The SuperB project

SuperB is a next generation asymmetric e+e- flavor factory with a baseline luminosity of 10^36 cm^-2 s^-1, 50-100 times the peak luminosity of the existing B-factories. The physics motivation is presented and the complementarity with the LHC is discussed. The conceptual design of the detector is also briefly described.Comment: 8 pages, 2 figures. Talk given at the Rencontres de Physique de la Vallee d'Aoste, La Thuile, Aosta Valley (Italy). March 1-7, 200

Computational Psychiatry and Psychometrics Based on Non-Conscious Stimuli Input and Pupil Response Output

It is well known from the technical literature that non-conscious perception of emotional stimuli affects behavior, perception, and even decision making [e.g., see Ref. (1) for a comprehensive review]. Non-conscious perception can be obtained by inducing sensory unawareness, e.g., through backward masking and binocular rivalry (1). Experiments adopting such paradigms have evidenced that non-consciously perceived emotional stimuli elicit activity in the amygdala, superior colliculus, basal ganglia, and pulvinar. More specifically, it has been shown that a subcortical fast route exists between the thalamus and the amygdala, which, in turn, project onto different cortical and subcortical structures [e.g., onto the nucleus accumbens, NAcc, when appetitive stimuli are perceived (2)]. These findings agree with the hypothesis about amygdala functionality proposed by LeDoux (3, 4). In fact, LeDoux has hypothized the existence of a thalamic pathway to the amygdala; such a pathway would allow to automatically detect evolutionary prepared visual stimuli (such as emotional faces, sexual-related stimuli, spiders, snakes, and injuries). Note that this model is also supported by other results acquired by different researchers that have employed masking in normal participants (5, 6) or have observed brain activity in patients affected by cortical blindness (7, 8). According to this model about amygdala functionality, the superior colliculus stimulates the pulvinar nucleus of the thalamus, which then arouses the amygdala (4, 9, 10). This suggests that salient features representing biologically prepared stimuli could be stored in the amygdala since birth. From an evolutionary perspective, this can be related to the fact that fast and implicit (or unconscious) reactions are needed in dangerous and highly dynamical environments. Moreover, even ontogenetic stimuli (e.g., weapons) are encoded within the amygdala through implicit learning during life (11, 12). These data evidence the importance of subcortical regions associated with implicit emotional processing. In fact, since the brain structure works like a hierarchical network (13) in which the limbic system represents a lower hierarchical level with respect to the higher cortical structure, it is likely that the overall perception and emotional appraisal are influenced by low-level evaluations. More specifically, the signals coming from lower and higher hierarchical levels determine prediction errors (or error signals) at intermediate levels; such error signals propagate through the entire hierarchical structure, determining cognitive perception, causes attributions, emotional evaluations, actions, and behaviors (14). Hence, if subcortical limbic-brainstem regions are defective, all the network hierarchy functioning will be compromised. As a matter of fact, a dysfunction in the limbic-brainstem regions is associated with various psychiatric disorders with higher cognitive deficits including autism, schizophrenia, posttraumatic stress disorders (PTSD), attention deficits/hyperactivity disorder (ADHD), neurosis, phobia, and others

Feasibility and coexistence of large ecological communities

The role of species interactions in controlling the interplay between the stability of ecosystems and their biodiversity is still not well understood. The ability of ecological communities to recover after small perturbations of the species abundances (local asymptotic stability) has been well studied, whereas the likelihood of a community to persist when the conditions change (structural stability) has received much less attention. Our goal is to understand the effects of diversity, interaction strengths and ecological network structure on the volume of parameter space leading to feasible equilibria. We develop a geometrical framework to study the range of conditions necessary for feasible coexistence. We show that feasibility is determined by few quantities describing the interactions, yielding a nontrivial complexity–feasibility relationship. Analysing more than 100 empirical networks, we show that the range of coexistence conditions in mutualistic systems can be analytically predicted. Finally, we characterize the geometric shape of the feasibility domain, thereby identifying the direction of perturbations that are more likely to cause extinctions

Integration of enzymatic data in <i>Bacillus subtilis</i> genome-scale metabolic model improves phenotype predictions and enables in silico design of poly-γ-glutamic acid production strains

Abstract Background Genome-scale metabolic models (GEMs) allow predicting metabolic phenotypes from limited data on uptake and secretion fluxes by defining the space of all the feasible solutions and excluding physio-chemically and biologically unfeasible behaviors. The integration of additional biological information in genome-scale models, e.g., transcriptomic or proteomic profiles, has the potential to improve phenotype prediction accuracy. This is particularly important for metabolic engineering applications where more accurate model predictions can translate to more reliable model-based strain design. Results Here we present a GEM with Enzymatic Constraints using Kinetic and Omics data (GECKO) model of Bacillus subtilis, which uses publicly available proteomic data and enzyme kinetic parameters for central carbon (CC) metabolic reactions to constrain the flux solution space. This model allows more accurate prediction of the flux distribution and growth rate of wild-type and single-gene/operon deletion strains compared to a standard genome-scale metabolic model. The flux prediction error decreased by 43% and 36% for wild-type and mutants respectively. The model additionally increased the number of correctly predicted essential genes in CC pathways by 2.5-fold and significantly decreased flux variability in more than 80% of the reactions with variable flux. Finally, the model was used to find new gene deletion targets to optimize the flux toward the biosynthesis of poly-γ-glutamic acid (γ-PGA) polymer in engineered B. subtilis. We implemented the single-reaction deletion targets identified by the model experimentally and showed that the new strains have a twofold higher γ-PGA concentration and production rate compared to the ancestral strain. Conclusions This work confirms that integration of enzyme constraints is a powerful tool to improve existing genome-scale models, and demonstrates the successful use of enzyme-constrained models in B. subtilis metabolic engineering. We expect that the new model can be used to guide future metabolic engineering efforts in the important industrial production host B. subtilis

Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity

Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.A. Huyghe ... J.M Polo ... et al

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (&lt;50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, &lt;50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters