Cancer survivors at work : Work-related problems and factors associated with their employment, work ability and social support from the work community

Due to the improved prognosis of many forms of cancer, an increasing number of cancer survivors are willing to return to work after their treatment. It is generally believed, however, that people with cancer are either unemployed, stay at home, or retire more often than people without cancer. This study investigated the problems that cancer survivors experience on the labour market, as well as the disease-related, sociodemographic and psychosocial factors at work that are associated with the employment and work ability of cancer survivors. The impact of cancer on employment was studied combining the data of Finnish Cancer Registry and census data of the years 1985, 1990, 1995 or 1997 of Statistics Finland. There were two data sets containing 46 312 and 12 542 people with cancer. The results showed that cancer survivors were slightly less often employed than their referents. Two to three years after the diagnosis the employment rate of the cancer survivors was 9% lower than that of their referents (64% vs. 73%), whereas the employment rate was the same before the diagnosis (78%). The employment rate varied greatly according to the cancer type and education. The probability of being employed was greater in the lower than in the higher educational groups. People with cancer were less often employed than people without cancer mainly because of their higher retirement rate (34% vs. 27%). As well as employment, retirement varied by cancer type. The risk of retirement was twofold for people having cancer of the nervous system or people with leukaemia compared to their referents, whereas people with skin cancer, for example, did not have an increased risk of retirement. The aim of the questionnaire study was to investigate whether the work ability of cancer survivors differs from that of people without cancer and whether cancer had impaired their work ability. There were 591 cancer survivors and 757 referents in the data. Even though current work ability of cancer survivors did not differ between the survivors and their referents, 26% of cancer survivors reported that their physical work ability, and 19% that their mental work ability had deteriorated due to cancer. The survivors who had other diseases or had had chemotherapy, most often reported impaired work ability, whereas survivors with a strong commitment to their work organization, or a good social climate at work, reported impairment less frequently. The aim of the other questionnaire study containing 640 people with the history of cancer was to examine extent of social support that cancer survivors needed, and had received from their work community. The cancer survivors had received most support from their co-workers, and they hoped for more support especially from the occupational health care personnel (39% of women and 29% of men). More support was especially needed by men who had lymphoma, had received chemotherapy or had a low education level. The results of this study show that the majority of the survivors are able to return to work. There is, however, a group of cancer survivors who leave work life early, have impaired work ability due to their illness, and suffer from lack of support from their work place and the occupational health services. Treatment-related, as well as sociodemographic factors play an important role in survivors' work-related problems, and presumably their possibilities to continue working.

Environmentally benign Fe chelates in plant nutrition

The low solubility of iron (Fe) depresses plant growth in calcareous soils. In order to improve Fe availability, calcareous soils are treated with synthetic ligands, such as ethylenediaminetetraacetic acid (EDTA) and ethylenediimi-nobis(2-hydroxyphenyl)acetic acid (EDDHA). However, high expenses may hinder their use (EDDHA), and the recalcitrance of EDTA against biodegra-dation may increase the potential of cadmium (Cd) and lead (Pb) leaching. This study evaluated the ability of biodegradable ligands, i.e. different stereo-isomers of ethylenediaminedisuccinic acid (EDDS), to provide Fe for lettuce (Lactuca sativa L.) and ryegrass (Lolium perenne cv. Prego), their effects on uptake of other elements and solubility in soils and their subsequent effects on the activity of oxygen-scavenging enzymes in lettuce. Both EDTA and EDDHA were used as reference ligands. In unlimed and limed quartz sand both FeEDDS(S,S) and a mixture of stereo-isomers of FeEDDS (25% [S,S]-EDDS, 25% [R,R]-EDDS and 50% [S,R]/[R,S]-EDDS), FeEDDS(mix), were as efficient as FeEDTA and FeEDDHA in providing lettuce with Fe. However, in calcareous soils only FeEDDS(mix) was comparable to FeEDDHA when Fe was applied twice a week to mimic drip irrigation. The Fe deficiency increased the manganese (Mn) concentration in lettuce in both acidic and alkaline growth media, whereas Fe chelates depressed it. The same was observed with zinc (Zn) and copper (Cu) in acidic growth media. EDDHA probably affected the hormonal status of lettuce as well and thus depressed the uptake of Zn and Mn even more. The nutrient concentrations of ryegrass were only slightly affected by the Fe availability. After Fe chelate splitting in calcareous soils, EDDS and EDTA increased the solubility of Zn and Cu most, but only the Zn concentration was increased in lettuce. The availability of Fe increased the activity of oxygen-scavenging enzymes (ascorbate peroxidase, guaiacol peroxidase, catalase). The activity of Cu/ZnSOD (Cu/Zn superoxide dismutase) and MnSOD in lettuce leaves followed the concentrations of Zn and Mn. In acidic quartz sand low avail-ability of Fe increased the cobalt (Co) and nickel (Ni) concentrations in let-tuce, but Fe chelates decreased them. EDTA increased the solubility of Cd and Pb in calcareous soils, but not their uptake. The biodegradation of EDDS was not affected by the complexed element, and [S,S]-EDDS was biodegraded within 28 days in calcareous soils. EDDS(mix) was more recalcitrant, and after 56 days of incubation water-soluble elements (Fe, Mn, Zn, Cu, Co, Ni, Cd and Pb) corresponded to 10% of the added EDDS(mix) concentration.

The kinetics and reactivity of several polyatomic free radicals in reactions with NO2, O2, Cl2, and HCl

In this thesis, the kinetics of several alkyl, halogenated alkyl, and alkenyl free radical reactions with NO2, O2, Cl2, and HCl reactants were studied over a wide temperature range in time resolved conditions. Laser photolysis photoionisation mass spectrometer coupled to a flow reactor was the experimental method employed and this thesis present the first measurements performed with the experimental system constructed. During this thesis a great amount of work was devoted to the designing, building, testing, and improving the experimental apparatus. Carbon-centred free radicals were generated by the pulsed 193 or 248 nm photolysis of suitable precursors along the tubular reactor. The kinetics was studied under pseudo-first-order conditions using either He or N2 buffer gas. The temperature and pressure ranges employed were between 190 and 500 K, and 0.5 45 torr, respectively. The possible role of heterogeneous wall reactions was investigated employing reactor tubes with different sizes, i.e. to significantly vary the surface to volume ratio. In this thesis, significant new contributions to the kinetics of carbon-centred free radical reactions with nitrogen dioxide were obtained. Altogether eight substituted alkyl (CH2Cl, CHCl2, CCl3, CH2I, CH2Br, CHBr2, CHBrCl, and CHBrCH3) and two alkenyl (C2H3, C3H3) free radical reactions with NO2 were investigated as a function of temperature. The bimolecular rate coefficients of all these reactions were observed to possess negative temperature dependencies, while pressure dependencies were not noticed for any of these reactions. Halogen substitution was observed to moderately reduce the reactivity of substituted alkyl radicals in the reaction with NO2, while the resonance stabilisation of the alkenyl radical lowers its reactivity with respect to NO2 only slightly. Two reactions relevant to atmospheric chemistry, CH2Br + O2 and CH2I + O2, were also investigated. It was noticed that while CH2Br + O2 reaction shows pronounced pressure dependence, characteristic of peroxy radical formation, no such dependence was observed for the CH2I + O2 reaction. Observed primary products of the CH2I + O2 reaction were the I-atom and the IO radical. Kinetics of CH3 + HCl, CD3 + HCl, CH3 + DCl, and CD3 + DCl reactions were also studied. While all these reactions possess positive activation energies, in contrast to the other systems investigated in this thesis, the CH3 + HCl and CD3 + HCl reactions show a non-linear temperature dependency on the Arrhenius plot. The reactivity of substituted methyl radicals toward NO2 was observed to increase with decreasing electron affinity of the radical. The same trend was observed for the reactions of substituted methyl radicals with Cl2. It is proposed that interactions of frontier orbitals are responsible to these observations and Frontier Orbital Theory could be used to explain the observed reactivity trends of these highly exothermic reactions having reactant-like transition states.

A Floor Control Server in a Distributed Conference Service

The conferencing systems in IP Multimedia (IM) networks are going through restructuring, accomplished in the near future. One of the changes introduced is the concept of floors and floor control in its current form with matching entity roles. The Binary Floor Control Protocol (BFCP) is a novelty to be exploited in distributed tightly coupled conferencing services. The protocol defines the floor control server (FCS), which implements floor control giving access to shared resources. As the newest tendency is to distribute the conferencing services, the locations of different functionality units play an important role in developing the standards. The floor control server location is not yet single-mindedly fixed in different standardization bodies, and the debate goes on where to place it within the media server, providing the conferencing service. The thesis main objective is to evaluate two distinctive alternatives in respect the Mp interface protocol between the respective nodes, as the interface in relation to floor control is under standardization work at the moment. The thesis gives a straightforward preamble in IMS network, nodes of interest including floor control server and conferencing. Knowledge on several protocols – BFCP, SDP, SIP and H.248 provides an important background for understanding the functionality changes introduced in the Mp interface and therefore introductions on those protocols and how they are connected to the full picture is given. The actual analysis on the impact of the floor control server into the Mp reference point is concluded in relation to the locations, giving basic flows, requirements analysis including a limited implementation proposal on supporting protocol parameters. The overall conclusion of the thesis is that even if both choices are seemingly useful, not one of the locations is clearly the most suitable in the light of this work. The thesis suggests a solution having both possibilities available to be chosen from in separate circumstances, realized with consistent standardization. It is evident, that if the preliminary assumption for the analysis is kept regarding to only one right place for the floor control server, more work is to be done in connected areas to discover the one most appropriate location.

Stress responses of Gram-positive bacteria to cationic antimicrobial peptides

As the resistance of bacteria to conventional antibiotics has become an increasing problem, new antimicrobial drugs are urgently needed. One possible source of new antibacterial agents is a group of cationic antimicrobial peptides (CAMPs) produced by practically all living organisms. These peptides are typically small, amphipathic and positively charged and contain well defined a-helical or b-sheet secondary structures. The main antibacterial action mechanism of CAMPs is considered to be disruption of the cell membrane, but other targets of CAMPs also exist. Some bacterial species have evolved defence mechanisms against the harmful effects of CAMPs. One of the most effective defence mechanisms is reduction of the net negative charge of bacterial cell surfaces. Global analysis of gene expression of two Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus, was used to further study the stress responses induced by different types of CAMPs. B. subtilis cells were treated with sublethal concentrations of a-helical peptide LL-37, b-sheet peptide protegrin 1 or synthetic analogue poly-L-lysine, and the changes in gene expression were studied using DNA macroarrays. In the case of S. aureus, three different a-helical peptides were selected for the transcriptome analyses: temporin L, ovispirin-1 and dermaseptin K4-S4(1-16). Transcriptional changes caused by peptide stress were examined using oligo DNA microarrays. The transcriptome analysis revealed two main cell signalling mechanisms mediating CAMP stress responses in Gram-positive bacteria: extracytoplasmic function (ECF)sigma factors and two-component systems (TCSs). In B. subtilis, ECF sigma factors sigW and sigM as well as TCS LiaRS responded to the cell membrane disruption caused by CAMPs. In S. aureus, CAMPs caused a similar stress response to antibiotics interfering in cell wall synthesis, and TCS VraSR was strongly activated. All of these transcriptional regulators are known to respond to several compounds other than CAMPs interfering with cell envelope integrity, suggesting that they sense cell envelope stress in general. Among the most strongly induced genes were yxdLM (in B. subtilis) and vraDE (in S. aureus) encoding homologous ABC transporters. Transcription of yxdLM and vraDE operons is controlled by TCSs YxdJK and ApsRS, respectively. These TCSs seemed to be responsible for the direct recognition of CAMPs. The yxdLM operon was specifically induced by LL-37, but its role in CAMP resistance remained unclear. VraDE was proven to be a bacitracin transporter. We also showed that the net positive charge of the cell wall affects the signalrecognition of different TCSs responding to cell envelope stress. Inactivation of the Dlt system responsible for the D-alanylation of teichoic acids had a strong and differential effect on the activity of the studied TCSs, depending on their functional role in cells and the stimuli they sense.

Clinical aspects of exhaled nitric oxide in adults : Associations with atopy, bronchial hyperresponsiveness, smoking and chronic obstruction

Measurement of fractional exhaled nitric oxide (FENO) has proven useful in assessment of patients with respiratory symptoms, especially in predicting steroid response. The objective of these studies was to clarify issues relevant for the clinical use of FENO. The influence of allergic sensitization per se on FENO in healthy asymptomatic subjects was studied, the association between airway inflammation and bronchial hyperresponsiveness (BHR) in steroid-naive subjects with symptoms suggesting asthma was examined, as well as the possible difference in this association between atopic and nonatopic subjects. Influence of smoking on FENO was compared between atopic and nonatopic steroid-naive asthmatics and healthy subjects. The short-term repeatability of FENO in COPD patients was examined in order to assess whether the degree of chronic obstruction influences the repeatability. For these purposes, we studied a random sample of 248 citizens of Helsinki, 227 army conscripts with current symptoms suggesting asthma, 19 COPD patients, and 39 healthy subjects. FENO measurement, spirometry and bronchodilatation test, structured interview. skin prick tests, and histamine and exercise challenges were performed. Among healthy subjects with no signs of airway diseases, median FENO was similar in skin prick test-positive and –negative subjects, and the upper normal limit of FENO was 30 ppb. In atopic and nonatopic subjects with symptoms suggesting asthma, FENO associated with severity of exercise- or histamine-induced BHR only in atopic patients. FENO in smokers with steroid-naive asthma was significantly higher than in healthy smokers and nonsmokers. Among atopic asthmatics, FENO was significantly lower in smokers than in nonsmokers, whereas no difference appeared among nonatopic asthmatics. The 24-h repeatability of FENO was equally good in COPD patients as in healthy subjects. These findings indicate that allergic sensitization per se does not influence FENO, supporting the view that elevated FENO indicates NO-producing airway inflammation, and that same reference range can be applied to both skin prick test-positive and -negative subjects. The significant correlation between FENO and degree of BHR only in atopic steroid-naive subjects with current asthmatic symptoms supports the view that pathogenesis of BHR in atopic asthma is strongly involved in NO-producing airway inflammation, whereas in development of BHR in nonatopic asthma other mechanisms may dominate. Attenuation of FENO only in atopic but not in nonatopic smokers with steroid-naive asthma may result from differences in mechanisms of FENO formation as well as in sensitivity of these mechanisms to smoking in atopic and nonatopic asthma. The results suggest, however, that in young adult smokers, FENO measurement may prove useful in assessment of airway inflammation. The short-term repeatability of FENO in COPD patients with moderate to very severe disease and in healthy subjects was equally good.

Snow characteristics in Dronning Maud Land, Antarctica

Snow cover is very sensitive to climate change and has a large feedback effect on the climate system due to the high albedo. Snow covers almost all surfaces in Antarctica and small changes in snow properties can mean large changes in absorbed radiation. In the ongoing discussion of climatic change, the mass balance of Antarctica has received increasing focus during recent decades, since its reaction to global warming strongly influences sea-level change. The aim of the present work was to examine the spatial and temporal variations in the physical and chemical characteristics of surface snow and annual accumulation rates in western Dronning Maud Land, Antarctica. The data were collected along a 350-km-long transect from the coast to the plateau during the years 1999-2004 as a part of the Finnish Antarctic Research Programme (FINNARP). The research focused on the most recent annual accumulation in the coastal area. The results show that the distance from the sea, and the moisture source, was the most predominant factor controlling the variations in both physical (conductivity, grain size, oxygen isotope ratio and accumulation) and chemical snow properties. The sea-salt and sulphur-containing components predominated in the coastal region. The local influences of nunataks and topographic highs were also visible on snow. The variations in all measured properties were wide within single sites mostly due to redistribution by winds and sastrugi topography, which reveals the importance of the spatially representative measurements. The mean accumulations occurred on the ice shelf, in the coastal region and on the plateau: 312 ± 28, 215 ± 43 and 92 ± 25 mm w.e., respectively. Depth hoar layers were usually found under the thin ice crust and were associated with a low dielectric constant and high concentrations of nitrate. Taking into account the vast size of the Antarctic ice sheet and its geographic characteristics, it is important to extend investigation of the distribution of surface snow properties and accumulation to provide well-documented data.

The Structure and Functions of Hantavirus Nucleocapsid Protein

Hantaviruses, members of the genus Hantavirus in the Bunyaviridae family, are enveloped single-stranded RNA viruses with tri-segmented genome of negative polarity. In humans, hantaviruses cause two diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), which vary in severity depending on the causative agent. Each hantavirus is carried by a specific rodent host and is transmitted to humans through excreta of infected rodents. The genome of hantaviruses encodes four structural proteins: the nucleocapsid protein (N), the glycoproteins (Gn and Gc), and the polymerase (L) and also the nonstructural protein (NSs). This thesis deals with the functional characterization of hantavirus N protein with regard to its structure. Structural studies of the N protein have progressed slowly and the crystal structure of the whole protein is still not available, therefore biochemical assays coupled with bioinformatical modeling proved essential for studying N protein structure and functions. Presumably, during RNA encapsidation, the N protein first forms intermediate trimers and then oligomers. First, we investigated the role of N-terminal domain in the N protein oligomerization. The results suggested that the N-terminal region of the N protein forms a coiled-coil, in which two antiparallel alpha helices interact via their hydrophobic seams. Hydrophobic residues L4, I11, L18, L25 and V32 in the first helix and L44, V51, L58 and L65 in the second helix were crucial for stabilizing the structure. The results were consistent with the head-to-head, tail-to-tail model for hantavirus N protein trimerization. We demonstrated that an intact coiled-coil structure of the N terminus is crucial for the oligomerization capacity of the N protein. We also added new details to the head-to-head, tail-to-tail model of trimerization by suggesting that the initial step is based on interaction(s) between intact intra-molecular coiled-coils of the monomers. We further analyzed the importance of charged aa residues located within the coiled-coil for the N protein oligomerization. To predict the interacting surfaces of the monomers we used an upgraded in silico model of the coiled-coil domain that was docked into a trimer. Next the predicted target residues were mutated. The results obtained using the mammalian two-hybrid assay suggested that conserved charged aa residues within the coiled-coil make a substantial contribution to the N protein oligomerization. This contribution probably involves the formation of interacting surfaces of the N monomers and also stabilization of the coiled-coil via intramolecular ionic bridging. We proposed that the tips of the coiled-coils are the first to come into direct contact and thus initiate tight packing of the three monomers into a compact structure. This was in agreement with the previous results showing that an increase in ionic strength abolished the interaction between N protein molecules. We also showed that residues having the strongest effect on the N protein oligomerization are not scattered randomly throughout the coiled-coil 3D model structure, but form clusters. Next we found evidence for the hantaviral N protein interaction with the cytoplasmic tail of the glycoprotein Gn. In order to study this interaction we used the GST pull-down assay in combination with mutagenesis technique. The results demonstrated that intact, properly folded zinc fingers of the Gn protein cytoplasmic tail as well as the middle domain of the N protein (that includes aa residues 80 248 and supposedly carries the RNA-binding domain) are essential for the interaction. Since hantaviruses do not have a matrix protein that mediates the packaging of the viral RNA in other negatve stranded viruses (NSRV), hantaviral RNPs should be involved in a direct interaction with the intraviral domains of the envelope-embedded glycoproteins. By showing the N-Gn interaction we provided the evidence for one of the crucial steps in the virus replication at which RNPs are directed to the site of the virus assembly. Finally we started analysis of the N protein RNA-binding region, which is supposedly located in the middle domain of the N protein molecule. We developed a model for the initial step of RNA-binding by the hantaviral N protein. We hypothesized that the hantaviral N protein possesses two secondary structure elements that initiate the RNA encapsidation. The results suggest that amino acid residues (172-176) presumably act as a hook to catch vRNA and that the positively charged interaction surface (aa residues 144-160) enhances the initial N-RNA interacation. In conclusion, we elucidated new functions of hantavirus N protein. Using in silico modeling we predicted the domain structure of the protein and using experimental techniques showed that each domain is responsible for executing certain function(s). We showed that intact N terminal coiled-coil domain is crucial for oligomerization and charged residues located on its surface form a interaction surface for the N monomers. The middle domain is essential for interaction with the cytoplasmic tail of the Gn protein and RNA binding.

Integrative functional genomics analysis of sustained polyploidy phenotypes in breast cancer cells identifies an oncogenic profile for GINS2

Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and that aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication and possibly through polyploid intermediate states. Here, we used a novel cell spot microarray technique to identify genes with a loss-of-function effect inducing polyploidy and/or allowing maintenance of polyploid cell growth of breast cancer cells. Integrative genomics profiling of candidate genes highlighted GINS2 as a potential oncogene frequently overexpressed in clinical breast cancers as well as in several other cancer types. Multivariate analysis indicated GINS2 to be an independent prognostic factor for breast cancer outcome (p = 0.001). Suppression of GINS2 expression effectively inhibited breast cancer cell growth and induced polyploidy. In addition, protein level detection of nuclear GINS2 accurately distinguished actively proliferating cancer cells suggesting potential use as an operational biomarker.

Measurement of the tt̅ production cross section in 2 fb-1 of pp̅ collisions at √s=1.96 TeV using lepton plus jets events with soft muon b tagging

We present a measurement of the tt̅ production cross section in pp̅ collisions at √s=1.96  TeV using events containing a high transverse momentum electron or muon, three or more jets, and missing transverse energy. Events consistent with tt̅ decay are found by identifying jets containing candidate heavy-flavor semileptonic decays to muons. The measurement uses a CDF run II data sample corresponding to 2  fb-1 of integrated luminosity. Based on 248 candidate events with three or more jets and an expected background of 79.5±5.3 events, we measure a production cross section of 9.1±1.6  pb.

Measurement of the tt̅ production cross section in 2 fb-1 of pp̅ collisions at √s=1.96 TeV using lepton plus jets events with soft muon b tagging

We present a measurement of the tt̅ production cross section in pp̅ collisions at √s=1.96  TeV using events containing a high transverse momentum electron or muon, three or more jets, and missing transverse energy. Events consistent with tt̅ decay are found by identifying jets containing candidate heavy-flavor semileptonic decays to muons. The measurement uses a CDF run II data sample corresponding to 2  fb-1 of integrated luminosity. Based on 248 candidate events with three or more jets and an expected background of 79.5±5.3 events, we measure a production cross section of 9.1±1.6  pb.

Measurement of the tt̅ production cross section in 2 fb-1 of pp̅ collisions at √s=1.96 TeV using lepton plus jets events with soft muon b tagging

We present a measurement of the $\ttbar$ production cross section in $\ppbar$ collisions at $\sqrt{s}=1.96$ TeV using events containing a high transverse momentum electron or muon, three or more jets, and missing transverse energy. Events consistent with $\ttbar$ decay are found by identifying jets containing candidate heavy-flavor semileptonic decays to muons. The measurement uses a CDF Run II data sample corresponding to $2 \mathrm{fb^{-1}}$ of integrated luminosity. Based on 248 candidate events with three or more jets and an expected background of $79.5\pm5.3$ events, we measure a production cross section of $9.1\pm 1.6 \mathrm{pb}$.

Integrin trafficking regulated by Rab21 is necessary for cytokinesis

Adherent cells undergo remarkable changes in shape during cell division. However, the functional interplay between cell adhesion turnover and the mitotic machinery is poorly understood. The endo/exocytic trafficking of integrins is regulated by the small GTPase Rab21, which associates with several integrin alpha subunits. Here, we show that targeted trafficking of integrins to and from the cleavage furrow is required for successful cytokinesis, and that this is regulated by Rab21. Rab21 activity, integrin-Rab21 association, and integrin endocytosis are all necessary for normal cytokinesis, which becomes impaired when integrin-mediated adhesion at the cleavage furrow fails. We also describe a chromosomal deletion and loss of Rab21 gene expression in human cancer, which leads to the accumulation of multinucleate cells. Importantly, reintroduction of Rab21 rescued this phenotype. In conclusion, Rab21-regulated integrin trafficking is essential for normal cell division, and its defects may contribute to multinucleation and genomic instability, which are hallmarks of cancer.