Cerebellar augmented joint control for a humanoid robot

The joints of a humanoid robot experience disturbances of markedly different magnitudes during the course of a walking gait. Consequently, simple feedback control techniques poorly track desired joint trajectories. This paper explores the addition of a control system inspired by the architecture of the cerebellum to improve system response. This system learns to compensate the changes in load that occur during a cycle of motion. The joint compensation scheme, called Trajectory Error Learning, augments the existing feedback control loop on a humanoid robot. The results from tests on the GuRoo platform show an improvement in system response for the system when augmented with the cerebellar compensator.

Raman microscopic study of the Li amphibole holmquistite, from the Martin Marietta Quarry, Bessemer City, NC, USA

The Raman spectrum of holmquistite, a Li-containing orthorhombic amphibole from Bessemer City, USA has been measured. The OH-stretching region is characterized by bands at 3661, 3646, 3634 and 3614 cm–1 assigned to 3 Mg–OH, 2 Mg + Fe2+–OH, Mg + 2Fe2+–OH and 3 Fe2+–OH, respectively. These Mg and Fe2+ cations are located at the M1 and M3 sites and have a Fe2+/(Fe2+ + Mg) ratio of 0.35. The 960–1110 cm–1 region represents the antisymmetric Si–O–Si and O–Si–O stretching vibrations. For holmquistite, strong bands are observed around 1022 and 1085 cm–1 with a shoulder at 1127 cm–1 and minor bands at 1045 and 1102 cm–1. In the region 650–800 cm–1 bands are observed at 679, 753 and 791 cm–1 with a minor band around 694 cm–1 attributed to the symmetrical Si–O–Si and Si–O vibrations. The region below 625 cm–1 is characterized by 14 vibrations related to the deformation modes of the silicate double chain and vibrations involving Mg, Fe, Al and Li in the various M sites. The 502 cm–1 band is a Li–O deformation mode while the 456, 551 and 565 cm–1 bands are Al–O deformation modes.

Sir Neville Howse (VC), Private John Simpson Kirkpatrick and Private Martin O’Meara (VC) and their contributions to Australian military medicine

Medical personnel serving with the Defence Forces have contributed to the evolution of trauma treatment and the advancement of prehospital care within the military environment. This paper investigates the stories of an Australian Medical Officer, Sir Neville Howse, and two stretcher bearers, Private John Simpson (Kirkpatrick) and Private Martin O’Meara, In particular it describes the gruelling conditions under which they performed their roles, and reflects on the legacy that they have left behind in Australian society. While it is widely acknowledged that conflicts such as World War One should never have happened, as civilian and defence force paramedics, we should never forget the service and sacrifice of defence force medical personnel and their contribution to the body of knowledge on the treatment of trauma. These men and women bravely provided emergency care in the most harrowing conditions possible. However, men like Martin O’Meara may not have been given the same status in society today as Sir Neville Howse or Simpson and his donkey, due to the public’s lack of awareness and acceptance of war neurosis and conditions such as post traumatic stress disorder, reactive psychosis and somatoform disorders which were suffered by many soldiers during their wartime service and on their return home after fighting in war.

The regulation of food intake in humans

Knowledge of the regulation of food intake is crucial to an understanding of body weight and obesity. Strictly speaking, we should refer to the control of food intake whose expression is modulated in the interests of the regulation of body weight. Food intake is controlled, body weight is regulated. However, this semantic distinction only serves to emphasize the importance of food intake. Traditionally food intake has been researched within the homeostatic approach to physiological systems pioneered by Claude Bernard, Walter Cannon and others; and because feeding is a form of behaviour, it forms part of what Curt Richter referred to as the behavioural regulation of body weight (or behavioural homeostasis). This approach views food intake as the vehicle for energy supply whose expression is modulated by a metabolic drive generated in response to a requirement for energy. The idea was that eating behaviour is stimulated and inhibited by internal signalling systems (for the drive and suppression of eating respectively) in order to regulate the internal environment (energy stores, tissue needs).

Commentary on papers by Professor Fletcher and Mr Martin

In light of the time available today, I will limit my comments to addressing that aspect of Professor Fletcher’s paper in which he refers to the 2012 report he co-authored with Professor Wessels of the Netherlands for the American Law Institute (ALI) and the International Insolvency Institute (III) on Transnational Insolvency: Global Principles for Cooperation in International Insolvency Cases. I will comment on the potential benefits for Australian courts as well as insolvency administrators and their advisers in referring to the ALI-III Report - in light of Australia’s adoption of the UNCITRAL Model Law. In so doing, I would like to acknowledge the support of the Australian Academy of Law, under the leadership of The Hon Dr Kevin Lindgren for the research project underpinning these comments, as well as to acknowledge the contributions of my colleagues Associate Professor Sheryl Jackson and Mark Wellard.

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10−14, odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

Establishing international networks: The internationalisation of Calleija Jewellers and their partnership with the exclusive Aston Martin

Calleija, a small to medium sized (SME) Australian and internationally recognised fine jeweller has secured a significant strategic global partnership with one of the world’s best-known luxury automobile brands, Aston Martin. Forging this international relationship to produce an elegant fine jewellery collection has given rise to a new network between the Australian jewellery industry and the European automobile industry. Calleija’s exclusive association with Aston Martin consolidates a shared passion for the finest quality and craftsmanship which was inspired by Aston Martin’s Supercar, the One-77. This inspiration lead to John Calleija being chosen by Aston Martin to design this latest high-luxury offering in which each design is limited to only 77 pieces utilising 30 unique designs (Calleija, 2012). The story behind Calleija’s internationalisation to the United Kingdom (UK) and their subsequent business-to-business strategic partnership with Aston Martin is no doubt a good sign for the Australian jewellery industry.

CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer

Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10(-11)). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4x10(-8)). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

FTO genotype is associated with phenotypic variability of body mass index

There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ~170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9, 10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

Directional dominance on stature and cognition in diverse human populations

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.