Signature of a three-dimensional photonic band gap observed on silicon inverse woodpile photonic crystals

We have studied the reflectivity of CMOS-compatible three-dimensional silicon inverse woodpile photonic crystals at near-infrared frequencies. Polarization-resolved reflectivity spectra were obtained from two orthogonal crystal surfaces corresponding to 1.88 pi sr solid angle. The spectra reveal broad peaks with high reflectivity up to 67 % that are independent of the spatial position on the crystals. The spectrally overlapping reflectivity peaks for all directions and polarizations form the signature of a broad photonic band gap with a relative bandwidth up to 16 %. This signature is supported with stopgaps in plane wave bandstructure calculations and with the frequency region of the expected band gap.Comment: 9 pages, 5 figure

Evaluating Animal-Assisted Interventions:An Empirical Illustration of Differences between Outcome Measures

Multiple authors have called for strong empirical evaluations to strengthen the foundation of Animal-Assisted Interventions. Carefully choosing the outcome measures of these studies is important, as choosing the wrong outcomes may lead to a failure to detect effects. The current study therefore compares and contrasts the use of several outcome measures, to assess the effect of an equine-assisted intervention for a child with Autism Spectrum Disorder: (1) a semi-structured interview with both parents, specifically designed for children with cognitive disabilities, (2) a general screening instrument filled out by both parents separately, which can be used to assess children’s psycho-social problems, and (3) systematic observations of social and communication skills during the equine-assisted sessions. All instruments indicated an improvement in the participant’s social and communication skills. We found differences between the interview and questionnaires with regard to parents’ perception of aggression regulation and interacting with peers. Differences with regard to parental reports and observations were found for play development and anxiety. The observations provided a detailed view of the child’s development during the intervention, which yielded an interesting hypothesis in terms of the current dose–response discussion in AAI for children with Autism Spectrum Disorder

Diminished counterregulatory responses to meal-induced hypoglycemia 4 years after RYGB

PURPOSE: Post-bariatric hypoglycemia is a complication of bariatric surgery, especially Roux-en-Y gastric bypass (RYGB). The counterregulatory hormonal and sympathetic neural responses were measured during a previously reported meal test in which 48% had an almost asymptomatic hypoglycemic event. MATERIALS AND METHODS: Forty-four randomly selected patients 4 years after RYGB. A liquid meal test (MMT) after overnight fasting. Based on the glucose nadir during the MMT, patients were divided in a hypo group (glucose < 3.3 mmol/L) and a non-hypo group (glucose ≥ 3.3 mmol/L). Cortisol, epinephrine, norepinephrine, blood pressure, and heart rate were measured up to 180 min after ingestion of the meal. Incremental areas under the curve (iAUC), peak, and delta hormone responses after the glucose nadir were calculated. Parameters were compared between the hypo and non-hypo groups. RESULTS: A total of 21/44 (48%) had an almost asymptomatic hypoglycemic event. Cortisol and epinephrine responses in the hypo group were not increased compared to the non-hypo group, and there were no signs of increased sympathetic nerve activity. Peak and delta cortisol were lower in the hypo compared to the non-hypo group. Norepinephrine was higher in the hypo group especially in the time frame 60-120 and 120-180 min after start of the meal. CONCLUSION: No increase in epinephrine and a lower cortisol response to hypoglycemia were observed compared to normoglycemia during a meal test in patients after RYGB. Norepinephrine levels were higher in the hypo group. These findings may suggest that possible recurrent hypoglycemia after RYGB results in blunting of counterregulatory responses indicative of hypoglycemia-induced autonomic failure. CLIN TRIAL REGISTER ID: ISRCTN 11738149

Modification of a PE/PPE substrate pair reroutes an Esx substrate pair from the mycobacterial ESX-1 type VII secretion system to the ESX-5 system

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1-5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1

Reinforcement Learning Agents acquire Flocking and Symbiotic Behaviour in Simulated Ecosystems

In nature, group behaviours such as flocking as well as cross-species symbiotic partnerships are observed in vastly different forms and circumstances. We hypothesize that such strategies can arise in response to generic predator-prey pressures in a spatial environment with range-limited sensation and action. We evaluate whether these forms of coordination can emerge by independent multi-agent reinforcement learning in simple multiple-species ecosystems. In contrast to prior work, we avoid hand-crafted shaping rewards, specific actions, or dynamics that would directly encourage coordination across agents. Instead we test whether coordination emerges as a consequence of adaptation without encouraging these specific forms of coordination, which only has indirect benefit. Our simulated ecosystems consist of a generic food chain involving three trophic levels: apex predator, mid-level predator, and prey. We conduct experiments on two different platforms, a 3D physics engine with tens of agents as well as in a 2D grid world with up to thousands. The results clearly confirm our hypothesis and show substantial coordination both within and across species. To obtain these results, we leverage and adapt recent advances in deep reinforcement learning within an ecosystem training protocol featuring homogeneous groups of independent agents from different species (sets of policies), acting in many different random combinations in parallel habitats. The policies utilize neural network architectures that are invariant to agent individuality but not type (species) and that generalize across varying numbers of observed other agents. While the emergence of complexity in artificial ecosystems have long been studied in the artificial life community, the focus has been more on individual complexity and genetic algorithms or explicit modelling, and less on group complexity and reinforcement learning emphasized in this article. Unlike what the name and intuition suggests, reinforcement learning adapts over evolutionary history rather than a life-time and is here addressing the sequential optimization of fitness that is usually approached by genetic algorithms in the artificial life community. We utilize a shift from procedures to objectives, allowing us to bring new powerful machinery to bare, and we see emergence of complex behaviour from a sequence of simple optimization problems

Protocol of the SOMNIA project : an observational study to create a neurophysiological database for advanced clinical sleep monitoring

Introduction Polysomnography (PSG) is the primary tool for sleep monitoring and the diagnosis of sleep disorders. Recent advances in signal analysis make it possible to reveal more information from this rich data source. Furthermore, many innovative sleep monitoring techniques are being developed that are less obtrusive, easier to use over long time periods and in the home situation. Here, we describe the methods of the Sleep and Obstructive Sleep Apnoea Monitoring with Non-Invasive Applications (SOMNIA) project, yielding a database combining clinical PSG with advanced unobtrusive sleep monitoring modalities in a large cohort of patients with various sleep disorders. The SOMNIA database will facilitate the validation and assessment of the diagnostic value of the new techniques, as well as the development of additional indices and biomarkers derived from new and/or traditional sleep monitoring methods. Methods and analysis We aim to include at least 2100 subjects (both adults and children) with a variety of sleep disorders who undergo a PSG as part of standard clinical care in a dedicated sleep centre. Full-video PSG will be performed according to the standards of the American Academy of Sleep Medicine. Each recording will be supplemented with one or more new monitoring systems, including wrist-worn photoplethysmography and actigraphy, pressure sensing mattresses, multimicrophone recording of respiratory sounds including snoring, suprasternal pressure monitoring and multielectrode electromyography of the diaphragm

MEK inhibition is a promising therapeutic strategy for MLL-rearranged infant acute lymphoblastic leukemia patients carrying RAS mutations

Acute lymphoblastic leukemia (ALL) in infants is an aggressive malignancy with a poor clinical outcome, and is characterized by translocations of the Mixed Lineage Leukemia (MLL) gene. Previously, we identified RAS mutations in 14-24% of infant ALL patients, and showed that the presence of a RAS mutation decreased the survival chances even further. We hypothesized that targeting the RAS signaling pathway could be a therapeutic strategy for RAS-mutant infant ALL patients. Here we show that the MEK inhibitors Trametinib, Selumetinib and MEK162 severely impair primary RAS-mutant MLL-rearranged infant ALL cells in vitro. While all RAS-mutant samples were sensitive to MEK inhibitors, we found both sensitive and resistant samples among RAS-wildtype cases. We confirmed enhanced RAS pathway signaling in RASmutant samples, but found no apparent downstream over-activation in the wildtype samples. However, we did confirm that MEK inhibitors reduced p-ERK levels, and induced apoptosis in the RAS-mutant MLL-rearranged ALL cells. Finally, we show that MEK inhibition synergistically enhances prednisolone sensitivity,