Style Separation and Synthesis via Generative Adversarial Networks

Style synthesis attracts great interests recently, while few works focus on its dual problem "style separation". In this paper, we propose the Style Separation and Synthesis Generative Adversarial Network (S3-GAN) to simultaneously implement style separation and style synthesis on object photographs of specific categories. Based on the assumption that the object photographs lie on a manifold, and the contents and styles are independent, we employ S3-GAN to build mappings between the manifold and a latent vector space for separating and synthesizing the contents and styles. The S3-GAN consists of an encoder network, a generator network, and an adversarial network. The encoder network performs style separation by mapping an object photograph to a latent vector. Two halves of the latent vector represent the content and style, respectively. The generator network performs style synthesis by taking a concatenated vector as input. The concatenated vector contains the style half vector of the style target image and the content half vector of the content target image. Once obtaining the images from the generator network, an adversarial network is imposed to generate more photo-realistic images. Experiments on CelebA and UT Zappos 50K datasets demonstrate that the S3-GAN has the capacity of style separation and synthesis simultaneously, and could capture various styles in a single model

DeepFacePencil: Creating Face Images from Freehand Sketches

In this paper, we explore the task of generating photo-realistic face images from hand-drawn sketches. Existing image-to-image translation methods require a large-scale dataset of paired sketches and images for supervision. They typically utilize synthesized edge maps of face images as training data. However, these synthesized edge maps strictly align with the edges of the corresponding face images, which limit their generalization ability to real hand-drawn sketches with vast stroke diversity. To address this problem, we propose DeepFacePencil, an effective tool that is able to generate photo-realistic face images from hand-drawn sketches, based on a novel dual generator image translation network during training. A novel spatial attention pooling (SAP) is designed to adaptively handle stroke distortions which are spatially varying to support various stroke styles and different levels of details. We conduct extensive experiments and the results demonstrate the superiority of our model over existing methods on both image quality and model generalization to hand-drawn sketches.Comment: ACM MM 2020 (oral

Neuronal-targeted TFEB accelerates lysosomal degradation of app, reducing Aβ generation and amyloid plaque pathogenesis

In AD, an imbalance between Aβ production and removal drives elevated brain Aβ levels and eventual amyloid plaque deposition. APP undergoes nonamyloidogenic processing via α-cleavage at the plasma membrane, amyloidogenic β- and γ-cleavage within endosomes to generate Aβ, or lysosomal degradation in neurons. Considering multiple reports implicating impaired lysosome function as a driver of increased amyloidogenic processing of APP, we explored the efficacy of targeting transcription factor EB (TFEB), a master regulator of lysosomal pathways, to reduce Aβ levels. CMV promoter-driven TFEB, transduced via stereotactic hippocampal injections of adeno-associated virus particles in APP/PS1 mice, localized primarily to neuronal nuclei and upregulated lysosome biogenesis. This resulted in reduction of APP protein, the α and β C-terminal APP fragments (CTFs), and in the steady-state Aβ levels in the brain interstitial fluid. In aged mice, total Aβ levels and amyloid plaque load were selectively reduced in the TFEB-transduced hippocampi. TFEB transfection in N2a cells stably expressing APP695, stimulated lysosome biogenesis, reduced steady-state levels of APP and α- and β-CTFs, and attenuated Aβ generation by accelerating flux through the endosome-lysosome pathway. Cycloheximide chase assays revealed a shortening of APP half-life with exogenous TFEB expression, which was prevented by concomitant inhibition of lysosomal acidification. These data indicate that TFEB enhances flux through lysosomal degradative pathways to induce APP degradation and reduce Aβ generation. Activation of TFEB in neurons is an effective strategy to attenuate Aβ generation and attenuate amyloid plaque deposition in AD. SIGNIFICANCE STATEMENT A key driver for AD pathogenesis is the net balance between production and clearance of Aβ, the major component of amyloid plaques. Here we demonstrate that lysosomal degradation of holo-APP influences Aβ production by limiting the availability of APP for amyloidogenic processing. Using viral gene transfer of transcription factor EB (TFEB), a master regulator of lysosome biogenesis in neurons of APP/PS1 mice, steady-state levels of APP were reduced, resulting in decreased interstitial fluid Aβ levels and attenuated amyloid deposits. These effects were caused by accelerated lysosomal degradation of endocytosed APP, reflected by reduced APP half-life and steady-state levels in TFEB-expressing cells, with resultant decrease in Aβ production and release. Additional studies are needed to explore the therapeutic potential of this approach

Enhancing astrocytic lysosome biogenesis facilitates Aβ clearance and attenuates amyloid plaque pathogenesis

In sporadic Alzheimer's disease (AD), impaired Aβ removal contributes to elevated extracellular Aβ levels that drive amyloid plaque pathogenesis. Extracellular proteolysis, export across the blood–brain barrier, and cellular uptake facilitate physiologic Aβ clearance. Astrocytes can take up and degrade Aβ, but it remains unclear whether this function is insufficient in AD or can be enhanced to accelerate Aβ removal. Additionally, age-related dysfunction of lysosomes, the major degradative organelles wherein Aβ localizes after uptake, has been implicated in amyloid plaque pathogenesis. We tested the hypothesis that enhancing lysosomal function in astrocytes with transcription factor EB (TFEB), a master regulator of lysosome biogenesis, would promote Aβ uptake and catabolism and attenuate plaque pathogenesis. Exogenous TFEB localized to the nucleus with transcriptional induction of lysosomal biogenesis and function in vitro. This resulted in significantly accelerated uptake of exogenously applied Aβ42, with increased localization to and degradation within lysosomes in C17.2 cells and primary astrocytes, indicating that TFEB is sufficient to coordinately enhance uptake, trafficking, and degradation of Aβ. Stereotactic injection of adeno-associated viral particles carrying TFEB driven by a glial fibrillary acidic protein promoter was used to achieve astrocyte-specific expression in the hippocampus of APP/PS1 transgenic mice. Exogenous TFEB localized to astrocyte nuclei and enhanced lysosome function, resulting in reduced Aβ levels and shortened half-life in the brain interstitial fluid and reduced amyloid plaque load in the hippocampus compared with control virus-injected mice. Therefore, activation of TFEB in astrocytes is an effective strategy to restore adequate Aβ removal and counter amyloid plaque pathogenesis in AD

Probing Meiotic Recombination and Aneuploidy of Single Sperm Cells by Whole-Genome Sequencing

Meiotic recombination creates genetic diversity and ensures segregation of homologous chromosomes. Previous population analyses yielded results averaged among individuals and affected by evolutionary pressures. We sequenced 99 sperm from an Asian male by using the newly developed amplification method—multiple annealing and looping-based amplification cycles—to phase the personal genome and map recombination events at high resolution, which are nonuniformly distributed across the genome in the absence of selection pressure. The paucity of recombination near transcription start sites observed in individual sperm indicates that such a phenomenon is intrinsic to the molecular mechanism of meiosis. Interestingly, a decreased crossover frequency combined with an increase of autosomal aneuploidy is observable on a global per-sperm basis.Chemistry and Chemical Biolog

Multiscale QM/MM modelling of catalytic systems with ChemShell

Hybrid quantum mechanical/molecular mechanical (QM/MM) methods are a powerful computational tool for the investigation of all forms of catalysis, as they allow for an accurate description of reactions occurring at catalytic sites in the context of a complicated electrostatic environment. The scriptable computational chemistry environment ChemShell is a leading software package for QM/MM calculations, providing a flexible, high performance framework for modelling both biomolecular and materials catalysis. We present an overview of recent applications of ChemShell to problems in catalysis and review new functionality introduced into the redeveloped Python-based version of ChemShell to support catalytic modelling. These include a fully guided workflow for biomolecular QM/MM modelling, starting from an experimental structure, a periodic QM/MM embedding scheme to support modelling of metallic materials, and a comprehensive set of tutorials for biomolecular and materials modelling

Nanocarbon-Based photovoltaics

Carbon materials are excellent candidates for photovoltaic solar cells: they are Earth-abundant, possess high optical absorption, and superior thermal and photostability. Here we report on solar cells with active layers made solely of carbon nanomaterials that present the same advantages of conjugated polymer-based solar cells - namely solution processable, potentially flexible, and chemically tunable - but with significantly increased photostability and the possibility to revert photodegradation. The device active layer composition is optimized using ab-initio density functional theory calculations to predict type-II band alignment and Schottky barrier formation. The best device fabricated is composed of PC70BM fullerene, semiconducting single-walled carbon nanotubes and reduced graphene oxide. It achieves a power conversion efficiency of 1.3% - a record for solar cells based on carbon as the active material - and shows significantly improved lifetime than a polymer-based device. We calculate efficiency limits of up to 13% for the devices fabricated in this work, comparable to those predicted for polymer solar cells. There is great promise for improving carbon-based solar cells considering the novelty of this type of device, the superior photostability, and the availability of a large number of carbon materials with yet untapped potential for photovoltaics. Our results indicate a new strategy for efficient carbon-based, solution-processable, thin film, photostable solar cells

Protocol of a Multicentre Randomised Controlled Trial Assessing Transperineal Prostate Biopsy to Reduce Infectiouscomplications

Introduction Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of postbiopsy infection is increasing due to increasing antibiotic resistance of rectal flora. Single-centre studies suggest that a clean, percutaneous transperineal approach to prostate biopsy may have a lower risk of infection. To date, there is no high-level evidence comparing transperineal versus transrectal prostate biopsy. We hypothesise that transperineal versus transrectal prostate biopsy under local anaesthesia has a significantly lower risk of infection, similar pain/discomfort levels and comparable detection of non-low-grade prostate cancer. Methods and analysis We will perform a multicentre, prospective randomised clinical trial to compare transperineal versus transrectal prostate biopsy for elevated prostate-specific antigen in the first biopsy, prior negative biopsy and active surveillance biopsy setting. Prostate MRI will be performed prior to biopsy, and targeted biopsy will be conducted for suspicious MRI lesions in addition to systematic biopsy (12 cores). Approximately 1700 men will be recruited and randomised in a 1:1 ratio to transperineal versus transrectal biopsy. A streamlined design to collect data and to determine trial eligibility along with the two-stage consent process will be used to facilitate subject recruitment and retention. The primary outcome is postbiopsy infection, and secondary outcomes include other adverse events (bleeding, urinary retention), pain/ discomfort/anxiety and critically, detection of non-low-grade (grade group ≥2) prostate cancer. Ethics and dissemination The Institutional Review Board of the Biomedical Research Alliance of New York approved the research protocol (protocol number #18-02-365, approved 20 April 2020). The results of the trial will be presented at scientific conferences and published in peer-reviewed medical journals. Trial registration number NCT04815876