bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambipolar Organic Field‐Effect Transistors Based on a Dual‐Function, Ultrathin and Highly Crystalline 2,9‐didecyldinaphtho[2,3‐b:2′,3′‐f]thieno[3,2‐b]thiophene (C10‐DNTT) Layer
Authors: Huang Shuyun , Peng Boyu , Chan Paddy Kwok Leung
Published: October 2017

Ultrathin organic semiconductor thin films have great value in the investigation of carrier transport behavior in organic field‐effect transistors (OFETs). Here, the dual solution shearing (DSS) method is adopted to deposit ultrathin and closely packed 2,9‐didecyldinaphtho[2,3‐b:2′,3′‐f]thieno[3,2‐b]thiophene (C10‐DNTT) films. This smooth, ultrathin and highly crystalline DSS‐processed C10‐DNTT layer can be utilized in p–n stacking bilayer ambipolar OFETs. It has two major functions in the bilayer OFET: (i) it acts as the p‐channel active layer; and (ii) it serves as the growth template of the upper n‐type semiconductor layer. The closely packed alkyl side chains of the C10‐DNTT molecules behave like long alkyl chains in the self‐assembled monolayer and can assist the packing and orientation of the following layer. The F16CuPc layer grown on DSS‐processed C10‐DNTT shows crystallized lamellae structure. The smooth C10‐DNTT surface can suppress the trap states and enhance the charge transfer between the p–n layer interface. The drain‐source current (IDS) in the p‐channel and n‐channel shows a threefold and fivefold increase compared with two‐step thermal evaporation. These findings demonstrate the potential of using solution‐processed ultrathin organic semiconductor in multilayer organic electronics, which cannot be easily achieved by the conventional thermal evaporation approach.
Ethnic derivation of the Ainu inferred from ancient mitochondrial DNA data
Authors: Adachi Noboru , Kakuda Tsuneo , Takahashi Ryohei , Kanzawa‐Kiriyama Hideaki , Shinoda Ken‐ichi
Published: October 2017

Objectives

The Ainu, the indigenous people living on the northernmost island of Japan, Hokkaido, have long been a focus of anthropological interest because of their cultural, linguistic, and physical identity. A major problem with genetic studies on the Ainu is that the previously published data stemmed almost exclusively from only 51 modern‐day individuals living in Biratori Town, central Hokkaido. To clarify the actual genetic characteristics of the Ainu, individuals who are less influenced by mainland Japanese, who started large‐scale immigration into Hokkaido about 150 years ago, should be examined. Moreover, the samples should be collected from all over Hokkaido.

Materials and methods

Mitochondrial DNA haplogroups of 94 Ainu individuals from the Edo era were successfully determined by analyzing haplogroup‐defining polymorphisms in the hypervariable and coding regions. Thereafter, their frequencies were compared to those of other populations.

Results

Our findings indicate that the Ainu still retain the matrilineage of the Hokkaido Jomon people. However, the Siberian influence on this population is far greater than previously recognized. Moreover, the influence of mainland Japanese is evident, especially in the southwestern part of Hokkaido that is adjacent to Honshu, the main island of Japan.

Discussion

Our results suggest that the Ainu were formed from the Hokkaido Jomon people, but subsequently underwent considerable admixture with adjacent populations. The present study strongly recommends revision of the widely accepted dual‐structure model for the population history of the Japanese, in which the Ainu are assumed to be the direct descendants of the Jomon people.
Quality of dispatch‐assisted cardiopulmonary resuscitation by lay rescuers following a standard protocol in Japan: an observational simulation study
Authors: Asai Hideki , Fukushima Hidetada , Bolstad Francesco , Okuchi Kazuo
Published: October 2017

Aim

Bystander cardiopulmonary resuscitation (CPR) is essential for improving the outcomes of sudden cardiac arrest patients. It has been reported that dispatch‐assisted CPR (DACPR) accounts for more than half of the incidence of CPR undertaken by bystanders. Its quality, however, can be suboptimal. We aimed to measure the quality of DACPR using a simulation study.

Methods

We recruited laypersons at a shopping mall and measured the quality of CPR carried out in our simulation. Dispatchers provided instruction in accordance with the standard DACPR protocol in Japan.

Results

Twenty‐three laypersons (13 with CPR training experience within the past 2 years and 10 with no training experience) participated in this study. The median chest compression rate and depth were 106/min and 33 mm, respectively. The median time interval from placing the 119 call to the start of chest compressions was 119 s. No significant difference was found between the groups with and without training experience. However, subjects with training experience more frequently placed their hands correctly on the manikin (84.6% versus 40.0%; P = 0.026). Twelve participants (52.2%, seven in trained and five in untrained group) interrupted chest compressions for 3–18 s, because dispatchers asked if the patient started breathing or moving.

Conclusion

This current simulation study showed that the quality of DACPR carried out by lay rescuers can be less than optimal in terms of depth, hand placement, and minimization of pauses. Further studies are required to explore better DACPR instruction methods to help lay rescuers perform CPR with optimal quality.
Morphology and properties of poly(ethylene terephthalate) and thermoplastic polyester elastomer blends modified in the melt by a diisocyanate chain extender and filled with a short glass fiber
Authors: Pesetskii S. S. , Shevchenko V. V. , Dubrovsky V. V.
Published: October 2017

The structural features and rheological, mechanical, and relaxation properties of poly(ethylene terephthalate) (PET) blends with 7–50 wt % polyester thermoplastic polyester elastomer (TPEE), a block copolymer of poly(butylene terephthalate) and poly(tetramethylene oxide), chemically modified by a diisocyanate chain extender (CE) and reinforced with 30% glass fibers (GF) were studied. The composites were obtained by reactive extrusion with a twin‐screw reactor–mixer with a unidirectional rotation of screws. The molecular–structural changes in the materials were judged against data provided by differential scanning calorimetry, scanning electron microscopy, relaxation spectrometry, and rheological analysis of the melts. Regardless of the TPEE concentration in the blends with GF‐reinforced PET, the addition of CE resulted in the growth of the indices of the mechanical properties at straining, bending, and impact loading and an increase in the melt viscosity. In addition, an increase in the average length of short GFs in the composites and an intensification of interphase adhesion in the polyester binder–GF surface system were observed. The introduction of CE promoted a slowdown in PET crystallization in the composites and intensified the interphase adhesion in the binder–GF system at temperatures higher and lower than the PET glass‐transition temperature. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45711.
Study of the fluorine adsorption onto zirconium oxide deposited strong alkaline anion exchange fiber
Authors: Mo Mengxia , Zeng Qingxuan , Li Mingyu
Published: October 2017

A kind of adsorbent, strong alkaline anion exchange fiber loaded with zirconium strong alkaline anion exchange fiber (Zr@SAAEF) was prepared. Zr(IV) was uniformly distributed on SAAEF through chemical bonds and physical deposition. Zr@SAAEF has a decent effect on the removal of fluorine in water and scanning electron microscopy images and Fourier transform infrared spectroscopy spectrum showed that the Zr(IV) was successfully loaded on the fiber by chemical bonding. The average adsorption capacity of fluorine was 28.14 mg/g with pH ranging from 5.0 to 8.9, when fluorine solution (100 mg/L) was adsorbed by 0.1 g SAAEF, and the extent of removal exceed 96% when the adsorbent dose was 0.3 g. The adsorption isotherms were well fitted with Langmuir equation, and the maximum adsorption capacities calculated by Langmuir equation were close to the experiment results. The adsorption was an endothermic reaction. These results implied that fluorine adsorption onto Zr@SAAEF belonged to chemical adsorption using monolayer coverage on surface of the fiber. The adsorption kinetics of fluorine onto Zr@SAAEF could be described by pseudo‐second‐order rate mode. Zr@SAAEF showed a decent ability for fluorine removal from aqueous solution. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45855.
Proteomic analysis of the venom of the predatory ant Pachycondyla striata (Hymenoptera: Formicidae)
Authors: Santos Pollyanna Pereira , Games Patricia Dias , Azevedo Dihego Oliveira , Barros Edvaldo , de Oliveira Leandro Licursi , de Oliveira Ramos Humberto Josué , Baracat‐Pereira Maria Cristina , Serrão José Eduardo
Published: October 2017

The ants use their venom for predation, defense, and communication. The venom of these insects is rich in peptides and proteins, and compared with other animal venoms, ant venoms remain poorly explored. The objective of this study was to evaluate the protein content of the venom in the Ponerinae ant Pachycondyla striata. Venom samples were collected by manual gland reservoir dissection, and samples were submitted to two‐dimensional gel electrophoresis and separation by ion‐exchange and reverse‐phase high‐performance liquid chromatography followed by mass spectrometry using tanden matrix‐assisted laser desorption/ionization with time‐of‐flight (MALDI‐TOF/TOF) mass spectrometry and electrospray ionization‐quadrupole with time‐of‐flight (ESI‐Q/TOF) mass spectrometry for obtaining amino acid sequence. Spectra obtained were searched against the NCBInr and SwissProt database. Additional analysis was performed using PEAKS Studio 7.0 (Sequencing de novo). The venom of P. striata has a complex mixture of proteins from which 43 were identified. Within the identified proteins are classical venom proteins (phospholipase A, hyaluronidase, and aminopeptidase N), allergenic proteins (different venom allergens), and bioactive peptides (U10‐ctenitoxin Pn1a). Venom allergens are among the most expressed proteins, suggesting that P. striata venom has high allergenic potential. This study discusses the possible functions of the proteins identified in the venom of P. striata.
Prerequisites of Isopeptide Bond Formation in Microcystin Biosynthesis
Authors: Meyer Sabine , Mainz Andi , Kehr Jan‐Christoph , Süssmuth Roderich D. , Dittmann Elke
Published: October 2017

The biosynthesis of the potent cyanobacterial hepatotoxin microcystin involves isopeptide bond formation through the carboxylic acid side chains of d‐glutamate and β‐methyl d‐aspartate. Analysis of the in vitro activation profiles of the two corresponding adenylation domains, McyE‐A and McyB‐A2, either in a didomain or a tridomain context with the cognate thiolation domain and the upstream condensation domain revealed that substrate activation of both domains strictly depended on the presence of the condensation domains. We further identified two key amino acids in the binding pockets of both adenylation domains that could serve as a bioinformatic signature of isopeptide bond‐forming modules incorporating d‐glutamate or d‐aspartate. Our findings further contribute to the understanding of the multifaceted role of condensation domains in nonribosomal peptide synthetase assembly lines.
Enzymatic Incorporation of Modified Purine Nucleotides in DNA
Authors: Abu El Asrar Rania , Margamuljana Lia , Abramov Mikhail , Bande Omprakash , Agnello Stefano , Jang Miyeon , Herdewijn Piet
Published: October 2017

A series of nucleotide analogues, with a hypoxanthine base moiety (8‐aminohypoxanthine, 1‐methyl‐8‐aminohypoxanthine, and 8‐oxohypoxanthine), together with 5‐methylisocytosine were tested as potential pairing partners of N8‐glycosylated nucleotides with an 8‐azaguanine or 8‐aza‐9‐deazaguanine base moiety by using DNA polymerases (incorporation studies). The best results were obtained with the 5‐methylisocytosine nucleotide followed by the 1‐methyl‐8‐aminohypoxanthine nucleotide. The experiments demonstrated that small differences in the structure (8‐azaguanine versus 8‐aza‐9‐deazaguanine) might lead to significant differences in recognition efficiency and selectivity, base pairing by Hoogsteen recognition at the polymerase level is possible, 8‐aza‐9‐deazaguanine represents a self‐complementary base pair, and a correlation exists between in vitro incorporation studies and in vivo recognition by natural bases in Escherichia coli, but this recognition is not absolute (exceptions were observed).
The safety and effectiveness of adenosine diphosphate receptor inhibitor pretreatment among acute myocardial infarction patients treated with percutaneous coronary intervention in community practice: Insights from the TRANSLATE‐ACS study
Authors: Effron Mark B. , Wang Tracy Y. , Fonarow Gregg C. , Henry Timothy D. , Zettler Marjorie E. , Baker Brian A. , McCoy Lisa A. , Peterson Eric D.
Published: October 2017

Objectives

To understand the optimal timing of adenosine diphosphate (ADP) receptor inhibitor pretreatment prior to percutaneous coronary intervention (PCI) among acute myocardial infarction (MI) patients.

Background

The role of ADP receptor inhibitor pretreatment in this population is unclear.

Methods

A total of 9,251 ADP receptor inhibitor‐naïve MI patients undergoing PCI at 229 TRANSLATE‐ACS sites were evaluated. Adjusted risks of in‐hospital major adverse cardiovascular events (MACE) and major bleeding were compared among patients with and without pretreatment using inverse probability‐weighted propensity adjustment.

Results

Of 9,251 patients treated with either prasugrel or clopidogrel during the index MI hospitalization, 4,056 (44%) received pretreatment (ST‐segment elevation MI [STEMI] 54.9%, non‐STEMI 45.1%); pretreatment was used more commonly among those receiving clopidogrel than prasugrel (52% vs. 20%, P < 0.0001). MACE risks were not significantly different between patients with and without pretreatment (clopidogrel 2.1% vs. 2.2%, adjusted hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.70–1.43; prasugrel 2.1% vs. 2.3%, adjusted odds ratio [OR] 0.82, 95% CI 0.42–1.60). No differences in major bleeding were observed among those receiving versus not receiving pretreatment (clopidogrel 3.1% vs. 3.5%, adjusted HR 0.94, 95% CI 0.65–1.36; prasugrel 2.5% vs. 2.7%, adjusted OR 0.93, 95% CI 0.42–2.02); results were similar when stratified by MI type.

Conclusions

ADP receptor inhibitor pretreatment (44%) is commonly used among acute MI patients undergoing PCI in contemporary practice, but no significant differences were found in in‐hospital MACE and/or bleeding risks between patients receiving versus not receiving pretreatment, regardless of ADP receptor inhibitor type.
Maintenance of valvular integrity with Impella left heart support: Results from the multicenter PROTECT II randomized study
Authors: Goldstein James A. , Dixon Simon R. , Douglas Pamela S. , Ohman E. Magnus , Moses Jeffrey , Popma Jeffrey J. , O'Neill William W.
Published: October 2017

Background

The Impella 2.5 axial flow pump, which is positioned across the aortic valve, is widely employed for hemodynamic support. The present study compared structural and functional integrity of the left heart valves in patients undergoing Impella vs intra‐aortic balloon pump in the randomized PROTECT II trial.

Methods and Results

Transthoracic echocardiograms were performed at baseline, 1 and 3 months in 445 patients in the PROTECT II trial. Serial studies were analyzed by an independent echocardiography core laboratory for aortic and mitral valve structure and function, and left ventricular ejection fraction (LVEF). During Impella support there was no appreciable change in the degree of baseline valvular regurgitation. There were no cases of structural derangement of the mitral or aortic valve after use of the Impella device. At 90‐day follow‐up, there was an average 22% relative increase in LVEF from baseline (27% ± 9 vs. 33% ± 11, P < 0.001).

Conclusions

The present echocardiographic analysis of the PROTECT II study confirms prior observations regarding the safety of the Impella 2.5 device with respect to mitral and aortic valve function.
Subcutaneous defibrillator implantation as a bridge until left ventricular function normalizes
Authors: Bisignani Antonio , De Bonis Silvana , San Pasquale Giovanni , Candreva Laura , Franchin Cristina , Malacrida Maurizio , Bisignani Giovanni
Published: October 2017

Key Clinical Message

Patients with reversible cardiac impairment may be, at least temporarily, at high risk of SCD and may go unprotected for considerable time. A less‐invasive definitive or bridge solution is the implantation of a subcutaneous cardioverter–defibrillator (S‐ICD). The less invasiveness of this procedure ensures easy removal of the system without exposing the patient to the risk of complications.
Aza versus Oxophilicity of SmI2: A Break of a Paradigm
Authors: Maity Sandeepan , Flowers Robert A. , Hoz Shmaryahu
Published: October 2017

Ligands that coordinate to SmI2 through oxygen are prevalent in the literature and make up a significant portion of additives employed with the reagent to perform reactions of great synthetic importance. In the present work a series of spectroscopic, calorimetric and kinetic studies demonstrate that nitrogen‐based analogues of many common additives have a significantly higher affinity for Sm than the oxygen‐based counterparts. In addition, electrochemical experiments show that nitrogen‐based ligands significantly enhance the reducing power of SmI2. Overall, this work demonstrates that the use of nitrogen‐based ligands provides a useful alternative approach to enhance the reactivity of reductants based on SmII.
Enantioseparation of racecadotril using polysaccharide‐type chiral stationary phases in polar organic mode
Authors: Szabó Zoltán‐István , Foroughbakhshfasaei Mohammadhassan , Noszál Béla , Tóth Gergő
Published: October 2017

Enantioseparation of the antidiarrheal drug, racecadotril, was investigated by liquid chromatography using polysaccharide‐type chiral stationary phases in polar organic mode. The enantiodiscrimininating properties of 4 different chiral columns (Chiralpak AD, Chiralcel OD, Chiralpak AS, Chiralcel OJ) with 5 different solvents (methanol, ethanol, 1‐propanol, 2‐propanol, and acetonitrile) at 5 different temperatures (5–40 °C) were investigated. Apart from Chiralpak AS column the other 3 columns showed significant enantioseparation capabilities. Among the tested mobile phases, alcohol type solvents were superior over acetonitrile, and significant differences in enantioselective performance of the selector were observed depending on the type of alcohol employed. Van't Hoff analysis was used for calculation of thermodynamic parameters which revealed that enantioseparation is mainly enthalpy controlled; however, enthropic control was also observed. Enantiopure standard was used to determine the enantiomer elution order, revealing chiral selector—and mobile‐phase dependent reversal of enantiomer elution order. Using the optimized method (Chiralcel OJ stationary phase, thermostated at 10 °C, 100% methanol, flow rate: 0.6 mL/min) baseline separation of racecadotril enantiomers (resolution = 3.00 ± 0.02) was achieved, with the R‐enantiomer eluting first. The method was validated according to the ICH guidelines, and its application was tested on capsule and granules containing the racemic mixture of the drug.
Anger and depressive ruminations as predictors of dysregulated behaviours in borderline personality disorder
Authors: Martino Francesca , Caselli Gabriele , Di Tommaso Jessica , Sassaroli Sandra , Spada Marcantonio M. , Valenti Barbara , Berardi Domenico , Sasdelli Anna , Menchetti Marco
Published: October 2017

Background

Anger and depressive ruminations have recently received empirical attention as processes related to borderline personality disorder (BPD). The Emotional Cascade Model (Selby, Anestis, & Joiner, 2008) suggests that negative affect (such as anger and sadness) may trigger rumination, which in turn may increase the duration and extent of negative affect, leading to dysregulated behaviours aimed at reducing such intense and unpleasant emotions.

Aim

The aim of this study is to explore the relationships between emotional dysregulation, anger and depressive ruminations, and their role in predicting dysregulated behaviours (such as aggression and self‐harm) in a clinical sample of patients with BPD.

Methods

Ninety‐one patients with a diagnosis of BPD were recruited from three outpatient community mental health centres and asked to complete a comprehensive assessment for personality disorder symptoms, emotion dysregulation, anger and depressive ruminations, aggression, and self‐harm.

Results

Anger and depressive ruminations were found to be significantly associated to, respectively, self‐harm and aggression, beyond the variance accounted by emotional dysregulation.

Conclusions

Rumination may act as a mediator between emotional dysregulation and dysregulated behaviours in BPD. Future research should examine whether clinical techniques aimed at reducing rumination may be helpful in reducing dysregulated behaviours in patients with BPD.
European Marketing Authorizations Granted Based on a Single Pivotal Clinical Trial: The Rule or the Exception?
Authors: Morant Anne Vinther , Vestergaard Henrik Tang
Published: October 2017

A minimum of two positive, adequate, and well‐controlled clinical trials has historically been the gold standard for providing substantial evidence to support regulatory approval of a new medicine. Nevertheless, the present analysis of European Marketing Authorizations granted between 2012 and 2016 showed that 45% of new active substances were approved based on a single pivotal clinical trial. For therapeutic areas such as oncology and cardiovascular diseases, approvals based on a single pivotal trial are the rule rather than the exception, whereas new medicines within the nervous system area were generally supported by two or more pivotal trials. While overall similar trends have been observed in the US, the recent US Food and Drug Administration approvals of nervous system medicines based on a single pivotal trial suggest that a case‐by‐case scientific evaluation of the totality of evidence is increasingly applied to facilitate faster access of new medicines to patients suffering from serious diseases.
Observation of arc modes in a magnetically rotating arc plasma generator
Authors: Wang Cheng , Cui Haichao , Zhang Zelong , Xia Weiluo , Xia Weidong
Published: October 2017

An arc plasma can present various forms under the influence of an external magnetic field. In this study, a magnetically rotating arc plasma generator has been developed to produce three arc modes, namely rigid arc, distorted arc, and diffuse arc, which are obtained by controlling the gas flow rate. The evolution of these arc modes are experimentally studied and discussed. Results show that, as the gas flow rate increases, the arc mode is first transformed from the rigid to the distorted mode, and then to the diffuse mode. Comparisons show that the location of the arc attachment is a key factor in determining the rigid and distorted modes. The diffuse arc is observed under larger gas flow rates, but the completely diffuse arc can exist only within a narrow range of gas flow rates. Compared to the distorted arc, the diffuse arc has not only better stability but also a wider high‐temperature plasma zone, which indicates that the diffuse mode may be more useful in industry.
Disseminated histoplasmosis in an immuno‐competent young male: Role of bone marrow examination in rapid diagnosis
Authors: Shaikh Muhammad Shariq , Majeed Memon Ayesha
Published: October 2017

Fungal infections are usually seen in elderly or immuno‐compromised individuals particularly with human immunodeficiency virus infection. In immuno‐competent individuals, they seldom present with overt clinical symptoms. In such cases diagnosis is made by combination of tests along with direct microscopic visualization of the organism. We present a case of immuno‐competent individual who presented with unexplained fever and found to have Histoplasma capsulatum infection on bone marrow examination.
Variation in reproductive isolation across a species range
Authors: Barnard‐Kubow Karen B. , Galloway Laura F.
Published: October 2017

Reproductive isolation is often variable within species, a phenomenon that while largely ignored by speciation studies, can be leveraged to gain insight into the potential mechanisms driving the evolution of genetic incompatibilities. We used experimental greenhouse crosses to characterize patterns of reproductive isolation among three divergent genetic lineages of Campanulastrum americanum that occur in close geographic proximity in the Appalachian Mountains. Substantial, asymmetrical reproductive isolation for survival due to cytonuclear incompatibility was found among the lineages (up to 94% reduction). Moderate reductions in pollen viability, as well as cytoplasmic male sterility, were also found between some Mountain populations. We then compared these results to previously established patterns of reproductive isolation between these Mountain lineages and a fourth, widespread Western lineage to fully characterize reproductive isolation across the complete geographic and genetic range of C. americanum. Reproductive isolation for survival and pollen viability was consistent across studies, indicating the evolution of the underlying genetic incompatibilities is primarily determined by intrinsic factors. In contrast, reproductive isolation for germination was only found when crossing Mountain populations with the Western lineage, suggesting the underlying genetic incompatibility is likely influenced by environmental or demographic differences between the two lineages. Cytoplasmic male sterility was also limited in occurrence, being restricted to a handful of Mountain populations in a narrow geographic range. These findings illustrate the complexity of speciation by demonstrating multiple, independent genetic incompatibilities that lead to a mosaic of genetic divergence and reproductive isolation across a species range.
Climate drives phenological reassembly of a mountain wildflower meadow community
Authors: Theobald Elli J. , Breckheimer Ian , HilleRisLambers Janneke
Published: October 2017

Spatial community reassembly driven by changes in species abundances or habitat occupancy is a well‐documented response to anthropogenic global change, but communities can also reassemble temporally if the environment drives differential shifts in the timing of life events across community members. Much like spatial community reassembly, temporal reassembly could be particularly important when critical species interactions are temporally concentrated (e.g., plant‐pollinator dynamics during flowering). Previous studies have documented species‐specific shifts in phenology driven by climate change, implying that temporal reassembly, a process we term “phenological reassembly,” is likely. However, few studies have documented changes in the temporal co‐occurrence of community members driven by environmental change, likely because few datasets of entire communities exist. We addressed this gap by quantifying the relationship between flowering phenology and climate for 48 co‐occurring subalpine wildflower species at Mount Rainier (Washington, USA) in a large network of plots distributed across Mt. Rainier's steep environmental gradients; large spatio‐temporal variability in climate over the 6 yr of our study (including the earliest and latest snowmelt year on record) provided robust estimates of climate‐phenology relationships for individual species. We used these relationships to examine changes to community co‐flowering composition driven by ‘climate change analog’ conditions experienced at our sites in 2015. We found that both the timing and duration of flowering of focal species was strongly sensitive to multiple climatic factors (snowmelt, temperature, and soil moisture). Some consistent responses emerged, including earlier snowmelt and warmer growing seasons driving flowering phenology earlier for all focal species. However, variation among species in their phenological sensitivities to these climate drivers was large enough that phenological reassembly occurred in the climate change analog conditions of 2015. An unexpected driver of phenological reassembly was fine‐scale variation in the direction and magnitude of climatic change, causing phenological reassembly to be most apparent early and late in the season and in topographic locations where snow duration was shortest (i.e., at low elevations and on ridges in the landscape). Because phenological reassembly may have implications for many types of ecological interactions, failing to monitor community‐level repercussions of species‐specific phenological shifts could underestimate climate change impacts.
Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis
Authors: Ferreira João Pedro , Machu Jean‐Loup , Girerd Nicolas , Jaisser Frederic , Thum Thomas , Butler Javed , González Arantxa , Diez Javier , Heymans Stephane , McDonald Kenneth , Gyöngyösi Mariann , Firat Hueseyin , Rossignol Patrick , Pizard Anne , Zannad Faiez
Published: October 2017

Aims

Myocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European‐Commission‐funded ‘FIBROTARGETS’ is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti‐fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure.

Methods and results

The FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community‐based population cohorts, cardiovascular risk cohorts, and heart failure cohorts.

Conclusions

The FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific ‘fibrotic’ phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti‐fibrotic therapies for heart failure.
An All‐in‐One Molecule for the One‐Step Synthesis of Functional Hybrid Silica Particles with Tunable Sizes
Authors: Graffion Julien , Dems Dounia , Demirelli Mesut , Coradin Thibaud , Delsuc Nicolas , Aimé Carole
Published: October 2017

Spherical particles with well‐defined diameters were obtained by self‐assembly of trityl‐based molecules. Thanks to the robustness of the organic scaffold, a variety of modifications could be covalently introduced into the network so as to stabilize the supramolecular structure by a sol–gel route. Using supramolecular chemistry, we showed that the synthesis of hybrid small molecules allowed engineering nanomaterials with tunable size and functionality. The use of a combination of different characterization techniques, including dynamic light scattering, cryoTEM, and solid‐state NMR spectroscopy, provided careful understanding of the relationship between the molecular and supramolecular structures for further chemical engineering of supramolecular hybrid materials.
Influence of Porosity on Product Distribution over Co/H‐ZSM‐22 Catalysts in the Upgrading of Palmitic Acid
Authors: Liu Mingjuan , Shi Yanchun , Bi Yunfei , Xing Enhui , Wu Yulong , Huang Shaobin , Yang Mingde
Published: October 2017

The catalytic conversion of palmitic acid was studied over Co/SiO2, H‐ZSM‐22 (HZ‐22), Co/H‐ZSM‐22 (Co/HZ‐22), mesoporous H‐ZSM‐22 (HZP‐22), and Co/H‐ZSM‐22 (Co/HZP‐22) catalysts. For the bifunctional catalysts, on the one hand, the porosity of zeolitic supports provided uniform accommodation for Co particles to realize the good distribution and downsizing of metal particles; on the other hand, the impregnation of Co into zeolitic supports improved the acidity of bifunctional catalysts that presented more weak/strong acid sites and stronger acid strength. Compared to sole metal centers over Co/SiO2 (no isomerization), the hydrodeoxygenation and hydroisomerization of palmitic acid were achieved simultaneously over bifunctional Co/HZ‐22 and Co/HZP‐22 catalysts (4 wt % Co loading) in one step. Mesoporous Co/HZP‐22 possessed an excellent catalytic performance during the upgrading of palmitic acid to yield the highest amount of iso‐alkanes. Importantly, the metal/zeolite bifunctional catalysts tailored the deoxygenation route significantly from hydrodecarbonylation (major) over sole metal catalysts or zeolites (only metal centers and only acid sites) to the hydrodeoxygenation route (major) over Co/zeolite bifunctional catalysts (both metal centers and acid sites).
A Simple Metric for Predicting Revenue from Electric Peak‐Shaving and Optimal Battery Sizing
Authors: Fisher Michael , Whitacre Jay , Apt Jay
Published: October 2017

A major use case for behind‐the‐meter (BTM) electricity storage is peak‐shaving for commercial and industrial customers who must pay peak‐demand charges. Quantifying the value proposition for individual customers currently requires an optimization model, the development of which can be costly in human and computing resources. We disclose here a simple econometric model to predict revenue from retail peak‐shaving. Geared toward electric utilities, third‐party storage providers, and consumers, this model eliminates the need to formulate a model in specialized optimization software. The model is based on a predictive metric that is derived from the building's load profile. During model fitting, we discovered that the revenue estimates generated are independent of the power capacity of the battery if the maximum power‐to‐energy ratio of the storage is held constant. This effect can be used to calculate the profit‐maximizing storage size, which we explore in a case study.
High-resolution mass spectrometry of skin mucus for monitoring physiological impacts and contaminant biotransformation products in fathead minnows exposed to wastewater effluent
Authors: Mosley Jonathan D. , Ekman Drew R. , Cavallin Jenna E. , Villeneuve Daniel L. , Ankley Gerald T. , Collette Timothy W.
Published: October 2017

High-resolution mass spectrometry is advantageous for monitoring physiological impacts and contaminant biotransformation products in fish exposed to complex wastewater effluent. We evaluated this technique using skin mucus from male and female fathead minnows (Pimephales promelas) exposed to control water or treated wastewater effluent at 5, 20, and 100% levels for 21 d, using an on-site, flow-through system providing real-time exposure. Both sex-specific and non-sex–specific responses were observed in the mucus metabolome, the latter suggesting the induction of general compensatory pathways for xenobiotic exposures. Altogether, 85 statistically significant treatment-dependent metabolite changes were observed out of the 310 total endogenous metabolites that were detected (156 of the 310 were annotated). Partial least squares-regression models revealed strong covariances between the mucus metabolomes and up-regulated hepatic messenger ribonucleic acid (mRNA) transcripts reported previously for these same fish. These regression models suggest that mucus metabolomic changes reflected, in part, processes by which the fish biotransformed xenobiotics in the effluent. In keeping with this observation, we detected a phase II transformation product of bisphenol A in the skin mucus of male fish. Collectively, these findings demonstrate the utility of mucus as a minimally invasive matrix for simultaneously assessing exposures and effects of environmentally relevant mixtures of contaminants. Environ Toxicol Chem 2018;37:788–796. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Abstract

Xenobiotic transformation pathways may be impacted by the exposure of fathead minnows to treated wastewater effluent, as reflected in fish skin mucus measured with high resolution mass spectrometry-based metabolomics and identified in part with the mummichog program. Subsequent data mining resulted in the discovery of a phase II transformation product of bisphenol A in the skin mucus of male fish.
Taxonomic notes on Convolvulus sect. Serospinescentes (Convolvulaceae)
Authors: Ranjbar Massoud , Ezazi Atafeh , Ghahremaninejad Farrokh
Published: October 2017

In the present study the taxonomic status of the species belonging to Convolvulus L. sect. Serospinescentes Boiss. (Convolvulaceae) is presented using morphological characters of specimens from the authors’ expeditions and other herbarium collections. Most species of the section are endemic to Iran. C. sect. Serospinescentes is geographically restricted to the Oman Sea margin, S and SE Iran, NE Oman, Mediterranean Sea margin, NE Egypt, Palestine and Turkey. Two new taxa, C. bazmanensis Ranjbar, Ezazi & F.Ghahrem. and C. oxysepalus Boiss. subsp. neyrizensis Ranjbar & Ezazi, are described and illustrated. The former species is collected from Sistan and Baluchestan Province and the latter from Fars Province. C. virgatus subsp. subaphyllus Boiss. is reported as a new record for the flora of Iran. The subsection Serospinescentes is raised to the rank of Convolvulus sect. Serospinescentes. In addition, a taxonomic key, detailed morphometric descriptions, illustrations and distribution maps for all species of the section are provided. The conservation status of taxa is evaluated according to the IUCN Red List Categories and Criteria.
Intrathyroidal carotid artery and nonrecurring right recurrent laryngeal nerve: A case report
Authors: Baker Aaron , Cottrill Elizabeth E. , Munizza Olivia , McGillen Kathryn , McKinnon Tyler , Goldenberg David
Published: October 2017

Background

When performing thyroidectomy, knowledge of normal anatomy and variants is vital to avoid injuring nearby structures. Typically, the bilateral carotids course posterolateral to the thyroid gland. We describe a rare variant of an intrathyroidal carotid artery, not previously described in the literature.

Methods

A 23‐year‐old woman with a strong family history of thyroid cancer presented with a left thyroid nodule, and a fine‐needle aspiration biopsy revealing papillary thyroid carcinoma. She underwent total thyroidectomy.

Results

Intraoperatively, the carotid was found coursing centrally through the right lobe parenchyma, associated with an ipsilateral nonrecurrent recurrent laryngeal nerve (NRLN) entering the cricothyroid joint superolaterally.

Conclusion

This is, to our knowledge, the first report of such an anatomic variant in the medical literature. Aberrant carotid artery anatomy may potentially cause life‐threatening surgical complications and should be considered preoperatively. Furthermore, recognition of concurrent recurrent laryngeal nerve (RLN) anomalies with vascular variations allows identification of nonrecurrent nerves.
Too many and too few: The paradoxical case of physicians in the Russian Federation
Authors: Gerry Christopher J. , Sheiman Igor
Published: October 2017

There is a paradox characterising the Russian health workforce. By international standards, Russia has a very high number of physicians per capita but at the same time is confronted by chronic real shortages of qualified physicians. This paper explores the reasons for this paradox by examining the structural characteristics of health workforce development in the context of the Soviet legacy and the comparative performance of other European countries. The paper uses data on comparative health workforce dynamics to argue that Russia is a European laggard, before then evaluating recent and current policies within that context. The health workforce challenges facing all low‐ and middle‐income countries are acute, and this paper confirms this IS the case for Russia—Europe's largest country. The paper argues that the physician shortage is driven by the model of health workforce development inherited from the Soviet period, with its emphasis on quantitative rather than structural indicators. We find that, in contrast to most European Union countries, Russia's stalled reform process leaves it facing a chronic shortage of appropriately trained physicians. We document the costs of failed and slow reforms during the last 2 decades, while cautiously welcoming some recent policy initiatives.
Impact of clinicopathological characteristics on the efficacy of neoadjuvant therapy in patients with human epidermal growth factor receptor‐2‐positive breast cancer
Authors: Zhao Bin , Zhao Hong
Published: October 2017

Neoadjuvant therapy has become increasingly common in human epidermal growth factor receptor‐2 (HER2)‐positive breast cancer. In this study, we examined the impact of different clinicopathological characteristics on pathological complete response (pCR) in patients treated with anti‐HER2 agents. The PubMed and Embase databases were searched from inception through April 2017 to identify studies that met pre‐specified criteria. The odds ratios (ORs) and 95% confidence intervals (CIs) were extracted directly or were calculated with other available information. Eleven randomized controlled trials (RCTs) that involved 3,269 HER2‐positive women were included in this meta‐analysis. Patients with hormone receptor (HR)‐negative breast cancer benefited more from anti‐HER2 therapy than did patients with HR‐positive tumours (OR, 2.25; 95% CI, 1.93‐2.62). Furthermore, this improvement in pCR was independent of anti‐HER2 agents, phase, combined chemotherapy, neoadjuvant duration, year the trials started and region where the trials were conducted. Patients with small tumours achieved greater benefits than patients with large tumours (OR, 1.25; 95% CI, 1.00‐1.55). Age did not predict an additional benefit from anti‐HER2 neoadjuvant treatment (OR, 1.02; 95% CI, 0.73‐1.45). The impact of nodal status on pCR was dependent on the anti‐HER2 agents. In conclusion, for HER2‐targeted neoadjuvant treatment in breast cancer, greater benefits were achieved in patients with small HR‐negative tumours compared with patients with large HR‐positive tumours. These results may improve drug development and treatment strategies, economic analyses and the design and interpretation of clinical trials.
SNP mutations occurring in thyroid hormone receptor influenced individual susceptibility to triiodothyronine: Molecular dynamics and site‐directed mutagenesis approaches
Authors: Liu Yaquan , Qu Kaili , Hai Ying , Li Xin , Zhao Lei , Zhao Chunyan
Published: October 2017

The increasing evidences have suggested that expression of single nucleotide polymorphisms (SNP) coded thyroid hormone receptors (THR) generally are associated with individual susceptibility to chemicals. In the present research, multiple molecular dynamics simulations on four SNP mutants (G332R, T337Δ, G345R, and G347E) were performed to investigate the structural and dynamical altering, which could lead to a binding capability variation to triiodothyronine (T3). It proved the structures of two SNP mutants (G345R and T337Δ) occurring in the THR proteins had experienced conformational change to a great extend, which also led to a significant decreasing in binding ability with T3. In addition, two mutates (G345R and G347E) and wild type THR proteins were expressed and purified based on site‐directed mutagenesis technology to test their binding abilities with T3 by fluorescence experiments. The fluorescence quenching efficiencies of two mutates displayed that the conjugation with T3 decreased with a significant rate in G345R system and a little rate in G347E system compared with its wild type. It was consistent with the molecular dynamic research that the SNP mutations did change structures of THR protein, and thereby decreased the binding behavior of T3 at different extent. The overall molecular‐level look at the protein structure may provide the structural basis to explain how one amino acid change can create a ripple effect on the protein structures and eventually affect the binding affinity of the ligands, which maybe the first stage to understand how SNP mutation results in individual difference in susceptibility to variant chemicals.
Antinociceptive Effects of S(+)‐Ketoprofen and Other Analgesic Drugs in a Rat Model of Pain Induced Uric Acid
Authors: López-Muñoz Francisco Javier , Ventura Rosa , Díaz M. Irene , Fernández-Guasti Alonso , Tost Digna , Cabré Francesc , Mauleón David
Published: October 2017

We investigated the antinociceptive properties of dexketoprofen trometamol (S(+)‐ketoprofen tromethamine salt; SKP), a new analgesic, antiinflammatory drug, using the pain‐induced functional impairment model in the rat (PIFIR), an animal model of arthritic pain. SKP was compared with racemic ketoprofen tromethamine salt (rac‐KP), R(−)‐ketoprofen tromethamine salt (RKP), ketorolac (KET), and morphine (MOR). We also assessed the effects of flurbiprofen (rac‐FB) and its enantiomers (SFB and RFB) in the same model. Groups of six rats received either vehicle or analgesic drug and antinociception was evaluated by evaluating the dose‐response curves over time. SKP was an effective antinociceptive drug in this model and was almost equally potent by either oral or intracerebroventricular administration. The oral potency of SKP was similar to that of oral KET and greater than that of oral MOR. No significant differences were observed between racemic ketoprofen and its enantiomers when administered orally. In the rat, significant bioinversion of RKP to SKP occurs when RKP is given orally. After oral administration of RKP, SKP was detectable in 30 min and surpassed the concentration of RKP after 3 h. Nevertheless, when the compounds were given intracerebroventricularly, some stereoselectivity in favor of SKP was observed. Stereoselectivity was observed with flurbiprofen, an analogue of ketoprofen that does not undergo significant metabolic inversion. Whereas SFB was an effective antinociceptive, RFB had no antinociceptive effect at the doses tested when given either orally or intracerebroventricularly.