Abstract platforms of computation

Computational formalisms have been pushing the boundaries of the field of computing for the last 80 years and much debate has surrounded what computing entails; what it is, and what it is not. This paper seeks to explore the boundaries of the ideas of computation and provide a framework for enabling a constructive discussion of computational ideas. First, a review of computing is given, ranging from Turing Machines to interactive computing. Then, a variety of natural physical systems are considered for their computational qualities. From this exploration, a framework is presented under which all dynamical systems can be considered as instances of the class of abstract computational platforms. An abstract computational platform is defined by both its intrinsic dynamics and how it allows computation that is meaningful to an external agent through the configuration of constraints upon those dynamics. It is asserted that a platform’s computational expressiveness is directly related to the freedom with which constraints can be placed. Finally, the requirements for a formal constraint description language are considered and it is proposed that Abstract State Machines may provide a reasonable basis for such a language

Acceptance and Commitment Therapy in a Low-Income Country in Sub-Saharan Africa: A Call for Further Research

A worsening trend of critical shortages in senior health care workers across low- and middle-income countries (LMICs) in sub-Saharan Africa has been documented for decades. This is especially the case in Ethiopia that has severe shortage of mental health professionals. Consistent with the WHO recommended approach of task sharing for mental health care in LMICs, Acceptance and Commitment Therapy (ACT), which is an empirically validated psychological intervention aimed at increasing psychological flexibility, may be delivered by trained laypersons who have a grassroots presence. In this paper, we discuss the need for and potential role of ACT to be delivered by health extension workers (HEWs) to address mental health care needs across Ethiopia. To this end, we also reviewed previous studies that have examined the effectiveness of ACT-based interventions in African countries including in Nigeria, Sierra Leone, Uganda, and South Africa. All studies revealed significant improvements of various mental health-related outcome measures such as decreased psychological distress and depressive symptoms, or increased subjective wellbeing and life satisfaction in the groups that received an ACT-based intervention. However, to date, there is no study that applied ACT in Ethiopia. Thus, more research is warranted to examine the effectiveness and, if proven successful, to scale up a task sharing approach of an ACT-based intervention being delivered by trained HEWs at a grassroots level, possibly paving the way for an innovative, sustainable mental health service in Ethiopia as well as other African LMICs

Super Resolution Fluorescence Microscopy and Tracking of Bacterial Flotillin (Reggie) Paralogs Provide Evidence for Defined-Sized Protein Microdomains within the Bacterial Membrane but Absence of Clusters Containing Detergent-Resistant Proteins

Biological membranes have been proposed to contain microdomains of a specific lipid composition, in which distinct groups of proteins are clustered. Flotillin-like proteins are conserved between pro—and eukaryotes, play an important function in several eukaryotic and bacterial cells, and define in vertebrates a type of so-called detergent-resistant microdomains. Using STED microscopy, we show that two bacterial flotillins, FloA and FloT, form defined assemblies with an average diameter of 85 to 110 nm in the model bacterium Bacillus subtilis. Interestingly, flotillin microdomains are of similar size in eukaryotic cells. The soluble domains of FloA form higher order oligomers of up to several hundred kDa in vitro, showing that like eukaryotic flotillins, bacterial assemblies are based in part on their ability to self-oligomerize. However, B. subtilis paralogs show significantly different diffusion rates, and consequently do not colocalize into a common microdomain. Dual colour time lapse experiments of flotillins together with other detergent-resistant proteins in bacteria show that proteins colocalize for no longer than a few hundred milliseconds, and do not move together. Our data reveal that the bacterial membrane contains defined-sized protein domains rather than functional microdomains dependent on flotillins. Based on their distinct dynamics, FloA and FloT confer spatially distinguishable activities, but do not serve as molecular scaffolds

Developing a Wellbeing Framework for Aboriginal and Torres Strait Islander Peoples Living with Chronic Disease (Wellbeing Study)

Addressing a need identified by Aboriginal and Torres Strait Islander peoples and their primary healthcare providers, this study developed a Wellbeing Framework for managing chronic disease in a manner that also supports wellbeing. Chronic care models that are currently in use usually focus upon the systems, resources and policies that are required to deliver care. The important roles of culture, spirituality, Country and family in maintaining health and wellbeing are notably absent from such models. Re-defining the way in which care is delivered to reflect Aboriginal and Torres Strait Islander peoples’ needs and values is essential for improving the accessibility and acceptability of primary healthcare services.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

CRX controls retinal expression of the X-linked juvenile retinoschisis (RS1) gene

X-linked juvenile retinoschisis is a heritable condition of the retina in males caused by mutations in the RS1 gene. Still, the cellular function and retina-specific expression of RS1 are poorly understood. To address the latter issue, we characterized the minimal promoter driving expression of RS1 in the retina. Binding site prediction, site-directed mutagenesis, and reporter assays suggest an essential role of two nearby cone-rod homeobox (CRX)-responsive elements (CRE) in the proximal −177/+32 RS1 promoter. Chromatin immunoprecipitation associates the RS1 promoter in vivo with CRX, the coactivators CBP, P300, GCN5 and acetylated histone H3. Transgenic Xenopus laevis expressing a green fluorescent protein (GFP) reporter under the control of RS1 promoter sequences show that the −177/+32 fragment drives GFP expression in photoreceptors and bipolar cells. Mutating either of the two conserved CRX binding sites results in strongly decreased RS1 expression. Despite the presence of sequence motifs in the promoter, NRL and NR2E3 appear not to be essential for RS1 expression. Together, our in vitro and in vivo results indicate that two CRE sites in the minimal RS1 promoter region control retinal RS1 expression and establish CRX as a key factor driving this expression

Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan

The association between soya foods and breast cancer risk was investigated in a prospective study of 34 759 women in Hiroshima and Nagasaki, Japan. Women completed dietary questionnaires in 1969–1970 and/or in 1979–1981 and were followed for incident breast cancer until 1993. The analysis involved 427 cases of primary breast cancer in 488 989 person-years of observation. The risk for breast cancer was not significantly associated with consumption of soya foods: for tofu, relative risks adjusted for attained age, calendar period, city, age at time of bombings and radiation dose to the breast were 0.99 (95% CI 0.80–1.24) for consumption two to four times per week and 1.07 (0.78–1.47) for consumption five or more times per week, relative to consumption once a week or less; for miso soup, relative risks were 1.03 (0.81–1.31) for consumption two to four times per week and 0.87 (0.68–1.12) for consumption five or more times per week, relative to consumption once a week or less. These results were not materially altered by further adjustments for reproductive variables and were similar in women diagnosed before age 50 and at ages 50 and above. Among 17 other foods and drinks examined only dried fish (decrease in relative risk with increasing consumption) and pickled vegetables (higher relative risk with higher consumption) were significantly related to breast cancer risk; these associations were not prior hypotheses and, because of the large number of comparisons made, they may be due to chance. © 1999 Cancer Research Campaig

A Neural Correlate of the Processing of Multi-Second Time Intervals in Primate Prefrontal Cortex

Several areas of the brain are known to participate in temporal processing. Neurons in the prefrontal cortex (PFC) are thought to contribute to perception of time intervals. However, it remains unclear whether the PFC itself can generate time intervals independently of external stimuli. Here we describe a group of PFC neurons in area 9 that became active when monkeys recognized a particular elapsed time within the range of 1–7 seconds. Another group of area 9 neurons became active only when subjects reproduced a specific interval without external cues. Both types of neurons were individually tuned to recognize or reproduce particular intervals. Moreover, the injection of muscimol, a GABA agonist, into this area bilaterally resulted in an increase in the error rate during time interval reproduction. These results suggest that area 9 may process multi-second intervals not only in perceptual recognition, but also in internal generation of time intervals

Sustainable computational science: the ReScience initiative

Computer science o ers a large set of tools for prototyping, writing, running, testing, validating, sharing and reproducing results, however computational science lags behind. In the best case, authors may provide their source code as a compressed archive and they may feel con dent their research is reproducible. But this is not exactly true. Jonathan Buckheit and David Donoho proposed more than two decades ago that an article about computational results is advertising, not scholarship. e actual scholarship is the full so ware environment, code, and data that produced the result. is implies new work ows, in particular in peer-reviews. Existing journals have been slow to adapt: source codes are rarely requested, hardly ever actually executed to check that they produce the results advertised in the article. ReScience is a peer-reviewed journal that targets computational research and encourages the explicit replication of already published research, promoting new and open-source implementations in order to ensure that the original research can be replicated from its description. To achieve this goal, the whole publishing chain is radically di erent from other traditional scienti c journals. ReScience resides on GitHub where each new implementation of a computational study is made available together with comments, explanations, and so ware tests

Coping with unpredictability: Dopaminergic and neurotrophic responses to omission of expected reward in Atlantic salmon (Salmo salar L.).

Comparative studies are imperative for understanding the evolution of adaptive neurobiological processes such as neural plasticity, cognition, and emotion. Previously we have reported that prolonged omission of expected rewards (OER, or 'frustrative nonreward') causes increased aggression in Atlantic salmon (Salmo salar). Here we report changes in brain monoaminergic activity and relative abundance of brain derived neurotrophic factor (BDNF) and dopamine receptor mRNA transcripts in the same paradigm. Groups of fish were initially conditioned to associate a flashing light with feeding. Subsequently, the expected food reward was delayed for 30 minutes during two out of three meals per day in the OER treatment, while the previously established routine was maintained in control groups. After 8 days there was no effect of OER on baseline brain stem serotonin (5-HT) or dopamine (DA) activity. Subsequent exposure to acute confinement stress led to increased plasma cortisol and elevated turnover of brain stem DA and 5-HT in all animals. The DA response was potentiated and DA receptor 1 (D1) mRNA abundance was reduced in the OER-exposed fish, indicating a sensitization of the DA system. In addition OER suppressed abundance of BDNF in the telencephalon of non-stressed fish. Regardless of OER treatment, a strong positive correlation between BDNF and D1 mRNA abundance was seen in non-stressed fish. This correlation was disrupted by acute stress, and replaced by a negative correlation between BDNF abundance and plasma cortisol concentration. These observations indicate a conserved link between DA, neurotrophin regulation, and corticosteroid-signaling pathways. The results also emphasize how fish models can be important tools in the study of neural plasticity and responsiveness to environmental unpredictability

Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients

Background: Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. Methods: Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. Results: KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome. Conclusions: In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT