Економічний механізм управління ризиками інвестиційних проектів у житловому будівництві

The article reveals some problems of risk management of investment activity of construction companies.The features of construction as a branch of production are defined, which are as follows: the long-term nature of investments in construction, a significant time gap between the moment of making investments and the moment of earning, as well as the risks of uncertainty of innovative activity. Their totality forms an extremely unstable environment for construction companies. The existing risk classifications by the following categories and features are considered: by the nature of economic activity of a construction organization (which in turn is divided into production, investment, innovation, commercial, etc. should separate relevant risks); the degree of controllability of the risks of a construction organization should be divided into unmanaged, hard-managed, well-managed; the source of risk factors should distinguish between the risks of the external and internal environment. The stages of the process of risk management of investment project activity in conditions of environmental uncertainty are presented: analysis of the external and internal environment of the investment project; determining the probability (frequency) of the event; Identifying the extent and magnitude of investment risk; determination of consequences of manifestation of risks (increase in prices of works, losses, increase of duration of construction, etc.); the choice of the necessary methods of minimizing the negative consequences, primarily aimed at reducing financial and other losses.The peculiarities of investment activity in the sphere of construction, the main risks in the implementation of investment projects are considered. There are various approaches to managing the risks of investing in the construction of construction projects. Integrated use or combination of the proposed methods and tools allows to increase the economic security of the implementation of risky investment projects, as well as to achieve and further maintain an acceptable level of risks of the investment activities of the organization.У статті розкриваються деякі проблеми управління ризиками інвестиційної діяльності будівельних компаній.Визначено особливості будівництва як галузі виробництва,  які полягають у наступному: довгостроковий характер інвестицій у будівництво, значний  часовий розрив між моментом здійснення інвестиційних вкладень і моментом отримання доходу, а також ризики невизначеності інноваційної діяльності. Їх сукупність формує вкрай нестабільне середовище функціонування будівельних підприємств. Розглянуто існуючі класифікації ризиків за такими категоріями і ознаками: • за характером господарської діяльності будівельної організації, (що в свою чергу поділяється на виробничу, інвестиційну, інноваційну, комерційну та ін. варто виокремити відповідні ризики); • за ступенем керованості ризики будівельної організації слід поділити на некеровані, важко керовані, добре керовані; • за джерелом виникнення ризикових факторів потрібно розрізняти ризики зовнішнього і внутрішнього середовища. Наведено етапи процесу управління ризиками інвестиційної проектної діяльності в умовах невизначеності навколишнього середовища: аналіз зовнішнього і внутрішнього середовища інвестиційного проекту; визначення імовірності (частоти) виникнення події;  виявлення ступеня та величини інвестиційного ризику; визначення наслідків прояву ризиків (подорожчання робіт, збитків, збільшення тривалості будівництва та ін.); вибір необхідних методів мінімізації негативних наслідків, насамперед спрямованих на зменшення фінансових та інших втрат.Розглядаються особливості інвестиційної діяльності у сфері будівництва, основні ризики при здійсненні інвестиційних проектів. Представлено різні підходи до управління ризиками інвестиційної діяльності  зі створення об’єктів будівництва. Комплексне використання або поєднання запропонованих методів та інструментів дозволяє забезпечити підвищення економічної безпеки реалізації ризикових інвестиційних проектів, а також досягнення і подальше підтримання прийнятного рівня ризиків інвестиційної діяльності організації

Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1

In myelinated axons, K+ channels are concealed under the myelin sheath in the juxtaparanodal region, where they are associated with Caspr2, a member of the neurexin superfamily. Deletion of Caspr2 in mice by gene targeting revealed that it is required to maintain K+ channels at this location. Furthermore, we show that the localization of Caspr2 and clustering of K+ channels at the juxtaparanodal region depends on the presence of TAG-1, an immunoglobulin-like cell adhesion molecule that binds Caspr2. These results demonstrate that Caspr2 and TAG-1 form a scaffold that is necessary to maintain K+ channels at the juxtaparanodal region, suggesting that axon–glia interactions mediated by these proteins allow myelinating glial cells to organize ion channels in the underlying axonal membrane

Protein 4.1B Contributes to the Organization of Peripheral Myelinated Axons

Neurons are characterized by extremely long axons. This exceptional cell shape is likely to depend on multiple factors including interactions between the cytoskeleton and membrane proteins. In many cell types, members of the protein 4.1 family play an important role in tethering the cortical actin-spectrin cytoskeleton to the plasma membrane. Protein 4.1B is localized in myelinated axons, enriched in paranodal and juxtaparanodal regions, and also all along the internodes, but not at nodes of Ranvier where are localized the voltage-dependent sodium channels responsible for action potential propagation. To shed light on the role of protein 4.1B in the general organization of myelinated peripheral axons, we studied 4.1B knockout mice. These mice displayed a mildly impaired gait and motility. Whereas nodes were unaffected, the distribution of Caspr/paranodin, which anchors 4.1B to the membrane, was disorganized in paranodal regions and its levels were decreased. In juxtaparanodes, the enrichment of Caspr2, which also interacts with 4.1B, and of the associated TAG-1 and Kv1.1, was absent in mutant mice, whereas their levels were unaltered. Ultrastructural abnormalities were observed both at paranodes and juxtaparanodes. Axon calibers were slightly diminished in phrenic nerves and preterminal motor axons were dysmorphic in skeletal muscle. βII spectrin enrichment was decreased along the axolemma. Electrophysiological recordings at 3 post-natal weeks showed the occurrence of spontaneous and evoked repetitive activity indicating neuronal hyperexcitability, without change in conduction velocity. Thus, our results show that in myelinated axons 4.1B contributes to the stabilization of membrane proteins at paranodes, to the clustering of juxtaparanodal proteins, and to the regulation of the internodal axon caliber

Діагностичні та лікувальні підходи при ехінококозі печінки

The purpose of the study was to improve the results of surgical treatment for echinococcosis of the liver and the quality of life of operated patients due to the improvement of diagnostic and therapeutic approaches, prevention of postoperative complications and recurrence of the disease. 22 patients were treated for echinococcosis of the liver. The duration of the operation was 2 hours in case of echinococcectomy with atypical resection of the liver, in case of laparoscopic echinococcectomy ‒ 1.2 hours, in case of puncture aspiration injection reaspiration technique ‒ 40 minutes. No fatal cases were observed. Recurrence of the disease was found in 9.1 %. A radical and effective operation is atypical resection of a part of the liver with an echinococcal cyst. Laparoscopic echinococcectomy is an alternative to open atypical resection of a part of the liver with an echinococcal cyst. The main condition for performing puncture aspiration injection reaspiration under ultrasound and X ‒ ray guidance is the absence of cystobiliary fistulae, since instillation of a cyst with a scolicidal solution can be the cause of sclerosing cholangitis. The anti-relapse antiparasitic therapy with albendazole 10‒15 mg/kg body weight twice a day or mebendazole 40‒50 mg/kg body weight three times a day in three 28-day courses with a break of 14 days should be carried out for 3‒6 months in the postoperative period.Метою дослідження було покращити результати хірургічного лікування при ехінококозі печінки та якості життя оперованих хворих за рахунок вдосконалення діагностично‒лікувальних підходів, профілактики післяопераційних ускладнень і рецидиву хвороби. На лікуванні з приводу ехінококозу печінки знаходилось 22 хворих. При ехінококектомії з атиповою резекцією печінки тривалість операції склала 2 години, при лапароскопічній ехінококектомії ‒ 1,2 години, при методиці PAIR ‒ 40 хв. Летальних випадків на спостерігали. Рецидив захворювання виявлено у 9,1 %. Радикальною і ефективною операцією є атипова резекція частини печінки з ехінококовою кістою. Лапароскопічна ехінококектомія є альтернативою відкритій атиповій резекції частини печінки з ехінококовою кістою. Головною умовою виконання puncture aspiration injection reaspiration під УЗ та рентген‒ навігацією є відсутність цистобіліарних нориць, так як інстиляція кісти сколіцидним розчином може бути причиною склерозуючого холангіту. У післяопераційному періоді на протязі 3‒6 місяців слід проводити протирецидивну антипаразитарну терапію альбендазолом по 10‒15 мг/кг ваги двічі на день або мебендазолом по 40‒50 мг/кг ваги тричі на день трьома 28‒ денними курсами з перервою 14 днів

The Tumor Suppressor PRDM5 Regulates Wnt Signaling at Early Stages of Zebrafish Development

PRDM genes are a family of transcriptional regulators that modulate cellular processes such as differentiation, cell growth and apoptosis. Some family members are involved in tissue or organ maturation, and are differentially expressed in specific phases of embryonic development. PRDM5 is a recently identified family member that functions as a transcriptional repressor and behaves as a putative tumor suppressor in different types of cancer. Using gene expression profiling, we found that transcriptional targets of PRDM5 in human U2OS cells include critical genes involved in developmental processes, and specifically in regulating wnt signaling. We therefore assessed PRDM5 function in vivo by performing loss-of-function and gain-of-function experiments in zebrafish embryos. Depletion of prdm5 resulted in impairment of morphogenetic movements during gastrulation and increased the occurrence of the masterblind phenotype in axin+/− embryos, characterized by the loss of eyes and telencephalon. Overexpression of PRDM5 mRNA had opposite effects on the development of anterior neural structures, and resulted in embryos with a shorter body axis due to posterior truncation, a bigger head and abnormal somites. In situ hybridization experiments aimed at analyzing the integrity of wnt pathways during gastrulation at the level of the prechordal plate revealed inhibition of non canonical PCP wnt signaling in embryos overexpressing PRDM5, and over-activation of wnt/β-catenin signaling in embryos lacking Prdm5. Our data demonstrate that PRDM5 regulates the expression of components of both canonical and non canonical wnt pathways and negatively modulates wnt signaling in vivo

Substrate Micropatterning as a New in Vitro Cell Culture System to Study Myelination

Artículo de publicación ISIMyelination is a highly regulated developmental process whereby oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system ensheathe axons with a multilayered concentric membrane. Axonal myelination increases the velocity of nerve impulse propagation. In this work, we present a novel in vitro system for coculturing primary dorsal root ganglia neurons along with myelinating cells on a highly restrictive and micropatterned substrate. In this new coculture system, neurons survive for several weeks, extending long axons on defined Matrigel tracks. On these axons, myelinating cells can achieve robust myelination, as demonstrated by the distribution of compact myelin and nodal markers. Under these conditions, neurites and associated myelinating cells are easily accessible for studies on the mechanisms of myelin formation and on the effects of axonal damage on the myelin sheath.Regenerative Medicine and Nanomedicine Initiative of the Canadian Institutes of Health Research (CIHR) RMF-7028 FONDECYT 1080252 CIHR Ministry of Industry of Canada Rio Tinto Alcan Molson Foundatio

A Claudin-9–Based Ion Permeability Barrier Is Essential for Hearing

Hereditary hearing loss is one of the most common birth defects, yet the majority of genes required for audition is thought to remain unidentified. Ethylnitrosourea (ENU)–mutagenesis has been a valuable approach for generating new animal models of deafness and discovering previously unrecognized gene functions. Here we report on the characterization of a new ENU–induced mouse mutant (nmf329) that exhibits recessively inherited deafness. We found a widespread loss of sensory hair cells in the hearing organs of nmf329 mice after the second week of life. Positional cloning revealed that the nmf329 strain carries a missense mutation in the claudin-9 gene, which encodes a tight junction protein with unknown biological function. In an epithelial cell line, heterologous expression of wild-type claudin-9 reduced the paracellular permeability to Na+ and K+, and the nmf329 mutation eliminated this ion barrier function without affecting the plasma membrane localization of claudin-9. In the nmf329 mouse line, the perilymphatic K+ concentration was found to be elevated, suggesting that the cochlear tight junctions were dysfunctional. Furthermore, the hair-cell loss in the claudin-9–defective cochlea was rescued in vitro when the explanted hearing organs were cultured in a low-K+ milieu and in vivo when the endocochlear K+-driving force was diminished by deletion of the pou3f4 gene. Overall, our data indicate that claudin-9 is required for the preservation of sensory cells in the hearing organ because claudin-9–defective tight junctions fail to shield the basolateral side of hair cells from the K+-rich endolymph. In the tight-junction complexes of hair cells, claudin-9 is localized specifically to a subdomain that is underneath more apical tight-junction strands formed by other claudins. Thus, the analysis of claudin-9 mutant mice suggests that even the deeper (subapical) tight-junction strands have biologically important ion barrier function

Verification of genes differentially expressed in neuroblastoma tumours: a study of potential tumour suppressor genes

<p>Abstract</p> <p>Background</p> <p>One of the most striking features of the childhood malignancy neuroblastoma (NB) is its clinical heterogeneity. Although there is a great need for better clinical and biological markers to distinguish between tumours with different severity and to improve treatment, no clear-cut prognostic factors have been found. Also, no major NB tumour suppressor genes have been identified.</p> <p>Methods</p> <p>In this study we performed expression analysis by quantitative real-time PCR (QPCR) on primary NB tumours divided into two groups, of favourable and unfavourable outcome respectively. Candidate genes were selected on basis of lower expression in unfavourable tumour types compared to favourables in our microarray expression analysis. Selected genes were studied in two steps: (1) using TaqMan Low Density Arrays (TLDA) targeting 89 genes on a set of 12 NB tumour samples, and (2) 12 genes were selected from the TLDA analysis for verification using individual TaqMan assays in a new set of 13 NB tumour samples.</p> <p>Results</p> <p>By TLDA analysis, 81 out of 87 genes were found to be significantly differentially expressed between groups, of which 14 have previously been reported as having an altered gene expression in NB. In the second verification round, seven out of 12 transcripts showed significantly lower expression in unfavourable NB tumours, <it>ATBF1</it>, <it>CACNA2D3</it>, <it>CNTNAP2</it>, <it>FUSIP1</it>, <it>GNB1</it>, <it>SLC35E2</it>, and <it>TFAP2B</it>. The gene that showed the highest fold change in the TLDA analysis, <it>POU4F2</it>, was investigated for epigenetic changes (CpG methylation) and mutations in order to explore the cause of the differential expression. Moreover, the fragile site gene <it>CNTNAP2 </it>that showed the largest fold change in verification group 2 was investigated for structural aberrations by copy number analysis. However, the analyses of <it>POU4F2 </it>and <it>CNTNAP2 </it>showed no genetic alterations that could explain a lower expression in unfavourable NB tumours.</p> <p>Conclusion</p> <p>Through two steps of verification, seven transcripts were found to significantly discriminate between favourable and unfavourable NB tumours. Four of the transcripts, <it>CACNA2D3</it>, <it>GNB1</it>, <it>SLC35E2</it>, and <it>TFAP2B</it>, have been observed in previous microarray studies, and are in this study independently verified. Our results suggest these transcripts to be markers of malignancy, which could have a potential usefulness in the clinic.</p

Human Neural Stem Cells Differentiate and Promote Locomotor Recovery in an Early Chronic Spinal coRd Injury NOD-scid Mouse Model

Traumatic spinal cord injury (SCI) results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns) were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+) and CD24(-/lo) population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for intervention