Virtual reality (VR) over wireless is emerging as an important use case of 5G networks. Fully-immersive VR experience requires the wireless delivery of huge data at ultra-low latency, thus leading to ...ultra-high transmission rate requirement for wireless communications. This challenge can be largely addressed by the recent network architecture known as mobile edge computing (MEC) network, which enables caching and computing capabilities at the edge of wireless networks. This paper presents a novel MEC-based mobile VR delivery framework that is able to cache parts of the field of views (FOVs) in advance and compute certain post-processing procedures on demand at the mobile VR device. To minimize the average required transmission rate, we formulate the joint caching and computing optimization problem to determine which FOVs to cache, whether to cache them in 2D or 3D as well as which FOVs to compute at the mobile device under cache size, average power consumption as well as latency constraints. When FOVs are homogeneous, we obtain a closed-form expression for the optimal joint policy which reveals interesting communications-caching-computing tradeoffs. When FOVs are heterogeneous, we obtain a local optima of the problem by transforming it into a linearly constrained indefinite quadratic problem and then applying concave convex procedure. Numerical results demonstrate the proposed mobile VR delivery framework can significantly reduce communication bandwidth while meeting low latency requirement.
PTEN-induced putative kinase 1 (PINK1) and Parkin act in a common pathway to regulate mitochondrial dynamics, the involvement of which in the pathogenesis of Parkinson's disease (PD) is increasingly ...being appreciated. However, how the PINK1/Parkin pathway influences mitochondrial function is not well understood, and the exact role of this pathway in controlling mitochondrial dynamics remains controversial. Here we used mammalian primary neurons to examine the function of the PINK1/Parkin pathway in regulating mitochondrial dynamics and function. In rat hippocampal neurons, PINK1 or Parkin overexpression resulted in increased mitochondrial number, smaller mitochondrial size and reduced mitochondrial occupancy of neuronal processes, suggesting that the balance of mitochondrial fission/fusion dynamics is tipped toward more fission. Conversely, inactivation of PINK1 resulted in elongated mitochondria, indicating that the balance of mitochondrial fission/fusion dynamics is tipped toward more fusion. Furthermore, overexpression of the fission protein Drp1 (dynamin-related protein 1) or knocking down of the fusion protein OPA1 (optical atrophy 1) suppressed PINK1 RNAi-induced mitochondrial morphological defect, and overexpression of PINK1 or Parkin suppressed the elongated mitochondria phenotype caused by Drp1 RNAi. Functionally, PINK1 knockdown and overexpression had opposite effects on dendritic spine formation and neuronal vulnerability to excitotoxicity. Finally, we found that PINK1/Parkin similarly influenced mitochondrial dynamics in rat midbrain dopaminergic neurons. These results, together with previous findings in Drosophila dopaminergic neurons, indicate that the PINK1/Parkin pathway plays conserved roles in regulating neuronal mitochondrial dynamics and function.
The efforts to discover HIV therapeutics have continued since the first human immunodeficiency virus (HIV) infected patient was confirmed in the 1980s. Ten years later, the first HIV drug, zidovudine ...(AZT), targeting HIV reverse transcriptase, was developed. Meanwhile, scientists were enlightened to discover new drugs that target different HIV genes, like integrase, protease, and host receptors. Combination antiretroviral therapy (cART) is the most feasible medical intervention to suppress the virus in people with HIV (PWH) and control the epidemic. ART treatment has made HIV a chronic infection rather than a fatal disease, but ART does not eliminate latent reservoirs of HIV-1 from the host cells; strict and life-long adherence to ART is required for the therapy to be effective in patients. In this review, we first discussed the scientific history of conventional HIV drug discovery since scientists need to develop more and more drugs to solve drug-resistant issues and release the side effects. Then, we summarized the novel research technologies, like gene editing, applied to HIV treatment and their contributions to eliminating HIV as a complementary therapy.
The effect of alterations in intestinal microbiota on microbial metabolites and on disease processes such as graft-versus-host disease (GVHD) is not known. Here we carried out an unbiased analysis to ...identify previously unidentified alterations in gastrointestinal microbiota-derived short-chain fatty acids (SCFAs) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amount of only one SCFA, butyrate, were observed only in the intestinal tissue. The reduced butyrate in CD326(+) intestinal epithelial cells (IECs) after allo-BMT resulted in decreased histone acetylation, which was restored after local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate-producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate disease severity.
Background
A meta-analysis was conducted to determine whether telomerase reverse transcriptase (TERT) rs2736098 polymorphism was related to the incidence of lung cancer.
Methods
We systematically ...searched the following three electronic databases: PubMed, Embase, and China National Knowledge Infrastructure (CNKI), for relevant articles. Statistical analysis was performed using the odds ratio (OR) and the corresponding 95% confidence interval (CI).
Results
Seven articles involving 3836 healthy controls and 3637 patients were included in this meta-analysis. TERT rs2736098 polymorphism was significantly related to lung cancer incidence (AA vs. GG: OR=1.83, 95% CI=1.58–2.12; AG vs. GG: OR=1.21, 95% CI=1.10–1.34; Dominant model: OR=1.33, 95% CI=1.22–1.46; Recessive model: OR=1.66, 95% CI=1.44–1.90). Moreover, this polymorphism was found to be correlated with the susceptibility to lung cancer when studies were stratified based on the sample size and the Hardy–Weinberg equilibrium.
Conclusion
The present findings indicate that the TERT rs2736098 polymorphism may be a risk factor for the development of lung cancer.
In the past decade, relative proteomic quantification using isobaric labeling technology has developed into a key tool for comparing the expression of proteins in biological samples. Although its ...multiplexing capacity and flexibility make this a valuable technology for addressing various biological questions, its quantitative accuracy and precision still pose significant challenges to the reliability of its quantification results. Here, we give a detailed overview of the different kinds of isobaric mass tags and the advantages and disadvantages of the isobaric labeling method. We also discuss which precautions should be taken at each step of the isobaric labeling workflow, to obtain reliable quantification results in large-scale quantitative proteomics experiments. In the last section, we discuss the broad applications of the isobaric labeling technology in biological and clinical studies, with an emphasis on thermal proteome profiling and proteogenomics.
A clear cognition on how structure difference affects crystalline structure variation within phyllosilicate especially for “2:1” layered phyllosilicate under irradiation is essential to explore the ...procedure for damage formation within matrix of clay used in disposal high radioactive waste (HLRW) practically and also beneficial for evaluating the effect of nuclear accident to environment, which is of great significance. In this work, phlogopite, muscovite and talc were irradiated by Co-60 γ rays in air at a dose rate of 54 Gy/min with doses at 0–1000 kGy. Then, variation in crystalline structure and intrinsic mechanism were explored. Main results show phlogopite occurred expansion while muscovite and talc occurred shrink in z-direction lattice. Simultaneously, H2O amount declined and valence for metal was elevated. For 1000 kGy-irradiated sample, interlayer space d varied 1% and binding energy for metal was elevated near 1.5–2 eV. It seems phlogopite, muscovite and talc show poor radiation-resistance. Main mechanisms involve intrinsic characteristic, framework break and H2O radiolysis. Upon irradiation, framework break and H2O radiolysis occurred synchronously. Framework break mainly resulted in shrink, H2O radiolysis mainly led extra OH introduction leading expansion. In reality, all these three materials showed extra OH introduction while only phlogopite occurred expansion. It seems the variation trend in lattice mainly relies on material's intrinsic characteristic, H2O radiolysis is secondary. To talc or muscovite, for compact stacking or idle space existence, they are difficult to expand, lattice shrink observed even under extra OH introduction. To phlogopite, for moderate structure, its lattice is easy to expand. For 1000 kGy-irradiated sample, the interlayer space d was enlarged by 1%. For H2O radiolysis, its amount declined and HO• radical was formed, elevating valence for metal as Mg/Al. It seems phyllosilicate shows poor radiation-resistance, and the apparent variation trend in lattice induced by γ ray irradiation seems mainly rely on material's intrinsic characteristic, H2O radiolysis is secondary.
•Phlogopite expanded while muscovite and talc occurred shrink under irradiation.•Main mechanisms involves H2O radiolysis and framework break.•Apparent structure variation mainly relies on materials' intrinsic characteristic.•H2O radiolysis could affect crystalline structure variation while is secondary.
Mobile edge computing (MEC) is expected to be an effective solution to deliver virtual reality (VR) videos over wireless networks. In contrast to previous computation-constrained MEC, which reduces ...the computation-resource consumption at the mobile device by increasing the communication-resource consumption, we develop a communications-constrained MEC framework to reduce communication-resource consumption by fully exploiting the computation and caching resources at the mobile VR device in this paper. Specifically, according to a task modularization, the MEC server only delivers the components which have not been stored in the VR device, and then the VR device uses the received components and other cached components to construct the task, yielding low communication cost but high delay. The MEC server also computes the task by itself to reduce the delay, however, it consumes more communication-resource due to the delivery of entire task. Therefore, we propose a task scheduling strategy to decide which computation model should the MEC server operates to minimize the communication-resource consumption under the delay constraint. Finally, the tradeoffs among communications, computing, and caching are also discussed, and we analytically find that given a target communication-resource consumption, the transmission rate is inversely proportional to the computing ability of mobile VR device.
L., a hyperaccumulator of cadmium (Cd), is considered a candidate plant for efficient phytoremediation. The hairy roots of
L are chosen here as a model plant system to investigate the response ...mechanism of
L. to Cd stress. High-throughput sequencing technology is used to identify genes related to Cd tolerance. A total of 2394 differentially expressed genes (DEGs) are identified by RNA-Seq analysis, among which 1564 genes are up-regulated, and 830 genes are down-regulated. Data from the gene ontology (GO) analysis indicate that DEGs are mainly involved in metabolic processes. Glutathione metabolism, in which glutathione synthetase and glutathione
-transferase are closely related to Cd stress, is identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A Western blot shows that glutathione synthetase and glutathione
-transferase are involved in Cd tolerance. These results provide a preliminary understanding of the Cd tolerance mechanism of
L. and are, hence, of particular importance to the future development of an efficient phytoremediation process based on hairy root cultures, genetic modification, and the subsequent regeneration of the whole plant.
Emerging Antibodies in Cancer Therapy Sun, Yaping; Xu, Jian
Advanced NanoBiomed Research (Online),
January 2023, 2023-01-00, 2023-01-01, Letnik:
3, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Since the first monoclonal antibody, Orthoclone OKT3, was approved in 1986 for the treatment of acute allograft rejection in renal transplant recipients, the number of antibody‐based therapies has ...increased remarkably, with more than 130 monoclonal antibodies being currently available. In particular, due to their robust binding affinity and high specificity, various monoclonal antibodies have achieved success as complementary antitumor drugs. Moreover, therapeutic potency can be improved by engineering Y‐shaped binding sites of the antibodies to simultaneously recognize two distinct antigens; such molecules are called bispecific antibodies and function as a bridge, with one site binding to a tumor‐specific antigen and the other to immune cells to activate host immune responses. In addition, the development of trispecific antibodies has led to further enhancement of therapeutic specificity and effects. Indeed, a variety of structurally engineered antibodies have proven effective in tumor therapy. This article provides insights into the clinical translation of emerging antibody constructs, firstly describing conventional T cell‐redirecting bispecific antibodies and subsequently discussing the application of bispecific and trispecific antibody constructs based on innate immune cell recruitment. Finally, bispecific antibodies against mutant p53 and KRAS that have been actively studied in cancer treatment are introduced.
Improving the function of the immune system is one of the effective strategies against malignant tumors. In particular, therapies involving the activation and redirection of innate immune cells, including natural killer cells and macrophages, have received considerable attention in recent years. Emerging bispecific and trispecific antibodies developed on this basis are also considered to have great potential in cancer therapy.