Удосконалення структури підприємства і системи управління щодо реалізації стратегії розвитку

Обґрунтовано два підходи до взаємозв’язків виробничо-економічних функцій підприємства, маркетингових досліджень і реалізації вироблюваної продукції в розрізі прогнозного проекту стратегічного розвитку. Сформульовано три підходи маркетингової трансформації процесів управління прогнозами стратегічного розвитку на основі реалізації продукції, що випускається. Доведено, що синхронизатором багатьох індивідуальних конфліктів стає концентрація зусиль щодо переміщення центру уваги із виробництва, де він до цього часу знаходився, у сферу маркетингу і фінансів, що дозволяє уникнути економічної кризової ситуації.Обоснованы два подхода к взаимосвязям производственно-экономических функций предприятия, маркетинговых исследований и реализации выпускаемой продукции в разрезе прогнозного проекта стратегического развития. Сформулированы три подхода маркетинговой трансформации процессов управления прогнозами стратегического развития на основе реализации выпускаемой продукции. Доказано, что синхронизатором многих индивидуальных конфликтов становится концентрация усилий по перемещению центра внимания с производства, где он до этого времени находился, в сферу маркетинга и финансов, что позволяет избежать экономической кризисной ситуации.Two approaches are justified interdependence of production and economic functions of the enterprise, market research and sales of products in the context of the forecast project development strategies. Disclosed three approaches marketing transformation processes management outlook strategic development through the implementation of our products. Proved that the synchronizer effort of moving the center of attention of industry where he was before that time, the scope of marketing and finance, avoiding economic crisis

Involvement of PPAR\u3b3 in the anticonvulsant activity of EP-80317, a ghrelin receptor antagonist

Ghrelin, des-acyl ghrelin and other related peptides possess anticonvulsant activities. Although ghrelin and cognate peptides were shown to physiologically regulate only the ghrelin receptor, some of them were pharmacologically proved to activate the peroxisome proliferator-activated receptor gamma (PPAR\u3b3) through stimulation of the scavenger receptor CD36 in macrophages. In our study, we challenged the hypothesis that PPAR\u3b3 could be involved in the anticonvulsant effects of EP-80317, a ghrelin receptor antagonist. For this purpose, we used the PPAR\u3b3 antagonist GW9662 to evaluate the modulation of EP-80317 anticonvulsant properties in two different models. Firstly, the anticonvulsant effects of EP-80317 were studied in rats treated with pilocarpine to induce status epilepticus (SE). Secondly, the anticonvulsant activity of EP-80317 was ascertained in the repeated 6-Hz corneal stimulation model in mice. Behavioral and video electrocorticographic (ECoG) analyses were performed in both models. We also characterized levels of immunoreactivity for PPAR\u3b3 in the hippocampus of 6-Hz corneally stimulated mice. EP-80317 predictably antagonized seizures in both models. Pre-treatment with GW9662 counteracted almost all EP-80317 effects both in mice and rats. Only the effects of EP-80317 on power spectra of ECoGs recorded during repeated 6-Hz corneal stimulation were practically unaffected by GW9662 administration. Moreover, GW9662 alone produced a decrease in the latency of tonic-clonic seizures and accelerated the onset of SE in rats. Finally, in the hippocampus of mice treated with EP-80317 we found increased levels of PPAR\u3b3 immunoreactivity. Overall, these results support the hypothesis that PPAR\u3b3 is able to modulate seizures and mediates the anticonvulsant effects of EP-80317

Validation of a new automatic smoking machine to study the effects of cigarette smoke in newborn lambs

The aim of this study was to describe the characteristics and validate the use of a new, custom-built automatic smoking machine (ASM), primarily designed to study the effects of an environmental tobacco smoke surrogate (ETS surrogate) exposure in animals of various sizes, including large animals. The equipment includes a programmable ASM coupled to a vented whole body chamber, where animals can be exposed to both mainstream and sidestream smoke. The user-friendly interface allows for full programming of puff volume (1-60 mL), time interval between two puffs (1-60 s) and between two cigarettes (1-60 min). Eight newborn lambs were exposed to either 10 (4 lambs, C10 group) or 20 (4 lambs, C20 group) cigarettes, 8 h per day for 15 days. Four additional control, lambs were exposed to air (C0 group). Weight gain was identical in all three groups of lambs. Urinary cotinine/creatinine ratio increased with the number of cigarettes smoked (C0: 11 ± 7 ng/mg; C10: 961 ± 539 ng/mg; C20: 1821 ± 312 ng/mg), with levels in the C10 and C20 groups in keeping with values published in infants exposed to ETS. Overall, results show that our new ASM is especially well suited for ETS surrogate exposure in non-restrained, non-anaesthetized large animals such as sheep

The High-Resolution Imaging (HRI) Portable Array: A Seismic (and Internet) Network Dedicated to Kilometric-scale Seismic Imaging

International audienceWe have developed a network of portable seismic stations dedicated to the high resolution imaging of geological, potentially hazardous, targets. These targets - volcanoes, fault zones, landslide areas - are characterized by strong medium heterogeneities, rugged topography, rough field conditions, and require dedicated equipment in order to maximize the number of recording points. This new network is designed to a) operate experiments with a limited size crew, b) run on low power for possible use in remote areas and difficult conditions, c) record both active and passive seismic sources. The actual network consists of 30 clusters of 9 channels digital acquisition system (DAS), equipped with 6 vertical sensors plus 1 three-component sensor. Each DAS uses Ethernet and 802.11 (WiFi) connections that permit to a single operator to remotely control the entire network. We present the main characteristics of this new portable array, describe the calibration method developed for our sensors and show examples of configuration and recordings for two recent experiments

Imaging heterogeneity of peptide delivery and binding in solid tumors using SPECT imaging and MRI

Background: As model system, a solid-tumor patient-derived xenograft (PDX) model characterized by high peptide receptor expression and histological tissue homogeneity was used to study radiopeptide targeting. In this solid-tumor model, high tumor uptake of targeting peptides was expected. However, in vivo SPECT images showed substantial heterogeneous radioactivity accumulation despite homogenous receptor distribution in the tumor xenografts as assessed by in vitro autoradiography. We hypothesized that delivery of peptide to the tumor cells is dictated by adequate local tumor perfusion. To study this relationship, sequential SPECT/CT and MRI were performed to assess the role of vascular functionality in radiopeptide accumulation. Methods: High-resolution SPECT and dynamic contrast-enhanced (DCE)-MRI were acquired in six mice bearing PC295 PDX tumors expressing the gastrin-releasing peptide (GRP) receptor. Two hours prior to SPECT imaging, animals received 25 MBq 111In(DOTA-(βAla)2-JMV594) (25 pmol). Images were acquired using multipinhole SPECT/CT. Directly after SPECT imaging, MR images were acquired on a 7.0-T dedicated animal scanner. DCE-MR images were quantified using semi-quantitative and quantitative models. The DCE-MR and SPECT images were spatially aligned to compute the correlations between radioactivity and DCE-MRI-derived parameters over the tumor. Results: Whereas histology, in vitro autoradiography, and multiple-weighted MRI scans all showed homogenous tissue characteristics, both SPECT and DCE-MRI showed heterogeneous distribution patterns throughout the tumor. The average Spearman’s correlation coefficient between SPECT and DCE-MRI ranged from 0.57 to 0.63 for the “exchange-related” DCE-MRI perfusion parameters. Conclusions: A positive correlation was shown between exchange-related DCE-MRI perfusion parameters and the amount of radioactivity accumulated as measured by SPECT, demonstrating that vascular function was an important aspect of radiopeptide distribution in solid tumors. The combined use of SPECT and MRI added crucial information on the perfusion efficiency versus radiopeptide upt

Squalamine: An Appropriate Strategy against the Emergence of Multidrug Resistant Gram-Negative Bacteria?

We reported that squalamine is a membrane-active molecule that targets the membrane integrity as demonstrated by the ATP release and dye entry. In this context, its activity may depend on the membrane lipid composition. This molecule shows a preserved activity against bacterial pathogens presenting a noticeable multi-resistance phenotype against antibiotics such as polymyxin B. In this context and because of its structure, action and its relative insensitivity to efflux resistance mechanisms, we have demonstrated that squalamine appears as an alternate way to combat MDR pathogens and by pass the gap regarding the failure of new active antibacterial molecules

Storage of Correlated Patterns in Standard and Bistable Purkinje Cell Models

The cerebellum has long been considered to undergo supervised learning, with climbing fibers acting as a ‘teaching’ or ‘error’ signal. Purkinje cells (PCs), the sole output of the cerebellar cortex, have been considered as analogs of perceptrons storing input/output associations. In support of this hypothesis, a recent study found that the distribution of synaptic weights of a perceptron at maximal capacity is in striking agreement with experimental data in adult rats. However, the calculation was performed using random uncorrelated inputs and outputs. This is a clearly unrealistic assumption since sensory inputs and motor outputs carry a substantial degree of temporal correlations. In this paper, we consider a binary output neuron with a large number of inputs, which is required to store associations between temporally correlated sequences of binary inputs and outputs, modelled as Markov chains. Storage capacity is found to increase with both input and output correlations, and diverges in the limit where both go to unity. We also investigate the capacity of a bistable output unit, since PCs have been shown to be bistable in some experimental conditions. Bistability is shown to enhance storage capacity whenever the output correlation is stronger than the input correlation. Distribution of synaptic weights at maximal capacity is shown to be independent on correlations, and is also unaffected by the presence of bistability

Rapid Detection of Carbapenem Resistance in Acinetobacter baumannii Using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry

Rapid detection of carbapenem-resistant Acinetobacter baumannii strains is critical and will benefit patient care by optimizing antibiotic therapies and preventing outbreaks. Herein we describe the development and successful application of a mass spectrometry profile generated by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) that utilized the imipenem antibiotic for the detection of carbapenem resistance in a large series of A. baumannii clinical isolates from France and Algeria. A total of 106 A. baumannii strains including 63 well-characterized carbapenemase-producing and 43 non-carbapenemase-producing strains, as well as 43 control strains (7 carbapenem-resistant and 36 carbapenem-sensitive strains) were studied. After an incubation of bacteria with imipenem for up to 4 h, the mixture was centrifuged and the supernatant analyzed by MALDI-TOF MS. The presence and absence of peaks representing imipenem and its natural metabolite was analyzed. The result was interpreted as positive for carbapenemase production if the specific peak for imipenem at 300.0 m/z disappeared during the incubation time and if the peak of the natural metabolite at 254.0 m/z increased as measured by the area under the curves leading to a ratio between the peak for imipenem and its metabolite being <0.5. This assay, which was applied to the large series of A. baumannii clinical isolates, showed a sensitivity of 100.0% and a specificity of 100.0%. Our study is the first to demonstrate that this quick and simple assay can be used as a routine tool as a point-of-care method for the identification of A. baumannii carbapenemase-producers in an effort to prevent outbreaks and the spread of uncontrollable superbugs

Efficient Olfactory Coding in the Pheromone Receptor Neuron of a Moth

The concept of coding efficiency holds that sensory neurons are adapted, through both evolutionary and developmental processes, to the statistical characteristics of their natural stimulus. Encouraged by the successful invocation of this principle to predict how neurons encode natural auditory and visual stimuli, we attempted its application to olfactory neurons. The pheromone receptor neuron of the male moth Antheraea polyphemus, for which quantitative properties of both the natural stimulus and the reception processes are available, was selected. We predicted several characteristics that the pheromone plume should possess under the hypothesis that the receptors perform optimally, i.e., transfer as much information on the stimulus per unit time as possible. Our results demonstrate that the statistical characteristics of the predicted stimulus, e.g., the probability distribution function of the stimulus concentration, the spectral density function of the stimulation course, and the intermittency, are in good agreement with those measured experimentally in the field. These results should stimulate further quantitative studies on the evolutionary adaptation of olfactory nervous systems to odorant plumes and on the plume characteristics that are most informative for the ‘sniffer’. Both aspects are relevant to the design of olfactory sensors for odour-tracking robots

Comparison of proteomic responses as global approach to antibiotic mechanism of action elucidation

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of Bacillus subtilis covering 91 antibiotics and comparator compounds, and a mathematical approach was developed to aid data analysis. Comparison of proteomic responses (CoPR) allows the rapid identification of antibiotics with dual mechanisms of action as shown for atypical tetracyclines. It also aids in generating hypotheses on mechanisms of action as presented for salvarsan (arsphenamine) and the antirheumatic agent auranofin, which is under consideration for repurposing. Proteomic profiling also provides insights into the impact of antibiotics on bacterial physiology through analysis of marker proteins indicative of the impairment of cellular processes and structures. As demonstrated for trans-translation, a promising target not yet exploited clinically, proteomic profiling supports chemical biology approaches to investigating bacterial physiology