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Interconnect delay is a key factor that affects the chip performance in layer assignment. Particularly in the advanced process technologies of 5nm and beyond, interconnect delay has grown significantly due to the increase of circuit scale. Moreover, coupling effect existed in wires reduces the accuracy of delay evaluation. On the other hand, the size of vias is often ignored in layer assignment, which enlarges the mismatch between global routing and detailed routing. To solve these problems, we propose VPT, a timing-aware layer assignment algorithm considering via pillars, which includes the following five key techniques: 1) via pillar structure combined with non-default-rule (NDR) wires is adopted to form a net delay optimization system for advanced process technologies; 2) a synthetical model that can adapt to varying types and sizes of both vias and wires is designed to evaluate overflow effectively; 3) a sorting strategy is devised to reduce uncertainty of layer assignment flow and improve stability of the proposed algorithm; 4) an awareness strategy based on multi-aspect congestion assessment is designed to reduce overflow significantly; 5) a net scalpel algorithm is devised to minimize the maximum delay of nets, so that the timing behaviors can be improved systematically. Experimental results on multiple benchmarks confirm that the proposed algorithm leads to lower delay and less overflow, while achieving the best solution quality among the existing algorithms with the shortest runtime.

Background. Type 2 diabetes was associated with a higher risk for permanent pacemaker (PPM) treatment. The difference in cardiovascular outcomes between patients with and without diabetes receiving PPM treatment remains unexplored. Method. Between January 2003 and December 2017, 1742 patients receiving naïve PPM treatment comprised this retrospective cohort study and were categorized into two groups by the diagnosis of diabetes: group with diabetes ( n = 632 , 36.3%) and group without diabetes ( n = 1110 , 63.7%). The primary outcome was cardiovascular events including heart failure (HF) hospitalization and acute myocardial infarction (AMI). The secondary outcomes of this study included pacemaker infection, pacing-induced cardiomyopathy, cerebrovascular accident, cardiovascular mortality, and all-cause mortality. Propensity score matching (PSM) was applied to reduce selection bias between the study groups. Result. During a mean follow-up period of 7.8 ± 4.8 years, 264 patients had a cardiovascular event. Before PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (19.8% vs. 12.5%, P < 0.001 ), and the incidences of pacing-induced cardiomyopathy, cardiovascular mortality, and all-cause mortality were all higher in patients with diabetes compared to patients without diabetes. After PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (18.8% vs. 12.3%, P = 0.015 ). The incidence of HF hospitalization was higher in patients with diabetes compared to patients without diabetes (15.3% vs. 10.2%, P = 0.037 ), whereas the incidence of AMI did not differ between the two groups. Moreover, after PSM, patients with diabetes had higher cumulative incidences of pacing-induced cardiomyopathy and all-cause mortality compared to patients without diabetes. Conclusions. The prevalence of diabetes was over one-third of naïve PPM recipients of this cohort, and diabetes increased the risk of cardiovascular events in PPM recipients, especially for HF hospitalization.

Pin access is increasingly important in advanced nodes. Neighboring or cell-boundary pins can have degraded pin accessibility, causing design rule violations (DRCs) during routing, which are runtime-expensive to resolve. Conventional physical design tool flow uses pessimistic and/or inaccurate understanding of pin access during the placement stage and keeps the location of cells fixed during routing. This can leave pin access issues unsolvable and block further routing solution improvement. The timeliness of our present work is confirmed by the recent ICCAD-2020 CAD Contest, Problem B formulation from Synopsys, Inc. HuY20. The organizers give a succinct motivation for what we study – to eliminate preserved margins and misalignment issues from conventional placement models. In this work, we develop an in-route, pin access-driven local placement refinement. Experiments across industry designs in a wide range of advanced technology nodes confirm that our optimization can significantly improve routing convergence (i.e., subsequent detailed routing runtime and initial detailed routing DRCs). Our optimization can reduce congestion and wirelength without timing degradation.

Research on mountain ecosystem services (MES) under the influence of climate change and human activities has gradually become the focus of academic attention in recent years. Here, this study analyzes the research hotspots and frontiers of this field based on metrics including main research forces, core journals and papers, research hotspots and topics by using the methods of bibliometrics and text mining. The results revealed the following: (1) the number of papers is increasing rapidly in recent years. From 2015 to 2019, 929 papers were published, with an average of 185 papers per year. But the average cited times of those papers is declining, dropped from 6.01 in 2016 to 4.2 in 2019. The USA, UK, and China rank the top three of the number of papers. Univ Maryland, Univ Oxford and Univ Wisconsin have the greatest influence, with an average of more than 77 citations per paper; (2) The most cited journals are PNAS, WETLANDS, ECOLOGY, AND SOCIETY, which are cited 191.54, 53.91, and 40.00 respectively. Most papers were published in OA journals including SUSTAINABILITY, WATER, Forests since 2017. Ten core papers undertaking knowledge transfer in this field have been identified; (3) analysis of the keywords found a new trend of integration of natural science and humanities. In two development stages of 2000–2014 and 2015–2019, the research hotspots mainly focused on mountain water resources, forest resources, land resources and the impact of climate change and human activities, and there are obvious differences and characteristics in different stages. The hotspot worthy of attention in the near future is the assessment of mountain ecosystem services capacity and value. This is the first comprehensive visualization and analysis of the research hotspots and trends of mountain ecosystem services.

In stark contrast to the conventional charge density wave (CDW) materials, the one-dimensional CDW on the In/Si(111) surface exhibits immediate damping of the CDW oscillation during the photoinduced phase transition. Here, by successfully reproducing the experimentally observed photoinduced CDW transition on the In/Si(111) surface by performing real-time time-dependent density functional theory (rt-TDDFT) simulations, we demonstrate that photoexcitation promotes valence electrons from Si substrate to empty surface bands composed primarily of the covalent p-p bonding states of the long In-In bonds, generating interatomic forces to shorten the long bonds and in turn drives coherently the structural transition. We illustrate that after the structural transition, the component of these surface bands occurs a switch among different covalent In bonds, causing a rotation of the interatomic forces by about {\pi}/6 and thus quickly damping the oscillations in feature CDW modes. These findings provide a deeper understanding of photoinduced phase transitions., Comment: 11 pages,3 figures

Hepatic fibrosis (HF) refers to the pathophysiological process of connective tissue dysplasia in the liver caused by various pathogenic factors. Nowadays, HF is becoming a severe threat to the health of human being. However, the drugs available for treating HF are limited. Currently, increasing natural agents derived from traditional Chinese medicines (TCMs) have been found to be beneficial for HF. A systemic literature search was conducted from PubMed, GeenMedical, Sci-Hub, CNKI, Google Scholar and Baidu Scholar, with the keywords of “traditional Chinese medicine,” “herbal medicine,” “natural agents,” “liver diseases,” and “hepatic fibrosis.” So far, more than 76 natural monomers have been isolated and identified from the TCMs with inhibitory effect on HF, including alkaloids, flavones, quinones, terpenoids, saponins, phenylpropanoids, and polysaccharides, etc. The anti-hepatic fibrosis effects of these compounds include hepatoprotection, inhibition of hepatic stellate cells (HSC) activation, regulation of extracellular matrix (ECM) synthesis & secretion, regulation of autophagy, and antioxidant & anti-inflammation, etc. Natural compounds and extracts from TCMs are promising agents for the prevention and treatment of HF, and this review would be of great significance to development of novel drugs for treating HF.

Photoinduced phase transition (PIPT) is always treated as a coherent process, but ultrafast disordering in PIPT is observed in recent experiments. Utilizing the real-time time-dependent density functional theory method, here we track the motion of individual vanadium (V) ions during PIPT in VO

Laser-induced nonthermal melting in semiconductors has been studied over the last four decades, but the underlying mechanism is still under debate. Here, by utilizing an advanced real-time time-dependent density functional theory simulation, we reveal that the photoexcitation-induced ultrafast nonthermal melting in silicon occurs via homogeneous nucleation with random seeds originating from a self-amplified local dynamic instability at the photoexcited states rather than by simultaneously breaking of all bonds, as suggested by the inertial model, phonon instability, or Coulombic repulsion mechanisms. Due to this local dynamic instability, any initial small random thermal displacements of atoms can be amplified by a charge transfer of photoexcited carriers, which in turn creates a local self-trapping center for the excited carriers and yields the random nucleation seeds. This finding provides fresh insights into photoinduced ultrafast nonthermal melting., 27 pages,8 figures

Photoinduced phase transition (PIPT) is always treated as a coherent process, but ultrafast disordering in PIPT is observed in recent experiments. Utilizing the real-time time-dependent density functional theory (rt-TDDFT) method, here, we track the motion of individual vanadium (V) ions during PIPT in VO2 and uncover that their coherent or disordered dynamics can be manipulated by tuning the laser fluence. We find that the photoexcited holes generate a force on each V-V dimer to drive their collective coherent motion, in competing with the thermal-induced vibrations. If the laser fluence is so weak that the photoexcited hole density is too low to drive the phase transition alone, the PIPT is a disordered process due to the interference of thermal phonons. We also reveal that the photoexcited holes populated by the V-V dimerized bonding states will become saturated if the laser fluence is too strong, limiting the timescale of photoinduced phase transition., Comment: 23 pages,10 figures

Ultrafast photoexcitation can induce a nonequilibrium dynamic with electron-lattice interaction, offering an effective way to study photoinduced phase transitions (PIPTs) in solids. The issue that atomic displacements after photoexcitation belong to coherent change or disordered process, has become a controversy in the PIPT community. Using real-time time-dependent density functional theory (rt-TDDFT) simulations, we obtain both the coherent and the disordered PIPTs (dimer dissociation) in IrTe2 with the different electronic occupations. More importantly, we found that in the disordered phase transition, there exists a local correlation between different dimers regarding their dissociation status. One can define vertical groups across the layers. The dimers in the same group will dissociate in a correlated fashion: they either all dissociate, or all not dissociate. On the other hand, the dimers in neighboring groups will have an anti-correlation: if the dimers in one group dissociate, the dimers in the neighboring group tend not to be dissociated, and vice versus., Comment: 13 pages,5 figures

Species of Clavaria (Clavariaceae, Agaricales) collected from China were studied using morphological and molecular methods. Two species, C. aspersa and C. hupingshanensis, are here described as new to science; the former possesses simple, scattered to gregarious or with pairs slightly fascicled, white basidiomata, whereas the latter has simple, gregarious to caespitose clusters, rose-white to seashell-pink basidiomata. In addition, C. amoenoides is described as a newly recorded species for China; this species is characterized by simple, very pale orange-yellow to picric-yellow basidiomata. A phylogenetic analysis was conducted based on a combined dataset of internal transcribed spacer, nuclear ribosomal RNA large subunit and the RNA polymerase Ⅱ second largest subunit sequences. The phylogenetic reconstruction resolved accessions of the three species into three independent lineages within the Clavaria. The morphology of the three species is described in detail and is illustrated with line drawings and photographs. Holotypes of the new species are deposited in the Mycological Herbarium of Hunan Normal University. The sequences newly generated in this study have been deposited in GenBank. An updated key to the known Clavaria species in China is provided.

It is convenient for designers to get the buckling loads of sparse stiffened panels quickly by using engineering calculation method to analyze the stability of composite stiffened panels, but it is still unable to meet the accuracy requirements of analysis of dense stiffened panels. The buckling loads of stiffened panels are closely related to the buckling modes. Based on capturing and analyzing the Compressive Buckling waveforms of T-shaped densely stiffened panels, this paper presents a formula for calculating the buckling loads according to the geometric coefficients. The results are very similar to those of finite element simulation, and can be used to calculate the buckling loads of sparse and dense stiffened panels with different stiffeners.

The hot carrier cooling occurs in most photoexcitation-induced phase transitions (PIPTs), but its role has often been neglected in many theoretical simulations as well as in proposed mechanisms. Here, by including the previously ignored hot carrier cooling in real-time time-dependent density functional theory (rt-TDDFT) simulations, we investigated the role of hot carrier cooling in PIPTs. Taking IrTe2 as an example, we reveal that the cooling of hot electrons from the higher energy levels of spatially extended states to the lower energy levels of the localized Ir-Ir dimer antibonding states strengthens remarkably the atomic driving forces and enhances atomic kinetic energy. These two factors combine to dissolute the Ir-Ir dimers on a timescale near the limit of atomic motions, thus initiating a deterministic kinetic phase transition. We further demonstrate that the subsequent cooling induces nonradiative recombination of photoexcited electrons and holes, leading to the ultrafast recovery of the Ir-Ir dimers observed experimentally. These findings provide a complete picture of the atomic dynamics in optically excited structural phase transitions., Comment: 20 pages, 8 figures

This paper presents an ultra-wide bandwidth (UWB) low-frequency radio astronomical cryogenic receiver for the Five-hundred-meter Aperture Spherical radio Telescope (FAST). It covers 6.6:1 bandwidth from 0.5 to 3.3 GHz. The receiver consists of a Quad-Ridged Flared Horn (QRFH), a cryogenic microwave unit, an optical transceiver and a warm microwave and frequency mixing unit. A QRFH with a concentric-loaded dielectric spear is developed: the average return losses are larger than 20 dB; the average ports polarization isolation is 43.87 dB; the average dish efficiency is higher than 65%. Many UWB cryogenic low loss components are developed for the fabrication of a cryogenic microwave unit. The average noise temperature lower than 14.2 K and 22.5 K are achieved as referred to the input ports of cryogenic Dewar and the output of horn, respectively. Compared to other similar advanced UWB receivers, such as Parkes 0.7–4.2 GHz (6:1 bandwidth) receiver and FAST 0.27–1.62 GHz (6:1 bandwidth) receiver, wider relative bandwidth of the proposed receiver is achieved and it is a new attempt to expand the bandwidth of UWB low-frequency receiver.

Background The association of postimplant tricuspid regurgitation (TR) and heart failure (HF) hospitalization in patients without HF and preexisting abnormal TR and TR pressure gradient (PG) remain unclear. Hypothesis This study aimed to explore the clinical outcomes of progressive postimplant TR after permanent pacemaker (PPM) implantation. Methods A total of 1670 patients who underwent a single ventricular or dual‐chamber transvenous PPM implantation at our hospital between January 2003 and December 2017 were included in the study. Patients with prior valvular surgery, history of HF, and baseline abnormal TR and TRPG were excluded. Finally, a total of 1075 patients were enrolled in this study. Progressive TR was defined as increased TR grade of ≥2 degrees and TRPG of >30 mmHg after implant. Results In 198 (18.4%) patients (group 1) experienced progressive postimplant TR and elevated TRPG, whereas 877 patients (group 2) did not have progressive postimplant TR. Group 1 had larger change in postimplant TRPG (group 1 vs. group 2; 12.8 ± 9.6 mmHg vs. 1.1 ± 7.6 mmHg; p

Objective Right ventricular (RV) septal pacing is considered a better pacing procedure compared with traditional apical pacing. This study aimed to investigate agreement among computed tomography (CT), three-dimensional echocardiography (3D-echo), and fluoroscopy for evaluating the tip of the RV pacing lead in the non-apical position in patients with permanent pacemaker implantation. Methods Fifty-four patients were prospectively enrolled. Data on patients’ characteristics and imaging findings were analyzed. The agreement rate in distinguishing the RV septal lead position among the three imaging modalities was determined. Results Thirty-three (61%) patients were men and the median age was 76 years. Overall, the agreement rate among the three imaging modalities was 87% (47/54; Kappa ratio: 0.734). The agreement of 3D-echo compared with thoracic CT (Kappa ratio: 0.893) was better than that for thoracic CT and fluoroscopy (Kappa ratio: 0.658). Agreement between fluoroscopy and 3D-echo was lowest (Kappa ratio: 0.632). Conclusions Agreement in evaluating the position of the septal lead between thoracic CT and 3D-echo is better than that between other imaging modalities. Our findings indicate that 3D-echo imaging might be the best imaging tool for defining the tip of the RV non-apical lead position and be useful for guiding positioning of the RV lead.

As the scale of VLSI circuits increases rapidly, multi-FPGA prototyping systems have been widely used for logic verification. Due to the limited number of connections between FPGAs, however, the routability of prototyping systems is a bottleneck. As a consequence, timing division multiplexing (TDM) technique has been proposed to improve the usability of prototyping systems, but it causes a dramatic increase in system delay. In this paper, we propose ALIFRouter, a practical architecture-level inter-FPGA router, to improve the chip performance by reducing the corresponding system delay. ALIFRouter consists of three major stages, including i) routing topology generation, ii) TDM ratio assignment, and iii) system delay optimization. Additionally, a multi-thread parallelization method is integrated into the three stages to improve the efficiency of ALIFRouter. With the proposed algorithm, major performance indicators of multi-FPGA systems such as signal multiplexing ratio can be improved significantly.

Although mitochondrial fission has been reported to increase proliferative capacity and collagen production, it can also contribute to mitochondrial impairment, which is detrimental to cell survival. The aim of the present study was to investigate the role of mitochondrial fission in cardiac fibroblasts (CF) activation and explore the mechanisms involved in the maintenance of mitochondrial health under this condition. For this, changes in the levels of mitochondrial fission/fusion-related proteins were assessed in transforming growth factor beta 1 (TGF-β1)-activated CF, whereas the role of mitochondrial fission during this process was also elucidated, as were the underlying mechanisms. The interaction between mitochondrial fission and mitophagy, the main defense mechanism against mitochondrial impairment, was also explored. The results showed that the mitochondria in TGF-β1-treated CF were noticeably more fragmented than those of controls. The expression of several mitochondrial fission-related proteins was markedly upregulated, and the levels of fusion-related proteins were also altered, but to a lesser extent. Inhibiting mitochondrial fission resulted in a marked attenuation of TGF-β1-induced CF activation. The TGF-β1-induced increase in glycolysis was greatly suppressed in the presence of a mitochondrial inhibitor, whereas a glycolysis-specific antagonist exerted little additional antifibrotic effects. TGF-β1 treatment increased cellular levels of reactive oxygen species (ROS) and triggered mitophagy, but this effect was reversed following the application of ROS scavengers. For the signals mediating mitophagy, the expression of Pink1, but not Bnip3l/Nix or Fundc1, exhibited the most significant changes, which could be counteracted by treatment with a mitochondrial fission inhibitor. Pink1 knockdown suppressed CF activation and mitochondrial fission, which was accompanied by increased CF apoptosis. In conclusion, mitochondrial fission resulted in increased glycolysis and played a crucial role in CF activation. Moreover, mitochondrial fission promoted reactive oxygen species (ROS) production, leading to mitophagy and the consequent degradation of the impaired mitochondria, thus promoting CF survival and maintaining their activation.

A prominent circadian variation is present in atrial fibrillation (AF) attacks that may be related to the expression of circadian clock genes. Little is known about the expression of circadian clock genes in AF. We prospectively enrolled 73 patients who had received pacemaker implantation, in order to define the burden of atrial high-rate episodes (AHREs) accurately. AF was diagnosed clinically in 43 (59%) patients (15 with persistent AF and 28 with paroxysmal AF). The expression levels of circadian clock genes of peripheral blood leukocytes were checked. There were more males and patients with a larger left atrial (LA) size and lower expression levels of BMAL1, CRY2, NR1D1, NR1D2, PER2, RORA, RORC, and TIM genes in persistent AF group than in other groups. There was a significant correlation between higher AHRE burden and larger LA size and between higher AHRE burden and decreased expression of circadian clock genes in patients with AF. LA volume and the expression of CRY1, NR1D1, and RORA are significantly associated with AHRE burden. However, the underlying mechanism needs to be elucidated in further studies.

Author(s): Liu, WH; Luo, JW; Li, SS; Wang, LW | Abstract: Photoinduced phase transitions can have complex and intriguing behaviors more than material ground-state dynamics. Understanding the underlying mechanism can help us to design new ways to manipulate the materials. A variety of mechanisms has been proposed to explain the photoinduced phase transitions of IrTe2, but a consensus has yet to be reached. Here, we study the photo-induced phase transitions of IrTe2 by performing the real-time time-dependent density functional theory (rt-TDDFT) simulations in combination with the occupation constrained DFT method. We reveal that the microscopic driving force for the photo-induced phase transitions arises from the tendency to lower the energy levels occupied by the excited carriers, through the increase or decrease of the associated atomic pair distances, depending on whether the newly occupied states are antibonding or bonding states, respectively. The geometric constraints between different bonds represented by the Poisson ratio can bring together different tendencies from different atomic pairs, thus forming a complex intriguing dynamic picture depending on the intensity of the excitation. We also find that phonons don't play a primary role, but can assist the phase transition. These findings imply that one can control the structural phase transitions by selectively exciting photocarriers into designated atomic states using appropriate photon sources.

As the scale of VLSI circuits and fabrication costs increase rapidly, multi-FPGA prototyping systems are widely adopted in industry to make logic verification faster and cheaper. Since routing signals can usually exceed the number of I/O pins in an FPGA, timing division multiplexing (TDM) technique is required to solve this problem. FPGA routing for developing a prototyping system is a big challenge due to the signal delay of TDM. This paper presents MSFRoute, a multi-stage FPGA routing framework for timing division multiplexing technique, to optimize the signal delay and the routability for prototyping systems. In this work, a TDM ratios assignment algorithm with an efficient parallelization method is proposed to optimize inter-FPGA signal delay. Meanwhile, we propose a practical system clock period optimization method to solve critical signal delay problem. Experimental results show that our routing framework reduces TDM ratios by up to 88.3% with an average reduction rate of 41.8%. With the proposed parallelization method, total flow of MSFRoute can get up to 4.38X speedup with a 2.77X speedup on average.

BackgroundThe association of post-implant tricuspid regurgitation (TR) and heart failure (HF) hospitalization in patients without HF and preexisting abnormal TR and TR pressure gradient (PG) remain unclear. This study aimed to explore the clinical outcomes about progressive post-implant TR after permanent pacemaker (PPM) implantation.Methods A total of 1,670 patients who underwent a single ventricular or dual-chamber transvenous PPM implantation at our hospital between January 2003 and December 2017 were included in the study. Patients with prior valvular surgery, heart failure (HF), and baseline abnormal TR and TRPG were excluded. Finally, a total of 1,075 patients were enrolled in this study. Progressive TR was defined as increased TR grade of ≥2 degrees and/or TRPG of >30 mmHg after implant.Results198 (18.4%) patients (group 1) experienced progressive post-implant TR and/or elevated TRPG. Group 1 had l larger changes in post-implant TRPG (group 1 vs. group 2; 12.8 ± 9.6 mmHg vs. 1.1 ± 7.6 mmHg; p < 0.001) than group 2 without progressive post-implant TR. Group 1 had a higher incidence of HF hospitalization compared to group 2 (13.6% vs. 4.7%; p < 0.001). Pre-implant TRPG (HR: 1.075; 95% confidence interval (CI): 1.032-1.121; p = 0.001) and post-implant left atrial dimension (HR: 1.076; 95% CI: 1.038-1.114; p < 0.001) were independent predictors of progressive post-implant TR. ConclusionsAfter a transvenous ventricular-based PPM implantation, 18.4% of patients experienced progressive post-implant TR and/or elevated TRPG. Higher pre-implant TRPG and larger post-implant LA dimension were independent predictors of progressive post-implant TR.

Background The impact of electrocardiography (ECG) morphology on clinical outcomes in patients with non-ST segment elevation myocardial infarction (NSTEMI) receiving percutaneous coronary intervention (PCI) is unknown. This study investigated whether different ST morphologies had different clinical outcomes in patients with NSTEMI receiving PCI. Methods This retrospective study analyzed record-linked data of 362 patients who had received PCI for NSTEMI between January 2008 and December 2010. ECG revealed ST depression in 67 patients, inverted T wave in 91 patients, and no significant ST-T changes in 204 patients. The primary endpoint was long-term all-cause mortality. The secondary endpoint was long-term cardiac death and non-fatal major adverse cardiac events. Results Compared to those patients whose ECG showed an inverted T wave and non-specific ST-T changes, patients whose ECG showed ST depression had more diabetes mellitus, advanced chronic kidney disease (CKD) and left main artery disease, as well as more in-hospital mortality, cardiac death and pulmonary edema during hospitalization. Patients with ST depression had a significantly higher rate of long-term total mortality and cardiac death. Finally, multiple stepwise Cox regression analysis showed that an advanced Killip score, age, advanced CKD, prior percutaneous transluminal coronary angioplasty and ST depression were independent predictors of the primary endpoint. Conclusions Among NSTEMI patients undergoing coronary angiography, those with ST depression had more in-hospital mortality and cardiac death. Long-term follow-up of patients with ST depression consistently reveals poor outcomes.

Layer assignment, a major step in global routing of integrated circuits, is usually performed to assign segments of nets to multiple layers. Besides the traditional optimization goals such as overflow and via count, interconnect delay plays an important role in determining chip performance and has been attracting much attention in recent years. Accordingly, in this paper, we propose MiniDelay, a timing-aware layer assignment algorithm to minimize delay for advanced technology nodes, taking both wire congestion and coupling effect into account. MiniDelay consists of the following three key techniques: 1) a non-default-rule routing technique is adopted to reduce the delay of timing critical nets, 2) an effective congestion assessment method is proposed to optimize delay of nets and via count simultaneously, and 3) a net scalpel technique is proposed to further reduce the maximum delay of nets, so that the chip performance can be improved in a global manner. Experimental results on multiple benchmarks confirm that the proposed algorithm leads to lower delay and few vias, while achieving the best solution quality among the existing algorithms with the shortest runtime.

Obstructive sleep apnea syndrome (OSAS) is a significant risk factor for left atrial (LA) remodeling. Intermittent hypoxemia occurs during the sleep cycle in patients with OSAS and plays a crucial role in cardiovascular pathologies such as stroke, arrhythmia, and coronary artery disease. However, there is very little information about the role of intermittent hypoxemia in LA remodeling in patients with OSAS. In total, 154 patients with sleep-related breathing disorders (SRBD) were prospectively recruited for this study. All enrolled SRBD patients underwent polysomnography and echocardiography. Significant OSAS was defined as an oxygen desaturation index (ODI) of ≥10 per hour. Intermittent hypoxia/reoxygenation (IHR) stimulation was used to test the effect of hypoxia on the viability, reactive oxygen species, apoptosis, and inflammation-associated cytokine expression in the HL-1 cell line. To investigate the effect of patients’ exosomes on HIF-1 and inflammation-associated cytokine expression, as well as the relationship between ODI and their expression, exosomes were purified from the plasma of 95 patients with SRBD and incubated in HL-1 cells. The LA size was larger in patients with significant OSAS than in those without. There was a significant association between ODI, lowest SpO2, mean SpO2, and LA size (all p < 0.05) but not between the apnea–hypopnea index and LA size. IHR condition caused increased LDH activity, reactive oxygen species (ROS) levels, and apoptosis in HL-1 cells and decreased cellular viability (all p < 0.05). The expression of HIF-1α, TNF-α, IL-6, and TGF-β increased in the IHR condition compared with the control (all p < 0.05). The expression of HIF-1α, IL-1β, and IL-6 increased in the HL-1 cells incubated with exosomes from those patients with significant OSAS than those without (all p < 0.05). There was a significantly positive correlation between ODI and the expression of HIF-1α, TNF-α, IL-1β, IL-6, and TGF-β; a significantly negative correlation between mean SpO2 and IL-6 and TGF-β; and a significantly negative correlation between the lowest SpO2 and HIF-1α (all p < 0.05). In conclusion, intermittent hypoxemia was strongly associated with LA remodeling, which might be through increased ROS levels, LDH activity, apoptosis, and the expression of HIF-1α and inflammation-associated cytokines.

Aims Anticoagulation therapy is indicated to prevent stroke in atrial flutter (AFL) and atrial fibrillation (AF) patients. However, the outcomes of solitary AFL patients may differ from those with AFL who develop AF during follow-up. This study aimed to investigate the differences in clinical outcomes: (i) among patients with solitary AFL, AF, and AFL developing AF thereafter and (ii) between solitary AFL patients with vs. without anticoagulation therapy. Methods and results This nationwide cohort study enrolled patients with solitary AFL, solitary AF, and AFL developing AF from a 12 years National Health Insurance Research Database in Taiwan. There were 230 367 patients without anticoagulation therapy in the solitary AF cohort, 8064 in the solitary AFL cohort, and 4495 in the AFL with AF cohort. The AFL with AF and solitary AF cohorts had higher incidences of ischaemic stroke and major bleeding than the solitary AFL cohort. Solitary AFL patients with anticoagulation therapy had a lower ischaemic stroke rate than those without (P

As very large-scale integration technology shrinks to fewer tracks per standard cell, e.g., from 10 to 7.5-track libraries (and lesser for 7 nm), there has been a rapid increase in the usage of multiple-row cells like two- and three-row flip-flops, buffers, etc., for design closure. Additionally, the usage of multibit flip-flops or flop trays to save power creates large cells that further complicate critical design tasks, such as placement. Detailed placement happens to be a key optimization transform, which is repeatedly invoked during the design closure flow to improve design parameters, such as wirelength, timing, and local wiring congestion. Advanced node designs, with hundreds of thousands of multiple-row cells, require a paradigm change for this critical design closure transform. The traditional approach of fixing multiple-row cells during detailed placement and only optimizing the locations of single-row standard cells can no longer obtain appreciable quality of results. It is imperative to have new techniques that can simultaneously optimize both multiple- and single-row height cell locations during detailed placement. In this paper, we propose a new density-aware detailed placer for heterogeneous-sized netlists. Our approach consists of a chain move scheme that generalizes the movement of heterogeneous-sized cells, a nested dynamic programming-based approach for ordered double-row placement and a network flow-based formulation to solve ordered multiple-row placement for wirelength and density optimization. Experimental results demonstrate the effectiveness of these techniques in wirelength minimization and density smoothing compared with the most recent detailed placers for designs with heterogeneous-sized cells.

Obstructive sleep apnea syndrome (OSAS) is an important risk factor for atrial fibrillation (AF). GJA1 gene encoding connexin43, a major protein in cardiac gap junctions, plays a crucial role in the synchronized contraction of the heart and in cardiac arrhythmia. However, little is known regarding the role of GJA1 expression in the incidence of AF in patients with OSAS. All prospectively enrolled OSAS patients underwent polysomnography, electrocardiography, a 24-h Holter test, and echocardiography. Moderate-to-severe OSAS was defined as an apnea-hypopnea index (AHI) ≥ 15. Exosomes were purified from the plasma of all OSAS patients and incubated in HL-1 cells to investigate the effect of exosomes from patients with and without AF on GJA1 expression. A total of 129 patients were recruited for this study, 26 were excluded due to an AHI &lt, 15. Of the 103 enrolled patients, 21 had AF, and 82 did not. Multivariate analysis showed diabetes mellitus, lower sleep efficiency, lower left ventricular ejection fraction, and larger left atrial (LA) size were independent predictors of AF occurrence in OSAS patients. The area under the receiver operating characteristic curve for LA with a size ≥38.5 mm for predicting AF occurrence in OSAS patients was 0.795 (95% confidence interval [0.666, 0.925]), p &lt, 0.001). GJA1 expression in HL-1 cells incubated with exosomes from OSAS patients with AF was lower than that with exosomes from patients without AF after controlling for age and sex and was negatively correlated with the AHI and oxygen desaturation index (ODI), especially during the non-rapid eye movement period (NREM) of OSAS patients with AF (all p &lt, 0.05). LA size was an independent predictor of AF occurrence in OSAS patients. The AHI and ODI in the NREM period of OSAS patients with AF were negatively correlated with GJA1 expression in HL-1 cells, which offers a hint that GJA1 may play a crucial role in the development of AF in patients with OSAS.

Ecological research on the Qinghai–Tibet Plateau (QTP) has become a hotspot in recent years, and a great number of related research papers have been published. Here, a bibliometrics method was utilized to analyze 4315 papers from the Web of Science published from 1990 to 2019, and a comprehensive overview based on metrics, including the publication growth, first author’ institutions and countries, research areas, international cooperation, high-impact journals and papers, and research hotspots and topics, is presented. The results revealed the following: (1) The number of published papers has grown exponentially, with China and India being the main research countries. However, China and the USA have the greatest weights in country cooperation. The Chinese Academy of Sciences has a relatively strong influence and plays the leading role in institutional cooperation. Wang Shiping, Zhang Zhenhua, Luo Caiyun, and seven other authors are highly influential. GLOBAL CHANGE BIOLOGY is the scientific journal that has published the greatest number of papers on the subject, and ‘Environmental Sciences & Ecology’ is the key research area; (2) Grazing, Precipitation, Soil moisture, Aboveground biomass, and Temperature are the top five core keywords. The research hotspots were mainly ecosystem services, biodiversity research, forest protection, and ecological adaptation under the background of climate change; and (3) Both new and old research topics appear in the periods 1990–1999, 2000–2009, 2010–2014, and 2015–2019, but all the periods focused on the impacts of rising temperature on natural elements, such as soil, forests, rivers, and lakes. Many recent also focused on the harmonious coexistence of human beings and nature. On the basis of these findings, some research suggestions and agendas are proposed for future research on the QTP. This is the first visualization and analysis of the hotspots and trends in ecological research on the QTP.

For multi-feature fusion in automatic recognition of pavement distress images, we proposed a multi-feature fusion method based on manifold learning. In this method, the intrinsic features o...

To investigate the postprocedural cardiovascular events and vascular outcomes, including hand ischemia and neurological compromise, after transulnar (TU) catheterization in ipsilateral radial artery occlusion.Previous randomized trials have shown that the transulnar (TU) approach for coronary angiogram and intervention has safety and outcomes similar to those of the transradial (TR) approach. However, the safety of the TU procedure when ipsilateral radial artery occlusion occurs is unknown.We retrospectively reviewed 87 TU cases with ipsilateral radial artery occlusion confirmed by a forearm angiogram. Eighty percent of these patients had a history of ipsilateral radial artery cannulation or surgery. We avoided the use of over-sized sheaths or applied a sheathless approach during surgery.No ulnar artery occlusion was observed by subsequent Doppler ultrasound or pulse oximetry. No patient developed hand ischemia or serious complications requiring surgery or blood transfusion during the follow-up period of 32.2 ± 24.0 months. Review of the preprocedural forearm angiograms showed that 95.7% of the patients possessed significant collaterals supplying flow from the interosseous artery to the occluded radial artery remnant. Thus, the blood circulation to the palmar arch and digital vessels was maintained even when the ulnar artery was temporarily occluded by an in-dwelling ulnar arterial sheath.TU catheterization was safe in patients with coexisting ipsilateral radial artery occlusions and feasible for use in complex intervention procedures. Cautious manipulation of ulnar artery cannulation and hemostasis helped decrease the risk of hand ischemia.

Low-energy impurity diffusion in a host material is often regarded as an adiabatic process, characterized by its adiabatic potential energy barrier. Here we show that the diffusion process in semiconductors can involve nonadiabatic electron excitations, rending it to be a more complicated process. Impurity diffusion in a device at working temperature can pump one electron up from localized impurity state into the host conduction band and causes the impurity to be a dynamic donor since it temporarily loses its electron to the host. This nonadiabatic process, against a common belief, fundamentally change the diffusion behavior, including its barrier height and diffusion path. Although we mainly demonstrate this process with Au metal impurity in bulk Si through time-dependent density functional theory simulations, we believe this could be a rather common phenomenon as it is shown that the similar phenomena also exist in Zn, Cd impurities diffusion in bulk Si, and Ti diffusion in $\mathrm{Ti}{\mathrm{O}}_{2}$. We believe this study can open up a new direction of inquiry for such diffusion behavior in semiconductor.

Detailed routing becomes the most complicated and runtime consuming stage in the physical design flow as technology nodes advance. Due to the inaccessibility of advanced routing rules and industrial designs, it is hard to conduct detailed routing academic researches using the modern real-world designs. ISPD18 hosts the first detailed routing contest [1] and releases a set of benchmarks synthesized by industrial tools with practical routing rules. ISPD18 contest spurs detailed routing researches and provides students the opportunity to become familiar with the industrial designs and rules. On top of ISPD18 detailed routing contest, we host another detailed routing contest in ISPD19 [2] to consider several advanced routing rules and make the contest problem one step closer to the real-world routing challenges in advanced technology nodes. ISPD19 detailed routing contest encourages participants to use double-cut vias to improve yield and result quality. In addition, in order to drive the development of efficient routing frameworks, the deterministic multithreading feature is encouraged but optional in this contest.

Closing timing using clock tree optimization (CTO) is a tremendously challenging problem that may require designer intervention. CTO is performed by specifying and realizing delay adjustments in an initially constructed clock tree. Delay adjustments are typically realized by inserting delay buffers or detour wires. In this paper, we propose a latency constraint guided buffer sizing and layer assignment framework for clock trees with useful skew, called the (BLU) framework. The BLU framework realizes delay adjustments during CTO by performing buffer sizing and layer assignment. Given an initial clock tree, the BLU framework first predicts the final timing quality and specifies a set of delay adjustments, which are translated into latency constraints. Next, buffer sizing and layer assignment is performed with respect to the latency constraints using an extension of van Ginneken's algorithm. Moreover, the framework includes a feature of reducing the power consumption by relaxing the latency constraints and a method of improving the timing performance by tightening the latency constraints. The experimental results demonstrate that the proposed framework is capable of reducing the capacitive cost with 13% on the average. The total negative slack (TNS) and worst negative slack (WNS) are reduced with up to 58% and 20%, respectively.

AimsThe clinical outcome and threshold of oral anticoagulation differs between patients with solitary atrial flutter (AFL) and those with AFL developing atrial fibrillation (AF) (AFL-DAF). We therefore investigated previously unevaluated predictors of AF development in patients with AFL, and also the predictive values of risk scores in predicting the occurrence of AF and ischaemic stroke.Methods and resultsParticipants were those diagnosed with AFL between 1 January 2001 and 31 December 2013. Patients were classified into solitary AFL and AFL-DAF groups during follow-up. Finally, 4101 patients with solitary AFL and 4101 patients with AFL-DAF were included after 1:1 propensity score matching with CHA2DS2-VASc scores and their components, AFL diagnosis year and other comorbidities. The group difference in the prevalence of ischaemic stroke/transient ischaemic attack (TIA) and congestive heart failure (CHF) was substantial, that of vascular disease was moderate, and that of diabetes and hypertension was negligible. Therefore, we reweighted the component of heart failure as 2 (the same with stroke/TIA) and vascular disease as 1 in the proposed A2C2S2-VASc score. The proposed A2C2S2-VASc and CHA2DS2-VASCscores showed patients with AFL who had higher delta scores and follow-up scores had higher risk of AF development. The delta score outperformed the follow-up score in both scoring systems in predicting ischaemic stroke.ConclusionThis study showed that new-onset CHF, stroke/TIA and vascular disease were predictors of AF development in patients with AFL. The dynamic score and changes in both CHA2DS2-VASCand the proposed A2C2S2-VASc score could predict the development of AF and ischaemic stroke.

Background MicroRNAs (miRs) regulate gene expression in heart failure. Circulating miRs as biomarkers for heart failure in mitral regurgitation patients (MR) remain unexplored. Methods This case–control study enrolled 32 MR patients with heart failure, 16 asymptomatic MR patients, and 12 control subjects without heart failure. We used next generation sequencing to study the gene expression profiles in the sera, and quantitative RT-PCR to study serum and tissue miRs in the left atria. Results Next generation sequencing analysis and enrichment analysis showed that 25 miRs were differentially expressed in the sera of MR patients with heart failure compared to control subjects. The circulating miR-148b-3p (p=0.002) and miR-409-3p (p=0.010) were significantly down-regulated in the MR patients with heart failure compared to control subjects. However, only circulation miR-148b-3p was significantly down-regulated in the MR patients without heart failure compared to control subjects (p=0.009). The tissue miR-409-3p was significantly down-regulated in the MR patients with heart failure compared to 3 purchased normal controls (p=0.041). Notably, the tissue RASGRP3 mRNA, target gene of miR-409-3p, was significantly up-regulated in the MR patients with heart failure compared to normal controls (p=0.010). The tissue FRY (p=0.010) and GADD45A (p=0.010) mRNAs, target genes of miR-148b-3p, were significantly up-regulated in the MR patients with heart failure compared to normal controls. Conclusions Circulating miR-148b-3p might serve as biomarker for future development of heart failure and miR-409-3p might serve as biomarker for incident heart failure in MR patients.

Supplemental Digital Content is available in the text, Atrial fibrillation (AF) is a major independent risk factor of stroke and anticoagulation therapy is needed in patients with AF after ischemic stroke. However, the detection rate of AF is low after ischemic stroke. Developing a prediction model for newly diagnosed AF after ischemic stroke will help to assess the subclinical AF. We identified 98,103 patients with diabetes mellitus (DM) and 261,893 patients without DM, who were not AF history and admitted for newly ischemic stroke from the National Health Insurance Research Database in Taiwan. The prediction model for 3-year incidence of AF after ischemic stroke was derived from multivariate logistic regression and also the accuracy rate of the prediction model was compared with CHA2DS2-VASC and CHADS2 scores as a reference. Four thousand nine hundred seventy six patients in the DM cohort and 16,127 patients in the non-DM cohort developed AF during 3 years of follow-up. The variables in the point-based prediction model for non-DM patients (range: -3–28), included age, heart failure, coronary artery disease, gout, obstructive pulmonary disease, hypertension, female, and statin use, while those for DM patients (range: -2–30) included age, heart failure, coronary artery disease, chronic kidney disease, hypertension, obstructive pulmonary disease, and statin use. Compared to the CHADS2 and CHA2DS2-VASc scoring systems, this scoring system was better at predicting 3-year risk of AF after ischemic stroke in both cohorts. This model might be useful in evaluating the benefit of insertable cardiac monitor implantation and anticoagulation agents in individual patients after ischemic stroke.

Background: There are few reports about non-vitamin K antagonist oral anticoagulant (NOAC) treatment for resolution of left atrium (LA) or left atrial appendage (LAA) thrombus. LAA thrombus is an important cause of cardiogenic cerebral thromboembolism, and the detection rate increases due to more and more patients receiving catheter ablation. However, the results from NOAC use for LA or LAA thrombus are still unknown in real-world practice. The aim of this study was to discover the resolution of LA or LAA thrombus after anticoagulant treatment in real-world practice. Method: From January 2013 to December 2016, a total 864 patients underwent transesophageal echocardiography (TEE), and 41 cases of LA or LAA thrombus were detected in our hospital. Among them, a total of 22 patients underwent follow-up TEE to detect the resolution of LA or LAA thrombus. Result: The average age of the study patients was 72.0 ± 11 years old, and 61% were male. The average CHA2DS2-VASc scores were 3.76 ± 2.01 points. A total of 22 patients underwent follow-up TEE, and 19 (86.4%) patients presented LA or LAA thrombus resolution. The average resolution duration was 258.47 ± 218.17 days. One-year all-cause mortality was 4.9%, and the incidence of ischemic stroke was 4.9%. Most physicians favored titration of the dosage of NOAC or warfarin in real-world practice. Conclusion: In real-world practice, most physicians favored titration of the dosage of NOAC or warfarin for LA or LAA thrombus. LA or LAA thrombus could exist if the patient received a reduced dose of NOAC. High frequency of LAA or LA thrombi could resolve, and a low incidence of ischemic stroke occurred after adjustment of oral anticoagulant treatment.

In advanced technology nodes, detailed routing becomes the most complicated and runtime consuming stage. To spur detailed routing research, ISPD 2018 initial detailed routing contest is hosted and it is the first ISPD contest on detailed routing problem. In this contest, the benchmarks synthesized by industrial tool and library are released, which consider the design rules like spacing table, cut spacing, end-of-line spacing, and min-area rules. In addition, the global routing guide is provided associated to each benchmark, and detailed routers are required to honor the routing guides as much as possible meanwhile minimize design-rule-checking (DRC) violations. The biggest benchmark released in this contest has near-millions of nets, so the runtime and memory scalability for detailed routers need to be well addressed. To reduce routers' runtime, the deterministic multithreading framework is encouraged but optional in this contest.