Chlamydial infertility in women: Diagnosis, epidemiology and immune response

This project primarily focused on the development of a novel, non-invasive peptide-based ELISA to diagnose C. trachomatis-related infertility in women. In this study, an in silico approach was applied to identify and design novel peptide antigens that are specific to women with C. trachomatis-related infertility. The serological assay was developed such that it could potentially replace invasive techniques for early infertility investigation. The thesis further investigated the sero-prevalence of chlamydial infertility in women from a low-resource, high prevalence setting. In addition, the thesis also identified immune markers that were associated with the C. trachomatis-related infertility in women.

Indian Ocean response to anomalous conditions in 2006

The equatorial Indian Ocean (EIO) exhibited anomalous conditions characteristic of an Indian Ocean dipole (IOD) during 2006. The eastern EIO had cold sea surface temperature anomalies (SSTA), lower sea level, shallow thermocline and higher chlorophyll than normal. The anomalies in the east, restricted to the south of the equator, were highest off Sumatra. The western pole of the IOD was marked by warm SSTA and deeper thermocline with maxima on either side of the equator. An ocean general circulation model of the Indian Ocean forced by QuikSCAT winds reproduces the IOD of 2006 remarkably well. The switch over to cooling in the east and warming in the west happened during May and July respectively. In the east, air-sea heat flux initiated cold SSTA in the model which were sustained later by oceanic processes. In the west, surface heat fluxes and horizontal advection caused warm SSTA and contribution by the latter decreased after August.

Microscopic Frictional Response of Sodium Oleate Self-Assembled on Steel

The article peruses the frictional response of an important metal working lubricant additive, sodium oleate. Frictional force microscopy is used to track the response of molecules self-assembled on a steel substrate of 3–4 nm roughness at 0% relative humidity. The friction-normal load characteristic emerges as bell-shaped, where the peak friction and normal load at peak friction are both sensitive to substrate roughness. The frictional response at loads lower than that associated with the peak friction is path reversible while at higher loads the loading and unloading paths are different. We suggest that a new low-friction interface material is created when the normal loads are high.

Circulating Glucocorticoid Bioactivity and Serum Glucocorticoid-Responsive Biomarkers during Steroid Therapy in Children and Adolescents with Inflammatory Bowel Disease

Objective: Glucocorticoid therapy is used worldwide to treat various inflammatory and immune conditions, including inflammatory bowel disease (IBD). In IBD, 80% of the patients obtain a positive response to the therapy; however the development of glucocorticoid-related side-effects is common. Our aim was therefore to study the possibility of optimizing glucocorticoid therapy in children and adolescents with IBD by measuring circulating glucocorticoid bioactivity (GBA) and serum glucocorticoid-responsive biomarkers in patients receiving steroid treatment for active disease. Methods: A total of sixty-nine paediatric IBD patients from the Paediatric Outpatient Clinics of the University Hospitals of Helsinki and Tampere participated in the studies. Control patients included 101 non-IBD patients and 41 disease controls in remission. In patients with active disease, blood samples were withdrawn before the glucocorticoid therapy was started, at 2-4 weeks after the initiation of the steroid and at 1-month intervals thereafter. Clinical response to glucocorticoid treatment and the development of steroid adverse events was carefully registered. GBA was analyzed with a COS-1 cell bioassay. The measured glucocorticoid therapy-responsive biomarkers included adipocyte-derived adiponectin and leptin, bone turnover-related collagen markers amino-terminal type I procollagen propeptide (PINP) and carboxyterminal telopeptide of type I collagen (ICTP) as well as insulin-like growth factor 1 (IGF-1) and sex hormone-binding globulin (SHBG), and inflammatory marker high-sensitivity C-reactive protein (hs-CRP). Results: The most promising marker for glucocorticoid sensitivity was serum adiponectin that associated with steroid therapy–related adverse events. Serum leptin indicated a similar trend. In contrast, circulating GBA rose in all subjects receiving glucocorticoid treatment but did not associate with the clinical response to steroids or with glucocorticoid therapy-related side-effects. Of notice, young patients (<10 years) showed similar GBA levels than older patients, despite receiving higher weight-adjusted doses of glucocorticoid. Markers of bone formation were lower in children with active IBD than in the control patients, probably reflecting the suppressive effect of the active inflammation. The onset of the glucocorticoid therapy further suppressed bone turnover. Inflammatory marker hs-CRP decreased readily after the initiation of the steroid, however the decrease did not associate with the clinical response to glucocorticoids. Conclusions: This is the first study to show that adipocyte-derived adiponectin associates with steroid therapy-induced side-effects. Further studies are needed, but it is possible that the adiponectin measurement could aid the recognition of glucocorticoid-sensitive patients in the future. GBA and the other markers reflecting glucocorticoid activity in different tissues changed during the treatment, however their change did not correlate with the therapeutic response to steroids or with the development of glucocorticoid-related side effects and therefore cannot guide the therapy in these patients. Studies such as as the present one that combine clinical data with newly developed biomolecular technology are needed to step-by-step build a general picture of the glucocorticoid actions in different tissues.

Role of 16S ribosomal RNA methylations in translation initiation in Escherichia coli

Translation initiation from the ribosomal P-site is the specialty of the initiator tRNAs (tRNA(fMet)). Presence of the three consecutive G-C base pairs (G29-C41, G30-C40 and G31-C39) in their anticodon stems, a highly conserved feature of the initiator tRNAs across the three kingdoms of life, has been implicated in their preferential binding to the P-site. How this feature is exploited by ribosomes has remained unclear. Using a genetic screen, we have isolated an Escherichia coli strain, carrying a G122D mutation in folD, which allows initiation with the tRNA(fMet) containing mutations in one, two or all the three G-C base pairs. The strain shows a severe deficiency of methionine and S-adenosylmethionine, and lacks nucleoside methylations in rRNA. Targeted mutations in the methyltransferase genes have revealed a connection between the rRNA modifications and the fundamental process of the initiator tRNA selection by the ribosome.

Slim P‐E hysteresis loop and anomalous dielectric response in sol-gel derived antiferroelectric PbZrO3 thin films

Sol-gel derived PbZrO3 (PZ) thin films have been deposited on Pt(111)/Ti/SiO2/Si substrate and according to the pseudotetragonal symmetry of PZ, the relatively preferred (110)t oriented phase formation has been noticed. The room temperature P‐E hysteresis loops have been observed to be slim by nature. The slim hysteresis loops are attributed to the [110]t directional antiparallel lattice motion of Pb ions and by the directionality of the applied electric field. Pure PZ formation has been characterized by the dielectric phase transition at 235 °C and antiferroelectric P‐E hysteresis loops at room temperature. Dielectric response has been characterized within a frequency domain of 100 Hz–1 MHz at various temperatures ranging from 40 to 350 °C. Though frequency dispersion of dielectric behaves like a Maxwell–Wagner type of relaxation, ω2 dependency of ac conductivity indicates that there must be G‐C equivalent circuit dominance at high frequency. The presence of trap charges in PZ has been determined by Arrhenius plots of ac conductivity. The temperature dependent n (calculated from the universal power law of ac conductivity) values indicate an anomalous behavior of the trapped charges. This anomaly has been explained by strongly and weakly correlated potential wells of trapped charges and their behavior on thermal activation. The dominance of circuit∕circuits resembling Maxwell–Wagner type has been investigated by logarithmic Nyquist plots at various temperatures and it has been justified that the dielectric dispersion is not from the actual Maxwell–Wagner-type response.

Seismic response of reinforced soil retaining wall models: Influence of backfill relative density

This paper presents the results of shaking table tests on model reinforced soil retaining walls in the laboratory. The influence of backfill relative density on the seismic response was studied through a series of laboratory model tests on retaining walls. Construction of model retaining walls in the laminar box mounted on shaking table, instrumentation and results from the shaking table tests are described in detail. Three types of walls: wrap- and rigid-faced reinforced soil walls and unreinforced rigid-faced walls constructed to different densities were tested for a relatively small excitation. Wrap-faced walls are further tested for higher base excitation at different frequencies and relative densities. It is observed from these tests that the effect of backfill density on the seismic performance of reinforced retaining walls is pronounced only at very low relative density and at the higher base excitation. The walls constructed with higher backfill relative density showed lesser face deformations and more acceleration amplifications compared to the walls constructed with lower densities when tested at higher base excitation. The response of wrap- and rigid-faced retaining walls is not much affected by the backfill relative density when tested at smaller base excitation. The effects of facing rigidity were evaluated to a limited extent. Displacements in wrap-faced walls are many times higher compared to rigid-faced walls. The results obtained from this study are helpful in understanding the relative performance of reinforced soil retaining walls constructed to when subjected to smaller and higher base excitation for the range of relative density employed in the testing program. (C) 2007 Elsevier Ltd. All rights reserved.

Author response: "Missed opportunity related to statistical methods"

"We thank MrGilder for his considered comments and suggestions for alternative analyses of our data. We also appreciate Mr Gilder’s support of our call for larger studies to contribute to the evidence base for preoperative loading with high-carbohydrate fluids..."

PE_PGRS Antigens of Mycobacterium tuberculosis Induce Maturation and Activation of Human Dendritic Cells

Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis, infects one-third of the world's population. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). DCs are sentinels of the immune system and are important for eliciting both primary and secondary immune responses to pathogens. In this context, to understand the molecular pathogenesis of tuberculosis and host response to mycobacteria and to conceive prospective vaccine candidates, it is important to understand how cell wall Ags of M.tuberculosis and, in particular, the proline-glutamic acid-polymorphicguanine-cytosine-rich sequence (PE_PGRS) family of proteins modulate DC maturation and function. In this study, we demonstrate that two cell wall-associated/secretory PE_PGRS proteins, PE_PGRS 17 (Rv0978c) and PE_PGRS 11 (Rv0754), recognize TLR2, induce maturation and activation of human DCs, and enhance the ability of DCs to stimulate CD4(+) T cells. We further found that PE_PGRS protein-mediated activation of DCs involves participation of ERK1/2, p38 MAPK, and NF-kappa B signaling pathways. Priming of human DCs with IFN-gamma further augmented PE_PGRS 17 or PE_PGRS 11 Ag-induced DC maturation and secretion of key proinflammatory cytokines. Our results suggest that by activating DCs, PE_PGRS proteins, important mycobacterial cell wall Ags, could potentially contribute in the initiation of innate immune responses during tuberculosis infection and hence regulate the clinical course of tuberculosis. The Journal of Immunology, 2010, 184: 3495-3504.

PE_PGRS Antigens of Mycobacterium tuberculosis Induce Maturation and Activation of Human Dendritic Cells

Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis, infects one-third of the world's population. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). DCs are sentinels of the immune system and are important for eliciting both primary and secondary immune responses to pathogens. In this context, to understand the molecular pathogenesis of tuberculosismand host response to mycobacteria and to conceive prospective vaccine candidates, it is important to understand how cell wall Ags of M. tuberculosis and, in particular, the proline-glutamic acid-polymorphic guanine-cytosine-rich sequence (PE_PGRS) family of proteins modulate DC maturation and function. In this study, we demonstrate that two cell wall-associated/secretory PE_PGRS proteins, PE_PGRS 17 (Rv0978c) and PE_PGRS 11 (Rv0754), recognize TLR2, induce maturation and activation of human DCs, and enhance the ability of DCs to stimulate CD4(+) T cells. We further found that PE_PGRS protein-mediated activation of DCs involves participation of ERK1/2, p38 MAPK, and NF-kappa B signaling pathways. Priming of human DCs with IFN-gamma further augmented PE_PGRS 17 or PE_PGRS 11 Ag-induced DC maturation and secretion of key proinflammatory cytokines. Our results suggest that by activating DCs, PE_PGRS proteins, important mycobacterial cell wall Ags, could potentially contribute in the initiation of innate immune responses during tuberculosis infection and hence regulate the clinical course of tuberculosis. The Journal of Immunology, 2010, 184: 3495-3504.

Replication of Japanese encephalitis virus in mouse brain induces alterations in lymphocyte response

The experimental model using intracerebral (i.c.) challenge was employed in many studies evaluating the protection against disease induced by Japanese encephalitis virus (JEV). We investigated alterations in peripheral lymphocyte response caused by i.c. infection of mice with JEV. Splenocytes from the i.c.-infected mice showed suppressed proliferative response to concanavalin A (con A) and anti-CD3 antibody stimulation. At the same time, the expression of CD25 (IL-2R) and production of IL-2 was inhibited. Addition of anti-CD28 antibody restored the decreased anti-CD3 antibody-mediated proliferation in the splenocytes. Moreover, the number of con A-stimulated cells secreting IL-4 was significantly reduced in splenocytes from i.c.-infected mice. These studies suggested that the i.c. infection with JEV might involve additional immune modulation effects due to massive virus replication in the brain.

Characterisation of head-hardened rail steel in terms of cyclic plasticity response and microstructure for improved material modelling

Stress- and strain-controlled tests of heat treated high-strength rail steel (Australian Standard AS1085.1) have been performed in order to improve the characterisation of the said material׳s ratcheting and fatigue wear behaviour. The hardness of the rail head material has also been studied and it has been found that hardness reduces considerably below four-millimetres from the rail top surface. Historically, researchers have used test coupons with circular cross-sections to conduct cyclic load tests. Such test coupons, typically five-millimetres in gauge diameter and ten‐millimetres in grip diameter, are usually taken from the rail head sample. When there is considerable variation of material properties over the cross-section it becomes likely that localised properties of the rail material will be missed. In another case from the literature, disks 47 mm in diameter for a twin-disk rolling contact test machine were obtained directly from the rail sample and used to validate ratcheting and rolling contact fatigue wear models. The question arises: How accurate are such tests, especially when large material property gradients exist? In this research paper, the effects of rail sampling location on the ratcheting behaviour of AS1085.1 rail steel were investigated using rectangular-shaped specimens obtained at four different depths to observe their respective cyclic plasticity behaviour. The microstructural features of the test coupons were also analysed, especially the pearlite inter-lamellar spacing which showed strong correlation with both hardness and cyclic plasticity behaviour of the material. This work ultimately provides new data and testing methodology to aid the selection of valid parameters for material constitutive models to better understand rail surface ratcheting and wear.

Response time measurement in flow induced signal generation on semiconductors

Measurable electrical signal is generated when a gas flows over a variety of solids, including doped semiconductors, even at the modest speed of a few meters per second. The underlying mechanism is an interesting interplay of Bernoulli's principle and the Seebeck effect. The electrical signal depends on the square of Mach number (M) and is proportional to the Seebeck coefficient (S) of the solids. Here we present experimental estimate of the response time of the signal rise and fall process, i.e. how fast the semiconductor materials respond to a steady flow as soon as it is set on or off. A theoretical model is also presented to understand the process and the dependence of the response time on the nature and physical dimensions of the semiconductor material used and they are compared with the experimental observations. (c) 2007 Elsevier B.V. All rights reserved.

Investigation of true remnant polarization response in heterostructured artificial biferroics

Epitaxial bilayered thin films composed of ferromagnetic La0.6Sr0.4MnO3 and ferroelectric 0.7Pb (Mg1/3Nb2/3)O3-0.3(PbTiO3) were fabricated on LaAlO3 (100) substrates by pulsed laser ablation. Ferroelectric, ferromagnetic and magneto-dielectric characterizations performed earlier indicated the possible existence of strain-mediated magneto-electric coupling in these biferroic heterostructures. In order to investigate their true remnant polarization characteristics, usable in devices, room-temperature polarization versus electric field, positive-up negative-down (PUND) pulse polarization studies and remnant hysteresis measurements were carried out. The PUND and remnant hysteresis measurements revealed the significant contribution of the non-remnant component in the observed polarization hysteresis response of these heterostructures. (C) 2010 Published by Elsevier Ltd

Seismic response of wrap-faced reinforced soil-retaining wall models using shaking table tests

This paper presents the results of shaking table tests on geotextile-reinforced wrap-faced soil-retaining walls. Construction of model retaining walls in a laminar box mounted on a shaking table, instrumentation, and results from the shaking table tests are discussed in detail. The base motion parameters, surcharge pressure and number of reinforcing layers are varied in different model tests. It is observed from these tests that the response of the wrap-faced soil-retaining walls is significantly affected by the base acceleration levels, frequency of shaking, quantity of reinforcement and magnitude of surcharge pressure on the crest. The effects of these different parameters on acceleration response at different elevations of the retaining wall, horizontal soil pressures and face deformations are also presented. The results obtained from this study are helpful in understanding the relative performance of reinforced soil-retaining walls under different test conditions used in the experiments.