Polymer nanocarrier system for endosome escape and timed release of siRNA with complete gene silencing and cell death in cancer cells

An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 μg/mL) with polo-like kinase 1 (PLK1) siRNA gave specific and near complete (>98%) cell death. The polymer further degrades to a benign polymer that showed no toxicity even at polymer concentrations of 200 μg/mL (or N/P ratio of 300), suggesting that our polymer nanocarrier can be used as a very effective siRNA delivery system and in a multiple dose administration. This work demonstrates that with a well-designed delivery device, siRNA can specifically kill cells without the inclusion of an additional clinically used highly toxic cochemotherapeutic agent. Our work also showed that this excellent delivery is sensitive for the study of off-target knockdown of siRNA.

Review essay -- Weber L and Pickering S (2011) Globalization and borders : death at the global frontier

The pertinence of this book cannot be overemphasised. The world’s refugee crisis has reached a two‐decade high with the United Nations recently announcing that ‘displacement is the new 21st century challenge’ (UNHCR 2013). The transnational movement of dislocated peoples fleeing conflict, persecution and poverty is a global responsibility requiring nation states to collaborate for humanitarian resolutions embedded in human rights. However, in times of human rights expansionism, and the relaxation of borders for maximising free‐trade and fiscal prosperity, the movement of people experiencing immense abuse and deprivation has witnessed an increase in draconian regulation within discourses of intolerance and deterrence. Weber and Pickering cogently and emphatically emphasise the human cost of inhumane and populist government immigration and border‐entry polices underpinned by ideologies of retribution, suspicion, and demonisation. It is a moving and engaging narrative: a book that exposes state prejudice and abuse, whilst advocating for the victims who undertake perilous journeys in search of safety from lives of violence and persecution. Moreover, it is a book that pushes ideological boundaries and seeks new criminological horizons, for which the authors must be sincerely congratulated. It is a text of innovation, inspired thinking and long lasting criminological value.

Distinguishing between mean-field, moment dynamics and stochastic descriptions of birth-death-movement processes

Mathematical descriptions of birth–death���movement processes are often calibrated to measurements from cell biology experiments to quantify tissue growth rates. Here we describe and analyze a discrete model of a birth–death-movement process applied to a typical two–dimensional cell biology experiment. We present three different descriptions of the system: (i) a standard mean–field description which neglects correlation effects and clustering; (ii) a moment dynamics description which approximately incorporates correlation and clustering effects, and; (iii) averaged data from repeated discrete simulations which directly incorporates correlation and clustering effects. Comparing these three descriptions indicates that the mean–field and moment dynamics approaches are valid only for certain parameter regimes, and that both these descriptions fail to make accurate predictions of the system for sufficiently fast birth and death rates where the effects of spatial correlations and clustering are sufficiently strong. Without any method to distinguish between the parameter regimes where these three descriptions are valid, it is possible that either the mean–field or moment dynamics model could be calibrated to experimental data under inappropriate conditions, leading to errors in parameter estimation. In this work we demonstrate that a simple measurement of agent clustering and correlation, based on coordination number data, provides an indirect measure of agent correlation and clustering effects, and can therefore be used to make a distinction between the validity of the different descriptions of the birth–death���movement process.

Towards a dignified and sustainable electricity generation sector in Australia : a comparative review of three models

Electricity is the cornerstone of modern life. It is essential to economic stability and growth, jobs and improved living standards. Electricity is also the fundamental ingredient for a dignified life; it is the source of such basic human requirements as cooked food, a comfortable living temperature and essential health care. For these reasons, it is unimaginable that today's economies could function without electricity and the modern energy services that it delivers. Somewhat ironically, however, the current approach to electricity generation also contributes to two of the gravest and most persistent problems threatening the livelihood of humans. These problems are anthropogenic climate change and sustained human poverty. To address these challenges, the global electricity sector must reduce its reliance on fossil fuel sources. In this context, the object of this research is twofold. Initially it is to consider the design of the Renewable Energy (Electricity) Act 2000 (Cth) (Renewable Electricity Act), which represents Australia's primary regulatory approach to increase the production of renewable sourced electricity. This analysis is conducted by reference to the regulatory models that exist in Germany and Great Britain. Within this context, this thesis then evaluates whether the Renewable Electricity Act is designed effectively to contribute to a more sustainable and dignified electricity generation sector in Australia. On the basis of the appraisal of the Renewable Electricity Act, this thesis contends that while certain aspects of the regulatory regime have merit, ultimately its design does not represent an effective and coherent regulatory approach to increase the production of renewable sourced electricity. In this regard, this thesis proposes a number of recommendations to reform the existing regime. These recommendations are not intended to provide instantaneous or simple solutions to the current regulatory regime. Instead, the purpose of these recommendations is to establish the legal foundations for an effective regulatory regime that is designed to increase the production of renewable sourced electricity in Australia in order to contribute to a more sustainable and dignified approach to electricity production.

The increased risks of death and extra lengths of hospital and ICU stay from hospital-acquired bloodstream infections : a case-control study

Objectives Hospital-acquired bloodstream infections are known to increase the risk of death and prolong hospital stay, but precise estimates of these two important outcomes from well-designed studies are rare, particularly for non-intensive care unit (ICU) patients. We aimed to calculate accurate estimates, which are vital for estimating the economic costs of hospital-acquired bloodstream infections.

Changes of mortality and causes of death from 1970 to 2005 and decomposition analysis in Shandong province [山东省1970-2005年人群死亡率极死因变化与差别分解分析]

Objective To describe the trend of overall mortality and major causes of death in Shandong population from 1970 to 2005,and to quantitatively estimate the influential factors. Methods Trends of overall mortality and major causes of death were described using indicators such as mortality rates and age-adjusted death rates by comparing three large-scale mortality surveys in Shandong province. Difference decomposing method was applied to estimate the contribution of demographic and non-demographic factors for the change of mortality. Results The total mortality had had a slight change since 1970s,but had increased since 1990s.However,both the mortality rates of age-adjusted and age-specific decreased significantly. The mortality of Group Ⅰ diseases including infectious diseases as well maternal and perinatal diseases decreased drastically. By contrast, the mortality of non-communicable chronic diseases (NCDs)including cardiovascular diseases(CVDs),cancer and injuries increased. The sustentation of recent overall mortality was caused by the interaction of demographic and non-demographic factors which worked oppositely. Non-demographic factors were responsible for the decrease of Group Ⅰ disease and the increase of injuries. With respect to the increase of NCDs as a whole. Demographic factors might take the full responsibility and the non-demographic factors were the opposite force to reduce the mortality. Nevertheless, for the increase of some leading NCD diseases as CVDs and cancer, the increase was mainly due to non-demographic rather than demographic factors. Conclusion Through the interaction of the aggravation of ageing population and the enhancement of non-demographic effect, the overall mortality in Shandong would maintain a balance or slightly rise in the coming years. Group Ⅰ diseases in Shandong had been effectively under control. Strategies focusing on disease control and prevention should be transferred to chronic diseases, especially leading NCDs, such as CVDs and cancer.

Surveillance report on cardiovascular causes of death in Shouguang, 1993-1997 [寿光市疾病监测点1993～1997年心血管疾病死亡监测报告]

This analysis showed that cardiovascular diseases were the number cause of death claiming 34% of all deaths. More than half (52%) of all cardiovascular deaths were due to Cerebrovascular diseases and about one-third (32%) were due to ischaemic heart disease. The mortality of cardiovascular diseases showed an increasing trend during this period (1993-1997). Abstract in Chinese 心血管疾病是威胁人们健康的重要疾病之一，在居民死因中占主要位置。为了解心血管疾病死亡状况，我们对寿光市农村疾病监测点１９９３～１９９７年居民死亡资料进行了统计分析，现报告如下。（标化死亡率采用１９９０年全国标准人口构成计算）。１９９３～１９９７年监测...

Analysis on causes of death of rural residents in Shouguang City [寿光市农村人群慢性病死因分析]

Among people living in rural areas of Shouguang City, Shandong, China, 88% of deaths were caused by chronic non-communicable diseases. Cardiovascular diseases, respiratory diseases and cancers accounted for 97% of all chronic disease causes and 85% of all causes of death. The proportion of chronic causes increased by 27% from 1993 to 2000. However, the mortality of respiratory diseases showed a decreasing trend over time. Abstract in Chinese 篇首： 随着生活水平的提高,慢性非传染性疾病在居民死因谱中所占比重越来越大,为准确反映居民的死因状况,为农村地区慢性病的控制工作提供科学依据,本文对寿光市农村疾病监测点1993～2000年居民的慢性病死因进行了分析.

Cuases of death among rural residents in Shouguang City, 1993-1997 [寿光市1993～1997年农村居民死因分析]

In this rural population, cardiovascular diseases, respiratory diseases, cancers and injuries were identified as the major causes of death, responsible for 34%, 30%, 20% and 9%, respectively. Abstract in Chinese 寿光市地处山东半岛中部,渤海莱洲湾南畔,是全国有名的“蔬菜之乡”。为全面了解我市农村居民的死因分布状况,我们对寿光市部分农村居民1993~1997年的死亡资料进行了统计分析。对象与方法自1993年始,从我市选取有代表性的两个乡镇49个自然村约5000..

Death of a five year old from meningococcal disease in Darwin : a case of unprecedented public alarm

On Saturday, 25 October 1997 a five year old boy died in the Intensive Care Unit (ICU) of Royal Darwin Hospital (RDH) from meningococcal disease. While disease is expected throughout Australia during the late winter and early spring months, and deaths occur, this case was remarkable in the Northern Territory with respect to the unprecedented public response to media reports of the death.

Perceptions of organ donors and willingness to donate organs upon death : a test of the prototype/willingness model

Understanding people's organ donation decisions may narrow the gap between organ supply and demand. In two studies, participants who had not recorded their posthumous organ donation decision (Study 1, N = 210; Study 2, N = 307) completed items assessing prototype/willingness model (PWM; attitude, subjective norm, donor prototype favorability and similarity, willingness) constructs. Attitude, subjective norm, and prototype similarity predicted willingness to donate. Prototype favorability and a Prototype Favorability × Similarity interaction predicted willingness (Study 2). These findings provide support for the PWM in altruistic health contexts, highlighting the importance of people's perceptions about organ donors in their donation decisions.

Escape from apoptosis after prolonged serum deprivation is associated with the regulation of the mitochondrial death pathway by Bcl-x(l)

Bcl-x(l) and Bax play important roles in the regulation of apoptosis. This study investigated the involvement of the mitochondrial death pathway and the role of Bcl-x(l) and Bax in the escape from apoptosis after prolonged serum deprivation in Madin-Darby canine kidney (MDCK) cells. Low level apoptosis and basal activity of the mitochondrial death pathway were detectable in normal cell growth. In serum deprivation, mitosis was partially suppressed, and the mitochondrial activity was stimulated. The level of apoptosis continuously rose over 48 h. This rise was concomitant with the increasing presence of cytochrome c in cytosol. However, both apoptosis and cytosolic cytochrome c fell dramatically at 72 h. Elevation of whole cell Bcl-x(l) and redistribution of Bcl-x(l) protein from cytosol to the membrane at 48 h and 72 h was observed. Redistribution of Bax protein from the membrane to cytosol occurred at 24 h, and remained steady to 72 h. Bax/Bcl-x(l) coimmunoprecipitation by anti-Bax antibody showed reduced Bax/Bcl-x(l) interaction at the membrane at 72 h, but not at 24 or 48 h. These results suggest that apoptosis upon serum withdrawal results from the leakage of cytochrome c to cytosol. Amelioration of the leakage of cytochrome c and apoptosis requires not only the increase of Bcl-x(l)/Bax ratio, but also the release of Bcl-x(l) from Bax at the membrane.

Sensationalizing death? Graphic disaster images in the tabloid and broadsheet press

Debates over the extent of graphic imagery of death in newspapers often suffer from generalized assertions that are based on inadequate or incomplete empirical evidence. Newspapers are believed to display death in very graphic ways, with particularly the tabloid press assumedly leading a race to the bottom. This article reports the results of a study of tabloid and broadsheet images of death from the 2010 Haiti earthquake in eight Western European and North American countries. It shows that, far from omnipresent, graphic images of death are relatively rare. While tabloids overall display a larger percentage of graphic images, this was not the case everywhere, with particularly the UK, Canada and the US displaying strong similarities between tabloids and broadsheets. In Austria, Germany, Norway and Switzerland, on the other hand, there were distinct differences between the two types. The article argues that different extents of tabloidization may account for these differences.