Специфика стратегии распределительной политики предприятий промышленности строительных материалов

Сужение основных регионов сбыта отечественных предприятий промышленности строительных материалов обусловило необходимость разработки и применения целевых маркетинговых стратегий, максимально учитывающих специфику отрасли рынка и акцентирующих финансовые и трудовые усилия в приоритетном адаптивном векторе. Все это вызывает необходимость активизировать усилия маркетологов в исследовании специфики комплекса промышленного маркетинга (КПМ) с последующей расстановкой приоритетов составляющих комплекса при стратегическом планировании. Применение авторской методики детерминирования приоритетных элементов КПМ посредством факторного, дискриминантного и кластерного анализа выявило однозначный приоритет распределительной политики как основного фактора формирования стратегической конкурентоспособности предприятия. Это обуславливает тот факт, что отечественным производителям необходимо активнее отстаивать свою позицию в вопросах реализации стратегии сезонного сбыта. Соответственно необходимо развивать соответствующую инфраструктуру, обеспечивающую сохранность продукции, а параллельно заключать долгосрочные годовые контракты и искать формы оптимального обоюдовыгодного разделения рисков со своими контрагентами.Shrinkage of major market regions of domestic constructional material producing enterprises caused the necessity of developing and applying goal-oriented marketing strategies maximally taking into account the specificity of market sectors and concentrating financial and labour efforts in a priority adaptive vector. All this necessitates intensification of marketing specialist work on the study of the specificity of industrial marketing complex with the follow­ing determination of the priorities of the complex components during strategic planning. Ap­plying the author’s methods of determining priority components of the industrial marketing complex by factor, discriminant and cluster analysis revealed definite priority of distribution policy as the major factor of the formation of strategic competitiveness of an enterprise. This preconditions the fact that for domestic manufacturers it is necessary to more actively advocate their position in implementing the strategy of seasonal market. Accordingly it is necessary to develop an appropriate infrastructure ensuring product safekeeping and at the same time con­clude long-term year-long contracts and also search for the forms of optimum mutually benefi­cial sharing risks with the contractors

Global engineering services: Shedding light on network capabilities

This paper addresses the operations challenges of effectively managing professional services on a global scale. The specific context for the study is professional engineering services and particularly those that are delivered globally - global engineering services (GES). Estimates suggest that the market for GES was around US$930 billion in 2012, rising to US$1.4 trillion by 2020 (ISG, 2013). Yet this influential sector receives scant attention in the operations management literature. The paper draws on six case studies to explore the operations management challenges of delivering GES. In doing so the paper introduces the concept of network capabilities for GES, highlighting the centrality that: (i) network resources - accessing and deploying dispersed resources, (ii) network coordination - coordinating and integrating network activities, and (iii) network learning - collective learning and knowledge management, all play in enabling the successful operational management of GES.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jom.2016.03.00

Dissecting Motor Neuron Disease With Drosophila melanogaster

Motor Neuron Disease (MND) typically affects patients during the later stages of life, and thus, MND is having an increasingly devastating impact on diagnosed individuals, their families and society. The umbrella term MND refers to diseases which cause the progressive loss of upper and/or lower motor neurons and a subsequent decrease in motor ability such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). The study of these diseases is complex and has recently involved the use of genome-wide association studies (GWAS). However, in the case of MND, it has been difficult to identify the complex genetics involved in subtypes, and functional investigation of new candidate disease genes is warranted. Drosophila is a powerful model for addressing these complex diseases. The UAS/Gal4/Gal80 system allows for the upregulation of Drosophila genes, the “knockdown” of genes and the ectopic expression of human genes or mutations in a tissue-specific manner; often resulting in Drosophila models which exhibit typical MND disease pathologies. These can then be further interrogated to identify disease-modifying genes or mutations and disease pathways. This review will discuss two common MNDs and the current Drosophila models which are being used to research their genetic basis and the different pathologies of MND

A fruit fly model for studying paclitaxel-induced peripheral neuropathy and hyperalgesia [version 2; referees: 2 approved, 1 approved with reservations]

Background: Paclitaxel-induced peripheral neuropathy is a common and limiting side effect of an approved and effective chemotherapeutic agent. The cause of this nociception is still unknown. Methods: To uncover the mechanism involved in paclitaxel-induced pain, we developed a Drosophila thermal nociceptive model to show the effects of paclitaxel exposure on third instar larvae. Results: We found that paclitaxel increases heat nociception in a dose-dependent manner, and at the highest doses also obstructs dendritic repulsion cues. Conclusions: Our simple system can be applied to identify regulators of chemotherapy-induced pain and may help to eliminate pain-related side-effects of chemotherapy

Molecular dissection of box jellyfish venom cytotoxicity highlights an effective venom antidote

The box jellyfish Chironex fleckeri is extremely venomous, and envenoming causes tissue necrosis, extreme pain and death within minutes after severe exposure. Despite rapid and potent venom action, basic mechanistic insight is lacking. Here we perform molecular dissection of a jellyfish venom-induced cell death pathway by screening for host components required for venom exposure-induced cell death using genome-scale lenti-CRISPR mutagenesis. We identify the peripheral membrane protein ATP2B1, a calcium transporting ATPase, as one host factor required for venom cytotoxicity. Targeting ATP2B1 prevents venom action and confers long lasting protection. Informatics analysis of host genes required for venom cytotoxicity reveal pathways not previously implicated in cell death. We also discover a venom antidote that functions up to 15 minutes after exposure and suppresses tissue necrosis and pain in mice. These results highlight the power of whole genome CRISPR screening to investigate venom mechanisms of action and to rapidly identify new medicines

Application of single molecule technology to rapidly map long DNA and study the conformation of stretched DNA

Herein we describe the first application of direct linear analysis (DLA) to the mapping of a bacterial artificial chromosome (BAC), specifically the 185.1 kb-long BAC 12M9. DLA is a single molecule mapping technology, based on microfluidic elongation and interrogation of individual DNA molecules, sequence-specifically tagged with bisPNAs. A DNA map with S/N ratio sufficiently high to detect all major binding sites was obtained using only 200 molecule traces. A new method was developed to extract an oriented map from an averaged map that included a mixture of head-first and tail-first DNA traces. In addition, we applied DLA to study the conformation and tagging of highly stretched DNA. Optimal conditions for promoting sequence-specific binding of bisPNA to an 8 bp target site were elucidated using DLA, which proved superior to electromobility shift assays. DLA was highly reproducible with a hybridized tag position localized with an accuracy of ±0.7 µm or ±2.1 kb demonstrating its utility for rapid mapping of large DNA at the single molecule level. Within this accuracy, DNA molecules, stretched to at least 85% of their contour length, were stretched uniformly, so that the map expressed in relative coordinates, was the same regardless of the molecule extension

Tubulin Polymerization Promoting Protein, Ringmaker, and MAP1B Homolog Futsch Coordinate Microtubule Organization and Synaptic Growth

Drosophila Ringmaker (Ringer) is homologous to the human Tubulin Polymerization Promoting Proteins (TPPPs) that are implicated in the stabilization and bundling of microtubules (MTs) that are particularly important for neurons and are also implicated in synaptic organization and plasticity. No in vivo functional data exist that have addressed the role of TPPP in synapse organization in any system. Here, we present the phenotypic and functional characterization of ringer mutants during Drosophila larval neuromuscular junction (NMJ) synaptic development. ringer mutants show reduced synaptic growth and transmission and display phenotypic similarities and genetic interactions with the Drosophila homolog of vertebrate Microtubule Associated Protein (MAP)1B, futsch. Immunohistochemical and biochemical analyses show that individual and combined loss of Ringer and Futsch cause a significant reduction in MT loops at the NMJs and reduced acetylated-tubulin levels. Presynaptic over-expression of Ringer and Futsch causes elevated levels of acetylated-tubulin and significant increase in NMJ MT loops. These results indicate that Ringer and Futsch regulate synaptic MT organization in addition to synaptic growth. Together our findings may inform studies on the close mammalian homolog, TPPP, and provide insights into the role of MTs and associated proteins in synapse growth and organization

The Genetics of Neuropathic Pain from Model Organisms to Clinical Application.

Neuropathic pain (NeuP) arises due to injury of the somatosensory nervous system and is both common and disabling, rendering an urgent need for non-addictive, effective new therapies. Given the high evolutionary conservation of pain, investigative approaches from Drosophila mutagenesis to human Mendelian genetics have aided our understanding of the maladaptive plasticity underlying NeuP. Successes include the identification of ion channel variants causing hyper-excitability and the importance of neuro-immune signaling. Recent developments encompass improved sensory phenotyping in animal models and patients, brain imaging, and electrophysiology-based pain biomarkers, the collection of large well-phenotyped population cohorts, neurons derived from patient stem cells, and high-precision CRISPR generated genetic editing. We will discuss how to harness these resources to understand the pathophysiological drivers of NeuP, define its relationship with comorbidities such as anxiety, depression, and sleep disorders, and explore how to apply these findings to the prediction, diagnosis, and treatment of NeuP in the clinic

Innate Immune Cell Recovery Is Positively Regulated by NLRP12 during Emergency Hematopoiesis

With enhanced concerns of terrorist attacks, dual exposure to radiation and thermal combined injury (RCI) has become a real threat with devastating immunosuppression. NLRP12, a member of the NOD-like receptor family, is expressed in myeloid and bone marrow cells and has been implicated as a checkpoint regulator of inflammatory cytokines as well as an inflammasome activator. We show that NLRP12 has a profound impact on hematopoietic recovery during RCI by serving as a checkpoint of TNF signaling and preventing hematopoietic apoptosis. Using a mouse model of RCI, increased NLRP12 expression was detected in target tissues. Nlrp12−/− mice exhibited significantly greater mortality, inability to fight bacterial infection, heightened levels of pro-inflammatory cytokines, overt granulocyte/monocyte progenitor cell apoptosis and failure to reconstitute peripheral myeloid populations. Anti-TNF antibody administration improved peripheral immune recovery. These data suggest that NLRP12 is essential for survival after RCI by regulating myelopoiesis and immune reconstitution