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In osteoarthritis (OA), degradation of cartilage pericellular matrix (PCM), the proteoglycan-rich immediate cell microniche, is a leading event of disease initiation. This study demonstrated that biomimetic proteoglycans (BPGs) can diffuse into human cartilage from both normal and osteoarthritic donors and are preferentially localized within the PCM. Applying immunofluorescence (IF)-guided AFM nanomechanical mapping, we show that this localization of BPGs increases the PCM micromodulus of both normal and OA specimens. These results illustrate the capability of BPGs to integrate with degenerative tissues and support the translational potential of BPGs for treating human OA and other diseases associated with proteoglycan degradation.

Abstract: The gas atomized Ag-9.26wt%Sn-0.44wt%La alloy powders were oxidized in air between 400 and 900 °C. The oxidation thermodynamics, kinetics and microstructure of the alloy were investigated. We suggested that the addition of La may accelerate oxidation of Sn and prevent the formation of the dense SnO2 film. The suitable oxidation temperature of the alloy powders is 800 °C in air. After internal oxidation, many cracks were observed on the surface of the alloy powders. In addition, the whole oxidation process of the alloy powders is controlled by the oxygen diffusion. The diffusion coefficient of oxygen in the alloy powders at 800 °C is about 1.5 times larger than that at 700 °C on the initial stage of internal oxidation, while that is 4.5 times on the subsequent stage.

Purpose: To investigate the association of thyroid cancer (TC) with 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (DBP) and examine whether there was an interaction between 25(OH)D and DBP in relation to TC risk. Methods: A matched case–control study based on multiple hospitals included 506 pairs of cases with newly diagnosed TC and controls. All subjects were divided into the quartiles according to the distribution of 25(OH)D and DBP in controls. Odds ratio (OR) and 95% confidence intervals (CIs) for the association of TC with 25(OH)D and DBP were estimated by conditional logistic regression. Results: Comparing the highest to lowest quartiles, a decreased TC risk was respectively associated with plasma 25(OH)D (OR 0.63, 95% CI 0.40–1.00, P-trend = 0.046) and DBP (OR 0.49, 95% CI 0.32–0.77, P-trend = 0.001). However, the association between DBP and TC might be modified by 25(OH)D (P-interaction = 0.014) and physical activity (P-interaction = 0.017). Compared to participants with 25(OH)D and DBP concentrations respectively below medians, those with both concentrations above medians had a lower risk of TC (OR 0.56, 95% CI 0.39–0.82). In stratified analysis based on clinical characteristics of tumor, significantly negative association between 25(OH)D, and DBP and TC were observed among the cases with early stage of tumor progression. Conclusions: This study suggested that 25(OH)D and DBP had protective effects against TC. But the negative association between TC and DBP might be modified by 25(OH)D and physical activity.

The dielectric properties of cartilage are essential for the development of reliable numerical models of electrical stimulation devices intended for the regeneration of cartilage. They are, however, not widely known. To determine the dielectric properties of cartilage, we propose a numerical workflow that incorporates detailed tissue-specific 3-D geometries based on fluorescent microscopic images and describes how different parameters can affect the results. We investigated a typical bioimpedance setup that can be used for impedance sensing and electrical stimulation. The obtained results provided valuable insights that can aid in the design and implementation of future experiments, ensuring their accuracy and reliability.

Scattering of high energy particles from nucleons probes their structure, as was done in the experiments that established the non-zero size of the proton using electron beams1. The use of charged leptons as scattering probes enables measuring the distribution of electric charges, which is encoded in the vector form factors of the nucleon2. Scattering weakly interacting neutrinos gives the opportunity to measure both vector and axial vector form factors of the nucleon, providing an additional, complementary probe of their structure. The nucleon transition axial form factor, FA, can be measured from neutrino scattering from free nucleons, νμn→ μ−pand ν¯μp→μ+n, as a function of the negative four-momentum transfer squared (Q2). Up to now, FA(Q2) has been extracted from the bound nucleons in neutrino–deuterium scattering3–9, which requires uncertain nuclear corrections10. Here we report the first high-statistics measurement, to our knowledge, of the ν¯μp→μ+ncross-section from the hydrogen atom, using the plastic scintillator target of the MINERvA11experiment, extracting FAfrom free proton targets and measuring the nucleon axial charge radius, rA, to be 0.73 ± 0.17 fm. The antineutrino–hydrogen scattering presented here can access the axial form factor without the need for nuclear theory corrections, and enables direct comparisons with the increasingly precise lattice quantum chromodynamics computations12–15. Finally, the tools developed for this analysis and the result presented are substantial advancements in our capabilities to understand the nucleon structure in the weak sector, and also help the current and future neutrino oscillation experiments16–20to better constrain neutrino interaction models.

Field ageing is investigated based on recovered binders. Fifteen sections were considered, consisting of unmodified and polymer-modified binders (PmB). Binders were recovered from the wearing course, after slicing the cores horizontally. To assess field and laboratory ageing tendencies, recovered binders were compared to a set of reference binders, tested before and after laboratory ageing. For three sites, the binders recovered from bottom slices were long-term aged and compared to the properties of top slices. Stiffness-based rheological parameters showed good relations to the carbonyl index. Field and laboratory ageing induced the same trends, but field ageing often turned out to be more severe. It was shown, for three sections, that a standard ageing test applied to the bottom slices is not enough to reach the ageing levels of the top slices. Finally, a relation between the vertical ageing profile and the void content of the corresponding asphalt mixtures was observed.

The statistics of day‐to‐day tidal variability within 35‐day running mean windows is obtained from Michelson Interferometer for Global High‐Resolution Thermospheric Imaging (MIGHTI)/Ionospheric Connection Explorer (ICON) observations in the 90–107 km height region for the year 2020. Temperature standard deviations for 18 diurnal and semidiurnal tidal components, and for four quasi‐stationary planetary waves are presented, as function of latitude, altitude, and day‐of‐year. Our results show that the day‐to‐day variability (DTDV) can be as large as 70% of the monthly mean amplitudes, thus providing a significant source of variability for the ionospheric E‐region dynamo and hence for the F‐region plasma. We further validate our results with COSMIC‐2 ionospheric observations and present an approach to extend the MIGHTI/ICON results to all latitudes using Hough Mode Extension fitting, to produce global tidal fields and their statistical DTDV that are suitable as lower boundary conditions for nudging and ensemble modeling of TIE‐GCM. In the future, this will likely help to establish a data‐driven perspective of space weather variability caused by the tidal weather of the lower atmosphere. Statistics of the day‐to‐day variability (DTDV) of diurnal and semidiurnal tides in the ionospheric dynamo region is obtained from Michelson Interferometer for Global High‐Resolution Thermospheric Imaging/Ionospheric Connection ExplorerDTDV is validated with COSMIC‐2 ionospheric observationsStatistics is extended to all latitudes using Hough Mode Extensions Statistics of the day‐to‐day variability (DTDV) of diurnal and semidiurnal tides in the ionospheric dynamo region is obtained from Michelson Interferometer for Global High‐Resolution Thermospheric Imaging/Ionospheric Connection Explorer DTDV is validated with COSMIC‐2 ionospheric observations Statistics is extended to all latitudes using Hough Mode Extensions

Wood adhesives derived from softwood bark residues pyrolysis oil have been developed for oriented strandboard (OSB), an exterior grade wood composite product. The phenolic-rich oil produced by the vacuum pyrolysis [...]

Molecular engineering of biological tissues using synthetic mimics of native matrix molecules can modulate the mechanical properties of the cellular microenvironment through physical interactions with existing matrix molecules, and in turn, mediate the corresponding cell mechanobiology. In articular cartilage, the pericellular matrix (PCM) is the immediate microniche that regulates cell fate, signaling, and metabolism. The negatively charged osmo-environment, as endowed by PCM proteoglycans, is a key biophysical cue for cell mechanosensing. This study demonstrated that biomimetic proteoglycans (BPGs), which mimic the ultrastructure and polyanionic nature of native proteoglycans, can be used to molecularly engineer PCM micromechanics and cell mechanotransduction in cartilage. Upon infiltration into bovine cartilage explant, we showed that localization of BPGs in the PCM leads to increased PCM micromodulus and enhanced chondrocyte intracellular calcium signaling. Applying molecular force spectroscopy, we revealed that BPGs integrate with native PCM through augmenting the molecular adhesion of aggrecan, the major PCM proteoglycan, at the nanoscale. These interactions are enabled by the biomimetic “bottle-brush” ultrastructure of BPGs and facilitate the integration of BPGs within the PCM. Thus, this class of biomimetic molecules can be used for modulating molecular interactions of pericellular proteoglycans and harnessing cell mechanosensing. Because the PCM is a prevalent feature of various cell types, BPGs hold promising potential for improving regeneration and disease modification for not only cartilage-related healthcare but many other tissues and diseases.

Background: The prognosis of biliary neuroendocrine neoplasms (NENs) patients is affected by the status of metastatic lymph nodes. The purpose of this study was to explore the prognostic value of the log odds of positive lymph nodes (LODDS) and develop a novel nomogram to predict the overall survival (OS) in biliary NENs patients. Methods: A total of 125 patients with histologically confirmed biliary NENs were selected from the Surveillance, Epidemiology and End Results (SEER) database and further divided into training and validation cohorts. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration plots. The net benefits and clinical utility of the nomogram were quantified and compared with those of the SEER staging system using decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). The risk stratifications of the nomogram and the SEER staging system were compared. Results: LODDS showed the highest accuracy in predicting OS for biliary NENs. The C-index (0.789 for the training cohort and 0.890 for the validation cohort) and the time-dependent AUC (> 0.7) indicated the satisfactory discriminative ability of the nomogram. The calibration plots showed a high degree of consistency. The DCA, NRI, and IDI indicated that the nomogram performed significantly better than the SEER staging system. Conclusion: A novel LODDS-incorporated nomogram was developed and validated to assist clinicians in evaluating the prognosis of biliary NENs patients.

In this paper, biomedical porous Ti–Nb–Ta–Zr with 40% porosity and 166 ± 21 μm macro-pore size was successfully fabricated by space holder method. The microstructure, Vickers hardness, compressive and electrochemistry behavior were studied. It results that a few second phases exist in β matrix of the porous Ti–Nb–Ta–Zr. Its Young's modulus is 0.8 GPa, close to 0.01–3 GPa for trabecular bone. The total recovery strain ratio and pseudoelastic strain ratio are 8.8% and 2.7%, respectively. It fails mainly by brittle cleavage with the fan-shaped and smooth cleaved facets. Although, local ductile fracture by a few dimples and a small amount of transcrystalline fracture with the cleavage of similarly oriented laths in a colony are observed on the fracture surface. The impedance spectrum of porous Ti–Nb–Ta–Zr has the characteristics of half capacitive arc resistance, showing good corrosion resistance in SBF solution.

•Cervical spinal hemangioblastoma (CSHBs) has rarely been reported in the cervical spine, and microsurgical treatment even less.•The study included eleven patients with CSHB treated by total tumor resection from January 2005 to December 2015.•Finding and blocking nutrient arteries during the operation is necessary to reduce bleeding.•All patients in this study were in good postoperative health, without recurrence during 6–48 months’ follow-up.•A discussion of a series deals with surgical considerations.

To investigate region-specific models for organ’s three-dimensional dose distribution prediction with neural network.

Joint biomechanical functions rely on the integrity of cartilage extracellular matrix. Understanding the molecular activities that govern cartilage matrix assembly is critical for developing effective cartilage regeneration strategies. This study elucidated the role of decorin, a small leucine-rich proteoglycan, in the structure and biomechanical functions of cartilage. In decorin-null cartilage, we discovered a substantial reduction of aggrecan content, the major proteoglycan of cartilage matrix, and mild changes in collagen fibril nanostructure. This loss of aggrecan resulted in significantly impaired biomechanical properties of cartilage, including decreased modulus, elevated hydraulic permeability, and reduced energy dissipation capabilities. At the cellular level, we found that decorin functions to increase the retention of aggrecan in the neo-matrix of chondrocytes, rather than to directly influence the biosynthesis of aggrecan. At the molecular level, we demonstrated that decorin significantly increases the adhesion between aggrecan and aggrecan molecules and between aggrecan molecules and collagen II fibrils. We hypothesize that decorin plays a crucial structural role in mediating the matrix integrity and biomechanical functions of cartilage by providing physical linkages to increase the adhesion and assembly of aggrecan molecules at the nanoscale.

To achieve zero-defect production during computer numerical control (CNC) machining processes, it is imperative to develop effective diagnosis systems to detect anomalies efficiently. However, due to the dynamic conditions of the machine and tooling during machining processes, the relevant diagnosis systems currently adopted in industries are incompetent. To address this issue, this paper presents a novel data-driven diagnosis system for anomalies. In this system, power data for condition monitoring are continuously collected during dynamic machining processes to support online diagnosis analysis. To facilitate the analysis, preprocessing mechanisms have been designed to de-noise, normalize, and align the monitored data. Important features are extracted from the monitored data and thresholds are defined to identify anomalies. Considering the dynamic conditions of the machine and tooling during machining processes, the thresholds used to identify anomalies can vary. Based on historical data, the values of thresholds are optimized using a fruit fly optimization (FFO) algorithm to achieve more accurate detection. Practical case studies were used to validate the system, thereby demonstrating the potential and effectiveness of the system for industrial applications.

To present the natural course and treatment modalities of spontaneous cervical epidural hematoma (SCEH), by reporting two rare cases with spontaneous resolution in both clinical and radiologic findings without surgery.

IG-105, N-(2, 6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide, a novel carbazole sulfonamide, shows a potent anticancer activity in a variety of human tumor cellsin vitroandin vivo. In the present study, a rapid and convenient liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and applied to the pharmacokinetic study of IG-105 in rats. Chromatographic separation was accomplished on a C18column using an isocratic mobile phase of acetonitrile-water-acetic acid (56:44:0.2, v/v/v). The ion transitions of IG-105 and combretastatin A4 (internal standard) in selected reaction monitoring mode were m/z 398→154 and m/z 317→286, respectively. The assay exhibited good linearity over the range of 2–512 ng/mL. Intra- and inter-day precisions were within 8.2 %, and the accuracies ranged from -6.0 to 3.7 %. The extraction recoveries were higher than 90 %, and the matrix effects were negligible. All quality control samples were stable at different storage conditions. The validated LC-MS/MS method was successfully applied to a preclinical pharmacokinetic study of IG-105 in rats after a single oral dose of 100, 250, or 1000 mg/kg which showed tumor growth inhibition activity. The absorption of IG-105 was proved to be rapid but saturated to a certain extent into the blood circulation, from where it was distributed and eliminated gradually.

Lithium-ion (Li-ion) batteries operate viaelectrochemical reactions between positive and negative electrodes, formed by complex porous microstructures. An improved understanding of these materials can lead to a greater insight into the link between microscopic electrode morphology and macroscopic performance. The practice of calendering electrodes after manufacturing has been widely used to increase the volumetric energy density and improve the electrical contact between electrode material particles and with the foil substrate. In this paper we present, for the first time to the authors’ knowledge, a technique to image battery electrodes in situand in 3D whilst undergoing uniaxial compression with the intent of emulating the calendering process. This technique allows the tracking of electrode strain during compression and its further application will lead to a thorough understanding of crack initiation and propagation mechanisms within electrode particles, ultimately optimising their design and performance.

Natural radioactivity was determined in sediment samples collected from the Xining section of the Huangshui River in northwest China. The activity concentrations of 226Ra, 232Th and 40K in the sediment samples range from 15.8 to 65.3, 24.3 to 86.0 and 432.6 to 702.4 Bq.kg-1with an average of 32.4, 43.0 and 527.5 Bq.kg-1, respectively. All investigated sediment samples have radium equivalent activity lower than the limit of 370 Bq.kg-1and an external hazard index less than unity. The mean outdoor air absorbed dose rate is 63.5 nGy.h-1and the corresponding outdoor annual effective dose rate is 0.078 mSv.y-1. The radiation level of the studied location is safe, and the sediment can be safely used in construction according to the current norms.

The National Aeronautics and Space Administration (NASA) Thermosphere Ionosphere Mesosphere Energetics and Dynamics (TIMED) Sounding of the Atmosphere using Broadband Radiometry (SABER) instrument performs near‐global measurements of the vertical kinetic temperature (Tk) profiles and volume mixing ratios of various trace species (including O3, CO2, and H2O), with data available from 2002 to present. In this work, the first comparative study of the latest publically available SABER version 2.0 operational retrieval is reported in order to assess the performance of satellite Tkprofiles relative to high‐resolution ground‐based lidar profiles. Collocated multiyear seasonal average Tkprofiles were compared at nine different locations, representing a variety of different latitudes. In general, the SABER v2.0 and lidar mean seasonal Tkprofiles agree well, with the smallest absolute values of ΔTk(z) (SABER minus lidar) found between 85 and 95 km, where the respective SABER and lidar uncertainties were smallest. At altitudes ≥100 km, the SABER Tk(z) typically exhibited warmer temperatures relative to the lidar Tk(z) profiles, whereas for altitudes ≤85 km, SABER Tk(z) was cooler. Relative to lidar, SABER tends to exhibit a warm bias during high‐latitude summertime, with the reasons for this currently still unclear. Overall, SABER was able to reproduce the general latitude‐ and season‐specific variations in the lidar Tkprofiles and shown to be statistically similar for most seasons, at most locations, for the majority of altitudes, and with no overall bias. The first comparative study of SABER version 2.0 operational temperature retrieval product with high‐resolution ground‐based lidar profilesA comparison of collocated multiyear seasonal average temperatures at nine locations (low, middle, and high latitudes) is presentedAn overall agreement for SABER and lidar data sets, but the presence of relative SABER warm bias during polar summer requires further investigation

Carbon nanotube (CNT) sponge exhibits unique porous and hierarchical structure that are beneficial to the design of ultralight and tough composites. In this study, CNT sponges (undoped and boron doped) reinforced polydimethylsiloxane (PDMS) composites were fabricated. Mechanical properties of the composite, including compressive modulus, rate-dependent modulus, stress relaxation behaviors, dynamic viscoelastic properties, and their dependency on temperature, were systematically investigated. A micromechanical model, Mori-Tanaka model, was validated to describe the mechanical behaviors of CNT sponge reinforced composites. By coupling with boron-doped CNT sponge, PDMS composites showed remarkable improvement of mechanical properties, including compressive modulus (70%), viscous modulus (243%) and damping capacity (50%). Such reinforcement effects can be controlled by the morphology of CNT sponges, as the boron-doped and undoped nanocomposites showed distinct viscoelastic behaviors. The results proved that CNT sponge reinforcement is a promising strategy to develop engineering composites with both outstanding mechanical stiffness and controllable viscoelastic performances.

Electrochemical energy devices offer a variety of alternate means for low-carbon, multi-scale energy conversion and storage. Reactions in these devices are supported by electrodes with characteristically complex microstructures. To meet the increasing capacity and lifetime demands across a range of applications, it is essential to understand microstructural evolutions at a cell and electrode level which are thought to be critical aspects influencing material and device lifetime and performance. X-ray computed tomography (CT) has become a highly employed method for non-destructive characterisation of such microstructures with high spatial resolution. However, sub-micron resolutions present significant challenges for sample preparation and handling particularly in 4D studies, (three spatial dimensions plus time). Here, microstructural information is collected from the same region of interest within two electrode materials: a solid oxide fuel cell and the positive electrode from a lithium-ion battery. Using a lab-based X-ray instrument, tomograms with sub-micron resolutions were obtained between thermal cycling. The intricate microstructural evolutions captured within these two materials provide model examples of 4D X-ray nano-CT capabilities in tracking challenging degradation mechanisms. This technique is valuable in the advancement of electrochemical research as well as broader applications for materials characterisation.

Purpose: To evaluate the association between cigarette smoking and glaucoma in the United States population. Patients and methods: US civilian, non-institutionalized population from 2005 to 2008 administrations of the National Health and Nutrition Examination Survey that were ≥40 years of age with visual fields and optic disc photographs were included. Diagnosis of glaucoma was based on the Rotterdam criteria. Logistic regression modeling was performed to assess the association between glaucoma and smoking history, while controlling for age, gender, ethnicity, household income, alcohol consumption, diabetes, and hypertension. Results: In 3864 participants, 212 (5.5%) had glaucoma (corresponds to a population weighted glaucoma prevalence of 3.7% in a total of 83 570 127 subjects). Population weighted proportion of current smokers was 20.6% and ex-smokers was 28.3%. Participants with glaucoma were older (63.0±11.6 vs56.1±11.2, P=0.002), likely to be male (57.1% vs49.2%, P=0.03), to be Black (36.3% vs20.7%, P<0.001), and to have diabetes (18.9% vs12.4%, P=0.006) and hypertension (50.5% vs39.7%, P=0.003). Current smokers had a lower odds of glaucoma compared to non-smokers (OR=0.61, 95% CI=0.41–0.88, P=0.009), and ex-smokers (OR=0.46, 95% CI=0.28–0.76, P=0.002). The effect estimates were similar in adjusted models, but not statistically significant. Among smokers, greater pack/day of smoking history was associated with statistically significantly higher odds of glaucoma (OR=1.70, 95% CI=1.08–2.67, P=0.02). Conclusions: Among cigarette smokers, heavy smoking defined by greater number of pack of cigarettes smoked per day is associated with higher odds of glaucoma. Health care providers should include this association when counseling patients on their smoking habit.

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Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T cells against leukemia and lymphoma with promising clinical results. Extending this approach to allogeneic T cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen-specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy. We transduced CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9), and demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model. Interleukin-15 (IL-15) production by the transduced CB-NK cells critically improved their function. Moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene. In conclusion, we have developed a novel approach to immunotherapy using engineered CB-derived NK cells, which are easy to produce, exhibit striking efficacy and incorporate safety measures to limit toxicity. This approach should greatly improve the logistics of delivering this therapy to large numbers of patients, a major limitation to current CAR-T-cell therapies.

Tool condition monitoring has been considered as one of the key enabling technologies for manufacturing optimization. Due to the high cost and limited system openness, the relevant developed systems have not been widely adopted by industries, especially Small and Medium-sized Enterprises. In this research, a cost-effective, wireless communication enabled, multi-sensor based tool condition monitoring system has been developed. Various sensor data, such as vibration, cutting force and power data, as well as actual machining parameters, have been collected to support efficient tool condition monitoring and life estimation. The effectiveness of the developed system has been validated via machining cases. The system can be extended to wide manufacturing applications.

PurposeTo investigate the retinal structural changes in endophthalmitis and their association with visual outcome.Patients and methodsForty-five eyes of 45 patients diagnosed with endophthalmitis were included. Spectral domain optical coherence tomography (SD-OCT) was performed after inflammation was controlled. The relationship between SD-OCT features and best-corrected visual acuity (BCVA) at the last follow-up was analyzed.ResultsThe structural changes included inner segment ellipsoid (ISe) disruption (49%), atrophy of retinal inner layers (24%), epimacular membrane (24%), and macular edema (24%). BCVA was worse in patients with ISe disruption (P=0.005) and retinal inner layers' atrophy (P=0.004) compared with those without. There was no significant difference of BCVA between the patients with and without epimacular membrane, or intraretinal cysts. Multivariate regression showed that atrophy of retinal inner layers (b=0.41±0.17, P=0.022) was the only independent factor associated with BCVA.ConclusionAtrophy of retinal inner layers is associated with visual impairment in endophthalmitis, despite successful management.

In this work, we investigate methods for gaining greater insight from hydrological model runs conducted for uncertainty quantification and model differentiation. We frame the sensitivity analysis questions in terms of the main purposes of sensitivity analysis: parameter prioritization, trend identification, and interaction quantification. For parameter prioritization, we consider variance‐based sensitivity measures, sensitivity indices based on the L1‐norm, the Kuiper metric, and the sensitivity indices of the DELSA methods. For trend identification, we investigate insights derived from graphing the one‐way ANOVA sensitivity functions, the recently introduced CUSUNORO plots, and derivative scatterplots. For interaction quantification, we consider information delivered by variance‐based sensitivity indices. We rely on the so‐called given‐data principle, in which results from a set of model runs are used to perform a defined set of analyses. One avoids using specific designs for each insight, thus controlling the computational burden. The methodology is applied to a hydrological model of a river in Belgium simulated using the well‐established Framework for Understanding Structural Errors (FUSE) on five alternative configurations. The findings show that the integration of the chosen methods provides insights unavailable in most other analyses. New and existing sensitivity analysis methods are combined to create a robust approach for identifying parameter importance and interactionsComputational demands are reduced and insights increased by using global and derivative‐based methodsDemonstration using the FUSE hydrological modeling framework highlights the new graphical presentation techniques

We designed a novel haploidentical hematopoietic stem cell transplantation (haplo-HSCT) system using idarubicin (IDA) intensified conditioning regimens and combination of antithymocyte globulin and basiliximab for GvHD prophylaxis. The outcomes of 110 high-risk acute leukemia patients undergoing haplo-HSCT were compared with 69 contemporaneous high-risk patients receiving HLA-matched sibling transplantation using uniform IDA-intensified regimens. The relapse incidence of haplo-HSCT was 23.4%, and 3-year overall survival (OS) and disease-free survival (DFS) achieved 62.9%, 59.1%, respectively. The cumulative incidences of II–IV and III–IV aGvHD were 28.6 and 14.3%, while limited and extensive cGvHD were 19.4, 13.8%. All these results were equivalent to those of concurrent identical sibling transplantation. Three-year OS and DFS for patients in advance stage reached 48.5, 47.3%. Furthermore, the relapse, 3-year OS of positive minimal residual disease (MRD) patients did not differ from negative MRD patients (18.9% vs 11.5%, 63.6% vs 69.6%), indicating our intensified haplo-HSCT technique could circumvent the dismal prognosis of MRD. These data provide reinforcing evidence that our haplo-HSCT system could dramatically improve the survival of high-risk acute leukemia with low relapse and acceptable transplantation-related mortality, and might be a promising therapeutic option for high-risk patients.

Adaptive responses to stressful stimuli involving behavioral, emotional and metabolic changes are orchestrated by the nervous and endocrine systems. Adipose tissue has been recognized as a highly active metabolic and endocrine organ, secreting adipokines that operate as hormones to mediate the crosstalk with other organs including the brain. The role of adipose tissue in sensing and responding to emotional stress and in behavioral regulation, however, remains largely unknown. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcriptional factor controlling adipokine gene expression. Here we show that chronic social defeat stress decreases messenger RNA and protein levels of PPARγ in adipose tissue of susceptible but not resilient mice, which was correlated with social avoidance behavior. A corresponding reduction in adipose adiponectin production was observed in susceptible mice. Rosiglitazone, a blood–brain barrier-impermeant PPARγ-selective agonist, elicited antidepressant- and anxiolytic-like behavioral effects in wild-type mice, with a concurrent increase in plasma adiponectin levels. These effects of rosiglitazone were absent in mice lacking adiponectin but having normal PPARγ expression in adipose tissue and brain. Moreover, pretreatment with the PPARγ-selective antagonist GW9662 blocked rosiglitazone-induced adiponectin expression and antidepressant/anxiolytic-like effects. Together, these results suggest that the behavioral responses to rosiglitazone are mediated through PPARγ-dependent induction of adiponectin. Our findings support an important role for the adipose PPARγ-adiponectin axis in susceptibility to stress and negative emotion-related behaviors. Selectively targeting PPARγ in adipose tissue may offer novel strategies for combating depression and anxiety.

Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear expression and impaired fear extinction. The underlying molecular and cellular mechanisms of PTSD are largely unknown. The current pharmacological and non-pharmacological treatments for PTSD are either ineffective or temporary with high relapse rates. Here we report that adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning. Infusions of adiponectin into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. Whole-cell patch-clamp recordings in brain slices revealed that intrinsic excitability of DG granule neurons was enhanced by adiponectin deficiency and suppressed after treatment with the adiponectin mimetic AdipoRon, which were associated with increased input resistance and hyperpolarized resting membrane potential, respectively. Moreover, deletion of AdipoR2, but not AdipoR1 in the DG, resulted in augmented fear expression and reduced extinction, accompanied by intrinsic hyperexcitability of DG granule neurons. Adiponectin and AdipoRon failed to induce facilitation of fear extinction and elicit inhibition of intrinsic excitability of DG neurons in AdipoR2 knockout mice. These results indicated that adiponectin action via AdipoR2 was both necessary and sufficient for extinction of contextual fear and intrinsic excitability of DG granule neurons, implying that enhancing or dampening DG neuronal excitability may cause resistance to or facilitation of extinction. Therefore, our findings provide a functional link between adiponectin/AdipoR2 activation, DG neuronal excitability and contextual fear extinction, and suggest that targeting adiponectin/AdipoR2 may be used to strengthen extinction-based exposure therapies for PTSD.

River ecosystems contribute significantly to CO2emissions. However, estimates of global riverine CO2emissions remain greatly uncertain owing to the absence of a comprehensive and spatially resolved CO2emission measurement. Based on intensive field measurements using floating chambers, riverine CO2evasion in the Wuding River catchment on the Loess Plateau was investigated. Lateral carbon derived from soil respiration and chemical weathering played a central role in controlling the variability of riverine CO2partial pressure (pCO2). In addition, in‐stream processing of allochthonous organic carbon was an also important source of CO2excess, modulating the influence of lateral carbon inputs. All the surveyed streams were net CO2sources, exhibiting pronounced spatial and seasonal variabilities. The mean CO2efflux was 172, 116, and 218 mmol m−2d−1in spring, summer, and autumn, respectively. Unlike the commonly observed strongest CO2emissions in headwater streams, the increasing CO2efflux with stream order in the Wuding River catchment reflects its unique geomorphologic landscape in controlling CO2emissions. While in reservoirs, the pCO2was more controlled by primary production with aquatic photosynthetic assimilation constraining it to a lower level. Both the magnitude and direction of CO2evasion from reservoirs have been greatly altered. Contrast to streams with large CO2effluxes, reservoirs were small carbon sources and even carbon sinks, due primarily to greatly reduced turbulence and enhanced photosynthesis. In view of the large number of reservoirs on the Loess Plateau, assessing the resulting changes to CO2emissions and their implications for regional carbon budgets warrants further research. Riverine pCO2was collectively affected by heterotrophic respiration of organic carbon and lateral carbon inflow via groundwaterAll streams were CO2sources for the atmosphere, and the CO2effluxes exhibited pronounced spatial and seasonal variabilitiesDam impoundment has significantly altered the magnitude and direction of riverine CO2evasion from reservoir waters

Properties of asphalt mixtures after ageing are fundamental parameters in determining long-term performance (e.g. durability) of these materials. With increasing popularity of reduced temperature mixtures, such as warm-mix asphalt, WMA, the question remains how a reduction in short-term ageing affects the properties after long-term ageing of bituminous materials. This paper aims to improve our understanding of the effect of asphalt manufacturing temperature on ageing and the resulting mechanical properties of bituminous binder by studying the effect of short- and long-term ageing of different bitumen samples as a function of short-term ageing temperatures. For this purpose, round robin experiments were conducted within the RILEM technical committee (TC) 252 chemo-mechanical characterisation of bituminous materials by 10 laboratories from 5 countries using four binders of the same grade (70/100 pen) from different crude sources. The short-term ageing was carried out using the standard procedure for rolling thin film oven test (RTFOT), but varying the temperatures. Long-term ageing was carried out using the standard procedure for pressure aging vessel (PAV) in addition to RTFOT. For the mechanical characterisation, rheological data were determined by using the dynamic shear rheometer (DSR) and conventional tests, with needle penetration and softening point using the ring and ball method. The results show that although different short-term ageing temperatures showed a significant difference in the mechanical properties of the binders, these differences vanished after long-term ageing with PAV.

Study design:Prospective study.Objectives:To describe the nutritional risk/status of Chinese children with spinal cord injury (SCI) at admission and determine the relationship between nutritional risk/status and demography/SCI characteristics.Setting:China Rehabilitation Research Center, Beijing, China.Methods:Baseline clinical data, appetite level, anthropometric measurements and Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) scores were obtained for pediatric SCI patients. The relationships among the demographic/SCI characteristics and STAMP score and z-scores of weight-for-age (WAZ), height-for-age (HAZ) and body mass index-for-age (BAZ) were assessed. The risk of undernutrition was compared with actual nutritional status.Results:Forty-five children including 12 boys and 33 girls were included. The risks of undernutrition using the STAMP tool and malnutrition were 51.1% and 55.6%, respectively. Children with different demographic characteristics had similar nutritional status and risk of malnutrition. The risk of undernutrition was associated with nutritional status, including WAZ (P<0.001), HAZ (P=0.001), BAZ (P<0.001) and appetite level (P<0.001). Compared with nutritional status, STAMP had a sensitivity of 100%, a specificity of 73.3% and an overall agreement of 82.2%. As the duration of SCI increased, the risks of overweight and stunting increased.Conclusions:Nutritional screening in all pediatric SCI patients should be performed periodically. The decreasing trends in nutritional status and appetite level after SCI require special attention. The STAMP may be an alternative method for assessing nutritional status in Chinese children with SCI.

The thickness of the plate in temperature gradient rolling is first divided into 2 melements, and mis an undetermined parameter which can be limited. Based on these thickness elements with different temperatures, the rolling force of this advanced process is first analyzed with slab method. Also the predictions of thickness ratio with different temperatures and reductions of each thickness elements are proposed in this paper. The results measured after rolling experiments are used to compare with these calculated by this model in order to verify its accuracy. In the experiment, a multi-metals riveting plate in the same temperature is designed to simulate a single metal one in gradient temperatures based on the thickness elements. Since the model is based on an analytical method which is strongly supported by the rolling theories, it can be applied in real gradient temperature rolling for ultra-heavy plate.

Self-lubricating antiwear composite coatings were fabricated on Ti6Al4V alloy by laser cladding. The dry sliding wear tests under various temperatures (ambient temperature, 350°C and 700°C) and normal loads (3, 6, 9 and 12 N) were accomplished, and the corresponding wear mechanisms were investigated. Results show that the composite coating presented lower friction coefficient at ambient temperature and 700°C, and the wear rate increased monotonously from ambient temperature to 700°C. The reasons are that the hard phases of TiC and TiWC2carbides enhance the wear capabilities at ambient temperature to 350°C. The CrS and Ti2CS sulphides have friction reducing effect at 700°C. The friction coefficient decreased and the wear rate increased with the increasing of normal load. It is ascribed to the effects of the CrS and Ti2CS sulphides at moderate normal load. It is implied that the tribological property of the composite coating showed the best at ambient temperature and moderate normal load.

This study investigated the friction performance of polyimide-matrix composites with various silica powder contents of different sizes. The friction tests were performed on a pin-on-disk tester at various velocities, ranging from 30 to 160 km/h. The experimental results indicate a silica powder size of 0.25±0.05 mm, a sample of 4 wt.% SiO2demonstrated a high friction coefficient and better wear performance as compared to a sample without silica. The influence of silica content and powder size on the friction coefficient is directly related to the friction velocity. At low friction velocity (30–90 km/h), the friction coefficient increases as the SiO2content increases, but decreases with increasing SiO2particle size. At high friction velocity (90–160 km/h), the content and particle size of SiO2have little influence on the friction coefficient. Experimental results indicate that large SiO2particles can effectively hinder the motion of third body, which is advantageous to the formation of a compact third body and to the protection of the friction surface.