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Resource contentions and performance interferences can lead to workload performance degradation in mixed-workload deployment clusters. Previous work guarantees the resource requirements of latency-sensitive tasks and reduces performance losses to batch jobs by reclaiming surplus resources from over-provisioned tasks. While the fragmentation of resources leads to a mismatch between provisioned resources and task requirements, resulting in high operation overheads and losses of task fairness. This paper proposes TERMS , the task management policies based on task relevance, resource distribution, and task fairness to achieve efficient and low-cost task management. TERMS mainly includes three types of management policies. The task scheduling policy can schedule new tasks according to task relevance. Task selection strategies select tasks for resource provisioning and task resumption based on resource requirements and task fairness. If necessary, the node selection strategy can be used to choose befitting target nodes based on task relevance and node resource information for task migration when eliminating straggler tasks. Evaluation results show that TERMS can further improve the performance of latency-sensitive services and batch jobs, reduce management overheads, and avoid operation failures. • Place latency-sensitive new tasks in the queue according to task relevance. • Select batch tasks to provision resources for latency-sensitive new tasks. • Select batch tasks to provision resources for latency-sensitive straggler tasks. • Ensure task fairness when tasks are preempted or resumed. • Choose befitting target nodes for latency-sensitive straggler task migration. [ABSTRACT FROM AUTHOR]

Different applications have different access characteristics and various performance requirements. Thus, the shared cloud object store entails providing tenant-specific policies. However, the limited configurability of existing storage policies makes it difficult to provide efficient and flexible policies to meet tenants' evolving needs. First, existing policies that only control request forwarding cannot provide sufficient optimizations for workload performance. Second, those policies lack the flexibility to adapt to the possible workload changes during runtime. In this paper, we propose Mass, a programmable framework to provide the enhanced storage policies for diverse workloads based on their access characteristics. We also design its enhancements, C-Mass, extending Mass's capabilities through container-based policy deployment to efficiently handle workload changes. Compared with existing storage policies, the latency and throughput of workloads under Mass are improved by up to 81.6% and 231.5%, respectively. Further, the workload performance under C-Mass is optimized by up to 40%. • We actively detect the workload characteristics and track their changes. • We propose Mass to provide workload-aware storage policies. • We set up prioritized queues to coordinate workloads. • We further build C-Mass over Mass to efficiently handle workload changes. [ABSTRACT FROM AUTHOR]

According to former research, the atherosclerotic plaque is thought to be aggravated by intraplaque neovessels (IPN) and intraplaque hemorrhage (IPH). Intriguingly, a lower incidence of IPH was found in plaque treated with melatonin. In this study, we attempted to investigate the impact and underlying mechanism regarding the influences of melatonin upon IPN. A mouse model was established by subjecting the high fat diet (HFD)-fed ApoE−/− mice to tandem stenosis (TS) surgery with melatonin and GW9662, a PPARγ antagonist, being given by gavage. In vitro experiment was conducted with HUVECs exposing to according treatments of VEGF, melatonin, GW9662, or Y27632. Plaque and IPN were attenuated by treatment with melatonin, which was then reversed by blocking PPARγ. Western blotting results showed that melatonin increased PPARγ and decreased RhoA/ROCK signaling in carotid artery. Elevated RhoA/ROCK signaling was observed in melatonin-treated mice when PPARγ was blocked. In accordance with it, experiments using protein and mRNA from HUVECs revealed that melatonin inhibited the RhoA/ROCK signaling by enhancing PPARγ. According to in vitro study, melatonin was able to inhibit cell migration and angiogenesis, which was aborted by GW9662. Blockage of ROCK using Y27632 was able to cease the effect of GW9662 and restored the suppression on cell migration and angiogenesis by melatonin. Our study demonstrates that melatonin is able to curb development of plaque and IPN formation by inhibiting the migration of endothelial cells via PPARγ- RhoA-ROCK pathway. That provides a therapeutic potential for both melatonin and PPARγ agonist targeting IPN, IPH, and atherosclerotic plaque. • Melatonin reduces intraplaque neovessels and intraplaque hemorrhage via PPARγ- RhoA-ROCK pathway. • Melatonin inhibits the angiogenic processes of endothelial cells via PPARγ- RhoA-ROCK pathway. • Activation of PPARγ contributes to the suppression of endothelial migration and intraplaque neovessels. [ABSTRACT FROM AUTHOR]

In this paper we discuss the MUSCL-Hancock scheme for the two-dimensional conservation laws and derive the bound-preserving conditions by a parameterized convex decomposition method which is proposed in [ Journal of Computational Physics, 474:111805, 2023 ] for one-dimensional problems. The CFL number equals the half of the one-dimensional value and then ensures the speed-up compared with the classical two-stage MUSCL scheme. The bound-preserving slope limiter on the preliminary reconstruction becomes problem dependent. The maximum-minimum preserving slope limiter for the scalar problems becomes the same with its one-dimensional version. A positivity-preserving slope limiter for the Euler system is designed including a different parameter from the scalar problems and more efficient operators than the existing limiters. Numerical experiments are reported to demonstrate the robustness of the proposed scheme. • Developed bound-preserving conditions of the 2D MUSCL-Hancock scheme. • The same slope limiter and half the CFL number compared to the 1D case. • Solved important models, such as nonlinear problem, incompressible advection problem and Euler equations. • Numerically checked the sharpness and the robustness of the scheme. [ABSTRACT FROM AUTHOR]

The carcinogenic function of arachidonate lipoxygenase12 (Alox12) has been reported in various cancers. However, little is known on the role of Alox12 in lung cancer. Here, we demonstrate that Alox12 is upregulated and contributes to biological activities of lung cancer through multiple mechanisms. We found that Alox12 mRNA and protein levels were increased by 2.5-fold in a panel of lung cancer cell lines compared to normal lung cells. The expression of Alox12 varied among lung cancer cell lines. The immunohistochemistry analysis on paired normal and tumor lung tissues from twenty patients showed that Alox12 protein level is higher in lung cancer than normal lung tissues from the majority of patients. We further observed the upregulation of Alox12-12-HETE signaling axis in lung cancer tissues. Overexpression of Alox12 promoted growth and migration in normal lung cells and lung cancer cells. In contrast, Alox12 inhibition via genetic and pharmacological approaches suppressed growth and migration, induced apoptosis, and sensitized lung cancer cells to chemotherapy. This is through suppressing RhoA signaling, inhibiting epithelial-to-mesenchymal transition (EMT) and NF-κB activity. Our work reveals the therapeutic value of inhibiting Alox12 in overcoming chemoresistance in lung cancer. • Alox12 is elevated in half of lung cancer patients analyzed. • Alox12 overexpression promotes normal and tumor lung cell growth and migration. • Alox12 knockdown inhibits lung cancer cells. • Alox12 depletion suppresses RhoA, EMT and NF-κB activity in lung cancer cells. [ABSTRACT FROM AUTHOR]

In this paper we introduce sharp stability conditions for the single-stage MUSCL-Hancock scheme: 1) the CFL number is (3 − 1) / 2 which admits almost 73 percent of the time step of classical two-stage MUSCL scheme and hence yields a considerable speed-up; 2) The preliminary TVD reconstruction is modified when necessary by a bound-preserving slope limiter which keeps the higher resolution. A direct extension on 2D nonlinear Euler system is obtained resulting a positivity-preserving scheme. Numerical examples verify the sharpness of these settings and demonstrate the robustness of the scheme for different type of problems. • New bound-preserving conditions for the MUSCL-Hancock scheme. • A parameterized convex decomposition analysis to optimize these stability conditions. • A new bound-preserving slope limiter to ensure the higher resolution. • An enlarged CFL number to speed up the simulation. • Experiments checked the sharpness of above settings and robustness for 2D Euler fluid. [ABSTRACT FROM AUTHOR]

In this paper, we give a recurrence relation for determining the coefficients a j such that Γ ( x + 1 ) ∼ 2 π x ( x e ) x ( 1 + 1 12 x + ∑ j = 0 ∞ a j x − j ) , x → ∞ . We provide a pair of recurrence relations for determining the constants α ℓ and β ℓ such that Γ ( x + 1 ) ∼ 2 π x ( x e ) x ( 1 + ∑ ℓ = 1 ∞ α ℓ ( x + β ℓ ) 2 ℓ − 1 ) , x → ∞ . Furthermore, we determine the best possible constants a and b such that the inequality 2 π n ( n e ) n ( 1 + 1 12 n − a ) ≤ n ! < 2 π n ( n e ) n ( 1 + 1 12 n − b ) holds for all integers n ≥ 1 . [ABSTRACT FROM AUTHOR]

Abstract: Mechanisms underlying bone cancer-induced pain are largely unknown. Previous studies indicate that neuroinflammation in the spinal dorsal horn is especially involved. Being first reported as a nonhistone chromosomal protein, high-mobility group box 1 (HMGB1) is now implicated as a mediator of inflammation. We hypothesized that HMGB1 could trigger the release of cytokines in the spinal dorsal horn and contribute to bone cancer pain. To test this hypothesis, we first built a bone cancer pain model induced by intratibal injection of Walker 256 mammary gland carcinoma cells. The structural damage to the tibia was monitored by radiological analysis. The mechanical allodynia was measured and the expression of spinal HMGB1 and IL-1β was evaluated. We observed that inoculation of cancer cells, but not heat-killed cells, induced progressive bone destruction from 9 d to 21 d post inoculation. Behavioral tests demonstrated that the significant nociceptive response in the cancer cells-injected rats emerged on day 9 and this kind of mechanical allodynia lasted at least 21 d following inoculation. Tumor cells inoculation significantly increased HMGB1 expression in the spinal dorsal horn, while intrathecal injecting a neutralizing antibody against HMGB1 showed an effective and reliable anti-allodynia effect with a dose-dependent manner. IL-1β was significantly increased in caner pain rats while intrathecally administration of anti-HMGB1 could decrease IL-1β. Together with previous reports, we predict that bone cancer induces HMGB1 production, enhancing spinal IL-1β expression and thus modulating spinal excitatory synaptic transmission and pain response. [Copyright &y& Elsevier]

Abstract: The centrosome plays a vital role in maintaining chromosomal stability. Known as the microtubule organizing center, the centrosome is involved in the formation of spindle poles during mitosis, which ensures the distribution of the correct number of chromosomes to daughter cells. Aberrant centrosome duplication could cause centrosome amplification and chromosomal instability. We have previously shown that poly(ADP-ribose) polymerase-1 (PARP-1) is important for centrosome function and chromosomal stability. In this study, we used PARP-1+/+, PARP-1+/− and PARP-1−/− primary mouse embryonic fibroblasts and found that the level of PARP-1 gene dosage correlates with PARP activity and the in vivo level of poly(ADP-ribosyl)ation, which could explain the mechanism by which PARP-1 haploinsufficiency affects centrosome duplication and chromosomal stability. Our results emphasize that correct regulation of poly(ADP-ribosyl)ation levels in vivo is important for maintenance of proper centrosome duplication and chromosomal stability. [Copyright &y& Elsevier]

Abstract: We have previously shown the importance of LTB4 in human pancreatic cancer. LTB4 receptor antagonists block growth and induce apoptosis in pancreatic cancer cells both in vitro and in vivo. Therefore, we investigated the effect of LTB4 on proliferation of human pancreatic cancer cells and the mechanisms involved. LTB4 stimulated DNA synthesis and proliferation of both PANC-1 and AsPC-1 human pancreatic cancer cells, as measured by thymidine incorporation and cell number. LTB4 stimulated rapid and transient activation of MEK and ERK1/2 kinases. The MEK inhibitors, PD98059 and U0126, blocked LTB4-stimulated ERK1/2 activation and cell proliferation. LTB4 also stimulated phosphorylation of p38 MAPK; however, the p38 MAPK inhibitor, SB203580, failed to block LTB4-stimulated growth. The activity of JNK/SAPK was not affected by LTB4 treatment. Phosphorylation of Akt was also induced by LTB4 and this effect was blocked by the PI-3 kinase inhibitor wortmannin, which also partially blocked LTB4-stimulated cell proliferation. In conclusion, LTB4 stimulates proliferation of human pancreatic cancer cells through MEK/ERK and PI-3 kinase/Akt pathways, while p38 MPAK and JNK/SAPK are not involved. [Copyright &y& Elsevier]

Previous experimental studies have shown that high dietary fat intake is associated with mammary carcinogenesis. In the current study, the effect of 5-LOX or 12-LOX inhibitors on human breast cancer cell proliferation and apoptosis, as well as the possible mechanisms were investigated. The LOX inhibitors, NDGA, Rev-5901, and baicalein all inhibited proliferation and induced apoptosis in MCF-7 (ER+) and MDA-MB-231 (ER−) breast cancer cell in vitro. In contrast, the LOX products, 5-HETE and 12-HETE had mitogenic effects, stimulating the proliferation of both cell lines. These inhibitors also induced cytochrome c release, caspase-9 activation, as well as downstream caspase-3, caspase-7 activation, and PARP cleavage. LOX inhibitor treatment also reduced the levels of anti-apoptotic proteins Bcl-2 and Mcl-1 and increased the levels of the pro-apoptotic protein bax. In conclusion, blockade of both 5-LOX and 12-LOX pathways induces apoptosis in breast cancer cells through the cytochrome c release and caspase-9 activation, with changes in the levels of Bcl-2 family proteins. [Copyright &y& Elsevier]

Abstract: Alcohol dehydrogenases (ADHs) from thermophilic microorganisms are interesting enzymes that have their potential applications in biotechnology and potentially provide insight into the mechanisms of action of thermo-tolerant proteins. The molecular mechanisms of ADHs under thermal stress in vivo have yet to be explored. Herein, we employed a proteomic strategy to survey the possible interactions of secondary-ADH (2-ADH) with other proteins in Thermoanaerobacter tengcongensis (T. tengcongensis) cultured at 75°C and found that 2-ADH, pyruvate-ferredoxin oxidoreductase (PFOR) and several glycolytic enzymes coexisted in a protein complex. Using anion exchange chromatography, the elution profile indicated that the native 2-ADH was present in two forms, PFOR-bound and PFOR-free. Immuno-precipitation and pull down analysis further validated the interactions between 2-ADH and PFOR. The kinetic behaviours of 2-ADH either in the recombinant or native form were evaluated with different substrates. The enzyme activity of 2-ADH was inhibited in a non-competitive mode by PFOR, implying the interaction of 2-ADH and PFOR negatively regulated alcohol formation. In T. tengcongensis, PFOR is an enzyme complex located at the upstream of 2-ADH in the alcohol generation pathway. These findings, therefore, offered a plausible mechanism for how alcohol metabolism is regulated by hetero-interactions between 2-ADH and PFOR, especially in anaerobic thermophiles. [Copyright &y& Elsevier]

Abstract: Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K m of PARP1-Ala762 was increased to a 1.2-fold of the K m of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K m. This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding the cancer risk of carriers of the PARP1 Val762Ala polymorphism. [Copyright &y& Elsevier]

Here, 38 wheat PYL genes (TaPYL s) belonging to 13 homoeologous groups were identified using the genome-search method, with 26 and 12 PYL genes identified in Triticum dicoccoides and Aegilops tauschii, respectively. Phylogenetic relationship, conserved domain and molecular evolution analysis revealed that PYL genes showed highly conservative between wheat and theprogenitors. Interaction network and miRNA target prediction found that TaPYLs could interact with the important components of ABA signaling pathway and Tae-miR966b-3p might be a hub regulator mediating wheat ABA signal network. Furthermore, the tissue-specific and stress-responsive TaPYLs were detected through RNA-seq analysis. Expressions of 10 TaPYLs were validated by QPCR analysis and the homoeologous genes showed significantly differential expression, suggesting subfunctionalization of them has occurred. Finally, 3D structures of the TaPYL proteins were predicted by homology modeling. This study lays the foundation for further functional study of PYL genes for development and stress tolerance improvement in wheat and beyond. • The PYL gene family was identified in wheat and its two progenitors at the genome-wide level. • PYL genes showed highly conservative in wheat and its progenitors from the perspective of sequence composition, exon-intron structure, conserved domain and 3D structure. • Expression profiles of these wheat PYL genes were systematically investigated using the available 58 RNA-seq samples. • Subfunctionalization has occurred in A, B and D homoeologous copies of wheat PYL genes. [ABSTRACT FROM AUTHOR]

Abstract We previously identified a set of the most frequently mutated cytoskeleton- and extracellular matrix-related proteins (CECMPs) in numerous cancer datasets. In this report, we used a bioinformatics approach to assess the impact of amino acid (AA) substitutions on the sensitivity of CECMPs to the ST14 protease (matriptase I), a transmembrane serine protease previously implicated in cancer development. Results indicated that AA substitutions in glioblastoma multiforme (GBM) CECMPs are skewed toward increased resistance to the ST14 protease, in comparison to the wild-type peptide sequence. Furthermore, the protease resistant AA substitutions represent relatively high binding affinities to HLA class I proteins, when assessing the binding specificities using HLA class I alleles matched to the source of the mutant AA. Moreover, samples representing AA substitutions that increased protease sensitivity also represented reduced overall and disease-free survival periods for patients with glioblastoma. To assess tumor specimen immunogenicity, we identified T-cell receptor (TCR) V(D)J recombinations in GBM exome files. The overlap between ST14 protease sensitive mutant barcodes and the TCR V(D)J recombination read positive barcodes represented significantly reduced survival. Highlights • In GBM, mutant ECM proteins appear largely resistant to the ST14 protease. • Patients with resistant proteins have a better survival. • The few patients with sensitive mutants have T-cell infiltrates. [ABSTRACT FROM AUTHOR]

Highlights: [•] Lentiviral vector construction and virus packaging. [•] Lentiviral ERK2 siRNA detection both in vitro and vivo. [•] Lentiviral ERK2 siRNA is able to prevent collagen expression and scar adhesion. [•] Lentiviral ERK2 siRNA is able to suppress the expression of TGF-β1 and IL-6. [ABSTRACT FROM AUTHOR]

Abstract: Adipose-derived stem cells (ASCs) have been successfully applied in treating bone defects both in animals and humans and promoted osteogenesis in vivo significantly. However, the mechanism of in vivo osteogenesis of ASCs was still little known, we hypothesized that this was mediated in part by interaction between implanted ASCs and local vein endothelial cells. In this study, human adipose-derived stem cells (hASCs) and human umbilical vein endothelial cells (HUVEC) were isolated and characterized. Cells were then either cultured alone or cocultured. Alkaline phosphatase (ALP) staining, quantitative measurement of ALP activity and Alizarin staining of hASCs cultured alone, HUVEC cultured alone and cells cocultured demonstrated that osteogenic differentiation of cocultured cells increased obviously. Osteocalcin (OC) expression of hASCs cocultured with HUVEC showed an obvious raise than hASCs cultured alone. HUVEC cultured alone showed BMP-2 secretion and increased with culturing time. Real-time PCR of the cocultured cells showed four osteogenic differentiation related genes raised with culturing time, while two adipogenic differentiation related genes showed a slightly decrease with culturing time. Results of our study with different culture models showed that in vitro osteogenesis of hASCs was enhanced by coculture with HUVEC which secreted BMP-2. This study not only provided us with an in vitro model of studying interaction between cells, but also helped us to understand the in vivo therapeutic mechanisms of ASCs. [Copyright &y& Elsevier]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is newly discovered virus which is the member of the order Bunyavirales, family phenuiviridae, phlebovirus genus. Its genome is composed of 3 segments of negative-sense RNA L, M and S. NSs is a non structure protein encoded by S segment which is important for viral replication and virulence. NSs protein of SFTSV is only involved in the regulation of host innate immune responses and suppression of IFN-promoter activities. So, the exact functions of this protein need to be studied deeply. To understand the exact role of NSs from SFTSV in viral replication and host immune response, a qualified antibody against this protein is required. In this study, NSs gene of SFTSV, was cloned into a bacterial expression vector (pGEX-6P-1) and the recombinant plasmid was transformed into Escherichia coli BL21 (DE3) cells. The SFTSV NSs fusion protein was purified using Glutathione Sepharose 4B and utilized as an antigen to immunize rabbits and obtain an anti-SFTSV NSs polyclonal antibody. Proper expression of the fusion protein and polyclonal antibody specificity were confirmed by western blotting and immunofluorescence analyses. The polyclonal antibody recognized NSs from SFTSV specifically. This is the first report that NSs can form viroplasm-like structures not only in infected cells but also in transfected cells with NSs plasmids. This polyclonal antibody will be useful for future studies of NSs functions. • The polyclonal antibody could specifically recognize SFTSV NSs protein. It's essential to study biological function of SFTSV NSs protein. [ABSTRACT FROM AUTHOR]