bluuebunny/crossref_metadata_2025 huggingface dataset:
Retracted: Amentoflavone Promotes Apoptosis in Non‐Small‐Cell Lung Cancer by Modulating Cancerous Inhibitor of PP2A
Authors: Shen Fei , Chen Yijiang , Chen Liang , Qin Jianwei , Li Zhi , Xu Jing
Published: August 2019

Non‐small‐cell lung cancer (NSCLC) is one of the most common human malignancies. Amentoflavone (AF) is one of bioflavonoid compounds isolated from Selaginella tamariscina Spring. This study was designed to examine the effect of AF on NSCLC. Our results indicated that AF decreased cell viability of both H1299 and H358 cells. Colony formation assay also showed that AF was able to suppress the anchorage‐independent growth of NSCLC cells. AF also triggered cell cycle arrest by downregulating cyclin D1, CDK4, and CDK6. The pro‐apoptotic activity of AF was confirmed by Hoechst staining and flow cytometry. The effect of AF on activation of caspase‐3, upregulation of Bax, and downregulation of Bcl‐2 was examined by western blot. The anti‐growth and pro‐apoptotic activities of AF were further validated in xenograft murine model. iTRAQ assay showed that cancerous inhibitor of PP2A (CIP2A) expression was markedly downregulated by AF treatment in H1299 cells. In addition, qRT‐PCR and western blot also showed that AF was able to dose‐dependently inhibit CIP2A expression. Meanwhile, the activity of protein phosphatase 2A (PP2A) was enhanced by AF treatment. The mRNA and protein expression of CIP2A as well as PP2A activity in xenograft tumor tissue were examined, which indicated that the in vivo anticancer activity of AF was associated with downregulation of CIP2A and reactivation of PP2A. Moreover, our results showed that the anti‐growth and pro‐apoptotic activities of AF were augmented by CIP2A knockdown and attenuated by ectopic CIP2A expression. Our results indicated that AF exhibited anticancer activity in NSCLC by targeting CIP2A. Anat Rec, 302:2201–2210, 2019. © 2019 American Association for Anatomy
Periconceptional folic acid and risk for neural tube defects among higher risk pregnancies
Authors: Petersen Julie M. , Parker Samantha E. , Benedum Corey M. , Mitchell Allen A. , Tinker Sarah C. , Werler Martha M.
Published: August 2019

Background

Women with a previous neural tube defect (NTD)‐affected pregnancy are recommended to consume 4,000 μg daily folic acid (FA) for prevention (10 times the general‐population recommendation). Protection from doses between 400 and 4,000 μg for this and other higher risk groups is unclear.

Methods

In the case–control Slone Birth Defects Study (1988–2015), we examined the associations between periconceptional FA doses and NTDs among four higher risk groups: NTD family history, periconceptional antiepileptic drug exposure (AED), pregestational diabetes, and prepregnancy obesity. Mothers completed standardized interviews about pregnancy events and exposures. FA categorizations were based on (a) supplements only and (b) supplements and diet (“total folate”). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) (adjusted for age and study center) using logistic regression.

Results

Cases and controls included: 45 and 119 with family history, 25 and 108 with AED exposure, 12 and 63 with pregestational diabetes, 111 and 1,243 with obesity. Daily FA supplementation was associated with lower NTD risk compared to no supplementation (adjusted ORs were 0.33 [95% CI 0.13, 0.76] for family history, 0.31 [0.09, 0.95] for AED exposure, 0.25 [0.04, 1.05] for pregestational diabetes, 0.65 [0.40, 1.04] for obesity). Though estimates were imprecise, as total folate increased stronger point estimates were observed, notably among family history. No mothers with a prior NTD‐affected pregnancy supplemented with 4,000 μg.

Conclusions

Our findings reinforce that all women of childbearing potential should consume at least 400 μg FA/day to protect against NTDs. Higher risk groups may benefit from higher doses.
Prominent Inhibitory Projections Guide Sensorimotor Computation: An Invertebrate Perspective
Authors: Hughes Samantha , Celikel Tansu
Published: August 2019

From single‐cell organisms to complex neural networks, all evolved to provide control solutions to generate context‐ and goal‐specific actions. Neural circuits performing sensorimotor computation to drive navigation employ inhibitory control as a gating mechanism as they hierarchically transform (multi)sensory information into motor actions. Here, the focus is on this literature to critically discuss the proposition that prominent inhibitory projections form sensorimotor circuits. After reviewing the neural circuits of navigation across various invertebrate species, it is argued that with increased neural circuit complexity and the emergence of parallel computations, inhibitory circuits acquire new functions. The contribution of inhibitory neurotransmission for navigation goes beyond shaping the communication that drives motor neurons, and instead includes encoding of emergent sensorimotor representations. A mechanistic understanding of the neural circuits performing sensorimotor computations in invertebrates will unravel the minimum circuit requirements driving adaptive navigation.
Combining Organocatalysis and Photoredox Catalysis: An Asymmetric Synthesis of Chiral β‐Amino α‐Substituted Tryptamines
Authors: Levitre Guillaume , Audubert Clément , Dumoulin Audrey , Goual Nawel , Retailleau Pascal , Moreau Xavier , Masson Géraldine
Published: August 2019

A stereoselective synthesis of functionalized β‐amino α‐substituted tryptamines has been achieved by a sequential asymmetric organocatalytic three‐component electrophilic amination and photocatalyzed Friedel‐Crafts reaction of indoles with moderate to high diastereoselectivities (up to >99 : 1 dr) and excellent enantioselectivities (up to >99 % ee). We also demonstrated that the β‐amino α‐substituted tryptamines can be successfully engaged in a further catalytic step, furnishing various α,β‐substituted tryptamines without erosion of enantioselectivity and with complete diastereoselectivity.
Sodium Storage in Coal/Biomass‐Derived Carbon/Carbon 3D Networks
Authors: Shen Hanting , Zhao Hanqing , Kang Mengmeng , Song Wei , Ye Jianqi , Miao Siyu , Zhao Dan , Zhao Yu , Mi Jie , Li Zhong
Published: August 2019

Coal plays an important role in human industrialization as a fossil fuel and has attracted attention recently as an ideal carbon precursor for next‐generation sodium‐ion‐battery anode materials. In this work, nitrogen‐doped three‐dimensional (3D) coal‐based carbon materials were constructed, in which coal‐based graphite microcrystals (CGCs) supply plentiful active sites for Na absorption, and chitosan‐derived 3D carbon networks accelerate the electron transfer. The materials exhibited a Na storage capacity of 283.3 mAh g−1 at 0.1 C, with capacitance retention of 94.3 % after the fifth cycle. Moreover, 170 mAh g−1 can be achieved at 2 C after 3000 cycles, which is twice that of pure CGCs. The materials are low cost and exhibit a good capacity, showing that they could be used in practical applications for sodium‐ion‐battery anodes.
Mono‐Aryl/Alkylthio‐Substituted (Hetero)acenes of Exceptional Thermal and Photochemical Stability by the Thio‐Friedel–Crafts/Bradsher Cyclization Reaction
Authors: Bałczewski Piotr , Kowalska Emilia , Różycka‐Sokołowska Ewa , Skalik Joanna , Owsianik Krzysztof , Koprowski Marek , Marciniak Bernard , Guziejewski Dariusz , Ciesielski Witold
Published: August 2019

The highly substituted mono‐aryl/alkylthio‐(hetero)acenes prepared in this study have been found to be thermally more stable (Tdecomp.=331–354 °C) than the known di‐aryl/alkylthio‐substituted acenes by an average of 25 °C. They are also much more photostable at 254 and 365 nm (in both argon and air) than the parent anthracene and other reported anthracenes. The most photostable aryl/alkylthio‐anthracenes at 254 nm were found to be 60–70 (in air) and 130 (in argon) times more stable in solution than the unsubstituted anthracene, and much more stable than known EDG/EWG‐substituted anthracenes (EDG=electron‐donating group, EWG=electron‐withdrawing group) with an extended aromatic core. Furthermore, the acenes showed significantly higher photostability at 365 nm in both air and argon. The anthracenes were obtained by the novel thio‐Friedel–Crafts/Bradsher cyclization reaction of hitherto unknown [o‐(1,3‐dithian‐2‐yl)aryl](aryl)methyl thioethers. The developed approach provides a general access to mono‐aryl/alkylthio‐substituted (hetero)acene frameworks containing at least three fused (hetero)aromatic rings. The characteristic feature of this approach, which leads to highly substituted acenes, is that the substituents, unlike in other methods, may be introduced at an early stage of the synthesis. DFT and TD‐DFT calculations confirmed the stabilizing role of the aryl/alkylthio substituent in the mono‐aryl/alkylthio‐substituted anthracenes, which are the most stable anthracenes prepared to date. Their high photostability is mainly due to the quenching of singlet oxygen by the acene and the quenching of the acene S1 state by molecular oxygen.
KRAS Binders Hidden in Nature
Authors: Bergner Andreas , Cockcroft Xiaoling , Fischer Gerhard , Gollner Andreas , Hela Wolfgang , Kousek Roland , Mantoulidis Andreas , Martin Laetitia J. , Mayer Moriz , Müllauer Barbara , Siszler Gabriella , Wolkerstorfer Bernhard , Kessler Dirk , McConnell Darryl B.
Published: August 2019

Invited for the cover of this issue is the group of Darryl McConnell and colleagues from Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria. The image depicts some of the KRAS binders found in Nature that are discussed in the paper. Read the full text of the article at 10.1002/chem.201902810.
Do Anionic π Molecules Aggregate in Solution? A Case Study with Multi‐interactive Ligands and Network Formation
Authors: Nakanishi Keisuke , Ohtsu Hiroyoshi , Fukuhara Gaku , Kawano Masaki
Published: August 2019

An anionic π molecule can form an aggregate when a multi‐interactivity is introduced, in sharp contrast to common anionic molecules that are generally difficult to stack on each other. We found that a multi‐interactive ligand, 2,5,8‐tri(4′‐pyridyl)‐1,3,4,6,7,9‐hexaazaphenalenate (TPHAP−) exhibited a large Stokes shift and an intramolecular charge transfer, both of which were sensitive to hydrogen‐bonding media. An anionic potassium salt of TPHAP−in methanol formed various aggregation states depending on the concentration examined; this was revealed by steady‐state spectroscopic and fluorescence lifetime measurements. Self‐assembling cadmium ions and the ligands can create several morphological crystals that are controlled by the ligand concentration, among which three new structures were determined by single‐crystal analysis. The X‐ray structures obtained suggest that the aggregation states of the ligand in solution can be transferred to the solid system of the porous coordination networks.
Poly(Lactide‐Co‐Glycolide) Nanoparticles Co‐Loaded with Chlorophyllin and Quantum Dots as Photodynamic Therapy Agents
Authors: Galliani Marianna , Signore Giovanni
Published: August 2019

Photodynamic therapy (PDT) is an approach to treating cancer and involves light‐induced activation of a photosensitizer that triggers the formation of reactive oxygen species (ROS) in targeted cells and subsequent cell death. Examples of photosensitizers are porphyrins, including the natural compound chlorophyll. These molecules can be delivered alone or co‐formulated with an agent, such as quantum dots (QDs), that is able to excite them through a fluorescence resonance energy transfer (FRET)‐based mechanism. We encapsulated a chlorophyllin copper complex and CdSe/ZnS core‐shell QDs into biodegradable nanoparticles (NPs) composed of poly(lactide‐co‐glycolide) (PLGA), that allow modification with specific targeting ligands. When excited at 365 nm, FRET occurs between co‐encapsulated QDs and chlorophyllin to result in the formation of ROS. This chlorophyllin‐QD coformulation allows generation of ROS both in an aqueous environment and in cells, thus confirming the potential of this formulation in PDT.
Four‐Coordinate Organoboron Platforms for Efficient Red Phosphorescent Organic Light‐Emitting Diodes
Authors: Liu Xiang‐Yang , Zhang Yi‐Jie , Fei Xiyu , Fung Man‐Keung , Fan Jian
Published: August 2019

So far both three‐ and four‐coordinate organoboron compounds have been widely applied in organic light‐emitting diode (OLED) materials. However, the use of four‐coordinate organoboron compounds as host materials is rarely reported. In this work, two new four‐coordinate organoboron compounds, namely 8‐(4‐(9H‐carbazol‐9‐yl)phenyl)‐6,6‐difluoro‐6H‐6λ4,7λ4‐benzo[4′,5′]imidazo[1′,2′:3,4][1,3,2]diazaborolo[1,5‐a]pyridine (B1PCz) and 8‐(3‐(9H‐carbazol‐9‐yl)phenyl)‐6,6‐difluoro‐6H‐6λ4,7λ4‐benzo[4′,5′]imidazo[1′,2′:3,4][1,3,2]diazaborolo[1,5‐a]pyridine (B1MCz), were successfully designed, synthesized, and fully characterized. The red OLEDs using B1PCz and B1MCz as host materials achieved relatively high device performance with a maximum external quantum efficiency of 14.8 % and 11.8 %, respectively. These results will expand the scope of organoboron compounds for OLED materials and reveal the great potential of four‐coordinate organoboron materials.
Removal of failed dental implants revisited: Questions and answers
Authors: Solderer Alex , Al‐Jazrawi Adrian , Sahrmann Philipp , Jung Ronald , Attin Thomas , Schmidlin Patrick R.
Published: August 2019

Objectives

This narrative review is aiming on showing reasons for implant failure, removal techniques, and respective clinical considerations; further, the survival rate of implants in previous failed sites is examined.

Materials and methods

Questions have been formulated, answered, and discussed through a literature search including studies assessing implant failure and removal up to 2018.

Results

Studies describing reasons for implant failure, implant removal techniques, and the reinsertion of implants in a previous failed site (n = 12) were included. To date, peri‐implantitis is the main reason for late implant failure (81.9%). Trephine burs seem to be the best‐known method for implant removal. Nevertheless, the counter‐torque‐ratchet‐technique, because of the low invasiveness, should be the first choice for the clinician. Regarding zirconia implant removal, only scarce data are available. Implantation in previously failed sites irrespective of an early or late failure results in 71% to 100% survival over 5 years.

Conclusion

If removal is required, interventions should be based on considerations regarding minimally invasive access and management as well as predictable healing. (Post)Operative considerations should primarily depend on the defect type and the consecutive implantation plans.
Morphological diversity of integumentary traits in fowl domestication: Insights from disparity analysis and embryonic development
Authors: Núñez‐León Daniel , Aguirre‐Fernández Gabriel , Steiner Andrea , Nagashima Hiroshi , Jensen Per , Stoeckli Esther , Schneider Richard A. , Sánchez‐Villagra Marcelo R.
Published: August 2019

The domestication of the fowl resulted in a large diversity of integumental structures in chicken breeds. Several integumental traits have been investigated from a developmental genetics perspective. However, their distribution among breeds and their developmental morphology remain unexplored. We constructed a discrete trait‐breed matrix and conducted a disparity analysis to investigate the variation of these structures in chicken breeds; 20 integumental traits of 72 chicken breeds and the red junglefowl were assessed. The analyses resulted in slight groupings of breed types comparable to standard breed classification based on artificial selection and chicken type use. The red junglefowl groups together with bantams and European breeds. We provide new data on the red junglefowl and four chicken breeds, demonstrating where and when variation arises during embryonic development. We document variation in developmental timing of the egg tooth and feather formation, as well as other kinds of developmental patterning as in the anlagen of different type of combs. Changes in epithelial‐mesenchymal signaling interactions may drive the highly diverse integument in chickens. Experimental and comparative work has revealed that the cranial neural crest mesenchyme mediates its interactions with the overlying epithelium and is the likely source of patterning that generates diversity in integumental structures.
Inosine pranobex enhances human NK cell cytotoxicity by inducing metabolic activation and NKG2D ligand expression
Authors: McCarthy Michael T. , Lin Da , Soga Tomoyoshi , Adam Julie , O'Callaghan Christopher A.
Published: August 2019

Inosine pranobex (IP) is a synthetic immunomodulating compound, indicated for use in the treatment of human papillomavirus‐associated warts and subacute sclerosing panencephalitis. Previous studies demonstrate that the immunomodulatory activity of IP is characterized by enhanced lymphocyte proliferation, cytokine production, and NK cell cytotoxicity. The activation of NKG2D signaling on NK cells, CD8+ T cells, and γδ T cells also produces these outcomes. We hypothesized that IP alters cellular immunity through the induction of NKG2D ligand expression on target cells, thereby enhancing immune cell activation through the NKG2D receptor. We tested this hypothesis and show that exposure of target cells to IP leads to increased expression of multiple NKG2D ligands. Using both targeted metabolic interventions and unbiased metabolomic studies, we found that IP causes an increase in intracellular concentration of purine nucleotides and tricarboxylic acid (TCA) cycle intermediates and NKG2D ligand induction. The degree of NKG2D ligand induction was functionally significant, leading to increased NKG2D‐dependent target cell immunogenicity. These findings demonstrate that the immunomodulatory properties of IP are due to metabolic activation with NKG2D ligand induction.
Four‐ and Five‐Coordinate Titanium(IV) Complexes Supported by the dpp‐bian Ligand in ROP of L‐Lactide
Authors: Morozov Alexander G. , Martemyanova Tatyana V. , Dodonov Vladimir A. , Kazarina Olga V. , Fedushkin Igor L.
Published: August 2019

A titanium(IV) alkoxido complex, (dpp‐bian)Ti(OBn)2 (2), as well as alkoxido chlorido complexes (dpp‐bian)TiCl(OCH2CH2OMe) (3) and (dpp‐bian)TiCl2OBn (4), were synthesized from the titanium(IV) dichloride precursor [(dpp‐bian)TiCl2]2 (1) by exchange with corresponding sodium salts (comps. 2 and 3) or by the alcoholysis with BnOH (comp. 4). The compounds 2–4 were fully characterized by elemental analysis, NMR or EPR, and IR spectroscopy. Molecular structures of the metal complexes in the solid state have been determined by single‐crystal XRD analysis. Compounds 2–4 were tested as catalysts in the ROP of L‐lactide in a toluene medium. Whereas complexes 2 and 3 produce cyclic PLAs with broad dispersities and unpredictable molecular weights, complex 4 acts as an efficient ROP catalyst which polymerizes the monomer in a highly controllable manner. It produces BnO‐capped PLAs with narrow molecular weight distributions as well as linear dependence of Mns on monomer conversion.
Programmable Interface Asymmetric Integration of Carbon Nanotubes and Gold Nanoparticles toward Flexible, Configurable, and Surface‐Enhanced Raman Scattering Active All‐In‐One Solar‐Driven Evaporators
Authors: Zhang Chang , Xiao Peng , Ni Feng , Yang Yanping , Gu Jincui , Zhang Lei , Xia Junyuan , Huang Youju , Wang Wenqin , Chen Tao
Published: August 2019

With the rapid development of industrialization and urbanization, water pollution and water shortage are increasingly serious problems. Detecting potential contaminants and further extracting purified water from polluted water is considered to be an effective way for sewage management and recycling. Herein, an all‐in‐one solar‐driven evaporator is developed by alternatively depositing carbon nanotube (CNT) films and gold nanoparticle films on flexible cotton fabric surfaces for both solar‐driven pollution detection and water collection. Based on the facile and robust interfacial self‐assembly strategy, a large‐area CNT film at the air/water interface and closely packed Au nanoparticle (AuNP) film assembled at the liquid/liquid interface are readily achieved, which can be further alternatively transferred onto the cotton fabric surface for solar‐to‐thermal conversion applications. Owing to the favorable flexibility and foldability of the cotton fabric, the CNT film–modified cotton enables the configurable transition from a 2D flat structure to adjusted 3D wave‐like structures for enhanced solar steam generation. Furthermore, when the AuNP film is further deposited onto the surface of the CNT film for polluted water evaporation, the resultant CNT‐loaded Au hybrid can realize effective pollutant detection through surface‐enhanced Raman scattering (SERS) signals.
Diglyme‐Based Thermoelectrochemical Cells Operable at Both Subzero and Elevated Temperatures
Authors: Kim Kyunggu , Lee Hochun
Published: August 2019

Thermoelectrochemical cells (TECs) are promising devices for harvesting low‐grade waste heat (<200 °C). Most TEC researches have thus far focused on aqueous redox couples, but aqueous solutions suffer from a limited operating temperature range (0–100 °C). Herein, TECs based on nonaqueous Li+/Li redox couples (Li‐TECs) using diglyme (2G) electrolytes featuring a wide liquidus range (from −64 to 162 °C) are introduced. Notably, a Li‐TEC with 1.8 m lithium bis(fluorosulfonyl)imide (LiFSI) 2G surpasses the current best nonaqueous TECs based on ionic liquid (IL) electrolytes at elevated temperatures: 30% higher output power for cold side temperature (Tcold) and hot side temperature (Thot) of 60 and 130 °C, respectively. In addition, unlike the TECs using ILs, the Li‐TEC displays stable operation even at Tcold of −25 °C, which, for Thot of 150 °C, yields an unprecedented high output voltage of 270 mV from a single Li‐TEC. Herein, the wide‐temperature‐range operation demonstrated takes the TECs one step closer to practical applications.
Ultra‐Thin Atomic Layer Deposited–Nb2O5 as Electron Transport Layer for Co‐Evaporated MAPbI3 Planar Perovskite Solar Cells
Authors: Subbiah Anand S. , Dhara Arpan K. , Mahuli Neha , Banerjee Suman , Sarkar Shaibal Kanti
Published: August 2019

Herein, the performance of atomic layer deposited (ALD)‐Nb2O5 is compared with existing standard electron transport layer (ETL) configuration in planar n‐i‐p perovskite solar cell architectures. By making use of a co‐evaporated perovskite absorber layer, electron transport materials, such as phenyl‐C61‐butyric acid methyl ester (PCBM), TiO2, and Nb2O5, are compared in stand‐alone and bilayer configurations. The device performance in terms of hysteresis, scan rate dependency, and stability is associated with ETL–perovskite interactions and ALD‐Nb2O5 fabricated using a PCBM interfacial layer exhibits superior behavior on all fronts. Using an atomic layer deposition technique can drastically reduce the process temperatures, resulting in conformal Nb2O5 suitable for evaporated perovskite absorbers with promise toward using them in flexible applications.
Leveraging cell‐specific differentially methylated regions to identify leukocyte infiltration in adipose tissue
Authors: Chu Su H. , Kelsey Karl T. , Koestler Devin C. , Loucks Eric B. , Huang Yen‐Tsung
Published: August 2019

Obesity is understood to be an inflammatory condition characterized in part by changes in resident immune cell populations in adipose tissue. However, much of this knowledge has been obtained through experimental animal models. Epigenetic mechanisms, such as DNA methylation may be useful tools for characterizing the changes in immune cell populations in human subjects. In this study, we introduce a simple and intuitive method for assessing cellular infiltration by blood into other heterogeneous, admixed tissues such as adipose tissue, and apply this approach in a large human cohort study. Associations between higher leukocyte infiltration, measured by evaluating a distance measure between the methylation signatures of leukocytes and adipose tissue, and increasing body mass index (BMI) or android fat mass (AFM) were identified and validated in independent replication samples for CD4 (pBMI = 0.009, pAFM = 0.020), monocytes (pBMI = 0.001, pAFM = 4.3 × 10−4), and dendritic cells (pBMI = 0.571, pAFM = 0.012). Patterns of depletion with increasing adiposity were observed for plasma B (pBMI = 0.430, pAFM = 0.004) and immature B (pBMI = 0.022, pAFM = 0.042) cells. CD4, dendritic, monocytes, immature B, and plasma B cells may be important agents in the inflammatory process. Finally, the method used to assess leukocyte infiltration in this study is straightforwardly extended to other cell types and tissues in which infiltration might be of interest.
Modeling CO2 flow in support of a shallow subsurface controlled leakage field test
Authors: Iglesias Rodrigo S. , Romio Cristiane , Melo Clarissa L. , Musse Ana Paula S. , do Rosário Fátima , Oldenburg Curtis M.
Published: August 2019

Controlled release of carbon dioxide (CO2) into the soil and atmosphere is performed to test detection and monitoring tools, for which several field laboratories were established by a number of institutions worldwide. Numerical simulations of CO2 behavior in the shallow subsurface region are other forms of validation and verification of the leakage pathways and destinations. These studies aim to improve monitoring and verification of CO2 in case of unexpected leakages for public assurance. In this work, we present the results of a numerical modeling study conducted to simulate the injection of CO2 as carried out during a field test in Viamão, southern Brazil, where 20 kg day–1 of CO2 was pumped for 30 days through a vertical well 3 m below ground in an altered granitic soil. Multiphase flow simulations were performed with the TOUGH2/EOS7CA software for unsaturated porous media, using field data and injection parameters, including sensitivity tests to permeability direction, diffusivity, and boundary conditions. Results with increased horizontal permeabilities are in better agreement with the field observations. In this condition, mass balance calculations indicate approximately 90% of injected CO2 (20 kg day–1 during 30 days) remains in the soil after 180 days from injection start, consistent with the measured flow through the soil–atmosphere interface. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Reflections on the Evolution of Smart Polymers
Authors: Gillies Elizabeth R.
Published: August 2019

Since Staudinger's recognition that polymers were long chain molecules with covalent bonds between repeating units, the field has evolved tremendously. In addition to their many structural roles, polymers have been developed to exhibit “smart” stimuli‐responsive behavior. This article will describe the evolution of selected classes of smart polymers including those responsive to changes in pH, temperature, light, and mechanical stimuli, as well as self‐immolative polymers and their application in drug delivery, sensors, and actuators. It will also highlight key advancements in polymer chemistry that enabled rapid progress over the past ∼20 years. Whether the key achievements were predictable will be discussed, and the extent to which polymer science remains an independent science versus a service tool will be addressed. Finally, some possibilities for the evolution of the field over the next 20–30 years will be described.
Where the Big Bucks Will Come From: Implementing Product Line Engineering for Railway Rolling Stock
Authors: Chalé Góngora Hugo Guillermo , Greugny François
Published: August 2019

This paper presents a mid‐term return of experience from Alstom's rolling stock division on its implementation of product line engineering (PLE). It describes the journey we have undertaken to implement PLE, the challenges we have had to face, and the manner in which we are finding our way (most of the time deliberately, sometimes fortuitously) to define a profitable reuse strategy and to structure our approach on PLE. The paper also presents some encouraging intermediate results and concludes with the perspectives and the future challenges in our search for product line systems engineering excellence.
Decision‐Driven Product Development
Authors: Hause Matthew , Korff Andreas
Published: August 2019

Product line engineering (PLE) is the engineering and management of a group of related products using a shared set of assets and a means of design and manufacturing. PLE can include systems, software, and assets and involves all aspects of engineering including electrical, electronic, mechanical, and chemical, just to name a few. Engineers normally consider PLE after the product has evolved and complexity becomes too much to manage. Leveraging PLE from the very beginning will identify cost savings and commonality and provide a natural means for product evolution. Orthogonal variability modeling (OVM) provides a natural decision set allowing engineers to perform trade‐offs for specific customers and guide system development along the most effective route. Using automotive examples, this paper will describe model‐based product line engineering (MB‐PLE), the process for creating product lines, and the benefits of this approach as applicable to the military ground vehicle domain. Finally, it will show how the adoption of MB‐PLE early in the development life cycle provides more benefits without the potential disruption and reengineering that can occur when engineers adopt it later in the life cycle.
Seasonal expression and cellular distribution of star and steroidogenic enzymes in quail testis
Authors: Rosati Luigi , Di Fiore Maria Maddalena , Prisco Marina , Di Giacomo Russo Federica , Venditti Massimo , Andreuccetti Piero , Chieffi Baccari Gabriella , Santillo Alessandra
Published: August 2019

The quail Coturnix coturnix is a seasonal breeder with a physiological switch on/off of gonadic activity. Photoperiod and temperature are the major environmental factors regulating the spermatogenesis. To more thoroughly comprehend the steroidogenic pathways that govern the seasonal reproductive cycle, we have investigated the localization of StAR protein and steroidogenic enzymes (3β‐HSD, 17β‐HSD, P450 aromatase, and 5α‐Red) as well as androgen and estrogen levels, in the testis of reproductive and nonreproductive quails. We demonstrated that StAR, 3β‐HSD, 17β‐HSD, P450 aromatase, and 5α‐Red were always present in the somatic (Leydig and Sertoli cells) and germ cells (spermatogonia, spermatocytes I and II, spermatids, and spermatozoa). In addition, by western blot analysis, we demonstrated that 17β‐HSD, P450 aromatase, and 5α‐Red showed the highest expression levels during the reproductive testis compared with nonreproductive one. Accordingly, we also found that during the reproductive phase the highest titres of testosterone, 17β‐estradiol, and 5α‐dihydrotestosterone are recorded. In conclusion, our findings demonstrated that in C. coturnix: (a) both somatic and germ cells are involved in the local synthesis of sex hormones; (b) 17β‐HSD, P450 aromatase, and 5α‐Red expressions, as well as testicular androgens and estrogens, increased in reproductive quail testis. This study strongly indicates that the steroidogenic process in quail testis exhibits seasonal changes with the promotion of both androgenic and estrogenic pathways in the reproductive period, suggesting their synergic mechanism in the spermatogenesis regulation.
Abdominal tuberculosis in children: A real‐world experience of 218 cases from an endemic region
Authors: Lal Sadhna B , Bolia Rishi , Menon Jagadeesh V , Venkatesh Vybhav , Bhatia Anmol , Vaiphei Kim , Yadav Rakesh , Sethi Sunil
Published: August 2019

Background and Aim

Abdominal tuberculosis (ATB) in children poses a diagnostic challenge because of its nonspecific clinical features, which often delay the diagnosis. Our aim was to present our real‐world experience and provide an insight into the presentation, pattern of distribution, and diagnosis of the disease.

Methods

A retrospective review was conducted of case records of all children ≤12 years of age diagnosed with ATB from January 2007 to January 2018. Clinical details and investigations were recorded and analyzed.

Results

A total of 218 children (110 boys), with a median age of 10 (0.25–12) years, were included. There was a median delay of 4 (0.5–36) months in establishing the diagnosis. Abdominal pain, fever, and loss of weight were the most common presenting features, with the triad of symptoms present in 54%. Multiple intra‐abdominal sites were involved in 118 (54%) patients, with a combination of the gastrointestinal tract (I) and abdominal lymph nodes (L) being the most common (53/118). Among children with single‐site involvement (n = 100), the most commonly involved was L in 39 (39%), followed by I in 35(35%). Loss of weight was more common in children with involvement of multiple sites (85/118 vs 60/100, P = 0.03). Overall, a confirmed diagnosis was possible in 94 participants (43.1%). Suggestive imaging had the highest diagnostic yield of 85%. Nine (4.1%) patients needed surgical management.

Conclusion

A triad of abdominal pain, fever, and weight loss is suggestive of ATB. Multiple intra‐abdominal sites are frequently involved. Microbiological confirmation is possible in only one‐third of the cases.
Evaluation of some distributional downscaling methods as applied to daily maximum temperature with emphasis on extremes
Authors: Lanzante John R. , Adams‐Smith Dennis , Dixon Keith W. , Nath Maryjo , Whitlock Carolyn E.
Published: August 2019

Statistical downscaling methods are extensively used to refine future climate change projections produced by physical models. Distributional methods, which are among the simplest to implement, are also among the most widely used, either by themselves or in conjunction with more complex approaches. Here, building off of earlier work we evaluate the performance of seven methods in this class that range widely in their degree of complexity. We employ daily maximum temperature over the Continental U.S. in a “Perfect Model” approach in which the output from a large‐scale dynamical model is used as a proxy for both observations and model output. Importantly, this experimental design allows one to estimate expected performance under a future high‐emissions climate‐change scenario. We examine skill over the full distribution as well in the tails, seasonal variations in skill, and the ability to reproduce the climate change signal. Viewed broadly, there generally are modest overall differences in performance across the majority of the methods. However, the choice of philosophical paradigms used to define the downscaling algorithms divides the seven methods into two classes, of better versus poorer overall performance. In particular, the bias‐correction plus change‐factor approach performs better overall than the bias‐correction only approach. Finally, we examine the performance of some special tail treatments that we introduced in earlier work which were based on extensions of a widely used existing scheme. We find that our tail treatments provide a further enhancement in downscaling extremes.
The role of N form supply for PGPM‐host plant interactions in maize
Authors: Mpanga Isaac Kwadwo , Gomez-Genao Ninoska , Moradtalab Narges , Wanke Daniel , Chrobaczek Victor , Ahmed Aneesh , Windisch Saskia , Geistlinger Joerg , Hafiz Fatema Binte , Walker Frank , Ludewig Uwe , Neumann Günter
Published: August 2019

The form of nitrogen (N) supply has a significant impact on rhizosphere chemistry and root growth responses of higher plants. The respective effects are also employed as management options to improve nutrient acquisition and to minimize nutrient losses in cropping systems. However, surprisingly little is known concerning the interactions with rhizosphere biota. In this study, we investigated the effects of selected bacterial and fungal inoculants with proven plant growth‐promoting and phosphate (P)‐solubilizing potential (plant growth‐promoting microorganisms, PGPM) in maize with nitrate or stabilized ammonium supply, on soils with limited P availability and sparingly soluble rock phosphate (Rock‐P) applied as P fertilizer. The combination of the bacterial inoculants Pseudomonas sp. DSMZ 13134 (Proradix) and Bacillus amyloliquefaciens FZB42 with ammonium sulphate fertilization, stabilized with the nitrification inhibitor 3,4‐dimethylpyrazole‐phosphate (DMPP), resulted in a superior shoot biomass production (79–111%) and shoot P accumulation (109–235%) as compared with nitrate supply. This effect could be partially attributed to (1) ammonium‐induced rhizosphere acidification via increased root extrusion of protons, (2) promotion of root hair elongation, and (3) increased shoot concentrations of hormonal growth regulators (indole‐3‐acetic acid, zeatin, gibberellic acid). The effects, induced by the microbial inoculants were mainly related to increased root length development (43–44%), associated with a 60% increase in auxin production potential. No inoculant effects were detected on root hair elongation or on chemical modifications of the rhizosphere involved in P solubilisation, such as rhizosphere acidification, release of carboxylates or secretory phosphohydrolases. However, the ammonium‐induced stimulation of root hair elongation increased preferential sites for root colonization by the selected inoculants, which may explain the increase in rhizosphere abundance of PGPMs, exemplarily recorded for the fungal inoculant Trichoderma harzianum OMG16 (210%). The presented data suggest a network of positive interactions between stabilized ammonium fertilization and plant growth‐promoting functions of various bacterial and fungal PGPM inoculants. This offers perspectives to increase the efficiency and the reproducibility of PGPM‐assisted fertilization strategies.
A novel drug delivery system of mixed micelles based on poly(ethylene glycol)‐poly(lactide) and poly(ethylene glycol)‐poly(ɛ‐caprolactone) for gambogenic acid
Authors: Lin Tong‐Yuan , Zhu Ting‐Ting , Xun Yan , Tao Yun‐Song , Yang Yu‐Qin , Xie Jia‐Li , Zhang Xiao‐Ming , Chen Shi‐Xiong , Ding Bai‐Jing , Chen Wei‐Dong
Published: August 2019

In this study, a novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)‐poly(lactide) (mPEG‐PLA) and poly(ethylene glycol)‐poly(ɛ‐caprolactone) (mPEG‐PCL), used as a novel nanocarrier to encapsulate gambogenic acid (GNA). GNA‐loaded mixed polymeric micelles (GNA‐MMs) was prepared by cosolvent evaporation method. The mean average size of GNA‐MMs was (83.23 ± 1.06) nm (n = 3) and entrapment efficiency (EE%) of GNA‐MMs was (90.18 ± 2.59) % (n = 3) as well as (12.36 ± 0.64) % (n = 3) for drug loading (DL%). Transmission electron microscopy revealed that the GNA‐MMs were spherical with “core‐shell” structures. Compared with free GNA solution, in vitro release of GNA from GNA‐MMs showed a two‐phase sustained release profile: an initial relatively fast phase and followed by a slower release phase. Pharmacokinetic results also indicated that the GNA‐MMs have longer systemic circulation time and slower plasma elimination rate than free GNA solution. Moreover, the in vitro cytotoxicity assay showed that the IC50 values on HepG2 cells for GNA‐MMs and free GNA were (5.67 ± 0.02) μM and (9.02 ± 0.03) μM, respectively. In addition, GNA‐MMs significantly increased the HepG2 cellular apoptosis in a concentration‐dependent manner. In conclusion, the results showed that mPEG‐PLA/mPEG‐PCL mixed micelles may serve as an ideal drug delivery system for GNA to prolong drug circulation time in body, enhance bioavailability and retained its potent antitumor effect.
Effect of the cerium (III) chloride heptahydrate on the corrosion inhibition of aluminum alloy
Authors: Kurtela Marin , Šimunović Vinko , Stojanović Ivan , Alar Vesna
Published: August 2019

In the present work, the corrosion protection of aluminum alloy AA2024‐T3 has been studied in NaCl solution, with and without the addition of cerium (III) chloride heptahydrate. The corrosion inhibitor efficiency after immersion into 10 mM NaCl, with or without 3 mM of CeCl3·7H2O at 20°C, 40°C, and 60°C was investigated. The performed quantitative tests include electrochemical techniques, such as the method of quasipotentiostatic polarization (Tafel extrapolation), cyclic polarization, and electrochemical impedance spectroscopy to determine corrosion rate (vcorr), inhibition efﬁciency (η %), protective ability (γ), degree of coverage (ϑ), and pitting nucleation resistance. The samples were analyzed with scanning electron microscopy and energy dispersive X‐ray analysis to evaluate and characterize the precipitates formed on the surface of aluminum samples and to determine dominant type of corrosion. The formation of Ce3+ precipitates occurred on cathodic intermetallic sites and the surface, in general, resulting in improved corrosion resistance. Tested cerium (III) chloride heptahydrate proved to be an effective inorganic corrosion inhibitor for AA2024‐T3 in chloride solution, which, by the action of cerium ions, reduced corrosion on the surface of the studied aluminum alloy.
Repurposing approved drugs on the pathway to novel therapies
Authors: Schein Catherine H.
Published: August 2019

The time and cost of developing new drugs have led many groups to limit their search for therapeutics to compounds that have previously been approved for human use. Many “repurposed” drugs, such as derivatives of thalidomide, antibiotics, and antivirals have had clinical success in treatment areas well beyond their original approved use. These include applications in treating antibiotic‐resistant organisms, viruses, cancers and to prevent burn scarring. The major theoretical justification for reusing approved drugs is that they have known modes of action and controllable side effects. Coadministering antibiotics with inhibitors of bacterial toxins or enzymes that mediate multidrug resistance can greatly enhance their activity. Drugs that control host cell pathways, including inflammation, tumor necrosis factor, interferons, and autophagy, can reduce the “cytokine storm” response to injury, control infection, and aid in cancer therapy. An active compound, even if previously approved for human use, will be a poor clinical candidate if it lacks specificity for the new target, has poor solubility or can cause serious side effects. Synergistic combinations can reduce the dosages of the individual components to lower reactivity. Preclinical analysis should take into account that severely ill patients with comorbidities will be more sensitive to side effects than healthy trial subjects. Once an active, approved drug has been identified, collaboration with medicinal chemists can aid in finding derivatives with better physicochemical properties, specificity, and efficacy, to provide novel therapies for cancers, emerging and rare diseases.
Penoscrotal reconstruction with superficial circumflex iliac artery perforator propeller flap
Authors: Han Hyun Ho , Ahn Ma Rip , Lee Jung Ho
Published: August 2019

Background

Successful penoscrotal reconstruction requires proper resurfacing of the defect and maintenance of the original shape of the penis and scrotum. We examined the feasibility of using the superficial circumflex iliac artery perforator (SCIP) propeller flap to effectively reconstruct penoscrotal defects.

Methods

Eleven male patients with an average age of 62.2 years were retrospectively evaluated. The average defect size was 21.3 × 10.5 cm2 (range: 10 × 8–24 × 16 cm2). An eccentrically located elliptical flap was constructed using a handheld Doppler device after detecting the perforator as the pivot point. The medial branch of the superficial circumflex iliac artery was used for all cases. Flaps were designed to cover 70–80% of the defect area and the average rotation arc was 165°.

Results

The average flap dimension was 19.7 × 7.7 cm2. Two cases showed partial necrosis in the flap tip area. There were no instances of total flap loss or lymphorrhea, or complications such as scar contracture, urination problems, erectile dysfunction, or discomfort during intercourse.

Conclusions

The SCIP flap is an effective and ideal method for penoscrotal reconstruction considering the loose, elastic, and thin nature of the tissue. Elevation is easily facilitated, and the thickness of the SCIP flap can be adjusted without microsurgery.
Ameliorative Effects of Probiotic Lactobacillus paracasei NL41 on Insulin Sensitivity, Oxidative Stress, and Beta‐Cell Function in a Type 2 Diabetes Mellitus Rat Model
Authors: Zeng Zhu , Yuan Qipeng , Yu Rui , Zhang Jinlan , Ma Huiqin , Chen Shangwu
Published: August 2019

Scope

The present study aims to assess the antidiabetic effect of Lactobacillus paracasei strain NL41 and its potential mechanisms in rats with type 2 diabetes mellitus (T2DM) induced by a high‐fat diet and low‐dose streptozotocin administration (HFD/STZ).

Methods and results

Eighteen Sprague–Dawley (SD) rats are randomly assigned to three groups: one control, one HFD/STZ model, and one HFD/STZ‐Lactobacillus protection group with administration of strain NL41 for 12 weeks. Blood is collected for biochemical parameters analysis and tissue samples for histological analysis. Treatment with strain NL41 results in excellent blood glucose regulation and significantly decreases insulin resistance, and HbA1c, glucagon, and leptin levels, accompanied by remarkable improvement of dyslipidemia and oxidative stress status in the animals. Islets of Langerhans, liver, and kidney are significantly protected in the NL41‐treated rats compared to the HFD/STZ‐T2DM model rats. Histochemistry shows that strain NL41 inhibits beta‐cell loss and alpha‐cell expansion, indicating pancreatic islets as the targeted tissues for the primary ameliorative effect of the probiotic strain on HFD/STZ‐T2DM rats. Crosstalk between the gut–liver and liver–pancreas endocrine axes is discussed.

Conclusion

Probiotic strain NL41 prevents HFD/STZ‐T2DM by decreasing insulin resistance and oxidative stress status, and protecting beta‐cell function.
Perfusion and apparent oxygenation in the human placenta (PERFOX)
Authors: Hutter Jana , Harteveld Anita A. , Jackson Laurence H. , Franklin Suzanne , Bos Clemens , van Osch Matthias J. P. , O'Muircheartaigh Jonathan , Ho Alison , Chappell Lucy , Hajnal Joseph V. , Rutherford Mary , De Vita Enrico
Published: August 2019

Purpose

To study placental function—both perfusion and an oxygenation surrogate ()—simultaneously and quantitatively in‐vivo.

Methods

Fifteen pregnant women were scanned on a 3T MR scanner. For perfusion measurements, a velocity selective arterial spin labeling preparation module was placed before a multi‐echo gradient echo EPI readout to integrate and perfusion measurements in 1 joint perfusion‐oxygenation (PERFOX) acquisition. Joint motion correction and quantification were performed to evaluate changes in and perfusion over GA.

Results

The optimized integrated PERFOX protocol and post‐processing allowed successful visualization and quantification of perfusion and in all subjects. Areas of high and high perfusion appear to correspond to placental sub‐units and show a systematic offset in location along the maternal‐fetal axis. The areas of highest perfusion are consistently closer to the maternal basal plate and the areas of highest closer to the fetal chorionic plate. Quantitative results show a strong negative correlation of gestational age with and weak negative correlation with perfusion.

Conclusions

A strength of the joint sequence is that it provides truly simultaneous and co‐registered estimates of local and perfusion, however, to achieve this, the time per slice is prolonged compared to a perfusion only scan which can potentially limit coverage. The achieved interlocking can be particularly useful when quantifying transient physiological effects such as uterine contractions. PERFOX opens a new avenue to elucidate the relationship between maternal supply and oxygen uptake, both of which are central to placental function and dysfunction.