bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct Probing of Polarization Charge at Nanoscale Level
Authors: Kwon Owoong , Seol Daehee , Lee Dongkyu , Han Hee , Lindfors‐Vrejoiu Ionela , Lee Woo , Jesse Stephen , Lee Ho Nyung , Kalinin Sergei V. , Alexe Marin , Kim Yunseok
Published: November 2017

Ferroelectric materials possess spontaneous polarization that can be used for multiple applications. Owing to a long‐term development of reducing the sizes of devices, the preparation of ferroelectric materials and devices is entering the nanometer‐scale regime. Accordingly, to evaluate the ferroelectricity, there is a need to investigate the polarization charge at the nanoscale. Nonetheless, it is generally accepted that the detection of polarization charges using a conventional conductive atomic force microscopy (CAFM) without a top electrode is not feasible because the nanometer‐scale radius of an atomic force microscopy (AFM) tip yields a very low signal‐to‐noise ratio. However, the detection is unrelated to the radius of an AFM tip and, in fact, a matter of the switched area. In this work, the direct probing of the polarization charge at the nanoscale is demonstrated using the positive‐up‐negative‐down method based on the conventional CAFM approach without additional corrections or circuits to reduce the parasitic capacitance. The polarization charge densities of 73.7 and 119.0 µC cm−2 are successfully probed in ferroelectric nanocapacitors and thin films, respectively. The obtained results show the feasibility of the evaluation of polarization charge at the nanoscale and provide a new guideline for evaluating the ferroelectricity at the nanoscale.
Rhodium(I)‐Catalyzed Arylation/Dehydroxylation of tert‐Propargylic Alcohols Leading to Tetrasubstituted Allenes
Authors: Liu Na , Zhi Yanle , Yao Jian , Xing Junhao , Lu Tao , Dou Xiaowei
Published: November 2017

Diverse tetrasubstituted allenes are obtained selectively by the reaction of tert‐propargylic alcohols and arylboroxines under rhodium catalysis. The reaction is assumed to proceed through an arylation/dehydroxylation process, which involves β‐hydroxide elimination of a β‐hydroxy alkenyl‐rhodium intermediate that is generated by regioselective arylrhodation of the tert‐propargylic alcohol. In addition, when enantioenriched propargylic alcohol was used to prepare optically active allene, high efficiency of central‐to‐axial chirality transfer was observed. The application of current method to structural modification of pharmaceutical drugs was also showcased by a highly diastereoselective transformation of mifepristone.

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Robust stabilization of a two‐stage continuous anaerobic bioreactor system
Authors: Duan Zhaoyang , Kravaris Costas
Published: November 2017

This article studies the problem of stabilizing a two‐stage continuous bioreactor system. A simple dynamic model of the system is first introduced based on a detailed mass balance model, and then used to derive a constant‐yield controller to stabilize the system at given design steady state conditions. Using Lyapunov stability analysis, this control law is proved to guarantee stability of the closed loop system over the entire positive orthant. Simulation results show the successful performance of the controller. The control law is proved to be robust with respect to errors in the kinetic parameters and in the inlet feed concentration, in the sense of preserving its stability region. Performance of the control system can be enhanced if a feed‐forward measurement of the inlet feed concentration can be incorporated in the control law. © 2017 American Institute of Chemical Engineers AIChE J, 64: 1295–1304, 2018
No sex difference in digit ratios (2D:4D) in the traditional Yali of Papua and its meaning for the previous hypotheses on the inter‐populational variability in 2D:4D
Authors: Marczak Michalina , Misiak Michał , Sorokowska Agnieszka , Sorokowski Piotr
Published: November 2017

Objectives

The ratio between the 2nd and 4th digit (2D:4D) is considered to be a sexually dimorphic trait in humans, with males having on average lower 2D:4D values than females. However, significant inter‐ and intra‐sexual differences in digit ratios across populations have been reported. In order to further explore factors influencing the variability of 2D:4D, we performed a study among the Yali, a traditional population from Papua.

Methods

We measured digit ratios of 79 adults (47 males) from the traditional Yali society, a polygamous group who inhabit a harsh high‐mountain environment almost directly on the equator.

Results

Statistical analysis of the data show no significant inter‐sexual difference in digit ratios in our sample.

Conclusions

We discuss the results in light of various factors that putatively shape the differences in digit ratios. We conclude that the results of our study contribute to the existing evidence suggesting that digit ratio might not be universally sexually dimorphic in humans.
“Minimal” holoprosencephaly in a 14q deletion syndrome patient
Authors: Della Giustina Elvio , Iodice Alessandro , Spagnoli Carlotta , Giovannini Simona , Frattini Daniele , Fusco Carlo , Gobbi Giuseppe , Zollino Marcella , Neri Giovanni
Published: November 2017

We report on a patient with terminal deletion of the long arm of chromosome 14 displaying brain interhemispheric fusion limited to the midline anterior frontal cortex associated with hypoplastic corpus callosum and incomplete rotation of the left hippocampus in a clinical setting of motor and intellectual disability with poor language, and social behavior abnormalities with aggressiveness. Some possible correlations between clinical signs and symptoms and various aspects of the complex brain malformation are briefly discussed and compared with other known abnormalities of chromosome 14. The different neuropathology of the most common forms and the new forms of holoprosencephaly recently described is also discussed and leads us to suggest classifying the interhemispheric fusion of this case as a “minimal” form of holoprosencephaly. This appears to be the first description in a 14q deletion patient.
A heterozygous mutation in RPGR associated with X‐linked retinitis pigmentosa in a patient with Turner syndrome mosaicism (45,X/46,XX)
Authors: Zhou Qi , Yao Fengxia , Wang Feng , Li Hui , Chen Rui , Sui Ruifang
Published: November 2017

Turner syndrome with retinitis pigmentosa (RP) is rare, with only three cases reported based on clinical examination alone. We summarized the 4‐year follow‐up and molecular findings in a 28‐year‐old patient with Turner syndrome and the typical features of short stature and neck webbing, who also had X‐linked RP. Her main complaints were night blindness and progressive loss of vision since the age of 9 years. Ophthalmologic examination, optical coherent tomographic imaging, and visual electrophysiology tests showed classic manifestations of RP. The karyotype of peripheral blood showed mosaicism (45,X [72%]/46,XX[28%]). A novel heterozygous frameshift mutation (c.2403_2406delAGAG, p.T801fsX812) in the RP GTPase regulator (RPGR) gene was detected using next generation sequencing and validated by Sanger sequencing. We believe that this is the first report of X‐linked RP in a patient with Turner syndrome associated with mosaicism, and an RPGR heterozygous mutation. We hypothesize that X‐linked RP in this woman is not related to Turner syndrome, but may be a manifestation of the lack of a normal paternal X chromosome with intact but mutated RPGR.
Tattooing tools and the Lapita cultural complex
Authors: TORRENCE ROBIN , KONONENKO NINA , SHEPPARD PETER , ALLEN MELINDA S. , BEDFORD STUART , KIRCH PATRICK , SPRIGGS MATTHEW
Published: November 2017

A use‐wear and residue study of 56 retouched obsidian flakes from seven Lapita sites in Papua New Guinea, Solomon Islands, and Vanuatu confirms that they had been used for tattooing. These specialised tools all bear one or more very small points formed by alternating retouch. A detailed comparison of use traces and pigments on these and 19 additional skin piercing tools analysed previously challenges the notion of homogeneity in cultural practices across the broad geographical range where Lapita pottery was used. The existence of shared innovations together with variation in the selection of pigments and the shape of the obsidian artefacts used for puncturing skin highlight a complex pattern of similarities and differences within this community of culture.
Nomenclature of Cutaneous Vasculitis
Authors: Sunderkötter Cord H. , Zelger Bernhard , Chen Ko‐Ron , Requena Luis , Piette ‎Warren , Carlson J. Andrew , Dutz Jan , Lamprecht Peter , Mahr Alfred , Aberer Elisabeth , Werth Victoria P. , Wetter David A. , Kawana Seiji , Luqmani Raashid , Frances Camille , Jorizzo Joseph , Watts J. Richard , Metze Dieter , Caproni Marzia , Alpsoy Erkan , Callen Jeffrey P. , Fiorentino David , Merkel Peter A. , Falk Ronald J. , Jennette J. Charles
Published: November 2017

Objective

To prepare a dermatologic addendum to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (CHCC2012) to address vasculitides affecting the skin (D‐CHCC). The goal was to standardize the names and definitions for cutaneous vasculitis.

Methods

A nominal group technique with a facilitator was used to reach consensus on the D‐CHCCnomenclature, using multiple face‐to‐face meetings, e‐mail discussions, and teleconferences.

Results

Standardized names, definitions, and descriptions were adopted for cutaneous components of systemic vasculitides (e.g., cutaneous IgA vasculitis as a component of systemic IgA vasculitis), skin‐limited variants of systemic vasculitides (e.g., skin‐limited IgA vasculitis, drug‐induced skin‐limited antineutrophil cytoplasmic antibody–associated vasculitis), and cutaneous single‐organ vasculitides that have no systemic counterparts (e.g., nodular vasculitis). Cutaneous vasculitides that were not included in theCHCC2012 nomenclature were introduced.

Conclusion

Standardized names and definitions are a prerequisite for developing validated classification and diagnostic criteria for cutaneous vasculitis. Accurate identification of specifically defined variants of systemic and skin‐limited vasculitides requires knowledgeable integration of data from clinical, laboratory, and pathologic studies. This proposed nomenclature of vasculitides affecting the skin, the D‐CHCC, provides a standard framework both for clinicians and for investigators.
Bimetallic Platinum‐Tin Nanoparticles on Hydrogenated Molybdenum Oxide for the Selective Hydrogenation of Functionalized Nitroarenes
Authors: Shu Yijin , Chan Hang Cheong , Xie Lifang , Shi Zhangping , Tang Yi , Gao Qingsheng
Published: November 2017

The front cover artwork for Issue 22/2017 is provided by the groups of Qingsheng Gao from Jinan University (China) and Yi Tang from Fudan University (China). The image shows a fast car driving in the right direction with meters indicating that the hydrogenation of functionalized nitroarenes is accelerated and directed by Pt‐Sn/H‐MoOx. See the Full Paper itself at https://doi.org/10.1002/cctc.201700880.
Highly Selective Electrochemical Conversion of CO2 to HCOOH on Dendritic Indium Foams
Authors: Xia Zheng , Freeman Matthew , Zhang Dongxiao , Yang Bin , Lei Lecheng , Li Zhongjian , Hou Yang
Published: November 2017

CO2 electrochemical reduction offers a potential technique to decrease the CO2 emission levels, but it has been hindered by the poor performance of electrocatalysts. In this work, the electrochemical reduction of CO2 has been studied by using a needle‐like porous indium electrode, which was electrodeposited in aqueous electrolytes containing Cl− using the hydrogen bubble dynamic template. This novel electrode displayed improved electrocatalytic activity, enhanced conversion efficiencies, and a lower onset potential −0.76 V vs. RHE), which was 0.3 V less than the indium foil electrode. Moreover, it exhibited enhanced faradaic efficiencies of 86 % for formate at −0.86 V vs. RHE and with a current density of 5.8 mA cm−2. This excellent catalytic activity is the result of a large electrochemical surface area and needle‐like dendrite structures in the presence of Cl− salts. Utilization of the novel nanostructured electrocatalysts and understanding of the role of salts can contribute to further improvements in CO2 reduction.
Graphene‐Like Multilayered CuS Nanosheets Assembled into Flower‐Like Microspheres and Their Electrocatalytic Oxygen Evolution Properties
Authors: Liang Huijun , Shuang Wei , Zhang Yatian , Chao Shunjun , Han Huijuan , Wang Xiaobing , Zhang Hua , Yang Lin
Published: November 2017

Graphene‐like two‐dimensional (2D) nanomaterials have many unique properties in diverse fields, but the synthesis method of graphene‐like CuS 2D nanomaterials is rarely studied. In this work, we reported that the CuS flower‐like superstructure microspheres with a solid core (CuS‐FSMs) were prepared by a facile hydrolysis method without a template or surfactant. The novel CuS‐FSM material showed a well‐define solid core of approximately 300–500 nm and a loose shell of 0.5–1 μm. More importantly, the loose shell of the CuS‐FSMs was constructed of graphene‐like CuS nanosheets (CuS‐GN). The formation mechanism indicated that the CuS‐FSMs were firstly formed on the surface of hexagonal prism‐shaped Cu3(TAA)3Cl3 precursors, and then the well‐defined solid core was produced through the Ostwald ripening of CuS‐GN. The electrocatalytic oxygen evolution reaction was employed as a probe reaction to gain insight into the properties of CuS‐FSMs, which exhibited a high limiting current density of 92.4 mA cm−2 and stability in 1 M KOH electrolyte.
Reversible Polymerization of Adamantane‐type [P4N10]10− Anions to Honeycomb‐type [P2N5]5− Layers under High‐Pressure
Authors: Bertschler Eva‐Maria , Niklaus Robin , Schnick Wolfgang
Published: November 2017

The high‐pressure polymorph Li5P2N5 of Li10P4N10 (=“2 Li5P2N5”) was synthesized by high‐pressure/high‐temperature reaction of LiPN2 and Li7PN4 or β‐Li10P4N10 at 9 GPa, using the Li3N self‐flux method in a Walker‐type multianvil assembly. Li5P2N5 is the first lithium nitridophosphate with a layered structure and is made up of corner sharing PN4 tetrahedra forming a corrugated honeycomb‐type layer of linked sechser‐rings in chair conformation. The arrangement of the P atoms is analogous to that of black phosphorus. The structure was elucidated from single‐crystal X‐ray data. To confirm the structure Rietveld refinement, 6Li, 7Li and 31P solid‐state NMR spectroscopy were conducted. To corroborate Li5P2N5 as the corresponding high‐pressure polymorph of β‐Li10P4N10 DFT calculations and temperature dependent X‐ray powder diffraction were carried out. DFT calculations estimated the transition pressure to 6.5 GPa (without accounting for temperature), which is in line with the synthesis pressure.
Diastereomeric Right‐ and Left‐Handed Helical Structures with Fourteen (R)‐Chiral Centers
Authors: Eto Ryo , Oba Makoto , Ueda Atsushi , Uku Tsubasa , Doi Mitsunobu , Matsuo Yosuke , Tanaka Takashi , Demizu Yosuke , Kurihara Masaaki , Tanaka Masakazu
Published: November 2017

The relationship between chiral centers and the helical‐screw control of their peptides has already been reported, but it has yet to be elucidated in detail. A chiral four‐membered ring α,α‐disubstituted α‐amino acid with a (R,R)‐butane‐2,3‐diol acetal moiety at the γ‐position, but no α‐chiral carbon, was synthesized. X‐ray crystallographic analysis unambiguously revealed that its homo‐chiral heptapeptide formed right‐handed (P) and left‐handed (M) 310‐helical structures at a ratio of 1:1. They appeared to be enantiomeric at the peptide backbone, but diastereomeric with fourteen (R)‐configuration chiral centers. Conformational analyses of homopeptides in solution also indicated that diastereomeric (P) and (M) helices existed at approximately equal amounts, with a slight preference toward right‐handedness, and they quickly interchanged at room temperature. The circumstances of chiral centers are important for the control of their helical‐screw direction.
Considerations About the Use of Biomarkers in Cancer Clinical Trials
Authors: Chabner Bruce A.
Published: November 2017

The rapid evolution of our understanding of cancer biology has affected every phase of patient management, from early detection to drug development and clinical management. Central to this issue is the challenge of using biomarkers to identify the driving mutations present and identifiable by current assays in many tumors. These biomarkers are integral to the process of selecting patients for the testing of new drugs, many of which are specifically designed to inhibit oncogenic pathways.
Pharmacokinetics, Pharmacodynamics, and Proposed Dosing of the Oral JAK1 and JAK2 Inhibitor Baricitinib in Pediatric and Young Adult CANDLE and SAVI Patients
Authors: Kim Hanna , Brooks Kristina M. , Tang Cheng Cai , Wakim Paul , Blake Mary , Brooks Stephen R. , Montealegre Sanchez Gina A. , de Jesus Adriana A. , Huang Yan , Tsai Wanxia Li , Gadina Massimo , Prakash Apurva , Janes Jonathan Marcus , Zhang Xin , Macias William L. , Kumar Parag , Goldbach‐Mansky Raphaela
Published: November 2017

Population pharmacokinetic (popPK) modeling was used to characterize the PK profile of the oral Janus kinase (JAK)1/JAK2 inhibitor, baricitinib, in 18 patients with Mendelian interferonopathies who are enrolled in a compassionate use program. Patients received doses between 0.1 to 17 mg per day. Covariates of weight and renal function significantly influenced volume‐of‐distribution and clearance, respectively. The half‐life of baricitinib in patients less than 40 kg was substantially shorter than in adult populations, requiring the need for dosing up to 4 times daily. On therapeutic doses, the mean area‐under‐the‐concentration‐vs.‐time curve was 2,388 nM*hr, which is 1.83‐fold higher than mean baricitinib exposures in adult patients with rheumatoid arthritis receiving doses of 4 mg once‐daily. Dose‐dependent decreases in interferon (IFN) biomarkers confirmed an in vivo effect of baricitinib on type‐1 IFN signaling. PopPK and pharmacodynamic data support a proposal for a weight‐ and estimated glomerular filtration rate‐based dosing regimen in guiding baricitinib dosing in patients with rare interferonopathies.
Metal Phosphides as Co‐Catalysts for Photocatalytic and Photoelectrocatalytic Water Splitting
Authors: Cao Shuang , Wang Chuan‐Jun , Fu Wen‐Fu , Chen Yong
Published: November 2017

Invited for this month′s cover is the group of Yong Chen and Wen‐Fu Fu at the Technical Institute of Physics and Chemistry of Chinese Academy of Sciences. The image shows a series of transition metal phosphides act as co‐catalysts for photocatalytic and photoelectrochemical water splitting. The Minireview itself is available at 10.1002/cssc.201701450.
Analysis of the row grounding technique in a memristor‐based crossbar array
Authors: Dozortsev Alexander , Goldshtein Israel , Kvatinsky Shahar
Published: November 2017

Using memristive devices within a crossbar array could pave the way for memories with higher density and speed than state‐of‐the‐art Flash memory, while maintaining relatively low energy. However, memristive crossbar arrays have great difficulty distinguishing logical states because of sneak path currents. The row grounding technique eliminates the sneak path effect, allowing reliable sampling of the memristor state. In this paper, we analyze the row grounding technique and propose several methods and constraints for the design of memristive crossbar arrays. When the row grounding technique is used for these arrays, our analysis shows that increasing the number of rows can help reduce read latency and energy, in contrast to the case of capacitive memory arrays. Simulation results confirm the theoretical analysis proposed in this paper. Copyright © 2017 John Wiley & Sons, Ltd.
Developmental retinal ganglion cell death and retinotopicity of the murine retinocollicular projection
Authors: Beros Jamie , Rodger Jennifer , Harvey Alan R.
Published: November 2017

During mammalian visual system development, retinal ganglion cells (RGCs) undergo extensive apoptotic death. In mouse retina, approximately 50% of RGCs present at birth (postnatal day 0; P0) die by P5, at a time when axons innervate central targets such as the superior colliculus (SC). We examined whether RGCs that make short‐range axonal targeting errors within the contralateral SC are more likely to be eliminated during the peak period of RGC death (P1‐P5), compared with RGCs initially making more accurate retinotopic connections. A small volume (2.3 nL) of the retrograde nucleophilic dye Hoechst 33342 was injected into the superficial left SC of anesthetized neonatal C57Bl/6J mice at P1 (n = 5) or P4 (n = 8), and the contralateral retina wholemounted 12 hr later. Retrogradely labelled healthy and dying (pyknotic) RGCs were identified by morphological criteria and counted. The percentage of pyknotic RGCs was analyzed in relation to distance from the area of highest density RGC labelling, presumed to represent the most topographically accurate population. As expected, pyknotic RGC density at P1 was significantly greater than P4 (p < 0.05). At P4, the density of healthy RGCs 500–750 µm away from the central region was significantly less, although this was not reflected in altered pyknotic rates. However, at P1 there was a trend (p = 0.08) for an increased proportion of pyknotic RGCs, specifically in temporal parts of the retina outside the densely labelled center. Overall, the lack of consistent association between short‐range targeting errors and cell death suggests that most postnatal RGC loss is not directly related to topographic accuracy. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 51–60, 2018
Two Complementary Cyclization Reactions for the Chemoselective Synthesis of Spirooxindoles
Authors: Zhou Pan , Hu Biao , Yang Jiao , Li Lingdan , Rao Kairui , Zhu Daofei , Yu Fuchao
Published: November 2017

Two complementary cascade cyclization reactions, namely, the KHSO4‐promoted [1+2+3] cyclization and the TMSCl‐promoted four‐component cascade cyclization, are described for the concise synthesis of highly functionalized spirooxindoles in excellent yields. The improved TMSCl‐promoted cyclization reaction of isatins, N,N‐dimethylenaminones, and amines was carried out under milder conditions than those of the [1+2+3] cyclization to afford the desired products. The observed chemoselectivity of this TMSCl‐promoted cyclization is explained by the design and preparation of an intermediate bis(enaminone). A gram‐scale synthesis and synthetic applications of this transformation were also evaluated.
Role of central versus peripheral opioid system in antinociceptive and anti‐inflammatory effect of botulinum toxin type A in trigeminal region
Authors: Drinovac Vlah V. , Filipović B. , Bach‐Rojecky L. , Lacković Z.
Published: November 2017

Background

Although botulinum toxin type A (BT‐A) is approved for chronic migraine treatment, its site and mechanism of action are still elusive. Recently our group discovered that suppression of CGRP release from dural nerve endings might account for antimigraine action of pericranially injected BT‐A. We demonstrated that central antinociceptive effect of BT‐A in sciatic region involves endogenous opioid system as well. Here we investigated possible interaction of BT‐A with endogenous opioid system within the trigeminal region.

Methods

In orofacial formalin test we investigated the influence of centrally acting opioid antagonist naltrexone (2 mg/kg, s.c.) versus peripherally acting methylnaltrexone (2 mg/kg, s.c.) on BT‐A's (5 U/kg, s.c. into whisker pad) or morphine's (6 mg/kg, s.c.) antinociceptive effect and the effect on dural neurogenic inflammation (DNI). DNI was assessed by Evans blue‐plasma protein extravasation.

Results

Naltrexone abolished the effect of BT‐A on pain and dural plasma protein extravasation, whereas peripherally acting methylnaltrexone did not change either BT‐A's effect on pain or its effect on dural extravasation. Naltrexone abolished the antinociceptive and anti‐inflammatory effects of morphine, as well. However, methylnaltrexone decreased the antinociceptive effect of morphine only partially in the second phase of the test and had no significant effect on morphine‐mediated reduction in DNI.

Conclusions

Morphine acts on pain in trigeminal region both peripherally and centrally, whereas the effect on dural plasma protein extravasation seems to be only centrally mediated. However, the interaction of BT‐A with endogenous opioid system, with consequent inhibition of nociceptive transmission as well as the DNI, occurs primarily centrally.

Significance

Botulinum toxin type A (BT‐A)'s axonal transport and potential transcytosis suggest that its antinociceptive effect might involve diverse neurotransmitters at different sites of trigeminal system. Here we discovered that the reduction in pain and accompanying DNI involves the interaction of BT‐A with central endogenous opioid system (probably at the level of trigeminal nucleus caudalis).
Availability and approval of cannabis‐based medicines for chronic pain management and palliative/supportive care in Europe: A survey of the status in the chapters of the European Pain Federation
Authors: Krcevski‐Skvarc N. , Wells C. , Häuser W.
Published: November 2017

Background

There is considerable public and political interest in the use of cannabis products for medical purposes.

Methods

The task force of the European Pain Federation (EFIC) conducted a survey with its national chapters representatives on the status of approval of all types of cannabis‐based medicines, the covering of costs and the availability of a position paper of a national medical association on the use of medical cannabis for chronic pain and for symptom control in palliative/supportive care.

Results

Thirty‐one out of 37 contacted councillors responded. Plant‐derived tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray is approved for spasticity in multiple sclerosis refractory to conventional treatment in 21 EFIC chapters. Plant‐derived THC (dronabinol) is approved for some palliative care conditions in four EFIC chapters. Synthetic THC analogue (nabilone) is approved for chemotherapy‐associated nausea and vomiting refractory to conventional treatment in four EFIC chapters’. Eight EFIC chapters’ countries have an exceptional and six chapters an expanded access programme for medical cannabis. German and Israeli pain societies recommend the use of cannabis‐based medicines as third‐line drug therapies for chronic pain within a multicomponent approach. Conversely, the German medical association and a team of finish experts and officials do not recommend the prescription of medical cannabis due to the lack of high‐quality evidence of efficacy and the potential harms.

Conclusions

There are marked differences between the countries represented in EFIC in the approval and availability of cannabis‐based products for medical use. EFIC countries are encouraged to collaborate with the European Medicines Agency to publish a common document on cannabis‐based medicines.

Significance

There are striking differences between European countries in the availability of plant‐derived and synthetic cannabinoids and of medical cannabis for pain management and for symptom control in palliative care and in the covering of costs by health insurance companies or state social security systems.
Functional characterization of E2F3b in human HepG2 liver cancer cell line
Authors: Lu Yujia , Li Wei
Published: November 2017

E2F3 is a transcription factor that has been shown to be overexpressed in hepatocellular carcinoma (HCC). It is well‐known that the E2F3 gene encodes two proteins E2F3a and E2F3b. Therefore, the functions of the two distinct isoforms need to be clarified separately. To characterize the function of E2F3b in HCC, the effects of ectopic expression of E2F3b on cell proliferation, cell cycle, apoptosis and gene expression were investigated. E2F3b promoted G1/S phase transition and markedly increased cell proliferation, but had minor effect on apoptosis. Microarray analyses identified 366 differentially expressed genes (171 upregulated and 195 downregulated) in E2F3b‐ overexpressing cells. Differential expression of 16 genes relevant to cell cycle and cell proliferation were further verified by real‐time PCR. Six genes, including CDC2, CCNE1, ARF, MAP4K2, MUSK, and PAX2 were confirmed to be upregulated by more than twofold; one gene, CCNA2 was validated to be downregulated by more than twofold. We also confirmed that E2F3b increased the protein levels of both cyclin E and Arf but did not affect cyclin D1 protein. These results suggest that E2F3b functions as an important promoter for cell proliferation and plays important roles in transcriptional regulation in HepG2 liver cancer cells.
Targeted Therapies: Immunologic Effects and Potential Applications Outside of Cancer
Authors: Kersh Anna E. , Ng Spencer , Chang Yun Min , Sasaki Maiko , Thomas Susan N. , Kissick Haydn T. , Lesinski Gregory B. , Kudchadkar Ragini R. , Waller Edmund K. , Pollack Brian P.
Published: November 2017

Two pharmacologic approaches that are currently at the forefront of treating advanced cancer are those that center on disrupting critical growth/survival signaling pathways within tumor cells (commonly referred to as “targeted therapies”) and those that center on enhancing the capacity of a patient's immune system to mount an antitumor response (immunotherapy). Maximizing responses to both of these approaches requires an understanding of the oncogenic events present in a given patient's tumor and the nature of the tumor‐immune microenvironment. Although these 2 modalities were developed and initially used independently, combination regimens are now being tested in clinical trials, underscoring the need to understand how targeted therapies influence immunologic events. Translational studies and preclinical models have demonstrated that targeted therapies can influence immune cell trafficking, the production of and response to chemokines and cytokines, antigen presentation, and other processes relevant to antitumor immunity and immune homeostasis. Moreover, because these and other effects of targeted therapies occur in nonmalignant cells, targeted therapies are being evaluated for use in applications outside of oncology.
Quorum quenching activity of indigenous quorum quenching bacteria and its potential application in mitigation of membrane biofouling
Authors: Gu Yanling , Huang Jinhui , Zeng Guangming , Shi Yahui , Hu Yi , Tang Bi , Zhou Jianxin , Xu Weihua , Shi Lixiu
Published: November 2017

BACKGROUND

Quorum sensing (QS) could regulate gene expression so as to mediate some bacterial behaviors such as the production of extracellular polymeric substances (EPS) and biofilm formation. In this study, a quorum quenching (QQ) bacterium was isolated from an indigenous lab‐scale membrane bioreactor (MBR) and encapsulated in a dumpling‐shaped microbial bag for biofouling control.

RESULTS

This QQ bacteria has a higher genetic homology with Acinetobacter bereziniae strain. The effect of time and temperature on the QQ activity of the microbial bag was tested by degrading N‐acyl homoserine lactone (AHL). The results showed the degradation of C8‐HSL (N‐Octanoyl‐DL‐homoserine lactone) and C6‐HSL (N‐Hexanoyl‐L‐homoserine lactone) could reach equilibrium within 2 h. In addition, a suitable temperature for AHL degradation was 20 °C, at which the rate of degradation of C6‐HSL and C8‐HSL by the microbial bag was 88% and 69%, respectively. The antifouling efficiency of the microbial bag was investigated by a constant pressure filtration system. With the microbial bag added, the decrease of permeability was obviously improved. After 14 days, the permeability with QQ decreased to 18% while the control experiment exhibited almost no permeability.

CONCLUSION

The excellent AHL degradation rate and the filtration test showed that this QQ bacteria has an excellent antifouling potential in membrane filtration systems. © 2017 Society of Chemical Industry
Design of a heterogeneous enzymatic catalyst on chitosan: investigation of the role of conjugation chemistry in the catalytic activity of a Laccase from Trametes versicolor
Authors: Apriceno Azzurra , Girelli Anna Maria , Scuto Francesca Romana
Published: November 2017

BACKGROUND

Three protocols are presented in order to immobilise a laccase (EC 1.10.3.2) from Trametes versicolor on chitosan. In particular, chitosan is functionalized with glutaraldehyde and epichlorohydrin to explore to what extent the conjugation of the enzyme is affected by a carbonyl‐ or epoxy‐modified surface, respectively. In addition, an oxidation procedure is tested to modify, for the first time, the carbohydrate moiety of the enzyme and exploit it for linking with the amine group of chitosan.

RESULTS

The system in which laccase is directly conjugated to chitosan seems to be the best‐performing since it is able to maintain 100% of initial activity over a 30 day period and at least 50% of the starting activity after 3 catalytic cycles.

CONCLUSION

The methods show the capability to develop three biocatalysts suitable for the immobilization of laccase. All of them provide covalent bonds that don't inactivate the enzyme through any conformational change and any distortion of the active pocket. Specifically, the oxidation procedure proves to be feasible for the preparation of stabilized glycoproteins without the introduction of foreign molecules, suggesting that the carbohydrate moiety of laccase does not appear to be closely related to the catalytic site of the protein. © 2017 Society of Chemical Industry
Measuring human placental blood flow with multidelay 3D GRASE pseudocontinuous arterial spin labeling at 3T
Authors: Shao Xingfeng , Liu Dapeng , Martin Thomas , Chanlaw Teresa , Devaskar Sherin U. , Janzen Carla , Murphy Aisling M. , Margolis Daniel , Sung Kyunghyun , Wang Danny J.J.
Published: November 2017

Background

Placenta influences the health of both a woman and her fetus during pregnancy. Maternal blood supply to placenta can be measured noninvasively using arterial spin labeling (ASL).

Purpose

To present a multidelay pseudocontinuous arterial spin labeling (pCASL) combined with a fast 3D inner‐volume gradient‐ and spin‐echo (GRASE) imaging technique to simultaneously measure placental blood flow (PBF) and arterial transit time (ATT), and to study PBF and ATT evolution with gestational age during the second trimester. The PBF values were compared with uterine arterial Doppler ultrasound to assess its potential clinical utility.

Study Type

This was a prospective study.

Subjects

Thirty‐four pregnant women.

Field Strength/Sequence

Multidelay 3D inner‐volume GRASE pCASL sequence on 3T MR scanners.

Assessment

Subjects underwent two longitudinal MRI scans within the second trimester, conducted between 14–16 and 19–22 weeks of gestational age, respectively. Placental perfusion was measured using the free‐breathing pCASL sequence at three postlabeling delays (PLDs), followed by offline motion correction and model fitting for estimation of PBF and ATT.

Statistical Tests

A paired t‐test was conducted to evaluate the significance of PBF/ATT variations with placental development. A two‐sample t‐test was conducted to evaluate the significance of PBF difference in subjects with and without early diastolic notch.

Results

The mean PBF and ATT for the second trimester were 111.4 ± 26.7 ml/100g/min and 1387.5 ± 88.0 msec, respectively. The average PBF increased by 10.4% (P < 0.05), while no significant change in ATT (P = 0.72) was found along gestational ages during the second trimester. PBF decreased 20.3% (P < 0.01) in subjects with early diastolic notches in ultrasound flow waveform patterns.

Data Conclusion

Multidelay pCASL with inner‐volume 3D GRASE is promising for noninvasive assessment of PBF during pregnancy. Its clinical use for the detection of aberrations in placental function and prediction of fetal developmental disorders awaits evaluation.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;47:1667–1676.
Investigation of sarin(Se) reactivity against human plasma proteins using liquid chromatography–tandem mass spectrometry
Authors: Saeidian Hamid , Hosseini Seyed Esmaeil , Amoozadeh Ali , Naseri Mohammad Taghi , Babri Mehran
Published: November 2017

Electron ionization mass spectrum of sarin(Se) was interpreted in compare of sarin MS spectrum. Inhibition of butyrylcholinesterase of human plasma by sarin and sarin(Se) was determined spectrophotometrically using modified Ellman method. It appeared that after incubation with sarin and sarin(Se), cholinesterase inhibition were 93% and 83%, respectively. Sarin, sarin(Se), and sarin(Se)‐d7 were spiked into a vial containing human plasma, and albumin adduct metabolites were identified using liquid chromatography–tandem mass spectrometry. The experiments show that these agents are attached to tyrosine on albumin in human blood. Corresponding deuterated adducts were used to confirm the proposed mechanisms for the formation of the fragments in mass spectrometry experiments.
Mechanisms involved in hemoglobin‐mediated oxidation of lipids in washed fish muscle and inhibitory effects of phospholipase A2
Authors: Tatiyaborworntham Nantawat , Richards Mark P
Published: November 2017

BACKGROUND

Hemoglobin (Hb) is a lipid oxidation promoter in fish muscle. Phospholipase A2 (PLA2; EC 3.1.1.4) is linked to an increased resistance to lipid oxidation of frozen–thawed cod fillets via an unknown mechanism. The present study aimed to investigate the mechanism of Hb‐mediated lipid oxidation with a focus on ferryl Hb and methemoglobin (metHb), the pro‐oxidative Hb species, and to examine how porcine pancreatic PLA2 inhibits Hb‐mediated lipid oxidation in washed cod muscle (WCM). Lipid hydroperoxides (LOOHs) and thiobarbituric acid reactive substances (TBARS) were measured as primary and secondary lipid oxidation products, respectively. The formation of metHb and ferryl Hb was also monitored.

RESULTS

Ferryl Hb and metHb formed during the Hb‐mediated lipid oxidation. PLA2 inhibited the formation of LOOHs and TBARS and suppressed the formation of metHb and ferryl Hb. WCM was pre‐oxidized by hemin to increase the amount of LOOHs. PLA2 promoted the depletion of LOOHs in the pre‐oxidized WCM with limited TBARS formation at the expense of the heme moiety of Hb.

CONCLUSION

The results of the present study suggest that ferryl Hb may play a role in Hb‐mediated lipid oxidation and that PLA2 from pig pancreas may work together with Hb as a novel antioxidant with an ability to remove pre‐formed LOOHs from a lipid substrate. © 2017 Society of Chemical Industry
Raising Nanofiber Output: The Progress, Mechanisms, Challenges, and Reasons for the Pursuit
Authors: Akampumuza Obed , Gao Hanchao , Zhang Hongnan , Wu Dequn , Qin Xiao‐Hong
Published: November 2017

The paper discusses the extent to the scale of the electrospun fiber membrane. Literatures show that two distinct methods of raising electrospun nanofiber production can be employed via spinning from a setup of multiple nozzles arranged side by side or from an expanse of polymer solution (needleless electrospinning). Both of these methods are thoroughly explored by considering the variations available within either of their respective productivities. Their mechanisms are duly dealt with by looking at principles and parameters behind the process performances and an analysis of the strategies devised to deal with the shortcomings and ensure process feasibility is given. It has to be noted that most of the available work on electrospinning and their applications is achieved via single needle electrospinning. In this review, a projection is taken to be accomplished whether the nanofiber production can be consistently raised to commercial levels at the exceptional application routes so far produced by the conventional electrospinning means.
Identification of Bioactive Scaffolds Based on QSAR Models
Authors: Nakagawa Tomoki , Miyao Tomoyuki , Funatsu Kimito
Published: November 2017

In medicinal chemistry, the molecular scaffolds commonly found in compounds with preferable biological activities are called bioactive scaffolds. They are important because if present in a structure, it is more likely that the compound will be bioactive. Traditionally, medicinal chemists use their knowledge to identify bioactive scaffolds from a given data set after systematic extraction of all candidate scaffolds. However, manually sorting all the scaffolds is not practical as the number of compounds in a data set is often very large. Herein, we propose a method to systematically identify bioactive scaffolds based on a structure generator and a QSAR model. Two proof‐of‐concept studies showed that known bioactive scaffolds as well as scaffolds containing important substructures were extracted. The proposed method does not depend on scaffold frequencies in a data set, which is different from currently used methods for bioactive scaffold identification.
Quantification of MRI visibility and artifacts at 3T of liquid fiducial marker in a pancreas tissue‐mimicking phantom
Authors: Schneider Sergej , Jølck Rasmus Irming , Troost Esther Gera Cornelia , Hoffmann Aswin Louis
Published: November 2017

Purpose

X‐ray‐based position verification of the target volume in image‐guided radiation therapy (IGRT) of patients with pancreatic ductal adenocarcinoma (PDAC) is currently performed on solid fiducial markers that are implanted under endoscopic ultrasonography. A new biodegradable liquid fiducial marker has recently been introduced. To assess its potential use for magnetic resonance imaging (MRI)‐guided photon or proton radiotherapy of PDAC, the MRI visibility and artifacts of this marker were quantified and compared against solid gold markers.

Material and methods

Different spherical volumes (10 μL, 25 μL, 50 μL, and 100 μL) of a biodegradable liquid fiducial marker as well as seven differently sized and oriented solid gold (0.35 mm diameter; 5 mm and 10 mm length) and iron–gold alloy fiducial markers (0.28 mm diameter; 1 cm and 2 cm length) were implanted in a spherical gel phantom, mimicking the proton spin relaxation properties of healthy pancreatic tissue at 3 Tesla. MR relaxometry was performed to quantify the size and magnitude of the decrease in the effective transversal relaxation time and relative proton density ρ(H) as a measure of potential visibility and to quantify the size and magnitude of the increase in magnetic field inhomogeneity ΔB0 as a measure of potential signal artifacts. The phantom was scanned in a 3.0 T PET/MR scanner with an eight‐channel head coil.

Results

The solid fiducial markers showed a direct linear relationship between the potentially visible size and artifact size. The liquid fiducial marker showed a tendency toward a potentially visible size at smaller artifacts. Liquid markers from 25 to 100 μL generated visible volumes comparable to the size of the solid markers. The magnitude of visibility was the highest for the liquid fiducial marker with volumes of 25–100 μL showing no correlation with the magnitude of artifact. The solid markers showed a strong nonlinear correlation between magnitude of visibility and artifact, whereas the solid marker consisting of a gold–iron alloy induced the strongest artifacts.

Conclusion

The liquid fiducial marker causes signal voids on MRI due to its absence of water hydrogen atoms without strongly affecting the magnetic field in the surrounding tissue. The alteration of the static magnetic field was found to be the main effect leading to the visibility of the solid fiducial markers. Hence, especially when a low level of image distortion is required, MRI characteristics of the liquid marker surpass those of solid gold markers currently being used for IGRT of PDAC.
Do operating reserves stabilize spending by nonprofit organizations?
Authors: Calabrese Thad D.
Published: November 2017

The public budgeting literature has a long and rich tradition that examines the role of budget stabilization funds as fiscal stabilizers for state and local governments during periods of declining revenues and deteriorating economic conditions. Similarly, nonprofit organizations may accumulate operating reserves that allow them to smooth out annual imbalances between revenues and expenses, especially when facing a fiscal shock. Agency theory, on the other hand, indicates that managers might use these reserves to enrich themselves at the expense of the organization. This article is a step toward addressing a gap in our knowledge by analyzing the implications of reserves on nonprofit spending in general and also on particular functions (program versus overhead spending). Using a long panel of data from 1995 to 2011 and controlling for sample selection bias, the empirical results suggest that operating reserves held by nonprofit organizations do reduce expense gaps during downturns, but the effect is small. The results also suggest that nonprofit managers value current spending more than reserving funds for the future. Further, operating reserves are not associated with agency problems as predicted by theory. The empirical results suggest that the current rule of thumb—that nonprofits ought to hold up to 6 months of operating reserves—is inadequate if these pools of savings are intended to maintain all spending at trend during poor fiscal times. If, however, reserves are intended to only offset trend deviations partially while alternative strategies are sought, then the current rule of thumb may be sufficient.
Adverse Childhood Experiences (ACEs) and Adiposity in Adolescents: A Cross‐Cohort Comparison
Authors: Soares Ana Luiza G. , Matijasevich Alicia , Menezes Ana M.B. , Assunção Maria Cecília , Wehrmeister Fernando C. , Howe Laura D. , Gonçalves Helen
Published: November 2017

Objective

This study aimed to assess the association between adverse childhood experiences (ACEs) and adiposity in adolescents from two cohorts in different socioeconomic contexts.

Methods

Data from the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom) and the 1993 Pelotas Cohort (Brazil) were used. Six ACEs were assessed in both cohorts up to age 15. At 15 years, body mass index (BMI) and waist circumference (WC) were measured, and at 18 years, BMI, fat mass index, and android fat percentage were assessed.

Results

Few associations were observed between ACEs and adiposity at 15 years, and they were not consistent across cohorts. For adiposity at age 15 in ALSPAC, physical abuse had a positive association with WC, and domestic violence had a positive association with both WC and BMI. A dose‐response relationship between the ACE score and both WC and BMI at 15 years was observed in ALSPAC. In the 1993 Pelotas Cohort, the associations found in crude analysis were no longer evident after adjustment.

Conclusions

This study found some evidence of an association between an ACE score and adiposity in adolescence in a United Kingdom cohort but no evidence of association in a Brazilian cohort. Residual confounding or context‐specific relationships could explain the different pattern of associations.