Synthesis of novel coumarin derivatives as potential inhibitors of HIV-1 protease

This research has focused on the development of novel coumann derivatives containing peptide-like side chains as potential HIV-1 protease inhibitors. The reaction of various salicylaldehyde derivatives with tert-butyl acrylate In the presence of 1,4- diazabicyclo[2.2.2]octane (DABCO) has afforded a series of Baylis-Hillman adducts in moderate yield. Cyclisation of the adducts in the presence of HCI afforded the corresponding 3-(chloromethyl)coumarin derivatives, which have been reacted with various amine hydrochlorides in the presence of Proton Sponge® to afford a series of novel 3- (aminomethyl)coumarin derivatives, which were fully characterised by NMR and HRMS methods. Various approaches to the introduction of hydroxyl or amino groups at the C-4 position of coumarin and the 3-(chloromethyl)coumarin derivatives have been explored; these have included dihydroxylation of the coumarin double bond, and the synthesis of 4- benzylaminocoumarin derivatives as potential intermediates. The Vilsmeier-Haack and Mannich reactions have also been investigated as possible methods of introducing the desired peptide-like functionality. Computer modelling of selected structures has indicated that some of the novel 3- (aminomethyl)coumarin derivatives may exhibit activity as inhibitors of HIV-1 protease. The planned enzyme inhibition assays were unfortunately precluded by the aqueous insolubility of the selected compounds. Three ¹³C NMR chemical shift algorithms, viz., Modgraph Neural Network, Modgraph HOSE and Chern Window, have been applied to selected compounds prepared in this study. The Modgraph Neural Network algorithm was found, in all cases, to provide the most accurate correlations with the experimentally-determined chemical shifts.KMBT_363Adobe Acrobat 9.54 Paper Capture Plug-i

Existing benchmark systems for assessing global warming potential of buildings – Analysis of IEA EBC Annex 72 cases

Life cycle assessment (LCA) is increasingly being used as a tool by the building industry and actors to assess the global warming potential (GWP) of building activities. In several countries, life cycle based requirements on GWP are currently being incorporated into building regulations. After the establishment of general calculation rules for building LCA, a crucial next step is to evaluate the performance of the specific building design. For this, reference values or benchmarks are needed, but there are several approaches to defining these. This study presents an overview of existing benchmark systems documented in seventeen cases from the IEA EBC Annex 72 project on LCA of buildings. The study characterizes their different types of methodological background and displays the reported values. Full life cycle target values for residential and non-residential buildings are found around 10-20 kg CO2e/m2/y, whereas reference values are found between 20-80 kg CO2e/m2/y. Possible embodied target- and reference values are found between 1-12 kg CO2e/m2/y for both residential and non-residential buildings. Benchmark stakeholders can use the insights from this study to understand the justifications of the background methodological choices and to gain an overview of the level of GWP performance across benchmark systems.publishedVersio

Who speaks for the future of Earth? How critical social science can extend the conversation on the Anthropocene

This paper asks how the social sciences can engage with the idea of the Anthropocene in productive ways. In response to this question we outline an interpretative research agenda that allows critical engagement with the Anthropocene as a socially and culturally bounded object with many possible meanings and political trajectories. In order to facilitate the kind of political mobilization required to meet the complex environmental challenges of our times, we argue that the social sciences should refrain from adjusting to standardized research agendas and templates. A more urgent analytical challenge lies in exposing, challenging and extending the ontological assumptions that inform how we make sense of and respond to a rapidly changing environment. By cultivating environmental research that opens up multiple interpretations of the Anthropocene, the social sciences can help to extend the realm of the possible for environmental politics

The geomorphology of the Anthropocene:emergence, status and implications

This is the peer reviewed version of the following article: BROWN, A.G. ... et al, 2017. The geomorphology of the Anthropocene: emergence, status and implications. Earth Surface Processes and Landforms, 42(1), pp.71-90., which has been published in final form at http://dx.doi.org/10.1002/esp.3943. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.The Anthropocene is proposed as a new interval of geological time in which human influence on Earth and its geological record dominates over natural processes. A major challenge in demarcating the Anthropocene is that the balance between human-influenced and natural processes varies over spatial and temporal scales owing to the inherent variability of both human activities (as associated with culture and modes of development) and natural drivers (e.g. tectonic activity and sea level variation). Against this backdrop, we consider how geomorphology might contribute towards the Anthropocene debate focussing on human impact on aeolian, fluvial, cryospheric and coastal process domains, and how evidence of this impact is preserved in landforms and sedimentary records. We also consider the evidence for an explicitly anthropogenic geomorphology that includes artificial slopes and other human-created landforms. This provides the basis for discussing the theoretical and practical contributions that geomorphology can make to defining an Anthropocene stratigraphy. It is clear that the relevance of the Anthropocene concept varies considerably amongst different branches of geomorphology, depending on the history of human actions in different process domains. For example, evidence of human dominance is more widespread in fluvial and coastal records than in aeolian and cryospheric records, so geomorphologically the Anthropocene would inevitably comprise a highly diachronous lower boundary. Even to identify this lower boundary, research would need to focus on the disambiguation of human effects on geomorphological and sedimentological signatures. This would require robust data, derived from a combination of modelling and new empirical work rather than an arbitrary ‘war of possible boundaries’ associated with convenient, but disputed, `golden spikes’. Rather than being drawn into stratigraphical debates, the primary concern of geomorphology should be with the investigation of processes and landform development, so providing the underpinning science for the study of this time of critical geological transition

GraphClust: alignment-free structural clustering of local RNA secondary structures

Motivation: Clustering according to sequence–structure similarity has now become a generally accepted scheme for ncRNA annotation. Its application to complete genomic sequences as well as whole transcriptomes is therefore desirable but hindered by extremely high computational costs

Developing fit-for-purpose self-report instruments for assessing consumer responses to tobacco and nicotine products: the ABOUT™ Toolbox initiative [version 1; referees: 2 approved]

Background. Determining the public health impact of tobacco harm reduction strategies requires the assessment of consumer perception and behavior associated with tobacco and nicotine products (TNPs) with different exposure and risk profiles. In this context, rigorous methods to develop and validate psychometrically sound self-report instruments to measure consumers’ responses to TNPs are needed. Methods. Consistent with best practice guidelines, including the U.S. Food and Drug Administration’s “Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims,” scientifically designed, fit-for-purpose, reliable, and valid instruments are now being applied to tobacco regulatory research. Results. This brief report presents the ABOUT™ Toolbox (Assessment of Behavioral OUtcomes related to Tobacco and nicotine products) initiative. This communication: (1) describes the methodological steps followed for the development and validation of the measurement instruments included in the ABOUT™ Toolbox, (2) presents a summary of the high-priority tobacco-related domains that are currently covered in the ABOUT™ Toolbox (i.e., risk perception, dependence, product experience, health and functioning, and use history), and (3) details how the measurement instruments are made accessible to the scientific community. Conclusions. By making the ABOUT™ Toolbox available to the tobacco research and public health community, we envision a rapidly expanding knowledge base, with the goals of (1) supporting consumer perception and behavior research to allow comparisons across a wide spectrum of TNPs, (2) enabling public health and regulatory communities to make better-informed decisions for future regulation of TNPs, and (3) enhancing surveillance activities associated with the impact of TNPs on population health

Evaluation at the Federal University of Applied Adminstrative Sciences

Dulisch, Linssen und Reiter (2001) legten ein umfassendes Evaluationskonzept für die FH Bund vor. In den zehn Fachbereichen und im Zentralbereich der FH Bund erfolgt/e eine Diskussion, Modifikation und konkrete Anpassung an die Belange vor Ort. Dieser Prozess wurde in einer Evaluationtagung an der FH Bund im Juni 2003 gebündelt. Die Tagung zeigte, dass alle Fachbereiche und der Zentralbereich Fortschritte machen, wenn auch in unterschiedlichem Tempo. Dieser Band dokumentiert den Status Quo der Evaluation in den Fachbereichen und dem Zentralbereich und folgt damit § 6 Hochschulrahmengesetz (HRG), wonach die Arbeit der Hochschulen bewertet und das Ergebnis der Bewertung veröffentlicht werden soll. Inhaltsübersicht: - Evaluation an Fachhochschulen - Überblick - Empfehlungen des Benchmarking Clubs - Evaluationstagung der FH Bund 2003 - Zentralbereich - Allgemeine und Innere Verwaltung - Arbeitsverwaltung - Auswärtige Angelegenheiten - Bundesgrenzschutz - Bundeswehrverwaltung - Finanzen - Landwirtschaftliche Sozialversicherung - Öffentliche Sicherheit - Gesamtkonzept - Öffentliche Sicherheit - Abteilung Kriminalpolizei - Sozialversicherung - Wetterdiens

Covert Reorganization of Implicit Task Representations by Slow Wave Sleep

There is evidence that slow wave sleep (SWS) promotes the consolidation of memories that are subserved by mediotemporal- and hippocampo-cortical neural networks. In contrast to implicit memories, explicit memories are accompanied by conscious (attentive and controlled) processing. Awareness at pre-sleep encoding has been recognized as critical for the off-line memory consolidation. The present study elucidated the role of task-dependent cortical activation guided by attentional control at pre-sleep encoding for the consolidation of hippocampus-dependent memories during sleep.A task with a hidden regularity was used (Number Reduction Task, NRT), in which the responses that can be implicitly predicted by the hidden regularity activate hippocampo-cortical networks more strongly than responses that cannot be predicted. Task performance was evaluated before and after early-night sleep, rich in SWS, and late-night sleep, rich in rapid eye movement (REM) sleep. In implicit conditions, slow cortical potentials (SPs) were analyzed to reflect the amount of controlled processing and the localization of activated neural task representations.During implicit learning before sleep, the amount of controlled processing did not differ between unpredictable and predictable responses, nor between early- and late-night sleep groups. A topographic re-distribution of SPs indicating a spatial reorganization occurred only after early, not after late sleep, and only for predictable responses. These SP changes correlated with the amount of SWS and were covert because off-line RT decrease did not differentiate response types or sleep groups.It is concluded that SWS promotes the neural reorganization of task representations that rely on the hippocampal system despite absence of conscious access to these representations.Original neurophysiologic evidence is provided for the role of SWS in the consolidation of memories encoded with hippocampo-cortical interaction before sleep. It is demonstrated that this SWS-mediated mechanism does not depend critically on explicitness at learning nor on the amount of controlled executive processing during pre-sleep encoding

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi