Failure of amino acid homeostasis causes cell death following proteasome inhibition

The ubiquitin-proteasome system targets many cellular proteins for degradation and thereby controls most cellular processes. Although it is well established that proteasome inhibition is lethal, the underlying mechanism is unknown. Here, we show that proteasome inhibition results in a lethal amino acid shortage. In yeast, mammalian cells, and flies, the deleterious consequences of proteasome inhibition are rescued by amino acid supplementation. In all three systems, this rescuing effect occurs without noticeable changes in the levels of proteasome substrates. In mammalian cells, the amino acid scarcity resulting from proteasome inhibition is the signal that causes induction of both the integrated stress response and autophagy, in an unsuccessful attempt to replenish the pool of intracellular amino acids. These results reveal that cells can tolerate protein waste, but not the amino acid scarcity resulting from proteasome inhibition.

New sale and leasing requirements for owners of swimming pools and their application to strata schemes

This article considers the changes to the Swimming Pools Act 1992 (NSW)(Act) which established a State-wide online register of all private swimming pools in NSW requiring pool owners to register their pools by 19 November 2013. Amendments to the Act introduced changes to the conveyancing and residential tenancy regulations to require vendors and landlords to have a valid Compliance Certificate issued for their swimming pool before offering the property for sale or lease. This article provides a brief overview of the new sale and leasing requirements effective from 29 April 2014, focusing on its application to lot owners within strata and community title schemes and other owners of water front properties with pools on Crown Land Reserves.

Supporting residents’ expression of sexuality : the initial construction of a sexuality assessment tool for residential aged care facilities

Background: Sexuality is a key component of quality of life and well-being and a need to express one’s sexuality continues into old age. Staff and families in residential aged care facilities often find expressions of sexuality by residents, particularly those living with dementia, challenging and facilities often struggle to address individuals’ needs in this area. This paper describes the development of an assessment tool which enables residential aged care facilities to identify how supportive their organisation is of all residents’ expression of their sexuality, and thereby improve where required. Methods: Multi-phase design using qualitative methods and a Delphi technique. Tool items were derived from the literature and verified by qualitative interviews with aged care facility staff, residents and families. The final item pool was confirmed via a reactive Delphi process. Results: A final item pool of sixty-nine items grouped into seven key areas allows facilities to score their compliance with the areas identified as being supportive of older people’s expression of their sexuality in a residential aged care environment. Conclusions: The sexuality assessment tool (SexAT) guides practice to support the normalization of sexuality in aged care homes and assists facilities to identify where enhancements to the environment, policies, procedures and practices, information and education/training are required. The tool also enables facilities to monitor initiatives in these areas over time.

Chinese resort of epic proportions

A travel article about Haikou, southern China. Publication title: "Mission Hills Resort in Hainan, China" A giant spa, 10 golf courses and amazing hazards in the swimming pool – what more do you need at a resort, asks Kari Gislason If I kept to this line, I could make it through the passage between the iceberg and the castle, however narrow...

Stochastic ranking method for thermostatically controllable appliances to provide regulation services

Demand response can be used for providing regulation services in the electricity markets. The retailers can bid in a day-ahead market and respond to real-time regulation signal by load control. This paper proposes a new stochastic ranking method to provide regulation services via demand response. A pool of thermostatically controllable appliances (TCAs) such as air conditioners and water heaters are adjusted using direct load control method. The selection of appliances is based on a probabilistic ranking technique utilizing attributes such as temperature variation and statuses of TCAs. These attributes are stochastically forecasted for the next time step using day-ahead information. System performance is analyzed with a sample regulation signal. Network capability to provide regulation services under various seasons is analyzed. The effect of network size on the regulation services is also investigated.

System dynamics model of the knowledge management process

To effectively manage the challenges being faced by construction organisations in a fast changing business environment, many organisations are attempting to integrate knowledge management (KM) into their business operations. KM activities interact with each other and form a process which receives input from its internal business environment and produces outputs that should be justified by its business performance. This paper aims to provide further understanding on the dynamic nature of the KM process. Through a combination of path analysis and system dynamic simulation, this study found that: 1) an improved business performance enables active KM activities and provide feedback and guidance for formulating learning-based policies; and 2) effective human resource recruitment policies can enlarge the pool of individual knowledge, which lead to a more conducive internal business environment, as well as a higher KM activity level. Consequently, the desired business performance level can be reached within a shorter time frame.

Gen Y recruitment: Understanding graduate intentions to join an organisation using the Theory of Planned Behaviour

Purpose Using the Theory of Planned Behaviour (TPB) framework, this study explored whether the standard TPB constructs explained variance in Gen Y individuals’ intentions to join their ideal organisation. Design/methodology/approach A mixed methods approach was used featuring qualitative and quantitative methods. Findings The overall TPB model accounted for a significant 51.6% of the variance in intention to join one’s ideal organisation in the next six months with the significant predictors in the model being subjective norm and perceived behaviour control but not attitude. Research limitations/implications Using graduating students from a single Australian university sample may mean that the current findings may not extend to all Gen Y individuals. The current study has demonstrated the explanatory utility of the TPB in relation to graduate Gen Y’s intention to join their ideal organisation, providing further evidence of the robustness of the TPB framework in an organisational setting. Practical implications These findings have implications for enhancing understanding of the most effective recruitment processes for Gen Y students entering the workforce. The findings could inform recruitment policies and strategies to attract Gen Y applicants. Originality/value To our knowledge this study is the first application of the TPB to this topic. The current research extends the recruitment literature with a theoretically-based investigation. Identification of factors which inform organisational recruitment strategies, allow organisations to stand out from their competitors and potentially achieve a larger application pool from which to select the best human capital and sustain competitive advantage.

Behavioral consistency, the homology assumption, and the problems of induction

The ultimate goal of profiling is to identify the major behavioral and personality characteristics to narrow the suspect pool. Inferences about offender characteristics can be accomplished deductively, based on the analysis of discrete offender behaviors established within a particular case. They can also be accomplished inductively, involving prediction based on abstract offender averages from group data (these methods and the logic on which they are based is detailed extensively in Chapters 2 and 4). As discussed, these two approaches are by no means equal.

Prediction of GMA welding characteristic parameter by artificial neural network system

Nowadays, demand for automated Gas metal arc welding (GMAW) is growing and consequently need for intelligent systems is increased to ensure the accuracy of the procedure. To date, welding pool geometry has been the most used factor in quality assessment of intelligent welding systems. But, it has recently been found that Mahalanobis Distance (MD) not only can be used for this purpose but also is more efficient. In the present paper, Artificial Neural Networks (ANN) has been used for prediction of MD parameter. However, advantages and disadvantages of other methods have been discussed. The Levenberg–Marquardt algorithm was found to be the most effective algorithm for GMAW process. It is known that the number of neurons plays an important role in optimal network design. In this work, using trial and error method, it has been found that 30 is the optimal number of neurons. The model has been investigated with different number of layers in Multilayer Perceptron (MLP) architecture and has been shown that for the aim of this work the optimal result is obtained when using MLP with one layer. Robustness of the system has been evaluated by adding noise into the input data and studying the effect of the noise in prediction capability of the network. The experiments for this study were conducted in an automated GMAW setup that was integrated with data acquisition system and prepared in a laboratory for welding of steel plate with 12 mm in thickness. The accuracy of the network was evaluated by Root Mean Squared (RMS) error between the measured and the estimated values. The low error value (about 0.008) reflects the good accuracy of the model. Also the comparison of the predicted results by ANN and the test data set showed very good agreement that reveals the predictive power of the model. Therefore, the ANN model offered in here for GMA welding process can be used effectively for prediction goals.

Patents for humanity

This article evaluates two policy initiatives by the United States Government to address access to essential medicines -- Priority Review vouchers and “Patents for Humanity." Such proposals are aimed at speeding up the regulatory review of inventions with humanitarian uses and applications by the United States Food and Drug Administration, and the United States Patent and Trademark Office. It is argued that such measures fall short of international standards and norms established by the World Intellectual Property Organization Development Agenda 2007; the World Trade Organization’s Doha Declaration on the TRIPS Agreement and Public Health 2001 and the WTO General Council Decision of August 30, 2003; and the World Health Organization’s declarations on intellectual property and public health. This article concludes that there is a need for broader patent law reform in the United States to address matters of patent law and public health. Moreover, there is a need to experiment with other, more promising alternative models of research and development -- such as medical innovation prizes, a Health Impact Fund, the Medicines Patent Pool, and Open Source Drug Discovery.

Franklin Barley: Patent law and plant breeders’ rights

This paper considers the relationship between patent law and plant breeders' rights in light of modern developments in biotechnology. It examines how a number of superior courts have sought to manage the tensions and conflicts between these competing schemes of intellectual property protection. Part 1 considers the High Court of Australia case of Grain Pool of Western Australia v the Commonwealth dealing with Franklin barley. Part 2 examines the significance of the Supreme Court of the United States decision in JEM Ag Supply Inc v Pioneer Hi-Bred International Inc with respect to utility patents and hybrid seed. Part 3 considers the Supreme Court of Canada case of Harvard College v the Commissioner of Patents dealing with the transgenic animal, oncomouse, and discusses its implications for the forthcoming appeal from the Federal Court case of Percy Schmeiser v Monsanto.

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood- and adult-onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages.

An immunodiagnostic assay for quantitation of specific ige to the major pollen allergen component, pas n 1, of the subtropical bahia grass

Background Pollens of the Panicoideae subfamily of grasses including Bahia (Paspalum notatum) are important allergen sources in subtropical regions of the world. An assay for specific IgE to the major molecular allergenic component, Pas n 1, of Bahia grass pollen (BaGP) would have immunodiagnostic utility for patients with pollen allergy in these regions. Methods Biotinylated Pas n 1 purified from BaGP was coated onto streptavidin ImmunoCAPs. Subjects were assessed by clinical history of allergic rhinitis and skin prick test (SPT) to aeroallergens. Serum total, BaGP-specific and Pas n 1-specific IgE were measured. Results: Pas n 1 IgE concentrations were highly correlated with BaGP SPT (r = 0.795, p < 0.0001) and BaGP IgE (r = 0.915, p < 0.0001). At 0.23 kU/l Pas n 1 IgE, the diagnostic sensitivity (92.4%) and specificity (93.1%) for the detection of BaGP allergy was high (area under receiver operator curve 0.960, p < 0.0001). The median concentrations of Pas n 1 IgE in non-Atopic subjects (0.01 kU/l, n = 67) and those with other allergies (0.02 kU/l, n = 59) showed no inter-group difference, whilst grass pollen-Allergic patients with allergic rhinitis showed elevated Pas n 1 IgE (6.71 kU/l, n = 182, p < 0.0001). The inter-Assay coefficient of variation for the BaGP-Allergic serum pool was 6.92%. Conclusions Pas n 1 IgE appears to account for most of the BaGP-specific IgE. This molecular component immunoassay for Pas n 1 IgE has potential utility to improve the sensitivity and accuracy of diagnosis of BaGP allergy for patients in subtropical regions.

Bahia grass pollen specific IgE is common in seasonal rhinitis patients but has limited cross-reactivity with Ryegrass

Background: Perennial Ryegrass is a major cause of rhinitis in spring and early summer. Bahia grass, Paspalum notatum, flowers late into summer and could account for allergic rhinitis at this time. We determined the frequency of serum immunoglobulin (Ig)E reactivity with Bahia grass in Ryegrass pollen allergic patients and investigated IgE cross-reactivity between Bahia and Ryegrass. Methods: Serum from 33 Ryegrass pollen allergic patients and 12 nonatopic donors were tested for IgE reactivity with Bahia and Ryegrass pollen extracts (PE) by enzyme-linked immunosorbent assay (ELISA), western blotting and inhibition ELISA. Allergen-specific antibodies from a pool of sera from allergic donors were affinity purified and tested for IgE cross-reactivity. Results: Seventy-eight per cent of the sera had IgE reactivity with Bahia grass, but more weakly than with Ryegrass. Antibodies eluted from the major Ryegrass pollen allergens, Lol p 1 and Lol p 5, showed IgE reactivity with allergens of Ryegrass and Canary but not Bahia or Bermuda grasses. Timothy, Canary and Ryegrass inhibited IgE reactivity with Ryegrass and Bahia grass, whereas Bahia, Johnson and Bermuda grass did not inhibit IgE reactivity with Ryegrass. Conclusions: The majority of Ryegrass allergic patients also showed serum IgE reactivity with Bahia grass PE. However, Bahia grass and Ryegrass had only limited IgE cross-reactivity indicating that Bahia grass should be considered in diagnosis and treatment of patients with hay fever late in' the grass pollen season.

A polymerase chain reaction-based method for isolating clones from a complimentary DNA library in sheep

The sheep (Ovis aries) is favored by many musculoskeletal tissue engineering groups as a large animal model because of its docile temperament and ease of husbandry. The size and weight of sheep are comparable to humans, which allows for the use of implants and fixation devices used in human clinical practice. The construction of a complimentary DNA (cDNA) library can capture the expression of genes in both a tissue- and time-specific manner. cDNA libraries have been a consistent source of gene discovery ever since the technology became commonplace more than three decades ago. Here, we describe the construction of a cDNA library using cells derived from sheep bones based on the pBluescript cDNA kit. Thirty clones were picked at random and sequenced. This led to the identification of a novel gene, C12orf29, which our initial experiments indicate is involved in skeletal biology. We also describe a polymerase chain reaction-based cDNA clone isolation method that allows the isolation of genes of interest from a cDNA library pool. The techniques outlined here can be applied in-house by smaller tissue engineering groups to generate tools for biomolecular research for large preclinical animal studies and highlights the power of standard cDNA library protocols to uncover novel genes.