Realistic, Extensible DNS and mDNS Models for INET/OMNeT++

The domain name system (DNS) is one of the core services in today's network structures. In local and ad-hoc networks DNS is often enhanced or replaced by mDNS. As of yet, no simulation models for DNS and mDNS have been developed for INET/OMNeT++. We introduce DNS and mDNS simulation models for OMNeT++, which allow researchers to easily prototype and evaluate extensions for these protocols. In addition, we present models for our own experimental extensions, namely Stateless DNS and Privacy-Enhanced mDNS, that are based on the aforementioned models. Using our models we were able to further improve the efficiency of our protocol extensions.Comment: Published in: A. F\"orster, C. Minkenberg, G. R. Herrera, M. Kirsche (Eds.), Proc. of the 2nd OMNeT++ Community Summit, IBM Research - Zurich, Switzerland, September 3-4, 201

Bifurcatriol, a New Antiprotozoal Acyclic Diterpene from the Brown Alga Bifurcaria bifurcata

Linear diterpenes that are commonly found in brown algae are of high chemotaxonomic and ecological importance. This study reports bifurcatriol (1), a new linear diterpene featuring two stereogenic centers isolated from the Irish brown alga Bifurcariabifurcata. The gross structure of this new natural product was elucidated based on its spectroscopic data (IR, 1D and 2D-NMR, HRMS). Its absolute configuration was identified by experimental and computational vibrational circular dichroism (VCD) spectroscopy, combined with the calculation of 13C-NMR chemical shielding constants. Bifurcatriol (1) was tested for in vitro antiprotozoal activity towards a small panel of parasites (Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi, and Leishmania donovani) and cytotoxicity against mammalian primary cells. The highest activity was exerted against the malaria parasite P. falciparum (IC50 value 0.65 μg/mL) with low cytotoxicity (IC50 value 56.6 μg/mL). To our knowledge, this is the first successful application of VCD and DP4 probability analysis of the calculated 13C-NMR chemical shifts for the simultaneous assignment of the absolute configuration of multiple stereogenic centers in a long-chain acyclic natural product

Match-making for posaconazole through systems thinking

Currently available drugs for Chagas’ disease are limited by toxicity and low efficacy in the chronic stage. Posaconazole, the most advanced new anti-chagasic drug candidate, did not fully confirm its initial potential in a Phase II clinical trial for chronic Chagas’ disease. Given that posaconazole is highly active against Trypanosoma cruzi in vitro, and was very well tolerated in clinical trials, it should not be abandoned. Rather, a combination therapy may provide a highly promising outlook. Systems-scale approaches facilitate the hunt for a combination partner for posaconazole, which acts by blocking sterol biosynthesis. Mounting evidence suggests the functional interactions between sterols and sphingolipids in vivo. Here, we propose combining sterol and sphingolipid biosynthesis inhibitors to advance drug development in Chagas’ disease

The Suitability of Environment Management Accounting (EMA) Models Applied by the German Mittelstand

The implementation of environmental management accounting (EMA) in Mittelstand companies is an uncharted area. Therefore, the aim of this study was to identify the ways, benefits, and disadvantages of implementing EMA in such companies. The choice of the approach and method depended on the following reasons: As the observed phenomena took place inside a company and depended on the attitudes of its members, an interpretivist and qualitative research approach was used that regarded a company as a socially constructed entity. The research was executed with a top-down deductive method starting with a literary review (on Mittelstand-like companies using EMA), and leading to hypotheses concerning the research aim. These assumptions were tested in a qualitative case study using a German Mittelstand company from the printing industry. To this end, the study used the company’s files, personal notes from management meetings, and interviews with experts from the focal company offering the deepest insight in the focal company. The analysis found two different results. Mittelstand companies will have trouble with implementing EMA. However, after having done this, they will only experience benefits and no disadvantages. During the EMA implementation there will probably be delays due to lacking expertise, conservative attitudes, and disturbed channels of information among the staff. However, these obstacles can be overcome with external experts guiding the EMA implementation, and with financial resources to pay them. EMA will then enable a Mittelstand company to track the flows of hazardous and harmless physical entities alike and its associated environmental and conventional costs. With this information the strategic management accounting (SMA) will be able to reduce these costs, to develop eco-friendly products, and to increase its resource efficiency, profits and competitiveness. In a Mittelstand company EMA should therefore be placed at the interface of proper accounting and SMA. FCA, ABC, flow cost accounting, input/output analysis, and EBSC seem to be the optimal methods to track and analyse a company’s physical flows and its related conventional and environmental costs. The former cost type depends on the quantities of the resources, with the latter one depending on the production of waste, the excessive use of water, wood, fuel, electric energy, hazardous chemicals and the process they are used in. To capture these costs it is best to use a set of primary metrics (reflecting the quantities of the resources) and secondary metrics (focussing on the flows and dangers of these resources). Measuring environmental costs of hazardous substances is difficult, since the production processes they are used in depend on chancy circumstances like accidents. Instead, it is also possible to use an EMA that only calculates the amounts of wood, water, waste, fuel, and electric energy needed for the use of hazardous substances. After multiplying these costs with a numerical and empirically obtained factor, the related environmental costs can now be measured both accurately and easily. Such a simplified EMA seems to be a promising method for Mittelstand companies with low technical skills

In vitro Antiprotozoal Activity of Extracts of five Turkish Lamiaceae Species

The in vitro antiprotozoal activities of crude methanolic extracts from the aerial parts of five Lamiaceae plants (Salvia tomentosa, S. sclarea, S. dichroantha, Nepeta nuda subsp. nuda and Marrubium astracanicum subsp. macrodon) were evaluated against four parasitic protozoa, i.e. Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani and Plasmodium falciparum. The cytotoxic potentials of the extracts on L6 cells were also evaluated. Melarsoprol, benznidazole, miltefosine, chloroquine and podophyllotoxin were used as reference drugs. All crude MeOH extracts showed antiprotozoal potential against at least three parasites, so they were dispersed in water and partitioned against n-hexane and chloroform to yield three subextracts that were screened in the same test systems. The n-hexane extract of N. nuda was the most active against T. brucei rhodesiense while the CHCl3 extracts of S. tomentosa and S. dichroantha showed significant activity against L. donovani. All organic extracts displayed in vitro antimalarial and moderate trypanocidal activities against T. cruzi with the n-hexane extract of S. sclarea being the most active against the latter. The extracts displayed low or no cytotoxicity towards mammalian L6 cells

Screening and HPLC-Based Activity Profiling for New Antiprotozoal Leads from European Plants

Based on a survey of remedies used in Renaissance Europe to treat malaria, we prepared and screened a library of 254 extracts from 61 plants for antiplasmodial activity in vitro. HPLC-based activity profiling was performed for targeted identification of active constituents in extracts. One of the most remarkable results was the identification of onopordopicrin, a germacranolide sesquiterpene lactone isolated from Arctium nemorosum as a potent inhibitor of P. falciparum with an IC50 of 6.9 μM. It was tested similarly against Trypanosoma brucei rhodesiense, the parasite which causes African sleeping sickness. With an IC50 of 0.37 μM, onopordopicrin was one of the most potent natural products reported so far. Cytotoxicity was determined against rat myoblast L6 cells (IC50: 3.06)

Inhibitory Activity of Marine Sponge-Derived Natural Products against Parasitic Protozoa

In this study, thirteen sponge-derived terpenoids, including five linear furanoterpenes: furospinulosin-1 (1), furospinulosin-2 (2), furospongin-1 (3), furospongin-4 (4), and demethylfurospongin-4 (5); four linear meroterpenes: 2-(hexaprenylmethyl)-2-methylchromenol (6), 4-hydroxy-3-octaprenylbenzoic acid (7), 4-hydroxy-3-tetraprenyl-phenylacetic acid (8), and heptaprenyl-p-quinol (9); a linear triterpene, squalene (10); two spongian-type diterpenes dorisenone D (11) and 11β-acetoxyspongi-12-en-16-one (12); a scalarane-type sesterterpene; 12-epi-deoxoscalarin (13), as well as an indole alkaloid, tryptophol (14) were screened for their in vitro activity against four parasitic protozoa; Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. Cytotoxic potential of the compounds on mammalian cells was also assessed. All compounds were active against T. brucei rhodesiense, with compound 8 being the most potent (IC50 0.60 μg/mL), whereas 9 and 12 were the most active compounds against T. cruzi, with IC50 values around 4 μg/mL. Compound 12 showed the strongest leishmanicidal activity (IC50 0.75 μg/mL), which was comparable to that of miltefosine (IC50 0.20 μg/mL). The best antiplasmodial effect was exerted by compound 11 (IC50 0.43 μg/mL), followed by compounds 7, 10, and 12 with IC50 values around 1 μg/mL. Compounds 9, 11 and 12 exhibited, besides their antiprotozoal activity, also some cytotoxicity, whereas all other compounds had low or no cytotoxicity towards the mammalian cell line. This is the first report of antiprotozoal activity of marine metabolites 1–14, and points out the potential of marine sponges in discovery of new antiprotozoal lead compounds

Adaptation of a culturally relevant nutrition and physical activity program for low-income, Mexican-origin parents with young children.

Latino children experience higher rates of obesity than do non-Latino white children. Family-centered nutrition interventions can slow the rate of weight gain in this population. Niños Sanos, Familia Sana (Healthy Children, Healthy Family) is a 5-year, community-based, participatory research study that targets rural Mexican-origin farmworker families with children aged 2 to 8 years in California's Central Valley. Adaptation of a culturally relevant obesity prevention program involved qualitative research to tailor key obesity prevention messages, pilot testing and implementation of key messages and activities at family nights, and continual modification to incorporate culturally innovative elements. Of the 238 families enrolled, 53% (125) attended the recommended minimum of 5 (of 10 possible) classes during the first year. A university and community partnership can guide development of a culturally tailored obesity prevention program that is suitable for reaching a high-risk Mexican-origin audience through cooperative extension and other public health programs

Mining sudanese medicinal plants for antiprotozoal agents

Neglected tropical diseases are major health hazards in developing countries. Annually, up to 30 million people are affected by either Chagas disease, African trypansomiasis or leishmaniasis, and more than 200 million by malaria. Most of the currently available drugs have drawbacks in terms of toxicity, limited oral availability, development of resistance, or non-affordability. Tropical plants of the arid zones are a treasure chest for the discovery of bioactive secondary metabolites. This study aims to compile Sudanese medicinal plants, validate their antiprotozoal activities, and identify active molecules. We have performed a survey of medicinal plants of Sudan and selected 62 that are being used in Sudanese traditional medicine. From these, we collected materials such as leaves, stem, bark, or fruit. The plant materials were extracted in 70% ethanol and further fractionated by liquid-liquid partitioning using solvents of increasing polarity. This resulted in a library of 235 fractions. The library was tested; in vitro; against; Plasmodium falciparum; (erythrocytic stages),; Trypanosoma brucei rhodesiense; (bloodstream forms),; Trypanosoma cruzi; (intracellular amastigotes), and; Leishmania donovani; (axenic amastigotes). Active fractions were also tested for cytotoxicity. Of the 235 fractions, 125 showed growth inhibitory activity >80% at 10 μg/ml, and >50% at 2 μg/ml against at least one of the protozoan parasites.; Plasmodium falciparum; was the most sensitive of the parasites, followed by; T. b. rhodesiense; and; L. donovani; . Only few hits were identified for; T. cruzi; , and these were not selective. Contrary to expectation based on phylogeny, but in agreement with previous results, a large number of extracts displayed mutual activity against; T. brucei; and; P. falciparum; . HPLC-based activity profiling for selected active extracts was performed to identify the bioactive principles. Active compounds identified by dereplication were guieranone A from; Guiera senegalensis; J.F.Gmel.; pseudosemiglabrin from; Tephrosia apollinea; (Delile) DC; ellagic acid and quercetin from; Terminalia leiocarpa; (DC.) Baill.; and catechin, ethyl gallate, and epicatechin gallate from; Vachellia nilotica; (L.) P.J.H.Hurter & Mabb. Also the extracts of; Croton gratissimus; var.; gratissimus; and; Cuscuta hyalina; Roth ex Schult. exhibited promising antitrypanosomatid activity. This assessment provides a comprehensive overview of Sudanese medicinal plants and supports the notion that they are a potential source of bioactive molecules against protozoan parasites