A recombinant Getah Virus expressing a GFP gene for rapid neutralization testing and antiviral drug screening assay.

Getah virus (GETV) is a re-emerging mosquito-borne RNA virus that induces fever, hind limb edema, swollen submandibular lymph nodes, and urticaria in horses. In pigs, the virus often results in stillbirths among pregnant sows, and neurological symptoms leading to death in piglets. Currently, there are no specific treatments or drugs available for GETV infection. The use of reporter viruses to monitor viral replication and spread in real-time within infected cells and animals provides a powerful tool for targeting antiviral drugs throughout the viral life cycle. Their fluorescence-tracked characteristics greatly facilitate virus neutralization tests (VNTs). In this study, we engineered two recombinant viruses by inserting different reporter protein genes at the 3' end of the structural protein gene, an unreported location that can accommodate exogenous genes. The rGEEiLOV and rGEEGFP viruses demonstrated genetic stability for at least five passages and replicated at a rate similar to that of the parental virus in BHK-21 cells. The rGEEGFP virus facilitated viral neutralization testing. Additionally, we used the reporter virus rGEEGFP to confirm ivermectin, a broad-spectrum antiparasitic agent, as a potential inhibitor of GETV in vitro. Ivermectin appears to inhibit the early replication stages of the virus and can block cell-to-cell viral transmission. In conclusion, rGEEGFP holds significant potential for antiviral screening to identify specific inhibitors against GETV and for use in viral neutralization tests.

A silicon diode-based optoelectronic interface for bidirectional neural modulation.

The development of advanced neural modulation techniques is crucial to neuroscience research and neuroengineering applications. Recently, optical-based, nongenetic modulation approaches have been actively investigated to remotely interrogate the nervous system with high precision. Here, we show that a thin-film, silicon (Si)-based diode device is capable to bidirectionally regulate in vitro and in vivo neural activities upon adjusted illumination. When exposed to high-power and short-pulsed light, the Si diode generates photothermal effects, evoking neuron depolarization and enhancing intracellular calcium dynamics. Conversely, low-power and long-pulsed light on the Si diode hyperpolarizes neurons and reduces calcium activities. Furthermore, the Si diode film mounted on the brain of living mice can activate or suppress cortical activities under varied irradiation conditions. The presented material and device strategies reveal an innovated optoelectronic interface for precise neural modulations.

Development of a monoclonal antibody specifically recognizing a linear epitope on the capsid protein of the emerging Group III Getah virus.

Getah virus (GETV) is an emerging mosquito-borne alphavirus that can infect horses, pigs and other animals. Given the public health threat posed by GETV, research on its pathogenesis, diagnosis and prevention is urgently needed. In the current study, prokaryotic expression systems were used to express the capsid protein of GETV. This protein was then used to immunize BALB/c mice in order to generate monoclonal antibodies (mAbs). Subsequently, hybridoma cells secreting a mAb (2B11-4) against the capsid protein were obtained using the hybridoma technique. A B cell linear epitope, 18-PAYRPWR-24, located at the capsid protein's N-terminal region was identified using western blotting analysis with the produced mAb, 2B11-4. Sequence alignment indicated that this epitope was highly conserved in group III (GIII) strains of GETV, but varied among the other genotypes. Western blotting showed that mAb 2B11-4 could discriminate Group III GETVs from other genotypes. This study describes the preparation of a mAb against the GETV capsid protein and the identification of the specific localization of B-cell epitopes, and will contribute towards a better understanding of the biological importance of the GETV capsid protein. It will also pave the way for developing immunological detection methods and genotype diagnosis for GETVs.

Making graphs compact by lossless contraction.

This paper proposes a scheme to reduce big graphs to small graphs. It contracts obsolete parts and regular structures into supernodes. The supernodes carry a synopsis S Q for each query class Q in use, to abstract key features of the contracted parts for answering queries of Q . Moreover, for various types of graphs, we identify regular structures to contract. The contraction scheme provides a compact graph representation and prioritizes up-to-date data. Better still, it is generic and lossless. We show that the same contracted graph is able to support multiple query classes at the same time, no matter whether their queries are label based or not, local or non-local. Moreover, existing algorithms for these queries can be readily adapted to compute exact answers by using the synopses when possible and decontracting the supernodes only when necessary. As a proof of concept, we show how to adapt existing algorithms for subgraph isomorphism, triangle counting, shortest distance, connected component and clique decision to contracted graphs. We also provide a bounded incremental contraction algorithm in response to updates, such that its cost is determined by the size of areas affected by the updates alone, not by the entire graphs. We experimentally verify that on average, the contraction scheme reduces graphs by 71.9% and improves the evaluation of these queries by 1.69, 1.44, 1.47, 2.24 and 1.37 times, respectively.

Quadrillion F-Theory Compactifications with the Exact Chiral Spectrum of the Standard Model.

We present O(10^{15}) string compactifications with the exact chiral spectrum of the standard model of particle physics. This ensemble of globally consistent F-theory compactifications automatically realizes gauge coupling unification. Utilizing the power of algebraic geometry, all global consistency conditions can be reduced to a single criterion on the base of the underlying elliptically fibered Calabi-Yau fourfolds. For toric bases, this criterion only depends on an associated polytope and is satisfied for at least O(10^{15}) bases, each of which defines a distinct compactification.