Reinforcement learning in dendritic structures

The discovery of binary dendritic events such as local NMDA spikes in dendritic subbranches led to the suggestion that dendritic trees could be computationally equivalent to a 2-layer network of point neurons, with a single output unit represented by the soma, and input units represented by the dendritic branches. Although this interpretation endows a neuron with a high computational power, it is functionally not clear why nature would have preferred the dendritic solution with a single but complex neuron, as opposed to the network solution with many but simple units. We show that the dendritic solution has a distinguished advantage over the network solution when considering different learning tasks. Its key property is that the dendritic branches receive an immediate feedback from the somatic output spike, while in the corresponding network architecture the feedback would require additional backpropagating connections to the input units. Assuming a reinforcement learning scenario we formally derive a learning rule for the synaptic contacts on the individual dendritic trees which depends on the presynaptic activity, the local NMDA spikes, the somatic action potential, and a delayed reinforcement signal. We test the model for two scenarios: the learning of binary classifications and of precise spike timings. We show that the immediate feedback represented by the backpropagating action potential supplies the individual dendritic branches with enough information to efficiently adapt their synapses and to speed up the learning process

A systematic review of the use of the Satiety Quotient

The satiating efficiency of food has been increasingly quantified using the Satiety Quotient (SQ). The SQ integrates both the energy content of food ingested during a meal and the associated change in appetite sensations. This systematic review examines the available evidence regarding its methodological use and clinical utility. A literature search was conducted in 6 databases considering studies from 1900 to April 2020 that used SQ in adults, adolescents and children. All study designs were included. From the initial 495 references found, 52 were included. Of the studies included, 33 were acute studies (29 in adults and 4 in adolescents) and 19 were longitudinal studies in adults. A high methodological heterogeneity in the application of the SQ was observed between studies. Five main utilizations of the SQ were identified: its association with i) energy intake; ii) anthropometric variables; iii) energy expenditure/physical activity; iv) sleep quality and quantity; as well as v) to classify individuals by their satiety responsiveness (i.e. low and high satiety phenotypes). Altogether, the studies suggest the SQ as an interesting clinical tool regarding the satiety responsiveness to a meal and its changes in responses to weight loss in adults. The SQ might be a reliable clinical indicator in adults when it comes to both obesity prevention and treatment. There is a need for more standardized use of the SQ in addition to further studies to investigate its validity in different contexts and populations, especially among children and adolescents

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

Detection of Extensive Cross-Neutralization between Pandemic and Seasonal A/H1N1 Influenza Viruses Using a Pseudotype Neutralization Assay

BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007) and against pandemic A/H1N1 (A/California/04/2009) were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools

Pure-glue hidden valleys through the Higgs portal

We consider the possibility that the Higgs boson can act as a link to a hidden sector in the context of pure-glue hidden valley models. In these models the standard model is weakly coupled, through loops of heavy messengers fields, to a hidden sector whose low energy dynamics is described by a pure-Yang-Mills theory. Such a hidden sector contains several metastable hidden glueballs. In this work we shall extend earlier results on hidden valleys to include couplings of the messengers to the standard model Higgs sector. The effective interactions at one-loop couple the hidden gluons to the standard model particles through the Higgs sector. These couplings in turn induce hidden glueball decays to fermion pairs, or cascade decays with multiple Higgs emission. The presence of effective operators of different mass dimensions, often competing with each other, together with a great diversity of states, leads to a great variability in the lifetimes and decay modes of the hidden glueballs. We find that most of the operators considered in this paper are not heavily constrained by precision electroweak physics, therefore leaving plenty of room in the parameter space to be explored by the future experiments at the LHC.Comment: 44 pages, 16 figures. Major revision for JHEP, corrected an error in Eq. 5.1, comments adde

Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania.

The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004-2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam

Assessing control of postural stability in community-living older adults using performance-based limits of stability

<p>Abstract</p> <p>Background</p> <p>Balance disability measurements routinely used to identify fall risks in frail populations have limited value in the early detection of postural stability deficits in community-living older adults. The objectives of the study were to 1) measure performance-based limits of stability (LOS) in community-living older adults and compare them to theoretical LOS computed from data proposed by the Balance Master^®system, 2) explore the feasibility of a new measurement approach based on the assessment of postural stability during weight-shifting tasks at performance-based LOS, 3) quantify intra-session performance variability during multiple trials using the performance-based LOS paradigm.</p> <p>Methods</p> <p>Twenty-four healthy community-living older adults (10 men, 14 women) aged between 62 to 85 (mean age ± sd, 71.5 ± 6 yrs) participated in the study. Subjects' performance-based LOS were established by asking them to transfer their body weight as far as possible in three directions (forward, right and left) without changing their base of support. LOS were computed as the maximal excursion of the COP in each direction among three trials. Participants then performed two experimental tasks that consisted in controlling, with the assistance of visual feedback, their centre of pressure (COP) within two predefined targets set at 100% of their performance-based LOS. For each tasks 8 trials were performed. Ground reaction forces and torques during performance-based LOS evaluation and experimental tasks were recorded with a force plate. Sway area and medio-lateral mean COP displacement speed variables were extracted from force plate recordings.</p> <p>Results</p> <p>Significant differences between theoretical LOS computed from maximum leaning angles derived from anthropometric characteristics and performance-based LOS were observed. Results showed that a motor learning effect was present as the participants optimized their weight-shifting strategy through the first three trials of each task using the visual biofeedback provided on their COP. Reliable measures of control of postural stability at performance-based LOS can be obtained after two additional trials after the learning phase (0.69 > ICC > 1.0).</p> <p>Conclusion</p> <p>Establishing performance-based LOS instead of relying on estimations of theoretical LOS offers a more individualized and realistic insight on the true LOS of an individual. Performance-based LOS can be used as targets during weight-shifting postural tasks with real time visual feedback of the COP displacement to assess postural stability of community-living older adults. In order to obtain reliable results, a learning phase allowing subjects to learn how to control their COP displacement is needed.</p

MTSS1 and SCAMP1 cooperate to prevent invasion in breast cancer

Cell–cell adhesions constitute the structural “glue” that retains cells together and contributes to tissue organisation and physiological function. The integrity of these structures is regulated by extracellular and intracellular signals and pathways that act on the functional units of cell adhesion such as the cell adhesion molecules/adhesion receptors, the extracellular matrix (ECM) proteins and the cytoplasmic plaque/peripheral membrane proteins. In advanced cancer, these regulatory pathways are dysregulated and lead to cell–cell adhesion disassembly, increased invasion and metastasis. The Metastasis suppressor protein 1 (MTSS1) plays a key role in the maintenance of cell–cell adhesions and its loss correlates with tumour progression in a variety of cancers. However, the mechanisms that regulate its function are not well-known. Using a system biology approach, we unravelled potential interacting partners of MTSS1. We found that the secretory carrier-associated membrane protein 1 (SCAMP1), a molecule involved in post-Golgi recycling pathways and in endosome cell membrane recycling, enhances Mtss1 anti-invasive function in HER2+/ER−/PR− breast cancer, by promoting its protein trafficking leading to elevated levels of RAC1-GTP and increased cell–cell adhesions. This was clinically tested in HER2 breast cancer tissue and shown that loss of MTSS1 and SCAMP1 correlates with reduced disease-specific survival. In summary, we provide evidence of the cooperative roles of MTSS1 and SCAMP1 in preventing HER2+/ER−/PR− breast cancer invasion and we show that the loss of Mtss1 and Scamp1 results in a more aggressive cancer cell phenotype

Closing in on a perturbative fourth generation

A perturbative new family of fermions is now severely constrained, though not excluded yet. We reconsider the current bounds (i.e., direct and from Higgs searches, R_b, oblique parameters) on the fourth generation parameter space assuming the case of a small CKM mixing with the third generation. We identify viable scenarios featuring either a light or a heavy Higgs boson. A set of representative benchmark points targeted for LHC searches is proposed with a normal (inverted) quark mass hierarchy where t' -> b'W (b' -> tW) decays are sizable. In the case where the fourth generation couplings to the lighter quark families are small, we suggest that search strategies at the LHC should include both pair (strong) and single (weak) production with bb+nW (n=2,...,6) final state signatures.Comment: 23 pages, 6 figures, v2: some issues clarified and references added. To appear in JHE