Бизнес-планирование во внешнеэкономической деятельности (ВЭД) предприятия, как инструмент качества корпоративного управления

In vitro models, including the widely used PC12 cell line, can increase insight into cellular and molecular mechanisms underlying neurodegenerative processes. An important determinant for the vulnerability of cells for chemical insults may be the endogenous level of oxidative stress. To test this hypothesis, we induced different degrees of cellular stress in PC12 cells by altering their ROS production using dexamethasone, l-dihydroxyphenylalanine (l-DOPA) and iron. These different PC12 models were subsequently used to investigate whether the degree of cellular stress could increase their susceptibility to environmental pollutants. The characteristics of these stressed PC12 cell subtypes and their vulnerability to the reference pesticide rotenone were investigated using a combination of biochemical (oxidative stress, cell viability, and α-synuclein expression) and functional (fluorescent calcium imaging) assays. Our combined data demonstrate that chemically-induced stress in PC12 cells increases the production of reactive oxygen species (ROS) and alters calcium homeostasis and α-synuclein expression. Moreover, l-DOPA and FeSO4 pre-treated PC12 cells show increased vulnerability to rotenone-induced cytotoxicity. These chemically-stressed cell models may therefore prove valuable to investigate how increased cellular stress influences neurotoxic outcome, for example in case of mixture toxicity

Core Allocations for Cooperation Problems in Vaccination

Vaccination is a very effective measure to fight an outbreak of an infectious disease, but it often suffers from delayed deliveries and limited stockpiles. To use these limited doses of vaccine effectively, health agencies can decide to cooperate and share their doses. In this study, we analyze this type of cooperation. Typically cooperation leads to an increased total return, but cooperation is only plausible when this total return can be distributed in a stable way. This makes cooperation a delicate matter. Using cooperative game theory, we derive theoretical sufficient conditions under which cooperation is plausible (i.e., the core is non-empty) and we show that the doses of vaccine can be traded for a market price in those cases. We perform numerical analyses to generalize these findings and we derive analytical expressions for market prices that can be used in general for distributing the total return. Our results demonstrate that cooperation is most likely to be plausible in case of severe shortages and in case of sufficient supply, with possible mismatches between supply and demand. In those cases, trading doses of vaccine for a market price often results in a core allocation of the total return. We confirm these findings with a case study on the redistribution of influenza vaccines

Hurricane Gustav (2008) Waves and Storm Surge: Hindcast, Synoptic Analysis, and Validation in Southern Louisiana

Hurricane Gustav (2008) made landfall in southern Louisiana on 1 September 2008 with its eye never closer than 75 km to New Orleans, but its waves and storm surge threatened to flood the city. Easterly tropical-storm-strength winds impacted the region east of the Mississippi River for 12-15 h, allowing for early surge to develop up to 3.5 m there and enter the river and the city's navigation canals. During landfall, winds shifted from easterly to southerly, resulting in late surge development and propagation over more than 70 km of marshes on the river's west bank, over more than 40 km of Caernarvon marsh on the east bank, and into Lake Pontchartrain to the north. Wind waves with estimated significant heights of 15 m developed in the deep Gulf of Mexico but were reduced in size once they reached the continental shelf. The barrier islands further dissipated the waves, and locally generated seas existed behind these effective breaking zones. The hardening and innovative deployment of gauges since Hurricane Katrina (2005) resulted in a wealth of measured data for Gustav. A total of 39 wind wave time histories, 362 water level time histories, and 82 high water marks were available to describe the event. Computational models-including a structured-mesh deepwater wave model (WAM) and a nearshore steady-state wave (STWAVE) model, as well as an unstructured-mesh "simulating waves nearshore'' (SWAN) wave model and an advanced circulation (ADCIRC) model-resolve the region with unprecedented levels of detail, with an unstructured mesh spacing of 100-200 m in the wave-breaking zones and 20-50 m in the small-scale channels. Data-assimilated winds were applied using NOAA's Hurricane Research Division Wind Analysis System (H*Wind) and Interactive Objective Kinematic Analysis (IOKA) procedures. Wave and surge computations from these models are validated comprehensively at the measurement locations ranging from the deep Gulf of Mexico and along the coast to the rivers and floodplains of southern Louisiana and are described and quantified within the context of the evolution of the storm

Интеллигенция как субъект и объект манипуляции

Humans are exposed to distinct structural classes of insecticides with different neurotoxic modes of action. Because calcium homeostasis is essential for proper neuronal function and development, we investigated the effects of insecticides from different classes (pyrethroid: (α-)cypermethrin; organophosphate: chlorpyrifos; organochlorine: endosulfan; neonicotinoid: imidacloprid) and mixtures thereof on the intracellular calcium concentration ([Ca(2+)]i). Effects of acute (20 min) exposure to (mixtures of) insecticides on basal and depolarization-evoked [Ca(2+)]i were studied in vitro with Fura-2-loaded PC12 cells and high resolution single-cell fluorescence microscopy. The data demonstrate that cypermethrin, α-cypermethrin, endosulfan, and chlorpyrifos concentration-dependently decreased depolarization-evoked [Ca(2+)]i, with 50% (IC50) at 78nM, 239nM, 250nM, and 899nM, respectively. Additionally, acute exposure to chlorpyrifos or endosulfan (10μM) induced a modest increase in basal [Ca(2+)]i, amounting to 68 ± 8nM and 53 ± 8nM, respectively. Imidacloprid did not disturb basal or depolarization-evoked [Ca(2+)]i at 10μM. Following exposure to binary mixtures, effects on depolarization-evoked [Ca(2+)]i were within the expected effect additivity range, whereas the effect of the tertiary mixture was less than this expected additivity effect range. These results demonstrate that different types of insecticides inhibit depolarization-evoked [Ca(2+)]i in PC12 cells by inhibiting voltage-gated calcium channels (VGCCs) in vitro at concentrations comparable with human occupational exposure levels. Moreover, the effective concentrations in this study are below those for earlier described modes of action. Because inhibition of VGCCs appears to be a common and potentially additive mode of action of several classes of insecticides, this target should be considered in neurotoxicity risk assessment studies

Hindcast and validation of Hurricane Ike (2008) waves, forerunner, and storm surge: HINDCAST AND VALIDATION OF HURRICANE IKE

[1] Hurricane Ike (2008) made landfall near Galveston, Texas, as a moderate intensity storm. Its large wind field in conjunction with the Louisiana‐Texas coastline's broad shelf and large scale concave geometry generated waves and surge that impacted over 1000 km of coastline. Ike's complex and varied wave and surge response physics included: the capture of surge by the protruding Mississippi River Delta; the strong influence of wave radiation stress gradients on the Delta adjacent to the shelf break; the development of strong wind driven shore‐parallel currents and the associated geostrophic setup; the forced early rise of water in coastal bays and lakes facilitating inland surge penetration; the propagation of a free wave along the southern Texas shelf; shore‐normal peak wind‐driven surge; and resonant and reflected long waves across a wide continental shelf. Preexisting and rapidly deployed instrumentation provided the most comprehensive hurricane response data of any previous hurricane. More than 94 wave parameter time histories, 523 water level time histories, and 206 high water marks were collected throughout the Gulf in deep water, along the nearshore, and up to 65 km inland. Ike's highly varied physics were simulated using SWAN + ADCIRC, a tightly coupled wave and circulation model, on SL18TX33, a new unstructured mesh of the Gulf of Mexico, Caribbean Sea, and western Atlantic Ocean with high resolution of the Gulf's coastal floodplain from Alabama to the Texas‐Mexico border. A comprehensive validation was made of the model's ability to capture the varied physics in the system

U.S. IOOS coastal and ocean modeling testbed: Evaluation of tide, wave, and hurricane surge response sensitivities to mesh resolution and friction in the Gulf of Mexico: IOOS TESTBED-RESOLUTION AND FRICTION

This paper investigates model response sensitivities to mesh resolution, topographical details, bottom friction formulations, the interaction of wind waves and circulation, and nonlinear advection on tidal and hurricane surge and wave processes at the basin, shelf, wetland, and coastal channel scales within the Gulf of Mexico. Tides in the Gulf of Mexico are modestly energetic processes, whereas hurricane surge and waves are highly energetic. The unstructured-mesh, coupled wind-wave and circulation modeling system, SWAN+ ADCIRC, is implemented to generate modeled tidal harmonic constituents and hurricane waves and surge for a Hurricane Ike (2008) hindcast. In the open ocean, mesh resolution requirements are less stringent in achieving accurate tidal signals or matching hurricane surge and wave responses; however, coarser resolution or the absence of intertidal zones decreases accuracy along protected nearshore and inland coastal areas due to improper conveyance and/or lateral attenuation. Bottom friction formulations are shown to have little impact on tidal signal accuracy, but hurricane surge is much more sensitive, especially in shelf waters, where development of a strong shore-parallel current is essential to the development of Ike's geostrophic setup. The spatial and temporal contributions of wave radiation stress gradients and nonlinear advection were charted for Ike. Nonlinear advection improves model performance by capturing an additional 10―20 cm of geostrophic setup and increasing resonant cross-shelf waves by 30―40 cm. Wave radiation stress gradients improve performance at coastal stations by adding an extra 20―40 cm to water levels

Mental healthcare goes online:Practitioners' experiences of providing mental healthcare during the COVID-19 pandemic

The outbreak of the COVID-19 pandemic has necessitated sudden and radical changes in mental health care delivery, as strict social distancing and lockdown measures were imposed in the early phases of the pandemic. Almost overnight, practitioners were forced to transfer their face-to-face care practice to online means. To understand the implications of this drastic change for mental health care, and to improve the online care offerings, an online qualitative survey was held among mental health care professionals in Netherlands (n = 51). Our findings indicate that technological and usability problems pose a significant challenge, as do difficulties to establish rapport with clients. Moreover, not all mental health issues and treatment forms are equally amenable to online interaction. In contrast, in many instances, practitioners were positive about the effectiveness of treatment, and reported flexibility, a lower threshold for contact, and lack of travel time as advantages. Their most prominent needs concern better technological, organizational, and logistical support. It is critical that these needs are acted upon by institutions and governments. In addition, current results inform future research on the improvement of e-mental health technologies

Обработка оптических измерений траектории летательных объектов

Рассмотрены методы уравнивания угловых измерений по способу наименьших квадратов: метод уравнивания измерений отдельно в каждом временном сечении, предполагающий нулевое математическое ожидание случайных ошибок измерений, и метод уравнивания избыточных оптических измерений с подавлением их постоянных систематических ошибок в предположении засоренности измерений как случайными, так и неизвестными по величине и знаку систематическими погрешностями.Розглянуто методи зрівнювання кутових вимірювань за способом найменших квадратів: метод зрівнювання вимірювань окремо в кожному часовому розрізі, що передбачає нульове математичне очікування випадкових похибок вимірювань, і метод зрівнювання надлишкових оптичних вимірювань із заглушенням їх постійних систематичних похибок у припущенні засміченості вимірювань як випадковими, так і невідомими за величиною та знаком систематичними похибками.The methods of equalizing angular measurements according to the method of least squares are examined: the method of equalizing measurements separately in each temporary section, that assumes the zero mathematical expectation of the random errors of measurements, and the method of equalizing excessive optical measurements with suppression of their constant systematic errors under the assumption of the obstruction of measurements by systematic errors both random and unknowns by value and sign

Філософсько-правові проблеми реалізації права на працю

Розкривається зміст категорії «праця». Досліджуються філософсько-правові про­блеми у сфері здійснення права на працю.Раскрывается содержание категории «труд». Исследуются философско-правовые проблемы в сфере осуществления права на труд.In the article the content of the category «labour» is revealed. The philosophical and legal problems in the field of realization of the right to work are being researched

Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults. I Antibody concentrations, avidity and functional activity

Streptococcus pneumoniae is a serious worldwide pathogen and the focus of numerous vaccine development projects. Currently the most widely accepted surrogate marker for evaluating the efficacy of a given vaccine is to utilize ELISA. Measurement of antibody concentration by ELISA without reduction in cross-reactive antibodies causes an overestimation of antibody concentration and therefore protection, this is most notable in the aged, an at risk group for this infection. We compared the immune response to the pneumococcal polysaccharides (PPS) 4 and 14 of 20 young to 20 elderly adults. Pre-and post-vaccination IgG antibody concentrations and antibody avidity against PPS4 and PPS14 were measured using two different enzyme-linked immunosorbant assay (ELISA) absorption protocols. All sera were pre-absorbed with either cell-wall polysaccharide (CPS), or CPS and serotype 22F polysaccharide. Pre- and post-vaccination IgG antibody concentrations for serotype 4, but not 14, were significantly lowered with the additional absorption with serotype 22F polysaccharide in both age groups. Young and elderly demonstrated a significant increase from pre- to post-immunization antibody concentration, using either absorption method; and opsonophagocytic antibody titers in response to both PPS4 and PPS14. The correlation coefficients between ELISA and opsonophagocytic assays were improved by additional absorption with serotype 22F in response to serotype 4, but not serotype 14 in all age groups. Opsonophagocytic antibody titers in a sub-group of elderly (>77 years of age) were significantly lower than the opsonophagocytic antibody concentrations in young adults. These results suggest the importance of eliminating cross-reactive antibodies from ELISA measurements by absorption of serum and an age-related impairment in the antibody response to pneumococcal polysaccharides