Phosphorylation stoichiometries of human eukaryotic initiation factors.

Eukaryotic translation initiation factors are the principal molecular effectors regulating the process converting nucleic acid to functional protein. Commonly referred to as eIFs (eukaryotic initiation factors), this suite of proteins is comprised of at least 25 individual subunits that function in a coordinated, regulated, manner during mRNA translation. Multiple facets of eIF regulation have yet to be elucidated; however, many of the necessary protein factors are phosphorylated. Herein, we have isolated, identified and quantified phosphosites from eIF2, eIF3, and eIF4G generated from log phase grown HeLa cell lysates. Our investigation is the first study to globally quantify eIF phosphosites and illustrates differences in abundance of phosphorylation between the residues of each factor. Thus, identification of those phosphosites that exhibit either high or low levels of phosphorylation under log phase growing conditions may aid researchers to concentrate their investigative efforts to specific phosphosites that potentially harbor important regulatory mechanisms germane to mRNA translation

Status and Prospects of Exotic Hadrons at Belle II

In the past twenty years, many new hadrons that are difficult to be explained within the conventional quark model have been discovered in the quarkonium region, which are called exotic hadrons. Belle II experiment, as the next-generation $B$ factory, provides a good platform to explore them. The charmonium-like states can be produced at Belle II in several ways, such as $B$ meson decays, initial-state radiation processes, two-photon collisions, and double charmonium productions. The bottomonium-like states can be produced directly in $e^+e^-$ colliding energies at Belle II with low continuum backgrounds. Belle II plans to perform a high-statistics energy scan from the $B\bar B$ threshold up to the highest possible energy of 11.24 GeV to search for new $Y_b$ states with $J^{PC}$ = $1^{--}$, $X_b$ (the bottom counterpart of $\chi_{c1}(3872)$ (also known as $X(3872)$)), and partners of $Z_b$ states. In this paper, we give a mini-review on the status and prospects of exotic hadrons at Belle II.Comment: 7 pages, 5 figure

Intergenerational Test Generation for Natural Language Processing Applications

The development of modern NLP applications often relies on various benchmark datasets containing plenty of manually labeled tests to evaluate performance. While constructing datasets often costs many resources, the performance on the held-out data may not properly reflect their capability in real-world application scenarios and thus cause tremendous misunderstanding and monetary loss. To alleviate this problem, in this paper, we propose an automated test generation method for detecting erroneous behaviors of various NLP applications. Our method is designed based on the sentence parsing process of classic linguistics, and thus it is capable of assembling basic grammatical elements and adjuncts into a grammatically correct test with proper oracle information. We implement this method into NLPLego, which is designed to fully exploit the potential of seed sentences to automate the test generation. NLPLego disassembles the seed sentence into the template and adjuncts and then generates new sentences by assembling context-appropriate adjuncts with the template in a specific order. Unlike the taskspecific methods, the tests generated by NLPLego have derivation relations and different degrees of variation, which makes constructing appropriate metamorphic relations easier. Thus, NLPLego is general, meaning it can meet the testing requirements of various NLP applications. To validate NLPLego, we experiment with three common NLP tasks, identifying failures in four state-of-art models. Given seed tests from SQuAD 2.0, SST, and QQP, NLPLego successfully detects 1,732, 5301, and 261,879 incorrect behaviors with around 95.7% precision in three tasks, respectively

Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble αβ-tubulin pool for microtubule dynamics.

Microtubule dynamics and polarity stem from the polymerization of αβ-tubulin heterodimers. Five conserved tubulin cofactors/chaperones and the Arl2 GTPase regulate α- and β-tubulin assembly into heterodimers and maintain the soluble tubulin pool in the cytoplasm, but their physical mechanisms are unknown. Here, we reconstitute a core tubulin chaperone consisting of tubulin cofactors TBCD, TBCE, and Arl2, and reveal a cage-like structure for regulating αβ-tubulin. Biochemical assays and electron microscopy structures of multiple intermediates show the sequential binding of αβ-tubulin dimer followed by tubulin cofactor TBCC onto this chaperone, forming a ternary complex in which Arl2 GTP hydrolysis is activated to alter αβ-tubulin conformation. A GTP-state locked Arl2 mutant inhibits ternary complex dissociation in vitro and causes severe defects in microtubule dynamics in vivo. Our studies suggest a revised paradigm for tubulin cofactors and Arl2 functions as a catalytic chaperone that regulates soluble αβ-tubulin assembly and maintenance to support microtubule dynamics

Smart Milli-capsules manipulated by nIR irradiation for controllable drug delivery in-vivo for renal cell carcinoma and neurodegenerative diseases

Cancer and neurodegeneration which are responsible for million deaths worldwide, have urgent requests for drug administration with little to no side-effects. Current designs of drug-delivery, however, are constrained by either treatment effectiveness caused by imprecise control of drug-concentrations, or treatment-related toxicities caused by drugs-themselves or drug-carrier-systems, as well as the safety and feasibility. In this study, on account of the penetration ability through tissues of near-infrared (nIR) lights and the nIR-absorption ability of graphene oxide (GO), the GO-based milli-capsule is constructed, with controlled drug release ability by photomechanical deformation and wireless nIR manipulation. When radiation powers increasing from 0.1 to 0.5 W, drug dosages are in the range of 0 μg (0 drop) to 225 μg (five drops). The cytotoxicity of GO-based capsules in vitro is evaluated by embedded GO as drugs and released GO in clear cell renal cell carcinoma (ccRCC). When the capsules irradiated under 0.5 W and released different amounts of GO-drops in ccRCC, GO-concentrations increase from 0 to 80 μg∙mL−1 and the proportions of apoptotic cells increase 2.85 times, which proves milli-capsules inhibit ccRCC cells proliferation in a GO-concentration-dependent manner by accurate GO-dosing control. Other drugs such as siRNA furnishing an additional practicability-proof for neurodegeneration therapy

A Novel Injectable Borate Bioactive Glass Cement As an Antibiotic Delivery Vehicle for Treating Osteomyelitis

Background: A novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model. Materials and Methods: The setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS) cement and for intravenous injection of vancomycin. Results: The BG cement had an injectability of \u3e90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18±2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects. Conclusions: These results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured

Gait Recognition as a Service for Unobtrusive User Identification in Smart Spaces

Recently, Internet of Things (IoT) has raised as an important research area that combines the environmental sensing and machine learning capabilities to flourish the concept of smart spaces, in which intelligent and customized services can be provided to users in a smart manner. In smart spaces, one fundamental service that needs to be provided is accurate and unobtrusive user identification. In this work, to address this challenge, we propose a Gait Recognition as a Service (GRaaS) model, which is an instantiation of the traditional Sensing as a Service (S2aaS) model, and is specially deigned for user identification using gait in smart spaces. To illustrate the idea, a Radio Frequency Identification (RFID)-based gait recognition service is designed and implemented following the GRaaS concept. Novel tag selection algorithms and attention-based Long Short-term Memory (At-LSTM) models are designed to realize the device layer and edge layer, achieving a robust recognition with 96.3% accuracy. Extensive evaluations are provided, which show that the proposed service has accurate and robust performance and has great potential to support future smart space applications

Establishment and Application of Real-time PCR Detection Method for Lactobacillus kefiranofaciens subsp. kefiranofaciens

This study developed a real-time polymerase chain reaction (real-time PCR) method for the detection of Lactobacillus kefiranofaciens subsp. kefiranofaciens. Based on the 16S rDNA gene sequence and whole genome sequence of the type strain of L. kefiranofaciens subsp. kefiranofaciens ZW3, specific primers were designed and screened. The fluorescent dye SYBR Green I was used in the real-time PCR method. Its specificity, sensitivity and repeatability were evaluated, and this method was applied to detect several strains of this species and its mixtures with other lactic acid bacteria. The results showed that the proposed method was highly specific, sensitive and repeatable. The standard curve was linear with a determination coefficient (R2) of 0.965. Moreover, this method could specifically detect L. kefiranofaciens subsp. kefiranofaciens from its mixture with other lactic acid bacteria. In summary, the real-time PCR method could quickly and accurately detect L. kefiranofaciens subsp. kefiranofaciens, providing a new method for the specific qualitative and quantitative detection of L. kefiranofaciens subsp. kefiranofaciens

DDC-PIM: Efficient Algorithm/Architecture Co-design for Doubling Data Capacity of SRAM-based Processing-In-Memory

Processing-in-memory (PIM), as a novel computing paradigm, provides significant performance benefits from the aspect of effective data movement reduction. SRAM-based PIM has been demonstrated as one of the most promising candidates due to its endurance and compatibility. However, the integration density of SRAM-based PIM is much lower than other non-volatile memory-based ones, due to its inherent 6T structure for storing a single bit. Within comparable area constraints, SRAM-based PIM exhibits notably lower capacity. Thus, aiming to unleash its capacity potential, we propose DDC-PIM, an efficient algorithm/architecture co-design methodology that effectively doubles the equivalent data capacity. At the algorithmic level, we propose a filter-wise complementary correlation (FCC) algorithm to obtain a bitwise complementary pair. At the architecture level, we exploit the intrinsic cross-coupled structure of 6T SRAM to store the bitwise complementary pair in their complementary states ($Q/\overline{Q}$), thereby maximizing the data capacity of each SRAM cell. The dual-broadcast input structure and reconfigurable unit support both depthwise and pointwise convolution, adhering to the requirements of various neural networks. Evaluation results show that DDC-PIM yields about $2.84\times$ speedup on MobileNetV2 and $2.69\times$ on EfficientNet-B0 with negligible accuracy loss compared with PIM baseline implementation. Compared with state-of-the-art SRAM-based PIM macros, DDC-PIM achieves up to $8.41\times$ and $2.75\times$ improvement in weight density and area efficiency, respectively.Comment: 14 pages, to be published in IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems (TCAD