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Data Availability Statement: The data presented in this study are available upon request from the corresponding authors. Copyright © 2023 by the authors. Sensing the cloud movement information has always been a difficult problem in photovoltaic (PV) prediction. The information used by current PV prediction methods makes it challenging to accurately perceive cloud movements. The obstruction of the sun by clouds will lead to a significant decrease in actual PV power generation. The PV prediction network model cannot respond in time, resulting in a significant decrease in prediction accuracy. In order to overcome this problem, this paper develops a visual transformer model for PV prediction, in which the target PV sensor information and the surrounding PV sensor auxiliary information are used as input data. By using the auxiliary information of the surrounding PV sensors and the spatial location information, our model can sense the movement of the cloud in advance. The experimental results confirm the effectiveness and superiority of our model.

A precisely determined Geocenter motion contributes to the realization of the origin of reference frame. On the other hand, A precisely defined and accurate reference frame improvesthe understanding Geocenter motion. We can determine Geocenter motion from the GPS data of Low-Earth Orbit (LEO) satellites. We can also estimate the motion from the Satellite Laser Ranging (SLR) data. The separate Geocenter motion solutions from LEO GPS or SLR data have been studied. The solutions have good agreements. If the solutions came from LEO GPS and SLR data, what are the differences and impacts? Based on this motivation, we investigate the Geocenter motion determination from the combination of the GPS and SLR data. In this study, the combination approach and the results will be described and analyzed., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

The goal for the next generation of terrestrial reference frames (TRF) is to achieve a 1mm and 0.1mm/yr accurate frame realization through the combination of reference station solutions by multi-technique geodetic observatories (GOs), quality benchmarks which are motivated by the user needs from commercial and scientific disciplines that rely on high precision positioning and spatial referencing. A potentially significant source of error in TRF realizations is the inter-system ties between the instruments at multi-technique stations, usually independently measured through ground-based local surveys. In this work, a successful endeavor to satisfy the tie accuracy goals while exceeding the 200m GGOS baseline guidelines is detailed for the McDonald Geodetic Observatory (MGO), located in the Davis Mountains, Texas, USA.MGO consists of a VLBI Geodetic Observing System (VGOS), infrastructure in place for a Space Geodesy Satellite Laser Ranging (SGSLR) telescope, and several GNSS stations spanning a 900m baseline and a 120m elevation change. The results of the local ties between the GNSS stations across the near-kilometer baseline, as measured between their antenna reference points, show sub-mm precision and 1mm accuracy. These results are validated through day to day repeatability across several metrology surveys conducted in 2021 and sub-mm consistency in direct comparisons with baselines derived from GPS monthly averaged solutions. This presentation will report these results, highlighting the novel designs and techniques employed in the procedure, processing, and error-budget analysis. We present framework for assessment of sensitivities of future TRF realizations to ingesting ties of this quality, and present preliminary results., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Zhen Gong,1 Li Xia,1 Rune Xu,1 Min Luo,1 Hongxiang Deng,1 Zhiping Kang,1 Leping Liu,1 Yaqing Liu,1 Fangjie Zhang,2 Jian Shi1 1Department of Rheumatology, Yiyang Central Hospital, Yiyang, Hunan, People’s Republic of China; 2Department of Emergency Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Fangjie ZhangDepartment of Emergency Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of ChinaTel +86 15116256248Email zhangfj@csu.edu.cnJian ShiDepartment of Rheumatology, Yiyang Central Hospital, No. 118 Kangfu North Road, Yiyang, Hunan, 413000, People’s Republic of ChinaTel +86 18607371607Email 408739063@qq.comPurpose: The purpose of the study was to retrospectively analyze the effects of febuxostat combined with arthroscopic debridement of monosodium urate crystal deposition and febuxostat treatment alone on uric acid levels and acute flares in gout patients.Patients and Methods: We retrospectively analyzed gout patients who were treated from February 2016 to December 2020. Patients were divided into a control group (febuxostat treatment alone) or a combined group (febuxostat combined with arthroscopic surgery). We recorded and analyzed clinical data including age, sex, body mass index, comorbidities, lesion affected joints, acute flare times, medications history, febuxostat side effects, arthroscopic complications, and serum creatinine and uric acid levels changes.Results: There were 80 patients in the control group and 93 patients in the combined group. At the beginning of treatment, the combined group had significantly higher disease severity (higher serum uric acid levels and more acute gout flare times). Arthroscopy was performed in 61 knees and 38 ankles, and 86 joints showed crystals deposition. Compared with baseline, follow-up results showed that serum creatinine significantly decreased in the combined group, and serum uric acid and acute gout flare times significantly decreased in both groups (all p < 0.05). In the comparison between the two groups at the follow-up endpoint, acute gout flare times did not differ significantly (p > 0.05), however, serum creatinine and uric acid levels were lower in the combined group compared with those in the control group (ps < 0.05).Conclusion: Febuxostat combined with arthroscopic debridement of monosodium urate crystal deposition or tophi had a superior effect on lowering uric acid levels and acute flare times in gout patients than did febuxostat alone.Keywords: arthroscopy, febuxostat, crystal deposition, tophi, gout

This report describes the physics case, the resulting detector requirements, and the evolving detector concepts for the experimental program at the Electron-Ion Collider (EIC). The EIC will be a powerful new high-luminosity facility in the United States with the capability to collide high-energy electron beams with high-energy proton and ion beams, providing access to those regions in the nucleon and nuclei where their structure is dominated by gluons. Moreover, polarized beams in the EIC will give unprecedented access to the spatial and spin structure of the proton, neutron, and light ions. The studies leading to this document were commissioned and organized by the EIC User Group with the objective of advancing the state and detail of the physics program and developing detector concepts that meet the emerging requirements in preparation for the realization of the EIC. The effort aims to provide the basis for further development of concepts for experimental equipment best suited for the science needs, including the importance of two complementary detectors and interaction regions. This report consists of three volumes. Volume I is an executive summary of our findings and developed concepts. In Volume II we describe studies of a wide range of physics measurements and the emerging requirements on detector acceptance and performance. Volume III discusses general-purpose detector concepts and the underlying technologies to meet the physics requirements. These considerations will form the basis for a world-class experimental program that aims to increase our understanding of the fundamental structure of all visible matter, 902 pages, 415 authors, 151 institutions

Jia Wang, Yuyao Pei, Feng Yu, Zhen Kang, Yufen Zheng Department of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yufen ZhengDepartment of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Longmian Road No. 639, Nanjing, Jiangsu Province, People’s Republic of ChinaTel +86 13218080696Email cathy8521@hotmail.comPurpose: Diabetes mellitus (DM) has been known as a major chronic health problem in China. Suboptimal management of diabetic patients may incur serious complications, even death. The quality of post-hospital care has a good relationship with community pharmacists. However, data describing the current situation from care between community pharmacists and patients in China are lacking. Our article is to investigate community pharmacists’ activities, evaluate their attitudes towards providing diabetes care, assess their understandings, and identify perceived barriers.Methods: A survey divided into four parts was carried out randomly in China. The part of basic characteristics, understandings, and pharmacists’ perceived barriers was rated with a few listed choices scales, while the Likert scale was used to identify on the part of attitudes. Quantitative data were shown in frequency and valid percent. One-way analysis of variance (ANOVA) and non-parametric test conducted on data. A P-value ≤ 0.05 was considered statistically significant.Results: A total of 737 surveys were collected. The respondent pharmacists maintained a simply moderate understanding of diabetes care and the pharmaceutical services provided met basic needs rather than clinical ones, though they showed a good momentum towards providing better service. The respondent pharmacists considered patients lacking knowledge on self-management, shortage of funds as the main barriers.Conclusion: Efforts are supposed to make to expand pharmacists’ scope of practice, lessen patients’ reluctance, and create platforms for pharmacists receiving further education.Keywords: diabetes, community pharmacy, general practice, attitudes, barriers

Elastic stiffness is one of the most fundamental properties of materials. Design of the microstructures with isotropic stiffness has been an attractive area in the field of metamaterials for over three decades. Despite many classes of isotropic microstructures, exploring novel isotropic microstructures based on innovative mechanics principles has attracted great and continuing interests. This paper presents a novel family of isotropic hierarchical microstructures (Iso-HMs). These hierarchical microstructures are modeled by replacing the solid parts of prescribed single-level microstructures with arrayed microstructures in the second level, where the key task is to identify the correct geometries of the second-level microstructures by conducting parameter space exploring. These Iso-HMs realize isotropic stiffness based on synergistic deformations of the members in the two levels, which is essentially different from existing isotropic microstructures replying on deformations of the members in a single level. Two categories of Iso-HMs with rectangular holes and Vidergauze-type struts are designed. Considering the large size difference in the designed Iso-HMs, additive manufacturing becomes a unique technique for manufacturing the designed Iso-HMs, where the size ratio between the 3D-printed specimens and the minimal features reaches 400:1. Both numerical and experimental results validate the isotropic stiffness of the designed Iso-HMs. Furthermore, the results of a microstructural instability analysis show that the designed Iso-HMs can gain improved buckling strength up to a hundred times higher than their single-level counterparts. The hierarchical design provides a new way to identify novel functional microstructures for applications, and the hierarchical configurations expand the space of the already-known families of isotropic microstructures.

This report describes the physics case, the resulting detector requirements, and the evolving detector concepts for the experimental program at the Electron-Ion Col- lider (EIC). The EIC will be a powerful new high-luminosity facility in the United States with the capability to collide high-energy electron beams with high-energy proton and ion beams, providing access to those regions in the nucleon and nu- clei where their structure is dominated by gluons. Moreover, polarized beams in the EIC will give unprecedented access to the spatial and spin structure of the proton, neutron, and light ions. The studies leading to this document were com- missioned and organized by the EIC User Group with the objective of advancing the state and detail of the physics program and developing detector concepts that meet the emerging requirements in preparation for the realization of the EIC. The effort aims to provide the basis for further development of concepts for experimen- tal equipment best suited for the science needs, including the importance of two complementary detectors and interaction regions. This report consists of three volumes. Volume I is an executive summary of our findings and developed concepts. In Volume II we describe studies of a wide range of physics measurements and the emerging requirements on detector acceptance and performance. Volume III discusses general-purpose detector concepts and the underlying technologies to meet the physics requirements. These considerations will form the basis for a world-class experimental program that aims to increase our understanding of the fundamental structure of all visible matter.

Peipei Zhang,1,* Xiangde Min,1,* Zhaoyan Feng,1 Zhen Kang,1 Basen Li,1 Wei Cai,1 Chanyuan Fan,1 Xi Yin,1 Jinke Xie,1 Wenzhi Lv,2 Liang Wang1 1Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Artificial Intelligence, Julei Technology Company, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang WangDepartment of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Qiaokou, Wuhan 430030, People’s Republic of ChinaTel +86-27-83663737Email wang6@tjh.tjmu.edu.cnPurpose: To compare the performance of histogram analysis and intra-perinodular textural transition (Ipris) for distinguishing between benign and malignant testicular lesions.Patients and Methods: This retrospective study included 76 patients with 80 pathologically confirmed testicular lesions (55 malignant, 25 benign). All patients underwent preoperative T2-weighted imaging (T2WI) on a 3.0T MR scanner. All testicular lesions were manually segmented on axial T2WI, and histogram and Ipris features were extracted. Thirty enrolled patients were randomly selected to estimate the robustness of the features. We used intraclass correlation coefficients (ICCs) to evaluate intra- and interobserver agreement of features, independent t-test or Mann–Whitney U-test to compare features between benign and malignant lesions, and receiver operating characteristic curve analysis to evaluate the diagnostic performance of features.Results: Eighteen histogram features and forty-eight Ipris features were extracted from T2WI of each lesion. Most (60/66) histogram and Ipris features had good robustness (ICC of both intra- and interobserver variabilities > 0.6). Three histogram and nine Ipris features were significantly different between the benign and malignant groups. The area under the curve values for Energy, TotalEnergy, and Ipris_shell1_id_std were 0.807, 0.808, and 0.708, respectively, which were relatively higher than those of other features.Conclusion: Ipris features may be useful for identifying benign and malignant testicular tumors but have no significant advantage over conventional histogram features.Keywords: magnetic resonance imaging, testicular disease, Ipris, texture analysis

As urbanisation accelerates, the urban landscape reshapes at a fast pace. Consequently, the urban built environment continuously evolves horizontally as well as vertically. However, more attention in the field of spatial analysis is given to horizontal dynamics, despite the importance of geoinformation in the vertical dimension. 3D modelling methods have gained popularity due to their powerful capability of capturing and analysing geoinformation in the vertical dimension and visualising objects lifelike in the urban built environment. Various urban applications with diverse 3D modelling methods at different research scales and purposes have emerged. However, there is no systematic overview of these different modelling methods. Therefore, it is imperative to provide an up-to-date review of these advances. In this paper, we aim to review urban 3D modelling methods widely used in the prior 5-year period (2015–2020). Our analysis focuses on five attributes, i.e., basic characteristics, data requirements, technical requirements, users requirements and ethical considerations. The discussion presents the current status of 3D modelling methods – a wide range of applications yet with substantial development potential. This paper closes with insights for future work regarding the necessities of 3D data structure support as well as interdisciplinary research, specifically for big data management and integration.

This paper presents our contribution to the development of a standardized 3D input data model for solar photovoltaic potential estimation. Presently, different input data and processing steps influence the calculation for estimating the potential of solar energy in the Netherlands. The variety in characteristics of input data and issues with temporal accuracy extracted from the national registers and databases makes it challenging to obtain a consistent and reliable result. To address this issue, we created a point cloud dataset that integrated from LiDAR point cloud and dense image matching which is complete, recent and positionally accurate. Furthermore, we made a 3D building model from the integrated point cloud and identified the effect of finer resolution in the photovoltaic potential analysis.

The widespread emergence of digital firms has important implications for international business theory. In this paper, we argue that because of systematic cross-industry differences in the local ecosystems digital firms need to develop in foreign markets, they will face differential costs and challenges of what we term liability of ecosystem integration (LoEI). The nature of the LoEI differs from both traditional concepts of the liability of foreignness (LoF) and the liability of outsidership (LoO). Rather than reflecting the need to overcome economic or psychic distance by learning about the host country (as with LoF) or investing in relationship-specific knowledge (as with LoO), overcoming LoEI requires investments in catalysing the co-development of a local ecosystem involving users, complementors and institutional actors specific to each business. We show how the level of LoEI a firm faces depends on the characteristics of its industry and its business model along three dimensions: the level of integration with local users, complementors, and institutions. These characteristics impact both firm's success in internationalisation and the level of concentration in the global market.

Objectives: Model-based RSA (mbRSA) using EGS models to detect migration of femoral stems has only been validated using straight stem designs in neutral position [ref:3], [ref:4], [ref:5]. Aim of this study was to investigate if mbRSA-EGS could be affected by femoral stem [for full text, please go to the a.m. URL]

Point clouds serve as the raw material for various models, such as Building Information Models (BIM). In this work, we investigate the reconstruction steps needed to create models that can be utilized directly for agent-based simulations. The input data for the reconstruction is captured with an indoor mobile mapping system. To show the prominence of this idea, we run social distancing and evacuation simulations on the reconstructed models. The simulations are run with multiple agents using a vision-based pedestrian model and A∗-based path finding algorithm. The limitations of this approach are discussed. The video of the simulation is shared with the audience. Link to the video: https://youtu.be/r2D3IxXt7Ls

Trueperella pyogenes (T. pyogenes) can cause a variety of infections in animals and lead to economic loss in animal husbandry. TatD DNases are considered to be potential virulence factors in Plasmodium falciparum and Streptococcus pneumoniae. However, the function of TatD DNases in T. pyogenes is still unclear. Therefore, the aim of this study was to illustrate the function of TatD DNases of T. pyogenes (TpTatDs) and investigate whether luteolin is able to inhibit DNase function. The findings of our study are anticipated to be crucial to treating infections caused by T. pyogenes. Bioinformatic analysis has been used for the prediction of crucial functional residues of TpTatDs. The function of TpTatDs was investigated in the presence of divalent cations by hydrolyzing DNA with recombinant TatD proteins. Luteolin is a candidate nuclease inhibitor evaluated in our study. The interactions between luteolin and TpTatDs were tested using molecular docking analysis and surface plasmon resonance (SPR) assays. The inhibitory effect of luteolin on TpTatDs was analyzed by agarose gel electrophoresis. Two genes in the genome of T. pyogenes are suspected to encode TatD DNases. According to the length of their nucleotide sequences, they were named tatD960 and tatD825. Both of the TpTatDs, which are magnesium-dependent, were able to hydrolyze linear DNA and plasmids. In this study, we found through molecular docking analysis and SPR assays that luteolin can stably bind with TpTatDs. The gel assay revealed that luteolin can inhibit the DNase activity of TpTatDs. Our results indicated that TatD DNases from T. pyogenes are Mg2+-dependent DNases and exhibit DNA endonuclease activity. Moreover, luteolin reduced their DNA hydrolysis ability by decreasing the binding between TpTatDs and DNA.

Background Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization–World Health Organization– Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries. Methods Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019. Results Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p Conclusions There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.

© 2019 Alkaline pretreatment was demonstrated to be effective in the enhancement of hydrogen production. However, the sludge solubilization rate of alkaline pretreatment is still limited. This study reports a new strategy of K2FeO4 + pH 9.5 for sludge mesophilic anaerobic fermentation. Experimental results showed that the combination of K2FeO4/pH 9.5 pretreatment had a greater hydrogen yield than the individual K2FeO4 and pH 9.5. The maximum hydrogen yield was 19.2 mL per gram volatile suspended solids (VSS) under the optimal condition (0.02 g per gram total suspended solids K2FeO4 + pH 9.5). Kinetic analysis showed that the highest hydrogen production potential of 19.9 mL/g VSS was obtained in the combined reactor, which well fitted the first-order kinetic model (R2 = 0.9925). Besides, the fermentation type was mainly acetic and butyric in the combined reactor, which contributed to hydrogen production. Further analyses showed that the combined pretreatment reduced hydrogen sulfide yield, providing an environmentally friendly method to sludge treatment.

The hybrid personal cooling system (HPCS) consisted of ventilation fans and phase change materials (PCMs) covered with insulation pads is a promising wearable cooling system to mitigate heat strain and heat-related illnesses of occupational workers with heavy labor in hot environments. Effects of clothing characteristics (e.g., thermal resistance of insulation pads, latent heat and melting temperature of PCMs) on the thermal performance of the HPCS have been investigated in detail in our previous study. Apart from the aforementioned factors, environmental conditions, i.e., environmental temperature and relative humidity, also significantly affect the thermal performance of the HPCS. In this paper, a numerical parametric study was performed to investigate the effects of the environmental temperature and relative humidity (RH) on the thermal management of the HPCS. Five levels of air temperature under environmental RH=50% were chosen (i.e., 32, 34, 36, 38 and 40 ºC) to study the impact of environmental temperature on the HPCS’s cooling performance. In addition, four levels of environmental RH at ambient temperatures of 36 and 40 ºC were selected (i.e., 30, 50, 70 and 90%) to examine the effect of RH on cooling performance of the HPCS. Results show that high environmental temperatures could accelerate the PCM melting process and thereby weaken the cooling performance of HPCS. In the moderately hot environment (36 °C), the HPCS presented good cooling performance with the maximum core temperature at around 37.5 °C during excise when the ambient RH≤70%, whereas good cooling performance could be only seen under RH≤50% in the extremely hot environment (40 °C). Thus, it may be concluded that the maximum environmental RH for the HPCS exhibiting good cooling performance decreases with the increase in the environmental temperature.

Aberrant p62 overexpression has been implicated in breast cancer development. Here, we found that p62 expression was elevated in breast cancer stem cells (BCSCs), including CD44+CD24− fractions, mammospheres, ALDH1+ populations and side population cells. Indeed, short-hairpin RNA (shRNA)-mediated knockdown of p62 impaired breast cancer cells from self-renewing under anchorage-independent conditions, whereas ectopic overexpression of p62 enhanced the self-renewal ability of breast cancer cells in vitro. Genetic depletion of p62 robustly inhibited tumor-initiating frequencies, as well as growth rates of BCSC-derived tumor xenografts in immunodeficient mice. Consistently, immunohistochemical analysis of clinical breast tumor tissues showed that high p62 expression levels were linked to poorer clinical outcome. Further gene expression profiling analysis revealed that p62 was positively correlated with MYC expression level, which mediated the function of p62 in promoting breast cancer stem-like properties. MYC mRNA level was reduced upon p62 deletion by siRNA and increased with p62 overexpression in breast cancer cells, suggesting that p62 positively regulated MYC mRNA. Interestingly, p62 did not transactivate MYC promoter. Instead, p62 delayed the degradation of MYC mRNA by repressing the expression of let-7a and let-7b, thus promoting MYC mRNA stabilization at the post-transcriptional level. Consistently, let-7a and let-7b mimics attenuated p62-mediated MYC mRNA stabilization. Together, these findings unveiled a previously unappreciated role of p62 in the regulation of BCSCs, assigning p62 as a promising therapeutic target for breast cancer treatments.

Despite recent progress in the development of methods for automated reconstruction of indoor models, a comparative performance evaluation of these methods is not available due to the lack of publicly available benchmark datasets and a common evaluation framework. The ISPRS Benchmark on Indoor Modelling is an effort to enable comparison and benchmarking of indoor modelling methods by providing a benchmark dataset and a comprehensive evaluation framework. In this paper, we propose a framework for the evaluation of indoor modelling methods, and discuss various quality aspects of the reconstruction methods as well as the reconstructed models. We discuss the challenges in quantitative quality evaluation of indoor models through comparison with a reference model, and propose suitable measures and methods for comparing an automatically reconstructed indoor model with a reference.

The plant growth promoting rhizobacteria (PGPR) and plant growth regulators (PGRs) can be applied to improve the growth and productivity of plants, with potential to be used for genetic improvement of drought tolerance. However, for genetic improvement to be achieved, a solid understanding of the physiological and biochemical changes in plants induced by PGPR and PGR is required. The present study was carried out to investigate the role of PGPR and PGRs on the physiology and biochemical changes in chickpea grown under drought stress conditions and their association with drought tolerance. The PGPR, isolated from the rhizosphere of chickpea, were characterized on the basis of colony morphology and biochemical characters. They were also screened for the production of indole-3-acetic acid (IAA), hydrogen cyanide (HCN), ammonia (NH3), and exopolysaccharides (EPS) production. The isolated PGPR strains, named P1, P2, and P3, were identified by 16S-rRNA gene sequencing as Bacillus subtilis, Bacillus thuringiensis, and Bacillus megaterium, respectively. The seeds of two chickpea varieties, Punjab Noor-2009 (drought sensitive) and 93127 (drought tolerant) were soaked for 2–3 h prior to sowing in 24 h old cultures of isolates. The salicylic acid (SA) and putrescine (Put) were sprayed (150 mg/L) on 25 day old chickpea seedlings. The results showed that chickpea plants treated with a consortium of PGPR and PGRs significantly enhanced the chlorophyll, protein, and sugar contents compared to irrigated and drought conditions. Leaf proline content, lipid peroxidation, and activities of antioxidant enzymes (CAT, APOX, POD, and SOD) all increased in response to drought stress but decreased due to the PGPR and PGRs treatment. An ultrahigh performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) analysis was carried out for metabolic profiling of chickpea leaves planted under controlled (well-irrigated), drought, and consortium (drought plus PGPR and PGRs) conditions. Proline, L-arginine, L-histidine, L-isoleucine, and tryptophan were accumulated in the leaves of chickpea exposed to drought stress. Consortium of PGPR and PGRs induced significant accumulation of riboflavin, L-asparagine, aspartate, glycerol, nicotinamide, and 3-hydroxy-3-methyglutarate in the leaves of chickpea. The drought sensitive chickpea variety showed significant accumulation of nicotinamide and 4-hydroxy-methylglycine in PGPR and PGR treated plants at both time points (44 and 60 days) as compared to non-inoculated drought plants. Additionally, arginine accumulation was also enhanced in the leaves of the sensitive variety under drought conditions. Metabolic changes as a result of drought and consortium conditions highlighted pools of metabolites that affect the metabolic and physiological adjustments in chickpea that reduce drought impacts.

Predictions for cold nuclear matter effects on charged hadrons, identified light hadrons, quarkonium and heavy flavor hadrons, Drell-Yan dileptons, jets, photons, gauge bosons and top quarks produced in $p+$Pb collisions at $\sqrt{s_{_{NN}}} = 8.16$ TeV are compiled and, where possible, compared to each other. Predictions of the normalized ratios of $p+$Pb to $p+p$ cross sections are also presented for most of the observables, providing new insights into the expected role of cold nuclear matter effects. In particular, the role of nuclear parton distribution functions on particle production can now be probed over a wider range of phase space than ever before., 84 pages, 44 figures, version accepted for publication in Nuclear Physics A

© 2016 The American Phytopathological Society. In Arabidopsis, NPR1 is a key transcriptional coregulator of systemic acquired resistance. Upon pathogen challenge, NPR1 translocates from the cytoplasm to the nucleus, in which it interacts with TGA-bZIP transcription factors to activate the expression of several pathogenesis-related (PR) genes. In a screen of a yeast two-hybrid library from wheat leaves infected with Puccinia striiformis f. sp. tritici, we identified a conserved rust protein that interacts with wheat NPR1 and named it PNPi (for Puccinia NPR1 interactor). PNPi interacts with the NPR1/NIM1-like domain of NPR1 via its C-terminal DPBB-1 domain. Using bimolecular fluorescence complementation assays, we detected the interaction between PNPi and wheat NPR1 in the nucleus of Nicotiana benthamiana protoplasts. A yeast three-hybrid assay showed that PNPi interaction with NPR1 competes with the interaction between wheat NPR1 and TGA2.2. In barley transgenic lines overexpressing PNPi, we observed reduced induction of multiple PR genes in the region adjacent to Pseudomonas syringae pv. tomato DC3000 infection. Based on these results, we hypothesize that PNPi has a role in manipulating wheat defense response via its interactions with NPR1.

FLT1 and its soluble form (sFLT1) arise as alternate transcripts from the same gene and sFLT1 can antagonize the effect of vascular endothelial growth factor (VEGF) on its cognate receptors. We investigated the effect of VEGF and protein kinase C (PKC) activation on sFLT1 abundance. We demonstrated that VEGF stimulates sFLT1 and FLT1 mRNA and protein levels in vascular endothelial cells via VEGFR2 and PKC. Using an FLT1 expression vector with N and C-terminal epitope tags, we show that PKC activation increases the cleavage of FLT1 into an N-terminal extracellular fragment and a C-terminal intracellular fragment with the cleavage occurring adjacent to the transmembrane domain. The trafficking and glycosylation inhibitors brefeldin, monensin and tunicamycin substantially reduced cleavage and release of the N-terminal ectodomain of FLT1 and inhibited secretion of the isoforms of sFLT1. The shed FLT1 ectodomain can bind VEGF and PlGF and inhibit VEGF-induced vascular tube formation thus confirming that it is functionally equivalent to the alternately spliced and secreted sFLT1 isoforms.

The ability to design biomaterials that interact with biological environments in a predictable manner necessitates an improved understanding of how surface chemistry influences events such as protein adsorption and cell adhesion. In this work, we examined mechanisms governing the interactions between 3T3 fibroblasts and nylon-3 polymers, which have a protein-like polyamide backbone and are highly amenable to tuning of chemical and physical properties. Protein adsorption and cell adhesion to a library of nylon-3 polymers were characterized and analyzed by partial least squares regression. This analysis revealed that specific chemical features of the nylon-3 polymers correlated with the extent of protein adsorption, which, in turn, correlated with cell adhesion in a serum-containing environment. In contrast, in a serum-free environment, cell adhesion could be predicted solely from chemical properties. Enzymatic treatments of 3T3 cells prior to plating indicated that proteins bound to the cell surface mediated cell-nylon-3 polymer interactions under serum-free conditions, with additional analysis suggesting that cell-associated fibronectin played a dominant role in adhesion in the absence of serum. The mechanistic insight gained from these studies can be used to inform the design of new polymer structures in addition to providing a basis for continued development of nylon-3 copolymers for tissue engineering applications.

Identifying the optimal treatment strategy for cancer is an important challenge, particularly for complex diseases like epithelial ovarian cancer (EOC) that are prone to recurrence. In this study we developed a quantitative, multivariate model to predict the extent of ovarian cancer cell death following treatment with an ErbB inhibitor (canertinib, CI-1033). A partial least squares regression model related the levels of ErbB receptors and ligands at the time of treatment to sensitivity to CI-1033. In this way, the model mimics the clinical problem by incorporating only information that would be available at the time of drug treatment. The full model was able to fit the training set data and was predictive. Model analysis demonstrated the importance of including both ligand and receptor levels in this approach, consistent with reports of the role of ErbB autocrine loops in EOC. A reduced multi-protein model was able to predict CI-1033 sensitivity of six distinct EOC cell lines derived from the three subtypes of EOC, suggesting that quantitatively characterizing the ErbB network could be used to broadly predict EOC response to CI-1033. Ultimately, this systems biology approach examining multiple proteins has the potential to uncover multivariate functions to identify subsets of tumors that are most likely to respond to a targeted therapy.

The vascular endothelial growth factor receptor, Flt1 is a transmembrane receptor co-expressed with an alternate transcript encoding a secreted form, sFlt1, that functions as a competitive inhibitor of Flt1. Despite shared transcription start sites and upstream regulatory elements, sFlt1 is in far greater excess of Flt1 in the human placenta. Phorbol myristic acid and dimethyloxalylglycine differentially stimulate sFlt1 compared to Flt1 expression in vascular endothelial cells and in cytotrophoblasts. An FLT1 minigene construct containing exon 13, 14 and the intervening region, recapitulates mRNA processing when transfected into COS-7, with chimeric intronic sFlt1 transcripts arising by intronic polyadenylation and other Flt1/sFlt1 transcripts by alternate splicing. Inclusion of exon 15 but not 14 had a modest stimulatory effect on the abundance of sFlt1. The intronic region containing the distal poly(A) signal sequences, when transferred to a heterologous minigene construct, inhibited splicing but only when cloned in sense orientation, consistent with the presence of a directional cis-element. Serial deletional and targeted mutational analysis of cis-elements within intron 13 identified intronic poly(A) signal sequences and adjacent cis-elements as the principal determinants of the relative ratio of intronic sFlt1 and spliced Flt1. We conclude that intronic signals reciprocally regulate splicing and polyadenylation and control sFlt1 expression.

Context: Recent published studies indicate a possible role for sFlt1 in the development of preeclampsia. Objective: The objective of the study was to investigate the expression and regulation of sFlt1-e15a, a recently described novel C-terminal variant isoform of sFlt1. Design: The studies included a computational comparative analysis of the genomic locus of sFlt1 across vertebrate species; an assessment of sFlt1 variants in human and rhesus cells and tissues; an analysis of sFlt1 variants transiently expressed in HeLa and COS-7 cells; an evaluation of the effect of hypoxia on sFlt1 expression in trophoblasts; and a comparison of placental sFlt1 expression between pregnancies complicated by preeclampsia and control pregnancies. Result and Conclusions: sFlt1-e15a emerged as an alternate transcript of Flt1 late in evolution with the insertion of an AluSq sequence into the primate genome after the emergence of the simian infraorder about 40 million years ago. sFlt1-e15a is particularly abundant in human plac...

The gene FLT1 produces at least two transcripts from a common transcription start site: full-length Flt1 contains 30 exons encoding a membrane-bound VEGF receptor; soluble Flt1 (sFlt1) shares the f...

A microcalorimetric technique based on the metabolic heat production from cultured cells was used to investigate the effect of kanamycin on the growth and metabolism of recombinant Escherichia coli. Power-time curves of growing recombinant Escherichia coli cell suspensions treated with different kanamycin doses were recorded and were described very accurately by the generalized logistic equation. The rate constant (k) is kanamycin concentration-dependent and the relationship between k and C (kanamycin dose) is nearly linear. The 50% inhibitory concentration IC50 was 88.49 µg/mL. The experimental results revealed that high doses of kanamycin inhibited the growth of recombinant E. coli during the log phase and promoted growth during the stationary phase. These results are important for deciding the optimum kanamycin dose for the maximal synthesis of human-like collagen.

In lung and collecting duct epithelia, glucocorticoid (GC)-stimulated Na+transport is preceded by an increase in the protein kinase sgk1, which in turn regulates the activity of the epithelial Na+channel (ENaC). We investigated the mechanism for GC-regulated human sgk1 expression in lung and renal epithelia. sgk1 mRNA was increased in these epithelia by GCs, and this was inhibited by actinomycin D and superinduced by cycloheximide, consistent with a transcriptional effect that did not require protein synthesis. To understand the basis for transcriptional regulation, the transcription initiation site was mapped and the 5′-flanking region cloned by PCR. A 3-kb fragment of the upstream region was coupled to luciferase and transfected into A549 cells. By deletion analysis, an imperfect GC response element (GRE) was identified that was necessary and sufficient for GC responsiveness. When tested with cell extracts, a specific protein recognized by an anti-GC receptor (GR) antibody bound the GRE in gel mobility shift assays. We conclude that GCs stimulate sgk1 expression in human epithelial cells via activation of a GRE in the 5′-flanking region of sgk1.

Metamaterials usually refer to artificial composite materials consisting of an array of periodically arranged microstructures, engineered to provide unusual material properties that may not be easily found in nature. This paper proposes a new topological shape optimization method for systematic computational design of a type of mechanical metamaterials with negative Poisson's ratios (auxetic materials), which integrates the numerical homogenization approach into a powerful parametric level set method (PLSM). The homogenization method is used to obtain the effective properties of the periodic microstructure, while the PLSM is applied to achieve shape evolutions and topological changes of the microstructure, until the desired material properties are achieved. The key concept of the PLSM is the interpolation of the implicit level set surface by using a given set of compactly supported radial basis functions (CSRBF), which are positioned at a number of given and fixed knots inside the design domain. Several typical numerical examples are used to demonstrate the favorable characteristics of the proposed method in the design of micro-structured metamaterials. © 2014 Elsevier B.V. All rights reserved.

Flt is one of the cell surface VEGF receptors which can be cleaved to release an N-terminal extracellular fragment which, like alternately transcribed soluble Flt1 (sFlt1), can antagonize the effects of VEGF. In HUVEC and in HEK293 cells where Flt1 was expressed, metalloprotease inhibitors reduced Flt1 N-terminal cleavage. Overexpression of ADAM10 and ADAM17 increased cleavage while knockdown of ADAM10 and ADAM17 reduced N-terminal cleavage suggesting that these metalloproteases were responsible for Flt1 cleavage. Protein kinase C (PKC) activation increased the abundance and the cleavage of Flt1 but this did not require any residues within the intracellular portion of Flt1. ALLN, a proteasomal inhibitor, increased the abundance of Flt1 which was additive to the effect of PKC. Removal of the entire cytosolic region of Flt1 appeared to stimulate cleavage of Flt1 and Flt1 was no longer sensitive to ALLN suggesting that the cytosolic region contained a degradation domain. Knock down of c-CBL, a ring finger ubiquitin ligase, in HEK293 cells increased the expression of Flt1 although it did not appear to require a previously published tyrosine residue (1333Y) in the C-terminus of Flt1. Increasing VEGFR2 expression increased VEGF-stimulated sFlt1 expression and progressively reduced the cleavage of Flt1 with Flt1 staying bound to VEGFR2 as a heterodimer. Our results imply that secreted sFlt1 and cleaved Flt1 will tend to have local effects as a VEGF antagonist when released from cells expressing VEGFR2 and more distant effects when released from cells lacking VEGFR2.

For the purpose of achieving high-resolution optimal solutions this paper proposes a nodal design variable-based adaptive method for topology optimization of continuum structures. The analysis mesh-independent density field, interpolated by the nodal design variables at a given set of density points, is adaptively refined/coarsened according to a criterion regarding the gray-scale measure of local regions. New density points are added into the gray regions and redundant ones are removed from the regions occupied by purely solid/void phases for decreasing the number of design variables. A penalization factor adaptivity technique is employed to prevent premature convergence of the optimization iterations. Such an adaptive scheme not only improves the structural boundary description quality, but also allows for sufficient further topological evolution of the structural layout in higher adaptivity levels and thus essentially enables high-resolution solutions. Moreover, compared with the case with uniformly and finely distributed density points, the proposed adaptive method can achieve a higher numerical efficiency of the optimization process. © 2013 The Chinese Society of Theoretical and Applied Mechanics; Institute of Mechanics, Chinese Academy of Sciences and Springer-Verlag Berlin Heidelberg.

Sgk1 is a relatively unstable kinase that regulates epithelial Na+transport in the distal nephron of the kidney. We identified a 5′ variant alternate transcript of human Sgk1 (Sgk1_v3) that is expressed in the connecting tubule and collecting duct, is regulated by aldosterone and insulin, and is predicted to encode an NH2-terminal variant Sgk1 isoform, Sgk1_i3. Sgk1_i3 contains a polybasic motif, KKR, in its NH2terminus that regulates ubiquitination and stability of the expressed protein in HEK293 cells. In Fisher rat thyroid, and mpkCCDc14cells, Sgk1_i3 had a significantly greater effect on Na+transport compared with Sgk1 and its stimulatory effect was dependent on the kinase domain. Sgk1_i3 increased the abundance of cleaved epithelial Na+channel (ENaC) subunits at the cell surface, which was inhibited by coexpression of Nedd4–2. Together, the data demonstrate that a renally expressed Sgk1 isoform, Sgk1_i3, shows improved stability, is regulated by insulin and aldosterone, and stimulates ENaC activity when heterologously expressed in collecting duct cells.

This report is based on a ten-week program on "Gluons and the quark sea at high-energies", which took place at the Institute for Nuclear Theory in Seattle in Fall 2010. The principal aim of the program was to develop and sharpen the science case for an Electron-Ion Collider (EIC), a facility that will be able to collide electrons and positrons with polarized protons and with light to heavy nuclei at high energies, offering unprecedented possibilities for in-depth studies of quantum chromodynamics. This report is organized around four major themes: i) the spin and flavor structure of the proton, ii) three-dimensional structure of nucleons and nuclei in momentum and configuration space, iii) QCD matter in nuclei, and iv) Electroweak physics and the search for physics beyond the Standard Model. Beginning with an executive summary, the report contains tables of key measurements, chapter overviews for each of the major scientific themes, and detailed individual contributions on various aspects of the scientific opportunities presented by an EIC.

Many techniques exist to reconstruct New Physics masses from LHC data, though these tend to either require high luminosity O(100) fb^-1, or an accurate measurement of missing transverse energy (MET) which may not be available in the early running of the LHC. Since in popular models such as SUSY a fairly sharp, triangular dilepton invariant mass spectrum can emerge already at low luminosity O(1) fb^-1, a Decay Kinematics (DK) technique can be used on events near the dilepton mass endpoint to estimate squark, slepton, and neutralino masses without relying on MET. With the first 2 fb^-1 of 7 TeV LHC data SPS1a masses can thus be found to 20% or better accuracy, at least several times better than what has been taken to be achievable., Comment: 4 pages, 3 figures

Much attention is paid to registration of terrestrial point clouds nowadays. Research is carried out towards improved efficiency and automation of the registration process. This paper reports a new approach for point clouds registration utilizing reflectance panoramic images. The approach follows a two-step procedure: pair-wise registration and global registrations. The pair-wise registration consists of image matching (pixel-to-pixel registration) and point clouds registration (point-to-point correspondence), provided the correspondence between image and point cloud (pixel-to-point) is known. The image matching process delivers corresponding points within the overlapping area of two images. These points are matched to their 3D equivalent points within the point clouds. False accepted correspondences are successfully removed by a geometric invariance check. An iterative least-square adjustment completes the pair wise registration. The global registration on all point clouds is obtained by a bundle adjustment using circularly self-closure constraint. The approach is tested with several data sets (indoor and outdoor scenes) acquired by the laser scanner FARO LS 880.

This writeup is a compilation of the predictions for the forthcoming Heavy Ion Program at the Large Hadron Collider, as presented at the CERN Theory Institute 'Heavy Ion Collisions at the LHC - Last Call for Predictions', held from May 14th to June 10th 2007.

The gene FLT1 produces at least two transcripts from a common transcription start site: full-length Flt1 contains 30 exons encoding a membrane-bound VEGF receptor; soluble Flt1 (sFlt1) shares the first 13 exons but utilizes poly(A) signal sequences within intron 13 to create a transcript that lacks downstream exons. To address the mechanisms that regulate human sFlt1, we mapped the 3' end of sFlt1 mRNA and defined the full extent of its 3' untranslated region (UTR). We identified a 3.2 Kb sFlt1 transcript that is cleaved within an alternatively spliced exon downstream of exon 14 and is predicted to encode a C-terminal variant of sFlt1 with an unusual polyserine tail. sFlt1 mRNA cleavage sites within intron 13 were identified in human placenta and in vascular endothelium by ribonuclease protection assay (RPA). A proximal and two distal mRNA cleavage sites were identified by RPA downstream of consensus polyadenylation signals that create variant transcripts with a 3' UTR ranging from 30 bases to approximately 4 Kb. Northern blot analysis and 3' rapid amplification of cDNA ends (RACE) in placenta confirmed the existence of distal intronic sFlt1 cleavage sites that give rise to a sFlt1 transcript of approximately 7 Kb. The identity of the distal signal sequences were then confirmed by mutagenesis of putative signal elements in a polyadenylation reporter assay. We demonstrate the heterogeneity of human sFlt1 that arises from alternate splicing and from alternative polyadenylation directed by strong intronic poly(A) signal sequences leading to C-terminal variants and to an sFlt1 transcript with a large 3' UTR containing several AU rich elements and poly(U) regions that may regulate mRNA stability.

Medroxyprogesterone acetate (MPA), a widely used synthetic progestational contraceptive, occasionally leads to Cushingoid side effects such as hypertension, fluid retention, and centripetal obesity. We investigated the effect of MPA on classic mineralocorticoid target genes, alpha-epithelial Na channel (ENaC) and sgk1, in the collecting duct. In adrenalectomized mice, aldosterone, dexamethasone, and MPA increased alpha-ENaC mRNA levels in kidney cortex. MPA and dexamethasone, but not progesterone, dose dependently increased alpha-ENaC and sgk1 mRNA in M-1 and in Madin-Darby canine kidney-C7 cells, both collecting duct cell lines. The stimulatory effect of MPA and dexamethasone on alpha-ENaC expression was inhibited by RU-38486, a combined glucocorticoid receptor (GR) and progesterone receptor (PR) antagonist, but not by Org31710, a pure PR antagonist. MPA and dexamethasone dose dependently increased alpha-ENaC promoter-driven luciferase activity in M-1 cells, which was not inhibited by Org31710, indicating that MPA regulates alpha-ENaC in a PR-independent manner. When tested in HT29 cells, MPA could only stimulate alpha-ENaC-driven reporter activity when GR was coexpressed, confirming the requirement for functional GR in the transcriptional effect of MPA. The activation of steroid receptors such as GR can explain the apparent glucocorticoid effects of MPA, independent of PR activation.

VIT32, a vasopressin-induced transcript, inhibits Na+ transport when coexpressed with the epithelial sodium channel in Xenopus laevis oocytes ( EMBO J 21: 5109–5117, 2002). To understand the mechanism of VIT32 gene regulation, we examined the effect of DDAVP and cAMP stimulation on VIT32 expression in M-1 mouse collecting duct cells and in H441 human airway epithelial cells. Elevation of cAMP with forskolin and IBMX increased VIT32 gene expression with a peak effect at 2 h. The increase in gene expression was abolished by H89 and by actinomycin D, suggesting that cAMP stimulates VIT32 mRNA expression by a PKA-mediated increase in gene transcription. An ∼1.5-kb fragment of the 5′-flanking region of VIT32 was cloned and was able to confer cAMP-stimulated reporter gene activity when transfected into M-1 and H441 cells. By deletion analysis and site-directed mutagenesis, a cAMP response element (CRE) was identified within the proximal promoter region that was sufficient to account for the increase in VIT32 gene expression seen with DDAVP and elevation of cAMP. Furthermore, DDAVP-stimulated VIT32 promoter-reporter activity was inhibited by H89 and by a dominant negative CREB construct. Finally, we were able to identify CREB as a nuclear protein that bound to the VIT32 CRE in gel mobility shift assays. In summary, DDAVP stimulates transcription of VIT32 via a CRE within the proximal promoter region of the VIT32 gene.

Aldosterone and glucocorticoids (GCs) stimulate Na+reabsorption in the collecting ducts by increasing the activity of the epithelial Na+channel (ENaC). Our laboratory has used Madin-Darby canine kidney-C7 cells to demonstrate that this effect is associated with an increase in α-ENaC gene transcription (Mick VE, Itani OA, Loftus RW, Husted RF, Schmidt TJ, and Thomas CP, Mol Endocrinol 15: 575–588, 2001). Cycloheximide (CHX) superinduced the GC-stimulated α-ENaC expression in a dose-dependent manner, but had no effect on basal or aldosterone-stimulated α-ENaC expression, whereas anisomycin inhibited basal and corticosteroid-stimulated α-ENaC expression. The superinduction of α-ENaC expression was also seen with hypotonicity, was blocked by RU-38486, and was independent of protein synthesis. CHX had no effect on α-ENaC mRNA half-life, confirming that its effect was via an increase in α-ENaC transcription. The effect of CHX and hypotonicity on α-ENaC expression was abolished by SB-202190, indicating an effect mediated via p38 MAPK. Consistent with this scheme, CHX increased pp38 and MKK6, an upstream activator of p38, stimulated α-ENaC promoter activity. These data confirm a model in which CHX activates p38 in Madin-Darby canine kidney-C7 cells to increase α-ENaC gene transcription in a GC-dependent manner.

Systemic pseudohypoaldosteronism type I (PHAI) is an autosomal recessive disorder that arises from loss of function mutations of the alpha, beta, or gamma subunit of Epithelial Na(+) Channel (ENaC). In addition to a severe renal phenotype in the neonatal period, patients with PHAI develop a childhood pulmonary syndrome characterized by cough and frequent respiratory infections. We tested a patient, born to consanguineous parents, who presented with dehydration, metabolic acidosis, hyperkalemia, elevated renin and aldosterone levels at birth, and recurrent respiratory symptoms in his first year. He demonstrated defective epithelial Na(+) transport in multiple organs (raised sweat Cl(-), 120 mM; raised salivary Na(+) and Cl(-), 118 and 111 mM, respectively; and little nasal amiloride-sensitive potential difference). No deleterious mutation was identified in the coding region of the three ENaC subunits. Reverse transcriptase-polymerase chain reaction of nasal epithelial RNA showed reduced betaENaC expression, and inability to amplify promoter elements indicated the possibility of a deletion in the 5' region. Using a probe that corresponded to exon 1A of betaENaC, we confirmed a large deletion (1,300 bp). In summary, a homozygous mutation in the promoter region of betaENaC leads to PHAI, the first description of a mutation in the regulatory regions of an ENaC subunit leading to a clinical phenotype.