Large Magnetoresistance in Fe/MgO/FeCo(001) Epitaxial Tunnel-Junctions on GaAs(001).

We present tunneling experiments on Fe~001!/MgO~20 Å!/FeCo~001! single-crystal epitaxial junctions of high quality grown by sputtering and laser ablation. Tunnel magnetoresistance measurements give 60% at 30 K, to be compared with 13% obtained recently on ~001!-oriented Fe/amorphous-Al2O3 /FeCo tunnel junctions. This difference demonstrates that the spin polarization of tunneling electrons is not directly related to the density of states of the free metal surface Fe~001! in this case but depends on the actual electronic structure of the entire electrode/barrier system.

Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia.

We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of "mitochondrial chaperonopathies" and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis.

Sonographic diagnosis of carpal tunnel syndrome: a study in 200 hospital workers

AbstractObjective:To describe the prevalence of carpal tunnel syndrome in a sample of 200 healthy hospital workers, establishing the respective epidemiological associations.Materials and Methods:Two hundred individuals were submitted to wrist ultrasonography to measure the median nerve area. They were questioned and examined for epidemiological data, body mass index, carpal tunnel syndrome signs and symptoms, and submitted to the Boston carpal tunnel questionnaire (BCTQ) to evaluate the carpal tunnel syndrome severity. A median nerve area ≥ 9 mm2 was considered to be diagnostic of carpal tunnel syndrome.Results:Carpal tunnel syndrome was diagnosed by ultrasonography in 34% of the sample. It was observed the association of carpal tunnel syndrome with age (p < 0.0001), paresthesia (p < 0.0001), Tinel's test (p < 0.0001), Phalen's test (p< 0.0001), BCTQ score (p < 0.0001), and years of formal education (p < 0.0001). Years of formal education was the only variable identified as an independent risk factor for carpal tunnel syndrome (95% CI = 1.03 to 1.24).Conclusion:The prevalence of carpal tunnel syndrome in a population of hospital workers was of 34%. The number of years of formal education was the only independent risk factor for carpal tunnel syndrome.

Paineviemärissä muodostuvan rikkivedyn vähentäminen kemikaloimalla

Anaerobisissa olosuhteissa muodostuva rikkivetykaasu on tyypillinen ongelma etenkin pitkillä paineviemäriosuuksilla. Sille ominainen epämiellyttävä haju aiheuttaa jätevedenkäsittelyverkostoissa ja viemärilinjojen lähialueilla merkittäviä hajuongelmia. Lisäksi rikkivedyn hapettuessa rikkihapoksi viemäri joutuu alttiiksi korroosiolle. Helsingin Etelä rannassa sijaitsevaan Munkkisaareen päätyy 4,4 km pitkä paineviemäri. Viemärin tuuletusputken kautta leviävä rikkivety on aiheuttanut hajuongelmia alueella. Korkeimmat mitatut rikkivetypitoisuudet tuuletusputken läheisyydessä olivat jopa 300 ppm. Tutkimuksessa tehtiin koeajoja erilaisilla hajunpoistokemikaaleilla rikkivetyongelman ratkaisemiseksi. Viemäriin annosteltiin sen alkupäässä jatkuvatoimisesti ferrosulfaattia ja ferrinitraattisulfaattia, sekä shokki-käsittelyllä natriumhydroksidia (lipeää). Munkkisaaressa mitatut rikkivetypitoisuudet osoittivat käytettyjen kemikaalien tehokkuuden rikkivedyn poistossa. Rikkivedyn saostamiseen tarkoitetut rautasuolat (ferrosulfaatti ja ferrinitraattisulfaatti) vähensivät 100 - 150 g annoksilla rikkivetyä yli 90 prosenttia. Natriumhydroksin annoksella 3600 g/m³ viemärin mikrobiologinen toiminta voitiin estää keskimäärin kymmeneksi päiväksi, mutta tehokas rikkivedyn muodostumisen esto vaatisi käsittelyn uusimisen noin 5 päivän välein. Normaaleissa viemärin olosuhteissa rikkivetyä muodostui vuorokauden aikana yhtä neliömetriä kohden noin 10 g. Kemikaalikäsittelyjen avulla muodostuminen aleni parhaimmillaan kymmenesosaan alkuperäisestä. Tulosten perusteella kemikaalien käytöllä viemärissä voisi välttyä kalliilta saneeraukselta Munkkisaaressa sekä muissa korroosiolle alttiiksi joutuvissa viemäreissä. Kemikalointikustannukset rautasuoloilla olivat noin 11 000 - 34 000 € ja lipeällä noin 7 000 € vuodessa.

Study of mesoscopic tunnel junctions between two normal metals

The main purpose of this work was to study different kinds of metal-based tunnel junctions at low temperatures. The problem which had to be solved was creating a junction with appropriate properties at these temperatures. The materials for junctions were found experimentally. The goal was to find an alloy material that can provide a high quality tunnel junction, which remains in the normal conductive state at low temperatures without applying magnetic field. The fabrication technology of such a device, based on an alloy of aluminium and manganese, is described in detail. In this thesis theoretical properties of tunnel junctions are considered and results of experiments with tunnel junctions are described and quantitative properties of the junctions are analyzed based on the experimental data.

Methods for construction and analysis of computational models in systems biology : applications to the modelling of the heat shock response and the self-assembly of intermediate filaments

Systems biology is a new, emerging and rapidly developing, multidisciplinary research field that aims to study biochemical and biological systems from a holistic perspective, with the goal of providing a comprehensive, system- level understanding of cellular behaviour. In this way, it addresses one of the greatest challenges faced by contemporary biology, which is to compre- hend the function of complex biological systems. Systems biology combines various methods that originate from scientific disciplines such as molecu- lar biology, chemistry, engineering sciences, mathematics, computer science and systems theory. Systems biology, unlike “traditional” biology, focuses on high-level concepts such as: network, component, robustness, efficiency, control, regulation, hierarchical design, synchronization, concurrency, and many others. The very terminology of systems biology is “foreign” to “tra- ditional” biology, marks its drastic shift in the research paradigm and it indicates close linkage of systems biology to computer science. One of the basic tools utilized in systems biology is the mathematical modelling of life processes tightly linked to experimental practice. The stud- ies contained in this thesis revolve around a number of challenges commonly encountered in the computational modelling in systems biology. The re- search comprises of the development and application of a broad range of methods originating in the fields of computer science and mathematics for construction and analysis of computational models in systems biology. In particular, the performed research is setup in the context of two biolog- ical phenomena chosen as modelling case studies: 1) the eukaryotic heat shock response and 2) the in vitro self-assembly of intermediate filaments, one of the main constituents of the cytoskeleton. The range of presented approaches spans from heuristic, through numerical and statistical to ana- lytical methods applied in the effort to formally describe and analyse the two biological processes. We notice however, that although applied to cer- tain case studies, the presented methods are not limited to them and can be utilized in the analysis of other biological mechanisms as well as com- plex systems in general. The full range of developed and applied modelling techniques as well as model analysis methodologies constitutes a rich mod- elling framework. Moreover, the presentation of the developed methods, their application to the two case studies and the discussions concerning their potentials and limitations point to the difficulties and challenges one encounters in computational modelling of biological systems. The problems of model identifiability, model comparison, model refinement, model inte- gration and extension, choice of the proper modelling framework and level of abstraction, or the choice of the proper scope of the model run through this thesis.

Role and regulatory mechanisms of heat shock factor 2

Protein homeostasis is essential for cells to prosper and survive. Various forms of stress, such as elevated temperatures, oxidative stress, heavy metals or bacterial infections cause protein damage, which might lead to improper folding and formation of toxic protein aggregates. Protein aggregation is associated with serious pathological conditions such as Alzheimer’s and Huntington’s disease. The heat shock response is a defense mechanism that protects the cell against protein-damaging stress. Its ancient origin and high conservation among eukaryotes suggest that the response is crucial for survival. The main regulator of the heat shock response is the transcription factor heat shock factor 1 (HSF1), which induces transcription of genes encoding protective molecular chaperones. In vertebrates, a family of four HSFs exists (HSF1-4), with versatile functions not only in coping with acute stress, but also in development, longevity and cancer. Thus, knowledge of the HSFs will aid in our understanding on how cells survive suboptimal circumstances, but will also provide insights into normal physiological processes as well as diseaseassociated conditions. In this study, the function and regulation of HSF2 have been investigated. Earlier gene inactivation experiments in mice have revealed roles for HSF2 in development, particularly in corticogenesis and spermatogenesis. Here, we demonstrate that HSF2 holds a role also in the heat shock response and influences stress-induced expression of heat shock proteins. Intriguingly, DNA-binding activity of HSF2 upon stress was dependent on the presence of intact HSF1, suggesting functional interplay between HSF1 and HSF2. The underlying mechanism for this phenomenon could be configuration of heterotrimers between the two factors, a possibility that was experimentally verified. By changing the levels of HSF2, the expression of HSF1-HSF2 heterotrimer target genes was altered, implementing HSF2 as a modulator of HSF-mediated transcription. The results further indicate that HSF2 activity is dependent on its concentration, which led us to ask the question of how accurate HSF2 levels are achieved. Using mouse spermatogenesis as a model system, HSF2 was found to be under direct control of miR-18, a miRNA belonging to the miR-17~92 cluster/Oncomir-1 and whose physiological function had remained unclear. Investigations on spermatogenesis are severely hampered by the lack of cell systems that would mimic the complex differentiation processes that constitute male germ cell development. Therefore, to verify that HSF2 is regulated by miR-18 in spermatogenesis, a novel method named T-GIST (Transfection of Germ cells in Intact Seminiferous Tubules) was developed. Employing this method, the functional consequences of miR-18-mediated regulation in vivo were demonstrated; inhibition of miR- 18 led to increased expression of HSF2 and altered the expression of HSF2 target genes Ssty2 and Speer4a. Consequently, the results link miR-18 to HSF2-mediated processes such as germ cell maturation and quality control and provide miR-18 with a physiological role in gene expression during spermatogenesis.Taken together, this study presents compelling evidence that HSF2 is a transcriptional regulator in the heat shock response and establishes the concept of physical interplay between HSF2 and HSF1 and functional consequences thereof. This is also the first study describing miRNA-mediated regulation of an HSF.