Onset of collective and cohesive motion

We study the onset of collective motion, with and without cohesion, of groups of noisy self-propelled particles interacting locally. We find that this phase transition, in two space dimensions, is always discontinuous, including for the minimal model of Vicsek et al. [Phys. Rev. Lett. {\bf 75},1226 (1995)] for which a non-trivial critical point was previously advocated. We also show that cohesion is always lost near onset, as a result of the interplay of density, velocity, and shape fluctuations.Comment: accepted for publication in Phys. Rev. Let

Mutations and amplification of oncogenes in endometrial cancer

Alterations in oncogenes are critical steps in the development of endometrial cancer. To investigate the potential clinical relevance of the amplification of the oncogenes c-erbB2, c-myc, and int-2 and the mutation of K-ras in endometrial cancer, 112 tumors were examined using PCR-based fluorescent DNA technology. Amplification of the three oncogenes and the mutation of K-ras were correlated with age, tumor size, lymph node status, metastases, stage, histological types, grade, steroid hormone receptor expression (estrogen receptor, ER; progesterone receptor, PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy. Oncogene amplification of c-erbB2 was detected in 18.9%, of c-myc in 2.7% and of int-2 in 4.2%, and K-ras mutation in 11.6%. No significant correlations could be detected between amplification of c-erbB2 and any of the other parameters. Mutation of K-ras is associated with positive expression of PgR. This might indicate that mutation and activation of K-ras are involved in the development of hormonal independence in endometrial cancer

Estimating the total number of phosphoproteins and phosphorylation sites in eukaryotic proteomes

Background: Phosphorylation is the most frequent post-translational modification made to proteins and may regulate protein activity as either a molecular digital switch or a rheostat. Despite the cornucopia of high-throughput (HTP) phosphoproteomic data in the last decade, it remains unclear how many proteins are phosphorylated and how many phosphorylation sites (p-sites) can exist in total within a eukaryotic proteome. We present the first reliable estimates of the total number of phosphoproteins and p-sites for four eukaryotes (human, mouse, Arabidopsis, and yeast). Results: In all, 187 HTP phosphoproteomic datasets were filtered, compiled, and studied along with two low-throughput (LTP) compendia. Estimates of the number of phosphoproteins and p-sites were inferred by two methods: Capture-Recapture, and fitting the saturation curve of cumulative redundant vs. cumulative non-redundant phosphoproteins/p-sites. Estimates were also adjusted for different levels of noise within the individual datasets and other confounding factors. We estimate that in total, 13 000, 11 000, and 3000 phosphoproteins and 230 000, 156 000, and 40 000 p-sites exist in human, mouse, and yeast, respectively, whereas estimates for Arabidopsis were not as reliable. Conclusions: Most of the phosphoproteins have been discovered for human, mouse, and yeast, while the dataset for Arabidopsis is still far from complete. The datasets for p-sites are not as close to saturation as those for phosphoproteins. Integration of the LTP data suggests that current HTP phosphoproteomics appears to be capable of capturing 70% to 95% of total phosphoproteins, but only 40% to 60% of total p-sites

A right-handed isotropic medium with a negative refractive index

The sign of the refractive index of any medium is soley determined by the requirement that the propagation of an electromagnetic wave obeys Einstein causality. Our analysis shows that this requirement predicts that the real part of the refractive index may be negative in an isotropic medium even if the electric permittivity and the magnetic permeability are both positive. Such a system may be a route to negative index media at optical frequencies. We also demonstrate that the refractive index may be positive in left-handed media that contain two molecular species where one is in its excited state.Comment: 4.1 pages, 4 figures, submitted to Physical Review Letter

MV cable lifetime improvement analysis through transformer tap changes

Cable life depends mainly on the thermal stress, which relates to the current applied on the cable. Voltage changes in medium voltage (MV) cables due to transformer tap changes will also change the current flowing through the cable, which will change the cable temperature. In order to extend the cable life, this paper aims to simulate and analyse the potential thermal lifetime improvement of cables through long-term tap changes within the statutory levels. Firstly, the IEC standard (60287) method for rating and modelling cables is applied to evaluate the cable temperature under different voltages and relative currents. Different cable configurations will also be considered in simulations as temperature is dependent on the cable dimensions. Then, typical thermal lifetime analytical expressions will be used to evaluate the long-term influence of voltage changes. Lastly, the obtained thermal lifetime assessments under different transformer tap changes and different cable configurations will provide a potential understanding of cable lifetime changes through implementation of permitted regulatory voltage changes

Antibubbles enable tunable payload release with low-intensity ultrasound

The benefits of ultrasound are its ease-of-use and its ability to precisely deliver energy in opaque and complex media. However, most materials responsive to ultrasound show a weak response, requiring the use of high powers, which are associated with undesirable streaming, cavitation, or temperature rise. These effects hinder response control and may even cause damage to the medium where the ultrasound is applied. Moreover, materials that are currently in use rely on all-or-nothing effects, limiting the ability to fine-tune the response of the material on the fly. For these reasons, there is a need for materials that can respond to low intensity ultrasound with programmable responses. Here it is demonstrated that antibubbles are a low-intensity-ultrasound-responsive material system that can controllably release a payload using acoustic pressures in the kPa range. Varying their size and composition tunes the release pressure, and the response can be switched between a single release and stepwise release across multiple ultrasound pulses. Observations using confocal and high-speed microscopy revealed different ways that can lead to release. These findings lay the groundwork to design antibubbles that controllably respond to low-intensity ultrasound, opening a wide range of applications ranging from ultrasound-responsive material systems to carriers for targeted delivery.Comment: Main Text: 14 pages, 4 figures. Embedded SI: 4 pages, 5 figure

Spectral Signature Generalization and Expansion Can Improve the Accuracy of Satellite Image Classification

Conventional supervised classification of satellite images uses a single multi-band image and coincident ground observations to construct spectral signatures of land cover classes. We compared this approach with three alternatives that derive signatures from multiple images and time periods: (1) signature generalization: spectral signatures are derived from multiple images within one season, but perhaps from different years; (2) signature expansion: spectral signatures are created with data from images acquired during different seasons of the same year; and (3) combinations of expansion and generalization. Using data for northern Laos, we assessed the quality of these different signatures to (a) classify the images used to derive the signature, and (b) for use in temporal signature extension, i.e., applying a signature obtained from data of one or several years to images from other years. When applying signatures to the images they were derived from, signature expansion improved accuracy relative to the conventional method, and variability in accuracy declined markedly. In contrast, signature generalization did not improve classification. When applying signatures to images of other years (temporal extension), the conventional method, using a signature derived from a single image, resulted in very low classification accuracy. Signature expansion also performed poorly but multi-year signature generalization performed much better and this appears to be a promising approach in the temporal extension of spectral signatures for satellite image classification

Polyploidy breaks speciation barriers in Australian burrowing frogs Neobatrachus

Polyploidy has played an important role in evolution across the tree of life but it is still unclear how polyploid lineages may persist after their initial formation. While both common and well-studied in plants, polyploidy is rare in animals and generally less understood. The Australian burrowing frog genus Neobatrachus is comprised of six diploid and three polyploid species and offers a powerful animal polyploid model system. We generated exome-capture sequence data from 87 individuals representing all nine species of Neobatrachus to investigate species-level relationships, the origin and inheritance mode of polyploid species, and the population genomic effects of polyploidy on genus-wide demography. We describe rapid speciation of diploid Neobatrachus species and show that the three independently originated polyploid species have tetrasomic or mixed inheritance. We document higher genetic diversity in tetraploids, resulting from widespread gene flow between the tetraploids, asymmetric inter-ploidy gene flow directed from sympatric diploids to tetraploids, and isolation of diploid species from each other. We also constructed models of ecologically suitable areas for each species to investigate the impact of climate on differing ploidy levels. These models suggest substantial change in suitable areas compared to past climate, which correspond to population genomic estimates of demographic histories. We propose that Neobatrachus diploids may be suffering the early genomic impacts of climate-induced habitat loss, while tetraploids appear to be avoiding this fate, possibly due to widespread gene flow. Finally, we demonstrate that Neobatrachus is an attractive model to study the effects of ploidy on the evolution of adaptation in animals

Cytosolic delivery of nucleic acids: The case of ionizable lipid nanoparticles

Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nano-delivery system for therapeutic nucleic acids. The great effort put in the development of ionizable lipids with increased in vivo potency brought LNPs from the laboratory benches to the FDA approval of patisiran in 2018 and the ongoing clinical trials for mRNA-based vaccines against SARS-CoV-2. Despite these success stories, several challenges remain in RNA delivery, including what is known as “endosomal escape.” Reaching the cytosol is mandatory for unleashing the therapeutic activity of RNA molecules, as their accumulation in other intracellular compartments would simply result in efficacy loss. In LNPs, the ability of ionizable lipids to form destabilizing non-bilayer structures at acidic pH is recognized as the key for endosomal escape and RNA cytosolic delivery. This is motivating a surge in studies aiming at designing novel ionizable lipids with improved biodegradation and safety profiles. In this work, we describe the journey of RNA-loaded LNPs across multiple intracellular barriers, from the extracellular space to the cytosol. In silico molecular dynamics modeling, in vitro high-resolution microscopy analyses, and in vivo imaging data are systematically reviewed to distill out the regulating mechanisms underlying the endosomal escape of RNA. Finally, a comparison with strategies employed by enveloped viruses to deliver their genetic material into cells is also presented. The combination of a multidisciplinary analytical toolkit for endosomal escape quantification and a nature-inspired design could foster the development of future LNPs with improved cytosolic delivery of nucleic acids