bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing estimates of evaporative demand in climate models using observed pan evaporation over China
Authors: Liu Wenbin , Sun Fubao
Published: July 2016

Here we assess estimates of atmospheric evaporative demand over China in 12 state‐of‐the‐art global climate models (GCMs) against observed D20 pan evaporation (Epan) over the period of 1961–2000. To do that, we use an energy‐relevant and physical‐based approach, namely, PenPan model, to comprehensively evaluate GCM performance with respect to their ability to simulate annual, seasonal, and monthly statistics of Epan (and its radiative and aerodynamic components, Ep,R and Ep,A). The results indicated that most GCMs generally captured the spatial pattern and seasonal cycle of Epan, Ep,R, and Ep,A. However, regional means of annual and monthly Epan, Ep,R, and Ep,A were underestimated by most GCMs mainly due to negatively biased surface air temperature (Ta) and vapor pressure deficit (vpd) outputted/simulated by the GCMs. Overall, the discrepancies among GCMs in estimating the regional statistics (regional means and seasonal cycles) of Ep,A were relatively larger than that of Ep,R, which indicates considerable uncertainties in the calculation of the aerodynamic component of evaporation based on the GCM outputs. Moreover, a few GCMs captured negative trends of regional mean annual and seasonal Epan, Ep,R, and Ep,A well over the period of 1961– 2000, but most showed positive trends. The underestimation of net radiation (Rn) and overestimation of wind speed at 2 m (u2) in most GCMs may, to some extent, accentuate/compensate the negative biases in GCM‐estimated annual and seasonal Epan, Ep,R, and Ep,A. The results demonstrate the importance of incorporating observation of pan evaporation and well‐validated PenPan model to evaluate GCM performance on atmospheric evaporative demand that is relevant to projections of future drought and regional water‐energy budgets.
Crosstalk effect mitigation in black body warm‐up cool‐down calibration for Terra MODIS longwave infrared photovoltaic bands
Authors: Sun Junqiang , Madhavan Sriharsha , Wang Menghua
Published: July 2016

The crosstalk phenomena in Terra MODerate‐resolution Imaging Spectroradiometer (MODIS) midwave‐to‐longwave infrared (LWIR) photovoltaic (PV) bands (bands 27‐30) have recently been individually studied and characterized, and a correction algorithm has been developed. The routine calibration of the four LWIR PV bands uses an onboard black body (BB) based on a quadratic model for the relationship between the at‐aperture radiance and the background subtracted instrument response. While the crosstalk correction has been successfully applied in both the routine BB calibration (scan basis) to correct the crosstalk effect in the linear term and the Earth view (EV) radiance in our previous investigations on the bands 27–29, the most recent work on band 30 demonstrated a newfound necessity to include the impact of the crosstalk effect on the nonlinear term as well as the offset. In this paper, we analyze the calibration calculation under a variety of conditions consistent with the MODIS Collection 6 settings to examine the impact of the crosstalk effect in the two terms derived from the BB warm‐up‐cool‐down (WUCD) calibration. We show that with correct account of the crosstalk effect in the WUCD calibration, the sudden changes and other abnormal features that have been observed in the two terms for many years are effectively and remarkably removed. In addition, imagery for bands 27–29 using the calibration result fully corrected for the electronic crosstalk effect shows further improvement over previous results that account for only the corrected linear term, whereas for the band 30 different testing scenes validate the previous fully corrected findings.
Soft Nanostructured Films for Actuated Surface‐Based siRNA Delivery
Authors: Kang Minjee , Leal Cecilia
Published: July 2016

Substrate‐mediated gene delivery is an emerging technology that enables spatial control of gene expression and localized delivery. This is of particular interest for siRNA where surface‐based release can greatly impact the fields of stem‐cell reprograming, wound healing, and medical device coatings in general. However, reports on the use of siRNA for substrate‐mediated delivery are scarce and have suffered from low efficiency. Here, an alternative strategy is reported by designing self‐assembled substrates that experience stimuli‐responsive topological transformations. Specifically, a methodology is established to promote the molecular organization of lipid films having 3D‐bicontinuous cubic, 2D‐inverted hexagonal, or 1D‐lamellar nanostructures encapsulating siRNA. In response to a compositional, temperature, or humidity stimulus, the nanostructures evolve from 1D‐lamellar or 2D‐hexagonal to 3D‐cubic resulting in efficient siRNA release to human cell cultures. Grazing incidence X‐ray diffraction reveals that film nanostructures are highly ordered and preferentially aligned. The results indicate that film structure substantially affects siRNA delivery, with the supported 3D‐bicontinuous cubic phase yielding the most effective reduction of gene expression. Subsequent studies suggest this enhanced performance arises due to the ability of this phase to cross cell membranes, particularly those of endocytic compartments. This work underpins that nanostructure tuning is decisive to the performance of therapeutic films.
Copper‐Catalyzed Cyanomethylation of Substituted Tetrahydroisoquinolines with Acetonitrile
Authors: Zhang Wei , Yang Shiping , Shen Zengming
Published: July 2016

A novel method for the synthesis of cyanomethylated tetrahydroisoquinolines has been developed with mild reaction conditions, good yields and a broad substrate scope. Acetonitrile, a common solvent, is for the first time used as a pronucleophile for this type of two sp3 C−H bonds cross‐dehydrogenative coupling (CDC) reaction. A new oxidative system (CuCl2/TEMPO/Cs2CO3) has been established by our group, in which the mild TEMPO reagent was found to be a highly efficient oxidant.

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A Palladium‐Catalyzed Domino Approach to 2,3‐Disubstituted Benzofurans via an Intermolecular Carbopalladation/C(sp3)−H Functionalization/Isomerization Sequence
Authors: Boominathan Siva Senthil Kumar , Hou Ruei‐Jhih , Hu Wan‐Ping , Huang Po‐Jui , Wang Jeh‐Jeng
Published: July 2016

A palladium‐catalyzed domino strategy has been developed for the synthesis of 2,3‐disubstituted benzofuran derivatives. This cascade reaction sequence involves intermolecular carbopalladation and C(sp3)−H functionalization followed by isomerization.

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The apportionment of tooth size and its implications in Australopithecus sediba versus other Plio‐pleistocene and recent African hominins
Authors: Irish Joel D. , Hemphill Brian E. , de Ruiter Darryl J. , Berger Lee R.
Published: July 2016

Objectives

Australopithecus sediba is characterized further by providing formerly unpublished and refined mesiodistal and buccolingual crown measurements in the MH1 and MH2 specimens. After size correction, these data were compared with those in other fossil and recent samples to facilitate additional insight into diachronic hominin affinities.

Materials and Methods

Six comparative samples consist of fossil species: A. africanus, A. afarensis, Homo habilis, Paranthropus robustus, P. boisei, and H. erectus. Others comprise H. sapiens and Pan troglodytes. Re‐estimates of “actual” dimensions in damaged A. sediba teeth were effected through repeated measurements by independent observers. X‐ray synchrotron microtomography allowed measurement of crowns obscured by matrix and noneruption. Tooth size apportionment analysis, an established technique for intraspecific comparisons, was then applied at this interspecific level to assess phenetic affinities using both within‐ and among‐group data.

Results

Comparison of these highly heritable dimensions identified a general trend for smaller posterior relative to larger anterior teeth (not including canines), contra Paranthropus, that allies A. sediba with other australopiths and Homo; however, specific reductions and/or shape variation in the species’ canines, third premolars, and anterior molars relative to the other teeth mirror the patterning characteristic of Homo.

Discusssion

Of all samples, including east African australopiths, A. sediba appears most like H. habilis, H. erectus and H. sapiens regarding how crown size is apportioned along the tooth rows. These findings parallel those in prior studies of dental and other skeletal data, including several that suggest A. sediba is a close relative of, if not ancestral to, Homo.
Food and pathogen adaptations in the Angolan Namib desert: Tracing the spread of lactase persistence and human African trypanosomiasis resistance into southwestern Africa
Authors: Pinto Joana C. , Oliveira Sandra , Teixeira Sérgio , Martins Dayana , Fehn Anne‐Maria , Aço Teresa , Gayà‐Vidal Magdalena , Rocha Jorge
Published: July 2016

Objectives: We investigated the frequency distribution and haplotype diversity of human African trypanosomiasis (HAT) resistance and lactase persistence (LP) variants in populations from the Angolan Namib to trace the spread of these genetic adaptations into southwestern Africa.

Materials and Methods: We resequenced two fragments of the LCT enhancer and the APOL1 gene and genotyped flanking short tandem repeat loci in six groups with different subsistence traditions living in the Angolan Namib, and in a comparative dataset including other populations from Africa and Europe. LP in the Angolan Namib is represented by the −14010*C allele, which is associated with a predominant haplotype that is shared with other southern and eastern African populations. While LP was found to be more frequent in foragers than in pastoralists, the frequencies of the two APOL1 variants associated with HAT‐resistance (G1 and G2) did not differ between the two groups. The G1 allele is mostly associated with a single widespread haplotype. The G2 allele is linked to several haplotypes that are molecularly related to haplotypes found in other African Bantu‐speaking populations. The putatively archaic G3 variant displayed more intra‐allelic diversity in Africa than in Europe.

Discussion: The LP adaptation was carried to southern Africa by non‐Bantu speaking pastoralists from eastern Africa, but an obvious link between its presence in southern Angola and groups speaking languages of the Khoe‐Kwadi family, as previously found in other areas, could not be confirmed. The presence of APOL1 variants G1 and G2 is linked to the Bantu expansions. Our results suggest that the G3 variant was retained in modern humans by incomplete lineage sorting.
Between the Lines: How the CFPB Will Police Financial Services Arbitration
Authors: Bleemer Russ
Published: July 2016

The Consumer Financial Protection Bureau on May 5 delivered a proposal to regulate arbitration by banning the waivers of class processes that often accompany the alternative dispute resolution process in consumer contracts, and require individualized processes.
Ephrin‐B2 prevents N‐methyl‐D‐aspartate receptor antibody effects on memory and neuroplasticity
Authors: Planagumà Jesús , Haselmann Holger , Mannara Francesco , Petit‐Pedrol Mar , Grünewald Benedikt , Aguilar Esther , Röpke Luise , Martín‐García Elena , Titulaer Maarten J. , Jercog Pablo , Graus Francesc , Maldonado Rafael , Geis Christian , Dalmau Josep
Published: July 2016

Objective

To demonstrate that ephrin‐B2 (the ligand of EphB2 receptor) antagonizes the pathogenic effects of patients' N‐methyl‐D‐aspartate receptor (NMDAR) antibodies on memory and synaptic plasticity.

Methods

One hundred twenty‐two C57BL/6J mice infused with cerebrospinal fluid (CSF) from patients with anti‐NMDAR encephalitis or controls, with or without ephrin‐B2, were investigated. CSF was infused through ventricular catheters connected to subcutaneous osmotic pumps over 14 days. Memory, behavioral tasks, locomotor activity, presence of human antibodies specifically bound to hippocampal NMDAR, and antibody effects on the density of cell‐surface and synaptic NMDAR and EphB2 were examined at different time points using reported techniques. Short‐ and long‐term synaptic plasticity were determined in acute brain sections; the Schaffer collateral pathway was stimulated and the field excitatory postsynaptic potentials were recorded in the CA1 region of the hippocampus.

Results

Mice infused with patients' CSF, but not control CSF, developed progressive memory deficit and depressive‐like behavior along with deposits of NMDAR antibodies in the hippocampus. These findings were associated with a decrease of the density of cell‐surface and synaptic NMDAR and EphB2, and marked impairment of long‐term synaptic plasticity without altering short‐term plasticity. Administration of ephrin‐B2 prevented the pathogenic effects of the antibodies in all the investigated paradigms assessing memory, depressive‐like behavior, density of cell‐surface and synaptic NMDAR and EphB2, and long‐term synaptic plasticity.

Interpretation

Administration of ephrin‐B2 prevents the pathogenic effects of anti‐NMDAR encephalitis antibodies on memory and behavior, levels of cell‐surface NMDAR, and synaptic plasticity. These findings reveal a strategy beyond immunotherapy to antagonize patients' antibody effects. Ann Neurol 2016;80:388–400
Selektive Synthese teilgeschützter unsymmetrischer Biphenole durch reagens‐ und metallfreie anodische Kreuzkupplung
Authors: Wiebe Anton , Schollmeyer Dieter , Dyballa Katrin M. , Franke Robert , Waldvogel Siegfried R.
Published: July 2016

Vorgestellt wird die oxidative Kreuzkupplung von Arenen ohne Abgangsfunktionalitäten oder Katalysatoren. Die selektive Synthese teilgeschützter unsymmetrischer 2,2′‐Biphenole gelang in hohen Ausbeuten an isoliertem Produkt mittels elektroorganischer Synthese. Der Einsatz von elektrischem Strom als Oxidationsmittel ist reagensfrei und verhindert somit die Bildung von Reagensabfällen. Das sichere Verfahren eignet sich für eine einfache ungeteilte Elektrolysezelle sowie für Reaktionen in großem Maßstab. Die Verwendung von O‐Silyl‐geschützten Phenolen resultiert sowohl in gesteigerten Ausbeuten als auch in erhöhten Selektivitäten bei der Synthese der unsymmetrischen 2,2′‐Biphenole. Die Nutzung sperriger Silylgruppen zum Schützen der OH‐Gruppe macht das Produkt weniger anfällig für Folgeoxidationen. Teilgeschützte 2,2′‐Biphenole sind vielseitige Ausgangsverbindungen, die üblicherweise nur aufwändig in geringen Ausbeuten zugänglich sind. Diese Synthesestrategie ermöglicht eine Vielzahl neuer Substratkombinationen für oxidative Kreuzkupplungen.
Pristinol, ein Sesquiterpen‐Alkohol mit ungewöhnlichem Gerüst aus Streptomyces pristinaespiralis
Authors: Klapschinski Tim A. , Rabe Patrick , Dickschat Jeroen S.
Published: July 2016

Eine Terpencyclase aus Streptomyces pristinaespiralis wurde als (+)‐(2S,3S,9R)‐Pristinol‐Synthase charakterisiert. Die Struktur dieses Sesquiterpenalkohols mit einem neuen Gerüst wurde durch NMR‐Spektroskopie und monochromatische anomale Röntgendispersion aufgeklärt. Isotopenmarkierungsexperimente ermöglichten es, zwischen verschiedenen Cyclisierungsmechanismen der Terpencyclase zu unterscheiden und den EI‐MS‐Fragmentierungsmechanismus des Pristinols zu studieren.
Isolation, Structure Elucidation, and (Bio)Synthesis of Haprolid, a Cell‐Type‐Specific Myxobacterial Cytotoxin
Authors: Steinmetz Heinrich , Li Jun , Fu Chengzhang , Zaburannyi Nestor , Kunze Birgitte , Harmrolfs Kirsten , Schmitt Viktoria , Herrmann Jennifer , Reichenbach Hans , Höfle Gerhard , Kalesse Markus , Müller Rolf
Published: July 2016

Myxobacteria are well‐established sources for novel natural products exhibiting intriguing bioactivities. We here report on haprolid (1) isolated from Byssovorax cruenta Har1. The compound exhibits an unprecedented macrolactone comprising four modified amino acids and a polyketide fragment. As configurational assignment proved difficult, a bioinformatic analysis of the biosynthetic gene cluster was chosen to predict the configuration of each stereocenter. In‐depth analysis of the corresponding biosynthetic proteins established a hybrid polyketide synthase/nonribosomal peptide synthetase origin of haprolid and allowed for stereochemical assignments. A subsequent total synthesis yielded haprolid and corroborated all predictions made. Intriguingly, haprolid showed cytotoxicity against several cell lines in the nanomolar range whereas other cells were almost unaffected by treatment with the compound.
The Cole–Cole plot for cure: The cure and reversion of natural rubber
Authors: Willoughby Bryan G.
Published: July 2016

Cure rheometry is routinely used in the rubber industry for processability assessment and cure‐time determination. This article examines these rheological outputs in Cole–Cole format to explore what new insights can be gained from this alternative data plot. It differs from the conventional Cole–Cole treatment in its application to a reacting system. The plots described here are therefore of G″(t) vs. G′(t). Initially some attention is directed to the basics of the Cole–Cole treatment and the likely features to be expected when applied to systems undergoing both cure and reversion. This article goes on to consider examples of both by studying a natural rubber vulcanization at temperatures of 160 °C and above. Through the Cole–Cole approach, it is thought possible to identify the competition between intermolecular and intramolecular sulfurization, and between crosslink and main‐chain scission. The approach offers considerable potential to expand the capabilities of cure rheometry. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44085.
EXPRESSION AND EFFECTS OF MUTANT Bombyx mori ACETYLCHOLINESTRASE1 IN BmN CELLS
Authors: Wang Bin‐Bin , Xie Yi , Li Fan‐Chi , Ni Min , Xu Kai‐Zun , Tian Jiang‐Hai , Hu Jing‐Sheng , Xue Bin , Shen Wei‐De , Li Bing
Published: July 2016

The main mechanism of toxicity of organophosphate (OP) and carbamate (CB) insecticides is their irreversible binding and inhibition of acetylcholinestrase (AChE), encoded by ace1 (acetylcholinestrase gene 1), leading to eventual death of insects. Mutations in AChE may significantly reduce insects susceptibility to these pesticides. Bombyx mori is an important beneficial insect, and no OP‐ or CB‐resistant strains have been generated. In this study, wild‐type ace1 (wace1) and mutant ace1 (mace1) were introduced into BmN cells, confirmed by screening and identification. The expression of wace1 and mace1 in the cells was confirmed by Western blot and their expression levels were about 21‐fold higher than the endogenous ace1 level. The activities of AChE in wace1 and mace1 transgenic cells were 10.6 and 20.2% higher compared to control cells, respectively. mace1 transgenic cells had higher remaining activity than wace1 transgenic cells under the treatment of physostigmine (a reversible cholinesterase inhibitor) and phoxim (an OP acaricide). The results showed that ace1 transgene can significantly improve ace1 expression, and ace1 mutation at a specific site can reduce the sensitivity to AChE inhibitors. Our study provides a new direction for the exploration of the relationship between AChE mutations and drug resistance.
Antimicrobial/Antibiofilm Activity and Cytotoxic Studies of β‐Thujaplicin Derivatives
Authors: Fotopoulou Theano , Ćirić Ana , Kritsi Eftichia , Calhelha Ricardo C. , Ferreira Isabel C.F.R. , Soković Marina , Zoumpoulakis Panagiotis , Koufaki Maria
Published: July 2016

Natural β‐thujaplicin displays a remarkable array of biological activities for the prevention or treatment of various disorders while its tropolone scaffold inspired the synthesis of new analogs. The main goal of the current study was to evaluate the influence of 4‐substituted piperazine moieties at position 7 of the β‐thujaplicin scaffold, on the antimicrobial activity. In order to determine the biological activity of the β‐thujaplicin derivatives, a microdilution method was used against a wide variety of bacteria and fungi. Pseudomonas aeruginosa PAO 1 was used for testing antiquorum and antibiofilm effects. Four human tumor cell lines (MCF‐7, NCI‐H460, HeLa, and HepG2) and a porcine liver derived cell line (PLP2) were used for testing antitumor and cytotoxic activity. The compounds present better antibacterial and antifungal activity in comparison with approved antimicrobials used as control agents. β‐Thujaplicin showed strong antibacterial and antifungal activities against all tested species. Further studies of their antibacterial activity revealed that all compounds presented good antibiofilm and antiquorum effects. Fungi were more susceptible than bacteria to the tested compounds, with the exception of MK150, which possessed the best antibacterial effect. None of the tested compounds, at the GI50 values obtained for the tumor cell lines, have shown toxicity for non‐tumor liver cells (PLP2). The prediction of physicochemical properties of the compounds was performed to further explain the structure–activity relationship. Finally, in order to explore a possible mechanism of action of the synthesized compounds, molecular docking studies were performed on CYP51 (14‐a lanosterol demethylase), an important component of the fungal cell membrane.
Voice identity processing in autism spectrum disorder
Authors: Schelinski Stefanie , Roswandowitz Claudia , von Kriegstein Katharina
Published: July 2016

People with autism spectrum disorder (ASD) have difficulties in identifying another person by face and voice. This might contribute considerably to the development of social cognition and interaction difficulties. The characteristics of the voice recognition deficit in ASD are unknown. Here, we used a comprehensive behavioral test battery to systematically investigate voice processing in high‐functioning ASD (n = 16) and typically developed pair‐wise matched controls (n = 16). The ASD group had particular difficulties with discriminating, learning, and recognizing unfamiliar voices, while recognizing famous voices was relatively intact. Tests on acoustic processing abilities showed that the ASD group had a specific deficit in vocal pitch perception that was dissociable from otherwise intact acoustic processing (i.e., musical pitch, musical, and vocal timbre perception). Our results allow a characterization of the voice recognition deficit in ASD: The findings indicate that in high‐functioning ASD, the difficulty to recognize voices is particularly pronounced for learning novel voices and the recognition of unfamiliar peoples’ voices. This pattern might be indicative of difficulties with integrating the acoustic characteristics of the voice into a coherent percept—a function that has been previously associated with voice‐selective regions in the posterior superior temporal sulcus/gyrus of the human brain. Autism Res 2017, 10: 155–168. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Category structure and processing in 6‐year‐old children with autism
Authors: Ellawadi Allison Bean , Fein Deborah , Naigles Letitia R.
Published: July 2016

This study investigated the categorization abilities of 6‐year‐old children with autism spectrum disorders (ASD) as compared to their peers with typical development (TD) using a category verification task. We examined the impact of stimulus typicality on multiple aspects of real‐time performance, including accuracy, reaction time, and performance stability. Both groups were more accurate in identifying typical category members than atypical ones; however, only the ASD group's accuracy was affected by item ordering, indicating less stable performance. Furthermore, category structure was predicted by concurrent language levels in the TD group but by concurrent nonverbal IQ in the ASD group; these latter two findings suggest that children with ASD process categories differently than their peers with TD. Autism Res 2017, 10: 327–336. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Microscopic insight into the DNA condensation process of a zwitterion‐functionalized polycation
Authors: Sun Hui , Zhou Li , Chen Xiaolu , Han Xia , Wang Rui , Liu Honglai
Published: July 2016

Zwitterion‐functionalized polycations are ideal gene carriers with long circulation, high cellular uptaking and low cell viability. However, the trade‐off between the DNA condensation efficiency and the cell viability must be addressed. The purpose of this study is to provide a microscopic insight into the DNA condensation process and to explore the effect of a zwitterionic block of zwitterion‐functionalized polycation, which is of great significance in designing novel gene delivery systems. Poly[2‐(dimethylamino)ethyl methacrylate‐b‐(sulfobetaine methacrylate)] (PDMAEMA‐b‐PSBMA) copolymers were synthesized and used as the model systems. Different from the conventional concept that the PSBMA zwitterionic block act only as the “stealthy” groups, the subtle differences in physical and colloidal characteristics between the polycation/DNA polyplexes show that the PSBMA segment is capable of wrapping DNA attributed to the quaternary ammonium cations, without compromising the DNA condensation capability. On the other hand, the incorporation of PSBMA block reduces the surface charge of the polyplexes, which substantially result in the inefficient transfection and the reduced cytotoxicity.
Discovery, isolation, and structural characterization of cyclotides from Viola sumatrana Miq
Authors: Niyomploy Ploypat , Chan Lai Yue , Poth Aaron G. , Colgrave Michelle L. , Sangvanich Polkit , Craik David J.
Published: July 2016

Cyclotides are cyclic peptides from plants in the Violaceae, Rubiaceae, Fabaceae, Cucurbitaceae, and Solanaceae families. They are sparsely distributed in most of these families, but appear to be ubiquitous in the Violaceae, having been found in every plant so far screened from this family. However, not all geographic regions have been examined and here we report the discovery of cyclotides from a Viola species from South‐East Asia. Two novel cyclotides (Visu 1 and Visu 2) and two known cyclotides (kalata S and kalata B1) were identified in V. sumatrana. NMR studies revealed that kalata S and kalata B1 had similar secondary structures. Their biological activities were determined in cytotoxicity assays; both had similar cytotoxic activity and were more toxic to U87 cells compared with other cell lines. Overall, the study strongly supports the ubiquity of cyclotides in the Violaceae and adds to our understanding of their distribution and cytotoxic activity.
Potent and Selective Monoamine Oxidase‐B Inhibitory Activity: Fluoro‐ vs. Trifluoromethyl‐4‐hydroxylated Chalcone Derivatives
Authors: Mathew Bijo , Mathew Githa Elizabeth , Uçar Gülberk , Baysal Ipek , Suresh Jerad , Mathew Sincy , Haridas Abitha , Jayaprakash Venkatesan
Published: July 2016

For various neurodegenerative disorders like Alzheimer's and Parkinson’s diseases, selective and reversible MAO‐B inhibitors have a great therapeutic value. In our previous study, we have shown that a series of methoxylated chalcones with F functional group exhibited high binding affinity toward human monoamine oxidase‐B (hMAO‐B). In continuation of our earlier study and to extend the understanding of the structure–activity relationships, a series of five new chalcones were studied for their inhibition of hMAO. The results demonstrated that these compounds are reversible and selective hMAO‐B inhibitors with a competitive mode of inhibition. The most active compound, (2E)‐1‐(4‐hydroxyphenyl)‐3‐[4‐(trifluoromethyl)phenyl]prop‐2‐en‐1‐one, exhibited a Ki value of 0.33 ± 0.01 μm toward hMAO‐B with a selectivity index of 26.36. A molecular docking study revealed that the presence of a H‐bond network in hydroxylated chalcone with the N(5) atom of FAD is crucial for MAO‐B selectivity and potency.
Fast‐track endovascular aortic repair: Interim report from the prospective LIFE registry
Authors: Krajcer Zvonimir , Ramaiah Venkatesh G. , Huetter Meredith , Miller Larry E.
Published: July 2016

Objective

To assess the feasibility, safety, and clinical utility of a fast‐track endovascular aneurysm repair (EVAR) protocol.

Background

Despite recent advances in EVAR technology and techniques, considerable opportunity exists to further improve EVAR efficiency and outcomes.

Methods

Eligible patients underwent elective EVAR with the Ovation Prime stent graft. Successful completion of the fast‐track protocol required bilateral percutaneous access, avoidance of general anesthesia and intensive care unit admission, and next‐day discharge. Patients were followed through 1‐month post‐treatment.

Results

Between October 2014 and September 2015, 129 patients were enrolled in the study. Vascular access, stent graft delivery, and stent graft deployment were successful in all patients. The fast‐track EVAR protocol was successfully completed in 114 (88%) patients. Bilateral percutaneous access was achieved in 97% of cases. Comparing patients who completed fast‐track requirements to those who failed at least one component, procedure time was 86 vs. 122 min, use of general anesthesia was 0% vs. 20%, need for intensive care unit stay was 0% vs. 13%, hospital stay was 1.1 vs. 2.1 days, and postoperative groin pain severity (0–10 scale) was 1.2 vs. 4.0. No type I or III endoleaks, serious device‐related adverse events, AAA ruptures, surgical conversions, or AAA‐related secondary procedures were reported. One (0.9%) patient in the fast‐track group died from acute respiratory failure.

Conclusions

Initial results from the LIFE study are encouraging and suggest that a fast‐track protocol is feasible, safe, and may improve efficiency of healthcare resource allocation in select patients undergoing EVAR. © 2016 Wiley Periodicals, Inc.
The first clinical experience with a novel directional coronary atherectomy catheter: Preliminary Japanese multicenter experience
Authors: Habara Maoto , Tsuchikane Etsuo , Nasu Kenya , Kinoshita Yoshihisa , Yaguchi Tomonori , Suzuki Yoriyasu , Matsuo Hitoshi , Terashima Mitsuyasu , Matsubara Tetsuo , Suzuki Takahiko
Published: July 2016

Aims

Despite development of drug eluting stents (DES), percutaneous coronary intervention (PCI) for bifurcation lesions using DES alone remains challenging. The aim of this study was to report on the initial clinical experience with a novel directional coronary atherectomy (DCA) catheter.

Methods and Results

Patients with de novo bifurcation lesions were entered into a prospective registry and a novel DCA catheter was used. Device, procedural success and in‐hospital outcomes were evaluated. A total of 14 patients with bifurcation lesions were enrolled. DCA was performed successfully in all cases without any major procedure‐related events (device success rate: 100%, procedural success rate: 100%). Four patients (29%) were treated without stent implantation and simple stenting was achieved in the other 10 patients. No in‐hospital major adverse cardiac event was observed.

Conclusions

PCI with a novel DCA catheter for bifurcation lesions may be safe and effective. The clinical significance of these findings needs to be determined in future studies. This study was performed to evaluate the safety and efficacy of a novel directional coronary atherectomy catheter for bifurcation lesions. Both the device and procedural success rates were 100%. Complex stenting could be avoided in all cases. No inhospital major adverse cardiac event was observed. The novel directional coronary atherectomy catheter may be safe and effective for bifurcation lesions, even in this drug eluting stent era. © 2016 Wiley Periodicals, Inc.
How to prevent and treat complications of the retrograde approach to chronic total occlusion percutaneous coronary intervention
Authors: Danek Barbara Anna , Brilakis Emmanouil S.
Published: July 2016

Key Points

The retrograde approach is important for achieving high success rates in chronic total occlusion percutaneous coronary intervention.

Operators must be aware of complications that can occur during retrograde CTO PCI; they must continually try to prevent them and be ready to treat them, if they occur.

Systematic, prospective study of complications in CTO PCI is needed for the development of additional preventive and treatment strategies.
End of the bare metal stent era?
Authors: Hillegass William B.
Published: July 2016

Key Points

Second‐generation drug eluting stents (2g‐DES) have lower rates of stent thrombosis (ST) than bare metal stents (BMS).

Second‐generation DES have exceedingly low rates of very late ST, significantly improving on first‐generation drug eluting stents (1g‐DES) and similar to BMS.

Emerging drug‐coated stent (DCS) technology appears superior to BMS in patients unable to tolerate prolonged dual antiplatelet therapy (DAPT).
Advanced data analysis and process monitoring across manufacturing plants using multilevel methods
Authors: de Noord Onno E.
Published: July 2016

Three‐level versions of Multilevel Simultaneous Component Analysis (MLSCA) and Multilevel Partial Least Squares (MLPLS) were developed, which are capable of separating between‐plant, between‐run and within‐run process variation, and modeling these three levels in a multivariate way. In comparison to the two‐level versions they allow to discriminate between overall differences between plants and the variation between runs within a plant. It was shown that the three‐level version of MLSCA has clear added value for the analysis of process runs from different plants. In MLPLS other projections of the multivariate data onto latent variables and different views of the data are obtained when relevant Y information is available. This has clear added value for obtaining insight into the relation between process data and Y. A special use of MLPLS is to diagnose aberrations in first principles models.

In batch process monitoring MLSCA at three levels allows simultaneous multivariate modelling of batch data from different manufacturing plants. By filtering out the between‐plant and between‐run sources of variation, and using only within‐run variation, monitoring models can be improved. Using within‐run data, it is possible to build monitoring models across manufacturing units and reduce the number of nuisance alarms, while improving abnormal situation detection and diagnosis. Model transfer is only possible if static between‐plant differences exist, but not if there are dynamic differences.
Reaction Mechanism of the Hydrogermylation/Hydrostannylation of Unactivated Alkenes with Two‐Coordinate EII Hydrides (E=Ge, Sn): A Theoretical Study
Authors: Zhao Lili , Hermann Markus , Jones Cameron , Frenking Gernot
Published: July 2016

Quantum chemical calculations using density functional theory with the TPSS+D3(BJ) and M06‐2X+D3(ABC) functionals have been carried out to understand the mechanisms of catalyst‐free hydrogermylation/hydrostannylation reactions between the two‐coordinate hydrido‐tetrylenes :E(H)(L+) (E=Ge or Sn, L+=N(Ar+)(SiiPr3); Ar+=C6H2{C(H)Ph2}2iPr‐2,6,4) and a range of unactivated terminal (C2H3R, R=H, Ph, or tBu) and cyclic [(CH)2(CH2)2(CH2)n, n=1, 2, or 4] alkenes. The calculations suggest that the addition reactions of the germylenes and stannylenes to the cyclic and acyclic alkenes occur as one‐step processes through formal [2+2] addition of the E−H fragment across the C−C π bond. The reactions have moderate barriers and are weakly exergonic. The steric bulk of the tetrylene amido groups has little influence on the activation barriers and on the reaction energies of the anti‐Markovnikov pathway, but the Markovnikov addition is clearly disfavored by the size of the substituents. The addition of the tetrylenes to the cyclic alkenes is less exergonic than the addition to the terminal alkenes, which agrees with the experimentally observed reversibility of the former reactions. The hydrogermylation reactions have lower activation energies and are more exergonic than the stannylene addition. An energy decomposition analysis of the transition state for the hydrogermylation of cyclohexene shows that the reaction takes place with simultaneous formation of the Ge−C and (Ge)H−C′ bonds. The dominant orbitals of the germylene are the σ‐type lone pair MO of Ge, which serves as a donor orbital, and the vacant p(π) MO of Ge, which acts as acceptor orbital for the π* and π MOs of the olefin. Inspection of the transition states of some selected reactions suggests that the differences between the activation energies come from a delicate balance between the deformation energies of the interacting species and their interaction energies.
Orthogonal Click Conjugation to the Liposomal Surface Reveals the Stability of the Lipid Anchorage as Crucial for Targeting
Authors: Fritz Thomas , Voigt Matthias , Worm Matthias , Negwer Inka , Müller Sophie S. , Kettenbach Kathrin , Ross Tobias L. , Roesch Frank , Koynov Kaloian , Frey Holger , Helm Mark
Published: July 2016

Synthetic access to multiple surface decorations are a bottleneck in the development of liposomes for receptor mediated targeting. This opens a complex multiparameter space, exploration of which is severely limited in terms of sample numbers and turnaround times. Here, we unlock this technological barrier by a combination of a milligram‐scale liposome formulation using dual centrifugation and orthogonal click chemistry on the liposomal surface. Application of these techniques to conceptually new amphiphilic compounds, which feature norbornene and alkyne groups at the apex of sterically stabilizing, hyperbranched polyglycerol moieties, revealed a particular influence of the membrane anchor of functional amphiphiles. Folic acid residues clicked to cholesterol‐based amphiphiles were inefficient in folate‐mediated cell targeting, while dialkyl‐anchored amphiphiles remained stable in the liposomal membrane and imparted efficient targeting properties. These findings are of specific importance considering the popularity of cholesterol as a lipophilic anchor.
Characterization of a Crosslinked Elastomeric‐Protein Inspired Polypeptide
Authors: Bochicchio Brigida , Bracalello Angelo , Pepe Antonietta
Published: July 2016

Materials inspired by natural proteins have a great appeal in tissue engineering for their biocompatibility and similarity to extracellular matrix (ECM). Chimeric polypeptides inspired by elastomeric proteins such as silk, elastin, and collagen are of outstanding interest in the field. A recombinant polypeptide constituted of three different blocks, each of them having sequences derived from elastin, resilin, and collagen proteins, was demonstrated to be a good candidate as biomaterial for its self‐assembling characteristics and biocompatibility. Herein, taking advantage of the primary amine functionalities present in the linear polypeptide, we crosslinked it with 1,6‐hexamethylene‐diisocyanate (HMDI). The characterization of the obtained polypeptide was realized by CD spectroscopy, AFM, and SEM microscopies. The obtained results, although not conclusive, demonstrate that the crosslinked polypeptide gave rise to porous networks, thin nanowires, and films not observable for the linear polypeptide. Chirality 28:606–611, 2016. © 2016 Wiley Periodicals, Inc.
Ansätze zur numerischen Berechnung von Brandeinwirkungen auf Bauteile
Authors: Kaudelka Sven , Knaust Christian , Krause Ulrich
Published: July 2016

Bei der Erstellung von brandschutztechnischen Nachweisen für Industriebauten werden häufig Ingenieurmethoden des Brandschutzes genutzt. Dazu zählen die Modellierung und Berechnung von Brandszenarien mittels numerischer Strömungsmechanik (computational fluid dynamics, CFD). In dieser Arbeit wurde ein auf numerischer Strömungs‐ und Strukturmechanik basierendes Verfahren zur brandschutztechnischen Bemessung von Bauteilen am Beispiel einer Industriehalle angewendet. Instationäre Temperaturverläufe aus der Heißgasschicht dienten dabei als Eingangswerte für die Bauteilberechnung. Aus den Ergebnissen wurde die äquivalente Branddauer berechnet, mit der die rechnerisch erforderlichen Feuerwiderstandsdauern der Bauteile bestimmt werden konnte.
Does corporate diversification create value in emerging markets? New evidence from Chile
Authors: Espinosa Christian , Jara Mauricio , Maquieira Carlos , Vieito João Paulo
Published: July 2016

Using a sample of 85 Chilean firms listed in the Santiago Stock Exchange from 2005 to 2013, we analyze the impact of corporate diversification on firm value. We consider voting rights of the main shareholder and institutional investors’ influence on firm value. We report firm‐value destruction for diversified firms. Regarding ownership concentration, we report a negative relation between the largest shareholder ownership and firm value. Separation between voting rights and cash flows rights of this shareholder is negatively related to firm value. While Pension Fund Administrators (AFP) mitigate firm value destruction in diversified firms, other institutional investors do not play an active role in controlling value destruction. Finally, if the largest owner is a family, we report firm‐value creation in diversified firms. Copyright © 2016 ASAC. Published by John Wiley & Sons, Ltd.
A Benzodithiophene‐Based Fluorescence Probe for Rapid Detection of Fluoride Ion
Authors: Tan Wenbin , Leng Taohua , Lai Guoqiao , Li Zhifang , Wu Jiefei , Shen Yongjia , Wang Chengyun
Published: July 2016

A novel and simple fluorescence probe was synthesized from benzo[1,2‐b:4,5‐b′]dithiophene (BDT) and trimethylsilylethyne via Sonogashira reaction, and showed highly selective and sensitive fluorescence decreasing response towards F−. The probe molecule turned to a weakly fluorescent terminal alkyne moiety because its trimethylsilyl (TMS) group was cleaved by fluoride, which was proved by 1H NMR titration. Whereas no distinct fluorescent changes were observed with the addition of other anions, such as Cl−, Br−, I−, AcO− and H2PO4−. Upon the addition of F−, the maximum fluorescence emission wavelength shifted from 460 nm to 450 nm with a decrease of fluorescence intensity by 40% within 20 s. Moreover, the detection limit towards F− was calculated to be as low as 73.5 nmol/L.
Origin of d‐π Interaction in Cobalt(II) Porphyrins under Synergistic Effects of Core Contraction and Axial Ligation: Implications for a Ligand Effect of Natural Distorted Tetrapyrrole
Authors: Liu Qiuhua , Zhang Xi , Zeng Wennan , Wang Jianxiu , Zhou Zaichun
Published: July 2016

The reactivity of the metalloporphyrins was closely related to their ligand effect at axial position. The electronic properties of six model Co(II) porphyrins are investigated by spectral and electrochemical methods. Structural parameters of the Co(II) complexes are directly obtained from their crystal structures. We demonstrate that the unpaired 3d electron of low‐spin Co(II) ions in nonplanar Co(II) porphyrin complexes activated by core contraction of porphyrin macrocycles can be further activated by the axial ligation of imidazole. The activated electron can combine with a π orbital of the porphyrin ring to form a new d‐π orbital, which can induce the Q‐band of Co(II) porphyrins to visibly split. Addition of imidazole causes the Co(II)/Co(III) and Co(II)/Co(I) reactions to shift to more negative potential. Our results indicate that strong axial ligation and core contraction both play important roles in electron transfer in redox catalysis involving Co(II) complexes.
Podosome dynamics and location in vascular smooth muscle cells require CLASP‐dependent microtubule bending
Authors: Zhu Xiaodong , Efimova Nadia , Arnette Christopher , Hanks Steven K. , Kaverina Irina
Published: July 2016

Extracellular matrix (ECM) remodeling during physiological processes is mediated by invasive protrusions called podosomes. Positioning and dynamics of podosomes define the extent of ECM degradation. Microtubules are known to be involved in podosome regulation, but the role of microtubule (MT) network configuration in podosome dynamics and positioning is not well understood. Here, we show that the arrangement of the microtubule network defines the pattern of podosome formation and relocation in vascular smooth muscle cells (VSMCs). We show that microtubule plus‐end targeting facilitates de novo formation of podosomes, in addition to podosome remodeling. Moreover, specialized bent microtubules with plus ends reversed towards the cell center promote relocation of podosomes from the cell edge to the cell center, resulting in an evenly distributed podosome pattern. Microtubule bending is induced downstream of protein kinase C (PKC) activation and requires microtubule‐stabilizing proteins known as cytoplasmic linker associated proteins (CLASPs) and retrograde actin flow. Similar to microtubule depolymerization, CLASP depletion by siRNA blocks microtubule bending and eliminates centripetal relocation of podosomes. Podosome relocation also coincides with translocation of podosome‐stimulating kinesin KIF1C, which is known to move preferentially along CLASP‐associated microtubules. These findings indicate that CLASP‐dependent microtubule network configuration is critical to the cellular location and distribution of KIF1C‐dependent podosomes. © 2016 Wiley Periodicals, Inc.
Comparing Drug Images and Repurposing Drugs with BioGPS and FLAPdock: The Thymidylate Synthase Case
Authors: Siragusa Lydia , Luciani Rosaria , Borsari Chiara , Ferrari Stefania , Costi Maria Paola , Cruciani Gabriele , Spyrakis Francesca
Published: July 2016

Repurposing and repositioning drugs has become a frequently pursued and successful strategy in the current era, as new chemical entities are increasingly difficult to find and get approved. Herein we report an integrated BioGPS/FLAPdock pipeline for rapid and effective off‐target identification and drug repurposing. Our method is based on the structural and chemical properties of protein binding sites, that is, the ligand image, encoded in the GRID molecular interaction fields (MIFs). Protein similarity is disclosed through the BioGPS algorithm by measuring the pockets’ overlap according to which pockets are clustered. Co‐crystallized and known ligands can be cross‐docked among similar targets, selected for subsequent in vitro binding experiments, and possibly improved for inhibitory potency. We used human thymidylate synthase (TS) as a test case and searched the entire RCSB Protein Data Bank (PDB) for similar target pockets. We chose casein kinase IIα as a control and tested a series of its inhibitors against the TS template. Ellagic acid and apigenin were identified as TS inhibitors, and various flavonoids were selected and synthesized in a second‐round selection. The compounds were demonstrated to be active in the low‐micromolar range.