Maze solvers demystified and some other thoughts

There is a growing interest towards implementation of maze solving in spatially-extended physical, chemical and living systems. Several reports of prototypes attracted great publicity, e.g. maze solving with slime mould and epithelial cells, maze navigating droplets. We show that most prototypes utilise one of two phenomena: a shortest path in a maze is a path of the least resistance for fluid and current flow, and a shortest path is a path of the steepest gradient of chemoattractants. We discuss that substrates with so-called maze-solving capabilities simply trace flow currents or chemical diffusion gradients. We illustrate our thoughts with a model of flow and experiments with slime mould. The chapter ends with a discussion of experiments on maze solving with plant roots and leeches which show limitations of the chemical diffusion maze-solving approach.Comment: This is a preliminary version of the chapter to be published in Adamatzky A. (Ed.) Shortest path solvers. From software to wetware. Springer, 201

Evaluation of Rehabilitation of Memory in Neurological Disabilities (ReMiND): a randomized controlled trial

OBJECTIVE:The evidence for the effectiveness of memory rehabilitation is inconclusive. The aim was to compare the effectiveness of two group memory rehabilitation programmes with a self-help group control. DESIGN:Single-blind randomized controlled trial. PARTICIPANTS:Participants with memory problems following traumatic brain injury, stroke or multiple sclerosis were recruited from community settings. INTERVENTIONS:Participants were randomly allocated, in cohorts of four, to compensation or restitution group treatment programmes or a self-help group control. All programmes were manual-based and comprised two individual and ten weekly group sessions. MAIN MEASURES:Memory functions, mood, and activities of daily living were assessed at baseline and five and seven months after randomization. RESULTS:There were 72 participants (mean age 47.7, SD 10.2 years; 32 men). There was no significant effect of treatment on the Everyday Memory Questionnaire (P = 0.97). At seven months the mean scores were comparable (restitution 36.6, compensation 41.0, self-help 44.1). However, there was a significant difference between groups on the Internal Memory Aids Questionnaire (P = 0.002). The compensation and restitution groups each used significantly more internal memory aids than the self-help group (P 0.05). CONCLUSIONS:There results show few statistically significant effects of either compensation or restitution memory group treatment as compared with a self-help group control. Further randomized trials of memory rehabilitation are needed

The momentum analyticity of two-point correlators from perturbation theory and AdS/CFT

The momentum plane analyticity of two point function of a relativistic thermal field theory at zero chemical potential is explored. A general principle regarding the location of the singularities is extracted. In the case of the N=4 supersymmetric Yang-Mills theory at large $N_c$, a qualitative change in the nature of the singularity (branch points versus simple poles) from the weak coupling regime to the strong coupling regime is observed with the aid of the AdS/CFT correspondence.Comment: 18 pages, 3 figures, typos fixed, 1 figure update

Induction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer

Uterine serous papillary carcinoma is a highly aggressive variant of endometrial cancer histologically similar to high grade ovarian cancer. Unlike ovarian cancer, however, it is a chemoresistant disease from onset, with responses to combined cisplatinum-based chemotherapy in the order of 20% and an extremely poor prognosis. In this study, we demonstrate that tumour lysate-pulsed autologous dendritic cells can elicit a specific CD8+ cytotoxic T lymphocyte response against autologous tumour target cells in three patients with uterine serous papillary cancer. CTL from patients 1 and 2 expressed strong cytolytic activity against autologous tumour cells, did not lyse autologous lymphoblasts or autologous EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Patient 3 CD8+ T cells expressed a modest but reproducible cytotoxicity against autologous tumour cells only at the time of the first priming. Further priming attempts with PBL collected from patient 3 after tumour progression in the lumboaortic lymph nodes were unsuccesful. Cytotoxicity against autologous tumour cells could be significantly inhibited by anti-HLA class I (W6/32) and anti-LFA-1 MAbs. Highly cytotoxic CD8+ T cells from patients 1 and 2 showed a heterogeneous CD56 expression while CD56 was not expressed by non-cytotoxic CD8+ T cells from patient 3. Using two colour flow cytometric analysis of intracellular cytokine expression at the single cell level, a striking dominance of IFN-γ expressors was detectable in CTL populations of patients 1 and 2 while in patient 3 a dominant population of CD8+ T cells expressing IL-4 and IL-10 was consistently detected. Taken together, these data demonstrate that tumour lysate-pulsed DC can be an effective tool in inducing uterine serous papillary cancer-specific CD8+ CTL able to kill autologous tumour cells in vitro. However, high levels of tumour specific tolerance in some patients may impose a significant barrier to therapeutic vaccination. These results may have important implications for the treatment in the adjuvant setting of uterine serous papillary cancer patients with active or adoptive immunotherapy

Local Optical Probe of Motion and Stress in a multilayer graphene NEMS

Nanoelectromechanical systems (NEMSs) are emerging nanoscale elements at the crossroads between mechanics, optics and electronics, with significant potential for actuation and sensing applications. The reduction of dimensions compared to their micronic counterparts brings new effects including sensitivity to very low mass, resonant frequencies in the radiofrequency range, mechanical non-linearities and observation of quantum mechanical effects. An important issue of NEMS is the understanding of fundamental physical properties conditioning dissipation mechanisms, known to limit mechanical quality factors and to induce aging due to material degradation. There is a need for detection methods tailored for these systems which allow probing motion and stress at the nanometer scale. Here, we show a non-invasive local optical probe for the quantitative measurement of motion and stress within a multilayer graphene NEMS provided by a combination of Fizeau interferences, Raman spectroscopy and electrostatically actuated mirror. Interferometry provides a calibrated measurement of the motion, resulting from an actuation ranging from a quasi-static load up to the mechanical resonance while Raman spectroscopy allows a purely spectral detection of mechanical resonance at the nanoscale. Such spectroscopic detection reveals the coupling between a strained nano-resonator and the energy of an inelastically scattered photon, and thus offers a new approach for optomechanics

A protocol for a systematic literature review: comparing the impact of seasonal and meteorological parameters on acute respiratory infections in Indigenous and non-Indigenous peoples

Background: Acute respiratory infections (ARI) are a leading cause of morbidity and mortality globally, and are often linked to seasonal and/or meteorological conditions. Globally, Indigenous peoples may experience a different burden of ARI compared to non-Indigenous peoples. This protocol outlines our process for conducting a systematic review to investigate whether associations between ARI and seasonal or meteorological parameters differ between Indigenous and non-Indigenous groups residing in the same geographical region. Methodology: A search string will be used to search PubMed®, CAB Abstracts/CAB Direct©, and Science Citation Index® aggregator databases. Articles will be screened using inclusion/exclusion criteria applied first at the title and abstract level, and then at the full article level by two independent reviewers. Articles maintained after full article screening will undergo risk of bias assessment and data will be extracted. Heterogeneity tests, meta-analysis, and forest and funnel plots will be used to synthesize the results of eligible studies. Discussion and registration: This protocol paper describes our systematic review methods to identify and analyze relevant ARI, season, and meteorological literature with robust reporting. The results are intended to improve our understanding of potential associations between seasonal and meteorological parameters and ARI and, if identified, whether this association varies by place, population, or other characteristics. The protocol is registered in the PROSPERO database (#38051)

Techniques for Arbuscular Mycorrhiza Inoculum Reduction

It is well established that arbuscular mycorrhizal (AM) fungi can play a significant role in sustainable crop production and environmental conservation. With the increasing awareness of the ecological significance of mycorrhizas and their diversity, research needs to be directed away from simple records of their occurrence or casual speculation of their function (Smith and Read 1997). Rather, the need is for empirical studies and investigations of the quantitative aspects of the distribution of different types and their contribution to the function of ecosystems. There is no such thing as a fungal effect or a plant effect, but there is an interaction between both symbionts. This results from the AM fungi and plant community size and structure, soil and climatic conditions, and the interplay between all these factors (Kahiluoto et al. 2000). Consequently, it is readily understood that it is the problems associated with methodology that limit our understanding of the functioning and effects of AM fungi within field communities. Given the ubiquous presence of AM fungi, a major constraint to the evaluation of the activity of AM colonisation has been the need to account for the indigenous soil native inoculum. This has to be controlled (i.e. reduced or eliminated) if we are to obtain a true control treatment for analysis of arbuscular mycorrhizas in natural substrates. There are various procedures possible for achieving such an objective, and the purpose of this chapter is to provide details of a number of techniques and present some evaluation of their advantages and disadvantages. Although there have been a large number of experiments to investigated the effectiveness of different sterilization procedures for reducing pathogenic soil fungi, little information is available on their impact on beneficial organisms such as AM fungi. Furthermore, some of the techniques have been shown to affect physical and chemical soil characteristics as well as eliminate soil microorganisms that can interfere with the development of mycorrhizas, and this creates difficulties in the interpretation of results simply in terms of possible mycorrhizal activity. An important subject is the differentiation of methods that involve sterilization from those focussed on indigenous inoculum reduction. Soil sterilization aims to destroy or eliminate microbial cells while maintaining the existing chemical and physical characteristics of the soil (Wolf and Skipper 1994). Consequently, it is often used for experiments focussed on specific AM fungi, or to establish a negative control in some other types of study. In contrast, the purpose of inoculum reduction techniques is to create a perturbation that will interfere with mycorrhizal formation, although not necessarily eliminating any component group within the inoculum. Such an approach allows the establishment of different degrees of mycorrhizal formation between treatments and the study of relative effects. Frequently the basic techniques used to achieve complete sterilization or just an inoculum reduction may be similar but the desired outcome is accomplished by adjustments of the dosage or intensity of the treatment. The ultimate choice of methodology for establishing an adequate non-mycorrhizal control depends on the design of the particular experiments, the facilities available and the amount of soil requiring treatment

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders