Integration of formal fault analysis in ASSERT: Case studies and lessons learnt

International audienceThe ASSERT European Integrated Project (Automated proof-based System and Software Engineering for Real-Time systems; EC FP6, IST-004033) has investigated, elaborated and experimented advanced methods based on the AltaRica language and support tool OCAS for architecture and fault approach propagation description analysis, and integrated in the complete ASSERT process. The paper describes lessons learnt from three case studies: safety critical spacecraft, autonomous deep exploration spacecraft, and civil aircraft

Алгоритм и математическая модель геометрического позиционирования асферического составного зеркала

In recent years, the largest terrestrial and orbital telescopes operating in a wide spectral range of wavelengths use the technology of segmented composite elements to form the main mirror. This approach allows: to expand the spectral operating range from 0.2 to 11.0 μm and to increase the diameter of the entrance pupil of the receiving optical system, while maintaining the optimal value of the exponent mS– mass per unit area.Two variants of adjusting the position of mirror segments are considered when forming an aspherical surface of the second order, with respect to the base surface of the nearest sphere, including geometrical and opto-technical positioning.The purpose of the research was to develop an algorithm for solving the problem of geometric positioning of hexagonal segments of a mirror telescope, constructing an optimal circuit for traversing elements when aligning to the nearest radius to an aspherical surface, and also to program the output calculation parameters to verify the adequacy of the results obtained.Various methods for forming arrays from regular hexagonal segments with equal air gaps between them are considered. The variant of construction of arrays through concentric rings of an equal step is offered.A sequential three-step method for distributing mosaic segments is presented when performing calculations for aligning the aspherical surface: multipath linear; multipath point; block trapezoidal.In the course of mathematical modeling an algorithm was developed to solve the problem of geometric positioning of flat hexagonal segments of a mirror telescope. In the Python programming language, program loops are designed to form the data array necessary to construct a specular reflective surface of a given aperture. In the software package Zemax, the convergence of optical beams from flat hexagonal elements to the central region of the aspherical surface is verified. В последние годы крупнейшие наземные и орбитальные телескопы, работающие в широком спектральном диапазоне длин волн, при формировании главного зеркала используют технологию сегментированных составных элементов. Такой подход позволяет: расширить спектральный рабочий диапазон от 0,2 до 11,0 мкм и увеличить диаметр входного зрачка приемной оптической системы, при сохранении оптимального значения показателя mS – масса на единицу площади. Цель исследований заключалась в разработке алгоритма для решения задачи геометрического позиционирования гексагональных сегментов зеркального телескопа, построения оптимальной схемы «обхода» элементов при юстировке на ближайший радиус к асферической поверхности, а также программной апробации выходных расчетных параметров с целью проверки адекватности полученных результатов.Рассмотрены два варианта юстировки положения зеркальных сегментов при формировании асферической поверхности второго порядка, относительно базовой поверхности ближайшей сферы, включающие геометрическое и оптотехническое позиционирование.Рассмотрены различные методики формирования массивов из регулярных шестиугольных сегментов с равными воздушными промежутками между ними. Предложен вариант построения массивов через концентрические кольца равного шага.Представлена последовательная трехступенчатая методика распределения сегментов мозаики при выполнении расчетов по юстировке асферической поверхности: многолучевая линейная; многолучевая точечная; блочная трапецеидальная.В ходе проведения математического моделирования разработан алгоритм для решения задачи геометрического позиционирования плоских гексагональных сегментов зеркального телескопа. На языке программирования Python составлены циклы программы для формирования массива данных необходимых для построения зеркальной отражающей поверхности заданной апертуры. В программном пакете Zemax выполнена проверка сходимости оптических лучей от плоских гексагональных элементов в центральную область асферической поверхности

Median raphe region stimulation alone generates remote, but not recent fear memory traces

The median raphe region (MRR) is believed to control the fear circuitry indirectly, by influencing the encoding and retrieval of fear memories by amygdala, hippocampus and prefrontal cortex. Here we show that in addition to this established role, MRR stimulation may alone elicit the emergence of remote but not recent fear memories. We substituted electric shocks with optic stimulation of MRR in C57BL/6N male mice in an optogenetic conditioning paradigm and found that stimulations produced agitation, but not fear, during the conditioning trial. Contextual fear, reflected by freezing was not present the next day, but appeared after a 7 days incubation. The optogenetic silencing of MRR during electric shocks ameliorated conditioned fear also seven, but not one day after conditioning. The optogenetic stimulation patterns (50Hz theta burst and 20Hz) used in our tests elicited serotonin release in vitro and lead to activation primarily in the periaqueductal gray examined by c-Fos immunohistochemistry. Earlier studies demonstrated that fear can be induced acutely by stimulation of several subcortical centers, which, however, do not generate persistent fear memories. Here we show that the MRR also elicits fear, but this develops slowly over time, likely by plastic changes induced by the area and its connections. These findings assign a specific role to the MRR in fear learning. Particularly, we suggest that this area is responsible for the durable sensitization of fear circuits towards aversive contexts, and by this, it contributes to the persistence of fear memories. This suggests the existence a bottom-up control of fear circuits by the MRR, which complements the top-down control exerted by the medial prefrontal cortex

Sensory Stimulation-Dependent Plasticity in the Cerebellar Cortex of Alert Mice

In vitro studies have supported the occurrence of cerebellar long-term depression (LTD), an interaction between the parallel fibers and Purkinje cells (PCs) that requires the combined activation of the parallel and climbing fibers. To demonstrate the existence of LTD in alert animals, we investigated the plasticity of local field potentials (LFPs) evoked by electrical stimulation of the whisker pad. The recorded LFP showed two major negative waves corresponding to trigeminal (broken into the N2 and N3 components) and cortical responses. PC unitary extracellular recording showed that N2 and N3 occurred concurrently with PC evoked simple spikes, followed by an evoked complex spike. Polarity inversion of the N3 component at the PC level and N3 amplitude reduction after electrical stimulation of the parallel fiber volley applied on the surface of the cerebellum 2 ms earlier strongly suggest that N3 was related to the parallel fiber–PC synapse activity. LFP measurements elicited by single whisker pad stimulus were performed before and after trains of electrical stimuli given at a frequency of 8 Hz for 10 min. We demonstrated that during this later situation, the stimulation of the PC by parallel and climbing fibers was reinforced. After 8-Hz stimulation, we observed long-term modifications (lasting at least 30 min) characterized by a specific decrease of the N3 amplitude accompanied by an increase of the N2 and N3 latency peaks. These plastic modifications indicated the existence of cerebellar LTD in alert animals involving both timing and synaptic modulations. These results corroborate the idea that LTD may underlie basic physiological functions related to calcium-dependent synaptic plasticity in the cerebellum

Deleterious GRM1 Mutations in Schizophrenia

We analysed a phenotypically well-characterised sample of 450 schziophrenia patients and 605 controls for rare non-synonymous single nucleotide polymorphisms (nsSNPs) in the GRM1 gene, their functional effects and family segregation. GRM1 encodes the metabotropic glutamate receptor 1 (mGluR1), whose documented role as a modulator of neuronal signalling and synaptic plasticity makes it a plausible schizophrenia candidate. In a recent study, this gene was shown to harbour a cluster of deleterious nsSNPs within a functionally important domain of the receptor, in patients with schizophrenia and bipolar disorder. Our Sanger sequencing of the GRM1 coding regions detected equal numbers of nsSNPs in cases and controls, however the two groups differed in terms of the potential effects of the variants on receptor function: 6/6 case-specific and only 1/6 control-specific nsSNPs were predicted to be deleterious. Our in-vitro experimental follow-up of the case-specific mutants showed that 4/6 led to significantly reduced inositol phosphate production, indicating impaired function of the major mGluR1signalling pathway; 1/6 had reduced cell membrane expression; inconclusive results were obtained in 1/6. Family segregation analysis indicated that these deleterious nsSNPs were inherited. Interestingly, four of the families were affected by multiple neuropsychiatric conditions, not limited to schizophrenia, and the mutations were detected in relatives with schizophrenia, depression and anxiety, drug and alcohol dependence, and epilepsy. Our findings suggest a possible mGluR1 contribution to diverse psychiatric conditions, supporting the modulatory role of the receptor in such conditions as proposed previously on the basis of in vitro experiments and animal studies

Determination of group I metabotropic glutamate receptor subtypes involved in the frequency of epileptiform activity in vitro using mGluR1 and mGluR5 mutant mice.

In mouse hippocampal slices, bicuculline elicited spontaneous epileptiform bursts with a duration of 200-300 ms and with a frequency of five to six events per minute. Application of group I metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG) increased the burst frequency up to 300% at concentrations of 50 to 100 microM, while it decreased the burst duration below 100 ms. In slices of subtype I mGluR1 or subtype I mGluR5 knockout mice, bicuculline elicited spontaneous epileptiform bursts with similar duration and frequency as those measured in wild-type mice but without the previous effects seen following application of DHPG at concentrations up to 100 microM. Likewise, in slices of wild-type mice, preincubation with mGluR1 antagonist, 1-aminoindan-1,5-dicarboxylic acid (AIDA) or mGluR5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocked in both cases completely the increase in frequency following DHPG application. These findings suggest an interactive mechanism between mGluR1 and mGluR5 receptors in the modulation of epileptiform bursting activity by DHPG that could indicate a common intracellular signaling mechanism or possibly direct interaction between these two receptors