bluuebunny/crossref_metadata_2025 huggingface dataset:
Warsaw breakage syndrome: Further clinical and genetic delineation
Authors: Alkhunaizi Ebba , Shaheen Ranad , Bharti Sanjay Kumar , Joseph‐George Ann M. , Chong Karen , Abdel‐Salam Ghada M. H. , Alowain Mohammed , Blaser Susan I. , Papsin Blake C. , Butt Mohammed , Hashem Mais , Martin Nicole , Godoy Ruth , Brosh Robert M. , Alkuraya Fowzan S. , Chitayat David
Published: September 2018

Warsaw breakage syndrome (WBS) is a recently recognized DDX11‐related rare cohesinopathy, characterized by severe prenatal and postnatal growth restriction, microcephaly, developmental delay, cochlear anomalies, and sensorineural hearing loss. Only seven cases have been reported in the English literature, and thus the information on the phenotype and genotype of this interesting condition is limited. We provide clinical and molecular information on five additional unrelated patients carrying novel bi‐allelic variants in the DDX11 gene, identified via whole exome sequencing. One of the variants was found to be a novel Saudi founder variant. All identified variants were classified as pathogenic or likely pathogenic except for one that was initially classified as a variant of unknown significance (VOUS) (p.Arg378Pro). Functional characterization of this VOUS using heterologous expression of wild type and mutant DDX11 revealed a marked effect on protein stability, thus confirming pathogenicity of this variant. The phenotypic data of the seven WBS reported patients were compared to our patients for further phenotypic delineation. Although all the reported patients had cochlear hypoplasia, one patient also had posterior labyrinthine anomaly. We conclude that while the cardinal clinical features in WBS (microcephaly, growth retardation, and cochlear anomalies) are almost universally present, the breakage phenotype is highly variable and can be absent in some cases. This report further expands the knowledge of the phenotypic and molecular features of WBS.
Pharmacophore Nanoarrays on DNA Origami Substrates as a Single‐Molecule Assay for Fragment‐Based Drug Discovery
Authors: Kielar Charlotte , Reddavide Francesco V. , Tubbenhauer Stefan , Cui Meiying , Xu Xiaodan , Grundmeier Guido , Zhang Yixin , Keller Adrian
Published: September 2018

The rational combination of techniques from the fields of nanotechnology, single molecule detection, and lead discovery could provide elegant solutions to enhance the throughput of drug screening. We have synthesized nanoarrays of small pharmacophores on DNA origami substrates that are displayed either as individual ligands or as fragment pairs and thereby reduced the feature size by several orders of magnitude, as compared with standard microarray techniques. Atomic force microscopy‐based single‐molecule detection allowed us to distinguish potent protein–ligand interactions from weak binders. Several independent binding events, that is, strong, weak, symmetric bidentate, and asymmetric bidentate binding are directly visualized and evaluated. We apply this method to the discovery of bidentate trypsin binders based on benzamidine paired with aromatic fragments. Pairing of benzamidine with the dye TAMRA results in tenfold enhancement of the trypsin binding yield.
Faceted‐Charge Patchy LnF3 Nanocrystals with a Selective Solvent Interaction
Authors: Martínez‐Esaín Jordi , Puig Teresa , Obradors Xavier , Ros Josep , Yáñez Ramón , Faraudo Jordi , Ricart Susagna
Published: September 2018

A fast and single‐step preparation of patchy LnF3 faceted‐charge nanocrystals are described. These hexagonal faceted nanocrystals allow the spontaneous selective adsorption of cations or anions in the different faces, producing stable and well‐defined patches of different charge. The mechanism for the formation of the patches and the properties of the obtained nanocrystals were characterized by a combination of experimental techniques and all‐atomic molecular dynamics simulations. The spontaneous dual‐charged surface as well as the luminescence effects that can be achieved by doping host–LaF3 systems make these new nanocrystals interesting both from a fundamental point of view and for a wide range of applications.
Chemotactic Micro‐ and Nanodevices
Authors: Plutnar Jan , Pumera Martin
Published: September 2018

Preparation of autonomous chemotactic micro‐ and nanomachines represents one of the most difficult challenges of modern materials science. To construct a device mimicking the behavior of many microorganisms, which evolved their chemotactic abilities during the millennia of evolution, places extreme demands on the imagination and abilities of researchers. However, with the chemotactic devices in hand, many novel and interesting applications of micromachines could be implemented. The introduction of an autonomous navigation, independent of the external control with electric, magnetic, or electromagnetic field is crucial for applications in environmental remediation and might be advantageous in medical applications. This Minireview summarizes the development in the field of chemotactic micro‐ and nanomachines, describes the trends in their construction, and compares the different approaches to their construction considering the areas of possible application of the devices.
Breeding sites of a narrowly distributed amphibian, a key element in its conservation in the face of global change
Authors: Cobos Marlon E. , Alonso Bosch Roberto
Published: September 2018

Global change processes (including climate change, sea‐level rise, and land‐use change, among others) represent significant threats to biodiversity. These changes are usually studied across broad areas, and understanding their effects on narrowly distributed endangered species is challenging. Peltophryne florentinoi is a critically endangered Cuban toad, restricted to two coastal localities and potentially threatened by these phenomena. Despite its endangered status, few analyses have focused on threats to its survival in the face of global change.

Current and future threats from global change to this species were evaluated using ecological niche modelling and multiscale geographic information system (GIS) approaches. Climate change effects were assessed by comparing the species niche with six future (2050) climate scenarios across its distribution area. Risks from sea‐level rise were evaluated by simulating potential coastal inundation under three scenarios of sea‐level rise. Recent land‐use changes were quantified using information on the loss of forest cover between 2000 and 2015.

Within the species distribution area, warmer and drier conditions can be expected in the future. Sea‐level rise will not have direct impacts on the species range; however, occasional inundations and saltwater intrusion may present additional stressors. Although only ~2% of the forest cover has been lost in the species range and its surroundings during 2000–2015, deforestation trends were variable during this period, and future losses in forest cover can be expected.

Considering these threats, and that the colonization of new areas seems unlikely, indirect and additive adverse effects on the species can be anticipated. These impacts will most probably be observed during the larval stage of this toad; hence, breeding sites constitute a key element in the conservation of this species. Long‐term studies and experimental manipulations may be the next steps towards a better understanding of the responses of P. florentinoi to expected changes. Initial conservation actions are proposed based on these results and the ecology of this species.
Recent Developments in Solid‐Phase Strategies towards Synthetic, Sequence‐Defined Macromolecules
Authors: Hill Stephen A. , Gerke Christoph , Hartmann Laura
Published: September 2018

Sequence‐control in synthetic polymers is an important contemporary research area because it provides the opportunity to create completely novel materials for structure–function studies. This is especially relevant for biomimetic polymers, bioactive and information security materials. The level of control is strongly dependent and inherent upon the polymerization technique utilized. Today, the most established method yielding monodispersity and monomer sequence‐definition is solid‐phase synthesis. This Focus Review highlights recent advances in solid‐phase strategies to access synthetic, sequence‐defined macromolecules. Alternatives strategies towards sequence‐defined macromolecules are also briefly summarized.
Radial Pole Paths SVSC for Linear Time Invariant Multi Input Systems with Constrained Inputs
Authors: Kaheni Mojtaba , Hadad Zarif Mohammed , Akbarzadeh Kalat Ali , Fadali Mohammed Sami
Published: September 2018

In this article a novel soft variable structure control method is proposed to reduce the settling time of liner time‐invariant multi‐input systems with constrained inputs. The method is a generalized pole placement technique which extends the desired pole locations to radial pole paths to reduce settling time while satisfying input constraints. The control signal obtained by this method is soft and is therefore suited to industrial applications. The paper provides a test for the stability of the control system based on the multivariable circle criterion and the Kalman‐Yakubovich‐Popov lemma. Simulation results where the method is applied to an aviation example, and comparison with pole placement, demonstrate how the method significantly increases the speed of response in spite of the input constraints.
Near‐infrared emitting Ca5(PO4)3Cl:Eu2+,Nd3+ phosphor for modification of the solar spectrum
Authors: Tawalare P.K. , Bhatkar V.B. , Omanwar S.K. , Moharil S.V.
Published: September 2018

Intense near‐infrared (NIR) emitting phosphors Ca5(PO4)3Cl:Eu2+,Nd3+ were synthesized using a conventional solid‐state reaction method and characterized using X‐ray diffraction, reflectance, photoluminescence (PL) emission and PL excitation (PLE) spectroscopy, and PL lifetime measurements. The emission could be excited by broad band radiation in the nUV region as a consequence of Eu2+→Nd3+ energy transfer. The efficiency of Eu2+→Nd3+ energy transfer was as high as 80.8%. Two components observed in the decay curves could be identified with Eu2+ substituting different Ca2+ sites. Eu2+ lifetimes were shortened after Nd3+ doping. Near infra‐red emission intensity was limited by Nd3+→Nd3+ energy transfer and the consequent concentration quenching. The critical distance for Nd3+→Nd3+ energy transfer was estimated to be 11.41 Å. Absorption of nUV radiations followed by conversion to NIR indicated the potential application in solar photovoltaics.
Incidence of cardiovascular disease up to 13 year after cancer diagnosis: A matched cohort study among 32 757 cancer survivors
Authors: Schoormans Dounya , Vissers Pauline A. J. , van Herk‐Sukel Myrthe P. P. , Denollet Johan , Pedersen Susanne S. , Dalton Susanne O. , Rottmann Nina , van de Poll‐Franse Lonneke
Published: September 2018

We examined the incidence of cardiovascular disease (CVD) among 32 757 cancer survivors and age‐, gender‐, and geographically matched cancer‐free controls during a follow‐up period of 1‐13 years, and explored whetherCVD incidence differed by received cancer treatment, traditional cardiovascular risk factors, age, or gender. Adult 1‐year cancer survivors without a history ofCVD diagnosed with breast (n = 6762), prostate (n = 4504), non‐Hodgkin (n = 1553), Hodgkin (n = 173), lung and trachea (n = 2661), basal cell carcinoma (BCC; n = 12 476), and colorectal (n = 4628) cancer during 1999‐2011 were selected from the Netherlands Cancer Registry and matched to cancer‐free controls without a history ofCVD. Drug dispenses and hospitalizations from thePHARMO Database Network were used as proxy forCVD. Data were analyzed using Cox regression analyses. Prostate (HR: 1.17; 95%CI: 1.01‐1.35) and lung and trachea (HR: 1.48; 95%CI: 1.10‐1.97) cancer survivors had an increased risk for developingCVD compared to cancer‐free controls. This increased risk among lung and trachea cancer survivors remained statistically significant after including traditional cardiovascular risk factors and cancer treatment information (HR: 1.41; 95%CI: 1.06‐1.89). Among prostate cancer survivors, the increased risk of incidentCVD was limited to those who received hormones and those without traditional cardiovascular risk factors. Breast, non‐Hodgkin,BCC, and colorectal cancer survivors showed no increasedCVD risk compared to cancer‐free controls. There was an increased risk of incidentCVD among prostate, and lung and trachea cancer survivors compared to age‐, gender‐ and geographically matched cancer‐free controls. Studies including longer follow‐up periods are warranted to examine whether cancer survivors are at increased risk of long‐term incidentCVD.
Bacterial Cell‐Surface Display of Semisynthetic Cyclic Peptides
Authors: Palei Shubhendu , Becher Kira S. , Nienberg Christian , Jose Joachim , Mootz Henning D.
Published: September 2018

Semisynthetic cyclic peptides containing both non‐proteinogenic building blocks, as the synthetic part, and a genetically encoded sequence amenable to DNA‐based randomization hold great potential to expand the chemical space in the quest for novel bioactive peptides. Key to an efficient selection of novel binders to biomacromolecules is a robust method to link their genotype and phenotype. A novel bacterial cell surface display technology has been developed to present cyclic peptides composed of synthetic and genetically encoded fragments in their backbones. The fragments were combined by protein trans‐splicing and intramolecular oxime ligation. To this end, a split intein half and an unnatural amino acid were displayed with the genetically encoded part on the surface of Escherichia coli. Addition of the synthetic fragment equipped with the split intein partner and an aminooxy moiety, as well as the application of a pH‐shift protocol, resulted in the onsurface formation of the semisynthetic cyclic peptide. This approach will serve for the generation of cyclic peptide libraries suitable for selection by fluorescence‐activated cell sorting, and more generally enables chemical modification of proteins on the bacterial surface.
Structural and Electronic Responses to the Three Redox Levels of Fe(NO)N2S2‐Fe(NO)2
Authors: Ghosh Pokhraj , Ding Shengda , Quiroz Manuel , Bhuvanesh Nattamai , Hsieh Chung‐Hung , Palacios Philip M. , Pierce Brad S. , Darensbourg Marcetta Y. , Hall Michael B.
Published: September 2018

The nitrosylated diiron complexes, Fe2(NO)3, of this study are interpreted as a mono‐nitrosyl Fe(NO) unit, MNIU, within an N2S2 ligand field that serves as a metallodithiolate ligand to a dinitrosyl iron unit, DNIU. The cationic Fe(NO)N2S2⋅Fe(NO)2+ complex, 1+, of Enemark–Feltham electronic notation {Fe(NO)}7‐{Fe(NO)2}9, is readily obtained via myriad synthetic routes, and shown to be spin coupled and diamagnetic. Its singly and doubly reduced forms, {Fe(NO)}7‐{Fe(NO)2}10, 10, and {Fe(NO)}8‐{Fe(NO)2}10, 1−, were isolated and characterized. While structural parameters of the DNIU are largely unaffected by redox levels, the MNIU readily responds; the neutral, S=
, complex, 10, finds the extra electron density added into the DNIU affects the adjacent MNIU as seen by the decrease its Fe‐N‐O angle (from 171° to 149°). In contrast, addition of the second electron, now into the MNIU, returns the Fe‐N‐O angle to 171° in 1−. Compensating shifts in FeMNIU distances from the N2S2 plane (from 0.518 to 0.551 to 0.851 Å) contribute to the stability of the bimetallic complex. These features are addressed by computational studies which indicate that the MNIU in 1− is a triplet‐state {Fe(NO)}8 with strong spin polarization in the more linear FeNO unit. Magnetic susceptibility and parallel mode EPR results are consistent with the triplet state assignment.
Visible‐Light‐Mediated Liberation and In Situ Conversion of Fluorophosgene
Authors: Petzold Daniel , Nitschke Philipp , Brandl Fabian , Scheidler Veronica , Dick Bernhard , Gschwind Ruth M. , König Burkhard
Published: September 2018

The first example for the photocatalytic generation of a highly electrophilic intermediate that is not based on radical reactivity is reported. The single‐electron reduction of bench‐stable and commercially available 4‐(trifluoromethoxy)benzonitrile by an organic photosensitizer leads to its fragmentation into fluorophosgene and benzonitrile. The in situ generated fluorophosgene was used for the preparation of carbonates, carbamates, and urea derivatives in moderate to excellent yields via an intramolecular cyclization reaction. Transient spectroscopic investigations suggest the formation of a catalyst charge‐transfer complex‐dimer as the catalytic active species. Fluorophosgene as a highly reactive intermediate, was indirectly detected via its next downstream carbonyl fluoride intermediate by NMR. Furthermore, detailed NMR analyses provided a comprehensive reaction mechanism including a water dependent off‐cycle equilibrium.
A New Phosphine‐Amine‐Oxazoline Ligand for Ru‐Catalyzed Asymmetric Hydrogenation of N‐Phosphinylimines
Authors: Ma Xiaochen , Qiao Lin , Liu Guixia , Huang Zheng
Published: September 2018

A series of chiral phosphine‐amine‐oxazoline (PAO) ligands with an NH moiety were synthesized and applied to the ruthenium‐catalyzed asymmetric hydrogenation of N‐phosphinylimines. The ligand bearing phenyl groups at the phosphorus moiety and isopropyl at the oxazoline moiety exhibits good activity and excellent enantioselectivity (up to 99% ee). This catalytic system provides an efficient and mild approach to access enantioriched amines.
Imatinib and everolimus in patients with progressing advanced chordoma: A phase 2 clinical study
Authors: Stacchiotti Silvia , Morosi Carlo , Lo Vullo Salvatore , Casale Alessandra , Palassini Elena , Frezza Anna Maria , Dinoi Gabriella , Messina Antonella , Gronchi Alessandro , Cavalleri Adalberto , Venturelli Elisabetta , Morelli Daniele , Pilotti Silvana , Collini Paola , Brich Silvia , Tamborini Elena , Mariani Luigi , Casali Paolo G.
Published: September 2018

Background

We present the results of an academic phase 2 study on imatinib plus everolimus in patients who have progressive advanced chordoma.

Methods

In January 2011, 43 adult chordoma patients were enrolled in the study and received imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting toxicity. Eligible patients had progressed in the 6 months before study entry. PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of immunohistochemistry and/or western blotting. The primary endpoint was the overall response rate (ORR) according to Choi criteria. Secondary endpoints were RECIST 1.1 response, progression‐free survival (PFS), overall survival (OS), correlation between S6/4EBP1 phosphorylation and response.

Results

Thirteen of 43 patients were pretreated with imatinib. Among 40 of the 43 patients who were evaluable by Choi criteria, the best responses were 9 with partial response (ORR, 20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease (ORR, 16.3%). Forty‐two patients were evaluable by RECIST criteria, with 1 partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months (range, 4.6‐17.6 months), and 58.8% and 48.1% of patients were progression‐free at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14 months; the median OS was 47.1 months. When assessable, S6/4EBP1 was phosphorylated in a high and moderate/low proportion of tumor cells in responsive and nonresponsive patients, respectively. Toxicity caused a temporary and definitive treatment discontinuation in 60.5% and 30.2% of patients, respectively.

Conclusions

Imatinib plus everolimus showed a limited activity in progressing advanced chordoma. Interestingly, the amount of tumor cells activated for mammalian target of rapamycin effectors correlated with the response. Toxicity was not negligible.
Epsilon‐Fe2O3 Nanocrystals inside Mesoporous Silicas with Tailored Morphologies of Rod, Platelet and Donut
Authors: Li Jheng‐Guang , Fornasieri Giulia , Bleuzen Anne , Gich Martí , Impéror‐Clerc Marianne
Published: September 2018

The ϵ‐Fe2O3 polymorph of iron oxide, which has outstanding physical properties, is successfully stabilized inside mesoporous silica particles with tailored shapes. Using mesoporous silica particles with three different morphologies of rod, platelet and donut, we obtain ϵ‐Fe2O3/mesoporous silica nanocomposites. Iron oxide is loaded inside the porosity using a two steps impregnation cycle: solvent‐free impregnation followed by oxidation under 1000 °C. The amount of loaded iron oxide can be enhanced using two successive impregnation cycles. We fully characterise these nanocomposite particles with a wide panel of techniques to establish the exact amount of loaded iron inside the porosity, the nature of the iron oxide phase and the size of the nanocrystals. As a result, we conclude that ϵ‐Fe2O3 nanocrystals can be confined and stabilized in all types of morphologies, even inside the donut morphology which possesses closed mesopores.
Transforming a Diamagnetic Ordered Mesoporous Silica Monolith into a Room Temperature Permanent Magnet through Multiscale Control of the Magnetic Properties
Authors: Trannoy Virgile , Altenschmidt Laura , Fornasieri Giulia , Bordage Amélie , Rivière Eric , Beaunier Patricia , Bleuzen Anne
Published: September 2018

Prussian blue analog (PBA) nanoparticles confined in the ordered mesoporosity of silica monoliths with two‐dimensional hexagonal structure are used as precursors and transformed into metal oxide or metal alloy by thermal treatment under oxidizing or reducing atmosphere. X‐ray diffraction and transmission electron microscopy show that, after appropriate thermal treatment, the ordered silica monoliths contain spherical nanocrystals of mixed oxide and metal alloy aligned along the cylindrical pore axis. Their size (4 nm) is controlled by the diameter of the cylindrical pores of the silica monolith and their aggregation state by the structure of the porosity and the synthesis route. Furthermore, the chemical composition of the starting PBA precisely determines that of the oxide or alloy nanocrystals. The magnetic properties of the monoliths, governed by strong interparticle interactions, are very sensitive to chemical composition, size and aggregation state of the nanoparticles. The multi‐scale control of the nanocomposite enables producing a light macroscopic permanent magnet, which is attracted to a NdBFe magnet at room temperature.
An automated and scalable formal process for detecting fault injection vulnerabilities in binaries
Authors: Given‐Wilson Thomas , Heuser Annelie , Jafri Nisrine , Legay Axel
Published: September 2018

Fault injection has increasingly been used both to attack software applications and to test system robustness. Detecting fault injection vulnerabilities has been approached with a variety of different but limited methods. This paper proposes an extension of a recently published general model checking based process to detect fault injection vulnerabilities in binaries. This new extension makes the general process scalable to real‐world implementations, which is demonstrated by detecting vulnerabilities in different cryptographic implementations.
Comparing feedback from faculty interactions and virtual assessment software in the development of psychomotor skills in preclinical fixed prosthodontics
Authors: Sadid‐Zadeh Ramtin , D'Angelo Elizabeth H. , Gambacorta Joseph
Published: September 2018

The purpose of this study was to determine the effectiveness of virtual assessment software as a means of immediate feedback for preclinical fixed prosthodontics course. The subjects of the study were second year dental students with no previous training in fixed prosthodontics. Nine students participated in the study. Participants completed 2 days of didactic training focused on the principles of tooth preparation and the use of intraoral scanners and virtual assessment software. Didactic training was followed by 12 sessions of practical exercises. Students were randomly assigned to one of three groups for training in the preparation of tooth no. 46 for a complete cast crown. Students received feedback from (a) faculty interaction only; (b) interactions with both faculty and virtual assessment software; or (c) interactions with only virtual assessment software. During Sessions 5, 10, and 12, students prepared tooth no. 46 for complete cast crown independently and without any immediate feedback to simulate a practical exam. Prepared teeth were collected at Sessions 5, 10, and 12, and two blinded faculty members assessed the teeth following an established rubric. Results from Session 12 showed that preparations that one of three students and two of three students respectively for student–faculty interaction and student–faculty–Compare software interaction groups did not meet acceptable standards. However, the students in student–Compare software interaction group generated acceptable preparations at week 12. These data suggest that immediate feedback via virtual assessment software may be as effective as one‐on‐one faculty instruction for dental students in fixed prosthodontics.
Community‐wide consequences of sexual dimorphism: evidence from nectar microbes in dioecious plants
Authors: Tsuji Kaoru , Fukami Tadashi
Published: September 2018

Intraspecific trait variation is receiving renewed interest as a factor affecting the structure of multi‐species communities within and across trophic levels. One pervasive form of intraspecific trait variation is sexual dimorphism in animals and plants, which might exert large effects particularly on the communities of host‐associated organisms, but the extent of these effects is not well understood. We investigated whether host‐associated microbial communities developed differently in the floral nectar of female and male individuals of the dioecious shrubs, Eurya emarginata and E. japonica. We found that nectar‐colonizing microbes such as bacteria and fungi were more than twice as prevalent and, overall, more than 10 times as abundant in male flowers as in female flowers. Microbial species composition also differed between flower sexes. To examine potential mechanisms behind these differences, we manipulated the frequency of flower visitation by animals and the order of arrival of microbial species to nectar. Animal visitation frequency affected microbial communities more greatly in male flowers, while arrival order affected them more in female flowers. These sex‐specific effects appeared attributable to differences in how animals and microbes altered the chemical characteristics of nectar that limited microbial growth. Taken together, our results provide evidence that sexual dimorphism can have large effects on the structure of host‐associated communities.
Prophylactic treatment against GM‐CSF, but not IL‐17, abolishes relapses in a chronic murine model of multiple sclerosis
Authors: Uyttenhove Catherine , Gaignage Mélanie , Donckers Dominique , Nasr Zakia , Cheou Pamela , van Snick Jacques , D'Auria Ludovic , van Pesch Vincent
Published: September 2018

The pathogenic role of IL‐17 and GM‐CSF has been unravelled in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). However, in most models, EAE is characterised by a monophasic attack which is not representative of the relapsing nature nor the chronicity displayed in MS. Here, we used proteolipid protein peptide (PLP139‐151) to trigger EAE‐relapses (EAE‐II) in SJL mice that had recovered from a primary‐EAE episode (EAE‐I). This procedure resulted in severe and irreversible disease that, unlike EAE‐I, was not abolished by anti‐IL‐17‐mAb. In contrast, prophylactic anti‐GM‐CSF‐mAb treatment prevented EAE‐I and ‐II. Strikingly, the expression of T‐cell transcription factors and cytokines/chemokines in mice treated with anti‐GM‐CSF during both EAE episodes was silenced. Anti‐GM‐CSF‐mAb treatment administered only during EAE‐II did not completely prevent relapses but mice ultimately reached full recovery. Anti‐GM‐CSF treatment also strongly impaired and ultimately resolved monophasic MOG35‐55‐induced EAE in C57Bl/6 mice. In such protected mice, anti‐GM‐CSF treatment also prevented a further relapse induced by MOG‐revaccination. These results underscore the critical role of GM‐CSF on pro‐inflammatory mediator production. Furthermore, we observed a strong preventive and curative effect of anti‐GM‐CSF neutralisation in two EAE models, relapsing and chronic. Altogether these findings are relevant for further MS research.
Tetrathiafulvalene Dimer Merged with a Binuclear Ring of Sn and Sb: Synthesis and Molecular Structures Induced by Heteroatoms
Authors: Hasegawa Masashi , Shirai Masaki , Mazaki Yasuhiro
Published: September 2018

In this study, we describe the synthesis and characterization of dimeric tetrathiafulvalene (TTF) derivatives that are doubly bridged by Sn (1) and Sb (2a) atoms as a new class of organic‐inorganic hybrid compounds able to provide enhanced dimensionality in the solid state. The antimony heterocyclic framework was constructed by a simple Sn–Sb metal exchange reaction of a 1,4‐distannine moiety with p‐tolyl antimony dichloride (p‐tolSbCl2). Compound 2a was obtained in cis and trans forms as a stable configurational isomer. From X‐ray crystallographic analysis, there were three conformational isomers in which the tolyl rings were directed in the endo or exo direction. Crystal packing revealed a supramolecular three‐dimensional network through intermolecular short contacts of Sb···S and Sb···π. These packing forces gave a trans‐2aexo–exo conformation in the crystal, although the theoretical calculations predict its instability compared with other conformers. Cyclic voltammetry (CV) measurements of 1 and cis/trans‐2a revealed two pairs of reversible redox processes corresponding to the formation of TTF/TTF·+ and TTF·+/TTF2+. Furthermore, CV of cis/trans‐2a also revealed the reduction waves derived from the reduction of SbIII. Dicationic and tetracationic species were prepared by chemical oxidation, and their electronic structures were also investigated by electronic spectroscopy.
Self‐Supporting CuCo2S4 Microspheres for High‐Performance Flexible Asymmetric Solid‐State Supercapacitors
Authors: Xie Tian , Gai Yansong , Shang Yuanyuan , Ma Chuanli , Su Linghao , Liu Jing , Gong Liangyu
Published: September 2018

Copper cobalt sulfide (CuCo2S4) microspheres were grown directly on a carbon cloth (CC) substrate via a facile hydrothermal synthesis route. The possible formation mechanism of flower‐like CuCo2S4 microspheres was also discussed. The resultant composite was explored as a binder‐free electrode for supercapacitors, delivering a high capacitance of 166.67 mAh g–1 at 1 A g–1, excellent rate capability (108.33 mAh g–1 at 10 A g–1) and pronounced long‐term cyclability up to 3000 cycles. A flexible solid state supercapacitor was also assembled with binder‐free electrode materials and exhibits an energy density of 17.12 Wh kg–1 at a power density of 194.4 W kg–1, and a good cycling stability with 78.4 % of initial capacity retention rate can be maintained at 1 A g–1 after 3000 cycles. In addition, the electrochemical performance of supercapacitor device is still quite stable even if it was bent 180° or twisted 150°. Two charged CuCo2S4/CC//AC supercapacitors in series can light 1 red color LED's (2 V) for 5 minutes. All these features indicate that the CuCo2S4/CC device is an excellent candidate for energy storage.
Metallo‐Scorpionates: First Generation of Trimetallic, Homoleptic [Ru]–M–[Ru] Complexes (M = Fe, Co, Ni, Cu)
Authors: Schlapp‐Hackl Inge , Hassenrück Christopher , Wurst Klaus , Kopacka Holger , Müller Thomas , Winter Rainer F. , Bildstein Benno
Published: September 2018

The first metallo‐scorpionate ligands, closely related to Trofimenko's scorpionates, are obtained by formal replacement of the hydrido‐boron moiety of hydrido‐tris(pyrazolyl)borate by an (arene)RuII fragment. Coordination to divalent and trivalent 3d‐transition metals (Fe, Co, Ni, Cu) gives access to a series of homoleptic, heterotrimetallic complexes containing linear metal chains bridged by pyrazole ligands. Synthetic aspects, spectroscopic, structural and electrochemical properties are reported and compared to those of standard scorpionate complexes.
Quaternary Phosphorus‐Induced Iodocuprate(I)‐Based Hybrids: Water Stabilities, Tunable Luminescence and Photocurrent Responses
Authors: Zhang Wen‐Ting , Liu Jian‐Zhi , Liu Jing‐Bo , Song Kai‐Yue , Li Yi , Chen Zhi‐Rong , Li Hao‐Hong , Jiang Rong
Published: September 2018

Four (triphenyl)phosphonium‐based quaternary phosphorus salts with different substituents (varying from methyl to n‐butyl) were selected to be structural directed agents (SDAs) to construct four iodocuprate(I) hybrids via solution method, i.e., [(PPh3Me)(Cu3I4)]n (1), [(PPh3Et)(Cu3I4)]n (2), (PPh3iPr)2(Cu2I4) (3), [(PPh3nBu)(Cu3I4)]n (4). The inorganic iodocuprates in 1, 2 and 4 are 1‐D (Cu3I4)nn– chains constructed from Cu5I11 units, but (Cu2I4)2– in 3 is a di‐nuclear cluster. Interestingly, the strength of Cu···Cu and π–π stacking interactions are weakened with the lengthening of alkyl groups on P‐atom. The best water stability of 4 can be ascribed to the better hydrophobicity of n‐butyl group, which deters the dispersing of organic and inorganic moieties and as a result, inhibit hydrolysis reaction. Furthermore, all compounds exhibit typical reversible luminescent thermochromic behaviors, among which 4 exhibits blue emission and the quenching of higher energy (HE) zone in 1 and 2 are led by strong π–π stacking interactions. Besides, effective and repeatable photocurrent responses can be detected in these compounds. In all, by systematically introducing alkyl groups into (triphenyl)phosphonium as SDAs to prepare hybrid iodocuprates, we can find that the longer alkyl groups can achieve stronger tunable PL materials with enhanced water stabilities.
A Series of Unprecedented Linear Mixed‐Metal‐Substituted Polyoxometalate Trimers: Syntheses, Structures, Luminescence, and Proton Conductivity Properties
Authors: Li Zhong , Lin Li‐Dan , Zhao Dan , Sun Yan‐Qiong , Zheng Shou‐Tian
Published: September 2018

In this paper, we report a series of novel mixed‐metal‐substituted organic‐inorganic hybrid polyoxometalates (POMs) H3[(CH3)4N]14[NaLn(PW11O39)3]·18H2O (1‐Ln, Ln = Nd, Sm, Eu) via one‐pot solvothermal synthesis methods, which present the first series of polyoxometalate trimers composed of both alkali‐metal‐ and lanthanide‐substituted keggin‐type POMs. The trimeric heterometallic polyoxoanions in 1‐Ln show an interesting linear arrangement and can be further packed together to generate a packing structure with cations [(CH3)4N]+ and H3O+ filling the gaps between polyoxoanions. Compounds 1‐Ln are characterized by single‐crystal X‐ray diffraction analysis, TGA, IR and PXRD. Additionally, the luminescence and proton conductive properties of 1‐Ln are also characterized.
Stereoselective Synthesis of 1‐Thio‐α‐d‐Ribofuranosides Using Ribofuranosyl Iodides as Glycosyl Donors
Authors: Oka Natsuhisa , Mori Ayumi , Ando Kaori
Published: September 2018

A method for the 1,2‐cis‐selective synthesis of 1‐thio‐α‐ribofuranosides has been developed. Ribofuranosyl iodides as glycosyl donors react effectively with thiols under mild basic conditions to afford various 1‐thio‐α‐ribofuranosides, including some that are unstable under acidic conditions.
Silica Gel Functionalized with 4‐Amino‐5‐(4pyridyl)‐4H‐1,2,4‐triazole‐3‐thiol and their Use as a Copper Sorbent and Electromediator for Voltammetric Detection of Ascorbic Acid
Authors: de Souza Magossi Maiara , Maraldi Vitor Alexandre , de Souza Magossi Mariana , Dias Filho Newton Luiz , Ribeiro do Carmo Devaney
Published: September 2018

In this work, the 3‐chloropropyl silica gel (SG) was prepared and organofunctionalized with 4‐amino‐5‐(4pyridyl)‐4H‐1,2,4‐triazole‐3‐thiol (SGA), that was characterized by infrared spectroscopy (FTIR) and cyclic voltammetry (CV). The cupric ions (Cu2+) sorption on the silica functionalized surface (CuSGA) were performed in aqueous solution, at room temperature. It was performed a systematic study about voltammetric behavior of CuSGA, where the cyclic voltammogram of graphite paste electrode modified with CuSGA exhibited a single redox pair with formal potential (Eθ′)=0.30 V assigned to the process Cu+/Cu2+, (KCl 1.0 mol L−1, v=20 mV s−1). The graphite paste electrode modified with CuSGA was sensitive to different concentrations of ascorbic acid and then an analytical curve could be constructed, with a linear response of 6.0×10−6 to 9.0×10−5 mol L−1 (R=0.9988) and a relative standard deviation of ±2.5 % (n=3). The detection limit (3σ) and amperometric sensitivity were 4.78×10−6 mol L−1 and 115.96 mA/mol L−1, respectively.
A Novel Sediment Microbial Fuel Cell Based Sensor for On‐Line and in situ Monitoring Copper Shock in Water
Authors: Wu Shaosong , Deng Huan , Han Cheng , Liu Li , Zhong Wenhui
Published: September 2018

To online and in situ monitor the heavy metal shock in water, a novel sediment microbial fuel cell based sensor was developed with anode being inserted into flooded soil and cathode submerged in overlaying water. Immediately after CuSO4 solutions were added into the overlaying water, the voltage signal generated by the sensor reached a peak and the increment from baseline voltage to peak voltage increased linearly with Cu2+ concentrations up to 160 mg L−1. After Cu2+ shock, charge transfer resistance (Rct) of anode and cathode was determined by using electrochemical impedance spectroscopy. Soil DNA and RNA was extracted and 16S rRNA and 16S rRNA gene of dominant exoelectrogenic bacteria (Geobacter and Clostridium) was quantified. Result showed that Cu2+ shock decreased cathodic charge transfer resistance (Rct) but did not affect anodic Rct. The addition of 320 mg L−1 Cu2+ significantly reduced abundance and activity of Geobacter and Clostridium in surface soil (0–3 cm in depth) but had no effect on exoelectrogenic bacteria in deeper soil. Moreover, baseline voltage was stable after Cu2+ shock. The result indicates that the sensor could online and in situ monitor Cu2+ shock which increased voltage signal by promoting cathodic reaction without dramatically inhibiting exoelectrogenic bacteria.
Pattern Recognition of Diabetes Related Biomarkers
Authors: Stefan‐van Staden Raluca‐Ioana , Mitrofan Grigorina , Ionescu‐Tirgoviste Constantin
Published: September 2018

Four stochastic microsensors were proposed for the molecular recognition of insulin, Proinsulin C Peptide (55–89), leptin, adiponectin and CRP in serum samples. The microsensors were design by physical immobilization of protoporphyrin PIX, phthalocyanine‐BODIPY dye (BODIPY=boron dipyrromethene), inulins such as TEX or ionic liquids such as L‐alanine‐tert‐butyl‐ester‐L‐lactate (L‐AlaC4‐Lac) in matrices such as diamond paste and Au‐TiO2/rGR paste. The proposed microsensors were reliable for the molecular recognition and quantification of the biomarkers. For the determination of Proinsulin C Peptide (55–89), insulin, leptin, adiponectin and CRP the immunoassay techniques are routinely used in clinical practice, requiring five types of detection kits, therefore one of the main advantage in using this method consists in determining in one run all the analytes.
Effects of hydroxyurea on CNV induction in the mouse germline
Authors: Arlt Martin F. , Rajendran Sountharia , Holmes Sandra N. , Wang Kathleen , Bergin Ingrid L. , Ahmed Samreen , Wilson Thomas E. , Glover Thomas W.
Published: September 2018

Copy number variants (CNVs) are important in genome variation and genetic disease, with new mutations arising frequently in the germline and somatic cells. Replication stress caused by aphidicolin and hydroxyurea (HU) is a potent inducer of de novo CNVs in cultured mammalian cells. HU is used extensively for long‐term management of sickle cell disease. Here, we examined the effects of HU treatment on germline CNVs in vivo in male mice to explore whether replication stress can act as a CNV mutagen in germline mitotic divisions as in cultured cells and whether this would support a concern for increased CNV mutations in offspring of men treated with HU. Several trials of HU administration were performed by oral gavage and subcutaneous pump, with CNVs characterized in C57BL/6 x C3H/HeJ hybrid mouse offspring by microarray and mate‐pair sequencing. HU had a short half‐life of ~14 min and a narrow dose window over which studies could be performed while maintaining fertility. Tissue histopathology and reticulocyte micronucleus assays verified that doses had a substantial tissue and genetic toxicity. CNVs were readily detected in offspring that originated in both paternal and maternal mouse strains, as de novo and inherited events. However, HU did not increase CNV formation above baseline levels. These results reveal a high rate of CNV mutagenesis in the mouse germline but do not support the hypothesis that HU would increase CNV formation during mammalian spermatogenesis, perhaps due to highly toxic effects on sperm development or experimental variables related to HU pharmacology in mice. Environ. Mol. Mutagen. 59:698–714, 2018. © 2018 Wiley Periodicals, Inc.
A companion to the preclinical common data elements for pharmacologic studies in animal models of seizures and epilepsy. A Report of the TASK3 Pharmacology Working Group of the ILAE/AES Joint Translational Task Force
Authors: Barker‐Haliski Melissa , Harte‐Hargrove Lauren C. , Ravizza Teresa , Smolders Ilse , Xiao Bo , Brandt Claudia , Löscher Wolfgang
Published: September 2018

Preclinical pharmacology studies in animal models of seizures and epilepsy have provided a platform to identify more than 20 antiseizure drugs in recent decades. To minimize variability in lab‐to‐lab studies and to harmonize approaches to data collection and reporting methodology in pharmacologic evaluations of the next generation of therapies, we present common data elements (CDEs), case report forms (CRFs), and this companion manuscript to help with the implementation of methods for studies in established preclinical seizure and epilepsy models in adult rodents. The development of and advocacy for CDEs in preclinical research has been encouraged previously by both clinical and preclinical groups. It is anticipated that adoption and implementation of these CDEs in preclinical studies may help standardize approaches to minimize variability and increase the reproducibility of preclinical studies. Moreover, they may provide a methodologic framework for pharmacology studies in atypical animal models or models in development, which may ultimately promote novel therapy development. In the present document, we refer selectively to animal models that have a long history of preclinical use, and in some cases, are clinically validated.
Mega‐blowouts in Qinghai–Tibet Plateau: Morphology, distribution and initiation
Authors: Luo Wanyin , Wang Zhongyuan , Lu Junfeng , Yang Linghai , Qian Guangqiang , Dong Zhibao , Bateman Mark D.
Published: September 2018

Blowouts are wind‐eroded landforms that are widely distributed in the north‐eastern part in Qinghai–Tibet Plateau (QTP), China. These blowouts are thought to form in response to climate change and/or human activity but little is known about their morphodynamics. Using field surveys, remote sensing and geographic information system (GIS) spatial analysis, the distribution and morphology of blowouts are analysed and their initiation considered. Results show the QTP mega‐blowouts are some of the largest in the world. The orientations of the trough shaped blowouts are parallel with the prevailing wind, but the saucer and bowl‐shaped blowouts are influenced by bi‐directional transport. Whilst regional patterns of blowout shape and size were observed to reflect the extent of aeolian sediments and wind regimes, the relationship between the different morphological parameters showed consistency. During initial stages of development, the length to width ratios of blowouts increase rapidly with area but after they reach a mega size this relationship stabilizes as blowouts widen. Initial luminescence dating shows that blowouts appear to have initiated ~100 to 500 years ago, coinciding with the Little Ice Age (LIA) climate event when northwest winds are known to have intensified. Further work is required to confirm this initiation period and establish the significance of mega blowouts for landscape degradation and human activities. © 2018 John Wiley & Sons, Ltd.
Physically constrained data‐driven correction for reduced‐order modeling of fluid flows
Authors: Mohebujjaman M. , Rebholz L.G. , Iliescu T.
Published: September 2018

We have recently proposed a data‐driven correction reduced‐order model (DDC‐ROM) framework for the numerical simulation of fluid flows, which can be formally written as follows.

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The new DDC‐ROM was constructed by using reduced‐order model spatial filtering and data‐driven reduced‐order model closure modeling (for the Correction term) and was successfully tested in the numerical simulation of a two‐dimensional channel flow past a circular cylinder at Reynolds numbers Re = 100,Re = 500, and Re = 1000. In this paper, we propose a physically constrained DDC‐ROM (CDDC‐ROM), which aims at improving the physical accuracy of the DDC‐ROM. The new physical constraints require that the CDDC‐ROM operators satisfy the same type of physical laws (ie, the Correction term's linear component should be dissipative, and the Correction term's nonlinear component should conserve energy) as those satisfied by the fluid flow equations. To implement these physical constraints, in the data‐driven modeling step, we replace the unconstrained least squares problem with a constrained least squares problem. We perform a numerical investigation of the new CDDC‐ROM and standard DDC‐ROM for a two‐dimensional channel flow past a circular cylinder at Reynolds numbers Re = 100,Re = 500, and Re = 1000. To this end, we consider a reproductive regime as well as a predictive (ie, cross‐validation) regime in which we use as little as 50% of the original training data. The numerical investigation clearly shows that the new CDDC‐ROM is significantly more accurate than the DDC‐ROM in both regimes.
Commercial Fisheries of the Upper Mississippi River: A Century of Sustained Harvest
Authors: Klein Zachary B , Quist Michael C , Miranda Leandro E , Marron Michelle M , Steuck Michael J , Hansen Kirk A
Published: September 2018

Commercial harvest is often considered as a primary cause of fish population declines in marine and inland systems throughout the world. However, much of the data supporting the negative attributes of commercial harvest are derived from marine fisheries and may not be directly applicable to inland fisheries. In this study, over 60 years of commercial fishery data from the Upper Mississippi River (UMR) was synthesized to better understand how inland commercial fisheries function and to address concerns associated with the exploitation of aquatic resources in freshwater systems. Overall, total commercial harvest in the UMR remained relatively stable over the study period and did not negatively influence fish populations or recreational fisheries. Our results address concerns associated with inland fisheries and highlight how proper management and interagency partnerships result in consistent and productive fisheries over large spatial and temporal scales.