Low-temperature X-ray microanalysis of the differentiating vascular tissue in root tips of Lemna minor L

The fracture faces of bulk-frozen tissue offer a number of advantages for the analysis of diffusible elements. They are easy to prepare, remain uncontaminated, and, unlike most frozen-hydrated sections, can be shown to exist in a fully hydrated state throughout examination and analysis. Root tips of Lemna minor briefly treated with a polymeric cryoprotectant are quench frozen in melting nitrogen. Fractures are prepared using the AMRAY Biochamber, lightly etched if necessary to reveal surface detail and carbon coated while maintaining the specimen at 110 K. The frozen-hydrated fracture faces are analysed at 110 K using the P/B ratio method which is less sensitive to changes in surface geometry and variations in beam current. The method has been used to investigate the distribution of seven elements (Na+, Mg⁺⁺, P, S, Cl^?, K+ and Ca⁺⁺) in the developing vascular tissue of the root tip. The microprobe can measure relative elemental ratios at the cellular level and the results from this present study reveal important variations in different parts of the root. The younger, more actively dividing cells, appear to have a slightly higher concentration of diffusible ions in comparison to the somewhat older tissues which have begun to differentiate into what are presumed to be functional vascular elements.     

Termination detection for dynamically distributed systems with non-first-in-first-out communication

We propose a new algorithm for detecting termination of distributed systems. The algorithm works correctly whether the system is static or dynamic, whether the interprocess communication is synchronous or asynchronous, and whether the communication channels are first-in-first-out or not. The algorithm requires, in the worst case, O(nm) control messages in all, where n is the number of processes in the system and m is the total number of messages transmitted during the operation of the system. After the system terminates, the algorithm is able to detect the termination using only O(n) control messages; it is optimal if the system concerned is static.     

Dynamic characteristic analysis of TBM tunnelling in mixed-face conditions

In this paper, by taking into account the periodically varying mesh stiffness in multiple pinions transmission and the speed–torque characteristics of variable frequency motor drives, the dynamic model for the revolving system of tunnel boring machine (TBM) has been established. Based on the soft ground/hard rock assumption of mixed-face conditions and the analysis of cutting force on each disc cutter and each drag bit, the time-varying excavation torque on the TBM cutterhead in mixed-face tunnelling is obtained. The dynamic excavation torque and cutterhead rotation speed are discussed and compared for TBM tunnelling in several typical mixed-face conditions, which are characterized by the area percentage of soft ground on the excavation face and the uniaxial compressive strength (UCS) of rock. The results show that the excavation torque may run up to a critical value and fluctuate greatly in extremely adverse excavation environments, which may lead to an unexpected TBM stoppage and even a catastrophic failure of the drive motor. To decrease the penetration per revolution in time through applying a lower advance velocity and a higher cutterhead revolution will significantly reduce the excavation torque and effectively avoid such situations.     

Secreted HSP90α-LRP1 Signaling Promotes Tumor Metastasis and Chemoresistance in Pancreatic Cancer

The extracellular heat shock protein 90α (eHSP90α) has been reported to promote cancer cell motility. However, whether pancreatic cancer (PC) cells expressed membrane-bound or secreted HSP90α, as well as its underlying mechanism for PC progression, were still unclear. Our study demonstrated that the amounts of secreted HSP90α proteins were discrepant in multiple PC cells. In addition, highly invasive Capan-2 cells have a higher level of secreted HSP90α compared with those of less invasive PL45 cells. The conditioned medium of Capan-2 cells or recombinant HSP90α treatment stimulated the migration and invasion of PC cells, which could be prevented with a neutralizing anti-HSP90α antibody. Furthermore, secreted HSP90α promoted elements of epithelial–mesenchymal transition in PL45 cells, including increases in vimentin and Snail expressions, decreases in E-cadherin expression, and changes in cell shape towards a mesenchymal phenotype, but these phenomena were reversed by the anti-HSP90α antibody in Capan-2 cells. In addition, high levels of low-density lipoprotein receptor-related protein 1 (LRP1) were associated with worsened patient survival in pancreatic adenocarcinoma. We demonstrated LRP1 as a receptor of eHSP90α for its stimulatory role in metastasis, by activating the AKT pathway. In addition, silencing LRP1 enhanced the chemosensitivity to gemcitabine and doxorubicin in Capan-2 cells. Therefore, our study indicated that blocking secreted HSP90α underlies an aspect of metastasis and chemoresistance in PC.     

HSPA4 Is a Biomarker of Placenta Accreta and Enhances the Angiogenesis Ability of Vessel Endothelial Cells

Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore their pathogenetic roles in PAS. For this purpose, we collected five placentas from pregnant subjects with PAS complications and another five placentas from normal pregnancy (NP) cases. Then, we enriched protein samples by specifically isolating the trophoblast villous, deeply invading into the uterine muscle layer in the PAS patients. Next, fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-TOF/MS were used to identify the proteins differentially abundant between PAS and NP placenta tissues. As a result, nineteen spots were determined as differentially abundant proteins, ten and nine of which were more abundant in PAS and NP placenta tissues, respectively. Then, specific validation with western blot assay and immunohisto/cytochemistry (IHC) assay confirmed that heat shock 70 kDa protein 4 (HSPA4) and chorionic somatomammotropin hormone (CSH) were PAS protein biomarkers. Further tube formation assays demonstrated that HSPA4 promoted the in vitro angiogenesis ability of vessel endothelial cells, which is consistent with the in vivo scenario of PAS complications. In this study, we not only identified PAS protein biomarkers but also connected the promoted angiogenesis with placenta invasion, investigating the pathogenetic mechanism of PAS.     

Molecular and Physiological Responses of Citrus sinensis Leaves to Long-Term Low pH Revealed by RNA-Seq Integrated with Targeted Metabolomics

Low pH-induced alterations in gene expression profiles and organic acids (OA) and free amino acid (FAA) abundances were investigated in sweet orange [Citrus sinensis (L.) Osbeck cv. Xuegan] leaves. We identified 503 downregulated and 349 upregulated genes in low pH-treated leaves. Further analysis indicated that low pH impaired light reaction and carbon fixation in photosynthetic organisms, thereby lowering photosynthesis in leaves. Low pH reduced carbon and carbohydrate metabolisms, OA biosynthesis and ATP production in leaves. Low pH downregulated the biosynthesis of nitrogen compounds, proteins, and FAAs in leaves, which might be conducive to maintaining energy homeostasis during ATP deprivation. Low pH-treated leaves displayed some adaptive responses to phosphate starvation, including phosphate recycling, lipid remodeling, and phosphate transport, thus enhancing leaf acid-tolerance. Low pH upregulated the expression of some reactive oxygen species (ROS) and aldehyde detoxifying enzyme (peroxidase and superoxidase) genes and the concentrations of some antioxidants (L-tryptophan, L-proline, nicotinic acid, pantothenic acid, and pyroglutamic acid), but it impaired the pentose phosphate pathway and V_E and secondary metabolite biosynthesis and downregulated the expression of some ROS and aldehyde detoxifying enzyme (ascorbate peroxidase, aldo-keto reductase, and 2-alkenal reductase) genes and the concentrations of some antioxidants (pyridoxine and γ-aminobutyric acid), thus disturbing the balance between production and detoxification of ROS and aldehydes and causing oxidative damage to leaves.     

Nitric Oxide Signalling in Descending Vasa Recta after Hypoxia/Re-Oxygenation

Reduced renal medullary oxygen supply is a key factor in the pathogenesis of acute kidney injury (AKI). As the medulla exclusively receives blood through descending vasa recta (DVR), dilating these microvessels after AKI may help in renoprotection by restoring renal medullary blood flow. We stimulated the NO-sGC-cGMP signalling pathway in DVR at three different levels before and after hypoxia/re-oxygenation (H/R). Rat DVR were isolated and perfused under isobaric conditions. The phosphodiesterase 5 (PDE5) inhibitor sildenafil (10⁻⁶ mol/L) impaired cGMP degradation and dilated DVR pre-constricted with angiotensin II (Ang II, 10⁻⁶ mol/L). Dilations by the soluble guanylyl cyclase (sGC) activator BAY 60-2770 as well as the nitric oxide donor sodium nitroprusside (SNP, 10⁻³ mol/L) were equally effective. Hypoxia (0.1% O₂) augmented DVR constriction by Ang II, thus potentially aggravating tissue hypoxia. H/R left DVR unresponsive to sildenafil, yet sGC activation by BAY 60-2770 effectively dilated DVR. Dilation to SNP under H/R is delayed. In conclusion, H/R renders PDE5 inhibition ineffective in dilating the crucial vessels supplying the area at risk for hypoxic damage. Stimulating sGC appears to be the most effective in restoring renal medullary blood flow after H/R and may prove to be the best target for maintaining oxygenation to this vulnerable area of the kidney.     

Erythropoietin in Optic Neuropathies: Current Future Strategies for Optic Nerve Protection and Repair

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/βcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.     

Proactive multipath routing with a predictive mechanism in software‐defined networks

With the growth of network traffic volume, link congestion cannot be avoided efficiently with conventional routing protocols. By utilizing the single shortest‐path routing algorithm from link state advertisement information, standard routing protocols lack of global awareness and are difficult to be modified in a traditional network environment. Recently, software‐defined network (SDN) provided innovative architecture for researchers to program their own network protocols. With SDN, we can divert heavy traffic to multiple paths in order to resolve link congestion. Furthermore, certain network traffics come in periodic fashion such as peak hours at working days so that we can leverage forecasting for resource management to improve its performance. In this paper, we propose a proactive multipath routing with a predictive mechanism (PMRP) to achieve high‐performance congestion resolution. PMRP has two main concepts: (a) a proactive mechanism where PMRP deploys M/M/1 queue and traffic statistics to simulate weighted delay for possible combinations of multipaths placement of all subnet pairs, and leverage genetic algorithm for accelerating selection of optimized solution, and (b) a predictive mechanism whereby PMRP uses exponential smoothing for demand traffic volumes and variance predictions. Experimental results show a 49% reduction in average delay as compared with single shortest routing, and a 16% reduction in average delay compared with utilization & topology‐aware multipath routing (UTAMP). With the predictive mechanism, PMRP can decrease an additional 20% average delay. Furthermore, PMRP reduces 93% of flow table usage on average as compared with UTAMP.