The C-Terminal Domain of the MutL Homolog from Neisseria gonorrhoeae Forms an Inverted Homodimer

The mismatch repair (MMR) pathway serves to maintain the integrity of the genome by removing mispaired bases from the newly synthesized strand. In E. coli, MutS, MutL and MutH coordinate to discriminate the daughter strand through a mechanism involving lack of methylation on the new strand. This facilitates the creation of a nick by MutH in the daughter strand to initiate mismatch repair. Many bacteria and eukaryotes, including humans, do not possess a homolog of MutH. Although the exact strategy for strand discrimination in these organisms is yet to be ascertained, the required nicking endonuclease activity is resident in the C-terminal domain of MutL. This activity is dependent on the integrity of a conserved metal binding motif. Unlike their eukaryotic counterparts, MutL in bacteria like Neisseria exist in the form of a homodimer. Even though this homodimer would possess two active sites, it still acts a nicking endonuclease. Here, we present the crystal structure of the C-terminal domain (CTD) of the MutL homolog of Neisseria gonorrhoeae (NgoL) determined to a resolution of 2.4 A. The structure shows that the metal binding motif exists in a helical configuration and that four of the six conserved motifs in the MutL family, including the metal binding site, localize together to form a composite active site. NgoL-CTD exists in the form of an elongated inverted homodimer stabilized by a hydrophobic interface rich in leucines. The inverted arrangement places the two composite active sites in each subunit on opposite lateral sides of the homodimer. Such an arrangement raises the possibility that one of the active sites is occluded due to interaction of NgoL with other protein factors involved in MMR. The presentation of only one active site to substrate DNA will ensure that nicking of only one strand occurs to prevent inadvertent and deleterious double stranded cleavage.

Periodontal and dental health and oral self-care among adults with diabetes mellitus.

ABSTRACT Bakhshandeh, Soheila. Periodontal and dental health and oral self-care among adults with diabetes mellitus. Department of Oral Public Health, Institute of Dentistry, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 2011. 49 pp. ISBN 978-952-10-7193-5(paperback). The aim of the present study was to assess oral health and treatment needs among Iranian adults with diabetes according to socio-demographic status, oral hygiene, diabetes related factors, and to investigate the relation between these determinants and oral health. Moreover, the effect of an educational oral health promotion intervention on their oral health and periodontal treatment needs was studied. The target population comprised adults with diabetes in Tehran, Iran. 299 dentate patients with diabetes, who were regular attendants to a diabetic clinic, were selected as the study subjects. Data collection was performed through a clinical dental examination and self-administered structured questionnaire. The questionnaire covered information of the subject s social background, medical history, oral health behaviour and smoking. The clinical dental examinations covered the registration of caries experience (DMFT), community periodontal index (CPI) and plaque index (PI). The intervention provided the adults with diabetes dental health education through a booklet. Reduction in periodontal treatment needs one year after the baseline examination was used as the main outcome. A high prevalence of periodontal pockets among the study population was found; 52% of the participants had periodontal pockets with a pocket depth of 4 to 5 mm and 35% had periodontal pockets with pocket depth of 6 mm or more. The mean of the DMFT index was 12.9 (SD=6.1), being dominated by filled teeth (mean 6.5) and missing teeth (mean 5.0). Oral self-care among adults with diabetes was inadequate and poor oral hygiene was observed in more than 80% of the subjects. The educational oral health promotion decreased periodontal treatment needs more in the study groups than in the control group. The poor periodontal health, poor oral hygiene and insufficient oral self-care observed in this study call for oral health promotion among adult with diabetes. An educational intervention showed that it is possible to promote oral health behaviour and to reduce periodontal treatment needs among adults with diabetes. The simplicity of the model used in this study allows it to be integrated to diabetes programmes in particular in countries with a developing health care system.

Terminal solid solubilities at 900–1000°C in the magnesium oxide-zinc oxide system measured using a magnesium fluoride solid-electrolyte galvanic cell

The terminal solid solubilities of the periclase (MgO-rich) and zincite (ZnO-rich) solid solutions in the MgO---ZnO system have been determined by measuring the activity of MgO using a solid-state galvanic cell of the type 02(g), Pt/MgO, MgF2//MgF2//{χMgO+(1-χ)ZnO}(s, sln), MgF2/Pt, O2(g) in the temperature range 900–1050°C. The ZnO activity was calculated by graphical Gibbs-Duhem integration. The activity-composition plots of both components exhibit a strong positive deviation from ideality and are characterised by a miscibility gap. The terminal solid solubilities of the periclase and zincite solid solutions obtained from the activity-composition plots are found to be in reasonable agreement with those reported in the literature.

Chinese immigrants to Finland: A qualitative study of housing, employment, access to health care and child care as sociological dimensions in their settlement process

The Master’s thesis is qualitative research based on interviews of 15 Chinese immigrants to Finland in order to provide a sociological perspective of the migration experience through the eyes of Chinese immigrants in the Finnish social welfare context. This research is mainly focused upon four crucial aspects of life in the settlement process: housing, employment, access to health care and child care. Inspired by Allardt’s theoretical framework ‘Having, Loving and Being’, social relationships and individual satisfaction are examined in the case of Chinese interviewees dealing with the four life aspects. Finland was not perceived as an attractive migration destination for most Chinese interviewees in the beginning. However, with longer residence in Finland, the Finnish social welfare system gradually became a crucial appealing factor in their permanent settlement in Finland. And meanwhile, social responsibility of attending their old parents in China, strong feelings of being isolated in Finland, and insufficient integration into the Finnish society were influential factors for their decision of returning to China. Social relationships with personal friends, migration brokers, schools, employers and family relatives had great influences in the four life aspects of Chinese immigrants in Finland. The social relationship with the Finnish social welfare sector is supportive to Chinese immigrants, but Chinese immigrants do not heavily rely on Finnish social protection. The housing conditions were greatly improved over time while the upward mobility in the Finnish labour market was not significant among Chinese immigrants. All Chinese immigrants were satisfied with their current housing by the time I interviewed them while most of them had subjective feelings of being alienated in the Finnish labour market, which seriously prevented them from integrating into the Finnish society. In general, Chinese immigrants were satisfied with the low cost of accessing the Finnish public health care services and affordable Finnish child day care services and financial subsidies for children from the Finnish social welfare sector. This research also suggests that employment is the central basis in well-being. Support from the Finnish social welfare sector can improve the satisfaction levels among immigrants, especially when it mitigates the effects of low-paid employment. As well, my empirical study of Chinese immigrants in Finland shows that Having (needs for materials), Loving (needs for social relations) and Being (needs for social integration) are all involved in the four concrete aspects (housing, employment, access to health care and child care).

Pain measurement and management in elderly patients : Clinical studies in long term hospital care and after cardiac surgery

The proportion of patients over 75 years of age, receiving all different types of healthcare, is constantly increasing. The elderly undergo surgery and anaesthetic procedures more often than middle-aged patients. Poor pain management in the elderly is still an issue. Although the elderly consumes the greatest proportion of prescribed medicines in Western Europe, most clinical pharmacological studies have been performed in healthy volunteers or middle-aged patients. The aim of this study was to investigate pain measurement and management in cognitively impaired patients in long term hospital care and in cognitively normal elderly patients after cardiac surgery. This thesis incorporated 366 patients, including 86 home-dwelling or hospitalized elderly with chronic pain and 280 patients undergoing cardiac surgery with acute pain. The mean age of patients was 77 (SD ± 8) years and approximately 8400 pain measurements were performed with four pain scales: Verbal Rating Scale (VRS), the Visual Analogue Scale (VAS), the Red Wedge Scale (RWS), and the Facial Pain Scale (FPS). Cognitive function, depression, functional ability in daily life, postoperative sedation and postoperative confusion were assessed with MMSE, GDS, Barthel Index, RASS, and CAM-ICU, respectively. The effects and plasma concentrations of fentanyl and oxycodone were measured in elderly (≥ 75 years) and middle-aged patients (≤ 60 years) and the opioid-sparing effect of pregabalin was studied after cardiac surgery. The VRS pain scores after movement correlated with the Barthel Index. The VRS was most successful in the groups of demented patients (MMSE 17-23, 11-16 and ≤ 10) and in elderly patients on the first day after cardiac surgery. The elderly had a higher plasma concentration of fentanyl at the end of surgery than younger patients. The plasma concentrations of oxycodone were comparable between the groups. Pain intensity on the VRS was lower and the sedation scores were higher in the elderly. Total oxycodone consumption during five postoperative days was reduced by 48% and the CAM-ICU scores were higher on the first postoperative day in the pregabalin group. The incidence of postoperative pain during movement was lower in the pregabalin group three months after surgery. This investigation demonstrates that chronic pain did not seem to impair daily activities in home-dwelling Finnish elderly. The VRS appeared to be applicable for elderly patients with clear cognitive dysfunction (MMSE ≤17) and it was the most feasible pain scale for the early postoperative period after cardiac surgery. After cardiac surgery, plasma concentrations of fentanyl in elderly were elevated, although oxycodone concentrations were at similar level compared to middle-aged patients. The elderly had less pain and were more sedated after doses of oxycodone. Therefore, particular attention must be given to individual dosing of the opioids in elderly surgical patients, who often need a smaller amount for adequate analgesia than middle-aged patients. The administration of pregabalin reduced postoperative oxycodone consumption after cardiac surgery. Pregabalin-treated patients had less confusion, and additionally to less postoperative pain on the first postoperative day and during movement at three months post-surgery. Pregabalin might be a new alternative as analgesic for acute postoperative and chronic pain management in the elderly. Its clinical role and safety remains to be verified in large-scale randomized and controlled studies. In the future, many clinical trials in the older category of patients will be needed to facilitate improvements in health care methods.

Unraveling the helix of change : An activity-theoretical study of health care change efforts and their consequences

M.A. (Educ.) Anu Kajamaa from the University of Helsinki, Center for Research on Activity, Development and Learning (CRADLE), examines change efforts and their consequences in health care in the public sector. The aim of her academic dissertation is, by providing a new conceptual framework, to widen our understanding of organizational change efforts and their consequences and managerial challenges. Despite the multiple change efforts, the results of health care development projects have not been very promising, and many developmental needs and managerial challenges exist. The study challenges the predominant, well-framed health care change paradigm and calls for an expanded view to explore the underlying issues and multiplicities of change efforts and their consequences. The study asks what kind of expanded conceptual framework is needed to better understand organizational change as transcending currently dominant oppositions in management thinking, specifically in the field of health care. The study includes five explorative case studies of health care change efforts and their consequences in Finland. Theory and practice are tightly interconnected in the study. The methodology of the study integrates the ethnography of organizational change, a narrative approach and cultural-historical activity theory. From the stance of activity theory, historicity, contradictions, locality and employee participation play significant roles in developing health care. The empirical data of the study has mainly been collected in two projects, funded by the Finnish Work Environment Fund. The data was collected in public sector health care organizations during the years 2004-2010. By exploring the oppositions between distinct views on organizational change and the multi-site, multi-level and multi-logic of organizational change, the study develops an expanded, multidimensional activity-theoretical framework on organizational change and management thinking. The findings of the study contribute to activity theory and organization studies, and provide information for health care management and practitioners. The study illuminates that continuous development efforts bridged to one another and anchored to collectively created new activity models can lead to significant improvements and organizational learning in health care. The study presents such expansive learning processes. The ways of conducting change efforts in organizations play a critical role in the creation of collective new practices and tools and in establishing ownership over them. Some of the studied change efforts were discontinuous or encapsulated, not benefiting the larger whole. The study shows that the stagnation and unexpected consequences of change efforts relate to the unconnectedness of the different organizational sites, levels and logics. If not dealt with, the unintended consequences such as obstacles, breaks and conflicts may stem promising change and learning processes.

Independent and mediating organizational commitment effects of trust in leadership on employees' job satisfaction and : a study within social and health care sector

The purpose of this study was to examine whether trust in supervisor and trust in senior management enhance employees' job satisfaction and organizational commitment, and whether trust mediates the relationship between perceived justice and these outcomes. Trust in supervisor was expected to mediate the effects of distributive justice and interactional justice, and trust in senior management was expected to mediate the effects of procedural justice. Theoretical background of the study is based on the framework for trust in leadership developed by Dirks and Ferrin (2002). According to the framework, perceived fairness of leaders' actions helps employees to draw inferences about the basis of the relationship and about leaders' characters. This allows trust formation. Reciprocation of care and concern in the relationship and confidence in leaders' characters are likely to enhance employees' job satisfaction and organizational commitment. This study was conducted with cross-sectional data (A/ = 960) of employees from social and health care sector. Hypotheses were studied using correlation analysis and several hierarchical regression analyses. Significances of the mediations were assessed using the Sobel test. Results partially supported the hypotheses. Trust in leadership was positively related to job satisfaction and organizational commitment. Trust in senior management mediated the relationship between procedural justice and the outcomes. Some support was also found for the mediating effect of trust in supervisor in the relationship between distributive justice and organizational commitment. Due to high correlation between trust in supervisor anil interactional justice, it wasn't possible to study the mediating e fleet of trust in supervisor in the relationship between interactional justice and the outcomes. Against expectations, results indicated that trust in senior management had a mediating effect in the relationship between distributive justice and organizational commitment, and in the relationship between interactional justice and organizational commitment. Results also indicated that trust in supervisor had a mediating effect in the relationship between procedural justice and organizational commitment.

Optimal explicit terminal guidance for a launch vehicle

It is observed that general explicit guidance schemes exhibit numerical instability close to the injection point. This difficulty is normally attributed to the demand for exact injection which, in turn, calls for finite corrections to be enforced in a relatively short time. The deviations in vehicle state which need corrective maneuvers are caused by the off-nominal operating conditions. Hence, the onset of terminal instability depends on the type of off-nominal conditions encountered. The proposed separate terminal guidance scheme overcomes the above difficulty by minimizing a quadratic penalty on injection errors rather than demanding an exact injection. There is also a special requirement in the terminal phase for the faster guidance computations. The faster guidance computations facilitate a more frequent guidance update enabling an accurate terminal thrust cutoff. The objective of faster computations is realized in the terminal guidance scheme by employing realistic assumptions that are accurate enough for a short terminal trajectory. It is observed from simulations that one of the guidance parameters (P) related to the thrust steering angular rates can indicate the onset of terminal instability due to different off-nominal operating conditions. Therefore, the terminal guidance scheme can be dynamically invoked based on monitoring of deviations in the lone parameter P.

Synthesis, structure and redox properties of (?-oxo)bis(?-carboxylato)diruthenium(III) complexes containing three different terminal ligands

Blue coloured, unstable, essentially diamagnetic and non-electrolytic diruthenium(III) complexes of the formation [Ru2O(O2CR)4(en)2(PPh3)2] were prepared by reacting [Ru2O(O2CR)4(PPh3)2] with 1,2-diaminoethane (en) in CH2Cl2 (R = C6H4-p-X; X = H, Me and OMe). The molecular structure of the complexes is proposed as [{(?1-O2CR)(?1-en)(PPH3)Ru}2(?-O)(?-O2CR)2] based on the 1H NMR spectral data. The electronic spectra of the complexes display a band near 569 nm with a shoulder at 630 nm. In CH2Cl2-0.1 M [Bun4N]ClO4, the complexes exhibit redox couples Ru2III,III/Ru2III,IV and Ru2III,IV/Ru2IV,IV near 0.1 and 1.2 V (vs SCE), respectively. The potentials are the lowest among diruthenium(III) complexes with a similar core structure.

Metal-Free Deprotection of Terminal Acetonides by Using tert-Butyl Hydroperoxide in Aqueous Medium

Employing aqueous tert-butyl hydroperoxide (70%) as an inexpensive reagent a useful methodology for the regioselective and chemoselective deprotection of terminal acetonide groups in aqueous medium is developed. A variety of acetonide derivatives on reaction with aqueous tert-butyl hydroperoxide in water:tert-butanol (1:1) furnish the corresponding acetonide deprotected diols in good yields. A large number of acid labile protecting functional groups and other functional moieties were found to be unaffected under the conditions employed for the present deprotection. This method has been successfully applied to sugar derivatives.

Interactions of 3' terminal and 5' terminal regions of physalis mottle virus genomic RNA with its replication complex

Physalis mottle virus (PhMV) belongs to the tymogroup of positive-strand RNA viruses with a genome size of 6 kb. Crude membrane preparations from PhMV-infected Nicotiana glutinosa plants catalyzed the synthesis of PhMV genomic RNA from endogenously bound template. Addition of exogenous genomic RNA enhanced the synthesis which was specifically inhibited by the addition of sense and antisense transcripts corresponding to 3' terminal 242 nucleotides as well as the 5' terminal 458 nucleotides of PhMV genomic RNA while yeast tRNA or ribosomal RNA failed to inhibit the synthesis. This specific inhibition suggested that the 5' and 3' non-coding regions of PhMV RNA might play an important role in viral replication.

Synthesis and structure of a novel terminal imido complex of titanium

The reaction of eta(5)-Cp*TiCl3 and (LiNHBu)-Bu-t in hexanes yields a novel [eta(5)-Cp*Ti(=(NBu)-Bu-t)((NHBu)-Bu-t)(2)]Li . (NH2Bu)-Bu-t complex with a terminal tert-butylimido moiety. The synthesis and X-ray structural characterization are described. (C) 1999 Elsevier Science S.A. All rights reserved.