Inverse design of arbitrary optical helicity patterns

Superposing multiple plane waves can generate helicity lattices in which the optical helicity varies regularly in space. Here we propose an inverse design method for constructing arbitrary helicity structures based on placing a digital object of dielectric inclusions in three-dimensional space. We apply the method to design structures that reproduce two-dimensional lattices embedded within a three-dimensional region using only a single plane wave as an input. In order to demonstrate the power and flexibility of our method, we go beyond the paradigm of a regular lattice and propose structures that can create arbitrary images consisting of regions of varying helicity, again using only a single plane wave as an input

Coronavirus Proteases as Therapeutic Targets: Development of Biosensors to Detect Inhibition of Protease Activity and Separation of the Multiple Functions of Coronavirus Papain-Like Proteases

Coronaviruses are important human pathogens and have the potential to severely impact public health on an international scale. The emergence of SARS-CoV and MERS-CoV highlight the need for research to identify antivirals and vaccines against coronaviruses. To develop therapeutics against current and potentially emergent coronaviruses, I utilized two approaches targeting the proteases encoded within all coronaviruses. The papain-like protease and 3C-like protease of coronaviruses are responsible for cleaving viral polyproteins early during infection, and this step is required for viral replication. To quantitatively assess the inhibition by small-molecule compounds on MERS-CoV protease activity, I developed a luciferase-based biosensor to monitor protease cleavage within cells. Using this assay, I demonstrated that an inhibitor that is efficacious against SARS-CoV had activity against the 3C-like protease of MERS-CoV. In the second approach, I investigated the multifunctional papain-like protease of SARS-CoV, which has been implicated in pathogenesis by acting as a deubiquitinating (DUB) enzyme and blocking host immune responses. To determine if PLpro DUB activity is responsible for innate immune antagonism, I mutated residues predicted to interact with ubiquitin and discovered that when this interaction was interrupted, PLpro was unable to antagonize innate immune pathways. Engineering these mutations into SARS-COV may generate an attenuated virus that could stimulate a protective immune response in the absence of disease

Designer quantum reflection from a micropore

We expand the theoretical toolbox for controllable quantum reflection by departing from a simple planar reflector. We introduce a circular hole (a micropore) of variable size, for which the electrostatic image potential can be exactly calculated. We combine this with two-dimensional simulations of wave-packet propagation at arbitrary angles of incidence to show that the quantum reflection probability can be tuned over a wide range of values

Pathosphere.org: pathogen detection and characterization through a web-based, open source informatics platform

Background The detection of pathogens in complex sample backgrounds has been revolutionized by wide access to next-generation sequencing (NGS) platforms. However, analytical methods to support NGS platforms are not as uniformly available. Pathosphere (found at Pathosphere.org) is a cloud - based open - sourced community tool that allows for communication, collaboration and sharing of NGS analytical tools and data amongst scientists working in academia, industry and government. The architecture allows for users to upload data and run available bioinformatics pipelines without the need for onsite processing hardware or technical support. Results The pathogen detection capabilities hosted on Pathosphere were tested by analyzing pathogen-containing samples sequenced by NGS with both spiked human samples as well as human and zoonotic host backgrounds. Pathosphere analytical pipelines developed by Edgewood Chemical Biological Center (ECBC) identified spiked pathogens within a common sample analyzed by 454, Ion Torrent, and Illumina sequencing platforms. ECBC pipelines also correctly identified pathogens in human samples containing arenavirus in addition to animal samples containing flavivirus and coronavirus. These analytical methods were limited in the detection of sequences with limited homology to previous annotations within NCBI databases, such as parvovirus. Utilizing the pipeline-hosting adaptability of Pathosphere, the analytical suite was supplemented by analytical pipelines designed by the United States Army Medical Research Insititute of Infectious Diseases and Walter Reed Army Institute of Research (USAMRIID-WRAIR). These pipelines were implemented and detected parvovirus sequence in the sample that the ECBC iterative analysis previously failed to identify. Conclusions By accurately detecting pathogens in a variety of samples, this work demonstrates the utility of Pathosphere and provides a platform for utilizing, modifying and creating pipelines for a variety of NGS technologies developed to detect pathogens in complex sample backgrounds. These results serve as an exhibition for the existing pipelines and web-based interface of Pathosphere as well as the plug-in adaptability that allows for integration of newer NGS analytical software as it becomes available

Learning a lesson from a famous puppet player Susumu Tange : A good practice of "Practical training of child-care skills" in Kyoto Women's college

textabstractCoronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of∼30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. If such compounds proved sufficiently potent, their efficacy might be directly assessed in MERS patients. We identified four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) inhibiting MERS-CoV replication in the lowmicromolar range (50% effective concentrations [EC50s], 3 to 8 μM). Moreover, these compounds also inhibit the replication of SARS coronavirus and human coronavirus 229E. Although their protective activity (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV. Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window during which to mount a protective immune response. Copyrigh

Clever girl: Benevolent sexism and cardiovascular threat

Benevolent sexism is a double-edged sword that uses praise to maintain gender inequality, which consequently makes women feel less efficacious, agentic and competent. This study investigated whether benevolently sexist feedback that was supportive could result in cardiovascular responses indicative of threat (lower cardiac output/higher total peripheral resistance). Women received either supportive non-sexist or supportive yet benevolent sexist feedback from a male evaluator following practice trials on a verbal reasoning test. As expected, women receiving benevolent sexist feedback exhibited cardiovascular threat during a subsequent test, relative to women receiving non-sexist feedback. There was no support for an alternative hypothesis that benevolent sexist feedback would lead to cardiovascular responses consistent with disengaging from the task altogether (i.e., lower heart rate and ventricular contractility). These findings illustrate that the consequences of benevolent sexism can occur spontaneously, while women are engaged with a task, and when the sexist feedback is intended as supportive

Inverse design of arbitrary optical helicity structures

Python scripts to perform simulation