-binding site [activation function 2 (AF-2)]. Different BF-3 mutations have been identified in PCa or androgen insensitivity syndrome patients, and they can strongly affect AR activity. Further, comparison of AR x-ray structures with and without bound ligands at BF-3 and AF-2 showed structural coupling between both pockets. Here, we combine experimental evidence and molecular dynamic simulations to investigate whether BF-3 mutations affect AR LBD function and dynamics possibly via allosteric conversation between surface sites. Our data indicate that AF-2 conformation is indeed closely coupled to BF-3 and provide mechanistic proof of their structural interconnection. BF-3 mutations may function as allosteric elicitors, probably shifting the AR LBD conformational ensemble toward conformations that alter AF-2 propensity to reorganize into subpockets that accommodate N-terminal domain and coactivator peptides. The induced conformation may result in either increased or decreased AR activity. Activating BF-3 mutations also favor the formation of another pocket (BF-4) in the vicinity of AF-2 and BF-3, which we also previously identified as a hot spot for a small compound. We discuss the possibility that BF-3 may be a protein-docking site that binds to the N-terminal domain and corepressors. AR surface sites are attractive pharmacological targets to develop allosteric modulators that might be alternative lead compounds for drug design.

High-Speed Solid-Rotor Induction Machine – Electromagnetic Calculation and Design

Within the latest decade high-speed motor technology has been increasingly commonly applied within the range of medium and large power. More particularly, applications like such involved with gas movement and compression seem to be the most important area in which high-speed machines are used. In manufacturing the induction motor rotor core of one single piece of steel it is possible to achieve an extremely rigid rotor construction for the high-speed motor. In a mechanical sense, the solid rotor may be the best possible rotor construction. Unfortunately, the electromagnetic properties of a solid rotor are poorer than the properties of the traditional laminated rotor of an induction motor. This thesis analyses methods for improving the electromagnetic properties of a solid-rotor induction machine. The slip of the solid rotor is reduced notably if the solid rotor is axially slitted. The slitting patterns of the solid rotor are examined. It is shown how the slitting parameters affect the produced torque. Methods for decreasing the harmonic eddy currents on the surface of the rotor are also examined. The motivation for this is to improve the efficiency of the motor to reach the efficiency standard of a laminated rotor induction motor. To carry out these research tasks the finite element analysis is used. An analytical calculation of solid rotors based on the multi-layer transfer-matrix method is developed especially for the calculation of axially slitted solid rotors equipped with wellconducting end rings. The calculation results are verified by using the finite element analysis and laboratory measurements. The prototype motors of 250 – 300 kW and 140 Hz were tested to verify the results. Utilization factor data are given for several other prototypes the largest of which delivers 1000 kW at 12000 min-1.

Thermal increment due to ErCr: YSGG and CO2 laser irradiation of different implant surfaces. A pilot study

Objective: An evaluation and comparison is made of the thermal increment at different implant surfaces during irradiation with CO2 and ErCr:YSGG lasers. Study design: Five threaded and impacted implants with four types of surfaces were inserted in an adult pig rib: two implants with a hydroxyapatite surface (HA)(impacted and threaded, respectively), a machined titanium surface implant (TI mach), a titanium plasma spray surface implant (TPS), and a sandblasted, acid-etched surface implant (SBAE). A 0.5-mm diameter bone defect was made in the implant apical zone, and a type-K thermocouple (Termopar)® was placed in contact with the implant. The implants were irradiated in the coronal zone of each implant with a CO2 (4 W continuous mode) and an ErCr:YSGG laser (1.5 W, pulsed mode) first without and then with refrigeration. The temperature variations at the implant apical surface were recorded. Results: An apical temperature increase was recorded in all cases during CO2 and ErCr:YSGG laser irradiation without refrigeration. However, when the ErCr:YSGG was used with a water spray, a decrease in temperature was observed in all implants. The acid-etched and sandblasted surfaces were those most affected by the thermal changes. Conclusions: The ErCr:YSGG laser with a water spray applied to the sealing cap or coronal zone of the implants does not generate thermal increments in the apical surface capable of adversely affecting osseointegration and the integrity of the peri-implant bone tissue

The initial oxidation of transition metal surfaces

Due to their numerous novel technological applications ranging from the example of exhaust catalysts in the automotive industry to the catalytic production of hydro- gen, surface reactions on transition metal substrates have become to be one of the most essential subjects within the surface science community. Although numerous applications exist, there are many details in the different processes that, after many decades of research, remain unknown. There are perhaps as many applications for the corrosion resistant materials such as stainless steels. A thorough knowledge of the details of the simplest reactions occuring on the surfaces, such as oxidation, play a key role in the design of better catalysts, or corrosion resistant materials in the future. This thesis examines the oxidation of metal surfaces from a computational point of view mostly concentrating on copper as a model material. Oxidation is studied from the initial oxidation to the oxygen precovered surface. Important parameters for the initial sticking and dissociation are obtained. The saturation layer is thoroughly studied and the calculated results arecompared with available experimental results. On the saturated surface, some open questions still remain. The present calculations demonstrate, that the saturated part of the surface is excluded from being chemically reactive towards the oxygen molecules. The results suggest, that the reason for the chemical activity of the saturated surface is due to a strain effect occuring between the saturated areas of the surface.

GdBaCo2O5+x layered perovskite as an intermediate temperature solid oxide fuel cell cathode

GdBaCo2O5+x (GBCO) was evaluated as a cathode for intermediate-temperature solid oxide fuel cells. A porous layer of GBCO was deposited on an anode-supported fuel cell consisting of a 15m thick electrolyte of yttria-stabilized zirconia (YSZ) prepared by dense screen-printing anda Ni–YSZ cermet as an anode (Ni–YSZ/YSZ/GBCO). Values of power density of 150 mW cm−2 at 700◦C and ca. 250 mW cm−2 at 800◦C are reported for this standard configuration using 5% of H2 in nitrogen as fuel. An intermediate porous layer of YSZ was introduced between the electrolyte and the cathode improving the performance of the cell. Values for power density of 300 mW cm−2 at 700◦C and ca. 500 mW cm−2 at 800◦C in this configuration were achieved.

Fatal Outcome of Multiple Clinical Presentations of Human Herpesvirus 8-related Disease After Solid Organ Transplantation.

Kaposi sarcoma is the most common human herpesvirus 8 (HHV-8)-related disease described after solid organ transplantation. Multicentric Castleman disease and hemophagocytic syndrome are other potential HHV-8-induced entities but are less frequently reported. We describe the case of a liver transplant recipient who presented with an acute febrile illness 1 year after transplantation with a rapidly fatal outcome. Autopsy revealed 3 distinct HHV-8-related entities: Kaposi sarcoma, HHV-8-associated multicentric Castleman disease with microlymphomas and a severe hemophagocytic syndrome. Retrospective serologic tests suggested that HHV-8 was likely transmitted by the seropositive donor at the time of transplantation. To our knowledge, this is the first case of copresentation of 3 clinical presentations of HHV-8-mediated human disease in the post-transplant setting. Considering the absence of systematic screening of organ donors/recipients for HHV-8 infection, HHV-8-related illness should be suspected in transplant recipients who present with acute febrile illness, systemic symptoms, lymphadenopathies, and/or multiorgan failure to rapidly document the diagnosis and provide timely an adequate treatment.

Privatization, cooperation and costs of solid waste services in small towns

This paper analyzes the cost implications of privatization and cooperation in the provision of solid waste services for a sample of small municipalities. In conducting this empirical analysis, a survey is first designed and administered to municipalities in the Spanish region of Aragon, and then an estimation of the determinants of service costs is undertaken, considering the possible endogeneity of delivery choices. Our findings indicate that cooperation is more effective than privatization in saving costs. Both production forms can enable small municipalities to cut costs by exploiting scale economies. However, the fact that inter-municipal cooperation involves lower transaction costs and is less likely to be affected by competition problems would seem to account for the fact that it is a more effective way of reducing costs.