Toward a PA-Inhibitor Complex Crystal System: Influenza Polymerase Acidic Protein Fusion Constructs and Protein Expression

Globally, three to five million people are afflicted on a yearly basis with serious illnesses due to influenza. In attempts to combat this epidemic, vaccines and antivirals are developed, yet they are not effective enough. The polymerase acidic protein (PA) is vital for viral replication, and inhibiting PA would potentially stop the virus from replicating. In order to inhibit PA effectively, the structure of the protein inhibition site is beneficial but has not yet been obtained because the site is blocked by another protein in crystal structures. Our solution is to fuse different proteins to PA to open up the structure to allow visualization of PA-inhibitor complexes. Various molecular biology techniques were used to create 18 different DNA constructs that were then transformed into bacterial cell lines to be expressed as protein

Tariff rate quotas and the economic impacts of agricultural trade liberalization in the WTO

Since their implementation at the Uruguay Round, tariff rate quotas (TRQs) have become a widely used instrument of trade policy in agricultural trade. With almost 1300 TRQs scheduled at the WTO, it seems worthwhile to examine their economic effects more closely. This is what this paper does. First, the theoretical background of TRQs is examined. Then a short overview of the Uruguay Round as their institutional background is given. We demonstrate that official statistics, which do not count TRQs as non-tariff barriers, are at least highly misleading. Very often, their effects are the same as those of regular quotas, including redistributive effects. The prominent example of the European Banana regime is used to illustrate all of these points. --Agriculture in International Trade,Commercial Policy,Protection,Promotion,Trade Negotiations

Die Entscheidungen des Dispute Settlement-Verfahrens der WTO im Hormonstreit zwischen der EU und den USA: Implikationen für den zukünftigen Umgang mit dem SPS-Abkommen

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Die Entscheidungen des ’Dispute Settlement’-Verfahrens der WTO im Hormonstreit zwischen der EU und den USA - Implikationen für den zukünftigen Umgang mit dem SPS-Abkommen

Institutions should reduce uncertainty and the costs of transaction with their regulating activities. This target was pursued at an international level with the foundation of the WTO. With an extensive treaty and a new dispute settlement procedure, the WTO was founded as the institutional platform for international co-operation. In view of the growing conflicts in international trade, the hope to create with this institution an international trade order, in which legally comprehensible decisions dominate and power-oriented politics are deterred, is fading. The case of the hormone dispute shows that the target of a fast harmonization of international standards cannot be reached in critical trade disputes. A solo effort in the area of trade measures that is introduced with the reason to protect consumers is still possible.WTO, Institutions, transaction costs, dispute settlement procedures, SPS-Agreement, Food Consumption/Nutrition/Food Safety, International Relations/Trade,

Wie wirken gemeldete SPS-Maßnahmen? Ein Gravitationsmodell des Rindfleischhandels der EU

For decades, nontariff trade barriers (NTBs) have been regarded as more problematic policy instruments than tariffs in international trade negotiations. This is due to the fact that trade impacts of nontariff trade barriers are less transparent than those of tariffs. Tariffication of nontariff agricultural trade barriers was finally decided under the Uruguay Round of GATT. Although the OECD concluded that a reduction of NTBs took place after 1994, this finding can be challenged. First, tariff-rate quotas (TRQs) are not counted as NTBs by law although they cause effects similar to those of quotas. The number of TRQs has increased strongly after the Uruguay Round. Second, sanitary and phytosanitary measures, i.e. SPS measures, have become more important as notifications under the SPS Agreement do show. There are only few empirical studies available which analyze the effects of these SPS measures. WTO Notifications under the SPS Agreement are utilized in this contribution for measuring trade impacts of sanitary and phytosanitary trade barriers. We explain the WTO data base on SPS notifications. Then, a gravitation model is applied to the EU beef trade in the period January 1995 to June 2001. It is investigated how SPS measures, introduced by non-EU countries in the context of BSE, affected bilateral trade with the EU. We distinguish between 31 product groups which might be affected, and a fixed-effects model is used for analyzing the panel data. We elaborate that SPS measures related to BSE reduced EU beef export revenues in the major product categories significantly. The NTBs did not reduce exports to zero, however, as might have been expected. The percentage reduction of export revenues was 49 % for live cattle, 74 % for fresh and cooled beef and 86 % for frozen beef. For most other product groups, the percentage decline in sales was significant but lower in percentage terms. Apparently, SPS notifications indicate that bilateral trade is restricted but it does not definitely show that the notified measures by the importing country are actually implemented and for which time period. It seems very important in future analyses of the SPS measures to distinguish carefully between SPS notifications and SPS measures. --SPS measures,SPS notifications,gravitation model,EU beef exports,bovine spongiform encephalopathy,WTO,nontariff trade barriers

Ein Umweltchemie-Praktikum an der Fachhochschule Darmstadt

It should be an aim of chemical education to make students meet aspects of environmental protection in the lab courses. Students at the Fachhochschule Darmstadt carry out model experiments on metal (Ag, Cu) and polymer (PMMA, PET, PS, paper) recycling and on air and water purification like gas washing, charcoal adsorption, or treatment with H2O2 and UV light. They are made familiar with analytical methods like AAS, UV/VIS spectroscopy and polarography to determine traces of heavy metals in the environment and work on a research project on decontamination of soil

The Role of Inorganics in Biomass Gasification: Catalytic Effects on Char Reactions and Toxic Emissions

This thesis studied the role of inorganic elements in biomass gasification, focusing on catalytic effects in char gasification and removal of toxic metals from the product gas. A combination of experimental, including gasification using thermogravimetric analysis and fluidized beds, and modeling techniques were used.Spruce and birch woods were leached of the naturally occurring ash forming elements and loaded with varying amounts of calcium or potassium. These woods were then gasified in either an isothermal thermogravimetric analysis device or a bubbling fluidized bed reactor. In the case of the spruce wood gasified using the thermogravimetric analysis device, char conversion models were evaluated against the measured data and an empirical model was developed which uses the concentration of calcium and potassium in wood to predict the conversion rate behavior of the char when gasified in CO2 . The results from the fluidized bed gasification tests of birch wood showed that calcium was the primary active catalyst in the wood and the increased reactivity resulting from calcium doping was clear even in the much larger scale of a fluidized bed compared to the thermogravimetric analysis. The potassium doped samples did not exhibit increased reactivity in the fluidized bed due a nonreactive layer of secondary char being deposited on the char surface.The behavior of arsenic in the product gas of chromated-copper arsenate wood was modeled using equilibrium calculations and measured experimentally in a bubbling fluidized bed. The equilibrium model accurately predicted that the product gas could be cleaned by cooling the gas below 260°C and filtering to remove condensed arsenic.While there are methods for modeling the effects of inorganics in catalyzing char gasification, further research into interconnected issues of surface area, pore sizes, pyrolysis conditions and inorganic concentrations is needed. Similarly, while equilibrium modeling has been shown to predict the behavior of arsenic during gasification in some cases, there are many gaps in understanding which arsenic compounds are most relevant

Analyse zu Behandlungsarten bei lokal fortgeschrittenem oder metastasiertem kutanem Plattenepithelkarzinom von 2007-2017 anhand eines Datensatzes der Universitätshautklinik Tübingen

Das kutane Plattenepithelkarzinom ist nach dem Basalzellkarzinom der zweithäufigste Hauttumor der hellhäutigen Bevölkerung. Die Inzidenz steigt stetig an und hat sich in den vergangenen 30 Jahren in Deutschland schätzungsweise vervierfacht. Betroffen sind vor allem Menschen hohen Alters. Ein weiterer Anstieg der Inzidenz ist auf den demografischen Wandel und die damit einhergehende alternde Bevölkerung zurückzuführen. Risikofaktoren sind neben kumulativer UV-Exposition vor allem ein hohes Lebensalter und eine Immunsuppression. Goldstandard der Initialtherapie ist die mikrografisch kontrollierte Exzision. Außerdem besteht die Möglichkeit einer Radiotherapie. Bei fortgeschrittenen Tumorerkrankungen kann eine systemische Tumortherapie notwendig werden. Bisher gibt es wenig Evidenz zur Systemtherapie mit EGFR-Inhibitoren oder Chemotherapeutika. Es existieren keine randomisierten verblindeten Studien an großen Kollektiven. Die Entscheidung zur Systemtherapie beruhte häufig auf Erfahrungswerten der Therapeuten und auf eingeschränkt übertragbaren Therapieschemata von Kopf-Hals-Tumoren. Ziel der Arbeit war die Analyse der Systemtherapien die - vor der Ära der Immuncheckpointinhibitoren - von 2007-2017 an der Universitätshautklinik Tübingen verabreicht wurden. Insgesamt wurden 291 Patienten mit aCSCC in der Tumorkonferenz in Tübingen vorgestellt. 82 Patienten erhielten die Empfehlung zur Systemtherapie mit mindestens einem Chemotherapeutikum oder/und Cetuximab. Nach Anwendung aller Ein- und Ausschlusskriterien wurden 59 Patienten in die Analyse der Systemtherapien eingeschlossen. 83,1% der Patienten waren männlich, das mediane Alter betrug 76 Jahre (IQR = [71; 80]). Bei Therapiebeginn hatten 72,9% ein mCSCC und 27,1% ein laCSCC. Es zeigte sich eine große Vielfalt an unterschiedlichen Therapieregimen. Insgesamt erhielten 23 (39,0%) Patienten eine Chemotherapie, 20 (33,9%) eine Therapie mit Cetuximab und 16 (27,1%) eine Kombination aus beiden Medikamenten. Das mediane Follow-Up belief sich auf 52,0 Wochen (IQR = [27,0; 97,0]). Die Therapie dauerte durchschnittlich 8,0 Wochen (IQR = [5,0; 16,0]) an. Für 56/59 Patienten lagen Daten zum Therapieansprechen vor. Es wurde ein ORR von 14,3% und eine DCR von 53,6% ermittelt. Die Wirksamkeit von EGFR-Inhibitoren und Chemotherapie war in diesem Kollektiv gering. Höhere Ansprechraten aus anderen Studien konnten unter realen Bedingungen nicht reproduziert werden. Zwischen laCSCC und mCSCC zeigte sich kein Unterschied bezüglich des Outcomes. Lediglich Patienten, die zu ihrer Systemtherapie eine adjuvante Radiotherapie erhalten hatten, zeigten ein verbessertes OS (p=0,014; HR 0,41) und PFS (p=0,009; HR 0,42). Allerdings fand sich in der univariaten Analyse der Patientencharakteristika beider Subgruppen eine ungleiche Altersverteilung, weswegen dieser Unterschied relativiert werden muss. Weitere Analysen sollten an größeren Kollektiven durchgeführt werden. Die Zulassung der Anti-PD-1-Antikörper ist ein Meilenstein in der Therapie vieler Tumorerkrankungen und hat auch die Systemtherapie des aCSCC und deren Studienlage deutlich verbessert. Besonders bei der Therapie älterer Patienten mit Komorbiditäten waren Behandelnde wegen etlicher Therapielimitationen bisher deutlich eingeschränkt und haben durch die Zulassung neuer Therapien bessere Behandlungsmöglichkeiten erhalten. Auch für immunsupprimierte Patienten mit aggressiven Krankheitsverläufen, bei denen auch unter Chemotherapie und zielgerichteter EGRF-Therapie häufig progredientes Tumorwachstum beobachtet wurde, haben sich vielversprechende Therapieoptionen ergeben. Dennoch gibt es Patienten, denen eine Therapie mit einem Immuncheckpointinhibitor nur eingeschränkt empfohlen werden kann und die auf alternative Therapien angewiesen sind. In diesen Fällen sind Chemotherapie und EGFR-Inhibitoren weiterhin wichtige Optionen, sofern eine Lokaltherapie nicht ausreichend ist. Weiterhin besteht die Notwendigkeit neuartiger effektiver Systemtherapien

Data-Driven Approach to Grade Change Scheduling Optimization in a Paper Machine

This paper proposes an efficient decision support tool for the optimal production scheduling of a variety of paper grades in a paper machine. The tool is based on a continuous-time scheduling model and generalized disjunctive programming. As the full-space scheduling model corresponds to a large-scale mixed integer linear programming model, we apply data analytics techniques to reduce the size of the decision space, which has a profound impact on the computational efficiency of the model and enables us to support the solution of large-scale problems. The data-driven model is based on an automated method of identifying the forbidden and recommended paper grade sequences, as well as the changeover durations between two paper grades. The results from a real industrial case study show that the data-driven model leads to good results in terms of both solution quality and CPU time in comparison to the full-space model.Peer reviewe

Polyhedral colloidal `rocks': low-dimensional networks

We introduce a model system of anisotropic colloidal `rocks'. Due to their shape, the bonding introduced via non-absorbing polymers is profoundly different from spherical particles: bonds between rocks are rigid against rotation, leading to strong frustration. We develop a geometric model which captures the essence of the rocks. Experiments and simulations show that the colloid geometry leads to structures of low fractal dimension. This is in stark contrast to gels of spheres, whose rigidity results from locally dense regions. At high density the rocks form a quasi one-component glass