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The decomposition of SF6 is closely related to the internal insulation status of equipment. Using SF6 decomposition component information can effectively diagnose the internal insulation fault of gas-insulated equipment. This method has been widely concerned by the power industry. However, due to the limited amount of SF6 fault decomposition component data accumulated now and the vast majority of them are laboratory simulation data, the application of this method in engineering is limited. According to the characteristics of SF6 decomposition component data, this article proposes a fault diagnosis strategy based on Gaussian process classification (GPC) and decision fusion (DF). On the basis of a large amount of experimental data and on-site fault data accumulated in the early stage, the existing data are expanded by piecewise cubic spline interpolation. To improve the generalization ability of fault diagnosis, the expanded SF6 decomposition component data is applied to the ensemble learning model. The basic learner of ensemble learning will introduce the GPC model based on Markov chain Monte Carlo (MCMC) sampling. At the same time, an improved scheme of Bagging integrated learning is proposed, in which the voting rule is improved to the combination rule of evidence theory. The proposed scheme of “data driven + model driven” improves the diagnostic accuracy to 97%. It provides a set of efficient diagnosis strategies for the power industry.

Few transcription factors have been examined for their direct roles in physically connecting enhancers and promoters. Here acute degradation of Yin Yang 1 (YY1) in erythroid cells revealed its requirement for the maintenance of numerous enhancer–promoter loops, but not compartments or domains. Despite its reported ability to interact with cohesin, the formation of YY1-dependent enhancer–promoter loops does not involve stalling of cohesin-mediated loop extrusion. Integrating mitosis-to-G1-phase dynamics, we observed partial retention of YY1 on mitotic chromatin, predominantly at gene promoters, followed by rapid rebinding during mitotic exit, coinciding with enhancer–promoter loop establishment. YY1 degradation during the mitosis-to-G1-phase interval revealed a set of enhancer–promoter loops that require YY1 for establishment during G1-phase entry but not for maintenance in interphase, suggesting that cell cycle stage influences YY1’s architectural function. Thus, as revealed here for YY1, chromatin architectural functions of transcription factors can vary in their interplay with CTCF and cohesin as well as by cell cycle stage.

Edge computing paradigms such as cloudlet, mobile edge computing (MEC) and fog computing, are promising to reduce network transmission delay while meeting intensive computing requirements at the network edge. As always assumed in theoretical studies, to expand service capability, it is desirable to integrate edge resources into a unified resource pool and make different edge facilities collaborate. However, this collaboration is difficult in practice since the heterogeneity among paradigms leads to resource isolation. This article focuses on clarifying and shielding heterogeneity among edge computing paradigms for collaboration. First, based on cloudlet, mobile edge computing and fog computing, three main edge computing paradigms, that is, small cloudy edge paradigm (SmaIIC), mobile integrated edge paradigm (Moblnt) and front ad hoc edge paradigm (FrontAH), are defined. So that the heterogeneity among them can be analyzed, according to which, collaboration challenges in computing resource trading, information communication and resource sharing are identified. Promising techniques such as blockchain-based smart contract, media-independent handover (MIH), and software-defined network and network function virtualization (SDN/NFV) are then introduced and integrated into a complete collaboration solution. Finally, taking the unmanned vehicular navigation as an example, the performance of collaboration is evaluated, considering additional costs introduced by collaborations, including trading, network hand-off and data transmission among edge facilities in different paradigms. Simulation results show that compared with existing schemes of the three paradigms, the collaboration can reduce the cost (i.e., weighted sum of energy consumption and delay) by at least 45.6 percent.

With the spread of emerging services, multi-dimensional extreme performance requirements have been put forward for the sixth generation (6G) networks. The integration of sensing, communications, and computing (ISCAC) is expected to transform the 6G networks from simple transmission pipelines to smart infrastructures with enhanced capabilities. To help the 6G networks live up to their potential, we firstly design a three-dimensional ISCAC network architecture from the perspectives of network space, horizontal functionality, and vertical functionality. Next, we propose two performance indicators for the ISCAC network to map the multi-dimensional resources into the same evaluation system. Based on the proposed indicator, an AoI-enabled resource management mechanism is developed. Finally, performance evaluations are carried out and the time average expectation of AoI can be reduced by up to 36.39% compared with the existing mechanism.

In this study, we propose a novel portable wearable cardiorespiratory sensor integrated with a smartphone, fabricated from plastic optical fiber (POF) and polydimethylsiloxane (PDMS) material. The sensor is designed for comprehensive cardiorespiratory monitoring, enabling accurate measurement of respiratory rate (BR), heart rate (HR), and HR variability (HRV). The prototype successfully captures heartbeat signals with excellent waveforms, revealing distinct BR and HR peaks in the frequency-domain plot. Our measurements show an average difference of 0.310 bpm for BR and 0.033 bpm for HR compared to reference values. Additionally, we performed 5-min HRV assessments under different conditions, yielding mean standard deviations of normal to normal (SDNN) of 52.87, 81.89, 49.41, and 28.22 ms for the control, specific breathing pattern, walking, and running groups, respectively. The cardiorespiratory sensor demonstrates its potential as a reliable alternative for daily monitoring of BR, HR, and HRV, offering versatility for various application scenarios with high safety and widespread usability.

Background: Fenofibrate was reported to be beneficial for cholestasis in combination with ursodeoxycholic acid. However, its therapeutic action as single therapy for chronic cholestasis and the underlying mechanism are not known. Methods: In the present study, wild-type (WT) mice were administered a 0.05% ANIT diet to mimic chronic cholestatic liver injury. Mice were dosed fenofibrate 25 mg/kg twice every day for 10 days to investigate the therapeutic action of fenofibrate on chronic cholestatic liver injury. Ppara-null (KO) mice were used to explore PPARa’s role in the therapeutic outcome. Results: Fenofibrate, administered at 25 mg/kg twice daily, substantially reversed ANIT-induced chronic cholestatic liver injury shown by biochemical and pathological end points. The modifications of bile acid metabolism were found to be adaptive responses. The JNK–AP1–CCL2/CXCL2 axis was activated in all the mice administered ANIT which developed chronic cholestatic liver injury. But it was substantially decreased by fenofibrate in WT mice rather than that in KO mice. Conclusions: Low-dose fenofibrate reversed chronic cholestatic liver injury in mice. The therapeutic action was dependent on PPARa activation and occurred by inhibiting chemotaxis via the JNK–AP1–CCL2/CXCL2 signaling. These data provided an exciting basis for optimization of therapeutic fenofibrate regimen in the clinic. Additionally, they suggested anti-chemotaxis of low-dose fenofibrate in single therapy to treat cholestatic liver diseases.

The recent use of ZnO nanoparticles (NPs) in agriculture has gained significant traction. However, the understanding of crop safety and environmental risk posed by ZnO NP exposure remains limited. As a result, this study administered varying concentrations of ZnO NPs (0, 10, 50, 200, 500, and 800 mg kg−1) to potato plants to determine their effect on food and soil quality. The results showed that while the number of tubers decreased, ZnO NPs enhanced the potato tuber quality and commodity rate and significantly increased Zn concentrations within various tissues. X-ray diffraction analysis showed that ZnO NPs at 50 mg kg−1did not penetrate the potato plants. From a soil environment viewpoint, higher ZnO NP concentrations significantly changed the physical and chemical properties of the soil but not the dominant groups of soil microbial communities. However, noticeable shifts in the relative proportions of these communities occurred. This study is the first to explore the biofortification efficiency and possible environmental risks of ZnO NPs on potato plants, providing a theoretical basis for the safe application of ZnO NPs in agriculture.

During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and cocompartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin-mediated structures. Heterochromatin protein 1 (HP1) proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M to G1 phase in the combined absence of HP1α, HP1β and HP1γ, constitutive heterochromatin compartments are normally re-established. In sum, condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not identified in interphase cells.

We consider a hypersonic vehicle optimal flight control problem. The problem is modeled as an optimal control problem of switched systems (OCPSS), which can become a parameter optimization problem (POP). Following that, to achieve the globally optimal solution of the POP, an improved continuous filled function (CFF) algorithm including one adjusting parameter is proposed based on a penalty function, in which the CFF is differentiable, excludes logarithmic terms or exponential terms, and does not require to minimize the cost function. Numerical results show that the proposed algorithm is effective.

Background:It is unknown whether early renal replacement therapy (RRT) initiation strategy in intensive care unit (ICU) patients with both acute respiratory distress syndrome (ARDS) and sepsis with or without renal failure is clinically beneficial. Patients and methods:A total of 818 patients with both ARDS and sepsis admitted to the ICU of Tianjin Medical University General Hospital were included in the analysis. Early RRT was defined as initiating the RRT strategy within 24 h of admission. The relationship between early RRT and clinical outcomes, including primary (30-day mortality) and secondary (90-day mortality, serum creatinine, Pao2/Fio2, duration of invasive mechanical ventilation, cumulative fluid output, and cumulative fluid balance) outcomes, was compared using propensity score matching (PSM). Results:A total of 277 patients (33.9% of the total population) underwent an early RRT initiation strategy before PSM. After PSM, a cohort of 147 patients with early RRT and 147 patients without early RRT with matched baseline characteristics (including serum creatinine at admission) were constructed. Early RRT was not significantly associated with 30- (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.85; P= 0.258) or 90-day mortality (HR, 1.30; 95% CI, 0.91–1.87, P= 0.150). At each time point within 72 h after admission, there was no significant difference in serum creatinine, Pao2/Fio2and duration of mechanical ventilation between the early and the no early RRT groups. Early RRT significantly increased total output at all time points within 72 h of admission and reached a statistically significant negative fluid balance at 48 h. Conclusions:Early RRT initiation strategies had no statistically significant survival benefit in ICU patients with both ARDS and sepsis, with or without renal failure, nor did they significantly improve serum creatinine and oxygenation or shorten the duration of mechanical ventilation. The use and timing of RRT in such patients should be thoroughly investigated.

SF6-decomposition-based insulation degradation of gas-insulated equipment has attracted considerable research attention in the power industry. However, because limited feature mining has been performed for SF6 decomposition components, diagnostic accuracy is reduced. Therefore, in this study, a novel diagnosis strategy was proposed based on various feature selection algorithms and convolutional neural network (CNN). In all, 19 characteristic products were obtained by combining original characteristic products. Various feature selection algorithms were used to mine feature information. A novel CNN structure was designed. The 1-D input layer was reorganized into the 2-D layer to improve the operation efficiency of the CNN. The robustness and generalization ability of the network were improved by adjusting the training step size and convolution kernel size or number. The diagnosis accuracy of the SF6 decomposition component was improved to 99%. Thus, a set of accurate and effective diagnosis schemes was proposed for the power industry.

Transcription at most promoters is divergent, initiating at closely spaced oppositely oriented core promoters to produce sense transcripts along with often unstable upstream antisense transcripts (uasTrx). How antisense transcription is regulated and to what extent it is coordinated with sense transcription is not well understood. Here, by combining acute degradation of the multi-functional transcription factor CTCF and nascent transcription measurements, we find that CTCF specifically suppresses antisense but not sense transcription at hundreds of divergent promoters. Primary transcript RNA-FISH shows that CTCF lowers burst fraction but not burst intensity of uasTrx and that co-bursting of sense and antisense transcripts is disfavored. Genome editing, chromatin conformation studies and high-resolution transcript mapping revealed that precisely positioned CTCF directly suppresses the initiation of uasTrx, in a manner independent of its architectural function. In sum, CTCF shapes the transcriptional landscape in part by suppressing upstream antisense transcription.

In power lines, the proportion of parallel cables is gradually increasing, but the uneven current distribution and sheath circulation affect the safe and stable operation of parallel cables. Existing studies show that cable current and sheath circulation are obviously affected by cable laying mode. At present, the designed cable laying mode is as “pin” laying and horizontal “I” laying. Combined with the above engineering difficulties, this paper focuses on the parameter optimization scheme of 220 kV two circuit parallel cables in the same direction when the metal sheath is cross connected and grounded. Firstly, the operation model of 220kV two circuits in-phase two parallel cables is established. The numerical differences between the current distribution non-uniformity coefficient and sheath circulating current of the cables are analyzed and calculated under the condition of “pin” laying and horizontal “I” laying. Meanwhile, the influence of different phase sequence arrangement on the current distribution non-uniformity coefficient and sheath circulating current of the cables is compared. Secondly, the cable laying mode of “symmetrical pin” is designed, and the improvement effect of uneven coefficient of cable current distribution and metal sheath circulating current under “symmetrical pin” laying is compared and analyzed. Finally, the differences of the above parameters in different phase sequence arrangements are compared and analyzed. The research results show that the symmetrical pin laying can improve the uneven distribution of current and sheath circulating current, which has important engineering practical value.

Higher-order chromatin structure regulates gene expression, and mutations in proteins mediating genome folding underlie developmental disorders known as cohesinopathies. However, the relationship between three-dimensional genome organization and embryonic development remains unclear. Here we define a role for bromodomain-containing protein 4 (BRD4) in genome folding, and leverage it to understand the importance of genome folding in neural crest progenitor differentiation. Brd4deletion in neural crest results in cohesinopathy-like phenotypes. BRD4 interacts with NIPBL, a cohesin agonist, and BRD4 depletion or loss of the BRD4–NIPBL interaction reduces NIPBL occupancy, suggesting that BRD4 stabilizes NIPBL on chromatin. Chromatin interaction mapping and imaging experiments demonstrate that BRD4 depletion results in compromised genome folding and loop extrusion. Finally, mutation of individual BRD4 amino acids that mediate an interaction with NIPBL impedes neural crest differentiation into smooth muscle. Remarkably, loss of WAPL, a cohesin antagonist, rescues attenuated smooth muscle differentiation resulting from BRD4 loss. Collectively, our data reveal that BRD4 choreographs genome folding and illustrates the relevance of balancing cohesin activity for progenitor differentiation.

Well screens are used in the open-hole-producing zone of a horizontal well to provide filtration to prevent sand production. After the well has been on production for a period of [...]

Animal chromosomes are partitioned into contact domains. Pathogenic domain disruptions can result from chromosomal rearrangements or perturbation of architectural factors. However, such broad-scale alterations are insufficient to define the minimal requirements for domain formation. Moreover, to what extent domains can be engineered is just beginning to be explored. In an attempt to create contact domains, we inserted a 2-kb DNA sequence underlying a tissue-invariant domain boundary—containing a CTCF-binding site (CBS) and a transcription start site (TSS)—into 16 ectopic loci across 11 chromosomes, and characterized its architectural impact. Depending on local constraints, this fragment variably formed new domains, partitioned existing ones, altered compartmentalization and initiated contacts reflecting chromatin loop extrusion. Deletions of the CBS or the TSS individually or in combination within inserts revealed its distinct contributions to genome folding. Altogether, short DNA insertions can suffice to shape the spatial genome in a manner influenced by chromatin context.

Silicon (Si)-based Schottky junction photoelectrodes have attracted considerable attention for photoelectrochemical (PEC) water splitting in recent years. To realize highly efficient Si-based Schottky junction photoelectrodes, the critical challenge is to enable the photoelectrodes to not only have a high Schottky barrier height (SBH), by which a high photovoltage can be obtained, but also ensure an efficient charge transport. Here, we propose and demonstrate a strategy to fabricate a high-performance NiSi/n-Si Schottky junction photoanode by metal silicidation in conjunction with dopant segregation (DS). The metal silicidation produces photoanodes with a high-quality NiSi/Si interface without a disordered SiO2layer, which ensures highly efficient charge transport, and thus a high saturated photocurrent density of 33 mA cm–2was attained for the photoanode. The subsequent DS gives the photoanodes a high SBH of 0.94 eV through the introduction of electric dipoles at the NiSi/n-Si interface. As a result, a high photovoltage and favorable onset potential of 1.03 V vs RHE was achieved. In addition, the strong alkali corrosion resistance of NiSi also endows the photoanode with a high stability during PEC operation in 1 M KOH. Our work provides a universal strategy to fabricate metal–silicide/Si Schottky junction photoelectrodes for high-performance PEC water splitting.

Background: As the pathogen of malaria, malaria parasite secretes a variety of proteins for its growth and reproduction. Objective: The identification of the secretory proteins of malaria parasite has crucial reference significance for the development of anti-malaria vaccines as well as medicine. Methods: In this study, a computational classification method was developed to identify the secreted proteins of Plasmodium. Amino acid composition, dipeptide composition, and tripeptide composition as well as reduced amino acids alphabets were proposed to illuminate protein sequences. We further used SVM to train and predict respectively and optimized the features. Results: 74 types of reduced amino acids alphabets were employed to predict secretory proteins. The results showed that the accuracy improved to 91.67% with 0.84 Mathew’s correlation coefficient (MCC) by dipeptide composition, and the highest prediction accuracy reached 92.26% after feature selection, which demonstrated that our method is prominent and reliable in the field of malaria parasite secreted proteins prediction. Conclusion: A intuitive web server iSP-RAAC (http://bioinfor.imu.edu.cn/isppseraac) was established for the convenience of most experimental scientists.

Features of higher-order chromatin organization—such as A/B compartments, topologically associating domains and chromatin loops—are temporarily disrupted during mitosis1,2. Because these structures are thought to influence gene regulation, it is important to understand how they are re-established after mitosis. Here we examine the dynamics of chromosome reorganization by Hi-C after mitosis in highly purified, synchronous mouse erythroid cell populations. We observed rapid establishment of A/B compartments, followed by their gradual intensification and expansion. Contact domains form from the ‘bottom up’—smaller subTADs are formed initially, followed by convergence into multi-domain TAD structures. CTCF is partially retained on mitotic chromosomes and immediately resumes full binding in ana/telophase. By contrast, cohesin is completely evicted from mitotic chromosomes and regains focal binding at a slower rate. The formation of CTCF/cohesin co-anchored structural loops follows the kinetics of cohesin positioning. Stripe-shaped contact patterns—anchored by CTCF—grow in length, which is consistent with a loop-extrusion process after mitosis. Interactions between cis-regulatory elements can form rapidly, with rates exceeding those of CTCF/cohesin-anchored contacts. Notably, we identified a group of rapidly emerging transient contacts between cis-regulatory elements in ana/telophase that are dissolved upon G1 entry, co-incident with the establishment of inner boundaries or nearby interfering chromatin loops. We also describe the relationship between transcription reactivation and architectural features. Our findings indicate that distinct but mutually influential forces drive post-mitotic chromatin reconfiguration.

Although quasi-two-dimensional (quasi-2D) perovskites are ideal material platforms for highly efficient linearly polarized electroluminescence owing to their anisotropic crystal structures, so far, there has been no practical implementation of these materials for the demonstration of linearly polarized perovskite light-emitting diodes (LP-PeLEDs). This scarcity is due to difficulty in orientation and phase distribution control of the quasi-2D perovskites while minimizing the defects, all of which are required to manifest aligned transition dipole moments (TDMs). To achieve this multifaceted goal, herein, we introduce a synergistic strategy to quasi-2D perovskites by incorporating both a trimethylolpropane triacrylate anchoring layer and 18-Crown-6 molecular passivator into the film fabrication process. It is found that the interfacial anchoring layer guides the oriented growth of perovskites along the (110) plane, whereas the molecular passivator reduces the number of defects and homogenizes the crystal phase. As a result, a quasi-2D perovskite film with macroscopically aligned TDM that renders high radiative recombination and the degree of linear polarization (DoLP) is constructed. This “coherence-programmed emission layer” demonstrates highly efficient LP-PeLEDs, not only achieving a maximum external quantum efficiency of ∼23.7%, a brightness of ∼36,142 cd/m2, and a DoLP of ∼38%, but also significantly improving the signal-to-interference-and-noise ratio in a multi-cell visible light communication system.

Development of piezoelectric biomaterials with high piezoelectric performance, while possessing excellent flexibility, biocompatibility, and biodegradability still remains a great challenge. Herein, a flexible, biocompatible and biodegradable piezoelectric β-glycine–alginate–glycerol (Gly-Alg-Glycerol) film with excellent in vitroand in vivosensing performance was developed. Remarkably, a single, monolithic β-glycine spherulite, instead of more commonly observed multiple spherulites, was formed in alginate matrix, thereby resulting in outstanding piezoelectric property, including high piezoelectric constant (7.2 pC/N) and high piezoelectric sensitivity (1.97 mV/kPa). The Gly-Alg-Glycerol film exhibited superior flexibility, enabling complex shape-shifting, e.g. origami pigeon, 40% tensile strain, and repeated bending and folding deformation without fracture. In vitro, the flexible Gly-Alg-Glycerol film sensor could detect subtle pulse signal, sound wave and recognize shear stress applied from different directions. In addition, we have demonstrated that the Gly-Alg-Glycerol film sensor sealed by polylactic acid and beeswax could serve as an in vivosensor to monitor physiological pressure signals such as heartbeat, respiration and muscle movement. Finally, the Gly-Alg-Glycerol film possessed good biocompatibility, supporting the attachment and proliferation of rat mesenchymal stromal cells, and biodegradability, thereby showing great potential as biodegradable piezoelectric biomaterials for biomedical sensing applications.

Background Accurate estimation of ischemic core on baseline imaging has treatment implications in patients with acute ischemic stroke (AIS). Machine learning (ML) algorithms have shown promising results in estimating ischemic core using routine noncontrast computed tomography (NCCT).Objective We used an ML-trained algorithm to quantify ischemic core volume on NCCT in a comparative analysis to pretreatment magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) in patients with AIS.Methods Patients with AIS who had both pretreatment NCCT and MRI were enrolled. An automatic segmentation ML approach was applied using Brainomix software (Oxford, UK) to segment the ischemic voxels and calculate ischemic core volume on NCCT. Ischemic core volume was also calculated on baseline MRI DWI. Comparative analysis was performed using Bland–Altman plots and Pearson correlation.Results A total of 72 patients were included. The time-to-stroke onset time was 134.2/89.5 minutes (mean/median). The time difference between NCCT and MRI was 64.8/44.5 minutes (mean/median). In patients who presented within 1 hour from stroke onset, the ischemic core volumes were significantly (p  =  0.005) underestimated by ML-NCCT. In patients presented beyond 1 hour, the ML-NCCT estimated ischemic core volumes approximated those obtained by MRI-DWI and with significant correlation (r=  0.56, p < 0.001).Conclusion The ischemic core volumes calculated by the described ML approach on NCCT approximate those obtained by MRI in patients with AIS who present beyond 1 hour from stroke onset.

Biocompatible, small-sized but well-dispersed gold nanoparticles (Au NPs) remain a major challenge for their synthesis. Here a convenient solution impregnation technique is developed to prepare such Au NPs under the regulation of degummed silk fibroin fibers (SFFs) extracted from Bombyx moricocoons. SFFs play multiple roles in the formation of Au NPs such as reactive substrate to capture AuCl4-ions by the chelation of -C = O, reducing agent for Au(0) by the reduction of -OH, and modifiers to render biocompatible Au NPs by some functional groups and biomolecules. The as-prepared Au NPs with a size of 7–10 nm are embedded in the solid SFF substrate, and can disperse well in the liquid system by the disintegration of SFFs into silk fibroin (SF) in a certain CaCl2solution. The biocompatible Au NPs exhibit uniform small size and distribute stably in both solid and solution states, which have distinctive properties and functional advantages, and bring great convenience to their storage and transportation.

OBJECTIVE--We have previously reported evidence of an inverse association between a urinary-isoprostane and type 2 diabetes risk in a pilot case-control study nested within the Insulin Resistance Atherosclerosis Study (IRAS). [...]

ABSTRACTLamin A (LA) is a critical structural component of the nuclear lamina. Mutations within the LA gene (LMNA) lead to several human disorders, most striking of which is Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disorder. HGPS cells are best characterized by an abnormal nuclear morphology known as nuclear blebbing, which arises due to the accumulation of progerin, a dominant mutant form of LA. The microtubule (MT) network is known to mediate changes in nuclear morphology in the context of specific events such as mitosis, cell polarization, nucleus positioning and cellular migration. What is less understood is the role of the microtubule network in determining nuclear morphology during interphase. In this study, we elucidate the role of the cytoskeleton in regulation and misregulation of nuclear morphology through perturbations of both the lamina and the microtubule network. We found that LA knockout cells exhibit a crescent shape morphology associated with the microtubule-organizing center. Furthermore, this crescent shape ameliorates upon treatment with MT drugs, Nocodazole or Taxol. Expression of progerin, in LA knockout cells also rescues the crescent shape, although the response to Nocodazole or Taxol treatment is altered in comparison to cells expressing LA. Together these results describe a collaborative effort between LA and the MT network to maintain nuclear morphology.

Hutchinson-Gilford progeria syndrome (HGPS) is a devastating premature aging disorder. It arises from a single point mutation in the LMNAgene. This mutation stimulates an aberrant splicing event and produces progerin, an isoform of the lamin A protein. Accumulation of progerin disrupts numerous physiological pathways and induces defects in nuclear architecture, gene expression, histone modification, cell cycle regulation, mitochondrial functionality, genome integrity and much more. Among these phenotypes, genomic instability is tightly associated with physiological aging and considered a main contributor to the premature aging phenotypes. However, our understanding of the underlying molecular mechanisms of progerin-caused genome instability is far from clear. In this review, we summarize some of the recent findings and discuss potential mechanisms through which, progerin affects DNA damage repair and leads to genome integrity.

Introduction:Application of machine learning (ML) algorithms has shown promising results in estimating ischemic core volumes using routine non-contrast CT (NCCT). We aimed to assess the performance of the e-Stroke Suite software (Brainomix, Oxford, United Kingdom) in assessing ischemic core volumes on NCCT compared to CTP in patients with acute ischemic stroke.Methods:In this retrospective study, consecutive patients with anterior circulation large vessel occlusions who underwent pretreatment NCCT and CTP and posttreatment MRI were included. Ischemic core volumes were automatically calculated on NCCTs using e-Stroke Suite (Brainomix) which uses a combination of traditional 3D graphics and ML classification techniques to identify ischemic core voxels. Estimated ischemic core volumes were also automatically calculated from CTP using Olea Sphere (Olea Medical SAS, SP23) using a combination of rCBF<25% and differential Time-to-peak (dTTP)>5 sec. Estimated core volumes were compared against the final infarct volume on posttreatment MRI in patients who achieved successful reperfusion (mTICI ≥2b).Results:83 patients [52 female; age (mean ± SD): 73.1 ±15.3] were included. The estimated ischemic core volumes (mean ± SD) were 18.9 ± 13.5 mL on NCCT and 17.5 ± 16.5 mL on CTP, not significantly different (p=0.54) and demonstrated significant correlation (r=0.51, p<0.001) (Figure 1). Among patients with successful recanalization (n=49), there was no significant difference in estimated ischemic core volume between NCCT vs. CTP (p=0.80) and NCCT vs. MRI (p=0.38). There was significant correlation between estimated ischemic core volume on NCCT vs. CTP (r=0.75, p<0.001) and vs. final MRI infarct volume (r=0.75, p<0.001).Conclusions:Results show estimated ischemic core volumes obtained automatically by ML-based approach (Brainomix) on NCCT correlates well with ischemic core volumes on acute CTP and with post-treatment MR infarct volume.

Background and Purpose:DWI-FLAIR mismatch is used to determine thrombolytic eligibility in patients with acute ischemic stroke (AIS) when time-to-stroke symptom (TSS) is unknown. Advances in artificial intelligence and machine learning (ML) techniques have shown promising results in automated assessment of TSS. We aimed to use the e-Stroke software (Brainomix, Oxford, UK) to automatically classify DWI-FLAIR mismatch in a cohort of patients with AIS and in a comparative analysis with an expert neuroradiologist.Methods:In this retrospective study, consecutive patients with AIS who had pretreatment MRI, and known TSS were included. DWI-FLAIR mismatch was evaluated by an expert neuroradiologist blinded to TSS. e-Stroke software, which uses a combination of statistical methods and ML classification techniques was used to automatically classify DWI-FLAIR status. TSS was dichotomized using a 4.5 hr cutoff to assess the diagnostic performance of the radiologist vs. e-Stroke software.Results:Thus far 113 patients are included, 53 female, age (mean ± SD): 68.9 ± 17. TSS was 371±249 min (mean ± SD) and the infarct volume was 16.4±26.5 ml (mean ± SD). A total of 60 patients had TSS > 4.5 hrs while 53 had TSS < 4.5 hrs. Diagnostic performance (sensitivity/specificity/accuracy in %) for determination of TSS using DWI-FLAIR mismatch was 75/58.5/66.7 for the radiologist and 43/85/64 for e-Stroke software; without statistical difference (AUC: 0.66 for radiologist, 0.64 for e-Stroke; Delong test, p= 0.59). Subgroup analysis of infarctions of at least 1mL or higher, improved the diagnostic performance for both radiologist (83.8/59.4/71.6) and e-Stroke software (66.7/75.0/71.0), without statistical difference (AUC: 0.71 for radiologist and 0.71 for e-Stroke; Delong test, p= 0.96).Conclusions:Results show that fully automated quantitative approach for DWI-FLAIR mismatch provides similar diagnostic accuracies to expert neuroradiologist in determination of TSS.

ABSTRACTNuclear lamins are the major components of the nuclear lamina at the periphery of the nucleus, supporting the nuclear envelope and participating in many nuclear processes, including DNA replication, transcription and chromatin organization. A group of diseases, the laminopathies, is associated with mutations in lamin genes. One of the most striking cases is Hutchinson-Gilford progeria syndrome (HGPS) which is the consequence of a lamin A dominant negative mutant named progerin. Due to the abnormal presence of a permanent C-terminal farnesyl tail, progerin gradually accumulates on the nuclear membrane, perturbing a diversity of signalings and transcriptional events. The accumulation of progerin has led to the speculation that progerin possesses higher stability than the wild type lamin A protein. However, the low solubility of lamin proteins renders traditional immunoprecipitation-dependent methods such as pulse-chase analysis ineffective for comparing the relative stabilities of mutant and wild type lamins. Here, we employ a novel platform for inferring differences in lamin stability, which is based on normalization to a co-translated reporter protein following porcine teschovirus-1 2A peptide-mediated co-translational cleavage. The results obtained using this method support the notion that progerin is more stable than lamin A. Moreover, treatment of FTI reduces progerin relative stability to the level of wild type lamin A.

Electronic transport plays a pivotal role in the electrolysis of semiconducting electrocatalysts for oxygen evolution reaction (OER), while it is mostly underestimated and largely unexplored. Here, by investigating the electronic transport behavior of seven archetypical crystalline Co/Ni/Fe-based (oxy)hydroxides (unary, binary, and ternary) under OER potential, we study how and the extent to which it affects the apparent catalytic performances. The electronic transports of unary metal (oxy)hydroxides follow the order of Co > Ni > Fe, and their binary or ternary compounds can generally impose one order of magnitude higher electrical conductivity. By studying the dependence of catalytic performances on electrical conductivities, we further unveil that charge transportability not only determines the electronic accessibility of catalytic nanoparticles but also, to our surprise, regulates the reaction kinetics of the electronically accessible active sites. Remarkably, the regulation extent of reaction kinetics correlates with the electrical conductivities of electrocatalysts, suggesting that the electrocatalytic process is strongly coupled with electronic transport. The work presents an overview of electronic transports of crystalline (oxy)hydroxides under OER potentials and highlights their pivotal role in unfolding catalytic potential, holding both fundamental and technical implications for the screen and design of efficient electrocatalysts.

To explore the underlying physiology of hostility (HOST) and to test the hypothesis that HOST has a greater impact on fasting glucose in African American (AA) women than it does on AA men or white men or women, using an intravenous glucose tolerance test (IVGTT) and the minimal model of glucose kinetics.

Purpose: To investigate the correlation of the urinary glucose tetrasaccharide, Glca1-6Glca1-4Glca1-4Glc, (Glc4) with skeletal muscle glycogen content and the long-term clinical response to enzyme replacement therapy with recombinant human acid alpha glucosidase in infantile Pompe disease.Methods: Eighteen patients, =6 months old, were enrolled in a clinical trial of enzyme replacement therapy for up to 142 weeks. Urinary Glc4, skeletal muscle glycogen, and other clinical and laboratory assessments were made at baseline and at regular intervals. Urinary Glc4was determined using an isotope-dilution tandem mass spectrometric assay. The clinical response to treatment was defined according to the motor function response. Trends in urinary Glc4were correlated with the clinical response and compared with serum enzyme markers of skeletal muscle damage, creatine kinase, aspartate aminotransferase, and alanine aminotransferase.Results: Urinary Glc4, in contrast to the serum markers, correlated closely with skeletal muscle glycogen content and with the clinical response. Patients with the best response to treatment maintained the lowest levels of Glc4throughout the trial.Conclusion: The results from this study support the use of urinary Glc4for monitoring patients with infantile-onset Pompe disease on therapy.

Purpose: The study’s purpose was to compare acarbose and maltose as inhibitors of maltase-glucoamylase activity for determining acid a-glucosidase activity in dried blood spot specimens for early identification of patients with infantile Pompe disease, a severe form of acid a-glucosidase deficiency.Methods: Acid a-glucosidase activities in dried blood spot extracts were determined fluorometrically using the artificial substrate 4-methylumbelliferyl-a-D-pyranoside. Acarbose or maltose was used to inhibit maltase-glucoamylase, an enzyme present in polymorphonuclear neutrophils that contributes to the total a-glucosidase activity at acidic pH.Results: Complete discrimination between patients with proven infantile Pompe disease (n = 20), obligate heterozygotes (n = 16), and controls (n = 150) was achieved using 8 µmol/L acarbose as the inhibitor. Higher acarbose concentration (80 µmol/L) did not improve the assay. By using 4 mM maltose as the inhibitor, heterozygotes and patients were not completely separated. The results using acarbose compared well with those using the skin fibroblast assay in the same group of patients with proven infantile Pompe disease.Conclusion: Acid a-glucosidase activity measurements in dried blood spot extracts can reliably detect infantile Pompe disease in patients. The convenience of collecting and shipping dried blood specimens plus rapid turnaround time makes this assay an attractive alternative to established methods.

An unconventional self-assembly process was integrated with traditional silicon microfabrication technologies to directly form hexagonally ordered nanoporous patterns on both SiO₂ and Si surfaces. Starting with an aluminium thin film deposited on a SiO₂ or Si substrate, an Al anodization process was employed to generate highly uniform nanoporous anodic aluminium oxide thin films with average pore diameters of 30–70 nm directly on SiO₂ and Si surfaces. The long-range order of the anodic aluminium oxide nanoporous structures was improved by thermally annealing the starting Al films to promote the grain size growth and by utilizing a multiple anodization process to enhance their uniformity. The formation of the hexagonally ordered nanoporous array may be attributed to the interplay between the topological requirement for space filling of pores and the kinetics of domain growth with time under a constant anodization voltage. These results demonstrate the feasibility of integrating self-assembled anodic aluminium oxide nanostructures with Si microfabrication technologies in the pursuit of future-generation Si nanoelectronic devices.

CCCTC-binding factor (CTCF) is a conserved zinc finger transcription factor implicated in a wide range of functions, including genome organization, transcription activation, and elongation. To explore the basis for CTCF functional diversity, we coupled an auxin-induced degron system with precision nuclear run-on. Unexpectedly, oriented CTCF motifs in gene bodies are associated with transcriptional stalling in a manner independent of bound CTCF.Moreover, CTCF at different binding sites (CBSs) displays highly variable resistance to degradation. Motif sequence does not significantly predict degradation behavior, but location at chromatin boundaries and chromatin loop anchors, as well as co-occupancy with cohesin, are associated with delayed degradation. Single-molecule tracking experiments link chromatin residence time to CTCF degradation kinetics, which has ramifications regarding architectural CTCF functions. Our study highlights the heterogeneity of CBSs, uncovers properties specific to architecturally important CBSs, and provides insights into the basic processes of genome organization and transcription regulation.

Recycling reinjection of CO2captured and purified from the produced gas of CO2flooding can not only enhance oil recovery, but also realize the geological storage of CO2, so as to provide good social and economic benefit. With the operation and advancement of CO2flooding development mode, one single CO2capture and purification process can hardly deal with the yearly increase and large-scale variation of CO2content in the produced gas. In order to provide support for the promotion of CO2-EOR technology oil and gas fields, to this end, this paper puts forward four schemes of multi-method CO2capture and purification process. It includes two-stage hydramine method, one-stage membrane separation + one-stage hydramine method, two-stage membrane separation + one-stage hydramine method, one-stage membrane separation + two-stage hydramine method. And based on the working condition data of CO2flooding in one certain oilfield, simulation was carried out by using HYSYS software. In addition, the enrichment degree of the CO2captured and purified by means of different schemes and its energy consumption and economy were analyzed mainly. And the following research results were obtained. First, when the CO2concentration of the produced gas is low, it is necessary to put the two-stage alcohol amine circulation process into production firstly to realize the deacidification of natural gas while purchasing some pure CO2to mix at a certain proportion, so as to reach the required CO2purity of reinjected gas. Second, as the CO2concentration of the produced gas increases, it is better to use the membrane separation technology before the two-stage alcohol amine circulation process, so that the enriched and purified gas can reach the required CO2purity of direction reinjection. In conclusion, the research results can provide engineering practical guidance for the formulation of the scheme to enrich and purify CO2from the produced gas of CO2flooding.

Nanocrystalline ß-SiC particulates with a grain-size range of 5-20 nm were prepared by heating a prepyrolyzed, chlorine-containing polysilanepolycarbosilane (PSPCS) to 1600°C. The transformation from the prepyrolyzed PSPCS to nanocrystalline SiC was investigated by differential thermal analysis, thermogravimetric analysis, X-ray diffractometry, mass spectrometry, and infrared spectroscopy. The results indicated that the nanocrystalline ß-SiC was formed by the crystallization of the PSPCS random network and the crosslinking of Si-Si, Si-Cl, and Si-CH2-Si bonds. Transmission electron microscopy observation showed that SiC particulates consisted of equiaxed, randomly oriented, ultrafine grains.

The low bioavailability of nitric oxide (NO) and its precursor, arginine, contributes to the microvascular pathophysiology of severe falciparum malaria. To better characterize the mechanisms underlying hypoargininemia in severe malaria, we measured the plasma concentrations of amino acids involved in de novoarginine synthesis in children with uncomplicated falciparum malaria (UM; n?=?61), children with cerebral falciparum malaria (CM; n?=?45), and healthy children (HC; n?=?109).

Using the leaves of test-tube seedlings of Actinidia deliciosa as expiants, the effect of different growth regulating substance on the Actinidia deliciosa leaves excised regeneration system was researched, including the differentiation of adventitious buds, the regeneration and rooting of regenerated shoots. The results indicated that the maximum adventitious buds regeneration frequency achieved 76.6% on the medium of Murashige and Skoog medium(MS) containing 5.0 mg*L[?]1 6-benzylaminopurine(6-BA) and 0.2 mg*L[?]1 1-naphthaleneacetic acid (NAA); the most suitable medium for shoot multiplication was MS with 2.0 mg*L[?]1 6-BA, 0.2 mg*L[?]1 NAA and 0.1 mg*L[?]1 gibberellin acid(GA3) and the multiplication coefficient was up to 4.76; 1/2MS with 0.7 mg*L[?]1 1h-indolo-3-butanoic acid(IBA) was the most suitable for the rooting of regenerated shoots, and the rooting rate was 100%.

In order to break the dormancy of kiwifruit seed, accelerate the process of seed germination, to understan the effects of different treatment methods on the germination of kiwifruit seeds. Different treatment methods were set up in this study. The results showed that GA3 soaked for 18h can make seeds break the dormancy; when only the filter paper is placed on the petri dish, the germination rate is the highest: the most suitable disinfection time is 10min. After dark conditions, the seed germination rate was 73.3%, which was much higher than that under non-dark conditions. In certain range, the higher the concentration of GA3, the higher the germination rate of kiwifruit seeds.

Aim: Radiation therapy has been proven “safe and effective” in the management of colorectal cancer liver metastases, especially for oligometastases. However, to date, there is no consensus on optimal prescribed doses or dose fraction schemes. The current study was conducted to investigate the effectiveness and safety of 2 different radiation therapy methods, conventional conformal radiation therapy and stereotactic body radiation therapy, in the treatment of limited colorectal cancer liver metastases.Methods: From December 2011 to December 2016, twenty-six patients with colorectal cancer having postoperative liver metastases (≤3) who were being treated with radiation therapy, either conventional conformal radiation therapy (50 Gy in 25 fractions) or stereotactic body radiation therapy (50 Gy in 10 fractions), were selected for this study. Overall survival and local control survival were analyzed by log-rank and Cox regression methods.Results: Radiation therapy delivered to each of the 26 patients with a total of 50 liver lesions. Conformal radiation therapy was delivered to 32 lesions in a total of 15 patients. Stereotactic body radiation therapy was delivered to 18 lesions in a total of 11 patients. Median follow-up was 13 months. Three-year overall survival and local control survival were 0% and 38.5%, 20.5%, and 53.0%, respectively, for the conformal radiation therapy and stereotactic body radiation therapy groups. The slightly better overall survival and local control survival in the stereotactic body radiation therapy group in comparison to the conformal radiation therapy group (P= .323 and .297) is insignificant. There were no differences in grade 3 hepatic toxicity between the 2 groups. Eastern Cooperative Oncology Group performance status and the number of liver lesions were significant prognostic factors in both univariate and multivariate analyses.Conclusions: Noninvasive radiation therapy provides satisfactory survival benefit for limited colorectal cancer liver metastases without intolerable toxicity and is therefore especially suitable for those elderly patients with poor performance status. Furthermore, stereotactic body radiation therapy with a higher biological equivalent dose and an abbreviated course of treatment has been shown to provide a better outcome than conventional conformal radiation therapy.

Mucopolysaccharidoses (MPSs) are complex lysosomal storage disorders that result in the accumulation of glycosaminoglycans (GAGs) in urine, blood, and tissues. Lysosomal enzymes responsible for GAG degradation are defective in MPSs. GAGs including chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS) are disease‐specific biomarkers for MPSs. This unit describes a stable isotope dilution‐tandem mass spectrometric method for quantifying CS, DS, and HS in urine samples. The GAGs are methanolyzed to uronic or iduronic acid‐N‐acetylhexosamine or iduronic acid‐N‐sulfo‐glucosamine dimers and mixed with internal standards derived from deuteriomethanolysis of GAG standards. Specific dimers derived from HS, DS, and CS are separated by ultra‐performance liquid chromatography (UPLC) and analyzed by electrospray ionization tandem mass spectrometry (MS/MS) using selected reaction monitoring for each targeted GAG product and its corresponding internal standard. This new GAG assay is useful for identifying patients with MPS types I, II, III, VI, and VII. Curr. Protoc. Hum. Genet. 76:17.12.1‐17.12.14. © 2013 by John Wiley & Sons, Inc.