Повышение эффективности контекстной рекламы в Интернете

Рассмотрены пути повышения эффективности рекламной кампании на площадках поисковых систем. Предложен подход к формированию рабочей группы ключевых слов, используемых в рекламных предложениях, разработан механизм изменения состава группы. Выработаны рекомендации по формированию и коррекции цены предложения на рекламном аукционе Google. Выполнена проверка предложенных решений на основе практических данных коммерческой фирмы, занимающейся контекстной рекламой на площадке поисковой системы.Розглянуто шляхи підвищення ефективності рекламної кампанії на площадках пошукових систем. Запропоновано підхід до формування робочої групи ключових слів, використовуваних у рекламних пропозиціях, розроблений механізм зміни складу групи. Вироблено рекомендації з формування й корекції ціни пропозиції на рекламному аукціоні Google. Виконано перевірку запропонованих рішень на основі практичних даних комерційної фірми, що займається контекстною рекламою на площадці пошукової системи.During article were examined new ways of Internet search system advertising efficiency increasing. Have been suggested method of creation optimal keywords workgroup(which are used in advertising sentences) approach. Have been worked out recommendations for bid fixing and correction. on Google advertising auction. Suggested conceptions were tested and implemented on real busyness information of internet-advertising company, which is mostly concentrated on context advertisin

Применение технологии набрызгбетонирования в Новоавстрийском Методе Туннелирования (NATM)

У статті проаналізовані суть і основні принципи Новоавстрійського Методу Тунелювання (NATM), що широко застосовується в зарубіжній практиці будівництва транспортних тунелів. Також розглянуто застосування технології торкретування, яка лежить в основі методу.Essence and basic principles of New Austrian Tunnelling Method (NATM), which widely used in foreign practice building of transport tunnels, is analysed in the article. Application of gunite technology, being the basis of method, is also considered

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

One TEF concept does not fit all: The case for human risk assessment of polychlorinated biphenyls

Human risk assessment of dioxins and dioxin-like compounds relies heavily on toxic equivalency factors (TEFs) that are mainly based on in vivo rodent studies. However, especially for the PCBs there are many uncertainties with respect to the actual dioxin-like activities and subsequent health effects in humans. For example, the relative effect potencies (REPs) for PCB126 are consistently up to two orders of magnitude lower in human cell models than in rodents and rodent cell cultures. For other dioxin-like (DL) PCBs, REPs can often not be obtained in human models due to a lack of AHR-mediated responses. In addition, DL-PCB-related effects such as thyroid disruption are largely attributed to mechanisms that are not (directly) AHR-mediated. Consequently, the AHR-mediated risk in humans for DL-PCBs is likely overestimated in the current TEF concept. The increasing availability of in vitro models using human cells will provide great opportunities to determine human-specific REP/TEFs based on toxicologically relevant endpoints. A better understanding of human-specific responses should lead to more reliable potency estimates of human effects and ultimately improved human risk assessment for DL-PCBs

Evaluation of relative effect potencies (REPs) for dioxin-like compounds to derive systemic or human-specific TEFs to improve human risk assessment

Toxic equivalency factors (TEFs) are generally applied for estimating human risk of dioxins and dioxin-like compounds using systemic (e.g., blood) levels, even though these TEFs are established based on intake doses in rodent studies. This review shows that systemic relative effect potencies (REPs) can deviate substantially from intake REPs, but are similar to in vitro-derived REPs. Interestingly, the in vitro REPs for 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) and 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) are up to one order of magnitude higher than their in vivo REPs and WHO-TEFs, based on oral intake. In addition, clear species-differences in in vitro REPs were apparent for some congeners. Especially the human-derived REP for polychlorinated biphenyl 126 is one to two orders of magnitude lower than rodent REPs and its current WHO-TEF. Next, suggested adapted systemic or human-specific TEFs for these congeners were applied to calculate changes in systemic TEQ concentrations in studies from the USA, Germany and Japan and compared with either the JECFA TDI or USEPA RfD of TCDD. Overall, the effect of such TEF changes for these three congeners on total TEQ roughly balances each other out in the general population. However, results may be different for situations in which a specific group of congeners dominates. For those congeners that show a distinct deviation between either intake and systemic REPs or between rodent- and human-based in vitro REPs, we propose that especially REPs derived from human-based in vitro models are weighted more heavily in establishing systemic or human-specific TEF values to improve human health risk assessment

Tissue distribution of dioxin-like compounds: potential impacts on systemic relative potency estimates

Relative effect potencies (REPs) for dioxins and dioxin-like compounds based on tissue concentration or internal dose ( REPs) can be considered of high relevance for human risk assessment. Within the EU-project SYSTEQ, REPs for 1,2,3,7,8-pentachlorodibenzodioxin (PeCDD), 2,3,4,7,8,-pentachlorodibenzofuran (4-PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,3',4,4',5-pentachlorobiphenyl (PCB 118) and 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) were calculated based on a plasma, adipose tissue or liver concentration in Sprague Dawley rats and C57bl/6 mice three days after a single oral dose. Compound-specific distribution as well as differences in accumulation and elimination can influence the tissue concentration and thereby the relative potency estimate of a congener. Here, we show that distribution patterns are generally similar for the tested congeners between the SYSTEQ dataset and other studies using either a single dose or subchronic dosing. Furthermore, the responding concentration for TCDD in single dose studies is comparable to the responding concentrations reported in subchronic studies. In contrast with data for laboratory rodents, available distribution data for humans in the general population display little or no hepatic sequestration. Because hepatic sequestration due to CYP1A2 protein binding may affect the amount of congener that is bioavailable for the AhR to produce hepatic responses, estimates of relative potencies between congeners with differing degrees of hepatic sequestration based on hepatic responses may be misleading for application to human risk assessment. Therefore, extra-hepatic concentration in blood serum/plasma or adipose tissue together with a biological extra-hepatic response might give a more accurate prediction of the relative potency of a congener for human responses under environmental conditions

Comparison of Intake and Systemic Relative Effect Potencies of Dioxin-like Compounds in Female Mice after a Single Oral Dose

BACKGROUND: Risk assessment for mixtures of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) is performed using the toxic equivalency factor (TEF) approach. These TEF values are derived mainly from relative effect potencies (REPs) linking an administered dose to an in vivo toxic or biological effect, resulting in "intake" TEFs. At present, there is insufficient data available to conclude that intake TEFs are also applicable for systemic concentrations (e. g., blood and tissues). OBJECTIVE: We compared intake and systemic REPs of 1,2,3,7,8-pentachlorodibenzodioxin (PeCDD), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 3,3', 4,4', 5-pentachlorobiphenyl (PCB-126), 2,3', 4,4', 5-pentachlorobiphenyl (PCB-118), and 2,3,3', 4,4', 5-hexachlorobiphenyl (PCB-156) in female C57BL/6 mice 3 days after a single oral dose. METHODS: We calculated intake REPs and systemic REPs based on administered dose and liver, adipose, or plasma concentrations relative to TCDD. Hepatic cytochrome P450 1Al-associated ethoxyresorufin-O-deethylase (EROD) activity and gene expression of Cyp1a1, 1a2 and 1b1 in the liver and peripheral blood lymphocytes (PBLs) were used as biological end points. RESULTS: We observed up to one order of magnitude difference between intake REPs and systemic REPs. Two different patterns were discerned. Compared with intake REPs, systemic REPs based on plasma or adipose levels were higher for PeCDD, 4-PeCDF, and PCB-126 but lower for the mono-ortho PCBs 118 and 156. CONCLUSIONS: Based on these mouse data, the comparison between intake REPs and systemic REPs reveals significant congener-specific differences that warrants the development of systemic TEFs to calculate toxic equivalents (TEQs) in blood and body tissues