In this paper, a novel joint design of user clustering and multi-dimensional resource allocation based on effective capacity (EC) is proposed for the multi-cell downlink ...multiple-input-multiple-output (MIMO) non-orthogonal multiple access (NOMA) networks. First, we propose a dynamic user clustering algorithm to divide users into a number of clusters, where all users in one cluster share a single beamforming vector. Then, we adopt zero-forcing beamforming (ZFBF) to significantly eliminate the inter-cluster interference. Finally, we design a joint optimization of channel allocation and power allocation, which aims to maximize the sum-EC of all users. The joint optimization is formulated as an NP-hard problem. To make the problem tractable, we divide the problem into two subproblems. Then, we propose an alternating optimization algorithm to obtain a suboptimal solution. The numerical results demonstrate that compared with traditional algorithms our proposed algorithm can achieve significant capacity gain and simultaneously have low-computational complexity.
High‐mobility group box 1 (HMGB1) is an abundant chromatin‐associated nuclear protein and released into the extracellular milieu during liver ischemia‐reperfusion (I/R), signaling activation of ...proinflammatory cascades. Because the intracellular function of HMGB1 during sterile inflammation of I/R is currently unknown, we sought to determine the role of intracellular HMGB1 in hepatocytes after liver I/R. When hepatocyte‐specific HMGB1 knockout (HMGB1‐HC‐KO) and control mice were subjected to a nonlethal warm liver I/R, it was found that HMGB1‐HC‐KO mice had significantly greater hepatocellular injury after I/R, compared to control mice. Additionally, there was significantly greater DNA damage and decreased chromatin accessibility to repair with lack of HMGB1. Furthermore, lack of hepatocyte HMGB1 led to excessive poly(ADP‐ribose)polymerase 1 activation, exhausting nicotinamide adenine dinucleotide and adenosine triphosphate stores, exacerbating mitochondrial instability and damage, and, consequently, leading to increased cell death. We found that this was also associated with significantly more oxidative stress (OS) in HMGB1‐HC‐KO mice, compared to control. Increased nuclear instability led to a resultant increase in the release of histones with subsequently more inflammatory cytokine production and organ damage through activation of Toll‐like receptor 9. Conclusion: The lack of HMGB1 within hepatocytes leads to increased susceptibility to cellular death after OS conditions. (Hepatology 2014;59:1984–1997)
The mechanisms that lead to the development of remote lung injury after trauma remain unknown, although a central role for the gut in the induction of lung injury has been postulated. We hypothesized ...that the development of remote lung injury after trauma/hemorrhagic shock requires activation of TLR4 in the intestinal epithelium, and we sought to determine the mechanisms involved. We show that trauma/hemorrhagic shock caused lung injury in wild-type mice, but not in mice that lack TLR4 in the intestinal epithelium, confirming the importance of intestinal TLR4 activation in the process. Activation of intestinal TLR4 after trauma led to increased endoplasmic reticulum (ER) stress, enterocyte apoptosis, and the release of circulating HMGB1, whereas inhibition of ER stress attenuated apoptosis, reduced circulating HMGB1, and decreased lung injury severity. Neutralization of circulating HMGB1 led to reduced severity of lung injury after trauma, and mice that lack HMGB1 in the intestinal epithelium were protected from the development of lung injury, confirming the importance of the intestine as the source of HMGB1, whose release of HMGB1 induced a rapid protein kinase C ζ-mediated internalization of surface tight junctions in the pulmonary epithelium. Strikingly, the use of a novel small-molecule TLR4 inhibitor reduced intestinal ER stress, decreased circulating HMGB1, and preserved lung architecture after trauma. Thus, intestinal epithelial TLR4 activation leads to HMGB1 release from the gut and the development of lung injury, whereas strategies that block upstream TLR4 signaling may offer pulmonary protective strategies after trauma.
On the Processing of Proghrelin to Ghrelin Zhu, Xiaorong; Cao, Yun; Voodg, Keith ...
Journal of biological chemistry/The Journal of biological chemistry,
12/2006, Volume:
281, Issue:
50
Journal Article
Peer reviewed
Open access
The orexigenic hormone ghrelin is a 28-amino-acid peptide derived from a 99-amino-acid precursor and acylated at Ser-3, which was initially isolated from rat stomach. In addition to stimulating ...appetite and growth, it also plays various important roles in energy homeostasis and in the cardiovascular and immune systems. Although analysis of its physiological effects has yielded many significant results, much less information is available on its biosynthesis and the mechanism of its acylation. In this report, we have studied the endoproteolytic processing of this molecule from its precursor (proghrelin) into mature ghrelin in various prohormone convertase null mouse strains generated in our laboratory and have identified the convertase responsible for this event. Using Western blotting, mass spectrometry, and immunocytochemical methods, we have demonstrated that (a) in mouse stomach, prohormone convertase 1/3 (PC1/3) is the endoprotease responsible for the conversion of proghrelin to ghrelin, (b) the acylation of this peptide is processing-independent, and (c) the expression of proghrelin mRNA is increased in the processing-deficient (PC1/3 null) mouse.
Diabetic retinopathy is the leading cause of vision loss in working-age adults. Early screening and diagnosis can help to facilitate subsequent treatment and prevent vision loss. Deep learning has ...been applied in various fields of medical identification. However, current deep learning-based lesion segmentation techniques rely on a large amount of pixel-level labeled ground truth data, which limits their performance and application. In this work, we present a weakly supervised deep learning framework for eye fundus lesion segmentation in patients with diabetic retinopathy.
First, an efficient segmentation algorithm based on grayscale and morphological features is proposed for rapid coarse segmentation of lesions. Then, a deep learning model named Residual-Attention Unet (RAUNet) is proposed for eye fundus lesion segmentation. Finally, a data sample of fundus images with labeled lesions and unlabeled images with coarse segmentation results is jointly used to train RAUNet to broaden the diversity of lesion samples and increase the robustness of the segmentation model.
A dataset containing 582 fundus images with labels verified by doctors, including hemorrhage (HE), microaneurysm (MA), hard exudate (EX) and soft exudate (SE), and 903 images without labels was used to evaluate the model. In ablation test, the proposed RAUNet achieved the highest intersection over union (IOU) on the labeled dataset, and the proposed attention and residual modules both improved the IOU of the UNet benchmark. Using both the images labeled by doctors and the proposed coarse segmentation method, the weakly supervised framework based on RAUNet architecture significantly improved the mean segmentation accuracy by over 7% on the lesions.
This study demonstrates that combining unlabeled medical images with coarse segmentation results can effectively improve the robustness of the lesion segmentation model and proposes a practical framework for improving the performance of medical image segmentation given limited labeled data samples.
There are growing interests in metal‐free heteroatom‐doped carbons for electrochemical CO2 reduction. Previous studies extensively focus on the effect of N‐doping, and their products severely suffer ...from low current density (mostly <2 mA cm−2) and limited selectivity (<90%). Here, it is reported that heteroatom codoping offers a promising solution to the above challenge. As a proof of concept, N,P‐codoped mesoporous carbon is prepared by annealing phytic‐acid‐functionalized ZIF‐8 in NH3. In CO2‐saturated 0.5 m NaHCO3, the catalyst enables CO2 reduction to CO with great selectivity close to 100% and large CO partial current density (≈8 mA cm−2), which are, to the best of knowledge, superior to all other relevant competitors. Theoretical simulations show that the improved activity and selectivity are stemmed from the enhanced surface adsorption of *COOH and *CO intermediates as a result of the synergy of N and P codoping.
High surface area N,P‐codoped mesoporous carbon is prepared from the NH3 annealing of phytic acid functionalized ZIF‐8. It can catalyze the CO2 reduction to CO with great selectivity close to unity and large CO partial current density, superior to all existing metal‐free heteroatom‐doped carbons to the best of knowledge.
Abstract
Electrocatalytic urea synthesis via coupling of nitrate with CO
2
is considered as a promising alternative to the industrial urea synthetic process. However, the requirement of sub‐reaction ...(NO
3
RR and CO
2
RR) activities for efficient urea synthesis is not clear and the related reaction mechanisms remain obscure. Here, the construction, breaking, and rebuilding of the sub‐reaction activity balance would be accompanied by the corresponding regulation in urea synthesis, and the balance of sub‐reaction activities was proven to play a vital role in efficient urea synthesis. With rational design, a urea yield rate of 610.6 mg h
−1
g
cat.
−1
was realized on the N‐doped carbon electrocatalyst, superior to that of noble‐metal electrocatalysts. Based on the operando SR‐FTIR measurements, we proposed that urea synthesis arises from the coupling of *NO and *CO to generate the key intermediate of *OCNO. This work provides new insights and guidelines into urea synthesis from the aspect of activity balance.
Growth factors like insulin-like growth factor 1 (IGF-1) is reported to mediate neurogenesis in the subgranular zone (SGZ) and the subventricular zone (SVZ) of the adult mammalian brain, but its ...regulatory mechanism remains unclear. We generated transgenic mice overexpressing IGF-1 specifically in neural stem cells (NSCs) and assessed the effect of IGF-1 on neurogenesis in adult mice NSCs. Overexpression of IGF-1 could stimulate the expression of phospho-Akt and phospho-ERK1/2 while inducing proliferation and differentiation of NSCs in the SGZ and SVZ. The MEK/ERK inhibitor U0126 could inhibit ERK1/2 phosphorylation, further inhibiting the proliferation of NSCs in the SGZ and SVZ but had no effect on the phosphorylation of Akt. By contrast, The PI3K/Akt inhibitor LY294002 inhibited phosphorylation of Akt and differentiation of NSCs in the SGZ and SVZ, resulting in no change in the proliferation of NSCs and ERK1/2 phosphorylation. These results demonstrate that IGF-1 upregulates the proliferation of NSCs by triggering MEK/ERK pathway signaling in the adult mice SGZ and SVZ. Meanwhile, IGF-1 also induces differentiation of NSCs via the PI3K/Akt pathway in adult mice. However, we found no evidence of crosstalk between the PI3K/Akt and MEK/ERK pathways in adult mice NSCs. Our work provides new experimental evidence of the involvement of the PI3K/Akt and MEK/ERK pathways in the proliferation and differentiation of the NSCs of adult mice.
The edge clouds in mobile edge computing networks are isolate which may belong to different companies or organizations, and hence the communication, computation, and storage resources are not ...efficiently utilized. To solve this problem, we propose the resource-sharing model of edge clouds which is based on blockchain technology and auction game. In this model, the blockchain platform is regarded as the bridge of the resource sharing, composed of edge clouds, clouds, third-party spectrum and computation management, identity authentication institutions, etc. It is used to record the users’ transaction information and broadcast the intelligent terminals’ resource requirements to all edge clouds in the blockchain platform through smart contracts. Then, an optimization problem of the joint allocation of communication and computation resources is formulated to maximize the utility of intelligent terminals. And an efficient improved sealed second-price auction game is proposed to allocate communication and computation resources and determine the optimal price of resources under the intelligent terminals’ QoS constraints. Simulation results show that the model can effectively improve the system resources utilization and the successful transaction rate.
Purpose
We developed and tested a novel method of creating intensity modulated proton arc therapy (IMPAT) plans that uses computing resources similar to those for regular intensity‐modulated proton ...therapy (IMPT) plans and may offer a dosimetric benefit for patients with ependymoma or similar tumor geometries.
Methods
Our IMPAT planning method consists of a geometry‐based energy selection step with major scanning spot contributions as inputs computed using ray‐tracing and single‐Gaussian approximation of lateral spot profiles. Based on the geometric relation of scanning spots and dose voxels, our energy selection module selects a minimum set of energy layers at each gantry angle such that each target voxel is covered by sufficient scanning spots as specified by the planner, with dose contributions above the specified threshold. Finally, IMPAT plans are generated by robustly optimizing scanning spots of the selected energy layers using a commercial proton treatment planning system (TPS). The IMPAT plan quality was assessed for four ependymoma patients. Reference three‐field IMPT plans were created with similar planning objective functions and compared with the IMPAT plans.
Results
In all plans, the prescribed dose covered 95% of the clinical target volume (CTV) while maintaining similar maximum doses for the brainstem. While IMPAT and IMPT achieved comparable plan robustness, the IMPAT plans achieved better homogeneity and conformity than the IMPT plans. The IMPAT plans also exhibited higher relative biological effectiveness (RBE) enhancement than did the corresponding reference IMPT plans for the CTV in all four patients and brainstem in three of them.
Conclusions
The proposed method demonstrated potential as an efficient technique for IMPAT planning and may offer a dosimetric benefit for patients with ependymoma or tumors in close proximity to critical organs. IMPAT plans created using this method had elevated RBE enhancement associated with increased linear energy transfer (LET) in both targets and abutting critical organs.
PDF
