bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Phenotypic Alterations of Alveolar Type II Cells in Response to Aflatoxin G1‐Induced Lung Inflammation
Authors: Shen Haitao , Liu Chunping , Shao Peilu , Yi Li , Wang Yuan , Mills Ko Emily , Tian Ziqiang , Zhao Xin , Wang Juan , Xing Lingxiao , Zhang Xianghong
Published: October 2014

Recently, we discovered that Aflatoxin G1 (AFG1) induces chronic lung inflammatory responses, which may contribute to lung tumorigenesis in Balb/C mice. The cancer cells originate from alveolar type II cells (AT‐II cells). The activated AT‐II cells express high levels of MHC‐II and COX‐2, may exhibit altered phenotypes, and likely inhibit antitumor immunity by triggering regulatory T cells (Tregs). However, the mechanism underlying phenotypic alterations of AT‐II cells caused by AFG1‐induced inflammation remains unknown. In this study, increased MHC‐II expression in alveolar epithelium was observed and associated with enhanced Treg infiltration in mouse lung tissues with AFG1‐induced inflammation. This provides a link between phenotypically altered AT‐II cells and Treg activity in the AFG1‐induced inflammatory microenvironment. AFG1‐activated AT‐II cells underwent phenotypic maturation since AFG1 upregulated MHC‐II expression on A549 cells and primary human AT‐II cells in vitro. However, mature AT‐II cells may exhibit insufficient antigen presentation, which is necessary to activate effector T cells, due to the absence of CD80 and CD86. Furthermore, we treated A549 cells with AFG1 and TNF‐α together to mimic an AFG1‐induced inflammatory response in vitro, and we found that TNF‐α and AFG1 coordinately enhanced MHC‐II, CD54, COX‐2, IL‐10, and TGF‐β expression levels in A549 cells compared to AFG1 alone. The phenotypic alterations of A549 cells in response to the combination of TNF‐α and AFG1 were mainly regulated by TNF‐α‐mediated induction of the NF‐κB pathway. Thus, enhanced phenotypic alterations of AT‐II cells were induced in response to AFG1‐induced inflammation. Thus, AT‐II cells are likely to suppress anti‐tumor immunity by triggering Treg activity. J. Cell. Physiol. 230: 1199–1211, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
Analytical techniques used for the characterization and authentification of six ancient religious manuscripts (XVIII–XIX centuries)
Authors: Vornicu Nicoleta , Deselnicu Viorica , Bibire Cristina , Ivanov Daniela , Doroftei Florica
Published: October 2014

This article presents the experimental results of a research on six manuscripts (three of the XVIII century and three of XIX century) belonging collection of old religious books to the Moldovan Metropolitan Church of Romania. Non‐invasive techniques (optical microscopy [OM], scanning electron microscopy/energy dispersive X‐ray system, X‐ray fluorescence analysis, shrinkage temperature, and Fourier transform infrared spectroscopy/attentuated total reflectance) provided information on the degree of degradation and identification of the leather bookbinding type. Moreover, visual assessment and OM revealed the extent of the surface degradation (wane, biological attack, change color, etc.). The degradation extent of the skin bindings was determined on the 12 samples. The insight on the mechanism of degradation was accomplished by analyzing the deterioration of collagen fibers in terms of shrinkage temperature and chemical modifications induced by oxidative and hydrolytic processes. Shrinkage temperature values were lower compared with the literature data for collagen, indicating that the leather bookbinding suffered intrinsic damage. Morphological analysis was accomplished by microscopy and allowed the identification of skin type and provided information about its processing technique. Mineral elements were identified for leather composition and contributed to the information regarding the origin and the extent of degradation of the leather bookbinding, of the studied manuscripts. The analyzed results were useful in determining the state of preservation and were able to provide an increased efficiency of further restoration. The correlation of the obtained data brought new contributions to the knowledge of the leather covers for the book technique in the XVIII and XIX centuries in monastic workshops of Eastern Europe. Microsc. Res. Tech. 78:70–84, 2015. © 2014 Wiley Periodicals, Inc.
Oxidative stress is independent of inflammation in the neurodegenerative sanfilippo syndrome type B
Authors: Trudel Stéphanie , Trécherel Eric , Gomila Cathy , Peltier Maxime , Aubignat Michaël , Gubler Brigitte , Morlière Patrice , Heard Jean‐Michel , Ausseil Jérôme
Published: October 2014

Mucopolysaccharidosis (MPS) type IIIB is a genetic deficiency of α‐N‐acetylglucosaminidase, inducing accumulation of partially degraded heparan sulfate (HS) oligosaccharides in tissues. In the central nervous system, this accumulation is associated with microglial activation, neurodegeneration, and oxidative stress. We have already shown that HS activates microglial cells through toll‐like receptor 4 (TLR4) and triggers neuroinflammation. The present study investigates whether oxidative stress is a direct consequence of inflammation or is an independent event directly caused by HS accumulation. The present study addresses causative links between oxidative stress and inflammation by analyzing the corresponding markers in the cortex of control mice, MPSIIIB mice (with neuroinflammation), and double mutant TLR4 knockout MPSIIIB mice (without neuroinflammation at early stages). Results showed that, although inflammation was not present in the cortex of 10‐day‐old double mutant MPSIIIB/TLR4–/– mice, the enzymatic activity of total superoxide dismutase (SOD) was already greater than in control animals. Moreover, at 3 and 8 months of age, the total enzymatic activities of glutathione peroxidase, SOD, and carbonyl protein levels in the cortex of MPSIIIB/TLR4–/– mice were similar to those measured in MPSIIIB mice and were higher than those in controls. The results indicate that the oxidative stress present at a very early stage in the brain of MPSIIIB mice is not the consequence of neuroinflammation. Insofar as it has an impact on the development of neurological disease, reducing oxidative stress might prevent or slow the progression of MPSIIIB. © 2014 Wiley Periodicals, Inc.
Humus balances of different farm production systems in main production areas in Austria
Authors: Kasper Martina , Freyer Bernhard , Hülsbergen Kurt‐Jürgen , Schmid Harald , Friedel Jürgen Kurt
Published: October 2014

The importance of the soil humus content is indisputable. Soil humus plays an important role in preserving soil fertility and exerts great influence on plant production and yield potential. However, proofing that management‐related changes in the stock of soil organic matter (SOM) have taken place against the background of spatial and temporal variation is a difficult task. In most cases, sampling over a long period of time is needed to verify these changes. Alternatively, potential changes in the SOM stock can be estimated using humus balancing models, which help to identify the need for humus reproduction on a farm. In general, a humus balance is the difference between the humus demand of cultivated crops and humus supply through crops and organic fertilizers. In this study, the ‘Dynamic Humus Unit Method' within the modelling program REPRO was applied to calculate the humus balance for 29 model‐farms that are representative of most of the agricultural production in Austria. Each model‐farm represents a specific production type (PT) and farming system in a defined region or main production area (MPA). This approach gives an overview of the humus balances at a large scale and allows a general trend in Austria to be estimated. Besides differing between conventional and organic farming systems, specific site conditions can also be selected in the model. The constructed model‐farms belong to different PTs such as “forage production”, “cash crops”, “refinement”, and “permanent crops”. The PT “permanent crops” refers to the cultivation of wine. The cropping system of each PT was analyzed in detail, while livestock keeping was considered only when applicable. Positive humus balances were found for all PTs except for permanent crops. The results ranged from –122 to 890 kg C ha−1 y−1. Regions and farm structure, e.g., forage production compared to cash crop, were found to have a greater influence than the kind of farming system (i.e., organic vs. conventional farming). Comparing the different PTs, forage production had the highest positive humus balances (219 to 890 kg C ha−1 y−1), followed by cash crop (24 to 239 kg C ha−1 y−1), refinement (–64 to 402 kg C ha−1 y−1) and permanent crops (–122 to –38 kg C ha−1 y−1). Regarding the farming system, organic farming led to more humus accumulation than conventional farming due to a higher share of fodder legumes and catch crops and more diverse crop rotations. The results were within the range of available empirical data on SOM change, and it was therefore concluded that the results are reasonable. In general, humus reproduction can be regarded as sufficient for agricultural production.
Combined effects of phosphorus nutrition and elevated carbon dioxide concentration on chlorophyll fluorescence, photosynthesis, and nutrient efficiency of cotton
Authors: Singh Shardendu K. , Reddy Vangimalla R.
Published: October 2014

To examine the combined effects of phosphorus (P) nutrition and CO2 on photosynthesis, chlorophyll fluorescence (CF), and nutrient utilization and uptake, two controlled‐environment experiments were conducted using 0.01, 0.05 and 0.20 mM external phosphate each at ambient and elevated CO2 (aCO2: 400 and eCO2: 800 µmol mol−1, respectively). The CF parameters were affected more by P nutrition than by CO2 treatment. Photoinhibition of photosystem II (PSII) was due to increased minimal CF (Fo′) and decreased maximal CF (Fm′), and efficiency of energy harvesting (Fv′/Fm′). In addition, reduced electron transport rate (ETR), the quantum yield of PSII (ΦPSII) and CO2 assimilation ($ \Phi _{\rm CO_2} $), and overall photochemical quenching in the P‐deficient leaves led to reduction in the efficiency of energy transfer to the PSII reaction center. Stimulation in the ΦPSII/$ \Phi _{\rm CO_2} $ and photorespiration (ETR/Pnet) was found under P deficiency, whereas the opposite was the case under CO2 enrichment. On average, photosynthetic rate (Pnet) and stomatal conductance declined by 50–53% at 0.05 mM P and by 70–72% at 0.01 mM P as compared to the 0.20 mM P treatment. However, P deficiency, especially at eCO2, tended to increase the intrinsic water‐use efficiency. In the P‐deficient plants, the decline in the P and N utilization efficiency (up to 91%) of biomass production was mainly associated with greater reduction in the biomass relative to the tissue P concentration as the P supply was reduced. However, it was significantly stimulated by eCO2 especially at higher P supply. The CO2 × P interaction was observed for some parameters such as Fo′, Fm′, P utilization efficiencies of photosynthesis and biomass production that might be attributed to the irresponsiveness of these parameters to eCO2 under low P treatment. Thus, P deficiency limited the beneficial effect of eCO2. A close relationship between total biomass and photosynthesis with the P and N utilization or uptake efficiencies was found. The P utilization efficiency of Pnet appeared to be stable across a range of leaf P concentrations, whereas the N‐utilization efficiency markedly increased with leaf P and differed between CO2 levels. An apparent effect of both the treatments (P and CO2) on N‐uptake and utilization efficiency also indicated the alteration in N acquisition and assimilation in cotton plants.
Artificial pores attract barley roots and can reduce artifacts of pot experiments
Authors: Pfeifer Johannes , Kirchgessner Norbert , Walter Achim
Published: October 2014

Soil compaction is a severe agricultural problem. It is characterized by an increased resistance to root penetration and by a decreased amount of porosity in the soil. Until today it is not clear whether crop roots are able to actively detect remaining pores in compacted soil. Moreover, little is known about the capability of roots to leave pores again if the mechanical resistance of the bulk soil allows so. The aim of this study was to investigate the root growth response of spring barley (Hordeum vulgare L. cv. Ascona) in different configurations of a compacted loamy soil containing pores. The three‐dimensional configurations of the root systems from three well watered and fertilized treatments were analyzed with X‐ray computed tomography. All soil‐filled cylindrical plastic pots (diameter: 60 mm, height: 210 mm) contained loose topsoil but differed in subsoil structure. In treatment ‘Loose' [L] the pots were entirely filled with loose soil. Treatment ‘Lower part compacted' [C] contained compacted soil in the lower part of the pots. Likewise, treatment ‘Pores' [P] contained compacted soil in the lower part too, but here 16 artificial pores (1 mm diameter) were generated in the central part of the compacted subsoil zone. Comparison of the two treatments with compacted soil [C] and [P] showed that the roots were able to detect pores. However, the roots frequently grew across the pores or left the pores again after having grown into them, leading to a significantly higher fraction of roots exploring the compacted soil in the treatment with pores compared to the treatment without pores. These findings are useful for designing controlled experiments in pots of limited size that can mimic root growth in relatively complex soil structures which are more similar to field situations than usual pot experiments.
Glycemic responses to intermittent hepatic inflow occlusion in living liver donors
Authors: Han Sangbin , Sangwook Ko Justin , Jin Sang‐Man , Man Kim Jong , Choi Soo Joo , Joh Jae‐Won , Hoon Chung Yang , Lee Suk‐Koo , Gwak Mi Sook , Kim Gaabsoo
Published: October 2014

The occurrence of glycemic disturbances has been described for patients undergoing intermittent hepatic inflow occlusion (IHIO) for tumor removal. However, the glycemic responses to IHIO in living liver donors are unknown. This study investigated the glycemic response to IHIO in these patients and examined the association between this procedure and the occurrence of hyperglycemia (blood glucose > 180 mg/dL). The data from 154 living donors were retrospectively reviewed. The decision to perform IHIO was made on the basis of the extent of bleeding that occurred during parenchymal dissection. One round of IHIO consisted of 15 minutes of clamping and 5 minutes of unclamping the hepatic artery and portal vein. Blood glucose concentrations were measured at predetermined time points, including the start and end of IHIO. Repeated hyperglycemic episodes occurred after unclamping. The mean maximum intraoperative blood glucose concentration was greater in donors who underwent ≥3 rounds of IHIO versus those who underwent 1 or 2 rounds (169 ± 30 versus 149 ± 31 mg/dL, P = 0.005). The incidence of intraoperative hyperglycemia was also greater in donors who underwent ≥3 rounds of IHIO versus those who underwent 1 or 2 rounds (38.7% versus 7.7%, odds ratio = 7.1, 95% confidence interval = 2.5‐20.4, P < 0.001). Donors who did not undergo IHIO and those who underwent 1 or 2 rounds of IHIO exhibited similar maximum glucose concentrations and similar incidence rates of hyperglycemia. In conclusion, IHIO induced repeated hyperglycemic responses in living donors, and donors who underwent ≥3 rounds of IHIO were more likely to experience intraoperative hyperglycemia. These results provide additional information on the risks and benefits of IHIO in living donors. Liver Transpl 21:180‐186, 2015. © 2014 AASLD.
Management of bleeding and transfusion during liver transplantation before and after the introduction of a rotational thromboelastometry–based algorithm
Authors: Roullet Stéphanie , Freyburger Geneviève , Cruc Maximilien , Quinart Alice , Stecken Laurent , Audy Magali , Chiche Laurence , Sztark François
Published: October 2014

Orthotopic liver transplantation (OLT) remains a potentially hemorrhagic procedure. Rotational thromboelastometry (ROTEM) is a point‐of‐care device used to monitor coagulation during OLT. Whether it allows blood loss and transfusions to be reduced during OLT remains controversial. Excellent correlations and predictive values have been found between ROTEM parameters and fibrinogen. We hypothesized that the use of a ROTEM‐based transfusion algorithm during OLT would lead to more fibrinogen transfusion and decreased bleeding and blood transfusion. Sixty adult patients were consecutively included in a prospective, without‐versus‐with study: 30 in the group without ROTEM results and 30 in the group with the ROTEM‐based algorithm. A small and nonsignificant increase in median fibrinogen transfusions was found for the with group (6.0 g versus 4.5 g, P = 0.50). It was not associated with a decrease in blood transfusions or in the number of patients exposed to blood products. Liver Transpl 21:169‐179, 2015. © 2014 AASLD.
Dopamine‐Based Coatings and Hydrogels: Toward Substitution‐Related Structure–Property Relationships
Authors: Cui Jiaxi , Iturri Jagoba , Paez Julieta , Shafiq Zahid , Serrano Cristina , d'Ischia Marco , del Campo Aránzazu
Published: October 2014

The influence of 6‐chloro and 6‐nitro substituents on the thickness, homogeneity, and general properties of coatings produced by controlled oxidative polymerization of dopamine and its β‐hydroxy derivative, norepinephrine, is investigated. Substitution at the catecholamine 6‐position affects the deposition kinetics due to modification of the oxidation potential of the catechol groups. Increasing the hydroxyl group acidity results likewise in changes in pH response and water uptake. A similar trend with pH is also observed in covalently crosslinked catechol‐functionalized PEG‐hydrogels, while an opposite behavior is measured in metal crosslinked films. These results pave the way toward the definition of structure–property relationships based on dopamine substitution effects in polycatecholamine layers and derived polymers.

image
Simple Synthesis of P(Cbz‐alt‐TBT) and PCDTBT by Combining Direct Arylation with Suzuki Polycondensation of Heteroaryl Chlorides
Authors: Lombeck Florian , Matsidik Rukiya , Komber Hartmut , Sommer Michael
Published: October 2014

Direct arylation (DA) of 2‐chlorothiophene and 2‐chloro‐3‐hexylthiophene with 4,7‐dibromo‐2,1,3‐benzothiadiazole is used to synthesize 4,7‐bis(5‐chloro‐2‐thienyl)‐2,1,3‐benzothiadiazole (TBTCl2) and 4,7‐bis(5‐chloro‐4‐hexyl‐2‐thienyl)‐2,1,3‐benzothiadiazole (DH‐TBTCl2) in one step. Suitable conditions of the Suzuki polycondensations (SPC) of TBTCl2 and DH‐TBTCl2 with the carbazole comonomer CbzPBE2 are established, furnishing PCDTBT and P(Cbz‐alt‐TBT) with high molecular weight and yield. Compared with control samples made from the corresponding dibromides, high‐temperature NMR and UV–vis spectroscopy indicate similar properties for PCDTBT but an increased content of Cbz–Cbz homocouplings for P(Cbz‐alt‐TBT).

image
Two‐stage face transplantation: A new concept in vascularized composite allotransplantation
Authors: Ramirez Alejandro E. , Lao William W. , Wang Yen‐Ling , Cheng Hui‐Yun , Wei Fu‐Chan
Published: October 2014

Background: Animal models and clinical cases of facial allotransplantation have been performed as a single stage procedure. A staged surgery might offer some advantages in selected cases. In this study, a two‐stage face transplantation approach was performed on rat and the feasibility and safety were evaluated. Methods: Brown Norway rats were used as donors and Lewis rats as recipients in the allotransplantation groups. A total of 33 hemiface‐scalp transplantations were performed. Syngeneic orthotopic transplantations were performed either in one‐stage (one single stage surgery; N = 3), local two‐stage [heterothopic transplantation to the neck during the first stage and graft rotation as a pedicled flap to cover the facial defect on postoperative day (POD) 2; N = 3], or distant two‐stage approaches (heterothopic transplantation to the groin during the first stage and free graft transfer to the face on postoperative day 2; N = 3). In the allotransplantation groups using the same approaches, 12 received no treatment (N = 4 each subgroup) and 12 received the same tapering dose of cyclosporine (10 to 2 mg/Kg/day; N = 4 each subgroup). Graft survival and the rejection grades were assessed clinically and pathologically. Results: All syngeneic transplants survived for the follow‐up period of 180 days. The mean rejection‐free survival and total survival of the allograft in the no treatment group was 6 ± 0.3 and 14.3 ± 4.5 days in the one‐stage group, 6 ± 0.4 and 18.5 ± 1 days in the local two‐stage group and 6 ± 0.2 and 14.3 ± 5.7 (P > 0.05). All allografts in the treatment groups did not develop rejection during the 42 days follow‐up period. Conclusions: It is feasible, reliable, reproducible, and safe to perform a two‐stage face transplantation in rats. This novel approach has the potential to be applied in research and eventually in selected clinical cases of facial allotransplantation. © 2014 Wiley Periodicals, Inc. Microsurgery 35:218–226, 2015.
Free flap monitoring using an implantable anastomotic venous flow coupler: Analysis of 119 consecutive abdominal‐based free flaps for breast reconstruction
Authors: Kempton Steve J. , Poore Samuel O. , Chen Jenny T. , Afifi Ahmed M.
Published: October 2014

Purpose

The purpose of this study is to evaluate the use of the venous anastomotic Flow Coupler in monitoring free flaps used for breast reconstruction in a consecutive series of patients.

Methods

Retrospective data were collected on patients undergoing free flap breast reconstruction from May 2012 to March 2014. The venous anastomotic Flow Coupler was used in the first 85 flaps and a non‐flow Coupler with clinical and external Doppler monitoring alone in the subsequent 34 flaps. Data collected included patient age, BMI, prior radiation, flap type, intra‐ and postoperative Flow Coupler events, along with rates of flap take back, salvage, and failure. Proportion data were compiled and statistically analyzed.

Results

One hundred nineteen consecutive abdominal based breast reconstruction free flaps were performed. The overall flap failure rate was 4.2% (4.7% Flow Coupler; 2.9% in non‐flow Coupler; P = 1.0). The Flow Coupler demonstrated 100% sensitivity in the intra‐ and postoperative settings. A positive predictive value of 36% was noted intraoperatively which was significantly higher compared to the non‐flow Coupler group (P = 0.015). Vessel thrombosis occurred in 17.6% of Flow Coupler flaps, which was significantly higher when compared to the non‐flow Coupler (2.9%; P = 0.038).

Conclusions

The Flow Coupler is a sensitive method to confirm patency of a microsurgical anastomosis. However, there is a high false positive rate in both the intraoperative and postoperative settings resulting in frequent intraoperative maneuvers to amend the cause of signal loss. Additionally, the Flow Coupler resulted in significantly more vascular thrombotic events when compared to the non‐flow Coupler. © 2014 Wiley Periodicals, Inc. Microsurgery 35:337–344, 2015.
Gegenbauer spectral method for time‐fractional convection–diffusion equations with variable coefficients
Authors: Izadkhah Mohammad Mahdi , Saberi‐Nadjafi Jafar
Published: October 2014

In this paper, we study the numerical solution to time‐fractional partial differential equations with variable coefficients that involve temporal Caputo derivative. A spectral method based on Gegenbauer polynomials is taken for approximating the solution of the given time‐fractional partial differential equation in time and a collocation method in space. The suggested method reduces this type of equation to the solution of a linear algebraic system. Finally, some numerical examples are presented to illustrate the efficiency and accuracy of the proposed method. Copyright © 2014 John Wiley & Sons, Ltd.
Characterization of aging and solvent treatments of painted surfaces using single‐sided NMR
Authors: Fife Gwendoline R. , Stabik Bascha , Kelley Allison E. , King Jared N. , Blümich Bernhard , Hoppenbrouwers René , Meldrum Tyler
Published: October 2014

Typical experiments conducted with single‐sided NMR are incapable of unique chemical identification and, thus, often rely on comparative measurements in scientific study. However, cultural heritage objects have unique natures and histories, making a genuine ‘control’ sample a rarity and complicating many scientific investigations. In this paper, we present some comparative results enabled by such a rare, control sample. Two paintings, The Dinner and The Dance from the 1616 set Pipenpoyse Wedding, were made by the same artist with indistinguishable materials and techniques. However, despite their shared history, The Dinner has undergone varnishing and subsequent varnish removal multiple times, whereas The Dance has not. NMR measurements on these two paintings show the effect of organic‐solvent‐based treatments on the stiffness of the paintings as measured by T2,eff, supporting visual and tactile observations that The Dinner is stiffer throughout its thickness than The Dance, probably due to ingress of natural resins and organic solvents into the paint and ground layers. In addition to a comparative analysis of these two paintings, initial experiments to compare solvent penetration with different varnish removal methods are described. Model canvas painting samples were treated with solvent in two ways—with free solvent on a swab and with cellulose gel thickened solvent in a tissue. Both treatment methods cause a measurable change in T2,eff; however, the thickened‐solvent method affects a narrower region of the model than does the free solvent. Copyright © 2014 John Wiley & Sons, Ltd.
Optimal patrol to uncover threats in time when detection is imperfect
Authors: Lin Kyle Y. , Atkinson Michael P. , Glazebrook Kevin D.
Published: October 2014

Consider a patrol problem, where a patroller traverses a graph through edges to detect potential attacks at nodes. An attack takes a random amount of time to complete. The patroller takes one time unit to move to and inspect an adjacent node, and will detect an ongoing attack with some probability. If an attack completes before it is detected, a cost is incurred. The attack time distribution, the cost due to a successful attack, and the detection probability all depend on the attack node. The patroller seeks a patrol policy that minimizes the expected cost incurred when, and if, an attack eventually happens. We consider two cases. A random attacker chooses where to attack according to predetermined probabilities, while a strategic attacker chooses where to attack to incur the maximal expected cost. In each case, computing the optimal solution, although possible, quickly becomes intractable for problems of practical sizes. Our main contribution is to develop efficient index policies—based on Lagrangian relaxation methodology, and also on approximate dynamic programming—which typically achieve within 1% of optimality with computation time orders of magnitude less than what is required to compute the optimal policy for problems of practical sizes. © 2014 Wiley Periodicals, Inc. Naval Research Logistics, 61: 557–576, 2014
Real‐time monitoring of thermal processes by reduced‐order modeling
Authors: Aguado José V. , Huerta Antonio , Chinesta Francisco , Cueto Elías
Published: October 2014

This work presents a simple technique for real‐time monitoring of thermal processes. Real‐time simulation‐based control of thermal processes is a big challenge because high‐fidelity numerical simulations are costly and cannot be used, in general, for real‐time decision making. Very often, processes are monitored or controlled with a few measurements at some specific points. Thus, the strategy presented here is centered on fast evaluation of the response only where it is needed. To accomplish this, classical harmonic analysis is combined with recent model reduction techniques. This leads to an advanced harmonic methodology, which solves in real time the transient heat equation at the monitored point.

In order to apply the reciprocity principle, harmonic analysis is used in the space‐frequency domain. Then, Proper Generalized Decomposition, a reduced order approach, pre‐computes a transfer function able to produce the output response for a given excitation. This transfer function is computed offline and only once. The response at the monitoring point can be recovered performing a computationally inexpensive post‐processing step. This last step can be performed online for real‐time monitoring of the thermal process. Examples show the applicability of this approach for a wide range of problems ranging from fast temperature evaluation to inverse problems. Copyright © 2014 John Wiley & Sons, Ltd.
Multilayered grouping parallel algorithm for multiple‐level multiscale analyses
Authors: Cho In Ho , Porter Keith A.
Published: October 2014

Multiscale analysis technique became a successful remedy to complicated problems in which nonlinear behavior is linked with microscopic damage mechanisms. For efficient parallel multiscale analyses, hierarchical grouping algorithms (e.g., the two‐level ‘coarse‐grained’ method) have been suggested and proved superior over a simple parallelization. Here, we expanded the two‐level algorithm to give rise to a multilayered grouping parallel algorithm suitable for large‐scale multiple‐level multiscale analyses. With practical large‐scale applications, we demonstrated the superior performance of multilayered grouping over the coarse‐grained method. Notably, we show that the unique data transfer rates of the symmetric multiprocessor cluster system can lead to the seemingly ‘super‐linear speedup’ and that there appears to exist the optimal number of subgroups of three‐tiered multiscale analysis. Copyright © 2014 John Wiley & Sons, Ltd.
A new optimal linear quadratic observer‐based tracker under input constraint for the unknown system with a direct feed‐through term
Authors: Tsai J. S. H. , Wu C. Y. , Lee C. H. , Guo S. M. , Su T. J.
Published: October 2014

This paper develops a new optimal linear quadratic observer‐based tracker with input constraint for the linear unknown system with a direct transmission term from input to measured output. The off‐line observer/Kalman filter identification method is used to determine the linear sampled‐data model with a direct feed‐through term. On the basis of this model, a high‐gain optimal linear quadratic analog observer‐based tracker is proposed, so that it can effectively induce a high quality performance on the state estimation and the trajectory tracking design. Besides, the prediction‐based digital redesign method is utilized to obtain a relatively low‐gain and implementable observer and digital tracker from the theoretically well‐designed high‐gain analog observer and tracker for the linear system with a direct transmission term from input to output. To reduce the magnitude of control input, which is caused by the high‐gain property to fit the requirement of the input constraint, the modified linear quadratic analog tracker is proposed. Thus, the control input can be compressed effectively without losing the original high performance of tracking much. Copyright © 2014 John Wiley & Sons, Ltd.
A prospective observational study of oseltamivir safety and tolerability in infants and young children ≤24 months
Authors: Rath Barbara A. , Blumentals William A. , Miller Mary K. , Starzyk Kathryn , Tetiurka Boguslaw , Wollenhaupt Martina
Published: October 2014

Purpose

Infants and young children are at elevated risk of influenza‐associated complications, but information on the safety of antiviral therapies is limited in this age group.

Methods

In this prospective open‐label observational safety study, children aged ≤24 months with a clinical diagnosis of influenza in routine practice received either no antiviral treatment (‘unexposed’ group) or oseltamivir treatment or prophylaxis (‘exposed’ group), according to the physician's judgment. Patients were followed up for 30 days after the baseline visit.

Results

Adverse events (AEs) were analysed in 1065 patients; they were reported in 390/711 (54.9%) in the unexposed group, 167/340 (49.1%) patients in the exposed group, and 6/14 prophylaxis patients. Cough and rhinitis were the most common events, reported more often in unexposed children (22.9 and 20.3% respectively) than in exposed children (13.2 and 10.0%; p < 0.001); pyrexia, diarrhoea and vomiting were less common, occurring at similar rates in exposed and unexposed patients. Nasal congestion (3.5%), bronchitis (5.6%) and upper respiratory tract infection (1.5%) were reported more frequently in exposed patients than in unexposed patients (0.7, 2.7 and 0.1% respectively; p < 0.05). In the exposed group, 11.2% of patients (n = 38) experienced 41 AEs considered at least possibly related to oseltamivir, none being assessed as serious. Overall, there were 79 serious AEs in 59 patients. Eleven discontinued treatment because of an AE.

Conclusions

Oseltamivir has a good tolerability profile in infants and children aged ≤24 months. These findings contributed to the recent FDA approval of oseltamivir for treating infants aged 2–51 weeks. Copyright © 2014 John Wiley & Sons, Ltd.
Proteinase K improves quantitative acylation studies
Authors: Fränzel Benjamin , Fischer Frank , Steegborn Clemens , Wolters Dirk Andreas
Published: October 2014

Acetylation is a common PTM of proteins but is still challenging to analyze. Only few acetylome studies have been performed to tackle this issue. Yet, the detection of acetylated proteins in complex cell lysates remains to be improved. Here, we present a proteomic approach with proteinase K as a suitable protease to identify acetylated peptides quantitatively. We first optimized the digestion conditions using an artificial system of purified bovine histones to find the optimal protease. Subsequently, the capability of proteinase K was demonstrated in complex HEK293 cell lysates. Finally, SILAC in combination with MudPIT was used to show that quantification with proteinase K is possible. In this study, we identified a sheer number of 557 unique acetylated peptides originating from 633 acetylation sites.
Depletion of reduction potential and key energy generation metabolic enzymes underlies tellurite toxicity in Deinococcus radiodurans
Authors: Anaganti Narasimha , Basu Bhakti , Gupta Alka , Joseph Daisy , Apte Shree Kumar
Published: October 2014

Oxidative stress resistant Deinococcus radiodurans surprisingly exhibited moderate sensitivity to tellurite induced oxidative stress (LD50 = 40 μM tellurite, 40 min exposure). The organism reduced 70% of 40 μM potassium tellurite within 5 h. Tellurite exposure significantly modulated cellular redox status. The level of ROS and protein carbonyl contents increased while the cellular reduction potential substantially decreased following tellurite exposure. Cellular thiols levels initially increased (within 30 min) of tellurite exposure but decreased at later time points. At proteome level, tellurite resistance proteins (TerB and TerD), tellurite reducing enzymes (pyruvate dehydrogense subunits E1 and E3), ROS detoxification enzymes (superoxide dismutase and thioredoxin reductase), and protein folding chaperones (DnaK, EF‐Ts, and PPIase) displayed increased abundance in tellurite‐stressed cells. However, remarkably decreased levels of key metabolic enzymes (aconitase, transketolase, 3‐hydroxy acyl‐CoA dehydrogenase, acyl‐CoA dehydrogenase, electron transfer flavoprotein alpha, and beta) involved in carbon and energy metabolism were observed upon tellurite stress. The results demonstrate that depletion of reduction potential in intensive tellurite reduction with impaired energy metabolism lead to tellurite toxicity in D. radiodurans.
The major cystic fibrosis causing mutation exhibits defective propensity for phosphorylation
Authors: Pasyk Stan , Molinski Steven , Ahmadi Saumel , Ramjeesingh Mohabir , Huan Ling‐Jun , Chin Stephanie , Du Kai , Yeger Herman , Taylor Paul , Moran Michael F. , Bear Christine E.
Published: October 2014

The major cystic fibrosis causing mutation, F508del‐CFTR (where CFTR is cystic fibrosis transmembrane conductance regulator), impairs biosynthetic maturation of the CFTR protein, limiting its expression as a phosphorylation‐dependent channel on the cell surface. The maturation defect can be partially rescued by low‐temperature (27°C) cell culture conditions or small‐molecule corrector compounds. Following its partial rescue, the open probability of F508del‐CFTR is enhanced by the potentiator compound, VX‐770. However, the channel activity of rescued F508del‐CFTR remains less than that of the Wt‐CFTR protein in the presence of VX‐770. In this study, we asked if there are allosteric effects of F508del on the phosphorylation‐regulated R domain. To identify defects in the R domain, we compared the phosphorylation status at protein kinase A sites in the R domain of Wt and F508del‐CFTR. Here we show that phosphorylation of Ser‐660, quantified by SRM‐MS, is reduced in F508del‐CFTR. Although the generation of a phosphomimic at this site (substituting aspartic acid for serine) did not modify the maturation defect, it did enhance F508del‐CFTR channel function after pharmacological rescue with corrector VX‐809, and treatment with the potentiator, VX‐770. These findings support the concept that defective phosphorylation of F508del‐CFTR partially accounts for its altered channel activity at the cell surface.
Proteomic signatures associated with p53 mutational status in lung adenocarcinoma
Authors: Taguchi Ayumu , Delgado Oliver , Çeliktaş Müge , Katayama Hiroyuki , Wang Hong , Gazdar Adi F. , Hanash Samir M.
Published: October 2014

p53 is commonly mutated in lung adenocarcinoma. Mutant p53 loses wild‐type function and some missense mutations further acquire oncogenic functions, while p53 wild‐type may also induce pro‐survival signaling. Therefore identification of signatures based on p53 mutational status has relevance to our understanding of p53 signaling pathways in cancer and identification of new therapeutic targets. To this end, we compared proteomic profiles of three cellular compartments (whole‐cell extract, cell surface, and media) from 28 human lung adenocarcinoma cell lines that differ based on p53 mutational status. In total, 11 598, 11 569, and 9090 protein forms were identified in whole‐cell extract, cell surface, and media, respectively. Bioinformatic analysis revealed that representative pathways associated with epithelial adhesion, immune and stromal cells, and mitochondrial function were highly significant in p53 missense mutations, p53 loss and wild‐type p53 cell lines, respectively. Of note, mRNA levels of peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1‐α), a transcription coactivator that promotes mitochondrial oxidative phosphorylation and mitochondrial biogenesis, was substantially higher in p53 wild‐type cell lines compared to either cell lines with p53 loss or with missense mutation. Small interfering RNA targeting PGC1‐α inhibited cell proliferation in p53 wild‐type cell lines, indicative of PGC1‐α and its downstream molecules as potential therapeutic targets in p53 wild‐type lung adenocarcinoma.
Total and isoform‐specific quantitative assessment of circulating fibulin‐1 using selected reaction monitoring MS and time‐resolved immunofluorometry
Authors: Overgaard Martin , Cangemi Claudia , Jensen Martin L. , Argraves William S. , Rasmussen Lars M.
Published: October 2014

Purpose

Targeted proteomics using SRM‐MS combined with stable‐isotope dilution has emerged as a promising quantitative technique for the study of circulating protein biomarkers. The purpose of this study was to develop and characterize robust quantitative assays for the emerging cardiovascular biomarker fibulin‐1 and its circulating isoforms in human plasma.

Experimental design

We used bioinformatics analysis to predict total and isoform‐specific tryptic peptides for absolute quantitation using SRM‐MS. Fibulin‐1 was quantitated in plasma by nanoflow‐LC‐SRM‐MS in undepleted plasma and time‐resolved immunofluorometric assay (TRIFMA). Both methods were validated and compared to a commercial ELISA (CircuLex). Molecular size determination was performed under native conditions by SEC analysis coupled to SRM‐MS and TRIFMA.

Results

Absolute quantitation of total fibulin‐1, isoforms ‐1C, and ‐1D was performed by SRM‐MS. Fibulin‐1C was the most abundant isoform in plasma. Circulating fibulin‐1 isoforms were homo ‐or hetero multimeric complexes (range 318–364 kDa). Good correlation was obtained between SRM‐MS and TRIFMA but not CircuLex.

Conclusions and clinical relevance

For biomarker studies using smaller cohorts, SRM‐MS provides an alternative measure of total and specific fibulin‐1 isoforms in undepleted plasma. For larger cohorts TRIFMA provides a faster platform for fibulin‐1 quantitation in plasma. While the correlation between these methods was acceptable, low correlation was obtained between the commercial CircuLex assay and SRM‐MS or TRIFMA.
Hold or fold—Proteins in advanced heart failure and myocardial recovery
Authors: Mahr Claudius , Gundry Rebekah L.
Published: October 2014

Advanced heart failure (AHF) describes the subset of heart failure patients refractory to conventional medical therapy. For some AHF patients, the use of mechanical circulatory support (MCS) provides an intermediary “bridge” step for transplant‐eligible patients or an alternative therapy for transplant‐ineligible patients. Over the past 20 years, clinical observations have revealed that approximately 1% of patients with MCS undergo significant reverse remodeling to the point where the device can be explanted. Unfortunately, it is unclear why some patients experience durable, sustained myocardial remission, while others redevelop heart failure (i.e. which hearts “hold” and which hearts “fold”). In this review, we outline unmet clinical needs related to treating patients with MCS, provide an overview of protein dynamics in the reverse‐remodeling process, and propose specific areas where we expect MS and proteomic analyses will have significant impact on our understanding of disease progression, molecular mechanisms of recovery, and provide new markers with prognostic value that can positively impact patient care. Complimentary perspectives are provided with the goal of making this important topic accessible and relevant to both a clinical and basic science audience, as the intersection of these disciplines is required to advance the field.
Raman spectroscopy on mechanically exfoliated pristine graphene ribbons
Authors: Terrés Bernat , Reichardt Sven , Neumann Christoph , Watanabe Kenji , Taniguchi Takashi , Stampfer Christoph
Published: October 2014

We present Raman spectroscopy measurements of non‐etched graphene nanoribbons, with widths ranging from 15 to 160 nm, where the D‐line intensity is strongly dependent on the polarization direction of the incident light. The extracted edge disorder correlation length is approximately one order of magnitude larger than on previously reported graphene ribbons fabricated by reactive ion etching techniques. This suggests a more regular crystallographic orientation of the non‐etched graphene ribbons here presented. We further report on the ribbons width dependence of the line‐width and frequency of the long‐wavelength optical phonon mode (G‐line) and the 2D‐line in the studied graphene ribbons.

Scanning force microscope image of graphene ribbons on hexagonal boron nitride and SiO substrates. The scale bar is 1m.
Mohawk Promotes the Tenogenesis of Mesenchymal Stem Cells Through Activation of the TGFβ Signaling Pathway
Authors: Liu Huanhuan , Zhang Can , Zhu Shouan , Lu Ping , Zhu Ting , Gong Xiaonan , Zhang Ziwang , Hu Jiajie , Yin Zi , Heng Boon Chin , Chen Xiao , Wei Ouyang Hong
Published: October 2014

The transcription factor Mohawk (Mkx) is expressed in developing tendons and is an important regulator of tenogenic differentiation. However, the exact roles of Mkx in tendinopathy and tendon repair remain unclear. Using gene expression Omnibus datasets and immunofluorescence assays, we found that Mkx expression level was dramatically lower in human tendinopathy tissue and it is activated at specific stages of tendon development. In mesenchymal stem cells (MSCs), ectopic Mkx expression strikingly promoted tenogenesis more efficiently than Scleraxis (Scx), a well-known master transcription factor of tendon. Significantly higher levels of tenogenic gene expression and collagen fibril growth were observed with Mkx versus Scx. Interestingly, it was observed that Mkx dramatically upregulated Scx through binding to the Tgfb2 promoter. Additionally, the transplantation of Mkx-expressing-MSC sheets promoted tendon repair in a mouse model of Achilles-tendon defect. Taken together, these data shed light on previously unrecognized roles of Mkx in tendinopathy, tenogenesis, and tendon repair as well as in regulating the TGFβ pathway. Stem Cells  2015;33:443–455
Human Myocardial Pericytes: Multipotent Mesodermal Precursors Exhibiting Cardiac Specificity
Authors: Chen William C. W. , Baily James E. , Corselli Mirko , Díaz Mary E. , Sun Bin , Xiang Guosheng , Gray Gillian A. , Huard Johnny , Péault Bruno
Published: October 2014

Perivascular mesenchymal precursor cells (i.e., pericytes) reside in skeletal muscle where they contribute to myofiber regeneration; however, the existence of similar microvessel-associated regenerative precursor cells in cardiac muscle has not yet been documented. We tested whether microvascular pericytes within human myocardium exhibit phenotypes and multipotency similar to their anatomically and developmentally distinct counterparts. Fetal and adult human heart pericytes (hHPs) express canonical pericyte markers in situ, including CD146, NG2, platelet-derived growth factor receptor (PDGFR) β, PDGFRα, alpha-smooth muscle actin, and smooth muscle myosin heavy chain, but not CD117, CD133, and desmin, nor endothelial cell (EC) markers. hHPs were prospectively purified to homogeneity from ventricular myocardium by flow cytometry, based on a combination of positive- (CD146) and negative-selection (CD34, CD45, CD56, and CD117) cell lineage markers. Purified hHPs expanded in vitro were phenotypically similar to human skeletal muscle-derived pericytes (hSkMPs). hHPs express mesenchymal stem/stromal cell markers in situ and exhibited osteo-, chondro-, and adipogenic potentials but, importantly, no ability for skeletal myogenesis, diverging from pericytes of all other origins. hHPs supported network formation with/without ECs in Matrigel cultures; hHPs further stimulated angiogenic responses under hypoxia, markedly different from hSkMPs. The cardiomyogenic potential of hHPs was examined following 5-azacytidine treatment and neonatal cardiomyocyte coculture in vitro, and intramyocardial transplantation in vivo. Results indicated cardiomyocytic differentiation in a small fraction of hHPs. In conclusion, human myocardial pericytes share certain phenotypic and developmental similarities with their skeletal muscle homologs, yet exhibit different antigenic, myogenic, and angiogenic properties. This is the first example of an anatomical restriction in the developmental potential of pericytes as native mesenchymal stem cells. Stem Cells  2015;33:557–573