The H\"older continuity of Lyapunov exponents for a class of Cos-type quasiperiodic Schr\"odinger cocycles

In this paper we obtain exact $\frac{1}{2}$-H\"older continuity of the Lyapunov exponents for quasi-periodic Sch\"odinger cocycles with $C^2$ cos-type potentials, large coupling constants, and fixed Diophantine frequency. Moreover, we prove the locally Lipschitz continuity of the Lyapunov exponent for a full measure spectral set. Furthermore, for any given $r$ between $\frac{1}{2}$ to $1$, we can find some energy on the spectrum and on which Lyapunov exponent is exactly $r$-H\"older continuous.Comment: 88 Page

3DPortraitGAN: Learning One-Quarter Headshot 3D GANs from a Single-View Portrait Dataset with Diverse Body Poses

3D-aware face generators are typically trained on 2D real-life face image datasets that primarily consist of near-frontal face data, and as such, they are unable to construct one-quarter headshot 3D portraits with complete head, neck, and shoulder geometry. Two reasons account for this issue: First, existing facial recognition methods struggle with extracting facial data captured from large camera angles or back views. Second, it is challenging to learn a distribution of 3D portraits covering the one-quarter headshot region from single-view data due to significant geometric deformation caused by diverse body poses. To this end, we first create the dataset 360{\deg}-Portrait-HQ (360{\deg}PHQ for short) which consists of high-quality single-view real portraits annotated with a variety of camera parameters (the yaw angles span the entire 360{\deg} range) and body poses. We then propose 3DPortraitGAN, the first 3D-aware one-quarter headshot portrait generator that learns a canonical 3D avatar distribution from the 360{\deg}PHQ dataset with body pose self-learning. Our model can generate view-consistent portrait images from all camera angles with a canonical one-quarter headshot 3D representation. Our experiments show that the proposed framework can accurately predict portrait body poses and generate view-consistent, realistic portrait images with complete geometry from all camera angles

VEGF Induces More Severe Cerebrovascular Dysplasia in Eng+/− than in Alk1+/− Mice

Brain arteriovenous malformations (BAVMs) are an important cause of intracranial hemorrhage (ICH) in young adults. A small percent of BAVMs is due to hereditary hemorrhagic telangiectasia 1 and 2 (HHT1 and 2), which are caused by mutations in two genes involved in transforming growth factor-β signaling: endoglin (Eng), and activin-like kinase 1 (Alk1). The BAVM phenotype has incomplete penetrance in HHT patients, and the mechanism is unknown. We tested the hypothesis that a “response-to-injury” triggers abnormal vascular (dysplasia) development, using Eng and Alk1 haploinsufficient mice. Adeno-associated virus (AAV) expressing vascular endothelial growth factor (VEGF) was used to mimic the injury conditions. VEGF overexpression caused a similar degree of angiogenesis in the brain of all groups, except that the cortex of Alk1+/− mice had a 33% higher capillary density than other groups. There were different levels of cerebrovascular dysplasia observed in haploinsufficient mice (Eng+/− > Alk1+/−), which simulates the relative penetrance of BAVM in HHT patients (HHT1 > HHT2). Few dysplastic capillaries were observed in AAV-LacZ-injected mice. Our data indicate that both angiogenic stimulation and genetic alteration are necessary for the development of vascular dysplasia, suggesting that anti-angiogenic therapies might be adapted to slow the progression of the disease and decrease the risk of spontaneous ICH

Structure-Based Discovery of Highly Selective Phosphodiesterase-9A Inhibitors and Implications for Inhibitor Design

A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC50 of 21 nM and 3.3 µM respectively for PDE9 and PDE5, and about three orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors

A tau fragment links depressive-like behaviors and cognitive declines in Alzheimer’s disease mouse models through attenuating mitochondrial function

IntroductionAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear.MethodsDepressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)-derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS.ResultsWe found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ–mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice.ConclusionThese results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer’s disease