The relation between cardiac 123I-mIBG scintigraphy and functional response 1 year after CRT implantation

Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection

Feed-Forward Chains of Recurrent Attractor Neural Networks Near Saturation

We perform a stationary state replica analysis for a layered network of Ising spin neurons, with recurrent Hebbian interactions within each layer, in combination with strictly feed-forward Hebbian interactions between successive layers. This model interpolates between the fully recurrent and symmetric attractor network studied by Amit el al, and the strictly feed-forward attractor network studied by Domany et al. Due to the absence of detailed balance, it is as yet solvable only in the zero temperature limit. The built-in competition between two qualitatively different modes of operation, feed-forward (ergodic within layers) versus recurrent (non- ergodic within layers), is found to induce interesting phase transitions.Comment: 14 pages LaTex with 4 postscript figures submitted to J. Phys.

The relationship between corporate governance mechanisms and firm value: evidence from the largest Australian firms

The mixed findings in the literature pertaining to the relationship between corporate governance mechanisms and firm value have resulted in the endogeneity issue of the former becoming central to discussions in corporate governance and corporate finance studies. As endogeneity can be in the form of reverse causality and/or in a dynamic sense, this thesis examines the relationships between corporate governance mechanisms that are proxied by ownership concentration and debt and firm value in the largest Australian firms from 1997 to 2008. The study investigates this issue through three different tests. First, the study examines whether there are any causal relationships between ownership concentration, debt and firm value. Second, the study investigates whether ownership concentration, debt and firm value are best treated as a group in order to assess their influence on each other. Therefore, the study assesses their substitutability or complementarity. Third, the study examines whether there are any non-linear relationships between ownership concentration and firm value on the one hand and debt on the other hand, as well as between debt and firm value. In investigating the dynamic endogeneity issue through these tests, the study employs two methodologies: two-way fixed effects (FE) and the two-step system generalised method of moments (GMM). In the first test, the study finds a causal relationship between ownership concentration and firm value as well as between debt and firm value. The causality is found to run from firm value to ownership concentration in a negative direction and from debt to firm value also in a negative direction. No causal relationship is found between ownership concentration and debt. However, further investigation by using sub-samples of ownership concentration reveals that there is causality between these two corporate governance mechanisms. It is found that causality runs from ownership concentration to debt in a negative direction. This test finds that firm value causes ownership concentration, thus providing evidence that endogeneity in the form of reverse causality exists. However, in the dynamic sense, it is found that dynamic endogeneity is not an issue in this test. The second test discovers that there is no evidence that ownership concentration, debt and firm value are effective as a group. Therefore, the study fails to identify their substitutability or complementarity. Furthermore, this test finds that dynamic endogeneity is not an issue in influencing ownership concentration, debt and firm value when they are tested as a group. In the final test, the study finds that there is a non-linear relationship between ownership concentration and firm value. This non-linear association is found to have an influence on the non-linearity between ownership concentration and debt. Further, the study also finds that debt and firm value are non-linear. It is found that the dynamic endogeneity issue does influence the non-linearity functions of ownership concentration but not the non-linearity functions of debt. The thesis concludes that dynamic endogeneity is not a serious issue in influencing the relationship between corporate governance mechanisms and firm value in the largest Australian firms

Time-Resolved Profiling Reveals ATF3 as a Novel Mediator of Endocrine Resistance in Breast Cancer

Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to resistance development. Even though recent novel approaches as the combination with CDK4/6 inhibitors increased the overall survival of relapsing patients, this remains relatively short and there is a urgent need to find alternative targetable pathways. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle, and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed in vivo in a mouse model, and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities

Reinforcement learning or active inference?

This paper questions the need for reinforcement learning or control theory when optimising behaviour. We show that it is fairly simple to teach an agent complicated and adaptive behaviours using a free-energy formulation of perception. In this formulation, agents adjust their internal states and sampling of the environment to minimize their free-energy. Such agents learn causal structure in the environment and sample it in an adaptive and self-supervised fashion. This results in behavioural policies that reproduce those optimised by reinforcement learning and dynamic programming. Critically, we do not need to invoke the notion of reward, value or utility. We illustrate these points by solving a benchmark problem in dynamic programming; namely the mountain-car problem, using active perception or inference under the free-energy principle. The ensuing proof-of-concept may be important because the free-energy formulation furnishes a unified account of both action and perception and may speak to a reappraisal of the role of dopamine in the brain

Preservation of large-scale chromatin structure in FISH experiments

The nuclear organization of specific endogenous chromatin regions can be investigated only by fluorescence in situ hybridization (FISH). One of the two fixation procedures is typically applied: (1) buffered formaldehyde or (2) hypotonic shock with methanol acetic acid fixation followed by dropping of nuclei on glass slides and air drying. In this study, we compared the effects of these two procedures and some variations on nuclear morphology and on FISH signals. We analyzed mouse erythroleukemia and mouse embryonic stem cells because their clusters of subcentromeric heterochromatin provide an easy means to assess preservation of chromatin. Qualitative and quantitative analyses revealed that formaldehyde fixation provided good preservation of large-scale chromatin structures, while classical methanol acetic acid fixation after hypotonic treatment severely impaired nuclear shape and led to disruption of chromosome territories, heterochromatin structures, and large transgene arrays. Our data show that such preparations do not faithfully reflect in vivo nuclear architecture. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00412-006-0084-2 and is accessible for authorized users

The synthetic psychology of the self

Synthetic psychology describes the approach of “understanding through building” applied to the human condition. In this chapter, we consider the specific challenge of synthesizing a robot “sense of self”. Our starting hypothesis is that the human self is brought into being by the activity of a set of transient self-processes instantiated by the brain and body. We propose that we can synthesize a robot self by developing equivalent sub-systems within an integrated biomimetic cognitive architecture for a humanoid robot. We begin the chapter by motivating this work in the context of the criteria for recognizing other minds, and the challenge of benchmarking artificial intelligence against human, and conclude by describing efforts to create a sense of self for the iCub humanoid robot that has ecological, temporally-extended, interpersonal and narrative components set within a multi-layered model of mind