Strategy Proposal for the Company Rajnošek, Ltd.

Import 22/07/2015Diplomová práce je zaměřena na zpracování návrhu strategie pro podnik Rajnošek s.r.o. Podnikatelská činnost tohoto podniku se týká autodopravy, zemních a jeřábnických prací v Jihomoravském kraji. V teoretické části jsou vymezeny základní pojmy, které nezbytně souvisí s tematickým celkem této práce. Také jsou zde popsány jednotlivé metody, které byly aplikovány na zkoumanou společnost při analýze celkového stavu firmy. V praktické části je nejprve detailně představen zvolený podnik a následně je provedeno několik typů analýzy, po jejichž vyhodnocení došlo k návrhu jednotlivých doporučení, jež by měla vést k žádoucím změnám a především k formulaci nejvhodnější firemní strategie.The thesis is focused on the development of the strategy proposal for the company Rajnošek s.r.o. The business activity of the company covers transport, earthworks and crane work in South-Moravian region. The theoretical part of the basic concepts that are necessarily associated with thematic units of this work . Also described are various methods that have been applied to the study of the organization in analyzing the overall condition of the company. In the practical part is the first detailed presentation of the selected company and subsequently made several types of analysis, evaluation, after which there was a draft of the recommendations which should lead to the desired changes and especially to the most appropriate formulation of corporate strategy.152 - Katedra podnikohospodářskávelmi dobř

The bulk mineralogy, elemental composition, and water content of the Winchcombe CM chondrite fall

On the micro-scale, the Winchcombe CM carbonaceous chondrite contains a number of lithological units with a variety of degrees of aqueous alteration. However, an understanding of the average hydration state is useful when comparing to other meteorites and remote observations of airless bodies. We report correlated bulk analyses on multiple subsamples of the Winchcombe meteorite, determining an average phyllosilicate fraction (PSF) petrologic type of 1.2 and an average water content of 11.9 wt%. We show the elemental composition and distribution of iron and iron oxidation state are consistent with measurements from other CM chondrites, however Winchcombe shows a low Hg concentration of 58.1 ±0.5 ng/g. We demonstrate that infrared reflectance spectra of Winchcombe are consistent with its bulk modal mineralogy, and comparable to other CM chondrites with similar average petrologic types. Finally, we also evaluate whether spectral parameters can estimate H/Si ratios and water abundances, finding generally spectral parameters underestimate water abundance compared to measured values.Output Status: Forthcoming/Available Onlin

Long-lived magnetism on chondrite parent bodies

publisher: Elsevier articletitle: Long-lived magnetism on chondrite parent bodies journaltitle: Earth and Planetary Science Letters articlelink: http://dx.doi.org/10.1016/j.epsl.2017.07.035 content_type: article copyright: © 2017 The Authors. Published by Elsevier B.V.© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). The attached file is the published version of the article

The Fusion Crust of the Winchcombe Meteorite: A Preserved Record of Atmospheric Entry Processes

Fusion crusts form during the atmospheric entry heating of meteorites and preserve a record of the conditions that occurred during deceleration in the atmosphere. The fusion crust of the Winchcombe meteorite closely resembles those of other stony meteorites, and in particular CM2 chondrites, since it is dominated by olivine phenocrysts set in a glassy mesostasis with magnetite, and is highly vesicular. Dehydration cracks are unusually abundant in Winchcombe. Failure of this weak layer is an additional ablation mechanism to produce large numbers of particles during deceleration, consistent with observation of pulses of plasma in videos of the Winchcombe fireball. Calving events might provide an observable phenomenon related to meteorites that are particularly susceptible to dehydration. Oscillatory zoning is observed within olivine phenocrysts the fusion crust, in contrast to other meteorites, perhaps owing to temperature fluctuations resulting from calving events. Magnetite monolayers are found in the crust, and have also not been previously reported, and form discontinuous strata. These features grade into magnetite-rims formed on the external surface of the crust and suggest trapping of surface magnetite by collapse of melt. Magnetite monolayers may be a feature of meteorites that undergo significant degassing. Silicate warts with dendritic textures were observed and are suggested to be droplets ablated from another stone in the shower. They, therefore, represent the first evidence for inter-shower transfer of ablation materials and are consistent with the other evidence in the Winchcombe meteorite for unusually intense gas loss and ablation, despite its low entry velocity.Output Status: Forthcoming/Available Online Additional co-authors: Christopher Hamann, Lutz Hecht, Laura E. Jenkins, Diane Johnson, Rosie Jones, Ashley J. King, Haithem Mansour, Sarah McMullan, Jennifer T. Mitchell, Gavyn Rollinson, Sara S. Russell, Natasha R. Stephen, Martin D. Suttle, Jon D. Tandy, Patrick Trimby, Eleanor K. Sansom, Vassilia Spathis, Francesca M. Willcocks, Penelope J. Wozniakiewic

Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs

Tuberculosis is a major global cause of both mortality and financial burden mainly in low and middle-income countries. Given the significant and ongoing rise of drug-resistant strains of Mycobacterium tuberculosis within the clinical setting, there is an urgent need for the development of new, safe and effective treatments. Here the development of a drug-like series based on a fused dihydropyrrolidino-pyrimidine scaffold is described. The series has been developed against M. tuberculosis lysyl-tRNA synthetase (LysRS) and cellular studies support this mechanism of action. DDD02049209, the lead compound, is efficacious in mouse models of acute and chronic tuberculosis and has suitable physicochemical, pharmacokinetic properties and an in vitro safety profile that supports further development. Importantly, preliminary analysis using clinical resistant strains shows no pre-existing clinical resistance towards this scaffold

Cooperation between Apoptotic and Viable Metacyclics Enhances the Pathogenesis of Leishmaniasis

Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death. As part of the normal metacyclogenic process occurring in axenic cultures and in the gut of sand fly vectors, a sub-population of metacyclic promastigotes exposes PS. Apoptotic death of the purified PS-positive (PSPOS) sub-population was confirmed by TUNEL staining and DNA laddering. Transmission electron microscopy revealed morphological alterations in PSPOS metacyclics such as DNA condensation, cytoplasm degradation and mitochondrion and kinetoplast destruction, both in in vitro cultures and in sand fly guts. TUNELPOS promastigotes were detected only in the anterior midgut to foregut boundary of infected sand flies. Interestingly, caspase inhibitors modulated parasite death and PS exposure, when added to parasite cultures in a specific time window. Efficient in vitro macrophage infections and in vivo lesions only occur when PSPOS and PS-negative (PSNEG) parasites were simultaneously added to the cell culture or inoculated in the mammalian host. The viable PSNEG promastigote was the infective form, as shown by following the fate of fluorescently labeled parasites, while the PSPOS apoptotic sub-population inhibited host macrophage inflammatory response. PS exposure and macrophage inhibition by a subpopulation of promastigotes is a different mechanism than the one previously described with amastigotes, where the entire population exposes PS. Both mechanisms co-exist and play a role in the transmission and development of the disease in case of infection by La. Since both processes confer selective advantages to the infective microorganism they justify the occurrence of apoptotic features in a unicellular pathogen

Brecciation at the grain scale within the lithologies of the Winchcombe Mighei‐like carbonaceous chondrite

The Mighei‐like carbonaceous (CM) chondrites have been altered to various extents by water–rock reactions on their parent asteroid(s). This aqueous processing has destroyed much of the primary mineralogy of these meteorites, and the degree of alteration is highly heterogeneous at both the macroscale and nanoscale. Many CM meteorites are also heavily brecciated juxtaposing clasts with different alteration histories. Here we present results from the fine‐grained team consortium study of the Winchcombe meteorite, a recent CM chondrite fall that is a breccia and contains eight discrete lithologies that span a range of petrologic subtypes (CM2.0–2.6) that are suspended in a cataclastic matrix. Coordinated multitechnique, multiscale analyses of this breccia reveal substantial heterogeneity in the extent of alteration, even in highly aqueously processed lithologies. Some lithologies exhibit the full range and can comprise nearly unaltered coarse‐grained primary components that are found directly alongside other coarse‐grained components that have experienced complete pseudomorphic replacement by secondary minerals. The preservation of the complete alteration sequence and pseudomorph textures showing tochilinite–cronstedtite intergrowths are replacing carbonates suggest that CMs may be initially more carbonate rich than previously thought. This heterogeneity in aqueous alteration extent is likely due to a combination of microscale variability in permeability and water/rock ratio generating local microenvironments as has been established previously. Nevertheless, some of the disequilibrium mineral assemblages observed, such as hydrous minerals juxtaposed with surviving phases that are typically more fluid susceptible, can only be reconciled by multiple generations of alteration, disruption, and reaccretion of the CM parent body at the grain scale

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data