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This thesis examines the implementation of Near-Nozzle Mixing (NNM) in the context of extrusion-based 3D Concrete Printing (E3DCP), with a focus on the Prototype Gradation-Ready Extrusion System (GRES) V1.3. It offers a systematic classification of NNM and assesses its efficacy through detailed mix quality analysis using cross-sectional image techniques. Employing cross-sectional image analysis techniques, the study evaluates the homogeneity and quality of the concrete mix after implementation through GRES V1.3. The findings highlight NNM’s ability to enhance material properties and the quality of 3D printed structures, allowing precise control over the mixing process just before extrusion. This thesis contributes to the field by providing a detailed classification of NNM and presenting evidence of its effectiveness in improving the structural integrity and quality of 3D printed concrete elements.

Daedalus MASE (Mission Assessment through Simulation Exercise) is an open-source package of scientific analysis tools aimed at research in the Lower Thermosphere-Ionosphere (LTI). It was created with the purpose to assess the performance and demonstrate closure of the mission objectives of Daedalus, a mission concept targeting to perform in-situ measurements in the LTI. However, through its successful usage as a mission-simulator toolset, Daedalus MASE has evolved to encompass numerous capabilities related to LTI science and modeling. Inputs are geophysical observables in the LTI, which can be obtained either through in-situ measurements from spacecraft and rockets, or through Global Circulation Models (GCM). These include ion, neutral and electron densities, ion and neutral composition, ion, electron and neutral temperatures, ion drifts, neutral winds, electric field, and magnetic field. In the examples presented, these geophysical observables are obtained through NCAR's Thermosphere-Ionosphere-Electrodynamics General Circulation Model. Capabilities of Daedalus MASE include: 1) Calculations of products that are derived from the above geophysical observables, such as Joule heating, energy transfer rates between species, electrical currents, electrical conductivity, ion-neutral collision frequencies between all combinations of species, as well as height-integrations of derived products. 2) Calculation and cross-comparison of collision frequencies and estimates of the effect of using different models of collision frequencies into derived products. 3) Calculation of the uncertainties of derived products based on the uncertainties of the geophysical observables, due to instrument errors or to uncertainties in measurement techniques. 4) Routines for the along-orbit interpolation within gridded datasets of GCMs. 5) Routines for the calculation of the global coverage of an in situ mission in regions of interest and for various conditions of solar and geomagnetic activity.

Yan-Yan Zhao,1,* Chun Wang,1,* Wei-Xiao Wang,2 Li-Mei Han,1 Caiyun Zhang,2 Jiao-Yang Yu,3 Wei Chen,2 Chun-Mei Hu1,4 1Department of Tuberculosis, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, People’s Republic of China; 2Clinical Research Center, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, People’s Republic of China; 3Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, 710069, People’s Republic of China; 4The Clinical Infectious Disease Center of Nanjing, Nanjing, 210003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Chen; Chun-Mei Hu, Email njyy039@njucm.edu.cn; njyy003@njucm.edu.cnBackground: Drug-resistant tuberculosis (TB) is an emerging threat to public health worldwide. Antimicrobial peptide (AMP) is a promising solution to solve the antimicrobial resistance crisis. The apolipoprotein E mimetic peptide COG1410 has been confirmed to simultaneously have neuroprotective, anti-inflammatory, and antibacterial activity. However, whether it is effective to inhibit growth of mycobacteria has not been investigated yet.Methods: The peptide COG1410 was synthesized with conventional solid-phase peptide synthesis and qualified by HPLC and mass spectrometry. Micro-dilution method was used to determine the minimal inhibitory concentration. A time-kill assay was used to determine the bactericidal dynamics of antimicrobial peptide and relative antibiotics. Static biofilm formation was conducted in 24-well plate and the biofilm was separated from planktonic cells and collected. The mechanism of action of COG1410 was explored by TEM observation and ATP leak assay. The localization of COG1410 was observed by confocal laser scan microscopy. The drug–drug interaction was determined by a checkerboard assay.Results: COG1

The lower thermosphere-ionosphere (LTI) is a key transition region between Earth’s atmosphere and space. Interactions between ions and neutrals maximize within the LTI and in particular at altitudes from 100 to 200 km, which is the least visited region of the near-Earth environment. The lack of in situ co-temporal and co-spatial measurements of all relevant parameters and their elusiveness to most remote-sensing methods means that the complex interactions between its neutral and charged constituents remain poorly characterized to this date. This lack of measurements, together with the ambiguity in the quantification of key processes in the 100–200 km altitude range affect current modeling efforts to expand atmospheric models upward to include the LTI and limit current space weather prediction capabilities. We present focused questions in the LTI that are related to the complex interactions between its neutral and charged constituents. These questions concern core physical processes that govern the energetics, dynamics, and chemistry of the LTI and need to be addressed as fundamental and long-standing questions in this critically unexplored boundary region. We also outline the range of in situ measurements that are needed to unambiguously quantify key LTI processes within this region, and present elements of an in situ concept based on past proposed mission concepts.

The lower thermosphere-ionosphere (LTI) is a key transition region between Earth’s atmosphere and space. Interactions between ions and neutrals maximize within the LTI and in particular at altitudes from 100 to 200 km, which is the least visited region of the near-Earth environment. The lack of in situ co-temporal and co-spatial measurements of all relevant parameters and their elusiveness to most remote-sensing methods means that the complex interactions between its neutral and charged constituents remain poorly characterized to this date. This lack of measurements, together with the ambiguity in the quantification of key processes in the 100–200 km altitude range affect current modeling efforts to expand atmospheric models upward to include the LTI and limit current space weather prediction capabilities. We present focused questions in the LTI that are related to the complex interactions between its neutral and charged constituents. These questions concern core physical processes that govern the energetics, dynamics, and chemistry of the LTI and need to be addressed as fundamental and long-standing questions in this critically unexplored boundary region. We also outline the range of in situ measurements that are needed to unambiguously quantify key LTI processes within this region, and present elements of an in situ concept based on past proposed mission concepts.

The unfixed flame propagation velocity of a gas explosion and the fixed response time of explosion suppression devices are the important reasons for the poor protective effect of active explosion suppression. A flexible explosion suppression method based on buffer energy absorption is detailed in this study. The explosion suppression system consists of an explosive characteristic monitoring system, an explosion suppression agent system, and an explosion suppression airbag. An empty pipe experiment and an explosion suppression experiment with a flexible-airbag gas-explosion suppression device were conducted in a 20.5 m-long pipe with an inner diameter of 180 mm. The flame propagation velocity and maximum overpressure values were compared between the two groups of experiments. The experimental results show that the flame wave propagation can be completely suppressed by the explosion suppression device under certain pressure. The occurrence time of maximum overpressure at each pressure measuring point is also analyzed. P3 is generally later than P4, which verifies the existence of energy absorption and explosion suppression effect of airbag. Finally, the energy absorption effect of the airbag is analyzed theoretically. The shock wave overpressure calculated in the sealing limit state of the airbag is 0.3432 MPa, and the maximum error is 7.8%, which provides reliable guidance and prediction for the experimental process in the future., This research was funded the National Natural Science Foundation of China (No. 52174176) and the Natural Science Foundation of Heilongjiang Province (No. QC2015054)., Peer Reviewed, Objectius de Desenvolupament Sostenible::8 - Treball Decent i Creixement Econòmic, Postprint (published version)

Cheng-Xi Sun,1 Li-Yan Han,2,3 Kai Wang,2,3 Shuai Gao2,3 1Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Institute of Hepatology, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Shuai Gao, Department of Hepatology, Qilu Hospital of Shandong University, No. 107, Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Tel +86-531-82169593, Fax +86-531-86927544, Email qilugaoshuai@sdu.edu.cn; gaoshuai361@163.comBackground: Acute-on-chronic hepatitis B liver failure (ACHBLF) is a clinical syndrome with an extremely high mortality. In this study, we aim to evaluate the potential role of serum exosomal long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in ACHBLF and its predictive value for 3-month mortality.Methods: From December 2017 to June 2022, we enrolled 110 patients with ACHBLF and 42 healthy controls (HCs). Exosomes were isolated from the serum of the participants. Serum exosomal lncRNA GAS5 was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The functional role of lncRNA GAS5 on hepatocyte phenotypes was investigated through loss-of-function and gain-of-function assays. Exosomal labeling and cell uptake assay were used to determine the exosomes-mediated transmission of lncRNA GAS5 in hepatocytes in vitro.Results: The serum exosomal lncRNA GAS5 was identified to be an independent predictor for 3-month mortality of ACHBLF. It yielded an area under the receiver operating characteristic curve (AUC) of 0.88, which was significantly higher than MELD score (AUC 0.73; P < 0.01). Further study found that lncRNA GAS5 could inhibit hepatocytes proliferation and increase hepatocytes apoptosis. Exosomes-mediated lncRNA GAS5 transfer promoted hepatocytes injury. The knocked down of lnc

Fritts, Wang, Lund, and Thorpe (2022, https://doi.org/10.1017/jfm.2021.1085) and Fritts, Wang, Thorpe, and Lund (2022, https://doi.org/10.1017/jfm.2021.1086) described a 3-dimensional direct numerical simulation of interacting Kelvin-Helmholtz instability (KHI) billows and resulting tube and knot (T&K) dynamics that arise at a stratified shear layer defined by an idealized, large-amplitude inertia-gravity wave. Using similar initial conditions, we performed a high-resolution compressible simulation to explore the emission of GWs by these dynamics. The simulation confirms that such shear can induce strong KHI with large horizontal scales and billow depths that readily emit GWs having high frequencies, small horizontal wavelengths, and large vertical group velocities. The density-weighted amplitudes of GWs reveal “fishbone” structures in vertical cross sections above and below the KHI source. Our results reveal that KHI, and their associated T&K dynamics, may be an important additional source of high-frequency, small-scale GWs at higher altitudes.

Guocong Huang,1 Wei Liu,2 Li Han,2 Yue Zhang,2 Siyao Liu,2 Jiali Zhang,2 Beifang Niu3,4 1Department of Thyroid and Breast Surgery, The First Hospital of Putian City, Fujian, People’s Republic of China; 2Beijing ChosenMed Clinical Laboratory Co. Ltd., Beijing, People’s Republic of China; 3Computer Network Information Center, Chinese Academy of Sciences, Beijing, People’s Republic of China; 4University of the Chinese Academy of Sciences, Beijing, People’s Republic of ChinaCorrespondence: Guocong Huang, Department of Thyroid and Breast surgery, The First Hospital of Putian City, No. 449 South Gate West Road, Chengxiang District, Putian, Fujian Province, 351100, People’s Republic of China, Email 88059466@qq.com Beifang Niu, Computer Network Information Center, Chinese Academy of Sciences, CAS Informatization Plaza No. 2 Dong Sheng Nan Lu, Haidian District, Beijing, 100083, People’s Republic of China, Email niubf@cnic.cnPurpose: Our objective was to evaluate the diagnostic performance of BRAFV600E mutation for malignant, and to identify clinical characteristics associated with positive BRAFV600E mutation in low-risk cytological and ultrasound diagnostic thyroid nodules. This aims to identify patients who may benefit from BRAFV600E mutation testing and subsequent surgical intervention.Patients and Methods: We analysis the clinical characteristics correlated with BRAFV600E mutation in our detection cohort, including 204 patients with 217 thyroid nodules, and separate analyses were performed in 103 thyroid nodules with benign cytological result. Signaling pathway and immune response associated with age and BRAFV600E mutation status were also evaluated in Asian patients with thyroid cancer from the Cancer Genome Atlas (TCGA) dataset.Results: The positive BRAFV600E mutation was significantly associated with higher Ultrasound (US) classification (p< 0.001) and fine-needle aspiration (FNA) categories (p< 0.001). BRAFV600E mutation as a risk factor for malignan

Daedalus MASE (Mission Assessment through Simulation Exercise) is an open-source package of scientific analysis tools aimed at research in the Lower Thermosphere-Ionosphere (LTI). It was created with the purpose to assess the performance and demonstrate closure of the mission objectives of Daedalus, a mission concept targeting to perform in-situ measurements in the LTI. However, through its successful usage as a mission-simulator toolset, Daedalus MASE has evolved to encompass numerous capabilities related to LTI science and modeling. Inputs are geophysical observables in the LTI, which can be obtained either through in-situ measurements from spacecraft and rockets, or through Global Circulation Models (GCM). These include ion, neutral and electron densities, ion and neutral composition, ion, electron and neutral temperatures, ion drifts, neutral winds, electric field, and magnetic field. In the examples presented, these geophysical observables are obtained through NCAR’s Thermosphere-Ionosphere-Electrodynamics General Circulation Model. Capabilities of Daedalus MASE include: 1) Calculations of products that are derived from the above geophysical observables, such as Joule heating, energy transfer rates between species, electrical currents, electrical conductivity, ion-neutral collision frequencies between all combinations of species, as well as height-integrations of derived products. 2) Calculation and cross-comparison of collision frequencies and estimates of the effect of using different models of collision frequencies into derived products. 3) Calculation of the uncertainties of derived products based on the uncertainties of the geophysical observables, due to instrument errors or to uncertainties in measurement techniques. 4) Routines for the along-orbit interpolation within gridded datasets of GCMs. 5) Routines for the calculation of the global coverage of an in situ mission in regions of interest and for various conditions of solar and geomagnetic activit

GPUs have become the \emph{defacto} hardware devices for accelerating Deep Neural Network (DNN) inference workloads. However, the conventional \emph{sequential execution mode of DNN operators} in mainstream deep learning frameworks cannot fully utilize GPU resources, even with the operator fusion enabled, due to the increasing complexity of model structures and a greater diversity of operators. Moreover, the \emph{inadequate operator launch order} in parallelized execution scenarios can lead to GPU resource wastage and unexpected performance interference among operators. In this paper, we propose \emph{Opara}, a resource- and interference-aware DNN \underline{Op}erator \underline{para}llel scheduling framework to accelerate DNN inference on GPUs. Specifically, \emph{Opara} first employs \texttt{CUDA Streams} and \texttt{CUDA Graph} to \emph{parallelize} the execution of multiple operators automatically. To further expedite DNN inference, \emph{Opara} leverages the resource demands of operators to judiciously adjust the operator launch order on GPUs, overlapping the execution of compute-intensive and memory-intensive operators. We implement and open source a prototype of \emph{Opara} based on PyTorch in a \emph{non-intrusive} manner. Extensive prototype experiments with representative DNN and Transformer-based models demonstrate that \emph{Opara} outperforms the default sequential \texttt{CUDA Graph} in PyTorch and the state-of-the-art operator parallelism systems by up to $1.68\times$ and $1.29\times$, respectively, yet with acceptable runtime overhead., Comment: 9 pages,10 figures

Since the reform and opening up of China, the rural built environment has changed dramatically. There is a need to understand how such changes have impacted rural children’s school travel mode choice to design the built environment and plan schools accordingly. This paper combines field measurement methods and questionnaires to obtain data on rural children’s school travel behavior and uses the multinomial logit (MNL) model to investigate the impacting factors. The results show the following insights: Age has a significant positive impact on children’s choice of bicycles and buses. The improvements in road layout and facility conditions are significantly and positively associated with children’s choice of electric bicycles for school. There is a significant positive correlation between a good and safe public environment and children’s choice of cycling. Furthermore, distance from home to school has a significant impact on the choice of children’s school travel mode: the greater the distance to school, the higher the probability that children will choose motorized modes of travel such as buses and private cars. This study provides empirical data and evidence in designing rural transport systems for school children based on their preferences concerning built environment factors., Design & Construction Management

The mesospheric polar vortex (MPV) plays a critical role in coupling the atmosphere-ionosphere system, so its accurate simulation is imperative for robust predictions of the thermosphere and ionosphere. While the stratospheric polar vortex is widely understood and characterized, the mesospheric polar vortex is much less well-known and observed, a short-coming that must be addressed to improve predictability of the ionosphere. The winter MPV facilitates top-down coupling via the communication of high energy particle precipitation effects from the thermosphere down to the stratosphere, though the details of this mechanism are poorly understood. Coupling from the bottom-up involves gravity waves (GWs), planetary waves (PWs), and tidal interactions that are distinctly different and important during weak vs. strong vortex states, and yet remain poorly understood as well. Moreover, generation and modulation of GWs by the large wind shears at the vortex edge contribute to the generation of traveling atmospheric disturbances and traveling ionospheric disturbances. Unfortunately, representation of the MPV is generally not accurate in state-of-the-art general circulation models, even when compared to the limited observational data available. Models substantially underestimate eastward momentum at the top of the MPV, which limits the ability to predict upward effects in the thermosphere. The zonal wind bias responsible for this missing momentum in models has been attributed to deficiencies in the treatment of GWs and to an inaccurate representation of the high-latitude dynamics. In the coming decade, simulations of the MPV must be improved.

By matching data on land transactions in China's primary land market with detailed curricula vitae of board directors in publicly listed firms, we identify a pattern of 'revolving-door' exchanges between local officials and firms. The officials discounted the price of land that they sold to the said firms, and were subsequently rewarded with board appointments upon retirement. Specifically, these 'client officials' are three times as likely to be recruited by the 'patron firms' as board directors and enjoy a salary that is 23% higher, and 81% more company shares by comparison with directors who did not help firms to secure cheap land deals. All of these, however, are conditional on patron firms being able to receive a price discount, which averaged 19.4% when they purchased them in normal times. However, when client officials were constrained from providing a price discount during a surprise audit, the likelihood of client officials recruited as board directors was halved, with the price discount and extra compensation received by the patrons and clients, respectively, vanishing altogether. By providing evidence of the reciprocal benefits received by both parties, we demonstrate that the revolving door is used as a 'payment' rather than a 'connection' device in the Chinese context.

Nuclear energy has significantly promoted the development of human society. However, nuclear pollution caused by nuclear accidents can lead to significant hazards to the environment and human health. As a major radioactive product, radioactive iodine (mainly existing as I−) detection has attracted significant attentions. In this study, zirconium(IV) is used to enhance the oxidation of environmental I− to form I2. Subsequently, the generated I2 oxidizes the chemical chromogenic substrate 3,3′,5,5′-tetramethylbenzidine, which is used for I− detection and realizes an ultralow limit of detection (LoD) of 0.176 nM. The LoD of our method, to the best of our knowledge, is the lowest among those of the available chemical methods for I− detection. Furthermore, our detection method also shows high specificity and reliability, making it a promising technique for detecting I− in practical environments.

To date, little is known about the past evolutionary trajectories of rare and endangered orchids native to mainland China, Japan, and Korea (the CJK region). In this study, we focus on two endangered orchids, Cypripedium japonicum (present in the three countries) and C. formosanum (endemic to Taiwan), to understand the divergence/speciation models that would have been operating in this group, including genetic diversity, geographic structure, and colonization pathways across the region. Using a combination of five cpDNA regions, we reconstructed phylogenetic trees and investigated the genetic diversity/structure of 20 populations. Ecological niche modeling was used to gain insight into the paleodistribution and dispersal corridors at the Last Glacial Maximum and to survey climatic niche differences. Populations from mainland China + Korea, Japan, and Taiwan formed three distinct monophyletic lineages and were placed into separate genetic clusters, agreeing with geographic barriers and species boundaries. Populations of C. japonicum in mainland China harbored the highest diversity, suggesting the presence of multiple glacial refugia. The Korean populations would have originated from either western/central or eastern China, probably using a dispersal corridor across the East China Sea shelf. The divergence of C. formosanum is proposed under an allopatric speciation model, also highly influenced by a climate niche shift. In the context of previous studies, a deep divergence in cpDNA sequences between Chinese + Korean and Japanese populations of C. japonicum may be taken as an example of the speciation events of the CJK flora since the late Neogene that have led to its current species richness.

Listing all k-cliques is a fundamental problem in graph mining, with applications in finance, biology, and social network analysis. However, owing to the exponential growth of the search space as k increases, listing all k-cliques is algorithmically challenging. DDegree and DDegCol are the state-of-the-art algorithms that exploit ordering heuristics based on degree ordering and color ordering, respectively. Both DDegree and DDegCol induce high time and space overhead for set intersections cause they construct and maintain all induced subgraphs. Meanwhile, it is non-trivial to implement the data level parallelism to further accelerate on DDegree and DDegCol. In this paper, we propose two efficient algorithms SDegree and BitCol for k-clique listing. We mainly focus on accelerating the set intersections for k-clique listing. Both SDegree and BitCol exploit the data level parallelism for further acceleration with single instruction multiple data (SIMD) or vector instruction sets. Furthermore, we propose two preprocessing techniques Pre-Core and Pre-List, which run in linear time. The preprocessing techniques significantly reduce the size of the original graph and prevent exploring a large number of invalid nodes. In the theoretical analysis, our algorithms have a comparable time complexity and a slightly lower space complexity than the state-of-the-art algorithms. The comprehensive experiments reveal that our algorithms outperform the state-of-the-art algorithms by 3.75x for degree ordering and 5.67x for color ordering on average., Comment: 15 pages, IEEE 2023

Listing all k-cliques is a fundamental problem in graph mining, with applications in finance, biology, and social network analysis. However, owing to the exponential growth of the search space as k increases, listing all k-cliques is algorithmically challenging. DDegree and DDegCol are the state-of-the-art algorithms that exploit ordering heuristics based on degree ordering and color ordering, respectively. Both DDegree and DDegCol induce high time and space overhead for set intersections cause they construct and maintain all induced subgraphs. Meanwhile, it is non-trivial to implement the data level parallelism to further accelerate on DDegree and DDegCol. In this paper, we propose two efficient algorithms SDegree and BitCol for k-clique listing. We mainly focus on accelerating the set intersections for k-clique listing. Both SDegree and BitCol exploit the data level parallelism for further acceleration with single instruction multiple data (SIMD) or vector instruction sets. Furthermore, we propose two preprocessing techniques Pre-Core and Pre-List, which run in linear time. The preprocessing techniques significantly reduce the size of the original graph and prevent exploring a large number of invalid nodes. In the theoretical analysis, our algorithms have a comparable time complexity and a slightly lower space complexity than the state-of-the-art algorithms. The comprehensive experiments reveal that our algorithms outperform the state-of-the-art algorithms by 3.75x for degree ordering and 5.67x for color ordering on average. © 2022 IEEE.

Introduction: Rural roads and built environment in China have been developed enormously, but it is not clear whether these roads fulfill the needs of school children as they need to travel long to school every day. Objective: It is crucial to understand the influencing factors of their travel mode choices to better design future country roads and built environment, aiming to promote physical activities of school children in a safe built environment. Method: This study thus attempts to explore the impacts of rural built environment attributes on children's school travel mode preferences. Eight rural built environment attributes are considered: distance from home to school; the number of intersections passed on the way to school; whether there are sidewalks/bicycle lanes; the traffic speed of school access routes; whether there are separation facilities between motor vehicles and non-motor vehicles; whether there are traffic lights and zebra crossings; availability of greenery such as lawns, flower ponds and street trees and whether there are shops on the way to school and at the school gate. Six hundred and thirty eight valid questionnaires were obtained through face-to-face interviews with school-age children in villages. A multinomial logit model was estimated to unravel the preferences and choices of rural school-age children in different models of school travel using the stated choice data. Results: All the eight attributes have significant impacts on rural children's school travel choices on foot, bicycle, electric bicycle or motorbike. And four rural road design attributes have significant effects on rural children's school travel by private cars. A travel path with pavements or bike lanes, few intersections, low traffic speeds, greenery and shops can facilitate children's school travels on foot or by bike. The conclusions can provide reference for the further upgrading planning, designing and construction of rural roads, as well as e, Design & Construction Management

This paper explores how tightening ideological control weakens media monitoring in China by examining accident reporting in 230 subnational newspapers from 2010 to 2020. In the reform era, commercial newspapers, completely owned but not fully funded by the state, effectively play a role of monitoring by reporting newsworthy and relatively safe topics such as accidents and disasters. The media ideological campaign launched in 2016 by President Xi Jinping dramatically reduced the amount of accident news coverage, especially the investigative reporting. Exploiting the fact that the rollout of this campaign is linked to Xi’s personal authority, I find that the reduction in local accident reporting is 1.31 standard error greater for media outlets in Xi’s client provinces than those in other provinces. This reduction is particularly strong for self-funding newspapers, suggesting that media freedom brought about by the marketization reform has been reversed.

The fabrication and manipulation of tunable micro- and macro-domain silver nanowires (AgNWs) remains challenging. In this letter, we explored the dispersion, orientation, reorientation, order parameters, twist nematic structures, and in-plane and vertical dynamic switching of AgNWs dispersed in a liquid crystal (LC) host. The order parameter of the orientational AgNWs is 0.91-0.94. Three-dimensional (3D) orientation and reorientation of AgNWs could be achieved through photoalignment and an electric field. This study reveals that the alignment of AgNWs is promising in the fabrication of liquid crystal display and optoelectronic devices, and it exhibits a variety of useful behaviors in the LC hosts of both theoretical and practical interest. ©

The lower-thermosphere-ionosphere (LTI) system consists of the upper atmosphere and the lower part of the ionosphere and as such comprises a complex system coupled to both the atmosphere below and space above. The atmospheric part of the LTI is dominated by laws of continuum fluid dynamics and chemistry, while the ionosphere is a plasma system controlled by electromagnetic forces driven by the magnetosphere, the solar wind, as well as the wind dynamo. The LTI is hence a domain controlled by many different physical processes. However, systematic in situ measurements within this region are severely lacking, although the LTI is located only 80 to 200 km above the surface of our planet. This paper reviews the current state of the art in measuring the LTI, either in situ or by several different remote-sensing methods. We begin by outlining the open questions within the LTI requiring high-quality in situ measurements, before reviewing directly observable parameters and their most important derivatives. The motivation for this review has arisen from the recent retention of the Daedalus mission as one among three competing mission candidates within the European Space Agency (ESA) Earth Explorer 10 Programme. However, this paper intends to cover the LTI parameters such that it can be used as a background scientific reference for any mission targeting in situ observations of the LTI.

Long-term and continuous observations of mesospheric–lower thermospheric winds are rare, but they are important to investigate climatological changes at these altitudes on timescales of several years, covering a solar cycle and longer. Such long time series are a natural heritage of the mesosphere–lower thermosphere climate, and they are valuable to compare climate models or long-term runs of general circulation models (GCMs). Here we present a climatological comparison of wind observations from six meteor radars at two conjugate latitudes to validate the corresponding mean winds and atmospheric diurnal and semidiurnal tides from three GCMs, namely the Ground-to-Topside Model of Atmosphere and Ionosphere for Aeronomy (GAIA), the Whole Atmosphere Community Climate Model Extension (Specified Dynamics) (WACCM-X(SD)), and the Upper Atmosphere ICOsahedral Non-hydrostatic (UA-ICON) model. Our results indicate that there are interhemispheric differences in the seasonal characteristics of the diurnal and semidiurnal tide. There are also some differences in the mean wind climatologies of the models and the observations. Our results indicate that GAIA shows reasonable agreement with the meteor radar observations during the winter season, whereas WACCM-X(SD) shows better agreement with the radars for the hemispheric zonal summer wind reversal, which is more consistent with the meteor radar observations. The free-running UA-ICON tends to show similar winds and tides compared to WACCM-X(SD).

The lower-thermosphere–ionosphere (LTI) system consists of the upper atmosphere and the lower part of the ionosphere and as such comprises a complex system coupled to both the atmosphere below and space above. The atmospheric part of the LTI is dominated by laws of continuum fluid dynamics and chemistry, while the ionosphere is a plasma system controlled by electromagnetic forces driven by the magnetosphere, the solar wind, as well as the wind dynamo. The LTI is hence a domain controlled by many different physical processes. However, systematic in situ measurements within this region are severely lacking, although the LTI is located only 80 to 200 km above the surface of our planet. This paper reviews the current state of the art in measuring the LTI, either in situ or by several different remote-sensing methods. We begin by outlining the open questions within the LTI requiring high-quality in situ measurements, before reviewing directly observable parameters and their most important derivatives. The motivation for this review has arisen from the recent retention of the Daedalus mission as one among three competing mission candidates within the European Space Agency (ESA) Earth Explorer 10 Programme. However, this paper intends to cover the LTI parameters such that it can be used as a background scientific reference for any mission targeting in situ observations of the LTI.

Li Han,1 Jing Wang,1 Xiao-Bin Ji,1 Zai-Yan Wang,1 Yi Wang,2 Li-Yue Zhang,2 Hong-Peng Li,2 Ze-Ming Zhang,1 Qing-Yun Li2 1Department of Respiratory Medicine, Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Ze-Ming Zhang Department of Respiratory Medicine, Shanghai University of Medicine & Health Science affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of ChinaEmail zhangzemingwang@sohu.comQing-Yun Li Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of ChinaEmail liqingyun68@hotmail.comBackground and Aims: Alveolar macrophages (AM) play a crucial role in the development of chronic obstructive pulmonary disease (COPD). The role that AM plays in the molecular pathways and clinical phenotypes associated with tobacco-related emphysema remain poorly understood. Thus, we investigated the transcriptomic profile of AM in COPD patients with a history of smoking and explored the molecular mechanisms associated with enriched pathways and hub genes.Methods: Four data sets (GSE2125, GSE8823, GSE13896 and GSE130928) were retrieved from the GEO Database. A total of 203 GEO samples (GSM) were collated for this study. About 125 of these cases were classified as smokers (91 as healthy non-COPD smokers and 34 as COPD smokers). Based on the bioinformatics obtained using the R3.6.1 program, the data were successively adopted for differential genetic expression analysis, enrichment analysis (EA), and then protein–protein interaction analysis (PPI) in a STRING database. Finally, Cytoscape 3.8 software was used to screen the hub genes. A further data analysis was performed using a set of 154 cases, classified as 64 he

Formally verifying Deep Reinforcement Learning (DRL) systems is a challenging task due to the dynamic continuity of system behaviors and the black-box feature of embedded neural networks. In this paper, we propose a novel abstraction-based approach to train DRL systems on finite abstract domains instead of concrete system states. It yields neural networks whose input states are finite, making hosting DRL systems directly verifiable using model checking techniques. Our approach is orthogonal to existing DRL algorithms and off-the-shelf model checkers. We implement a resulting prototype training and verification framework and conduct extensive experiments on the state-of-the-art benchmark. The results show that the systems trained in our approach can be verified more efficiently while they retain comparable performance against those that are trained without abstraction., Comment: 14 pages, 7 figures

$k$-truss model is a typical cohesive subgraph model and has been received considerable attention recently. However, the $k$-truss model only considers the direct common neighbors of an edge, which restricts its ability to reveal fine-grained structure information of the graph. Motivated by this, in this paper, we propose a new model named $(k, \tau)$-truss that considers the higher-order neighborhood ($\tau$ hop) information of an edge. Based on the $(k, \tau)$-truss model, we study the higher-order truss decomposition problem which computes the $(k, \tau)$-trusses for all possible $k$ values regarding a given $\tau$. Higher-order truss decomposition can be used in the applications such as community detection and search, hierarchical structure analysis, and graph visualization. To address this problem, we first propose a bottom-up decomposition paradigm in the increasing order of $k$ values to compute the corresponding $(k, \tau)$-truss. Based on the bottom-up decomposition paradigm, we further devise three optimization strategies to reduce the unnecessary computation. We evaluate our proposed algorithms on real datasets and synthetic datasets, the experimental results demonstrate the efficiency, effectiveness and scalability of our proposed algorithms., Comment: 15 pages

Jun-Hong Zhou,1,&ast; Kang Yu,2,&ast; Hui Ding,1 Zhao-Hua Zhu,3,&ast; Li-Hua Han,1,&ast; Ting Zhang1 1Department of Obstetrics, Sunshine Union Hospital, Weifang, 261000, Shandong, People’s Republic of China; 2The Reproductive Medicine Center of Weifang People’s Hospital, Weifang, 261000, Shandong, People’s Republic of China; 3Department of Obstetrics, Traditional Chinese Medicine Hospital of Weifang, Weifang, 261000, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ting Zhang; Hui DingDepartment of Obstetrics, Sunshine Union Hospital, No. 9000 of Yingqian Street, Kuiwen District, Weifang, 261000, Shangdong, People’s Republic of ChinaTel +86 15169502878Email zhangting_nn@163.com; dinghui88con@163.comObjective: This study aimed to explore the impact of gestational diabetes mellitus (GDM) on the results of newborn hearing screening.Methods: A total of 666 pregnant women who gave birth in the Obstetric Department of Sunshine Ronghe Hospital from August 2017 to May 2018 were randomly selected, and 69 of these pregnant women had GDM and were assigned into group 1 (excluding other diseases). The average age of these patients was 31.07 years. A further 597 pregnant women had no GDM and were assigned into group 2 (excluding other diseases). The average age of these patients was 30.02 years. The results of newborn hearing screening results in group 1 and group 2 were compared.Results: Comparisons of abnormal hearing screening between 2 groups are significant different (P < 0.05). In the GDM group, the results of hearing screening of newborns delivered by vaginal delivery and cesarean delivery were compared, yielding a P-value of > 0.05, and the difference was not statistically significant. In the non-GDM group, the results of hearing screening of newborns delivered by vaginal delivery and cesarean delivery were compared, yielding a P-value of > 0.05, and the difference was not statist

The lower-Thermosphere-ionosphere (LTI) system consists of the upper atmosphere and the lower part of the ionosphere and as such comprises a complex system coupled to both the atmosphere below and space above. The atmospheric part of the LTI is dominated by laws of continuum fluid dynamics and chemistry, while the ionosphere is a plasma system controlled by electromagnetic forces driven by the magnetosphere, the solar wind, as well as the wind dynamo. The LTI is hence a domain controlled by many different physical processes. However, systematic in situ measurements within this region are severely lacking, although the LTI is located only 80 to 200 km above the surface of our planet. This paper reviews the current state of the art in measuring the LTI, either in situ or by several different remote-sensing methods. We begin by outlining the open questions within the LTI requiring high-quality in situ measurements, before reviewing directly observable parameters and their most important derivatives. The motivation for this review has arisen from the recent retention of the Daedalus mission as one among three competing mission candidates within the European Space Agency (ESA) Earth Explorer 10 Programme. However, this paper intends to cover the LTI parameters such that it can be used as a background scientific reference for any mission targeting in situ observations of the LTI..

Joan Flasch Artists' Book Collection

This paper examines whether a conditional grant program for teacher trainees helped attract better students to teaching majors in Chinese universities. The Free Education for Future Teachers program implemented in top teachers’ colleges provides tuition exemption and a generous stipend package to students in teaching majors under the condition that the recipients teach in their home provinces after graduation. By comparing score changes between teaching and nonteaching (“regular”) majors and between program colleges and nonprogram teachers’ colleges, we find that this grant program helps attract students scoring 0.4–0.5 percentiles higher in the score distribution to teaching majors. Further analysis shows that the program impact is stronger in places where more students are likely to be credit-constrained. Our results suggest that conditional grants targeting university-based teacher training programs are effective in improving the selection of teachers.

The selection of political officials is under-studied in economic analysis of authoritarian politics. In the absence of elections, the autocracy alone is burdened with the task of selecting the right candidate for every political position. This paper tries to empirically investigate an authoritarian political selection market where a dictator “sells” potentially valuable political membership to eligible supporters who have to pay a “price” in terms of screening cost. We highlight one dilemma that many contemporary autocracies face, namely the need to recruit educated elites who usually have better options in the private sector and are less dependent on the regime. This paper argues that autocracies can minimize this challenge by actively screening for unobservable loyalty conditional on observed technical skills. Using micro-level Chinese Communist Party college recruitment data, we show that the party adopts a discriminative strategy of lowering (but not removing) the screening cost for high-ability students and more intensively screening for loyalty among low-ability students. Using brainwashing course scores as a measurement of loyalty provides suggestive evidence that party members of a given ability level have more loyalty than nonmembers at the same ability level. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Light-responsive materials with high adsorption capacity and sunlight-triggered regenerability are highly desired for their low-cost and environmentally friendly industrial separation processes. Here we report a poly(spiropyran acrylate) (PSP) functionalized metal–organic framework (MOF) as a sunlight-regenerable ion adsorbent for sustainable water desalination. Under dark conditions, the zwitterionic isomer quickly adsorbs multiple cations and anions from water within 30 minutes, with high ion adsorption loadings of up to 2.88 mmol g−1 of NaCl. With sunlight illumination, the neutral isomer rapidly releases these adsorbed salts within 4 minutes. Single-column desalination experiments demonstrated that PSP–MOF works efficiently for water desalination. A freshwater yield of 139.5 l kg−1 d−1 and a low energy consumption of 0.11 Wh l−1 would be reached for desalinating 2,233 ppm synthetic brackish water. Importantly, this adsorbent shows excellent stability and cycling performance. This work opens up a new direction for designing stimuli-responsive materials for energy-efficient and sustainable desalination and water purification.

Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC.

Herein we report the selectivity, stability, and electrochemical characterization of cobalt hexacyanoferrate, the Co–Fe Prussian Blue derivative (CoFePB), as a formate/formic acid oxidation electrocatalyst in aqueous media. CoFePB is able to quantitatively catalyze (100% Faradaic efficiency within less than 8% standard error at pH 5) the electrochemical oxidation of formate to CO2 over a pH range of 1–13. This quantitative formate elecrooxidation is possible due to the exclusive selectivity of the catalyst in a wide potential window (from ca. 1.2 to 1.7 V vs RHE), where no other substrate in aqueous conditions is activated: neither other organic molecules, such as alcohols or acids, nor water itself. CoFePB is one of the first heterogeneous noble-metal-free catalysts reported for the electrooxidation of small hydrocarbon molecules. Importantly, the catalyst showed a very high tolerance against surface poisoning during the reaction, as supported by the cyclic voltammetry and electrochemical impedance spectroscopy data, thereby allowing CoFePB to operate at greater current density than state-of-the-art noble metal catalysts. For example, we observed that CoFePB is able to achieve a formate oxidation current ∼10 mA cm–2 at pH 5, 0.4 M formate at 1.4 V vs RHE, whereas a Pt disk and Pd(5%)/C electrodes had currents of 0.4 and 1.4 mA cm–2, respectively, under identical conditions. The remarkable selectivity, stability, and high current density of CoFePB, in contrast to state-of-the-art catalysts based on platinum-group metals, is an important step in the search for inexpensive earth-abundant materials for oxidation of organic molecules for use in liquid fuel cells or for selective organic molecule sensors. Furthermore, because CoFePB is not poisoned by intermediates and can achieve higher current density than Pt or Pd, improvement of the catalyst onset potential can lead to higher power density formate oxidation fuel cells using earth-abundant metals than with Pt or Pd.

The Poisson's ratio and residual strain of ultra-thin films (<100 nm) are characterized using the phenomenon of transverse wrinkling in stretched bridges. The test methodology utilizes residual stress driven structures and easy to replicate clean-room fabrication and metrology techniques that can be seamlessly incorporated into a thin-film production assembly line. Freestanding rectangular ultra-thin film bridges are fabricated using dimensions that generate repeatable transverse wrinkling patterns. Numerical modeling based on the non-linear Koiter plate and shell energy formulation is conducted to correlate the Poisson's ratio and residual strain to the measured wrinkling deformation. Poisson's ratio affects the peak amplitudes without significantly changing the wavelength of the wrinkles. By contrast, the strain affects both the wavelength and amplitude. The proof of concept is demonstrated using 65 nm thick copper films. A Poisson's ratio of 0.34 ± 0.05 and a tensile residual strain of [Formula presented] are measured. The measured residual strain is in good agreement with the residual strain of [Formula presented] measured using alternate residual stress-driven test structures of the same films.

Li-Hong Han,1,2,* Yan-Yan Xue,1,* Yi-Cen Zheng,3 Xiao-Yan Li,1 Rong-Rong Lin,1 Zhi-Ying Wu,1 Qing-Qing Tao1 1Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Neurology, Second People’s Hospital of Luqiao District, Taizhou, People’s Republic of China; 3Department of Psychology, Tulane University School of Science and Engineering, New Orleans, LA, USA*These authors contributed equally to this workCorrespondence: Zhi-Ying Wu; Qing-Qing Tao Email zhiyingwu@zju.edu.cn; qingqingtao@zju.edu.cnObjective: Early-onset dementia (EOD) is a relatively uncommon form of dementia that afflicts people before age 65. Only a few studies analyzing the genetics of EOD have been performed in the Chinese Han population. Diagnosing EOD remains a challenge due to the diverse genetic and clinical heterogeneity of these diseases. The aim of this study was to investigate the genetic spectrum and clinical features of Chinese patients with EOD.Materials and Methods: A total of 49 EOD patients were recruited. Targeted next-generation (NGS) analyses were performed to screen for all of the known genes associated with dementia. Possible pathogenic variants were confirmed by performing Sanger sequencing. The genetic spectrum and clinical features of the EOD patients were analyzed.Results: Seven previously reported pathogenic variants (p.I213T and p.W165C in PSEN1; p.D678N in APP; c.1349_1352del in TBK1; p.P301L and p.R406W in MAPT; p.R110C in NOTCH3) and two novel variants of uncertain significance (p.P436L in PSEN2; c.239-11G>A in TARDBP) were identified.Conclusion: Our study demonstrated the genetic spectrum and clinical features of EOD patients, and it reveals that genetic testing of known causal genes in EOD patients can help to make a precise diagnosis.Keywords: Chi

Ling Peng,1,2 Li Han,2 Xiao-Ning Li,2 Ya-Fang Miao,2 Fei Xue,2 Chao Zhou1,3 1School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Respiratory Medicine, Zhoupu Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 3Department of Respiratory Medicine, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, Shanghai, People’s Republic of ChinaCorrespondence: Chao ZhouDepartment of Respiratory Medicine, Guangming Traditional Chinese Medicine Hospital of Pudong New Area, No. 339 DongMen Street. Pudong New District, Shanghai 201399, People’s Republic of ChinaTel +86-21-68019069Email zhou2000sh@163.comBackground: The differential diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with acute pulmonary embolism (APE) complications are difficult because of the variability of clinical presentations and the shortage of an unfailing screening biomarkers or instruments.Objective: Aimed to detect and compare the expression of serum microRNAs (miR-1233, miR-134) in AECOPD patients complicated with APE.Patients/Methods: Blood samples were collected from 52 AECOPD patients (13 patients with APE complications, 39 patients without APE) and 10 patients with stable COPD. Serum miRNAs expression was detected with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The levels of plasma D-dimers were determined by detection with an enzyme-linked immunosorbent assay (ELISA). The receiver-operator characteristic (ROC) curve was used for evaluating the diagnostic accuracy of the studied miRNAs.Results: According to the Wells score, 42 of the 52 AECOPD patients were unlikely to have APE (≤ 4 points), whereas the remaining 10 (> 4 points) were likely to have APE. There were 4 cases (4/13 30.8%) in the AECOPD combined with APE group with a Wells sco

Jianwen Wang, Xuehai Wang, Kai Liu, Li Gu, Lei Yu, Li Han, Zhaojin Meng Department of Otolaryngology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai 264200, Shandong, People’s Republic of ChinaCorrespondence: Xuehai WangDepartment of Otolaryngology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai 264200, Shandong, People’s Republic of ChinaEmail xuehai581@163.comIntroduction: Radiotherapy is one of the most important methods in the treatment of patients with hypopharyngeal squamous cell carcinoma (HSCC). However, radioresistance will be developed after repeated irradiation. Among many key factors contributing to radioresistance, enhanced autophagy is recognized as one of the most important. The ultraviolent irradiation resistance-associated gene (UVRAG) is reported to be a crucial gene involved in the process of autophagy. Here, we test whether UVRAG has effect on the radioresistance of HSCC.Methods: HSCC cell line Fadu cells were treated with irradiation to test levels of autophagy. Tumor tissues from primary and recurrent HSCC patients were tested by immunohistochemistry. Then, we knocked down UVRAG to test its role in cell growth and the malignant behaviors. Response of cells to treatment was examined using LDH release assay, immunofluorescence, Western blot analysis and colony formation.Results: We found that irradiation induced autophagy in Fadu cells. Immunohistochemistry of primary and irradiated HSCC tumor tissues showed that UVRAG was upregulated after irradiation treatment. Inhibiting UVRAG with siRNA interfered cell growth, cell cycle, malignant behaviors and autophagic flux in Fadu cells. Knocking down UVRAG increased DNA damage and cell death induced by irradiation. Finally, we found that inhibiting UVRAG induced lysosomal membrane permeabilization, which contributed to radiosensitization of Fadu cells.Conclusion: Our findings supported the oncogenic properties

Sha-Jie Dang,1,2,* Rui-Li Li,3,* Jun Wang,1 Wen-Bin Zeng,1 Yun He,1 Hui-Yu Yue,1 Si-Yuan Li,4 Li-Chun Han2,5 1Department of Anesthesia, Shaanxi Provincial Cancer Hospital, Xi’an, Shaanxi, People’s Republic of China; 2The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Anesthesia, The Second Affiliated Hospital of Xian Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 5Department of Anesthesia, Xi’an Daxing Hospital, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Chun HanDepartment of Anesthesia, Xi’an Daxing Hospital, Xi’an, Shaanxi 710016, People’s Republic of ChinaEmail hanlichun696@163.comSi-Yuan LiDepartment of Anesthesia, The Second Affiliated Hospital of Xian Jiaotong University, Xi’an, Shaanxi 710004, People’s Republic of ChinaEmail foxlsy@163.comBackground: This study aims to compare analgesic effect and side effects of oxycodone and sufentanil in transition analgesia and patient-controlled intravenous analgesia (PCIA) after gynecological tumor operation under general anesthesia.Patients and Methods: A prospective, randomized, double-blind research was conducted. Patients undergoing elective gynecological tumor surgery were randomized into four groups: Group S (sufentanil transition analgesia and sufentanil PCIA), Group OS (oxycodone transition analgesia and sufentanil PCIA), Group SO (sufentanil transition analgesia and oxycodone PCIA) and Group O (oxycodone transition analgesia and oxycodone PCIA). The primary outcomes were Numerical Rating S

Digitalization has transformed design radically in the past few decades. In the early 60's, architect Utzon had to struggle to find a feasible structural solution for the free-form curved surface that he designed for the Sydney Opera house. Four decades later, Frank Gehry could create very complex geometric models with ease. It is clear that the digital revolution is producing a similar revolution in design by providing new intellectual tools (Mitchell, 1999). Nevertheless, it is always a challenge for designers to learn and employ the new technologies to their practice. Two groups of people are involved in this revolution: the developers (software engineers) and the users (designers). The revolution cannot exist if either one is not participating. However, often a disconnection exists between them that may slow down the process.

Both an increase in osteoclast and a decrease in osteoblast numbers contribute to skeletal aging. Markers of cellular senescence, including expression of the cyclin inhibitor p16, increase with aging in several bone cell populations. The elimination of p16-expressing cells in old mice, using the INK-ATTAC transgene, increases bone mass indicating that senescent cells contribute to skeletal aging. However, the identity of the senescent cells and the extent to which ablation of p16-expressing cells may prevent skeletal aging remain unknown. Using mice expressing the p16-3MR transgene, we examined whether elimination of p16-expressing cells between 12 and 24 months of age could preserve bone mass; and whether elimination of these cells from 20 to 26 months of age could restore bone mass. The activation of the p16-3MR transgene by ganciclovir (GCV) greatly diminished p16 levels in the brain, liver, and osteoclast progenitors from the bone marrow. The age-related increase in osteoclastogenic potential of myeloid cells was also abrogated by GCV. However, GCV did not alter p16 levels in osteocytes-the most abundant cell type in bone-and had no effect on the skeletal aging of p16-3MR mice. These findings indicate that the p16-3MR transgene does not eliminate senescent osteocytes but it does eliminate senescent osteoclast progenitors and senescent cells in other tissues, as described previously. Elimination of senescent osteoclast progenitors, in and of itself, has no effect on the age-related loss of bone mass. Hence, other senescent cell types, such as osteocytes, must be the seminal culprits.