Three Dimensional Quantitative Structure-Activity Relationships of Sulfonamides Binding Monoclonal Antibody by Comparative Molecular Field Analysis

The three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MabSMR) produced against sulfamerazine, was carried out by comparative molecular field analysis (CoMFA). The affinities of MabSMR, expressed as Log10IC50, for 17 sulfonamide analogs were determined by competitive fluorescence polarization immunoassay (FPIA). Removal of two outliers from the initial set of 17 sulfonamide analogs improved the predictability of the models. The 3D-QSAR model of 15 sulfonamides resulted in q2cv values of 0.600, and r2 values of 0.995, respectively. This novel study combining FPIA with CoMFA demonstrates that multidisciplinary research can be used as a useful tool to investigate antigen-antibody interactions and provide information required for design of novel haptens, which may result in new antibodies with properties already optimized by an antibody-based immunoassay

STL-SGD: Speeding Up Local SGD with Stagewise Communication Period

Distributed parallel stochastic gradient descent algorithms are workhorses for large scale machine learning tasks. Among them, local stochastic gradient descent (Local SGD) has attracted significant attention due to its low communication complexity. Previous studies prove that the communication complexity of Local SGD with a fixed or an adaptive communication period is in the order of $O (N^{\frac{3}{2}} T^{\frac{1}{2}})$ and $O (N^{\frac{3}{4}} T^{\frac{3}{4}})$ when the data distributions on clients are identical (IID) or otherwise (Non-IID), where $N$ is the number of clients and $T$ is the number of iterations. In this paper, to accelerate the convergence by reducing the communication complexity, we propose \textit{ST}agewise \textit{L}ocal \textit{SGD} (STL-SGD), which increases the communication period gradually along with decreasing learning rate. We prove that STL-SGD can keep the same convergence rate and linear speedup as mini-batch SGD. In addition, as the benefit of increasing the communication period, when the objective is strongly convex or satisfies the Polyak-\L ojasiewicz condition, the communication complexity of STL-SGD is $O (N \log{T})$ and $O (N^{\frac{1}{2}} T^{\frac{1}{2}})$ for the IID case and the Non-IID case respectively, achieving significant improvements over Local SGD. Experiments on both convex and non-convex problems demonstrate the superior performance of STL-SGD.Comment: Accepted by AAAI202

Noninvasive Submillimeter-Precision Brain Stimulation by Optically-Driven Focused Ultrasound

High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited millimeter-level precision. Here, we report an optically-driven focused ultrasound (OFUS) for non-invasive brain stimulation with submillimeter precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with a lateral resolution of 83 micrometers, which is two orders of magnitude smaller than that of conventional transcranial focused ultrasound (tFUS). Effective OFUS neurostimulation in vitro with a single ultrasound cycle is shown. Submillimeter transcranial stimulation of mouse motor cortex in vivo is demonstrated. An acoustic energy of 0.02 J/cm^2, two orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. By delivering a submillimeter focus non-invasively, OFUS opens a new way for neuroscience studies and disease treatments.Comment: 36 pages, 5 main figures, 13 supplementary figure

Caulobacter and Novosphingobium in tumor tissues are associated with colorectal cancer outcomes

Diversity and composition of the gut microbiome are associated with cancer patient outcomes including colorectal cancer (CRC). A growing number of evidence indicates that Fusobacterium nucleatum (Fn) in CRC tissue is associated with worse survival. However, few studies have further analyzed the differences in bacteria in tumor tissues of different patients depending on the survival time of CRC patients. Therefore, there is a need to further explore the bacterial differences in tumor tissues of patients with different prognoses and to identify key bacteria for analysis. Here, we sought to compare the differences in tumor microbiome between patients with long-term survival (LS) longer than 3 years or 4 and 5 years and patients with short-term survival (SS) in the present study cohort. We found that there were significant differences in tumor microbiome between the LS and SS and two bacteria—Caulobacter and Novosphingobium—that are present in all of the three groups. Furthermore, by analyzing bacteria in different clinical features, we also found that lower levels of microbiome (Caulobacter and Novosphingobium) have long-term survival and modulating microbiome in tumor tissue may provide an alternative way to predict the prognosis of CRC patients

pVHL suppresses kinase activity of Akt in a proline-hydroxylation-dependent manner

Activation of the serine-threonine kinase Akt promotes the survival and proliferation of various cancers. Hypoxia promotes the resistance of tumor cells to specific therapies. We therefore explored a possible link between hypoxia and Akt activity. We found that Akt was prolyl-hydroxylated by the oxygen-dependent hydroxylase EglN1. The von Hippel–Lindau protein (pVHL) bound directly to hydroxylated Akt and inhibited Akt activity. In cells lacking oxygen or functional pVHL, Akt was activated to promote cell survival and tumorigenesis. We also identified cancer-associated Akt mutations that impair Akt hydroxylation and subsequent recognition by pVHL, thus leading to Akt hyperactivation. Our results show that microenvironmental changes, such as hypoxia, can affect tumor behaviors by altering Akt activation, which has a critical role in tumor growth and therapeutic resistance