ATP-sensitive potassium channel subcellular trafficking during ischemia, reperfusion, and preconditioning

Ischemic preconditioning is an endogenous cardioprotective mechanism in which short periods of ischemia and reperfusion provide protection when given before a subsequent ischemic event. Early mechanistic studies showed ATP-sensitive potassium (KATP) channels to play an important role in ischemic preconditioning. KATP channels link intracellular energy metabolism to membrane excitability and contractility. It is thought that KATP channels provide a cardioprotective role during ischemia by inducing action potential shortening, reducing an excessive Ca^2+ influx, and by preventing arrhythmias. However, the mechanisms by which KATP channels protect during ischemic preconditioning are not known. In this study, we investigated a novel potential mechanism in which alterations in subcellular KATP channel trafficking during ischemia and ischemic preconditioning may result in altered levels of surface channel density, and therefore, a greater degree of cardioprotection. In the optimization of our experiments, we compared various antibodies for their specificity and sensitivity for channel subunit detection in immunoblotting. In addition, we examined the effects of varying salt concentrations during tissue homogenization in order to determine the optimal conditions for protein isolation. Furthermore, we examined the effect of heating the samples prior to SDS-PAGE for improved detection of channel proteins by immunoblotting. The subcellular trafficking of some membrane proteins is altered by ischemia. For example, the glucose transporter, Glut4, translocates from endosomal compartments to the sarcolemma (Sun, Nguyen, DeGrado, Schwaiger, & Brosius, 1994). Conflicting data exists regarding the effects of ischemia on KATP channel subcellular trafficking and the regulation of KATP channel surface density (Edwards et al., 2009 and Bao, Hadjiolova, Coetzee, & Rindler, 2011). We therefore, sought to test our hypothesis that KATP channels are internalized from the surface of cardiomyocytes to endosomal compartments during ischemia, and this internalization can be reduced and/or reversed by ischemic preconditioning. We subjected isolated Langendorff-perfused mouse hearts to ischemia, reperfusion, or ischemic preconditioning events and measured the density of KATP channels in the sarcolemmal and endosomal compartments. We also determined the degree of injury by staining heart slices with triphenyltetrazolium chloride and compared infarct sizes between hearts subjected to ischemia and ischemic preconditioning. Our data demonstrated that KATP channels are, in fact, internalized during ischemia and that reperfusion led to a slow recovery of surface KATP channel density. Interestingly, ischemic preconditioning reduced the size of infarcts induced by ischemia and also prevented the ischemia-induced decrease of KATP channel surface density, thereby, contributing to cardioprotection

Weather-based estimation of wildfire risk

Catastrophic wildfires in California have become more frequent in past decades, while insured losses per event have been rising substantially. On average, California ranks the highest among states in the U.S. in the number of fires as well as the number of acres burned each year. The study of catastrophic wildfire models plays an important role in the prevention and mitigation of such disasters. Accurate forecasts of potential large fires assist fire managers in preparing resources and strategic planning for fire suppression. Furthermore, fire forecasting can a priori inform insurers on potential financial losses due to large fires. This paper describes a probabilistic model for predicting wildland fire risks using the two-stage Heckman procedure. Using 37 years of spatial and temporal information on weather and fire records in Southern California, this model measures the probability of a fire occurring and estimates the expected size of the fire on a given day and location, offering a technique to predict and forecast wildfire occurrences based on weather information that is readily available at low cost.biased sampling, forest fires, fire occurrence probabilities, fire weather

Self-Employment Among Chinese Immigrants in New Zealand

This paper examines the self-employment patterns of Chinese immigrants in New Zealand, using labour force data provided in the 1996 Census of Population and Dwellings and survey data from interviews in New Zealand and Hong Kong. As expected, the census data show that the propensities to enter self-employment increase with age and length of residence in New Zealand. Amongst the Chinese immigrants who came to New Zealand after 1986, the pursuit of self-employment is unlikely to be confined to immigrants approved under the business immigration schemes. Structural barriers to employment, such as non-recognition of overseas qualifications and experiences, can also drive many contemporary Chinese immigrants into self-employment. The second part of the paper reflects on the business experiences of recent Chinese migrants in New Zealand, drawing on research carried out on the migration of entrepreneurs to New Zealand from Hong Kong during the 1990's. We conclude our paper by discussing some of the implications of the Government's recent business immigration policy changes. We emphasize the need for a post-settlement policy and other initiatives that will ensure that immigrants are able to maximize their opportunities to contribute effectively to New Zealand's economy and society

Validation of Chinese Multidimensional Depression Assessment Scale (MDAS) in Inner Mongolia pregnant women and risk factors of antenatal depression in Inner Mongolia in the era of one-child policy

BACKGROUND:Pregnancy involves physiological changes in reproductive and endocrine systems, and social role changes that can increase the risk of mental health problems. In China, greater emphasis has been given to postpartum depression and its negative impact on infant development. This study examined depression in pregnant women in Inner Mongolia, who are under the influence of cultural values of collectivism and social factors specific to China. Chinese society adheres firmly to traditional values, while market reform, birth-control policy, together with high parental investment in childcare and rearing construct a unique and sometimes unfavorable environment for Chinese women that may influence their depression expression. THE AIMS OF THIS STUDY ARE TWOFOLD:First, it validated the Chinese Multidimensional Depression Assessment Scale (MDAS), a holistic self-report questionnaire measuring depression severity in four domains of depression-emotional, somatic, cognitive and interpersonal in pregnant women in Inner Mongolia; second, it examined the influences of demographic characteristics (including age, education and employment), pregnancy characteristics (week of gestation, first pregnancy), self-esteem, social support, social activity, work stress, and work-family balance on depression. METHODS:A total of 234 pregnant women, mostly in their third trimester, were recruited in an antenatal hospital in Inner Mongolia and self-reported questionnaires were completed. RESULTS:Using Confirmatory factor analysis (CFA), MDAS gave rise to a best-fit four-factor model corresponding to each subscale when it was first developed. MDAS also reported high Cronbach's alpha (0.96) and good convergent validity. Using hierarchical multiple linear regressions with significant demographic variables controlled for, self-esteem, work-family conflict, and social support were found to be significant predictors for depression. CONCLUSIONS:MDAS is a valid scale to be used with Chinese pregnant women, especially in more collectivistic geographical areas. Risk factors specific to the Chinese context add insights to the experience of antenatal depression in China and contribute to understanding depression in from a global mental health perspective

Highly efficient multimetallic catalysts for sequential reactions

This thesis describes investigations into metal-catalysed sequential reactions using both single metal and bimetallic Rh(I) and Ir(I) complexes containing N-donor ligands as catalysts. Two types of bimetallic catalyst systems were developed including the combined use of single metal complexes and bimetallic complexes. All catalyst systems were highly effective for catalysing the synthesis of heterocyclic compounds using sequential reactions. The complexes [M(bpm)(CO)2]BArF4 (M = Rh, Ir; bpm = bis(1-pyrazolyl)methane; BArF4 = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) were found to be highly efficient for the dihydroalkoxylation reaction forming spiroketals and fused bicyclic acetals. The catalysed dihydroalkoxylation reactions for a series of alkynediols showed that the Rh(I) complex favours the formation of 6-membered spiroketals while the Ir(I) complex favours the formation of 5-membered O-rings. A dual metal (Rh(I) and Ir(I)) catalyst system was used here for the first time to promote the formation of mixed 5,6- and 6,5-spiroketals and was found to be a more effective catalyst system than the individual single metal complexes. A new bitopic ligand [1,8-bis(bis(1-pyrazolyl)methyl)anthracene] was synthesised. A series of homobimetallic complexes [M2(COD)2(L)][BArF4]2 and [M2(CO)4(L)][BArF4]2 (M = Rh, Ir) each containing two bis(1-pyrazolyl)methane motifs bridged by one of three well-defined rigid aromatic scaffolds, where L is m-C6H4[CH(pz)2]2 (Lm), p-C6H4[CH(pz)2]2 (Lp) and anthracene-dibpm (LAnt), were synthesised. The solid-state structures of the three sets of homobimetallic complexes showed very different spatial relationships between the ligand pairs in each. For the catalysed dihydroalkoxylation reaction, the homobimetallic complexes are more active catalysts that the single metal complexes. The order of catalytic activity of the bimetallic complexes were found to be M2(LAnt) > M2(Lm) > M2(Lp). The order of activity can be attributed to the degree of bimetallic cooperativity, where the anthracene-linked complexes achieve the greatest level of cooperativity in solution and the two metal centers of the anthracene system are closest together in space. For the catalysed tandem hydroamination/hydrosilation of 4-phenyl-3-butyn-1-amine with silanes, a combination of the dirhodium and diiridium complexes were found to be a more efficient catalyst than the single metal complexes. A series of chiral ligands and their complexes were synthesised and tested for the catalysed dihydroalkoxylation reaction but showed no significant stereoselectivity in the products formed

Self-Employment Among Chinese Immigrants in New Zealand

This paper examines the self-employment patterns of Chinese immigrants in New Zealand, using labour force data provided in the 1996 Census of Population and Dwellings and survey data from interviews in New Zealand and Hong Kong. As expected, the census data show that the propensities to enter self-employment increase with age and length of residence in New Zealand. Amongst the Chinese immigrants who came to New Zealand after 1986, the pursuit of self-employment is unlikely to be confined to immigrants approved under the business immigration schemes. Structural barriers to employment, such as non-recognition of overseas qualifications and experiences, can also drive many contemporary Chinese immigrants into self-employment. The second part of the paper reflects on the business experiences of recent Chinese migrants in New Zealand, drawing on research carried out on the migration of entrepreneurs to New Zealand from Hong Kong during the 1990's. We conclude our paper by discussing some of the implications of the Government's recent business immigration policy changes. We emphasize the need for a post-settlement policy and other initiatives that will ensure that immigrants are able to maximize their opportunities to contribute effectively to New Zealand's economy and society

In planta proteomics and proteogenomics of the biotrophic barley fungal pathogen blumeria f.sp. hordei

Whilst there is increasing evidence tht the outcome of the interation between a pathogen and a host is dependent on protein-protein interactions, very little information is available on in planta proteomics of biotrophic plant pathogens. Here a proteogenomic approach has been employed to supplement the annotation of the recently sequenced genome and to cast light on the biology of the infection process of the economically important barley powdery mildew pathogen, Blumeria graminis f.sp horde

Facilitating student interaction capabilities: The interplay of individual, group and course-related factors

Marketing education increasingly recognizes the active role of students in their learning experience. Students co-create learning outcomes through interacting with course resources and other students. However, there is little understanding of the factors that support the development of students’ ability to interact in this learning environment. This paper examines the influence of individual and group characteristics that exist at group formation, on the development of the group and ultimately its interaction capabilities. We identify that individual goal orientation and motivation predict shared academic goals and commitment to learning. Over a period of time, these factors promote a shared vision and recognition of peer learning opportunities provided by the course, and subsequently drive student interaction capabilities. The results imply that in order to enhance interaction among students, marketing educators should focus efforts on developing peer learning opportunities and consider individual and group goals and commitment to learning when forming student groups.This work was supported by the University of Adelaide under Faculty of Professions, Learning & Teaching Grant

An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma.

Lessons learnedTKM-080301 showed a favorable toxicity profile at the studied dose.TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted