On transmissible load formulations in topology optimization

Transmissible loads are external loads defined by their line of action, with actual points of load application chosen as part of the topology optimization process. Although for problems where the optimal structure is a funicular, transmissible loads can be viewed as surface loads, in other cases such loads are free to be applied to internal parts of the structure. There are two main transmissible load formulations described in the literature: a rigid bar (constrained displacement) formulation or, less commonly, a migrating load (equilibrium) formulation. Here, we employ a simple Mohr’s circle analysis to show that the rigid bar formulation will only produce correct structural forms in certain specific circumstances. Numerical examples are used to demonstrate (and explain) the incorrect topologies produced when the rigid bar formulation is applied in other situations. A new analytical solution is also presented for a uniformly loaded cantilever structure. Finally, we invoke duality principles to elucidate the source of the discrepancy between the two formulations, considering both discrete truss and continuum topology optimization formulations

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky

MacaqueNet: Advancing comparative behavioural research through large-scale collaboration

There is a vast and ever-accumulating amount of behavioural data on individually recognised animals, an incredible resource to shed light on the ecological and evolutionary drivers of variation in animal behaviour. Yet, the full potential of such data lies in comparative research across taxa with distinct life histories and ecologies. Substantial challenges impede systematic comparisons, one of which is the lack of persistent, accessible and standardised databases. Big-team approaches to building standardised databases offer a solution to facilitating reliable cross-species comparisons. By sharing both data and expertise among researchers, these approaches ensure that valuable data, which might otherwise go unused, become easier to discover, repurpose and synthesise. Additionally, such large-scale collaborations promote a culture of sharing within the research community, incentivising researchers to contribute their data by ensuring their interests are considered through clear sharing guidelines. Active communication with the data contributors during the standardisation process also helps avoid misinterpretation of the data, ultimately improving the reliability of comparative databases. Here, we introduce MacaqueNet, a global collaboration of over 100 researchers (https://macaquenet.github.io/) aimed at unlocking the wealth of cross-species data for research on macaque social behaviour. The MacaqueNet database encompasses data from 1981 to the present on 61 populations across 14 species and is the first publicly searchable and standardised database on affiliative and agonistic animal social behaviour. We describe the establishment of MacaqueNet, from the steps we took to start a large-scale collective, to the creation of a cross-species collaborative database and the implementation of data entry and retrieval protocols. We share MacaqueNet's component resources: an R package for data standardisation, website code, the relational database structure, a glossary and data sharing terms of use. With all these components openly accessible, MacaqueNet can act as a fully replicable template for future endeavours establishing large-scale collaborative comparative databases

Changes to the Fossil Record of Insects through Fifteen Years of Discovery

The first and last occurrences of hexapod families in the fossil record are compiled from publications up to end-2009. The major features of these data are compared with those of previous datasets (1993 and 1994). About a third of families (>400) are new to the fossil record since 1994, over half of the earlier, existing families have experienced changes in their known stratigraphic range and only about ten percent have unchanged ranges. Despite these significant additions to knowledge, the broad pattern of described richness through time remains similar, with described richness increasing steadily through geological history and a shift in dominant taxa, from Palaeoptera and Polyneoptera to Paraneoptera and Holometabola, after the Palaeozoic. However, after detrending, described richness is not well correlated with the earlier datasets, indicating significant changes in shorter-term patterns. There is reduced Palaeozoic richness, peaking at a different time, and a less pronounced Permian decline. A pronounced Triassic peak and decline is shown, and the plateau from the mid Early Cretaceous to the end of the period remains, albeit at substantially higher richness compared to earlier datasets. Origination and extinction rates are broadly similar to before, with a broad decline in both through time but episodic peaks, including end-Permian turnover. Origination more consistently exceeds extinction compared to previous datasets and exceptions are mainly in the Palaeozoic. These changes suggest that some inferences about causal mechanisms in insect macroevolution are likely to differ as well

Fragment‐Merging Strategies with Known Pyrimidine Scaffolds Targeting Dihydrofolate Reductase from <i>Mycobacterium tuberculosis</i>

Funder: EPRSCFunder: DAAD; doi: http://dx.doi.org/10.13039/501100001655Funder: Cambridge Trust; doi: http://dx.doi.org/10.13039/501100003343Funder: Emmanuel College, CambridgeFunder: Ministry of Education, MalaysiaDihydrofolate reductase (DHFR) is a key enzyme involved in the folate pathway that has been heavily targeted for the development of therapeutics against cancer and bacterial and protozoa infections amongst others. Despite being an essential enzyme for Mycobacterium tuberculosis (Mtb) viability, DHFR remains an underexploited target for tuberculosis (TB) treatment. Herein, we report the preparation and evaluation of a series of compounds against Mtb DHFR (MtbDHFR). The compounds have been designed using a merging strategy of traditional pyrimidine‐based antifolates with a previously discovered unique fragment hit against MtbDHFR. In this series, four compounds displayed a high affinity against MtbDHFR, with sub‐micromolar affinities. Additionally, we determined the binding mode of six of the best compounds using protein crystallography, which revealed occupation of an underutilised region of the active site

Fragment-Merging Strategies with Known Pyrimidine Scaffolds Targeting Dihydrofolate Reductase from Mycobacterium tuberculosis.

Dihydrofolate reductase (DHFR) is a key enzyme involved in the folate pathway that has been heavily targeted for the development of therapeutics against cancer and bacterial and protozoa infections amongst others. Despite being an essential enzyme for Mycobacterium tuberculosis (Mtb) viability, DHFR remains an underexploited target for tuberculosis (TB) treatment. Herein, we report the preparation and evaluation of a series of compounds against Mtb DHFR (MtbDHFR). The compounds have been designed using a merging strategy of traditional pyrimidine-based antifolates with a previously discovered unique fragment hit against MtbDHFR. In this series, four compounds displayed a high affinity against MtbDHFR, with sub-micromolar affinities. Additionally, we determined the binding mode of six of the best compounds using protein crystallography, which revealed occupation of an underutilised region of the active site