Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance

Seliciclib (R-Roscovitine) was identified as an inhibitor of CDKs and has undergone drug development and clinical testing as an anticancer agent. In this review, the authors describe the discovery of Seliciclib and give a brief summary of the biology of the CDKs Seliciclib inhibits. An overview of the published in vitro and in vivo work supporting the development as an anti-cancer agent, from in vitro experiments to animal model studies ending with a summary of the clinical trial results and trials underway is presented. In addition some potential non-oncology applications are explored and the potential mode of action of Seliciclib in these areas is described. Finally the authors argue that optimisation of the therapeutic effects of kinase inhibitors such as Seliciclib could be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division

Resistance to heat and cold stress in Drosophila melanogaster: intra and inter population variation in relation to climate

International audienc

Large N limit of SO(N) scalar gauge theory

In this paper we study the large $N_c$ limit of SO(N_c) gauge theory coupled to a real scalar field following ideas of Rajeev. We see that the phase space of this resulting classical theory is Sp_1(H)/U(H_+) which is the analog of the Siegel disc in infinite dimensions. The linearized equations of motion give us a version of the well-known 't Hooft equation of two dimensional QCD.Comment: 16 pages, no figure

Large N limit of SO(N) gauge theory of fermions and bosons

In this paper we study the large N_c limit of SO(N_c) gauge theory coupled to a Majorana field and a real scalar field in 1+1 dimensions extending ideas of Rajeev. We show that the phase space of the resulting classical theory of bilinears, which are the mesonic operators of this theory, is OSp_1(H|H )/U(H_+|H_+), where H|H refers to the underlying complex graded space of combined one-particle states of fermions and bosons and H_+|H_+ corresponds to the positive frequency subspace. In the begining to simplify our presentation we discuss in detail the case with Majorana fermions only (the purely bosonic case is treated in our earlier work). In the Majorana fermion case the phase space is given by O_1(H)/U(H_+), where H refers to the complex one-particle states and H_+ to its positive frequency subspace. The meson spectrum in the linear approximation again obeys a variant of the 't Hooft equation. The linear approximation to the boson/fermion coupled case brings an additonal bound state equation for mesons, which consists of one fermion and one boson, again of the same form as the well-known 't Hooft equation.Comment: 27 pages, no figure

Visual-cortical enhancement by acoustic distractors: The effects of endogenous spatial attention and visual working memory load

Past work has shown that when a peripheral sound captures our attention, it activates the contralateral visual cortex as revealed by an event-related potential component labelled the auditory-evoked contralateral occipital positivity (ACOP). This cross-modal activation of the visual cortex has been observed even when the sounds were not relevant to the ongoing task (visual or auditory), suggesting that peripheral sounds automatically activate the visual cortex. However, it is unclear whether top-down factors such as visual working memory (VWM) load and endogenous attention, which modulate the impact of task-irrelevant information, may modulate this spatially-specific component. Here, we asked participants to perform a lateralized VWM task (change detection), whose performance is supported by both endogenous spatial attention and VWM storage. A peripheral sound that was unrelated to the ongoing task was delivered during the retention interval. The amplitude of sound-elicited ACOP was analyzed as a function of the spatial correspondence with the cued hemifield, and of the memory array set-size. The typical ACOP modulation was observed over parieto-occipital sites in the 280–500 ms time window after sound onset. Its amplitude was not affected by VWM load but was modulated when the location of the sound did not correspond to the hemifield (right or left) that was cued for the change detection task. Our results suggest that sound-elicited activation of visual cortices, as reflected in the ACOP modulation, is unaffected by visual working memory load. However, endogenous spatial attention affects the ACOP, challenging the hypothesis that it reflects an automatic process

Do Humans and Deep Convolutional Neural Networks Use Visual Information Similarly for the Categorization of Natural Scenes?

The investigation of visual categorization has recently been aided by the introduction of deep convolutional neural networks (CNNs), which achieve unprecedented accuracy in picture classification after extensive training. Even if the architecture of CNNs is inspired by the organization of the visual brain, the similarity between CNN and human visual processing remains unclear. Here, we investigated this issue by engaging humans and CNNs in a two-class visual categorization task. To this end, pictures containing animals or vehicles were modified to contain only low/high spatial frequency (HSF) information, or were scrambled in the phase of the spatial frequency spectrum. For all types of degradation, accuracy increased as degradation was reduced for both humans and CNNs; however, the thresholds for accurate categorization varied between humans and CNNs. More remarkable differences were observed for HSF information compared to the other two types of degradation, both in terms of overall accuracy and image-level agreement between humans and CNNs. The difficulty with which the CNNs were shown to categorize high-passed natural scenes was reduced by picture whitening, a procedure which is inspired by how visual systems process natural images. The results are discussed concerning the adaptation to regularities in the visual environment (scene statistics); if the visual characteristics of the environment are not learned by CNNs, their visual categorization may depend only on a subset of the visual information on which humans rely, for example, on low spatial frequency information

Genetic effects of static magnetic fields. Body size increase and lethal mutations induced in populations of Drosophila melanogaster after chronic exposure

International audienc

Evaluation of the single jet flow rate for a multi-hole GDI nozzle

Fuel injectors featuring differentiated hole-to-hole dimensions improve the fuel distribution in the cylinder ensuring a more efficient and cleaner combustion for GDI (Gasoline Direct Injection) engines. A proper diagnostic system able to detect the actual fuel flow rate exiting each hole of a GDI nozzle is requested in order to optimize the matching between the spray and the combustion chamber. Measuring the spray impact force of a single plume allows the detection of the momentum flux exiting the single hole and, under appropriate hypotheses, the evaluation of the corresponding mass flow rate time-profile. In this paper two methodologies for the hole-specific flow rate evaluation, both based on the spray momentum technique, were applied to two different GDI nozzles, one featuring equal hole dimensions and one with two larger holes. Three different energizing times at 100 bar of fuel pressure were tested in order to cover a wide range of operating conditions. The results were validated in terms of injected mass by means of a proper device able to collect and weigh the fuel injected by each single nozzle hole, and in terms of mass flow rate using a Zeuch-method flow meter as reference. Both the proposed methodologies showed an excellent accuracy in the fuel amount detection with percentage error lower than 5% for standard energizing times and lower than 10% for very short injections working in ballistic conditions. The mass flow rate time-profile proved a good accuracy in the detection of the start and end of injection and the static flow rate level

Stable Fermion Bag Solitons in the Massive Gross-Neveu Model: Inverse Scattering Analysis

Formation of fermion bag solitons is an important paradigm in the theory of hadron structure. We study this phenomenon non-perturbatively in the 1+1 dimensional Massive Gross-Neveu model, in the large $N$ limit. We find, applying inverse scattering techniques, that the extremal static bag configurations are reflectionless, as in the massless Gross-Neveu model. This adds to existing results of variational calculations, which used reflectionless bag profiles as trial configurations. Only reflectionless trial configurations which support a single pair of charge-conjugate bound states of the associated Dirac equation were used in those calculations, whereas the results in the present paper hold for bag configurations which support an arbitrary number of such pairs. We compute the masses of these multi-bound state solitons, and prove that only bag configurations which bear a single pair of bound states are stable. Each one of these configurations gives rise to an O(2N) antisymmetric tensor multiplet of soliton states, as in the massless Gross-Neveu model.Comment: 10 pages, revtex, no figures; v2: typos corrected, references added; v3: version accepted for publication in the PRD. referencess added. Some minor clarifications added at the beginning of section