3D optomechanical metamaterials

Ideally, many materials should have a “knob” that allows for changing its properties at will, including the possibility to flip the sign of its behavior. This “knob” could be used to continuously tune the properties or in the sense of a digital switch. Such extreme level of stimulus–responsiveness has come into reach with recently increased possibilities of manufacturing complex rationally designed artificial materials called metamaterials on the micrometer scale. Here, we present mechanical metamaterials composed of liquid–crystal elastomers, whose director field is arranged into a designed complex three-dimensional (3D) pattern during the 3D laser printing process. External light from a blue LED, with intensities in the range of 10–30 W/cm$^{2}$, serves as the stimulus. In the first example, we repeatedly flip the sign of the Poisson’s ratio of an achiral architecture within classical elasticity. In the second example, we flip the sign of the twist per strain in a chiral metamaterial beyond classical elasticity. The presented examples overcome major limitations in responsive mechanical metamaterials and we foresee many possible three-dimensional responsive micro-architectures manufactured along these lines

Highlights from the 24th conference on retroviruses and opportunistic infections, 13-16 February 2017, Seattle, Washington, USA

From the 13th to 16th February 2017, researchers from around the world convened for the 24th annual Conference on Retroviruses and Opportunistic Infections (CROI) at the Washington State Convention Center in Seattle, Washington. The conference was organised by the International Antiviral Society-USA (IAS-USA) in partnership with the CROI Foundation. The conference included over 1000 oral and poster presentations of peer-reviewed original research as well as lectures and symposia featuring insights from leading basic, translational and clinical researchers. Highlighted here are key data presented at the conference

Expression Profiling of the Wheat Pathogen Zymoseptoria tritici Reveals Genomic Patterns of Transcription and Host-Specific Regulatory Programs

Host specialization by pathogens requires a repertoire of virulence factors as well as fine-tuned regulation of gene expression. The fungal wheat pathogen Zymoseptoria tritici (synonym Mycosphaerella graminicola) is a powerful model system for the discovery of genetic elements that underlie virulence and host specialization. We transcriptionally profiled the early stages of Z. tritici infection of a compatible host (wheat) and a noncompatible host (Brachypodium distachyon). The results revealed infection regulatory programs common to both hosts and genes with striking wheat-specific expression, with many of the latter showing sequence signatures of positive selection along the Z. tritici lineage. Genes specifically regulated during infection of wheat populated two large clusters of coregulated genes that may represent candidate pathogenicity islands. On evolutionarily labile, repeat-rich accessory chromosomes (ACs), we identified hundreds of highly expressed genes with signatures of evolutionary constraint and putative biological function. Phylogenetic analyses suggested that gene duplication events on these ACs were rare and largely preceded the diversification of Zymoseptoria species. Together, our data highlight the likely relevance for fungal growth and virulence of hundreds of Z. tritici genes, deepening the annotation and functional inference of the genes of this model pathogen

A Facile Approach for 4D Microprinting of Multi‐Photoresponsive Actuators

For microscale 4D photoresponsive actuators, light is crucial in two ways. First, the underlying additive manufacturing techniques rely on photopolymerization processes triggered by the absorption of light. Second, the absorption of light serves as the actuation stimulus. The two absorptions can be conflicting. While the microstructure requires strong absorption at the actuation wavelength(s), this absorption should not interfere with that of the manufacturing process. Herein, a simple strategy is proposed to overcome these limitations and allow for the fabrication of multi-photoresponsive 3D microstructures that can be actuated at different wavelengths of light. Two-photon 3D laser printing is selected as the fabrication technique and liquid crystalline (LC) elastomers as the functional materials. In a first step, 3D microstructures are fabricated using an aligned LC ink formulation. Thereafter, up to five different dyes exhibiting absorptions that extend over the entire visible regime (400–700 nm) are successfully incorporated into the LC microstructures by an exchange process enabling a programmable actuation by irradiating with the suitable wavelength. Furthermore, by combining dyes exhibiting orthogonal absorptions, wavelength-selective actuations are demonstrated

Orientifolds, RG Flows, and Closed String Tachyons

We discuss the fate of certain tachyonic closed string theories from two perspectives. In both cases our approach involves studying directly configurations with finite negative tree-level cosmological constant. Closed string analogues of orientifolds, which carry negative tension, are argued to represent the minima of the tachyon potential in some cases. In other cases, we make use of the fact, noted in the early string theory literature, that strings can propagate on spaces of subcritical dimension at the expense of introducing a tree-level cosmological constant. The form of the tachyon vertex operator in these cases makes it clear that a subcritical-dimension theory results from tachyon condensation. Using results of Kutasov, we argue that in some Scherk-Schwarz models, for finely-tuned tachyon condensates, a minimal model CFT times a subcritical dimension theory results. In some instances, these two sets of ideas may be related by duality.Comment: 15 pages, 2 figures, uses harvmac; v2: references adde

A prospective, single-arm, open-label, non-randomized, phase IIa trial of a nonavalent prophylactic HPV vaccine to assess immunogenicity of a prime and deferred-booster dosing schedule among 9-11 year-old girls and boys - clinical protocol

Background Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24months following a single dose of the nonavalent HPV vaccine among preteen girls and boys. Methods This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL (R) 9) over 24months, with a deferred booster dose at 24months and an optional booster at 30months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose. Discussion Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm.National Cancer Institute [HHSN26100009, CA023074]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Plasma membrane profiling defines an expanded class of cell surface proteins selectively targeted for degradation by HCMV US2 in cooperation with UL141.

Human cytomegalovirus (HCMV) US2, US3, US6 and US11 act in concert to prevent immune recognition of virally infected cells by CD8+ T-lymphocytes through downregulation of MHC class I molecules (MHC-I). Here we show that US2 function goes far beyond MHC-I degradation. A systematic proteomic study using Plasma Membrane Profiling revealed US2 was unique in downregulating additional cellular targets, including: five distinct integrin α-chains, CD112, the interleukin-12 receptor, PTPRJ and thrombomodulin. US2 recruited the cellular E3 ligase TRC8 to direct the proteasomal degradation of all its targets, reminiscent of its degradation of MHC-I. Whereas integrin α-chains were selectively degraded, their integrin β1 binding partner accumulated in the ER. Consequently integrin signaling, cell adhesion and migration were strongly suppressed. US2 was necessary and sufficient for degradation of the majority of its substrates, but remarkably, the HCMV NK cell evasion function UL141 requisitioned US2 to enhance downregulation of the NK cell ligand CD112. UL141 retained CD112 in the ER from where US2 promoted its TRC8-dependent retrotranslocation and degradation. These findings redefine US2 as a multifunctional degradation hub which, through recruitment of the cellular E3 ligase TRC8, modulates diverse immune pathways involved in antigen presentation, NK cell activation, migration and coagulation; and highlight US2's impact on HCMV pathogenesis.This study was financially supported by grant 101-2917-I-564-035 from the Taiwan National Science Council to JLH; by a Wellcome Trust Fellowship (093966/Z/10/Z) to MPW; an MRC Project Grant and Wellcome Trust Programme Grant (G1000236, WT090323MA) to GWW and PT, European Regional Development Fund and the State Budget of Czech Republic (RECAMO, CZ.1.05/ 2.1.00/03.0101) to ER; a Wellcome Trust Principal Research Fellowship (084957/Z/08/Z) to PJL; and a Medical Research Council (MRC) grant (MC_UU_12014/3) to GSW and AJD. This study was additionally supported by the Cambridge Biomedical Research Centre, UK.This is the final published version. It first appeared at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004811

Lessons learnt from easing COVID-19 restrictions: an analysis of countries and regions in Asia Pacific and Europe.

The COVID-19 pandemic is an unprecedented global crisis. Many countries have implemented restrictions on population movement to slow the spread of severe acute respiratory syndrome coronavirus 2 and prevent health systems from becoming overwhelmed; some have instituted full or partial lockdowns. However, lockdowns and other extreme restrictions cannot be sustained for the long term in the hope that there will be an effective vaccine or treatment for COVID-19. Governments worldwide now face the common challenge of easing lockdowns and restrictions while balancing various health, social, and economic concerns. To facilitate cross-country learning, this Health Policy paper uses an adapted framework to examine the approaches taken by nine high-income countries and regions that have started to ease COVID-19 restrictions: five in the Asia Pacific region (ie, Hong Kong [Special Administrative Region], Japan, New Zealand, Singapore, and South Korea) and four in Europe (ie, Germany, Norway, Spain, and the UK). This comparative analysis presents important lessons to be learnt from the experiences of these countries and regions. Although the future of the virus is unknown at present, countries should continue to share their experiences, shield populations who are at risk, and suppress transmission to save lives