Generating vegetation-spectra as a basis for global monitoring of annual vegetation cycles using DOAS satellite observations

Vegetation-cycles are of general interest for many applications. Be it for harvest-predictions, global monitoring of climate-change or as input to atmospheric models.rnrnCommon Vegetation Indices use the fact that for vegetation the difference between Red and Near Infrared reflection is higher than in any other material on Earth’s surface. This gives a very high degree of confidence for vegetation-detection.rnrnThe spectrally resolving data from the GOME and SCIAMACHY satellite-instrumentsrnprovide the chance to analyse finer spectral features throughout the Red and Near Infrared spectrum using Differential Optical Absorption Spectroscopy (DOAS). Although originally developed to retrieve information on atmospheric trace gases, we use it to gain information on vegetation. Another advantage is that this method automatically corrects for changes in the atmosphere. This renders the vegetation-information easily comparable over long time-spans.rnThe first results using previously available reference spectra were encouraging, but also indicated substantial limitations of the available reflectance spectra of vegetation. This was the motivation to create new and more suitable vegetation reference spectra within this thesis.rnThe set of reference spectra obtained is unique in its extent and also with respect to its spectral resolution and the quality of the spectral calibration. For the first time, this allowed a comprehensive investigation of the high-frequency spectral structures of vegetation reflectance and of their dependence on the viewing geometry.rnrnThe results indicate that high-frequency reflectance from vegetation is very complex and highly variable. While this is an interesting finding in itself, it also complicates the application of the obtained reference spectra to the spectral analysis of satellite observations.rnrnThe new set of vegetation reference spectra created in this thesis opens new perspectives for research. Besides refined satellite analyses, these spectra might also be used for applications on other platforms such as aircraft. First promising studies have been presented in this thesis, but the full potential for the remote sensing of vegetation from satellite (or aircraft) could bernfurther exploited in future studies.

Anwendungen von Rezeptoren auf Triphenylenketal-Basis

Im Rahmen dieser Arbeit wurde die Bindung von Koffein und verwandten Oxopurinen in C¬3-symmetrischen Rezeptoren auf der Basis von Triphenylenketalen untersucht. Dabei stand vor allem die Evaluierung für eine spätere Anwendung im Vordergrund. Für die Anwendung als Chemosensor wurden mehrere optische Verfahren getestet. Die Verwendung von UV/Vis-Spektroskopie gelingt nur unter Einsatz eines elektronenarmen Konkurrenzgastes, welcher durch das stärker bindende Koffein unter Entfärbung verdrängt wird. Obwohl dieser Effekt sogar mit bloßem Auge zu erkennen ist und somit eine einfache Untersuchung ermöglichen würde, machen die besondere Reaktivität des Konkurrenzgastes und dessen geringe Affinität zum Rezeptor eine weitere Anwendung als Chemosensor für Koffein unwahrscheinlich. Den entscheidenden Durchbruch lieferte der Wechsel auf Fluoreszenzspektroskopie. Die Bindung von Gästen lässt sich mit dieser Methode direkt beobachten und für quantitative Studien nutzen. Die Signalzunahme bei Zugabe von Koffein liegt bei maximal 30%. Durch Verwendung eines vom Koffein abgeleiteten Konkurrenzgastes können weitere Verbesserungen erzielt werden. So konnte eine maximale Signaldynamik von fast 400% erzielt werden. Durch die Entwicklung eines geeigneten Probenvorbereitungsprotokolls war es möglich, mit dem fluoreszenzbasierten System einen Nachweis von Koffein an kommerziell verfügbaren Getränkeproben durchzuführen. Die Ergebnisse waren in guter Übereinstimmung mit HPLC-Kontrollexperimenten. Die Eignung von Rezeptoren auf Triphenylenketalbasis für die enantiofaciale Differenzierung an Heteroaromaten wurde durch Untersuchung verschiedener Wirt-Gast-Komplexe mittels CD-Spektroskopie und Tieftemperatur-NMR systematisch demonstriert. Rezeptoren mit Menthyl-Substituenten liefern laut NMR die stärkste Seitendifferenzierung. Anhand des CD wird ein vollständiges und schlüssiges Bild über den Zusammenhang zwischen dem Raumbedarf am Gast, der Ausrichtung der chiralen Gruppen am Wirt und dem erhaltenen CD hergestellt. Durch umfangreiche molekulardynamische Simulationen und nachfolgende semiempirische Berechnungen wurden Referenzspektren berechnet, welche die Zuordnung der Stereochemie anhand des CD eindeutig belegen. Die Ergebnisse sind zudem in guter Übereinstimmung mit den Ergebnissen aus röntgenkristallographischen Untersuchungen. (Diese Methode ließ sich erfolgreich auf die helicale Faltung von Alkanen in Kapseln von Rebek, jr. umsetzen.) Obwohl die Energieunterschiede zwischen den diastereomeren Komplexen klein sind, konnte anhand der CD-Spektroskopie somit erstmalig die enantiofaciale Differenzierung an einem heterocyclischen System bei Raumtemperatur beobachtet werden. Die beste enantiofaciale Differenzierung erzielen die Menthyl-abgeleiteten Rezeptoren. Diese sind hinsichtlich einer möglichen Anwendung als chirales „Auxiliar“ ungeeignet, da sie mit den sperrigen Cyclohexylgruppen auch den Raum oberhalb des gebundenen Gastes blockieren. Daher wird für die weitere Entwicklung auf die praktische Einführung chiraler Information in Form des Isocyanats verzichten werden müssen. Stattdessen zielen aktuelle Bemühungen auf den Aufbau chiraler Rückgrate, welche den Raum in der unteren Peripherie des Gastes beeinflussen.

Modellkomplexe oligonuklearer Metalloproteine auf Basis von Salen-Liganden und Spin-Crossover-Verbindungen als Chemosensoren

Der erste Teil der hier vorgestellten Arbeit verfolgt die Synthese potentieller Modellverbindungen oligonuklearer Metalloproteine auf Basis von Salen-Liganden. Dazu wurden zwei Ligandensysteme mit unterschiedlich raumerfüllenden Alkyl-Substituenten modifiziert und auf ihre koordinativen Eigenschaften hin untersucht. Für das Ligandensystem auf Basis des Bis-(salicylidenamino)-propan-2-ols konnten fünf Derivate (H3L1, H3L2A,H3L2B, H3L3, H3L4), für das zweite verwendete Ligandensystem auf Basis des 1H-3,5-Bis-(salicylidenaminomethyl)-pyrazols konnten zwei weitere Derivate (H3L5A, H3L5B) dargestellt und zu Koordinationsverbindungen umgesetzt werden.rnFür den hier verwendeten Bis-(salicylidenamino)-propan-2-ol Liganden H3L1, welcher die geringsten sterischen Anforderungen stellt, konnten mono-, tri- und tetranukleare Koordinationsverbindungen synthetisiert werden. Dabei gelingt es dem Liganden, sich sowohl in planarer als auch in unterschiedlich stark gewinkelter Konformation um ein oder mehrere Metallzentren anzuordnen, wobei der Ligand ein N2O2- seines N2O3-Donorsets zur Koordination nutzt. Die Verbindung {[Ni7(HL1)2(L1)2(OBz)4(OMe)(H2O)]}n zeigt, dass eine Verkettung der so gestalteten dreikernigen Einheiten über das freie Propanol-Sauerstoffatomdes Ligandenrückgrats möglich ist. Mit zunehmendem sterischen Anspruch der angefügten Alkylsubstituenten nimmt die geometrische Flexibilität und somit das Potential des Liganden zur Ausbildung höhernuklearer Strukturen ab. So ist für Liganden mit mittlerem sterischen Anspruch neben mononuklearen Komplexen noch die Gestaltung dinuklearer Systeme möglich. Erhöht man den sterischen Anspruch des Liganden weiter, findet nur noch eine Reaktion zu mononuklearen Verbindungen statt.rnMit den Pyrazol-basierten Ligandensystemen H3L5A und H3L5B konnten dinukleare Kupfer- und Nickelverbindungen synthetisiert werden.rnDer zweite Teil dieser Arbeit befasst sich mit der Gestaltung von Spin-Crossover Systemen (SCO). Dazu soll ein Spinübergang innerhalb des gestalteten schaltbaren Systems an die Anwesenheit eines Signalstoffs gekoppelt werden, so dass diese SCO-Verbindung als Sensor für den Signalstoff eingesetzt werden kann. Dazu wurden zwei unterschiedliche Ansätze entwickelt und untersucht.rnDie erste Methode beruht auf der Kombination eines zum Spin-Crossover befähigten Metallzentrums, eines Capping-Liganden, eines zur Signalstofferkennung funktionalisierten Co-Liganden sowie eines entsprechenden Signalstoffs. Als Capping-Liganden wurden tetra- und pentadentateLigandensysteme eingesetzt und mit unterschiedlich Picolyl-substituierten Monoaza-[12]-krone-4-Derivaten umgesetzt, wobei die Monoazakrone zur Komplexierung des Signalstoffs,hier in Form eines Alkalimetallions, zur Verfügung steht. Nach dieser ersten Methode konnten im Zeitraum dieser Arbeit noch keine zufriedenstellenden Ergebnisse erzielt werden.rnEine vielversprechende zweite Möglichkeit beruht auf der Verwendung eines mehrzähnigen, etablierten Spin-Crossover Liganden,welcher in seiner Peripherie mit einer Bindungstasche zur Aufnahme des Signalstoffmodifiziert wird.Mit Hilfe des so gestalteten Liganden 4'-(4'''-Benzo-[15]-krone-5)-methyloxy-2,2':6',2''-terpyridin ([b15c5]-tpy) gelang die Umsetzung zu entsprechenden Eisen(II)- und Kobalt(II)komplexen der Zusammensetzung [M([b15c5]-tpy)2]2+. Alle synthetisierten Eisen(II)-Komplexe liegen aufgrund der hohen Ligandenfeldstärke des Terpyridins über einen Temperaturbereich von 300 – 400 K in ihrer diamagnetischen Low Spin Form vor. Die entsprechenden Kobalt(II)-Komplexe zeigen über einen Temperaturbereich von 2 – 350 K ein kontinuierliches, aber unvollständiges Spin-Crossover Verhalten.rnDer Einfluss von Signalstoffen auf das Spin-Crossover Verhalten der Kobalt(II)-Systeme wurde in einem ersten Versuch unter der Verwendung von Natriumionen als Signalstoff untersucht. Dabei stellte sich heraus, dass Natriumionen für dieses System zwar nicht als Auslöser eines SCO verwendet werden können, sie aber dennoch eine starke Auswirkung auf den Verlauf des Spin-Crossovers haben.

Algorithmen zur labelfreien quantitativen Proteomanalyse auf Basis datenunabhängig-akquirierter LC-MS-Daten

Moderne ESI-LC-MS/MS-Techniken erlauben in Verbindung mit Bottom-up-Ansätzen eine qualitative und quantitative Charakterisierung mehrerer tausend Proteine in einem einzigen Experiment. Für die labelfreie Proteinquantifizierung eignen sich besonders datenunabhängige Akquisitionsmethoden wie MSE und die IMS-Varianten HDMSE und UDMSE. Durch ihre hohe Komplexität stellen die so erfassten Daten besondere Anforderungen an die Analysesoftware. Eine quantitative Analyse der MSE/HDMSE/UDMSE-Daten blieb bislang wenigen kommerziellen Lösungen vorbehalten. rn| In der vorliegenden Arbeit wurden eine Strategie und eine Reihe neuer Methoden zur messungsübergreifenden, quantitativen Analyse labelfreier MSE/HDMSE/UDMSE-Daten entwickelt und als Software ISOQuant implementiert. Für die ersten Schritte der Datenanalyse (Featuredetektion, Peptid- und Proteinidentifikation) wird die kommerzielle Software PLGS verwendet. Anschließend werden die unabhängigen PLGS-Ergebnisse aller Messungen eines Experiments in einer relationalen Datenbank zusammengeführt und mit Hilfe der dedizierten Algorithmen (Retentionszeitalignment, Feature-Clustering, multidimensionale Normalisierung der Intensitäten, mehrstufige Datenfilterung, Proteininferenz, Umverteilung der Intensitäten geteilter Peptide, Proteinquantifizierung) überarbeitet. Durch diese Nachbearbeitung wird die Reproduzierbarkeit der qualitativen und quantitativen Ergebnisse signifikant gesteigert.rn| Um die Performance der quantitativen Datenanalyse zu evaluieren und mit anderen Lösungen zu vergleichen, wurde ein Satz von exakt definierten Hybridproteom-Proben entwickelt. Die Proben wurden mit den Methoden MSE und UDMSE erfasst, mit Progenesis QIP, synapter und ISOQuant analysiert und verglichen. Im Gegensatz zu synapter und Progenesis QIP konnte ISOQuant sowohl eine hohe Reproduzierbarkeit der Proteinidentifikation als auch eine hohe Präzision und Richtigkeit der Proteinquantifizierung erreichen.rn| Schlussfolgernd ermöglichen die vorgestellten Algorithmen und der Analyseworkflow zuverlässige und reproduzierbare quantitative Datenanalysen. Mit der Software ISOQuant wurde ein einfaches und effizientes Werkzeug für routinemäßige Hochdurchsatzanalysen labelfreier MSE/HDMSE/UDMSE-Daten entwickelt. Mit den Hybridproteom-Proben und den Bewertungsmetriken wurde ein umfassendes System zur Evaluierung quantitativer Akquisitions- und Datenanalysesysteme vorgestellt.

Molecular basis of maturation promoting factor

Maturation promoting factor (MPF), which is functionally defined by its ability to induce Xenopus oocyte maturation, is an M phase (meiosis and mitosis) specific activity that is present in all species tested. It was hypothesized that MPF is a universal trigger of the interphase to M phase transition during the cell cycle. The current model for the molecular basis of MPF is that MPF is a protein kinase having the cdc2 protein as its catalytic subunit and is identical to the M phase-specific histone H1 kinase. In the present study, I have shown that more than just cdc2 kinase contributes to MPF activity, and M phase-specific H1 kinase is composed of at least two entities, instead of just cdc2 kinase. Therefore, the simple model of MPF = cdc2 kinase = M phase-specific H1 kinase should be ruled out.^ My study began with the characterization of the mitosis-specific monoclonal antibody MPM-2. MPM-2 reacts specifically with M phase cells from different species by recognizing a discrete set of proteins once they are phosphorylated at the G$\sb2$/M transition. I found that phosphorylation of MPM-2 antigens coincided with the appearance of MPF activity during oocyte maturation stimulated by progesterone. If MPM-2 was injected into oocytes before the stimulation, MPF activity failed to appear, and the oocytes could not mature. Furthermore, MPM-2 was able to deplete MPF activity from M phase extracts. These results identified MPM-2 as a probe that recognizes either MPF itself or a regulator of MPF.^ Since M phase-specific H1 kinase was believed to be identical to cdc2 kinase and MPF, I proceeded to determine whether MPM-2 recognized the M phase-specific H1 kinase. I found that MPM-2 did recognize an M phase-specific H1 kinase. However, this kinase was not cdc2 kinase. This kinase (MPM-2 kinase) is present in a latent form in immature oocytes and is activated in tandem with the activation of MPF during oocyte maturation. It appears to accelerate progesterone-induced oocyte maturation. Therefore, MPM-2 kinase may be a novel positive regulator of MPF activation.^ MPM-2 depletes MPF activity, but not cdc2 kinase activity. This discrepancy caused me to question the equivalency of MPF with cdc2 kinase. I found that when a high percentage of MPF activity was recovered from gel filtration of mature oocyte extract, the recovered MPF activity was due to two factors, cdc2 kinase and a factor recognized by MPM-2. This factor might activate and stabilize cdc2 kinase. Identification of this factor in the present study may contribute to the understanding of the autoactivation of MPF. ^

Lake surface water temperatures of European Alpine lakes (1989–2013) based on the Advanced Very High Resolution Radiometer (AVHRR) 1 km data set

Lake water temperature (LWT) is an important driver of lake ecosystems and it has been identified as an indicator of climate change. Consequently, the Global Climate Observing System (GCOS) lists LWT as an essential climate variable. Although for some European lakes long in situ time series of LWT do exist, many lakes are not observed or only on a non-regular basis making these observations insufficient for climate monitoring. Satellite data can provide the information needed. However, only few satellite sensors offer the possibility to analyse time series which cover 25 years or more. The Advanced Very High Resolution Radiometer (AVHRR) is among these and has been flown as a heritage instrument for almost 35 years. It will be carried on for at least ten more years, offering a unique opportunity for satellite-based climate studies. Herein we present a satellite-based lake surface water temperature (LSWT) data set for European water bodies in or near the Alps based on the extensive AVHRR 1 km data record (1989–2013) of the Remote Sensing Research Group at the University of Bern. It has been compiled out of AVHRR/2 (NOAA-07, -09, -11, -14) and AVHRR/3 (NOAA-16, -17, -18, -19 and MetOp-A) data. The high accuracy needed for climate related studies requires careful pre-processing and consideration of the atmospheric state. The LSWT retrieval is based on a simulation-based scheme making use of the Radiative Transfer for TOVS (RTTOV) Version 10 together with ERA-interim reanalysis data from the European Centre for Medium-range Weather Forecasts. The resulting LSWTs were extensively compared with in situ measurements from lakes with various sizes between 14 and 580 km2 and the resulting biases and RMSEs were found to be within the range of −0.5 to 0.6 K and 1.0 to 1.6 K, respectively. The upper limits of the reported errors could be rather attributed to uncertainties in the data comparison between in situ and satellite observations than inaccuracies of the satellite retrieval. An inter-comparison with the standard Moderate-resolution Imaging Spectroradiometer (MODIS) Land Surface Temperature product exhibits RMSEs and biases in the range of 0.6 to 0.9 and −0.5 to 0.2 K, respectively. The cross-platform consistency of the retrieval was found to be within ~ 0.3 K. For one lake, the satellite-derived trend was compared with the trend of in situ measurements and both were found to be similar. Thus, orbital drift is not causing artificial temperature trends in the data set. A comparison with LSWT derived through global sea surface temperature (SST) algorithms shows lower RMSEs and biases for the simulation-based approach. A running project will apply the developed method to retrieve LSWT for all of Europe to derive the climate signal of the last 30 years. The data are available at doi:10.1594/PANGAEA.831007.

Examining invisible social control as predictor of daily smoking and negative affect after a self-set quit date

Objectives: The dual-effects model of social control proposes that social control leads to better health practices, but also arouses psychological distress. However, findings are inconsistent in relation to health behavior and psychological distress. Recent research suggests that the most effective control is unnoticed by the receiver (i.e., invisible). There is some evidence that invisible social control is beneficial for positive and negative affective reactions. Yet, investigations of the influence of invisible social control on daily smoking and distress have been limited. In daily diaries, we investigated how invisible social control is associated with number of cigarettes smoked and negative affect on a daily basis. Methods: Overall, 99 smokers (72.0% men, mean age M = 40.48, SD = 9.82) and their non-smoking partners completed electronic diaries from a self-set quit date for 22 consecutive days within the hour before going to bed, reporting received and provided social control, daily number of cigarettes smoked, and negative affect. Results: Multilevel analyses indicated that between-person levels of invisible social control were associated with lower negative affect, whereas they were unrelated to number of cigarettes smoked. On days with higher-than-average invisible social control, smokers reported less cigarettes smoked and more negative affect. Conclusions: Between-person level findings indicate that invisible social control can be beneficial for negative affect. However, findings on the within-person level are in line with the assumptions of the dual-effects model of social control: Invisible social control reduced daily smoking and simultaneously increased daily negative affect within person.

Procedure for the identification of population characteristics for targeting intervention services on the basis of outcome-goal priorities: Case management services for the chronic mentally ill

Although the processes involved in rational patient targeting may be obvious for certain services, for others, both the appropriate sub-populations to receive services and the procedures to be used for their identification may be unclear. This project was designed to address several research questions which arise in the attempt to deliver appropriate services to specific populations. The related difficulties are particularly evident for those interventions about which findings regarding effectiveness are conflicting. When an intervention clearly is not beneficial (or is dangerous) to a large, diverse population, consensus regarding withholding the intervention from dissemination can easily be reached. When findings are ambiguous, however, conclusions may be impossible.^ When characteristics of patients likely to benefit from an intervention are not obvious, and when the intervention is not significantly invasive or dangerous, the strategy proposed herein may be used to identify specific characteristics of sub-populations which may benefit from the intervention. The identification of these populations may be used both in further informing decisions regarding distribution of the intervention and for purposes of planning implementation of the intervention by identifying specific target populations for service delivery.^ This project explores a method for identifying such sub-populations through the use of related datasets generated from clinical trials conducted to test the effectiveness of an intervention. The method is specified in detail and tested using the example intervention of case management for outpatient treatment of populations with chronic mental illness. These analyses were applied in order to identify any characteristics which distinguish specific sub-populations who are more likely to benefit from case management service, despite conflicting findings regarding its effectiveness for the aggregate population, as reported in the body of related research. However, in addition to a limited set of characteristics associated with benefit, the findings generated, a larger set of characteristics of patients likely to experience greater improvement without intervention. ^

Shift in speed selectivity of visual cortical neurons: A neural basis of perceived motion contrast

The perceived speed of motion in one part of the visual field is influenced by the speed of motion in its surrounding fields. Little is known about the cellular mechanisms causing this phenomenon. Recordings from mammalian visual cortex revealed that speed preference of the cortical cells could be changed by displaying a contrast speed in the field surrounding the cell’s classical receptive field. The neuron’s selectivity shifted to prefer faster speed if the contextual surround motion was set at a relatively lower speed, and vice versa. These specific center–surround interactions may underlie the perceptual enhancement of speed contrast between adjacent fields.

Homogeneous Spatial Units (HSU) - a Pan-European geographical basis for environmental and socio-economic modelling

The spatial data set delineates areas with similar environmental properties regarding soil, terrain morphology, climate and affiliation to the same administrative unit (NUTS3 or comparable units in size) at a minimum pixel size of 1km2. The scope of developing this data set is to provide a link between spatial environmental information (e.g. soil properties) and statistical data (e.g. crop distribution) available at administrative level. Impact assessment of agricultural management on emissions of pollutants or radiative active gases, or analysis regarding the influence of agricultural management on the supply of ecosystem services, require the proper spatial coincidence of the driving factors. The HSU data set provides e.g. the link between the agro-economic model CAPRI and biophysical assessment of environmental impacts (updating previously spatial units, Leip et al. 2008), for the analysis of policy scenarios. Recently, a statistical model to disaggregate crop information available from regional statistics to the HSU has been developed (Lamboni et al. 2016). The HSU data set consists of the spatial layers provided in vector and raster format as well as attribute tables with information on the properties of the HSU. All input data for the delineation the HSU is publicly available. For some parameters the attribute tables provide the link between the HSU data set and e.g. the soil map(s) rather than the data itself. The HSU data set is closely linked the USCIE data set.

ELPA (European Leaf Physiognomic Approach): Grid data set of the leaf physiognomic composition of the extant European hardwood vegetation

Physiognomic traits of plant leaves such as size, shape or margin are decisively affected by the prevailing environmental conditions of the plant habitat. On the other hand, if a relationship between environment and leaf physiognomy can be shown to exist, vegetation represents a proxy for environmental conditions. This study investigates the relationship between physiognomic traits of leaves from European hardwood vegetation and environmental parameters in order to create a calibration dataset based on high resolution grid cell data. The leaf data are obtained from synthetic chorologic floras, the environmental data comprise climatic and ecologic data. The high resolution of the data allows for a detailed analysis of the spatial dependencies between the investigated parameters. The comparison of environmental parameters and leaf physiognomic characters reveals a clear correlation between temperature related parameters (e.g. mean annual temperature or ground frost frequency) and the expression of leaf characters (e.g. the type of leaf margin or the base of the lamina). Precipitation related parameters (e.g. mean annual precipitation), however, show no correlation with the leaf physiognomic composition of the vegetation. On the basis of these results, transfer functions for several environmental parameters are calculated from the leaf physiognomic composition of the extant vegetation. In a next step, a cluster analysis is applied to the dataset in order to identify "leaf physiognomic communities". Several of these are distinguished, characterised and subsequently used for vegetation classification. Concerning the leaf physiognomic diversity there are precise differences between each of these "leaf physiognomic classes". There is a clear increase of leaf physiognomic diversity with increasing variability of the environmental parameters: Northern vegetation types are characterised by a more or less homogeneous leaf physiognomic composition whereas southern vegetation types like the Mediterranean vegetation show a considerable higher leaf physiognomic diversity. Finally, the transfer functions are used to estimate palaeo-environmental parameters of three fossil European leaf assemblages from Late Oligocene and Middle Miocene. The results are compared with results obtained from other palaeo-environmental reconstructing methods. The estimates based on a direct linear ordination seem to be the most realistic ones, as they are highly consistent with the Coexistence Approach.

Structural basis and prediction of substrate specificity in protein serine/threonine kinases

The large number of protein kinases makes it impractical to determine their specificities and substrates experimentally. Using the available crystal structures, molecular modeling, and sequence analyses of kinases and substrates, we developed a set of rules governing the binding of a heptapeptide substrate motif (surrounding the phosphorylation site) to the kinase and implemented these rules in a web-interfaced program for automated prediction of optimal substrate peptides, taking only the amino acid sequence of a protein kinase as input. We show the utility of the method by analyzing yeast cell cycle control and DNA damage checkpoint pathways. Our method is the only available predictive method generally applicable for identifying possible substrate proteins for protein serine/threonine kinases and helps in silico construction of signaling pathways. The accuracy of prediction is comparable to the accuracy of data from systematic large-scale experimental approaches.

OMERACT-OARSI Initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited.

Background: The OARSI Standing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains (pain, function, and patient's global assessment) as a single variable for clinical trials (1). For each domain, a response was defined by both a relative and an absolute change, with different cut-offs with regard to the drug, the route of administration and the OA localization. Objective: To propose a simplified set of responder criteria with a similar cut-off, whatever the drug, the route or the OA localization. Methods: Data driven approach: (1) Two databases were considered The 'elaboration' database with which the formal OARSI sets of responder criteria were elaborated and The 'revisit' database. (2) Six different scenarios were evaluated: The two formal OARSI sets of criteria Four proposed scenarios of simplified sets of criteria Data from clinical randomized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different databases ('elaboration' versus 'revisit') and those of the four proposed simplified scenarios within the 'revisit' database. The placebo effect, active effect, treatment effect, and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios. Experts' opinion approach: Results were discussed among the participants of the OMERACT VI meeting, who voted to select the definite OMERACT-OARSI set of criteria (one of the six evaluated scenarios). Results: Data driven approach: Fourteen trials totaling 1886 CA patients and fifteen studies involving 8164 CA patients were evaluated in the 'elaboration' and the 'revisit' databases respectively. The variability of the performances observed in the 'revisit' database when using the different simplified scenarios was similar to that observed between the two databases ('elaboration' versus 'revisit') when using the formal scenarios. The treatment effect and the required sample arm size were similar for each set of criteria. Experts' opinion approach: According to the experts, these two previous performances were the most important of an optimal set of responder criteria. They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response, with similar cut-offs whatever the drug, the route of administration or the CA localization. Conclusion: This data driven and experts' opinion approach is the basis for proposing an optimal simplified set of responder criteria for CA clinical trials. Other studies, using other sets of CA patients, are required in order to further validate this proposed OMERACT - OARSI set of criteria. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A new fuzzy additive model for determining the common set of weights in Data Envelopment Analysis

The main advantage of Data Envelopment Analysis (DEA) is that it does not require any priori weights for inputs and outputs and allows individual DMUs to evaluate their efficiencies with the input and output weights that are only most favorable weights for calculating their efficiency. It can be argued that if DMUs are experiencing similar circumstances, then the pricing of inputs and outputs should apply uniformly across all DMUs. That is using of different weights for DMUs makes their efficiencies unable to be compared and not possible to rank them on the same basis. This is a significant drawback of DEA; however literature observed many solutions including the use of common set of weights (CSW). Besides, the conventional DEA methods require accurate measurement of both the inputs and outputs; however, crisp input and output data may not relevant be available in real world applications. This paper develops a new model for the calculation of CSW in fuzzy environments using fuzzy DEA. Further, a numerical example is used to show the validity and efficacy of the proposed model and to compare the results with previous models available in the literature.

Applications of Radial Basis Neural Networks for Area Forest

This paper proposes a new method using radial basis neural networks in order to find the classification and the recognition of trees species for forest inventories. This method computes the wood volume using a set of data easily obtained. The results that are obtained improve the used classic and statistical models.