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Malignant melanoma is the most aggressive form of skin cancer, and it is characterized by poor prognosis in patients with metastatic diseases. Accurate prediction of prognosis is crucial for therapeutic decisions. In this study, bioinformatics analysis was used to explore the prognostic value of growth factor receptor-bound protein 2-associated binding protein 3 (GAB3) mRNA. RNA transcriptome sequencing data and clinical data from The Cancer Genome Atlas and genotype-tissue expression (GTEx) were analyzed for differentially expressed genes in high and low GAB3 mRNA expression groups in melanoma. Performing gene enrichment analysis and constructing protein-protein interaction networks. High expression of GAB3 was significantly correlated with a lower T stage, melanoma Clark level, Breslow depth, and melanoma ulceration. And high GAB3 expression was also associated with better progression-free interval in T1 and T2 stages and N0 stage and longer overall survival in T1 and T2 stages, N0 stage, and N1 stage. GAB3 promoted high levels of infiltration of macrophages and activated natural killer cells in melanoma. High expression of GAB3 predicted a positive prognosis in early-stage melanoma that may be mediated by the anticancer immune response.

Defects in the posttranscriptional modifications of mitochondrial tRNAs have been linked to human diseases, but their pathophysiology remains elusive. In this report, we investigated the molecular mechanism underlying a deafness-associated tRNAIle 4295A>G mutation affecting a highly conserved adenosine at position 37, 3′ adjacent to the tRNA’s anticodon. Primer extension and methylation activity assays revealed that the m.4295A>G mutation introduced a tRNA methyltransferase 5 (TRMT5)-catalyzed m1G37 modification of tRNAIle. Molecular dynamics simulations suggested that the m.4295A>G mutation affected tRNAIle structure and function, supported by increased melting temperature, conformational changes and instability of mutated tRNA. An in vitro processing experiment revealed that the m.4295A>G mutation reduced the 5′ end processing efficiency of tRNAIle precursors, catalyzed by RNase P. We demonstrated that cybrid cell lines carrying the m.4295A>G mutation exhibited significant alterations in aminoacylation and steady-state levels of tRNAIle. The aberrant tRNA metabolism resulted in the impairment of mitochondrial translation, respiratory deficiency, decreasing membrane potentials and ATP production, increasing production of reactive oxygen species and promoting autophagy. These demonstrated the pleiotropic effects of m.4295A>G mutation on tRNAIle and mitochondrial functions. Our findings highlighted the essential role of deficient posttranscriptional modifications in the structure and function of tRNA and their pathogenic consequence of deafness.

Thick electrode was promising to increase the energy density in device (battery or supercapacitor) scale, but always suffered the ion polarization upon high rate discharge. We reported the use of 3D Al foam (current collector) to host graphene (with high surface area but very low packing density) to fabricate 450 ​μm thick electrode with mass loading of 10–15 ​mg ​cm−2. The space confinement effect of Al wires on graphene at any regions offered sufficient ordered diffusion channel of liquids, alleviating the ion polarization significantly, compared to the same thick graphene sheet pasted on 2D Al foil by simulation with COMSOL software. The 100 ​F pouch supercapacitor with ionic liquids at 4 ​V exhibited low contact resistance, high specific capacitance in a wide range of current densities, and simultaneously the volumetric energy density of 18 ​Wh L−1 and the power density of 5 ​kW ​kg−1, far better than those of current commercial device.

The tissue specificity of mitochondrial tRNA mutations remains largely elusive. In this study, we demonstrated the deleterious effects of tRNAThr 15927G>A mutation that contributed to pathogenesis of coronary artery disease. The m.15927G>A mutation abolished the highly conserved base-pairing (28C-42G) of anticodon stem of tRNAThr. Using molecular dynamics simulations, we showed that the m.15927G>A mutation caused unstable tRNAThr structure, supported by decreased melting temperature and slower electrophoretic mobility of mutated tRNA. Using cybrids constructed by transferring mitochondria from a Chinese family carrying the m.15927G>A mutation and a control into mitochondrial DNA (mtDNA)-less human umbilical vein endothelial cells, we demonstrated that the m.15927G>A mutation caused significantly decreased efficiency in aminoacylation and steady-state levels of tRNAThr. The aberrant tRNAThr metabolism yielded variable decreases in mtDNA-encoded polypeptides, respiratory deficiency, diminished membrane potential and increased the production of reactive oxygen species. The m.15927G>A mutation promoted the apoptosis, evidenced by elevated release of cytochrome c into cytosol and increased levels of apoptosis-activated proteins: caspases 3, 7, 9 and PARP. Moreover, the lower wound healing cells and perturbed tube formation were observed in mutant cybrids, indicating altered angiogenesis. Our findings provide new insights into the pathophysiology of coronary artery disease, which is manifested by tRNAThr mutation-induced alterations.

Mammalian mitochondrial tRNA (mt-tRNA) plays a central role in the synthesis of the 13 subunits of the oxidative phosphorylation complex system (OXPHOS). However, many aspects of the context-dependent expression of mt-tRNAs in mammals remain unknown. To investigate the tissue-specific effects of mt-tRNAs, we performed a comprehensive analysis of mitochondrial tRNA expression across five mice tissues (brain, heart, liver, skeletal muscle, and kidney) using Northern blot analysis. Striking differences in the tissue-specific expression of 22 mt-tRNAs were observed, in some cases differing by as much as tenfold from lowest to highest expression levels among these five tissues. Overall, the heart exhibited the highest levels of mt-tRNAs, while the liver displayed markedly lower levels. Variations in the levels of mt-tRNAs showed significant correlations with total mitochondrial DNA (mtDNA) contents in these tissues. However, there were no significant differences observed in the 2-thiouridylation levels of tRNALys, tRNAGlu, and tRNAGln among these tissues. A wide range of aminoacylation levels for 15 mt-tRNAs occurred among these five tissues, with skeletal muscle and kidneys most notably displaying the highest and lowest tRNA aminoacylation levels, respectively. Among these tissues, there was a negative correlation between variations in mt-tRNA aminoacylation levels and corresponding variations in mitochondrial tRNA synthetases (mt-aaRS) expression levels. Furthermore, the variable levels of OXPHOS subunits, as encoded by mtDNA or nuclear genes, may reflect differences in relative functional emphasis for mitochondria in each tissue. Our findings provide new insight into the mechanism of mt-tRNA tissue-specific effects on oxidative phosphorylation.

Shunpo He,1 Zhenzhen Ye,1 Qingwei Yang,2 Jianzhong Lin,2 Xingyu Chen,2 Zhongjie Chen,2 Liangyi Chen2 1The Graduate School of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Neurology, Zhongshan Hospital, Xiamen University, Xiamen, People’s Republic of ChinaCorrespondence: Qingwei Yang; Xingyu ChenDepartment of Neurology, Zhongshan Hospital, Xiamen University, No. 203 of Hubin South Road, Siming District, Xiamen, 361001, People’s Republic of ChinaTel +86 592-2292113Fax +86 592-2590120Email yamgqimgwei@aliyun.com; chemximgyu@163.comBackground and Aim: Transient global amnesia (TGA) was first described by Bender in 1956 and is characterized by sudden, temporary, and anterograde memory loss. This study aimed to explore the possible mechanisms of and lesions responsible for TGA.Methods: Retrospective data were collected from all patients with TGA admitted to Zhongshan Hospital, affiliated with Xiamen University, between October 1, 2011, and October 30, 2018. Information about the TGA condition, previous history, and clinical examination of the TGA and control groups was recorded. Functional magnetic resonance imaging was performed on the patients to explore the possible lesions responsible for TGA.Results: A total of 73 patients with TGA and 73 age- and gender-matched controls were included in the analysis. The differences in the migraine history (9/2, p = 0.038) were statistically significant in both groups, but no statistically significant difference was observed regarding the history of hypertension, diabetes, and other diseases. In addition, seven patients with TGA had lesions located in the hippocampal CA1 region; the dome column and hippocampal CA1 region exist in the same functional loop and play a synergistic role. The average follow-up period in the groups was 36 months. During the follow-up period, no significant differences in cerebral infarction, cerebral hemorrhage, CHD, or TGA attack between the groups were observed.Conclusion: Migraine may be a risk factor of TGA, and cerebral infarction may be one of the pathogeneses. The brain area responsible for TGA may involve a memory loop comprising the hippocampal CA1 region and the fornix column among other parts.Keywords: transient global amnesia, risk factors, magnetic resonance imaging, responsible lesions, prognosis

As the primary productive force, education plays a huge role in the development of modern society. Traditional educational activities mainly focus on the teaching of students’ superficial knowledge and skills, which are no longer able to meet the current society’s demand for talents. At present, it is required to promote the development of in-depth thinking of college students, stimulate their innovation and creativity, and enable students to better contribute to social production. Therefore, it is very important to introduce the concept of deep learning for college students and establish a student-based teaching model. The author mainly uses mobile learning technology to analyze the functional role of mobile learning technology in promoting deep learning activities for college students, and proposes ways to effectively grasp mobile learning technology in future university informatization education activities.

Graphene is a hot star in materials science with various potential application aspects, including in Li-ion battery and supercapacitor. The burst of scientific papers in this area seems to validate the performance of graphene, but also arouses large dispute. Herein, we share our judgment of these trends to all, encouraging the discussion and enhancing the understanding of the structure-performance relationship of graphene.

The study examined how a conversation partner’s gender and gender-language consistency influence communicators’ gender-based language (i.e., references to emotion and tentativeness) and gender identity salience. In an email exchange, an experiment manipulated an ostensible conversation partner’s gender and use of references to emotion in ways stereotypically consistent or inconsistent with the partner’s gender. The conversation partner’s gender and gender-language consistency affected communicators’ references to emotion in ways that generally confirmed hypotheses. Participants’ references to emotion were congruent with the conversation partner’s use of references to emotion regardless of participants’ own gender. Results pertaining to tentative language and gender salience demonstrated no substantive differences.

We consider the location service in a mobile ad-hoc network (MANET), where each node needs to maintain its location information by 1) frequently updating its location information within its neighboring region, which is called neighborhood update (NU), and 2) occasionally updating its location information to certain distributed location server in the network, which is called location server update (LSU). The trade off between the operation costs in location updates and the performance losses of the target application due to location inaccuracies (i.e., application costs) imposes a crucial question for nodes to decide the optimal strategy to update their location information, where the optimality is in the sense of minimizing the overall costs. In this paper, we develop a stochastic sequential decision framework to analyze this problem. Under a Markovian mobility model, the location update decision problem is modeled as a Markov Decision Process (MDP). We first investigate the monotonicity properties of optimal NU and LSU operations with respect to location inaccuracies under a general cost setting. Then, given a separable cost structure, we show that the location update decisions of NU and LSU can be independently carried out without loss of optimality, i.e., a separation property. From the discovered separation property of the problem structure and the monotonicity properties of optimal actions, we find that 1) there always exists a simple optimal threshold-based update rule for LSU operations; 2) for NU operations, an optimal threshold-based update rule exists in a low-mobility scenario. In the case that no a priori knowledge of the MDP model is available, we also introduce a practical model-free learning approach to find a near-optimal solution for the problem.

With the emergence of cloud computing, users are increasingly using storage services of cloud providers to satisfy their storage needs. However, these cloud providers are not 100% reliable, resulting in periodic service outages. End users require a solution that minimizes the impact of cloud service outages and optimizes the chances of successfully retrieving stored objects in cases of provider failures. In this paper, we propose to build a federated cloud agent, enabling end users to simultaneously deploy storage objects to multiple cloud service providers, based on their unit storage costs and failure probabilities. We study two service provider failure models: the first case assumes that at most one service provider fails at any given time, and the second case assumes that cloud service providers may fail independently with certain probabilities. We cast both scenarios as constrained optimization problems to minimize the overall storage cost while enhancing the chances of recovering all the storage objects in case of service outages. In the experiments, we evaluated the proposed optimal storage schemes against a fixed server deployment strategy and find our schemes can achieve good recovery ratios, while incurring minimal storage costs.

We develop an analytical framework to study the throughput and routing overhead for proactive and reactive routing strategies in random access mobile ad hoc networks. To characterize the coexistence of the routing control traffic and data traffic, we model the interaction as a multi-class queue model at each node, where the aggregate control traffic and data traffic are two different classes of customers of the queue. We investigate the scaling property of the throughput, maximum mobility degree supported by the network and mobility-induced throughput deficiencies, under both classes of routing strategies. The proposed analytical model can be extended to incorporate various optimization techniques in routing. We present one exemplary technique and discuss its impacts on the scaling properties of throughput and routing overhead. The connection between the derived throughput result and some well-known network throughput capacity results in the literature is also addressed.

We consider the scenario of distributed data aggregation in wireless sensor networks, where each sensor can obtain and estimate the information of the whole sensing field through local data exchange and aggregation. The intrinsic trade-off between energy and delay in aggregation operations imposes a crucial question on nodes to decide optimal instants for forwarding their samples. The samples could be composed of the information from their own sensor readings or an aggregation of information with other samples forwarded from neighboring nodes. By considering the randomness of the sample arrival instants and the uncertainty of the availability of the multiaccess communication channel due to the asynchronous nature of information exchange among neighboring nodes, we propose a decision process model to analyze this problem and determine the optimal decision policies at nodes with local information. We show that, once the statistics of the sample arrival and the availability of the channel satisfy certain conditions, there exist optimal control-limit type policies which are easy to implement in practice. In the case that the required conditions are not satisfied, we provide two learning algorithms to solve a finite-state approximation model of the decision problem. Simulations on a practical distributed data aggregation scenario demonstrate the effectiveness of the developed policies, which can also achieve a desired energy-delay tradeoff.

In mobile ad hoc networks, relaying is one of the most fundamental functions. In this paper, we analyze the stability of several relaying strategies. By using the notion of node lifetime instead of the commonly used link lifetime, our analysis offers a complementary and unique finding not available in the literature previously. Our results show that a route of parallel relays have a significantly longer lifetime than a route of serial relays although the latter of the two has previously predominated the networking research.

In order to adapt to the time-varying nature of wireless channels, various channel-adaptive schemes have been proposed to exploit inherent spatial diversity in wireless ad hoc networks where there are usually alternate forwarding nodes available at a given forwarding node. However, existing schemes along this line are designed based on heuristics, implying room for performance enhancement. Thereby, to seek a theoretical foundation for improving spatial diversity gain, we formulate the selection of the next-hop relay as a sequential decision problem and derive a general "Optimal Stopping Relaying (OSR)" framework for designing such spatial-diversity schemes. As a particular example, assuming Rayleigh fading channels, we implement an OSR strategy to optimize information efficiency (IE) in a protocol stack consisting of Greedy Perimeter Stateless Routing (GPSR) and IEEE 802.11 MAC protocols. We present an analysis of the algorithm for a single node. In addition, we perform extensive simulations (using QualNet) to evaluate the end-to-end performance of the proposed forwarding strategy. The results demonstrate the superiority of OSR over other existing schemes.

For several decades, research activities in mobile ad hoc networking have predominantly relied on the notion of serial relays where a data packet hops from one node to another in a serial fashion. Recent research activities in signal processing and information theory suggest that parallel relays have a greater potential than serial relays. In this paper, a significant diversity gain of using parallel relays over serial relays is highlighted, the lifetimes of a single-path route of parallel relays and multi-path routes of serial relays are compared, and the routing overheads for each type of routes are also investigated. This study strongly supports that parallel relays have great advantages over serial relays in dense and mobile ad hoc networks.

Ultra-wideband (UWB) systems spread the transmitted signal power over an extremely large frequency band, and the power spectral density of the signal is very low. Due to the wide bandwidth of the transmitted signal, UWB signal energy spreads over the frequency bands allocated to other radio systems. Evaluating the interference issues of these narrowband systems to UWB systems in its overlay band is an important issue for understanding and designing efficient UWB systems. An analysis of the power spectral density (PSD) of generic narrowband signals is presented. The theoretical and simulation results reveal that the bit-error-rate (BER) performance of a direct sequence UWB (DS-UWB) system with a minimum mean square error (MMSE) receiver is robust in the presence of narrowband interference caused by existing applications.

Leaf senescence in many plant species is associated with increased oxidative damage to cellular macromolecules by reactive oxygen species (ROS). Since ROS levels and their damage products in many plants are known to increase during senescence, it is possible that these changes are due to a decline in the levels of certain antioxidant enzymes. Using specific assays, we find that the developmental transition to bolting and flowering is associated with up to a 5-fold decline in ascorbate peroxidase activity and an increase in chloroplastid superoxide dismutase. As expected, these changes are associated with a measured increase in lipid peroxidation products. By HPLC separation of the products, we identified the different positional isomers and find that stereospecific lipid peroxidation occurs after the bolting transition. The product distribution suggests that enzyme-mediated lipid peroxidation, via a lipoxygenase, is responsible for the observed increase. Surprisingly, though consistent with the known induction of antioxidant defenses by hydrogen peroxide, the activity of APX rebounds with further development (reproduction and seed setting) and this increase (up to 5-fold) is associated with declines in lipid peroxidation and with the onset of visible senescence symptoms. Thus, in Arabidopsis, ROS increases are associated with the developmental transition to flowering, perhaps due to programmed declines in APX activity, and apparently lead to the oxidative activation of lipoxygenase and subsequent lipid peroxidation. The reactivation of APX at later stages appears to help reduce the lipid peroxidation rate, although the senescence program continues unabated.

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