bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolving Vision of Regulatory Science in the Global Medical Community
Authors: Kondo Tatsuya , Hayashi Yoshikazu , Sato Junko , Sekine Shohko , Hoshino Tatsuro , Sato Daisaku
Published: August 2019

“Regulatory science” (RS) has been defined in various ways, but, nevertheless, the definitions of RS in different parts of the world include many common elements. It seems to be a common view that RS is not basic or applied science but, rather, focuses on the estimation and prediction of safety and efficacy. Thus, we think RS overall should incorporate not only RS specifically for medical product assessment but also RS engineering to provide prediction and estimation tools for those purposes, including guideline/guidance development. It is important as well to consider the potential contribution of RS to rational medicine (i.e., to evidence‐based medicine in a broader context), and especially to real‐world evidence generation. We will look at how definitions of RS have evolved, and how we believe RS might develop in the future. Taking a patient‐centric view, we re‐emphasize RS is an ethical science contributing to society and human welfare.
Impact of environmental policy on firm's market performance: The case of ISO 14001
Authors: Riaz Hammad , Saeed Abubakr
Published: August 2019

Environmental Management System, that is, ISO 14001, helps to build corporate reputation, legitimacy, and can also be considered as firms' strategic response to institutional pressure to reduce the impact of business activity on natural environment. It arises the question: does ISO 14001 pay off financially? Unfortunately, this question remains broadly unanswered. Current studies on this issue show mixed and inconclusive findings. By employing rigorous event study approach, this paper compares ISO 14001 certified firms with their noncertified counterpart based on different matching criteria that include size, return on asset, and industry. The results indicate that the ISO 14001 is negatively evaluated by the investors in both the short and long run. This paper also suggests implications for policy makers, managers, and other nonprofit organizations.
A mathematical method to realize complex poles in a high‐order passive switched‐capacitor filter
Authors: Niaboli Guilani Mohammad , Ardeshir Gholamreza
Published: August 2019

A high‐order discrete‐time IIR low‐pass with complex poles using charge sampling is presented in a single‐stage structure by using a mathematical strategy. In comparison with the analog complex‐poles Gm‐C filters, the proposed filter consumes lower power and has good linearity, and all of the tunings are implemented only by capacitor sizes. The proposed filter is a seventh‐order Butterworth, but this method can be generalized to implement other complex pole filters like Tchebyshev and Elliptic. Post‐layout simulation results in 130‐nm complementary metal‐oxide‐semiconductor (CMOS) show an IIP3 of +18 dBm and a noise figure of 5 dB. The filter has a rejection of more than 110 dB in its stop band and consumes 1.5 mW with a 1.6‐V supply voltage, and circuit occupies an about 0.12 mm2 of silicon.
Circuit‐based logical layer 2 bridging in software‐defined data center networking
Authors: Wang Yao‐Chun , Lin Ying‐Dar
Published: August 2019

With the expansion of the size of data centers, software‐defined networking (SDN) is becoming a trend for simplifying the data center network management with central and flexible flow control. To achieve L2 abstractions in a multitenant cloud, Open vSwitch (OVS) is commonly used to build overlay tunnels (eg, Virtual eXtensible Local Area Network [VXLAN]) on top of existing underlying networks. However, the poor VXLAN performance of OVS is of huge concern. Instead of solving the performance issues of OVS, in this paper, we proposed a circuit‐based logical layer 2 bridging mechanism (CBL2), which builds label‐switched circuits and performs data‐plane multicasting in a software‐defined leaf‐spine fabric to achieve scalable L2 without overlay tunneling. Our evaluations indicate that direct transmission in OVS improves throughput performance by 58% compared with VXLAN tunneling, and data‐plane multicasting for ARP reduces address resolution latency from 149 to 0.5 ms, compared with control‐plane broadcast forwarding. The evaluation results also show that CBL2 provides 0.6, 0.4, and 11‐ms protection switching time, respectively, in the presence of switch failure, link failure, and port shutdown in practical deployment.
Turbulent diffusion modelling of sediment in turbidity currents: An experimental validation of the Rouse approach
Authors: Eggenhuisen Joris T. , Tilston Mike C. , de Leeuw Jan , Pohl Florian , Cartigny Matthieu J. B.
Published: August 2019

The margins of submarine channels are characterized by deposits that fine away from the channel thalweg. This grain‐size trend is thought to reflect upward fining trends in the currents that formed the channels. This assumption enables reconstruction of turbidity currents from the geologic record, thereby providing insights into the overall sediment load of the system. It is common to assume that the density structure of a turbidity current can be modelled with simple diffusion models, such as the Rouse equation. Yet the Rouse equation was developed to describe how particles should be distributed through the water column in open‐channel flows, which fundamentally differ from turbidity currents in terms of their flow structure. Consequently, a rigorous appraisal of the Rouse model in deep‐marine settings is needed to validate the aforementioned flow reconstructions. The present study addresses this gap in the literature by providing a robust evaluation of the Rouse model's predictions of vertical particle segregation in two experimental turbidity currents that differ only in terms of their initial bed slopes (4° versus 8°). The concentration profiles of the coarsest sediment, which is suspended predominantly in the lower part of the flow, is accurately reproduced by the Rouse equation. Significant mismatches appear, however, in the concentration of finer grained sediment, especially towards the top of the flow. This problem is caused by the mixing with clear water at the top of turbidity currents. Caution is therefore advised in applying a Rouse model to levee overspill and levee‐crest deposits. Nonetheless, the Rouse model shows good agreement with laboratory measurements in the lower regions of the flow and for the coarser grains that are predominantly transported in the lower sections of submarine channels.
Stability and plasticity of positional memory during limb regeneration in Ambystoma mexicanum
Authors: Iwata Reiko , Makanae Aki , Satoh Akira
Published: August 2019

Background

Urodele amphibians are capable of regenerating their organs after severe damage. During such regeneration, participating cells are given differentiation instructions by the surrounding cells. Limb regeneration has been investigated as a representative phenomenon of organ regeneration. Cells known as blastema cells are induced after limb amputation. In this process, dermal fibroblasts are dedifferentiated and become undifferentiated similar to limb bud cells. Just like limb bud cells, the induced blastema cells are positioned along the three limb developmental axes: the dorsoventral, the anteroposterior, and the proximodistal. The accurate developmental axes are essential for reforming the structures correctly. Despite the importance of the developmental axes, the relationship between the newly establishing developmental axes and existing limb axes was not well described with molecular markers.

Results

In this study, we grafted skin from GFP‐transgenic axolotls and traced the cell lineage with position‐specific gene expressions in order to investigate the correlation of the newly established axes and cellular origin. Shh‐ and Lmx1b‐expressing cells emerged from the posterior skin and dorsal skin, respectively, even though the skin was transplanted to an inconsistent position. Shox2, a posterior marker gene, could be activated in cells derived from distal skin.

Conclusions

Our results suggest that the location memories on anteroposterior and dorsoventral axes are relatively stable in a regenerating blastema though cellular differentiation is reprogrammed.
Nano Ag‐Decorated MoS2 Nanosheets from 1T to 2H Phase Conversion for Photocatalytically Reducing CO2 to Methanol
Authors: Zheng Yinan , Yin Xiaohong , Jiang Yue , Bai Junsong , Tang Yuan , Shen Yongli , Zhang Ming
Published: August 2019

Exfoliated MoS2 with a 2H phase has unique semiconductor properties and is used for the photocatalytic reduction of CO2 herein. Flower‐like MoS2 nanosheets are synthesized by the hydrothermal method and are used to fabricate an enlarged lamellar structure with a 1T phase of MoS2 in the presence of lithium ions under sonication; the 1T‐to‐2H phase conversion of MoS2 is successfully realized in o‐dichlorobenzene solution. To improve the photocatalytic performance, Ag nanoparticles are combined with the as‐prepared 2H‐MoS2 to form the Schottky knot. The obtained Ag/2H‐MoS2 composites are characterized and evaluated for their compositions, morphologies, microstructures, and photocatalytic activities in the reduction of CO2 to methanol. Herein, it was found that the electron and hole excited by light on the composites are more effectively separated through deposited nano Ag, and their photocatalytic ability of reducing CO2 to methanol is promoted simultaneously. The highest yield of methanol up to 365.08 μmol−1 g−1 h−1 appears at 20 wt% Ag on MoS2. Finally, a reasonable photocatalytic reaction mechanism is proposed.
Electrochemical Evaluation of a Napthalene Diimide Derivative for Potential Application in Aqueous Organic Redox Flow Batteries
Authors: Wiberg Cedrik , Owusu Francis , Wang Ergang , Ahlberg Elisabet
Published: August 2019

A quaternary amine‐functionalized naphthalene diimide (NDI) moiety is synthesized and considered as a redox‐active species for application in aqueous organic redox flow batteries. For the first time, this NDI is characterized electrochemically in aqueous solutions, using cyclic and rotating disk electrode voltammetry, bulk electrolysis, as well as 1H‐nuclear magnetic resonance (1H‐NMR) spectroscopy. The molecule reaches a solubility of 0.68 m in water and reversibly delivers two electrons at attractive potentials for flow battery applications. Further exploration with 1H‐NMR reveals a strong dimerization of the NDI species with an equilibrium constant of 146 m−1. Using diffusion NMR coupled with rotating disk electrode voltammetry, it is shown that the dimer retains limited redox‐activity, yielding two electrons per dimer unit. However, using galvanostatic bulk electrolysis, close to the theoretical capacity is obtained, indicating a fast dissociation reaction of the reduced dimer. Finally, the NDI species shows excellent stability; after constant cycling for 1 week, no degradation is detected. In conclusion, NDI is demonstrated to be a highly attractive candidate for aqueous redox flow batteries.
Experimental study on evolution in the characteristics of permeability, deformation, and energy of coal containing gas under triaxial cyclic loading‐unloading
Authors: Chu Yapei , Sun Haitao , Zhang Dongming
Published: August 2019

To further more deeply understand the influence of cyclic loading‐unloading on coal seams during mining and reduce the rock burst and coal and gas outburst disasters and ensure safety during coal mining, triaxial cyclic loading‐unloading tests were performed on coal samples. The permeability recovery rate, residual deformation, and dissipated energy ratio were defined to analyze the evolution in the characteristics of permeability, deformation, and energy observed during the triaxial cyclic loading‐unloading test. The results show as following: (a) The absolute permeability recovery rate first gradually decreases and then increases before failure, while the relative permeability recovery rate decreases sharply during the compaction stage, remains stable during the elastic phase, and gradually increases before failure; (b) The cumulative residual deformation increases with increase number of cyclic loading‐unloading, while relative residual deformation first decreases gradually, then stabilities, and then rises sharply before failure; (c) With increases in deviatoric stress, the total energy of coal samples increased as an exponential function. The dissipated energy ratio gradually decreased in the initial stages of cyclic loading‐unloading, then tended to stabilize in the elastic stage and then increase gradually before failure. This study provides precursor conditions for the early warning of rock burst and coal and gas outburst disasters, which has great importance for reducing coal mine dynamics disasters.
Evolutionary lability inHoxcluster structure and gene expression inAnolislizards
Authors: Feiner Nathalie
Published: August 2019

Hox genes orchestrate development by patterning the embryonic axis. Vertebrate Hox genes are arranged in four compact clusters, and the spacing between genes is assumed to be crucial for their function. The genomes of squamate reptiles are unusually rich and variable in transposable elements (TEs), and it has been suggested that TE invasion is responsible for the Hox cluster expansion seen in snakes and lizards. Using de novo TE prediction on 17 genomes of lizards and snakes, I show that TE content of Hox clusters are generally 50% lower than genome-wide TE levels. However, two distantly related lizards of the species-rich genus Anolis have Hox clusters with a TE content that approaches genomic levels. The age distribution of TEs in Anolis lizards revealed that peaks of TE activity broadly coincide with speciation events. In accordance with theoretical models of Hox cluster regulation, I find that Anolis species with many TEs in their Hox clusters show aberrant Hox gene expression patterns, suggesting a functional link between TE accumulation and embryonic development. These results are consistent with the hypothesis that TEs play a role in developmental processes as well as in evolutionary diversifications.
Postoperative infection predicts poor survival in locoregionally advanced oral cancer
Authors: Mascarella Marco A. , Azzi Jayson Lee , da Silva Sabrina Daniela , Mlynarek Alex , Forest Veronique‐Isabelle , Hier Michael , Richardson Keith , Sadeghi Nader
Published: August 2019

Background

We ascertain the association of postoperative infection on survival in patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC).

Methods

A retrospective study of patients with stage III/IVA OCSCC undergoing curative‐intent surgery was performed. Postoperative infection was considered within 30 days after surgery. Kaplan‐Meier survival curves were used to compare overall survival (OS) in patients with postoperative infection. Cox regression and propensity‐score matching were used to adjust for confounders.

Results

Fifty‐four of 114 patients had a postoperative infection. The 5‐year OS in patients with a postoperative infection (24.1%) was lower than those without (65.2%; P < .0001). Postoperative infection was a negative predictor of OS after adjusting for patient, antibiotic, pathologic, and operative factors; the adjusted hazard ratio for OS was 2.54 (95% confidence interval, 1.27‐5.09).

Conclusion

Postoperative infection is a strong negative predictor of OS in patients with OCSCC undergoing ablative surgery.
EphA2‐to‐YAP pathway drives gastric cancer growth and therapy resistance
Authors: Huang Changhao , Yuan Weijie , Lai Chen , Zhong Shangwei , Yang Chen , Wang Ran , Mao Linfeng , Chen Zihua , Chen Zhikang
Published: August 2019

Yes‐associated protein (YAP) is a transcriptional coactivator that promotes cell proliferation, stem cell maintenance and tissue homeostasis. The YAP activity is primarily regulated through an inhibitory phosphorylation by the serine/threonine kinases of Hippo pathway. Here, we show that receptor tyrosine kinase (RTK) erythropoietin‐producing hepatocellular receptor A2 (EphA2) interacts with and phosphorylates YAP protein, leading to stabilization, nuclear translocation and activation of YAP in gastric cancer (GC) cells. EphA2 induces chemotherapy‐resistance by increasing YAP stability and nuclear YAP protein. Knockdown of YAP blocks EphA2‐induced tumor growth in GC xenograft mouse models. Importantly, the coactivation of EphA2 and YAP is manifested in clinical human GC, and is related to GC recurrence. Thus, our results establish a novel EphA2‐to‐YAP pathway that drives GC growth, progression and therapy‐resistance, targeting this pathway would be an efficient way for the treatment of GC, particularly chemotherapy‐resistant GC.
HO‐1 downregulation favors BRAFV600 melanoma cell death induced by Vemurafenib/PLX4032 and increases NK recognition
Authors: Furfaro Anna L. , Ottonello Selene , Loi Giulia , Cossu Irene , Piras Sabrina , Spagnolo Francesco , Queirolo Paola , Marinari Umberto M. , Moretta Lorenzo , Pronzato Maria A. , Mingari Maria C. , Pietra Gabriella , Nitti Mariapaola
Published: August 2019

Heme oxygenase 1 (HO‐1) plays a pivotal role in preventing cell damage. Indeed, through the antioxidant, antiapoptotic and anti‐inflammatory properties of its metabolic products, it favors cell adaptation against different stressors. However, HO‐1 induction has also been related to the gain of resistance to therapy in different types of cancers and its involvement in cancer immune‐escape has been hypothesized. We have investigated the role of HO‐1 expression in Vemurafenib‐treated BRAFV600 melanoma cells in modulating their susceptibility to NK cell‐mediated recognition. Different cell lines, isolated in house from melanoma patients, have been exposed to 1–10 μM PLX4032, which efficiently reduced ERK phosphorylation. In three lines, Vemurafenib was able to induce only a limited decrease in cell viability, while HO‐1 expression was upregulated. HO‐1 silencing/inhibition was able to induce a further significant reduction of Vemurafenib‐treated melanoma viability. Moreover, while NK cell degranulation and killing activity were decreased upon interaction with melanoma exposed to Vemurafenib, HO‐1 silencing was able to completely restore NK cell ability to degranulate and kill. Furthermore, melanoma cell treatment with Vemurafenib downregulated the expression of ligands of NKp30 and NKG2D activating receptors, and HO‐1 silencing/inhibition was able to restore their expression. Our results indicate that HO‐1 downregulation can both improve the efficacy of Vemurafenib on melanoma cells and favor melanoma susceptibility to NK cell‐mediated recognition and killing.
Analysis of how compliant layers and encapsulation affect power generated from piezoelectric stacked composites for bone healing medical devices
Authors: Cadel Eileen S. , Frazer Lance L. , Krech Ember D. , Fischer Kenneth J. , Friis Elizabeth A.
Published: August 2019

Use of piezoelectric materials to harvest energy from human motion is commonly investigated. Traditional piezoelectric materials are inefficient at low frequencies but composite structures can increase efficiency at these frequencies. Compliant layer adaptive composite stack (CLACS) is a new piezoelectric PZT (lead zirconate titanate) structure designed for orthopedic implants to use loads generated during walking to provide electrical stimulation for bone healing. The CLACS structure increases power efficiency and structural properties as compared to PZT alone. The purpose of this study was to investigate the effects of compliant layer and encapsulation thicknesses on strain‐related parameters for CLACS predicted by finite element models. Percent changes in strain as compliant layer thickness increased were compared to percent changes in power experimentally produced by CLACS given similar geometries and loading conditions. Percent changes in PZT z‐strain matched the trends for increases in experimental power, but was not directly proportional. PZT z‐strain and radial strain increased as compliant layer and top and bottom encapsulation thickness increased. PZT z‐strain and radial strain decreased as side encapsulation thickness increased for a normalized distributed force on the PZT. The overall goal of this study was to inform future design decisions regarding CLACS structures specifically for use in orthopedic implants.
Layer‐by‐layer bioassembly of poly(lactic) acid membranes loaded with coculture of HBMSCs and EPCs improves vascularization in vivo
Authors: Guduric Vera , Siadous Robin , Babilotte Joanna , Seimbille Maxime , Bareille Reine , Rey Sylvie , Thébaud Noëlie B. , Le Nihouannen Damien , Fricain Jean‐Christophe , Devillard Raphaël , Luzanin Ognjan , Catros Sylvain
Published: August 2019

Layer‐by‐layer (LBL) BioAssembly method was developed to enhance the control of cell distribution within 3D scaffolds for tissue engineering applications. The objective of this study was to evaluate in vivo the development of blood vessels within LBL bioassembled membranes seeded with human primary cells, and to compare it to cellularized massive scaffolds. Poly(lactic) acid (PLA) membranes fabricated by fused deposition modeling were seeded with monocultures of human bone marrow stromal cells or with cocultures of these cells and endothelial progenitor cells. Then, four cellularized membranes were assembled in LBL constructs. Early osteoblastic and endothelial cell differentiation markers, alkaline phosphatase, and von Willebrand's factor, were expressed in all layers of assemblies in homogenous manner. The same kind of LBL assemblies as well as cellularized massive scaffolds was implanted subcutaneously in mice. Human cells were observed in all scaffolds seeded with cells, but not in the inner parts of massive scaffolds. There were significantly more blood vessels observed in LBL bioassemblies seeded with cocultures compared to all other samples. LBL bioassembly of PLA membranes seeded with a coculture of human cells is an efficient method to obtain homogenous cell distribution and blood vessel formation within the entire volume of a 3D composite scaffold.
Effect of long alkyl chains of aniline donor on the photovoltaic performance of D‐π‐A zinc porphyrin for dye‐sensitized solar cells
Authors: Chen Yu‐Hsuan , Liu Jie‐Jun , Yeh Chen‐Yu
Published: August 2019

Three novel dyes of JJ1, JJ2, and JJ6 featured zinc porphyrin as a basic core structure; N, N‐alkyl‐4‐(prop‐1‐yn‐1‐yl)aniline as an electron donor linked to meso‐10‐position; 4‐(prop‐1‐yn‐1‐yl)benzoic acid as an electron acceptor linked to meso‐20‐position; and 2,6‐bis(dodecyloxy)phenyl or 2,6‐bis(octyloxy)phenyl respectively linked to meso‐5 and meso‐15‐positions of zinc porphyrin have been synthesized and used for dye‐sensitized solar cells. Porphyrin JJ6 featured the shortest alkyl group (─C4H9) on the donor, whereas JJ2 contained the longest alkyl groups (─C12H25), and JJ1 has a medium length of octyl groups. With these new porphyrin sensitizers, we observed that JJ6 has 7.55% power conversion efficiency under simulated one‐sun illumination (AM 1.5 G, 100 mW/cm2) with JSC = 18.64 mA/cm2, VOC = 0.66 V, and fill factor (FF) = 0.61, which was higher than the other two; JJ1 (7.35%) with JSC = 18.83 mA/cm2, VOC = 0.68 V, and FF = 0.60; and JJ2 (6.33%) with JSC = 15.69 mA/cm2, VOC = 0.62 V, and FF = 0.65. The power conversion efficiency of JJ6 and JJ1 were higher than JJ2, demonstrating that the lengthy alkyl groups on the aniline cause a decrease in efficiency of the devices.
The gridded weather typing classification version 2: A global‐scale expansion
Authors: Lee Cameron C.
Published: August 2019

Synoptic climatology uses classifications of atmospheric data to relate the larger‐scale atmosphere to surface‐based responses. One of the two primary modes of classification is the weather typing classification, whereby the multivariate surface‐based meteorological conditions at an individual location are categorized into a daily weather type (WT), and this methodology is then iterated at numerous locations within the domain in order to identify synoptic‐scale air masses. One such classification that was recently developed is the gridded weather typing classification (GWTC) for North America. The current research describes the extension of this GWTC methodology, and dataset, to the global scale, along with a number of other key updates. Using data from the Climate Forecast System, the global GWTC (GWTC‐2) classifies every day from 1979 to present into one of 11 intuitive weather types. With half‐degree spatial resolution, this results in over 259,000 global locations and more than 3.7 billion location/days currently classified, with another 7–8 million added each month. Updates to the GWTC methodology also allow for the identification and visualization of more extreme weather types compared to the previous version, and the extension of the classification over the global ocean will allow for new oceanographic applications.
Improving processes by aligning Capability Maturity Model Integration and the Scaled Agile Framework®
Authors: Sreenivasan Srijith , Kothandaraman Krishnamurthy
Published: August 2019

Refined over the years with feedback from practitioners, Capability Maturity Model Integration (CMMI) is one of the most popular models for improving processes used to develop products and services. Scaled Agile Framework (SAFe®) is a disciplined structure to foster agile practices at the enterprise level. Organizations can achieve several synergies and benefits by using CMMI v2.0 in a SAFe environment. Whereas CMMI provides guidance on what process improvement teams need to do with respect to each of the model's practice areas, SAFe provides them with information on how to implement those practices. The experiences of a mid‐size IT firm in implementing CMMI in a SAFe environment highlight the importance of program increment planning, iteration management, iteration execution, built‐in quality, and enterprise management, as well as the implementation challenges that are likely to arise when streamlining processes to improve customer satisfaction.
Platelet‐rich fibrin elicits an anti‐inflammatory response in macrophages in vitro
Authors: Nasirzade Jila , Kargarpour Zahra , Hasannia Sadegh , Strauss Franz Josef , Gruber Reinhard
Published: August 2019

Background

Platelet‐rich fibrin (PRF) serves as a reservoir of bioactive molecules to support wound healing and bone regeneration. The beneficial action of PRF might involve macrophage polarization from proinflammatory M1 toward pro‐resolving M2 phenotypes. This study aims to evaluate the effect of PRF on macrophage polarization.

Methods

Murine primary macrophages and RAW 264.7 cells were exposed to saliva and lipopolysaccharides (LPS) with and without PRF lysates obtained by repeated freeze‐thawing or the secretome of PRF membranes, termed PRF conditioned medium. The expression of the M1 marker genes interleukin 1β (IL1β) and interleukin 6 (IL6) along with the M2 markers arginase‐1 and chitinase‐like 3 (Chil3 or YM1) were evaluated by real time polymerase chain reaction. Immunoassay and immunofluorescence staining were performed for IL6 and p65 translocation, a subunit nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐kB), respectively.

Results

We report here that PRF lysates and PRF conditioned medium, the latter containing the secretome, greatly decreased the proinflammatory response of primary macrophages and RAW 264.7 cells as indicated by the expression of IL1β and IL6. The anti‐inflammatory activity of PRF lysates was further confirmed by IL6 immunoassay. Moreover, PRF lysates suppressed the translocation of p65 from the cytoplasm into the nucleus after incubation with saliva. In support of M2 polarization, PRF lysates and PRF conditioned medium enhanced the expression of arginase‐1 and YM1 in primary macrophages.

Conclusion

Our results indicate that PRF holds an anti‐inflammatory activity and shifts the macrophage polarization from an M1 toward an M2 phenotype.
Effects of silencing TT8 and HB12 on in vitro nutrients degradation and VFA production in relation to molecular structures of alfalfa (Medicago sativa)
Authors: Lei Yaogeng , Hannoufa Abdelali , Wang Yuxi , Christensen David , Yu Peiqiang
Published: August 2019

BACKGROUND

Transparent Testa8 (TT8) and Homeobox12 (HB12) are two transcriptional factors in plant phenylpropanoid pathways and were reported to be positively related to lignin content. Alfalfa with silenced TT8 (TT8i) and HB12 (HB12i) was therefore generated using the RNA interference (RNAi) technique. Although lignin was found to be high in HB12i, such gene‐silencing of alfalfa resulted in nutrient profiles that might be suitable for grazing. To extend the nutritional evaluation of transformed alfalfa, ground samples of 11 HB12i, 5 TT8i and 4 wild type (WT) were incubated in rumen fluid : buffer solution for 0, 2, 4, 8, 12, 24 and 48 h at 39 °C. Dry matter (DM) and neutral detergent fiber (NDF) degradations at each time point, and production of volatile fatty acids (VFA) at 4, 12, 24 and 48 h were analyzed, as well as degradation and production kinetics. The correlations and regressions between nutritive profiles and attenuated total reflection Fourier transform infrared (ATR‐FTIR) spectral parameters were determined.

RESULTS

Both transformed genotypes had lower DM degradation and HB12i had lower VFA production compared with WT. Structural carbohydrate (STC) parameters were found to be negatively correlated with DM degradation and VFA production. The kinetics of DM degradation and VFA production were predicted from spectral parameters with good estimation power.

CONCLUSION

Silencing of HB12 and TT8 affected fermentation characteristics of alfalfa and some fermentation characteristics were predictable from spectral parameters using ATR‐FTIR spectroscopy. © 2019 Society of Chemical Industry
gem‐Diethyl Pyrroline Nitroxide Spin Labels: Synthesis, EPR Characterization, Rotamer Libraries and Biocompatibility
Authors: Bleicken Stephanie , Assafa Tufa E. , Zhang Hui , Elsner Christina , Ritsch Irina , Pink Maren , Rajca Suchada , Jeschke Gunnar , Rajca Andrzej , Bordignon Enrica
Published: August 2019

Invited for this month's cover picture is the group of Professor Enrica Bordignon at the Ruhr University Bochum. The cover picture shows an artistic view of E. coli cells and two spin‐labeled recombinantly produced proteins, which can be inserted into the cells for EPR studies. The primary sequence of the proteins is schematically shown with the one‐letter amino acid code, and cysteine residues are functionalized with the two new gem diethyl nitroxide spin labels designed to better sustain the reducing cellular environment. Read the full text of their Full Paper at 10.1002/open.201900119.
Prognostic role of pleural effusion or ascites in localized rhabdomyosarcoma
Authors: Di Carlo Daniela , Ferrari Andrea , Toffolutti Tiziana , Milano Giuseppe Maria , Manzitti Carla , Ruggiero Antonio , Dall'Igna Patrizia , Melchionda Fraia , Zanetti Ilaria , Scarzello Giovanni , Bisogno Gianni
Published: August 2019

Purpose

The presence of pleural effusion or ascites at the time of diagnosis is generally considered a poor prognostic factor for children with rhabdomyosarcoma (RMS), and treatment is usually intensified despite the fact that there are no published studies to support this decision. We investigated the prognostic role of the presence of pleural effusion or ascites at diagnosis in patients with localized RMS consecutively enrolled in the Italian Soft Tissue Sarcoma Committee protocols over a 30‐year period.

Methods

We reviewed the radiological reports at diagnosis of 150 children with supradiaphragmatic and infradiaphragmatic RMS, noting any presence of effusion and its extent (minimal, moderate, or massive). All patients received intensive chemotherapy, surgery, and standard or hyperfractionated radiotherapy.

Results

Effusion was identified in 32 children (21.3%), 14 with pleural effusion and 18 with ascites. As for its extent, 13 children presented with minimal, 12 with moderate, and 7 with massive effusion. The 5‐year progression‐free survival (PFS) rate was 49.8% (confidence interval [CI] 31.7–65.5) and 49.5% (CI 40–58.2) for patients with and without effusion, respectively (P = .5). When only patients with moderate or massive effusion were considered, however, their PFS was 36.8% (CI 16.5–57.5) versus 51.2% (CI 42.2–59.5) in patients with minimal or no effusion (P = .01). On the whole, patients with pleural effusion had a very poor outcome with a 5‐year PFS of 35.7% (CI 13–59.4).

Conclusions

The presence of moderate or massive effusion seems to be an unfavorable prognostic factor in children with RMS, and justifies their inclusion in experimental studies.
The interplay between emotion regulation, emotional well‐being, and cognitive functioning in brain tumor patients and their caregivers: An exploratory study
Authors: Aerts Hannelore , Van Vrekhem Tineke , Stas Lara , Marinazzo Daniele
Published: August 2019

Objective

Brain tumor patients may suffer from a range of health‐impairing problems reducing their quality of life. To identify potential targets for interventions, we examined the influence of different emotion regulation strategies on affective and cognitive functioning as indices of quality of life in patients and their caregivers in the early phase of treatment.

Methods

To this end, we conducted an exploratory longitudinal study on a small cohort, measuring emotion regulation, emotional well‐being, and cognitive functioning on the day before each patient's tumor resection (28 patients and 11 caregivers) and several months after neurosurgery (22 patients and 10 caregivers).

Results

Results showed that emotion regulation strategies are relatively stable from preoperative to postoperative assessment. Nevertheless, several associations between emotion regulation strategies and quality of life indices were evident after tumor resection. In particular, our results were largely in line with previous research findings in healthy and other patient populations, corroborating the adaptive character of cognitive reappraisal, whereas suppression and expression of emotions were related to reduced cognitive and affective functioning, respectively.

Conclusions

Based on these results, we suggest that further intervention or qualitative studies explore whether therapeutic interventions directed toward mastery of cognitive reappraisal techniques and appropriate expression of emotions could lead to improved long‐term adjustment among brain tumor patients and their caregivers.
Extracorporeal shock wave therapy decreases COX‐2 by inhibiting TLR4‐NFκB pathway in a prostatitis rat model
Authors: Jeon Seung Hwan , Zhu Guan Qun , Kwon Eun Bi , Lee Kyu Won , Cho Hyuk Jin , Ha U‐Syn , Hong Sung‐Hoo , Lee Ji Youl , Bae Woong Jin , Kim Sae Woong
Published: August 2019

Background

This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism.

Methods

RWPE‐2 cells were randomly divided into three groups: (a) RWPE‐2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE‐2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme‐linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague‐Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 β‐estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA.

Results

ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX‐2) through inhibiting TLR4‐NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2‐COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate.

Conclusions

ESWT improved CP/CPPS and reduced inflammation by degrading COX‐2 in microenvironment through TLR4‐NFκB‐inhibiting pathway. TRAF2 regulator in ERK1/2‐COX‐2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.
End user–oriented node resource allocation: An application‐based method
Authors: Zhang Xin , Huang Ning , Li Biwei
Published: August 2019

For a network, how to allocate limited resources to achieve high network reliability has been concerned by engineers. From the perspective of the users, the quality of applications is the most intuitive perception of network reliability. Previous allocation methods focus little on applications, which makes it difficult to optimize resource with given application requirements. This paper proposes an application‐based resource allocation method during network design. Under given application scenario and resource constraints, the allocation model is constructed to maximize application reliability, which is presented as a novel user‐oriented metric to assess the quality of applications. Furthermore, improved genetic algorithm (GA) is adopted to obtain optimal allocation strategy. To improve the efficiency of the algorithm, application‐affected node importance is evaluated to generate initial population. Simulation results demonstrate that the proposed method can achieve higher application reliability than the other three allocation methods when applied to an Avionics Full Duplex Switched Ethernet (AFDX) case. This makes it possible to optimize resource allocation in the light of different application demands in network design.
Dynamic prediction of Alzheimer's disease progression using features of multiple longitudinal outcomes and time‐to‐event data
Authors: Li Kan , Luo Sheng
Published: August 2019

This paper is motivated by combining serial neurocognitive assessments and other clinical variables for monitoring the progression of Alzheimer's disease (AD). We propose a novel framework for the use of multiple longitudinal neurocognitive markers to predict the progression of AD. The conventional joint modeling longitudinal and survival data approach is not applicable when there is a large number of longitudinal outcomes. We introduce various approaches based on functional principal component for dimension reduction and feature extraction from multiple longitudinal outcomes. We use these features to extrapolate the health outcome trajectories and use scores on these features as predictors in a Cox proportional hazards model to conduct predictions over time. We propose a personalized dynamic prediction framework that can be updated as new observations collected to reflect the patient's latest prognosis, and thus intervention could be initiated in a timely manner. Simulation studies and application to the Alzheimer's Disease Neuroimaging Initiative dataset demonstrate the robustness of the method for the prediction of future health outcomes and risks of target events under various scenarios.
Nanocomposite having Flower ‐Shaped Morphology as Electrode for Electrochemical Supercapacitor Applications
Authors: Chaudhary Swati , Kuntal Dheeraj , Althurthi Bharani  Venkata Kiran Kumar , Veera Venkata Ramana Challa , Goli Nagaraju , Thomas Sabu
Published: August 2019

In the present research work, we reported the nanocomposite having flower shaped morphology as electrode by the combination of metal (Cu) nanoparticles, metal oxide (ZnO nanorods) with reduced graphene oxide (rGO) for electrochemical super capacitor applications by using one pot synthesis method. The nanocomposite was characterized by XRD, Infrared, Raman spectroscopies and morphological studies were done using SEM and TEM. The electrochemical properties of nanocomposites were studied by measuring the specific capacitance using cyclic voltammetry (CV) and galvanostatic charge‐discharge techniques in different electrolyte solutions, among them 3.0 M KOH solution showed high capacitance. The experimental results, indicated that the homogeneous distribution of ZnO nanorods and Cu nanoparticles in rGO, which provides the short path for electrons transport and ions diffusion. The specific capacitance value achieved for nanocomposite is 365.5 F/g. From the studies, it can be concluded that the nanocomposite is a promising electrode material for electrochemical super capacitor applications.
Improving Cytotoxicity by Changing a Linker from Diphenylether to Diphenylmethane and now to Phenylene in Binuclear Dithiocarbamate Complexes: Synthesis and Cytotoxicity Study
Authors: Singh Vinay K , Pillai Vineeta , Patel Shailykumari K. , Buch Lipi
Published: August 2019

α‐chloroamide 1,3‐bis(2‐chloroacetamido)phenylene (L’) is selected as a lead compound to derive 1,3‐bis(2‐(alkylamino)acetamido)phenylene (L1‐L3). A programmed self‐assembly involving L1‐L3, CS2 and NiII, CuII or ZnII ions affords access to a new series of 32‐membered binuclear macrocyclic dithiocarbamates [MII2‐μ2‐bis‐{(κ2S,S‐S2CN(R)CH2CONH)2C6H4}]{R=Cy, M=NiII 1 a, CuII 1 b, ZnII 1 c; R=iPr, M=NiII 2 a, CuII 2 b, ZnII 2 c; R=nBu, M=NiII 3 a, CuII 3 b, ZnII 3 c}. Compounds were characterized by spectroscopic (1H, 13C, DEPT 135, 1H DOSY NMR, HRMS/ESI MS, UV‐visible, Fluorescence, IR) and by the TGA. Evidently, L’ forms a fascinating 2D infinite supramolecular molecular sheet. All the compounds were screened for their in vitro cytotoxic activity against malignant tumor Hep G2 (hepatoma) cell line by the MTT assay. A majority of compounds ca L’, L1, 1 a, 1 b, 1 c, 2 a, 2 b, 2 c, L3,3 a, 3 b, 3 c display IC50 values lower than cisplatin and specificity for carcinoma Hep G2 over normal liver cell line (WRL‐68). Evidently cytotoxic potentials of L1‐L3 improved tremendously upon formation of their corresponding bimetallic dithiocarbamate complexes. The shrinking of cells can be clearly visualized by acridine orange/ethidium bromide (AO/EB) staining indicating the induction of apoptosis as part of the mechanism of action of these compounds. Further, DFT level calculations have been performed on representative compounds to reinforce the experimental results.
Recent Advances in Nanoformulated Chemotherapeutic Drug Delivery (2015‐2019)
Authors: Dorababu Atukuri
Published: August 2019

An attempt was made to summarize the chemotherapeutic drug formulations at nanoscale. The number of biocompatible materials like carbohydrates, proteins, peptides, chitosan, and other water soluble materials would enhance the hydrophilicity of chemotherapeutic drugs. Some of the formulations were responsible for the improved anticancer activity, drug loading capability, higher encapsulation efficiency etc. Nanodrug formulations were engineered in such a way that hydrophobic anticancer agents were transformed to possess hydrophilic features which would allow them to self‐assemble into nanodrug carriers and hence longer blood circulation times of drug, sustained drug release were achieved. Tumor cell targetability was also achieved by selectively conjugating biomolecules with anticancer drugs. Drug loaded nanovectors exhibited improved cytotoxic activities compared to free drug molecules. Few classes of nanoformulations possessing major advantages were described in this review. These classes of drug delivery system possess a greater number of advantages over the other drug delivery systems. The amphiphilicity was enhanced by the complexation of the drugs and supramolecular micellation. Combination of the two or more drugs was successfully experimented via nanoprecipitation methods. Synergistic enhancement of the cytotoxic activity and good tumor growth inhibition evident by the introduction of chemotherapeutic nanopharmacology and nanodrug delivery methods were explained.
Synthesis of New Indole and Adamantane Amido Derivatives with Pharmacological Interest
Authors: Karoutzou Olga , Benaki Dimitra , Papanastasiou Ioannis , Vocat Anthony , Cole Stewart T.
Published: August 2019

The synthesis and preliminary pharmacological evaluation of new indole and adamantane amido derivatives is described. The design was based on the pharmacophoric properties of 4‐{4‐[4‐(trifluoromethoxy)phenoxy]piperidin‐1‐yl), 6‐[4‐(trifluoro methoxy)phenyl]pyridin‐3‐yl and 4‐(trifluoro)phenyl tails, which are present as side chains in the structures of promising drug candidates, currently in clinical tests. These pharmacophores were incorporated into the indole and adamantane scaffolds, respectively. The new derivatives were evaluated for their antimycobacterial potential. The following amides, N‐[2‐(5‐methoxy‐1H‐indol‐3‐yl)ethyl]‐4‐{4‐[4(trifluoromethoxy)phenoxy]piperidin‐1‐yl}benzamide (1 b) and N‐{4‐[4‐(4‐(trifluoromethoxy)phenoxy)piperidin‐1‐yl]benzyl}‐1H‐indolyl‐2‐carboxamide (2 b), are endowed with antitubercular properties, which merit further investigation.
Bimetallic Porphyrin MOF Anchored onto rGO Nanosheets as a Highly Efficient 2D Electrocatalyst for Oxygen Evolution Reaction in Alkaline Conditions
Authors: Meng Junjing , Zhou Yan , Chi Hehai , Li Kuang , Wan Junmin , Hu Zhiwen
Published: August 2019

Due to consequent non‐renewable resource consumption and environmental pollution,the renewable hydrogen energy has been a new energy candidate. But the sluggish kinetics of oxygen evolution reaction (OER) still hampersthe hydrogen production by water electrolysis. So, to design and synthesize an efficient OER catalyst for electrochemical conversion technologiesstill keeps challenge. Herein, an ideal precursor of bimetallic porphyrinicMOF (Co–CuTCPP)/reduced graphene oxide (Co–CuTCPP/rGO) composite has been fabricated by an ultrathin porphyrinic MOF (Co–CuTCPP) nanosheet loaded onto graphene oxide (GO)via hydrothermal process. Owing to synergetic effect of the rGOand bimetallic porphyrin MOF scaly structure, the optimized Co–CuTCPP/rGO‐10 catalyst exhibited high electrocatalytic activity with a low overpotential of 396 mV at 10 mA cm−2 and a Tafel slope of 58 mV dec−1, and had good stabilityin alkaline conditions. So, the lowcost, stable, and heterogeneous electrocatalyst might be a promising candidate for the OER devices in alkaline conditions without requirement of pyrolysis process.
An NBD‐Based Mitochondrial Targeting Ratiometric Fluorescent Probe for Hydrogen Sulfide Detection
Authors: Jia Xu , Li Wei , Guo Zihan , Guo Zhenbo , Li Yin , Zhang Pingzhu , Wei Chao , Li Xiaoliu
Published: August 2019

Hydrogen sulfide (H2S) is an important endogenous gaseous signaling molecule with multiple biological functions. In this study, an NBD‐based ratiometric fluorescent probe (MR‐1) was successfully designed and synthesized for selectively detection H2S. The probe exhibits high selectivity and fast emission intensity ratio changes in response to H2S in solution. The modification of triphenylphosphine in the probe enables it to be used for the imaging mitochondrial H2S in living HeLa cells.
Synthesis, Characterization of Pyridyl Heterocyclic Olefins (PHOs) and Activation of Heterocumulenes
Authors: Zhang Xianhui , Wang Liang , Wang Qinggang , Ge Fang , Wang Xiaowu
Published: August 2019

A series of new patterns of heterocyclic olefins (NHOs) based on pyridyl backbone were synthesized. Reactions of pyridyl heterocyclic olefins (PHOs) with heterocumulenes (CO2, CS2, isocyanate, isothiocyanate) afforded two different types of products including addition and insertion products. Insertion products represented rare example in such reactions. The reactivity between PHOs and heterocumulenes was primarily manipulated by the Lewis acidity of the heterocumulenes, while the product stability and selectivity were controlled by both the PHOs and heterocumulenes.
Das Kehler Hängedach
Authors: Wilhelm Viktor
Published: August 2019

Im Gewerbegebiet der Stadt Kehl wurde neuerdings ein Hängedach auf „mechanische Bäume” aufgebracht. Von der Revitalisierung dieses Gebiets profitiert nicht nur die Stadt, sondern auch die umliegenden baulichen Strukturen. Welches Potenzial in dieser Bauaufgabe steckt, zeigt die neue Platzüberdachung an einer Waschanlage in Kehl‐Sundheim.