Salmonella enterica– Mechanisms of fluoroquinolone and macrolide resistance

Salmonella enterica – Fluorokinoloni- ja makrolidiresistenssimekanisimit Vakavia salmonellainfektioita on pitkään hoidettu fluorokinoloniantibiooteilla, kuten siprofloksasiinilla. Fluorokinolonien runsas käyttö niin ihmisillä kuin eläimilläkin on kuitenkin johtanut fluorokinoloniresistenttien salmonellakantojen lisääntymiseen. Vuoteen 2002 asti kaikki matalan tason fluorokinoloniresistenssiä ilmentävät salmonellakannat olivat resistenttejä nalidiksiinihapolle, joka on vanha ensimmäisen polven kinoloniantibiootti jota ei enää käytetä infektioiden hoidossa. Vuonna 2003 havaitsimme aivan uudentyyppisen resistenssifenotyypin salmonelloissa. Kaikki uuden fenotyypin kannat osoittivat matalaa fluorokinoloniresistenssiä (MIC ≥0.125 mg/L), mutta useat kannat olivat yllättäen aikaisempaa herkempiä nalidiksiinihapolle (MIC ≤32 mg/L). Ilmiöllä on suuri merkitys salmonellan antibioottiherkkyyksien määrittämisessä, sillä jos kanta on ollut nalidiksiinihapolle herkkä, sitä on pidetty herkkänä myös fluorokinoloneille. Väitöskirjatyössä määritettiin vuosina 2003–2007 Suomessa kerättyjen kotimaisten ja ulkomaalaisten S. enterica -kantojen fluorokinoloniresistenssiä sekä tutkittiin uuden salmonellafenotyypin epidemiologiaa ja resistenssimekanismeja. Lisäksi tutkittiin salmonellan hoidossa mahdollisesti käyttökelpoisen makrolidiantibioottijohdannaisen, atsitromysiinin tehoa salmonelloihin ja erityisesti matalaa fluorokinoloniresistenssiä ilmentäviin kantoihin. Tutkimuksessa havaittiin, että matalaa fluorokinoloniresistenssiä osoittavien salmonellakantojen määrä vähenee. Lasku oli voimakkainta Kaakkois-Aasiasta tuoduissa kannoissa. Uusi resistenssifenotyyppi on plasmidivälitteinen ja qnr-geenit olivat ainoa plasmidivälitteinen kinoloniresistenssimekanismi, joka kannoista löydettiin. Myöskään kromosomaalisten gyrA, gyrB ja parE -geenien QRDR-alueelta ei löydetty fluorokinoloniresistenssiä aiheuttavia mutaatioita. Transformaatiolla osoitettiin qnr-plasmidien olevan siirtyviä ja uusi resistenssifenotyyppi saatiin ilmennettyä myös herkässä vastaanottajakannassa. Nämä tulokset osoittavat, että vaikka S. enterican qnr-fenotyyppi on toistaiseksi levinnyt pääasiassa Kaakkois-Aasiaan, se siirtyy helposti bakteerista toiseen ja tulee todennäköisesti aiheuttamaan hoito-ongelmia myös muualla maailmassa. Uudentyyppinen qnr-fenotyyppi voi olla vaikea havaita perinteisellä herkkyysmäärityksellä. Siksi laboratorioissa tulisi aina määrittää sekä siprofloksasiiniettä nalidiksiinihappoherkkyydet. Atsitromysiinin osoitettiin olevan herkkyysmääritysten mukaan tehokas salmonelloja kohtaan mukaanlukien matala-asteista fluorokinoloniresistenssiä ilmentävät bakteerikannat.

Identification of Some Additional Loss Components in High-Power Low-Voltage Permanent Magnet Generators

Permanent magnet generators (PMG) represent the cutting edge technology in modern wind mills. The efficiency remains high (over 90%) at partial loads. To improve the machine efficiency even further, every aspect of machine losses has to be analyzed. Additional losses are often given as a certain percentage without providing any detailed information about the actual calculation process; meanwhile, there are many design-dependent losses that have an effect on the total amount of additional losses and that have to be taken into consideration. Additional losses are most often eddy current losses in different parts of the machine. These losses are usually difficult to calculate in the design process. In this doctoral thesis, some additional losses are identified and modeled. Further, suggestions on how to minimize the losses are given. Iron losses can differ significantly between the measured no-load values and the loss values under load. In addition, with embedded magnet rotors, the quadrature-axis armature reaction adds losses to the stator iron by manipulating the harmonic content of the flux. It was, therefore, re-evaluated that in salient pole machines, to minimize the losses and the loss difference between the no-load and load operation, the flux density has to be kept below 1.5 T in the stator yoke, which is the traditional guideline for machine designers. Eddy current losses may occur in the end-winding area and in the support structure of the machine, that is, in the finger plate and the clamping ring. With construction steel, these losses account for 0.08% of the input power of the machine. These losses can be reduced almost to zero by using nonmagnetic stainless steel. In addition, the machine housing may be subjected to eddy current losses if the flux density exceeds 1.5 T in the stator yoke. Winding losses can rise rapidly when high frequencies and 10–15 mm high conductors are used. In general, minimizing the winding losses is simple. For example, it can be done by dividing the conductor into transposed subconductors. However, this comes with the expense of an increase in the DC resistance. In the doctoral thesis, a new method is presented to minimize the winding losses by applying a litz wire with noninsulated strands. The construction is the same as in a normal litz wire but the insulation between the subconductors has been left out. The idea is that the connection is kept weak to prevent harmful eddy currents from flowing. Moreover, the analytical solution for calculating the AC resistance factor of the litz-wire is supplemented by including an end-winding resistance in the analytical solution. A simple measurement device is developed to measure the AC resistance in the windings. In the case of a litz-wire with originally noninsulated strands, vacuum pressure impregnation (VPI) is used to insulate the subconductors. In one of the two cases studied, the VPI affected the AC resistance factor, but in the other case, it did not have any effect. However, more research is needed to determine the effect of the VPI on litz-wire with noninsulated strands. An empirical model is developed to calculate the AC resistance factor of a single-layer formwound winding. The model includes the end-winding length and the number of strands and turns. The end winding includes the circulating current (eddy currents that are traveling through the whole winding between parallel strands) and the main current. The end-winding length also affects the total AC resistance factor.

Reducing contact resistance in graphene devices

In this thesis, the contact resistance of graphene devices was investigated because high contact resistance is detrimental to the performance of graphene field-effect transistors (GFET). Method for increasing so-called edge-contact area was applied in device fabrication process, as few nanometers thick Ni layer was used as a catalytic etchant during the annealing process. Finally, Ni was also used as a metal for contact. GFETs were fabricated using electron beam lithography using graphene fabricated by chemical vapor deposition (CVD). Critical part of the fabrication process was to preserve the high quality of the graphene channel while etching the graphene at contact areas with Ni during the annealing. This was achieved by optimizing the combination of temperature and gas flows. The structural properties of graphene were studied using scanning electron microscopy, scanning confocal μ-Raman spectroscopy and optical microscopy. Evaluation of electric transport properties including contact resistance was carried out by transmission line method and four-probe method. The lowest contact resistance found was about at 350 Ωμm. In addition, different methods to transfer CVD graphene synthesized on copper were studied. Typical method using PMMA as a supporting layer leaves some residues after its removal, thus effecting on the performance of a graphene devices. In a metal assisted transfer method, metal is used as an interfacial layer between PMMA and graphene. This allows more effective removal of PMMA. However, Raman spectra of graphene transferred by metal assisted method showed somewhat lower quality than the PMMA assisted method