bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental comparison of energy landscape features of ubiquitin family proteins
Authors: Nandi Tathagata , Yadav Anju , Ainavarapu Sri Rama Koti 
Published: October 2019

AbstractSmall ubiquitin‐related modifiers (SUMO1 and SUMO2) are ubiquitin family proteins, structurally similar to ubiquitin, differing in terms of their amino acid sequence and functions. Therefore, they provide a great platform for investigating sequence‐structure‐stability‐function relationship. Here, we used chemical denaturation in comparing the folding‐unfolding pathways of the SUMO proteins with their structural homologue ubiquitin (UF45W‐pseudo wild‐type [WT] tryptophan variant) with structurally analogous tryptophan mutations (SUMO1 [S1F66W], SUMO2 [S2F62W]). Equilibrium denaturation studies report that ubiquitin is the most stable protein among the three. The observed denaturant‐dependent folding rates of SUMOs are much lower than ubiquitin and primarily exhibit a two‐state folding pathway unlike ubiquitin, which has a kinetic folding intermediate. We hypothesize that, as SUMO proteins start off as slow folders, they avoid stabilizing their folding intermediates and the presence of which might further slow‐down their folding rates. The denaturant‐dependent unfolding of ubiquitin is the fastest, followed by SUMO2, and slowest for SUMO1. However, the spontaneous unfolding rate constant is the lowest for ubiquitin (~40 times), and similar for SUMOs. This correlation between thermodynamic stability and kinetic stability is achieved by having different unfolding transition state positions with respect to the solvent‐accessible surface area, as quantified by the Tanford β
u values: ubiquitin (0.42) > SUMO2 (0.20) > SUMO1 (0.16). The results presented here highlight the unique energy landscape features which help in optimizing the folding‐unfolding rates within a structurally homologous protein family.
Environmental impacts on the flux of mass through deep convection
Authors: Storer Rachel L. , Posselt Derek J. 
Published: October 2019

AbstractThough deep convective clouds are important to numerous aspects of the climate system, they remain a source of much uncertainty. The varying large‐scale dynamics, relatively short development time, range of spatial scales, and complex microphysics involved in deep convection lead to difficulty in both observation of these clouds and modelling their impacts on larger spatial and longer temporal scales. This study utilizes an ensemble of high‐resolution cloud‐resolving simulations of deep convection forming in a spectrum of different environments to explore the sensitivity of deep convection, and in particular convective mass flux to changes in the initial conditions. We find that convection strength is strongly sensitive to small perturbations in the environment, specifically the convective available potential energy (CAPE) and boundary‐layer humidity. That storm effects on the environment, such as mass transport and tropospheric moistening through detrainment, are sensitive to these initial conditions points to the importance of better representing such parameters in global models.
Mesoscale precipitation systems and their role in the rapid development of a monsoon depression over the Bay of Bengal
Authors: Fujinami Hatsuki , Hirata Hidetaka , Kato Masaya , Tsuboki Kazuhisa 
Published: October 2019

AbstractThe structure of mesoscale precipitation within monsoon depressions is still not as well‐known as the synoptic‐scale composite cloud and precipitation structure. Here, using observational data from multi‐satellite sensors and a cloud‐resolving regional model, we investigate the three‐dimensional structure of mesoscale precipitation systems in the different stages of the life cycle of a monsoon depression. Effects of latent heating from the precipitation systems and the Bay of Bengal (BoB) on the development of the monsoon depression are also evaluated in sensitivity experiments with the model. A typical monsoon depression developed on 17 August 2016 over the BoB. In the rapid development phase, satellite observations reveal mesoscale convective systems with deep convective precipitation cells and stratiform precipitation near the head of the BoB. Extremely deep and intense convective cells appear along a ring‐like rain band when a closed cyclonic circulation becomes obvious around the northernmost part of the BoB. The deep convection appears frequently, particularly along the western‐to‐southwestern side of the low, a convergence‐prone area between northerlies with air masses of large convective available potential energy (CAPE) that makes up the western–southwestern part of the closed cyclonic circulation, and strong monsoon westerlies with relatively stable air masses to the south of the low. Sensitivity experiments reveal that both cloud/precipitation processes and evaporation from the BoB are essential for the rapid development of the monsoon depression over the BoB. Evaporation from the BoB adds a large amount of moisture to the atmospheric boundary layer near the low. Southwesterlies and southerlies on the eastern side of the low draw in warm, humid boundary‐layer air to the closed cyclonic circulation, which maintains a large‐CAPE environment in the low and enhances deep convection. A possible positive feedback process including moist convection that leads to the rapid intensification of monsoon depressions over the BoB is discussed.
Flow‐dependent stochastic coupling for climate models with high ocean‐to‐atmosphere resolution ratio
Authors: Rackow Thomas , Juricke Stephan 
Published: October 2019

AbstractThis study introduces a new flow‐dependent distribution sampling (FDDS) scheme for air–sea coupling. The FDDS scheme is implemented in a climate model and used to improve the simulated mean and variability of atmospheric and oceanic surface fields and thus air–sea fluxes. Most coupled circulation models use higher resolutions in the sea ice and ocean compared to the atmospheric model component, thereby explicitly simulating the atmospheric subgrid‐scale at the interface. However, the commonly applied averaging of surface fields and air–sea fluxes tends to smooth fine‐scale structures, such as oceanic fronts. The stochastic FDDS scheme samples the resolved spatial ocean (and sea ice) subgrid distribution that is usually not visible to a coarser‐resolution atmospheric model. Randomly drawn nodal ocean values are passed to the corresponding atmospheric boxes for the calculation of surface fluxes, aiming to enhance surface flux variability. The resulting surface field perturbations of the FDDS scheme are based on resolved dynamics, displaying pronounced seasonality with realistic magnitude. The AWI Climate Model is used to test the scheme on interannual time‐scales. Our set‐up features a high ocean‐to‐atmosphere resolution ratio in the Tropics, with grid‐point ratios of about 60:1. Compared to the default deterministic averaging, changes are largest in the Tropics leading to an improved spatial distribution of precipitation with bias reductions of up to 50%. Enhanced sea‐surface temperature variability in boreal winter further improves the seasonal phase locking of temperature anomalies associated with the El Niño–Southern Oscillation. Mean 2m temperature, sea ice thickness and concentration react with a contrasting dipole pattern between hemispheres but a joint increase of monthly and interannual variability. This first approach to implement a flow‐dependent stochastic coupling scheme shows considerable benefits for simulations of global climate, and various extensions and modifications of the scheme are possible.
Enhancement of cardiac lymphangiogenesis by transplantation of CD34+VEGFR-3+ endothelial progenitor cells and sustained release of VEGF-C
Authors: Zhang Hai-feng , Wang Yong-li , Tan Yu-zhen , Wang Hai-jie , Tao Ping , Zhou Pei 
Published: October 2019

Abstract
Impairment of cardiac lymphatic vessels leads to cardiac lymphedema. Recent studies have suggested that stimulation of lymphangiogenesis may reduce cardiac lymphedema. However, effects of lymphatic endothelial progenitor cells (LEPCs) on cardiac lymphangiogenesis are poorly understood. Therefore, this study investigated effectiveness of LEPC transplantation and VEGF-C release with self-assembling peptide (SAP) on cardiac lymphangiogenesis after myocardial infarction (MI). CD34+VEGFR-3+ EPCs isolated from rat bone marrow differentiated into lymphatic endothelial cells after VEGF-C induction. VEGF-C also stimulated the cells to incorporate into the lymphatic capillary-like structures. The functionalized SAP could adhere with the cells and released VEGF-C sustainedly. In the condition of hypoxia and serum deprivation or abdominal pouch assay,
the SAP hydrogel protected the cells from apoptosis and necrosis. At 4 weeks after intramyocardial transplantation of the cells and VEGF-C loaded with SAP hydrogel in rat MI models, cardiac lymphangiogenesis was increased, cardiac edema and reverse remodeling were reduced, and cardiac function was improved significantly. Delivery with SAP hydrogel favored survival of the engrafted cells. VEGF-C released from the hydrogel promoted differentiation and incorporation of the cells as well as growth of pre-existed lymphatic vessels. Cardiac lymphangiogenesis was beneficial for elimination of the inflammatory cells in the infarcted myocardium. Moreover, angiogenesis and myocardial regeneration were enhanced after reduction of lymphedema. These results demonstrate that the combined delivery of LEPCs and VEGF-C with the functionalized SAP promotes cardiac lymphangiogenesis and repair of the infarcted myocardium effectively. This study represents a novel therapy for relieving myocardial edema in cardiovascular diseases.
Assessment of the appropriate use criteria for amyloid PET in an unselected memory clinic cohort: The ABIDE project
Authors: de Wilde Arno , Ossenkoppele Rik , Pelkmans Wiesje , Bouwman Femke , Groot Colin , van Maurik Ingrid , Zwan Marissa , Yaqub Maqsood , Barkhof Frederik , Lammertsma Adriaan A. , Biessels Geert Jan , Scheltens Philip , van Berckel Bart N. , van der Flier Wiesje M. 
Published: October 2019

AbstractIntroductionThe objective of this study was to assess the usefulness of the appropriate use criteria (AUC) for amyloid imaging in an unselected cohort.MethodsWe calculated sensitivity and specificity of appropriate use (increased confidence and management change), as defined by Amyloid Imaging Taskforce in the AUC, and other clinical utility outcomes. Furthermore, we compared differences in post–positron emission tomography diagnosis and management change between “AUC‐consistent” and “AUC‐inconsistent” patients.ResultsAlmost half (250/507) of patients were AUC‐consistent. In both AUC‐consistent and AUC‐inconsistent patients, post–positron emission tomography diagnosis (28%–21%) and management (32%–17%) change was substantial. The Amyloid Imaging Taskforce's definition of appropriate use occurred in 55/507 (13%) patients, detected by the AUC with a sensitivity of 93%, and a specificity of 56%. Diagnostic changes occurred independently of AUC status (sensitivity: 57%, specificity: 53%).DiscussionThe current AUC are not sufficiently able to discriminate between patients who will benefit from amyloid positron emission tomography and those who will not.
Decadal Shift in Nitrogen Inputs and Fluxes Across the Contiguous United States: 2002–2012
Authors: Sabo Robert D. , Clark Christopher M. , Bash Jesse , Sobota Daniel , Cooter Ellen , Dobrowolski James P. , Houlton Benjamin Z. , Rea Anne , Schwede Donna , Morford Scott L. , Compton Jana E. 
Published: October 2019

AbstractThe effectiveness of policies and management actions in reducing the release of excess nitrogen (N) to the environment is best assessed if N fluxes across air, land, and water are regularly quantified at relevant scales. Here we compiled 2002, 2007, and 2012 inventories of inputs and nonhydrologic N outputs along with fossil fuel emissions, food demand, and terrestrial N surpluses for all subbasins of the contiguous United States using peer‐reviewed, publicly available data sets. We found that at the national scale, total inputs, outputs, and surpluses changed little (±6%) between 2002 and 2012 and remained dominated by agricultural processes, despite efforts to curb N losses. This consistency at the national scale, however, obscured large counteracting shifts at regional levels driven by variable fluxes across regions. Throughout the eastern United States, declines in deposition and fertilizer inputs combined with increased crop yields resulted in a decrease in terrestrial N surpluses, which may explain recent water quality improvements in the region. On the other hand, fertilizer N inputs in the Midwest increased at a greater rate than crop harvest N increased, leading to a larger terrestrial surplus N. A large relative increase (~320%) in N emissions in the West due to an unusual wildfire season in 2012 was also observed. These changes coincided with national policies that decreased N emissions and increased demand for domestic biofuels, potentially highlighting the capacity to change the source and magnitude of N inputs and fluxes across the landscape through market and regulatory actions.
A high-sensitivity MEMS gravimeter with a large dynamic range
Authors: Tang Shihao , Liu Huafeng , Yan Shitao , Xu Xiaochao , Wu Wenjie , Fan Ji , Liu Jinquan , Hu Chenyuan , Tu Liangcheng 
Published: October 2019

AbstractPrecise measurement of variations in the local gravitational acceleration is valuable for natural hazard forecasting, prospecting, and geophysical studies. Common issues of the present gravimetry technologies include their high cost, high mass, and large volume, which can potentially be solved by micro-electromechanical-system (MEMS) technology. However, the reported MEMS gravimeter does not have a high sensitivity and a large dynamic range comparable with those of the present commercial gravimeters, lowering its practicability and ruling out worldwide deployment. In this paper, we introduce a more practical MEMS gravimeter that has a higher sensitivity of 8 μGal/√Hz and a larger dynamic range of 8000 mGal by using an advanced suspension design and a customized optical displacement transducer. The proposed MEMS gravimeter has performed the co-site earth tides measurement with a commercial superconducting gravimeter GWR iGrav with the results showing a correlation coefficient of 0.91.
Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine
Authors: Lima Ana Rita , Pinto Joana , Azevedo Ana Isabel , Barros-Silva Daniela , Jerónimo Carmen , Henrique Rui , de Lourdes Bastos Maria , Guedes de Pinho Paula , Carvalho Márcia 
Published: October 2019

Abstract

Background
The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management.

Methods
A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection.

Results
Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients’ urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%.

Conclusions
It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.
Tumour cell-derived debris and IgG synergistically promote metastasis of pancreatic cancer by inducing inflammation via tumour-associated macrophages
Authors: Chen Qi , Wang Jianxin , Zhang Qi , Zhang Jingying , Lou Yu , Yang Jiaqi , Chen Yiwen , Wei Tao , Zhang Jian , Fu Qihan , Ye Mao , Zhang Xiaozhen , Dang Xiaowei , Liang Tingbo , Bai Xueli 
Published: October 2019

Abstract

Background
The progression and metastasis of pancreatic ductal adenocarcinoma (PDAC) is highly dependent on the tumour microenvironment. Most tumour-associated macrophages (TAMs) are M2 phenotype macrophages, which normally show anti-inflammatory functions in numerous disorders. Previously, we found that alternatively activated macrophages showed pro-inflammatory characteristics upon stimulation with hepatoma cell-derived debris; however, the molecular mechanism was unclear.

Methods
In vitro and in vivo experiments were employed to investigate the molecular mechanism. Using pancreatic cancer cell lines, mouse models and human tissues, we obtained a general picture of tumour cell-derived debris promoting metastasis of pancreatic cancer by inducing inflammation via TAMs.

Results
We showed that M2 macrophage-derived inflammation also exists in PDAC. Debris from PDAC cells induced potent IL-1β release by M2 macrophages via TLR4/TRIF/NF-κB signalling, and this effect was further boosted by IgG that was also derived from PDAC cells. Increased IL-1β promoted epithelial–mesenchymal transition and consequent metastasis of PDAC cells. A selective COX-2 inhibitor, celecoxib, enhanced the anti-tumoural efficacy of gemcitabine.

Conclusions
These data revealed a pro-inflammatory mechanism in PDAC, which indicated that IL-1β and COX-2 could be therapeutic targets of an anti-inflammatory strategy to treat PDAC.
Clinical Factors in Trunk Capillary Malformations in the Neonate: When to Suspect Other Associated Malformations? A Case–Control Study
Authors: Delgado-Miguel Carlos , Vicente Miriam , Serrano-Muñoz Antonio Jesus , Miguel-Ferrero Miriam , Diaz Mercedes , Triana Paloma , López-Gutiérrez Juan Carlos 
Published: October 2019

Abstract
Introduction Capillary malformations (CMs) can be sporadic or syndromic, in association with other underlying venous malformation (VM) or lymphatic malformation (LM). The objective of this study is to describe the clinical patterns in the neonate that allow us to differentiate sporadic CMs from those associated with other vascular malformations.
Materials and Methods A case–control study was performed in neonates with CM located in the trunk, followed at our institution between 2008 and 2018. The patients were divided into two groups: group A (cases: CM associated with VM or LM) and group B (controls: sporadic CM without associated malformations). Demographic and clinical variables collected in the clinical history were evaluated (color, location, multifocality, bilaterality, position regarding the vascular axis, and involvement of the midline).
Results Thirty-eight patients were included (18 cases and 20 controls) without differences in gender and age. In group A, the totality of patients presented CM with uniform color and lateral location (p < 0.001). In this group, bilateral and multifocal involvements were lower than in group B, without significant differences between both groups. The distribution of CMs in group A was always parallel to the vascular axis and the midline was always respected, without observing these characteristics in the group B (p < 0.001).
Conclusion The presence of a CM in the trunk of a neonate with uniform color, lateral location, parallel position to the vascular axis, and absence of involvement of the midline should make us suspect other underlying vascular malformations, which should be studied with complementary tests.
Venous Thromboembolism despite Ongoing Prophylaxis after Fast-Track Hip and Knee Arthroplasty: A Prospective Multicenter Study of 34,397 Procedures
Authors: Petersen Pelle Baggesgaard , Jørgensen Christoffer Calov , Kehlet Henrik ,   on behalf of the Lundbeck Foundation Centre for Fast-track Hip Knee Replacement Collaborative Group
Published: October 2019

Abstract
Introduction Venous thromboembolism (VTE) is a serious complication to total hip and knee arthroplasty (THA/TKA). However, recent publications found low 90-day incidences of VTE with in-hospital only thromboprophylaxis after fast-track THA and TKA, but with a subgroup with VTE despite thromboprophylaxis.
Objectives We aimed to investigate in detail the incidence and risk for VTE despite ongoing thromboprophylaxis after fast-track THA and TKA.
Materials and Methods This is a prospective unselected multicenter cohort from January 2010 to August 2017. Data on preoperative characteristics were entered into the Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement database (www.FTHK.dk). Length of stay (LOS) and complete 90-day follow-up was obtained from the Danish National Patient Registry and review of medical records. Patients with preoperative use of potent anticoagulants were excluded.
Results Of 34,397 procedures, 32 (0.09%, 22.4% of all VTE) had VTE after median 2 (interquartile range: 2–4) days despite ongoing thromboprophylaxis. Twenty-nine (2.1% of LOS > 5 days) occurred with LOS > 5 days and 3 during primary admission with LOS ≤ 5 days. Note that 78% of VTEs despite ongoing thromboprophylaxis occurred without any identifiable pre-VTE complication. Risk factors were age from 81 to 85 years (odds ratio [OR] 6.3 [95% confidence interval: 1.8–22.4], p = 0.005), body mass index (BMI) < 18.5 (OR 11.1 [1.1–109.2], p = 0.040), BMI 35 to 40 (OR 5.1 [1.0–26.2], p = 0.050), and BMI ≥ 40 (OR 21.8 [4.6–103.6], p < 0.001).
Conclusion VTE after fast-track THA/TKA occurred after median 2 days in 0.09% (22% of all VTE) despite ongoing thromboprophylaxis. Further investigation of this “high-risk” population might help to improve the optimal choice for patient-specific thromboprophylaxis to further reduce incidence of postoperative VTE.
Understanding Factors Associated with Quality of Life in Patients with Venous Thromboembolism
Authors: Erickson Reaghan M. , Feehan Michael , Munger Mark A. , Tak Casey , Witt Daniel M. 
Published: October 2019

Abstract
Introduction Quality of life (QoL) deficits have been noted among patients with venous thromboembolism (VTE) but understanding of the drivers of that poorer QoL is limited. The objective of this study was to examine associations between a variety of factors and QoL in patients with VTE.
Methods Adult patients who had experienced at least one VTE episode within the past 2 years completed an online survey between May and July 2016 with responses to a variety of questions designed to ascertain QoL scores, Optum Short Form-12, and potential factors associated with these scores.
Results Most of the 907 patients were female (56.7%) and Caucasian (88.6%). Physical and mental QoL scores below the general population average were present in 76.0 and 56.7% of patients, respectively. Multiple regression modeling revealed several factors associated with below average physical QoL scores including unemployment (odds ratio [OR] 3.77, 95% confidence interval [CI] 1.76–8.05), gastrointestinal bleeding (OR 2.54, 95% CI 1.28–5.01), high depression scores (OR 4.02, 95% CI 1.88–8.58), or difficulty accessing VTE care (OR 4.24, 95% CI 1.77–10.17). Factors associated with below average mental QoL scores included experiencing VTE within the last month (OR 3.85, 95% CI 1.58–9.41), unemployment (OR 2.83, 95% CI 1.30–6.16), or high depression (OR 3.85, 95% CI 1.60–9.28) and/or anxiety (OR 9.17, 95% CI 4.81–17.47) scores.
Conclusion Most patients with recently diagnosed VTE reported below average QoL. Many of the factors associated with below average QoL are modifiable, indicating that patients with VTE could potentially benefit from interventions aimed at improving QoL.