bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Deep Eutectic Solvents with Flexible Hydrogen‐Bonded Supramolecular Networks for Highly Efficient Uptake of NH3
Authors: Li Yuhui , Ali Mohammad Chand , Yang Qiwei , Zhang Zhiguo , Bao Zongbi , Su Baogen , Xing Huabin , Ren Qilong
Published: July 2017

Serious environmental concerns have led to a great demand for efficient uptake of NH3 by solvents. However, traditional aqueous absorbents have many shortcomings and efforts to use ionic liquids have met with limited success. A hybrid deep eutectic solvents (DESs) designed with a flexible hydrogen‐bonded supramolecular network exhibits both exceptional NH3 uptake capacity and superior desorption–regeneration performance, along with superb NH3/CO2 selectivity and environmental merit. Elucidated by molecular dynamic simulations and spectroscopic analysis, the abundant hydrogen‐bonding sites in the hybrid DESs bind every atom of the NH3 molecule and enable strong physical reversible solvation, whereas the multiple interactions among the hybrid components create a flexible hydrogen‐bonded supramolecular network and allow for solvent‐unbreaking absorption to ensure the full participation of the solvent and process stability. A mass solubility of NH3 up to 0.13 g g−1 was achieved at 313 K and 101 kPa by the hybrid DES choline chloride/resorcinol/glycerol (1:3:5), which is higher than all reported ionic liquids and ordinary DESs. Moreover, the performance remained the same after ten absorption–desorption cycles and the DESs could be easily regenerated.
Synthesis, Structure, and Reactivity of a Stable Phosphonium–Sulfinyl Yldiide
Authors: Garduno‐Alva Azucena , Lenk Romaric , Escudié Yannick , González Mariana Lozano , Bousquet Laura , Saffon‐Merceron Nathalie , Toledano Cecilio Alvarez , Bagan Xavier , Branchadell Vicenç , Maerten Eddy , Baceiredo Antoine
Published: July 2017

The synthesis of a stable lithium phosphonium–sulfinyl yldiide was explored. The compound was fully characterized by NMR spectroscopy and X‐ray crystallography. The electronic structure of2was analyzed by DFT calculations, which indicated strong ylidic character. Yldiide2was stable enough to catalyze the hydroacylation of benzaldehyde. More interestingly, the Wittig reaction with activated ketones proceeded smoothly at room temperature owing to the presence of the lithium cation.
Chemoenzymatic Synthesis of Racemic and Enantiomerically Pure Phosphaaspartic Acid and Phosphaarginine
Authors: Qian Renzhe , Kuliszewska Edyta , Macoratti Elena , Hammerschmidt Friedrich
Published: July 2017

Diisopropyl allyloxymethylphosphonate prepared by a one‐pot procedure was isomerized to give racemic 1‐hydroxy‐3‐butenylphosphonate with LDA by a [2,3]‐sigmatropic rearrangement. Chloroacetylation delivered an ester, which was resolved in a two‐phase system by using the lipase from Thermomyces lanuginosus. Racemic and (S)‐α‐hydroxyphosphonate 6 were converted to (±)‐ and (R)‐phosphaaspartic acid by functional‐group manipulation. (±)‐, (R)‐ and (S)‐6 were first esterified with 4‐nitrobenzenesulfonyl chloride before hydroboration to transform the double bond into a hydroxyethyl group. The hydroxyl group was manipulated to give a guanidinyl group and the 4‐nitrobenzenesulfonyloxy to give an amino group. Global deprotection of the α‐aminophosphonates yielded the desired phosphaamino acids.
Silver nanoparticles functionalized with ampicillin
Authors: Rogowska Agnieszka , Rafińska Katarzyna , Pomastowski Paweł , Walczak Justyna , Railean‐Plugaru Viorica , Buszewska‐Forajta Magdalena , Buszewski Bogusław
Published: July 2017

The resistance of pathogenic bacteria to antibiotics has become a serious problem. The emphasis is placed on the development of new, effective antimicrobial strategies. One of them is the use of AgNPs in association with antibiotic drugs. The aim of this study was to obtain silver nanoparticles functionalized with ampicillin and to investigate the mechanism of binding antibiotics to nanoparticle using high‐performance liquid chromatography approach. To confirm the occurrence of silver nanoparticles functionalization, FTIR, MALDI‐TOF MS, and DLS analysis and zeta potential measurements were performed. Moreover we assessed the antibacterial activity of biologically synthesized nanoparticles functionalized with ampicillin against a range of gram (+) and gram (−) bacteria strains such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus epidermidis, and Escherichia coli.
CE and nanomaterials – Part II: Nanomaterials in CE
Authors: Adam Vojtech , Vaculovicova Marketa
Published: July 2017

The scope of this two‐part review is to summarize publications dealing with CE and nanomaterials together. This topic can be viewed from two broad perspectives, and this article is trying to highlight these two approaches: (i) CE of nanomaterials, and (ii) nanomaterials in CE. The second part aims at summarization of publications dealing with application of nanomaterials for enhancement of CE performance either in terms of increasing the separation resolution or for improvement of the detection. To increase the resolution, nanomaterials are employed as either surface modification of the capillary wall forming open tubular column or as additives to the separation electrolyte resulting in a pseudostationary phase. Moreover, nanomaterials have proven to be very beneficial for increasing also the sensitivity of detection employed in CE or even they enable the detection (e.g., fluorescent tags of nonfluorescent molecules).
Differential uptake of gold nanoparticles by 2 species of tadpole, the wood frog (Lithobates sylvaticus) and the bullfrog (Lithobates catesbeianus)
Authors: Thompson Lucas B. , Carfagno Gerardo L.F. , Andresen Kurt , Sitton Andrea J. , Bury Taylor , Lee Laura L. , Lerner Kevin T. , Fong Peter P.
Published: July 2017

Engineered nanoparticles are aquatic contaminants of emerging concern that exert ecotoxicological effects on a wide variety of organisms. We exposed cetyltrimethylammonium bromide–capped spherical gold nanoparticles to wood frog and bullfrog tadpoles with conspecifics and in combination with the other species continuously for 21 d, then measured uptake and localization of gold. Wood frog tadpoles alone and in combination with bullfrog tadpoles took up significantly more gold than bullfrogs. Bullfrog tadpoles in combination with wood frogs took up significantly more gold than controls. The rank order of weight-normalized gold uptake was wood frogs in combination > wood frogs alone > bullfrogs in combination > bullfrogs alone > controls. In all gold-exposed groups of tadpoles, gold was concentrated in the anterior region compared with the posterior region of the body. The concentration of gold nanoparticles in the anterior region of wood frogs both alone and in combination with bullfrogs was significantly higher than the corresponding posterior regions. We also measured depuration time of gold in wood frogs. After 21 d in a solution of gold nanoparticles, tadpoles lost >83% of internalized gold when placed in gold-free water for 5 d. After 10 d in gold-free water, tadpoles lost 94% of their gold. After 15 d, gold concentrations were below the level of detection. Our finding of differential uptake between closely related species living in similar habitats with overlapping geographical distributions argues against generalizing toxicological effects of nanoparticles for a large group of organisms based on measurements in only one species. Environ Toxicol Chem 2017;36:3351–3358. © 2017 SETAC

Abstract

Uptake of gold nanoparticles is species dependent and generalizing the impacts of nanomaterials to aquatic organisms should be avoided.
The individual experience of ageing prisoners: systematic review and meta‐synthesis through a Good Lives Model framework
Authors: Di Lorito Claudio , Völlm Birgit , Dening Tom
Published: July 2017

Objective

The existing literature on ageing prisoners tends to focus on such aspects as diagnosis and physical ill‐health. In contrast, the experience of imprisonment from the perspective of ageing prisoners has received less attention. Grounded in a Good Lives Model theoretical framework, we reviewed and meta‐synthesised literature around their experience of life in prison, its impact on their wellbeing and how prison services are currently addressing their complex needs. We further identify potential areas of improvement.

Methods

1. Systematic search on Assia, PsycInfo, MedLine, Embase, Web of Science, Google and Gov.uk. 2. Extraction and categorisation of data on NVivo. 3. Development of themes through thematic analysis and meta‐synthesis. 4. Identification of potential areas of improvement.

Results

We selected 25 studies for our review, of which 13 were from the USA, seven from the UK, two from Australia and one each from Ireland, Switzerland and Israel. We identified three themes: The hardship of imprisonment, addressing health and social care needs, and the route out of prison.

Conclusions

Ageing prisoners have unique and complex health and social care needs which, to varying degree across different countries, are mostly unmet. Promising initiatives to address their needs are emerging, but, at present time, the overall experience of incarceration for the ageing prisoner is quite poor, given the inconsistent physical, emotional and social care support offered from prison intake to release and beyond. Copyright © 2017 John Wiley & Sons, Ltd.
Ribavirin suppresses hepatic lipogenesis through inosine monophosphate dehydrogenase inhibition: Involvement of adenosine monophosphate‐activated protein kinase‐related kinases and retinoid X receptor α
Authors: Satoh Shinya , Mori Kyoko , Onomura Daichi , Ueda Youki , Dansako Hiromichi , Honda Masao , Kaneko Shuichi , Ikeda Masanori , Kato Nobuyuki
Published: July 2017

Ribavirin (RBV) has been widely used as an antiviral reagent, specifically for patients with chronic hepatitis C. We previously demonstrated that adenosine kinase, which monophosphorylates RBV into the metabolically active form, is a key determinant for RBV sensitivity against hepatitis C virus RNA replication. However, the precise mechanism of RBV action and whether RBV affects cellular metabolism remain unclear. Analysis of liver gene expression profiles obtained from patients with advanced chronic hepatitis C treated with the combination of pegylated interferon and RBV showed that the adenosine kinase expression level tends to be lower in patients who are overweight and significantly decreases with progression to advanced fibrosis stages. In our effort to investigate whether RBV affects cellular metabolism, we found that RBV treatment under clinically achievable concentrations suppressed lipogenesis in hepatic cells. In this process, guanosine triphosphate depletion through inosine monophosphate dehydrogenase inhibition by RBV and adenosine monophosphate‐activated protein kinase‐related kinases, especially microtubule affinity regulating kinase 4, were required. In addition, RBV treatment led to the down‐regulation of retinoid X receptor α (RXRα), a key nuclear receptor in various metabolic processes, including lipogenesis. Moreover, we found that guanosine triphosphate depletion in cells induced the down‐regulation of RXRα, which was mediated by microtubule affinity regulating kinase 4. Overexpression of RXRα attenuated the RBV action for suppression of lipogenic genes and intracellular neutral lipids, suggesting that down‐regulation of RXRα was required for the suppression of lipogenesis in RBV action. Conclusion: We provide novel insights about RBV action in lipogenesis and its mechanisms involving inosine monophosphate dehydrogenase inhibition, adenosine monophosphate‐activated protein kinase‐related kinases, and down‐regulation of RXRα. RBV may be a potential reagent for anticancer therapy against the active lipogenesis involved in hepatocarcinogenesis. (Hepatology Communications 2017;1:550–563)
Structured illumination microscopy with interleaved reconstruction (SIMILR)
Authors: Ma Ying , Li Di , Smith Zachary J. , Li Dong , Chu Kaiqin
Published: July 2017

Structured illumination microscopy (SIM) is the commonly used super‐resolution (SR) technique for imaging subcellular dynamics. However, due to its need for multiple illumination patterns, the frame rate is just a fraction of that of conventional microscopy and is thus too slow for fast dynamic studies. A new SR image reconstruction method that maximizes the use of each subframe of the acquisition series is proposed for improving the super‐resolved frame rate by N times for N illumination directions. The method requires no changes in raw data and is appropriate for many versions of SIM setup, including those implementing fast illumination pattern generation mechanism based on spatial light modulator or digital micromirror device. The performance of the proposed method is demonstrated through imaging the highly dynamic endoplasmic reticulum where continuous rapid growths or shape changes of tiny structures are observed.
Depth‐resolved multimodal imaging: Wavelength modulated spatially offset Raman spectroscopy with optical coherence tomography
Authors: Chen Mingzhou , Mas Josep , Forbes Lindsey H. , Andrews Melissa R. , Dholakia Kishan
Published: July 2017

A major challenge in biophotonics is multimodal imaging to obtain both morphological and molecular information at depth. We demonstrate a hybrid approach integrating optical coherence tomography (OCT) with wavelength modulated spatially offset Raman spectroscopy (WM‐SORS). With depth colocalization obtained from the OCT, we can penetrate 1.2‐mm deep into strong scattering media (lard) to acquire up to a 14‐fold enhancement of a Raman signal from a hidden target (polystyrene) with a spatial offset. Our approach is capable of detecting both Raman and OCT signals for pharmaceutical particles embedded in turbid media and revealing the white matter at depth within a 0.6‐mm thick brain tissue layer. This depth resolved label‐free multimodal approach is a powerful route to analyze complex biomedical samples.
Hsd3b2 associated in modulating steroid hormone synthesis pathway regulates the differentiation of chicken embryonic stem cells into spermatogonial stem cells
Authors: Zhang Chen , Wang Man , He Nana , Ahmed Mahmoud F. , Wang Yilin , Zhao Ruifeng , Yu Xinjian , Jin Jing , Song Jiuzhou , Zuo Qisheng , Zhang Yani , Li Bichun
Published: July 2017

Steroid hormones regulate differentiation of various types of cell during embryogenesis. Testosterone is one of the androgens that bind to receptors to regulate gene expression and promote spermatogenesis. Our results showed that testosterone, as a product of steroid hormones synthesis pathway, could facilitate the differentiation of embryonic stem cells (ESCs) into spermatogonial stem cells (SSCs). The analysis of the steroid hormones synthesis pathway demonstrated that 3beta‐hydroxysteroid dehydrogenase2 (Hsd3b2) plays a major role in the synthesis of testosterone. In the absence of Hsd3b2, the expression of downstream genes such as Cyp1a1, Ugt1a1, and Hsd17b7 was not maintained. This reduction is probably due to the down‐regulation of the steroid hormones synthesis pathway. Furthermore, qRT‐PCR, immunofluorescence, and flow cytometry analysis confirmed that the steroid hormones synthesis pathway could facilitate the differentiation of ESCs. Altogether, these results lead to a model in which Hsd3b2 regulates ESCs differentiation via modulating the activity of steroid hormones synthesis pathway.
The xenoestrogens biphenol‐A and nonylphenol differentially regulate metalloprotease‐mediated shedding of EGFR ligands
Authors: Urriola‐Muñoz Paulina , Li Xue , Maretzky Thorsten , McIlwain David R. , Mak Tak W. , Reyes Juan G. , Blobel Carl P. , Moreno Ricardo D.
Published: July 2017

The xenoestrogens bisphenol‐A (BPA) and nonylphenol (NP) are endocrine disruptors used in the plastic polymer industry to manufacture different products for human use. Previous studies have suggested a role of these compounds in the shedding of signaling molecules, such as tumor necrosis factor α (TNF‐α). The aim of this work was to evaluate the effect of BPA and NP on the sheddase ADAM17 and its newly discovered regulators iRhom1 and iRhom2 in the release of EGFR‐ligands. We report that BPA and NP can stimulate the release of the ADAM17‐substrates HB‐EGF and TGF‐α. In cells lacking ADAM17 (Adam17−/− mEFs) BPA‐stimulated release of HB‐EGF, but not TGF‐α, was strongly reduced, whereas NP‐stimulated shedding of HB‐EGF and TGF‐α was completely abolished. Inactivation of both ADAM17 and the related ADAM10 (Adam10/17−/− mEFs) completely prevented the release of these substrates. In the absence of iRhom1, BPA‐ or NP‐stimulated release of HB‐EGF or TGF‐α was comparable to wild‐type control mEFs, conversely the BPA‐induced release of HB‐EGF was abolished in iRhom2−/− mEFs. The defect in shedding of HB‐EGF in iRhom2−/− mEF cells could be rescued by overexpressing iRhom2. Interestingly, the NP‐stimulated release of HB‐EGF was not affected by the absence of iRhom2, suggesting that NP could potentially activate both ADAM10 and ADAM17. We tested this hypothesis using betacellulin (BTC), an EGFR‐ligand that is a substrate for ADAM10. We found that NP, but not BPA stimulated the release of BTC in Adam17−/−, iRhom2−/−, or iRhom1/2−/−, but not in Adam10/17−/− cells. Taken together, our results suggest that BPA and NP stimulate the release of EGFR‐ligands by differentially activating ADAM17 or ADAM10. The identification of specific effects of these endocrine disruptors on ADAM10 and ADAM17 will help to provide a better understanding of their roles in cell signaling and proinflammatory processes, and provide new potential targets for treatment of reproductive or inflammatory diseases such as asthma or breast cancer that are promoted by xenoestrogens.
tPA variant tPA‐A296–299 Prevents impairment of cerebral autoregulation and necrosis of hippocampal neurons after stroke by inhibiting upregulation of ET‐1
Authors: Armstead William M. , Hekierski Hugh , Yarovoi Serge , Higazi Abd Al‐Roof , Cines Douglas B.
Published: July 2017

Tissue‐type plasminogen activator (tPA) is neurotoxic and exacerbates uncoupling of cerebral blood flow (CBF) and metabolism after stroke, yet it remains the sole FDA‐approved drug for treatment of ischemic stroke. Upregulation of c‐Jun‐terminal kinase (JNK) after stroke contributes to tPA‐mediated impairment of autoregulation, but the role of endothelin‐1 (ET‐1) is unknown. Based on the Glasgow Coma Scale, impaired autoregulation is linked to adverse outcomes after TBI, but correlation with hippocampal histopathology after stroke has not been established. We propose that given after stroke, tPA activates N‐Methyl‐D‐Aspartate receptors (NMDA‐Rs) and upregulates ET‐1 in a JNK dependent manner, imparing autoregulation and leading to histopathology. After stroke, CBF was reduced in the hippocampus and reduced further during hypotension, which did not occur in hypotensive sham pigs, indicating impairment of autoregulation. Autoregulation and necrosis of hippocampal CA1 and CA3 neurons were further impaired by tPA, but were preserved by the ET‐1 antagonist BQ 123 and tPA‐A,296–299 a variant that is fibrinolytic but does not bind to NMDA‐Rs. Expression of ET‐1 was increased by stroke and potentiated by tPA but returned to sham levels by tPA‐A296–299 and the JNK antagonist SP600125. Results show that JNK releases ET‐1 after stroke. Tissue‐type plasminogen activator ‐A296–299 prevents impairment of cerebral autoregulation and histopathology after stroke by inhibiting upregulation of ET‐1.
Biochar‐Based Fertilization with Liquid Nutrient Enrichment: 21 Field Trials Covering 13 Crop Species in Nepal
Authors: Schmidt Hans‐Peter , Pandit Bishnu Hari , Cornelissen Gerard , Kammann Claudia I.
Published: July 2017

Biochar produced in cost‐efficient flame curtain kilns (Kon‐Tiki) was nutrient enriched either with cow urine or with dissolved mineral (NPK) fertilizer to produce biochar‐based fertilizers containing between 60–100 kg N, 5–60 kg P2O5 and 60–100 kg K2O, respectively, per ton of biochar. In 21 field trials, nutrient‐enriched biochars were applied at rates of 0·5–2 t ha−1 into the root zone of 13 different crops. Treatments combining biochar, compost and organic or chemical fertilizer were evaluated; control treatments contained same amounts of nutrients but without biochar. All nutrient‐enriched biochar substrates improved yields compared with their respective no‐biochar controls. Biochar enriched with dissolved NPK produced on average 20% ± 5·1% (N = 4 trials) higher yields than standard NPK fertilization without biochar. Cow urine‐enriched biochar blended with compost resulted on average in 123% ± 76·7% (N = 13 trials) higher yields compared with the organic farmer practice with cow urine‐blended compost and outcompeted NPK‐enriched biochar (same nutrient dose) by 103% ± 12·4% (N = 4 trials) respectively. Thus, the results of 21 field trials robustly revealed that low‐dosage root zone application of organic biochar‐based fertilizers caused substantial yield increases in rather fertile silt loam soils compared with traditional organic fertilization and to mineral NPK or NPK‐biochar fertilization. This can be explained by the nutrient carrier effect of biochar, causing a slow nutrient release behaviour, more balanced nutrient fluxes and reduced nutrient losses, especially when liquid organic nutrients are used for the biochar enrichment. The results open up new pathways for optimizing organic farming and improving on‐farm nutrient cycling. Copyright © 2017 John Wiley & Sons, Ltd.
A Novel Poly(N‐Isopropylacrylamide‐co‐acryloylamidobenzo‐12‐crown‐4) Microgel with Rapid Stimuli‐Responsiveness for Molecule‐Specific Adsorption of γ‐Cyclodextrin
Authors: Wei Yun‐Yan , Liu Zhuang , Luo Feng , Zhang Lei , Wang Wei , Ju Xiao‐Jie , Xie Rui , Chu Liang‐Yin
Published: July 2017

A novel poly(N‐isopropylacrylamide‐co‐acryloylamidobenzo‐12‐crown‐4) (PNB) microgel with rapid γ‐cyclodextrin (CD)‐responsive characteristics and adsorption property is developed. The microgel is composed of benzo‐12‐crown‐4 (B12C4) units as molecule‐recognition receptors and poly(N‐isopropylacrylamide) networks as phase‐transition actuators as well as adsorbent backbone chains. The PNB microgels significantly increase their volumes induced by γ‐CD, and adsorb γ‐CD molecules within PNB networks because of formation of γ‐CD/B12C4 inclusion complexes. Detection of γ‐CD‐concentration and the molecule‐specific adsorption processes of the microgels are investigated systematically. The PNB microgels provide a new tool for rapid concentration measurement and effective separation of γ‐CD.
Plasma Exchange‐responsive Tardive Delayed Pseudochoreoathetosis in a Patient with Anti‐Hu Neuronopathy
Authors: De Santis Tiziana , Morino Stefania , Antonini Giovanni , Pontieri Francesco E.
Published: July 2017

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Medialis pedis flap for reconstruction of weight bearing heel
Authors: Park Jin Sung , Lee Jae Hoon , Lee Jung Suk , Baek Jong Hun
Published: July 2017

Background

Among the various flaps available for the reconstruction of the heel, a medial plantar flap has been widely accepted as the most ideal. This flap, however, involves the medial plantar nerve and its cutaneous branches, which may lead to postoperative hyperesthesia and dual sensation. The purpose of this report was to report the outcomes of the use of the medialis pedis flap for the coverage of weight bearing heel soft tissue defect.

Patients and methods

A total of 8 patients who had undergone reconstruction of the weight bearing heel with the medialis pedis flap were enrolled for this study. There were 6 male and 2 female patients and the mean age was 46 years. The causes of the defects included pressure sore, crushing injury and malignant melanoma. The mean size of the defects was 3 × 4 cm. Five cases were reconstructed with island flaps and 3 were covered with free flaps.

Results

The mean size of the flaps was 3×5 cm. All flaps survived. One case developed arterial insufficiency and was treated with a vein graft. Ambulation in normal shoes was possible in all the patients. Seven cases did not report pain, but 1 case complained of mild pain. No case reported complications including pain at the donor site, ulcerations, sensory loss, hyperesthesia, or sensory disturbance. The mean follow‐up period was 14.4 months.

Conclusions

The medialis pedis flap may be considered a useful flap for the reconstruction of soft tissue defects smaller than 5 cm in the weight bearing heel.
Extensions of the Glivenko‐type congruences on a Stone lattice
Authors: Badawy Abd El‐Mohsen
Published: July 2017

In this paper, the notions of annulets and normal filters are introduced in Stone lattices and their properties are studied. A set of equivalent conditions is obtained to characterize normal filters of a Stone lattice. The extensions of the Glivenko‐type congruences on a Stone lattice are investigated via annulets and normal filters. A description of the lattice of all extensions of the Glivenko‐type congruences on a Stone lattice is given. A one‐to‐one correspondence between the class of all extensions and the class of all normal filters of a Stone lattice is obtained. Finally, we observe that every 2 extensions of the Glivenko‐type congruences are permutable.
Patient‐reported outcomes from SYNERGY, a randomized, double‐blind, multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients
Authors: Robinson Dudley , Kelleher Con , Staskin David , Mueller Elizabeth R. , Falconer Christian , Wang Jianye , Ridder Arwin , Stoelzel Matthias , Paireddy Asha , van Maanen Rob , Hakimi Zalmai , Herschorn Sender
Published: July 2017

Aims

To evaluate patient‐reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial.

Methods

Following a 4‐week placebo run‐in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2‐week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB‐q Symptom Bother score, health‐related quality of life (HRQOL) Total score, treatment satisfaction‐visual analogue scale (TS‐VAS), and patient perception of bladder condition (PPBC) questionnaires.

Results

Overall, 3527 patients were randomized into the study, with 3494 receiving double‐blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB‐q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB‐q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups.

Conclusions

PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB‐q Symptom Bother score, HRQOL Total score, and PPBC.
Medium‐Chain Enriched Diacylglycerol (MCE‐DAG) Oil Decreases Body Fat Mass in Mice by Increasing Lipolysis and Thermogenesis in Adipose Tissue
Authors: Kim Haeun , Choe Jee‐Hwan , Choi Jong Hun , Kim Hun Jung , Park Soo Hyun , Lee Moon Won , Kim Wooki , Go Gwang‐woong
Published: July 2017

Medium chain fatty acid (MCFA) escapes the formation of chylomicrons in the small intestine, resulting in energy expenditure through beta‐oxidation. Diacylglycerol (DAG) is susceptible to oxidation rather than being stored in the adipose tissue. This study was conducted to verify the effect of MCE‐DAG oil on body fat mass in vivo. Male C57BL/6 mice were randomly assigned to four groups (n = 12) as follows: (1) normal diet (18% kcal from fat), (2) canola oil as a control (40% kcal from canola oil), (3) MCE‐DAG10 (10% kcal from MCE‐DAG + 30% kcal from canola oil), and (4) MCE‐DAG20 (20% kcal from MCE‐DAG + 20% kcal from canola oil). The body weight and fat mass of MCE‐DAG20 group mice were decreased relative to those of control mice (P < 0.05 and P < 0.001, respectively). Serum triacylglycerol (TAG) was decreased in both MCE‐DAG10 and MCE‐DAG20 groups (P < 0.01 and P < 0.05, respectively). Hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) were increased in the MCE‐DAG20 group relative to the control in white adipose tissue (WAT) (P < 0.05). Uncoupling protein 1 (UCP1) was also increased in the MCE‐DAG20 group relative to the control in brown adipose tissue (BAT) (P < 0.05). In summary, MCE‐DAG reduced body fat mass likely by stimulating lipolysis in WAT and thermogenesis in BAT.
Localised estimation and control of linear instabilities in two-dimensional wall-bounded shear flows
Authors: Tol H. J. , Kotsonis M. , de Visser C. C. , Bamieh B.
Published: July 2017

A new framework is presented for estimation and control of instabilities in wall-bounded shear flows described by the linearised Navier–Stokes equations. The control design considers the use of localised actuators/sensors to account for convective instabilities in an ${\mathcal{H}}_{2}$ optimal control framework. External sources of disturbances are assumed to enter the control domain through the inflow. A new inflow disturbance model is proposed for external excitation of the perturbation modes that contribute to transition. This model allows efficient estimation of the flow perturbations within the localised control region of a conceptually unbounded domain. The state-space discretisation of the infinite-dimensional system is explicitly obtained, which allows application of linear control theoretic tools. A reduced-order model is subsequently derived using exact balanced truncation that captures the input/output behaviour and the dominant perturbation dynamics. This model is used to design an ${\mathcal{H}}_{2}$ optimal controller to suppress the instability growth. The two-dimensional non-periodic channel flow is considered as an application case. Disturbances are generated upstream of the control domain and the resulting flow perturbations are estimated/controlled using point wall shear measurements and localised unsteady blowing and suction at the wall. The controller is able to cancel the perturbations and is robust to both unmodelled disturbances and sensor inaccuracies. For single-frequency and multiple-frequency disturbances with low sensor noise a nearly full cancellation is achieved. For stochastic forced disturbances and high sensor noise an energy reduction in perturbation wall shear stress of 96 % is shown.
Small-amplitude supersolitons near supercritical plasma compositions
Authors: Olivier Carel P. , Verheest Frank , Maharaj Shimul K.
Published: July 2017

Supercritical plasma compositions in parameter space are considered for a general fluid model consisting of an arbitrary number of species. This is done by applying a Taylor series expansion of the Sagdeev potential about the acoustic speed and the equilibrium electrostatic potential. A novel finding in this study is the description of small-amplitude supersolitons. Our analysis allows us to determine the plasma compositional criteria for such structures, as well as lower and upper bounds of their velocities and amplitudes. We therefore establish an interesting link between supercritical plasma compositions and the existence of supersolitons. The results are illustrated via a case study where plasmas consisting of cold ions and two Boltzmann electron species are considered.
Backtracking with cut via a distributive law and left-zero monoids
Authors: PIRÓG MACIEJ , STATON SAM
Published: July 2017

We employ the framework of algebraic effects to augment the list monad with the pruning cut operator known from Prolog. We give two descriptions of the resulting monad: as the monad of free left-zero monoids, and as a composition via a distributive law of the list monad and the ‘unary idempotent operation’ monad. The scope delimiter of cut arises as a handler.
Ultra-processed foods and the limits of product reformulation
Authors: Scrinis Gyorgy , Monteiro Carlos Augusto
Published: July 2017

The nutritional reformulation of processed food and beverage products has been promoted as an important means of addressing the nutritional imbalances in contemporary dietary patterns. The focus of most reformulation policies is the reduction in quantities of nutrients-to-limit – Na, free sugars, SFA,trans-fatty acids and total energy. The present commentary examines the limitations of what we refer to as ‘nutrients-to-limit reformulation’ policies and practices, particularly when applied to ultra-processed foods and drink products. Beyond these nutrients-to-limit, there are a range of other potentially harmful processed and industrially produced ingredients used in the production of ultra-processed products that are not usually removed during reformulation. The sources of nutrients-to-limit in these products may be replaced with other highly processed ingredients and additives, rather than with whole or minimally processed foods. Reformulation policies may also legitimise current levels of consumption of ultra-processed products in high-income countries and increased levels of consumption in emerging markets in the global South.
Individual Differences in Attentional Capture by Pictures of Fear and Disgust as Indexed by Cardiac Responses
Authors: Ruiz-Padial Elisabeth , Mendoza Medialdea M.T. , Reyes del Paso G. , Thayer J.F.
Published: July 2017

Abstract. Emotional stimuli automatically capture attention in ways that are relevant to the survival value of the stimuli. We have previously shown that individual differences in resting heart rate variability (HRV) were related to attentional capture by negative (fearful) and neutral distractors. However, different negative emotions such as fear and disgust may differentially capture attention. In the present study we investigated the effect of automatic attention capture by disgust and fear stimuli on behavioral and phasic heart rate responses as well as its relationship with resting heart rate variability (HRV). Twenty-eight participants (14 men) were divided into two groups based on their resting HRV. Phasic cardiac responses as well as reaction times and errors on a digit categorization task were assessed with disgust, fear, and neutral pictures as distractors. In the high HRV group disgusting distractors produced the strongest interference on the ongoing cognitive task indicated by more errors and longer reaction times as well as a deeper cardiac deceleration compared to fearful or neutral distractors. In contrast, the low HRV group showed faster reaction times to fear evoking pictures, whereas their heart rate responses and number of errors did not distinguish between the three emotional categories. Our results suggest that high HRV participants showed the emotional context appropriate responses while low HRV participants seem to be hypervigilant to fear.
MicroRNA-148a deficiency promotes hepatic lipid metabolism and hepatocarcinogenesis in mice
Authors: Cheng Li , Zhu Yahui , Han Han , Zhang Qiang , Cui Kaisa , Shen Hongxing , Zhang Jinxiang , Yan Jun , Prochownik Edward , Li Youjun
Published: July 2017

miRNAs are involved in many physiologic and disease processes by virtue of degrading specific mRNAs or inhibiting their translation. miR-148a has been implicated in the control of tumor growth and cholesterol and triglyceride homeostasis using in vitro or in vivo gene expression- and silencing-based approaches. Here miR-148a knockout (KO) mice were used to investigate the intrinsic role of miR-148a in liver physiology and hepatocarcinogenesis in mice. miR-148a downregulation was found to be correlated with poor clinical outcomes in hepatocellular carcinoma (HCC) patients. Under regular chow diet (RCD) or high fat diet (HFD), miR-148a deletion significantly accelerated DEN-induced hepatocarcinogenesis in mice. Mechanistically, miR-148a deletion promotes lipid metabolic disorders in mice. Moreover, restoration of miR-148a reversed these defects. Finally, miR-148a was found to directly inhibit several key regulators of hepatocarcinogenesis and lipid metabolism. These findings reveal crucial roles for miR-148a in the hepatic lipid metabolism and hepatocarcinogenesis. They further identify miR-148a as a potential therapeutic target for certain liver diseases, including cancer.
Inhibition of autophagy as a treatment strategy for p53 wild-type acute myeloid leukemia
Authors: Folkerts Hendrik , Hilgendorf Susan , Wierenga Albertus T J , Jaques Jennifer , Mulder André B , Coffer Paul J , Schuringa Jan Jacob , Vellenga Edo
Published: July 2017

Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34+ AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53mut), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53R273H. AML CD34+ cells were more sensitive to the autophagy inhibitor hydroxychloroquine (HCQ) than normal bone marrow CD34+ cells. Similar, inhibition of autophagy by knockdown of ATG5 or ATG7 triggered apoptosis, which coincided with increased expression of p53. In contrast to wild-type p53 AML (TP53wt), HCQ treatment did not trigger a BAX and PUMA-dependent apoptotic response in AMLs harboring TP53mut. To further characterize autophagy in the leukemic stem cell-enriched cell fraction AML CD34+ cells were separated into ROSlow and ROShigh subfractions. The immature AML CD34+-enriched ROSlow cells maintained higher basal autophagy and showed reduced survival upon HCQ treatment compared with ROShigh cells. Finally, knockdown of ATG5 inhibits in vivo maintenance of AML CD34+ cells in NSG mice. These results indicate that targeting autophagy might provide new therapeutic options for treatment of AML since it affects the immature AML subfraction.
Flat clathrin lattices are dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling of specific receptors
Authors: Leyton-Puig Daniela , Isogai Tadamoto , Argenzio Elisabetta , van den Broek Bram , Klarenbeek Jeffrey , Janssen Hans , Jalink Kees , Innocenti Metello
Published: July 2017

Clathrin lattices at the plasma membrane coat both invaginated and flat regions forming clathrin-coated pits and clathrin plaques, respectively. The function and regulation of clathrin-coated pits in endocytosis are well understood but clathrin plaques remain enigmatic nanodomains. Here we use super-resolution microscopy, molecular genetics and cell biology to show that clathrin plaques contain the machinery for clathrin-mediated endocytosis and cell adhesion, and associate with both clathrin-coated pits and filamentous actin. We also find that actin polymerization promoted by N-WASP through the Arp2/3 complex is crucial for the regulation of plaques but not pits. Clathrin plaques oppose cell migration and undergo actin- and N-WASP-dependent disassembly upon activation of LPA receptor 1, but not EGF receptor. Most importantly, plaque disassembly correlates with the endocytosis of LPA receptor 1 and down-modulation of AKT activity. Thus, clathrin plaques serve as dynamic actin-controlled hubs for clathrin-mediated endocytosis and signalling that exhibit receptor specificity.
Dynamic-template-directed multiscale assembly for large-area coating of highly-aligned conjugated polymer thin films
Authors: Mohammadi Erfan , Zhao Chuankai , Meng Yifei , Qu Ge , Zhang Fengjiao , Zhao Xikang , Mei Jianguo , Zuo Jian-Min , Shukla Diwakar , Diao Ying
Published: July 2017

Solution processable semiconducting polymers have been under intense investigations due to their diverse applications from printed electronics to biomedical devices. However, controlling the macromolecular assembly across length scales during solution coating remains a key challenge, largely due to the disparity in timescales of polymer assembly and high-throughput printing/coating. Herein we propose the concept of dynamic templating to expedite polymer nucleation and the ensuing assembly process, inspired by biomineralization templates capable of surface reconfiguration. Molecular dynamic simulations reveal that surface reconfigurability is key to promoting template–polymer interactions, thereby lowering polymer nucleation barrier. Employing ionic-liquid-based dynamic template during meniscus-guided coating results in highly aligned, highly crystalline donor–acceptor polymer thin films over large area (>1 cm2) and promoted charge transport along both the polymer backbone and the π–π stacking direction in field-effect transistors. We further demonstrate that the charge transport anisotropy can be reversed by tuning the degree of polymer backbone alignment.
Potential increase in coastal wetland vulnerability to sea-level rise suggested by considering hydrodynamic attenuation effects
Authors: Rodríguez José F. , Saco Patricia M. , Sandi Steven , Saintilan Neil , Riccardi Gerardo
Published: July 2017

The future of coastal wetlands and their ecological value depend on their capacity to adapt to the interacting effects of human impacts and sea-level rise. Even though extensive wetland loss due to submergence is a possible scenario, its magnitude is highly uncertain due to limited understanding of hydrodynamic and bio-geomorphic interactions over time. In particular, the effect of man-made drainage modifications on hydrodynamic attenuation and consequent wetland evolution is poorly understood. Predictions are further complicated by the presence of a number of vegetation types that change over time and also contribute to flow attenuation. Here, we show that flow attenuation affects wetland vegetation by modifying its wetting-drying regime and inundation depth, increasing its vulnerability to sea-level rise. Our simulations for an Australian subtropical wetland predict much faster wetland loss than commonly used models that do not consider flow attenuation.
Improved genome recovery and integrated cell-size analyses of individual uncultured microbial cells and viral particles
Authors: Stepanauskas Ramunas , Fergusson Elizabeth A. , Brown Joseph , Poulton Nicole J. , Tupper Ben , Labonté Jessica M. , Becraft Eric D. , Brown Julia M. , Pachiadaki Maria G. , Povilaitis Tadas , Thompson Brian P. , Mascena Corianna J. , Bellows Wendy K. , Lubys Arvydas
Published: July 2017

Microbial single-cell genomics can be used to provide insights into the metabolic potential, interactions, and evolution of uncultured microorganisms. Here we present WGA-X, a method based on multiple displacement amplification of DNA that utilizes a thermostable mutant of the phi29 polymerase. WGA-X enhances genome recovery from individual microbial cells and viral particles while maintaining ease of use and scalability. The greatest improvements are observed when amplifying high G+C content templates, such as those belonging to the predominant bacteria in agricultural soils. By integrating WGA-X with calibrated index-cell sorting and high-throughput genomic sequencing, we are able to analyze genomic sequences and cell sizes of hundreds of individual, uncultured bacteria, archaea, protists, and viral particles, obtained directly from marine and soil samples, in a single experiment. This approach may find diverse applications in microbiology and in biomedical and forensic studies of humans and other multicellular organisms.
Achieving ultrahigh triboelectric charge density for efficient energy harvesting
Authors: Wang Jie , Wu Changsheng , Dai Yejing , Zhao Zhihao , Wang Aurelia , Zhang Tiejun , Wang Zhong Lin
Published: July 2017

With its light weight, low cost and high efficiency even at low operation frequency, the triboelectric nanogenerator is considered a potential solution for self-powered sensor networks and large-scale renewable blue energy. As an energy harvester, its output power density and efficiency are dictated by the triboelectric charge density. Here we report a method for increasing the triboelectric charge density by coupling surface polarization from triboelectrification and hysteretic dielectric polarization from ferroelectric material in vacuum (P ~ 10−6 torr). Without the constraint of air breakdown, a triboelectric charge density of 1003 µC m−2, which is close to the limit of dielectric breakdown, is attained. Our findings establish an optimization methodology for triboelectric nanogenerators and enable their more promising usage in applications ranging from powering electronic devices to harvesting large-scale blue energy.
Glucose Deficiency Elevates Acid-Sensing Ion Channel 2a Expression and Increases Seizure Susceptibility in Temporal Lobe Epilepsy
Authors: Zhang Haitao , Gao Guodong , Zhang Yu , Sun Yang , Li Huanfa , Dong Shan , Ma Wei , Liu Bei , Wang Weiwen , Wu Hao , Zhang Hua
Published: July 2017

Brain hypometabolism is a common epilepsy-related finding in both patients and animal models. Fluorodeoxyglucose positron emission tomography studies have shown that recurrent seizures lead to reduced glucose metabolism in certain brain regions, but no studies have definitively determined whether this induces epileptogenesis. There is evidence that acid-sensing ion channel 2a (ASIC2a) affects epilepsy susceptibility. Transcription factor CP2 (TFCP2) regulates ASIC2a expression. We report that suppressed TFCP2 expression and elevated ASIC2a expression were associated with glucose hypometabolism in the hippocampi of humans with epilepsy and of rat epilepsy model brains. In cultured PC12 cells, we determined that glucose deficiency led to TFCP2 downregulating ASIC2a. Moreover, electrophysiological recordings from cultured rat hippocampal slices showed that ASIC2a overexpression resulted in more action potentials in CA1 pyramidal neurons and increased seizure susceptibility. Our findings suggest that hippocampal glucose hypometabolism elevates ASIC2a expression by suppressing TFCP2 expression, which further enhances the intrinsic excitability of CA1 pyramidal neurons and increases seizure susceptibility in patients with temporal lobe epilepsy.
Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease
Authors: Hsueh Brian , Burns Vanessa M. , Pauerstein Philip , Holzem Katherine , Ye Li , Engberg Kristin , Wang Ai-Chi , Gu Xueying , Chakravarthy Harini , Arda H. Efsun , Charville Gregory , Vogel Hannes , Efimov Igor R. , Kim Seung , Deisseroth Karl
Published: July 2017

Three-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.