bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Secondary and Tertiary Oxime Carbamate Derivatives and their Structure‐Dependent Bioactivity
Authors: Sivakumar Rajamanickam , Thanikachalam Venugopal , Kim Bong‐Gi , Kim Sung Dong
Published: June 2017

Biologically active novel piperidin‐4‐one oxime carbamates were synthesized from 3‐ethyl‐1‐methyl‐2,6‐diphenylpiperidin‐4‐one oxime, 1,1′‐carbonyldiimidazole (CDI), and primary or secondary amines in the presence of sodium hydride as base. Commercially available, cheaper, and safer CDI was utilized as carbonyl source, instead of toxic phosgene/triphosgene and carbon monoxide. The devised method is feasible for primary and secondary amines to make their corresponding oxime carbamate derivatives, through oxime–imidazolide intermediate, in high yield. When the antimicrobial activity of obtained oxime carbamate derivatives was investigated in comparison with streptomycin and amphotericin B as standards, the oxime carbamate containing heteroaromatic thiazole ring exhibits outstanding antimicrobial effectiveness, regardless of bacterial or fungal types.
Radiation from accelerated electrons: Simulation in four‐dimensions
Authors: Fazarinc Zvonko
Published: June 2017

This educational paper caters to engineers wishing to penetrate the complexity of electrodynamics. Only a computer simulation can provide the fourth dimension and to justify the title we develop the linkage between the theory and the relevant executable algorithms. These can provide unique insights into the internal events and a temporal evolution can lead to a deeper understanding of radiation phenomena arising from nature's first principles. There is no escape from the relativistic overhead associated with motion and some effort is expended on supporting the uninitiated reader.
GPMS: An educational supportive graduation project management system
Authors: Awad Mamoun
Published: June 2017

Senior Graduation Project highlights a significant milestone for undergraduate and graduate students in their journey of perusing their scientific degrees. It is considered a must‐complete requirement in most colleges. No doubt that managing the educational tasks, such as selecting projects, creating rubrics, scheduling, submitting reports, resource managements, assessment, etc., involved in senior projects can be challenging for students and educators. In this paper, we present an innovative Graduation Project Management System (GPMS) to keep track of different senior project educational processes starting from selecting projects going through grading until assessment. GPMS is equipped with data analytic gadget to monitor students’ pedagogical habits. This online system is based on open source technologies, namely, Java, Apache/Tomcat, WEKA, and MySql database management system (DBMS), and it is very flexible, adaptable, and configurable for most colleges.
Angupyrones A – E, α‐Pyrone Analogues with ARE‐Activation from a Sponge‐Associated Fungus Truncatella angustata
Authors: Zhao Yang , Liu Dong , Proksch Peter , Yu Siwang , Lin Wenhan
Published: June 2017

TLC‐DPPH guided fractionation of a sponge‐associated fungus Truncatella angustata with a solid culture resulted in the isolation of five new α‐pyrone‐based analogues namely angupyrones A – E (1 – 5), and 3‐ethyl‐4‐hydroxy‐6‐methyl‐2‐pyrone. Their structures were determined on the basis of extensive spectroscopic analyses, including the modified Mosher's method, bulkiness rule, and specific rotation for the configurational assignments. Angupyrones A – E exhibited moderate antioxidant response element activation in HepG2C8 cells, while the preliminary structure‐activity relationship was discussed.
A novel mechanical mitral valve replacement using Sapien XT
Authors: Koehle Megan , Strote Justin A. , Guadagnoli Mark , Oldemeyer J. Bradley
Published: June 2017

Patient Presentation

We report the case of a 66 year old female who presented to our institution fourteen years after receiving a St. Jude Mechanical Mitral Valve Replacement. She presented in refractory NYHA class IV congestive heart failure with comorbidities of acute renal failure, liver failure, and mental status changes. She was found to have immobility of one of the mitral valve disks with resultant severe mitral stenosis with a mean pressure gradient of 12 mmHg.

Evaluation and Management

The patient was found to have an STS predicted mortality of 39% with redo surgical MVR, and evaluation by the valve team led to a recommendation of a hybrid surgical and transcatheter procedure. The patient underwent femoral bypass and hypothermia with a sternotomy and left atrial approach. The mechanical discs were removed utilizing needle drivers without removal of the St. Jude ring. Subsequently, a 26 mm Edwards Sapien XT valve was deployed under direct and fluoroscopic visualization.

The patient had an event free post‐operative course, and one year following the procedure has had an outstanding clinical response with NYHA class II congestive heart failure. Her echocardiogram reveals normal valve function with a MPG of 4 mmHg without mitral regurgitation.

Conclusion

Transatrial hybrid TMVR within the ring of a St. Jude mechanical mitral valve appears to be a feasible procedure which may be used in the future to decrease morbidity and mortality associated with high‐risk redo‐MVR in patients with mechanical mitral valve prostheses.
Nondisclosure in Triadic Supervision: A Phenomenological Study of Counseling Students
Authors: Lonn Marlise R. , Juhnke Gerald
Published: June 2017

Triadic supervision is common within counselor training; however, limited research in professional counseling literature exists describing counseling students' experiences of choosing what to disclose within triadic supervision. Using transcendental phenomenological research, the authors investigated supervisees' nondisclosure within triadic supervision. Critical nondisclosure themes were relationships, presence of peer, and sharing time.
Applying Information Processing Theory to Supervision: An Initial Exploration
Authors: Tangen Jodi L. , Borders L. DiAnne
Published: June 2017

Although clinical supervision is an educational endeavor (Borders & Brown, ), many scholars neglect theories of learning in working with supervisees. The authors describe 1 learning theory—information processing theory (Atkinson & Shiffrin, , ; Schunk, )—and the ways its associated interventions may enhance the supervision enterprise.
Advisory Relationship as a Moderator Between Research Self‐Efficacy, Motivation, and Productivity Among Counselor Education Doctoral Students
Authors: Kuo Patty Beyrong , Woo Hongryun , Bang Na Mi
Published: June 2017

The authors examined the relationship between research self‐efficacy, motivation, and productivity, as well as advisory relationship as a moderator, among 190 counselor education doctoral students. Research self‐efficacy and motivation predicted productivity. Advisory relationship moderated the relationship between intrinsic and failure avoidance motivation and productivity.
The Synthesis and Evaluation of Fluoro‐, Trifluoromethyl‐, and Iodomuscimols as GABA Agonists
Authors: Abdul Manan Mohd Abdul Fatah , Cordes David B. , Slawin Alexandra M. Z. , Bühl Michael , Liao Vivian W. Y. , Chua Han. C. , Chebib Mary , O'Hagan David
Published: June 2017

Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABAA receptors. Only the C‐4 fluorine‐containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (α1β2γ2) and extrasynaptic (α4β2γ) GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α4β2γ) receptor.
Electrochemical Graphitization: An Efficient Conversion of Amorphous Carbons to Nanostructured Graphites
Authors: Jin Xianbo , He Rui , Dai Sheng
Published: June 2017

This concept paper describes a new electrochemical method for the graphitization of amorphous carbons. The graphitization is achieved by a simple cathodic polarization of the carbons at merely ≈1100 K in molten CaCl2. This electrochemical process is applicable to both graphitizable and non‐graphitizable carbons, generating porous graphitic structures of high‐crystallinity nanosheets. The transformation of carbon blacks, microspheres, and fibers to porous graphites, hollow graphite spheres, and pipes with porous shells have been demonstrated and the potential graphitization mechanism discussed.
Allosteric Modulation of Human Serum Albumin Induced by Peptide Ligand
Authors: Hou Jingfei , Peng Jiaxi , Yu Yue , Lin Yuchen , Liu Changliang , Duan Hongyang , Yang Yanlian , Wang Chen
Published: June 2017

Human serum albumin (HSA) is an abundant protein in plasma that can bind and transport many small molecules, and the corresponding affinity‐controlled drug delivery shows great advantage in the biological system. Peptide SA06 is a reported ligand comprising 20 amino acids, and is known to non‐covalently bind with HSA to extend the lifetime and improve the pharmacokinetic performance. The structural information of the HSA‐peptide complex is keen for obtaining molecular insight of the binding mechanism. We studied the secondary structural change and structure‐affinity relations of Peptide SA06 with HSA by using circular dichroism (CD) spectroscopy in solution. Noticeable allosteric effect can be identified by compositional increase of α‐helix structures when the peptide was co‐incubated with HSA. Furthermore, the equilibrium dissociation constant of Peptide SA06 with HSA can be determined by CD‐based method. This work provides structural evidence on the allosteric interaction between peptide ligand and HSA, and sheds light on optimization of therapeutic properties in the affinity‐controlled delivery systems.
Navigating air travel and cardiovascular concerns: Is the sky the limit?
Authors: Hammadah Muhammad , Kindya Bryan R. , Allard‐Ratick Marc P. , Jazbeh Sammer , Eapen Danny , Wilson Tang W.H. , Sperling Laurence
Published: June 2017

As the population ages and our ability to care for patients with cardiac disease improves, an increasing number of passengers with cardiovascular conditions will be traveling long distances. Many have had cardiac symptoms, recent interventions, devices, or surgery. Air travel is safe for most individuals with stable cardiovascular disease. However, a thorough understanding of the physiologic changes during air travel is essential given the potential impact on cardiovascular health and the risk of complications in passengers with preexisting cardiac conditions. It is important for clinicians to be aware of the current recommendations and precautions that need to be taken before and during air travel for passengers with cardiovascular concerns.
Heart failure in patients admitted for acute coronary syndromes: A report from a large national registry
Authors: Jeger Raban V. , Pfister Otmar , Radovanovic Dragana , Eberli Franz R. , Rickli Hans , Urban Philip , Pedrazzini Giovanni , Stauffer Jean‐Christophe , Nossen Jörg , Erne Paul ,   for the AMIS‐Plus Investigators
Published: June 2017

Background

Data on temporal trends of heart failure (HF) in acute coronary syndrome (ACS) are scarce.

Hypothesis

Improved treatment options may have led to lower case‐fatality rates (CFRs) during the last years in ACS complicated by HF.

Methods

Patients of the nationwide Acute Myocardial Infarction in Switzerland (AMIS)–Plus ACS registry were analyzed from 2000 to 2014.

Results

Of 36 366 ACS patients, 3376 (9.3%) had acute or chronic HF, 2111 (5.8%) de novo acute HF (AHF), 964 (2.7%) chronic HF (CHF), and 301 (0.8%) acute decompensated CHF (ADCHF). In‐hospital CFRs were highest in patients with ADCHF (32.6%) and de novo AHF (29.7%), followed by patients with CHF (12.9%) and without HF (3.2%, P < 0.001). Although in‐hospital CFRs gradually decreased in CHF patients (14.3% to 4.5%, P = 0.003) and patients without HF (3.5% to 2.2%, P < 0.001), they remained high in patients with ADCHF (36.4% to 40.0%, P = 0.45) and de novo AHF (50.0% to 29.4%, P = 0.37). Although there was an increase in specific ACS therapies in the cohort over time, ACS patients with HF received significantly less pharmacological and interventional ACS therapies than patients without HF. There was no significant change in HF medication rates except less frequent use of β‐blockers and diuretics in de novo AHF patients in recent years.

Conclusions

HF is present in 1 out of 10 patients presenting with ACS and is associated with high in‐hospital CFRs, particularly in acute HF. Although advances in ACS therapy improved in‐hospital CFRs in patients with no HF or CHF, CFRs remained unchanged and high in patients with acute HF and ACS over the last decade.
Synthesis and Biological Evaluation of Glycyrrhetic Acid Derivatives as Potential VEGFR2 Inhibitors
Authors: Yan Tian‐Long , Bai Li‐Fei , Zhu Hai‐Liang , Zhang Wei‐Ming , Lv Peng‐Cheng
Published: June 2017

Vascular endothelial growth factor receptor 2 (VEGFR2) has been proven to play a major role in the regulation of tumor angiogenesis. A series of novel glycyrrhetic acid derivatives were synthesized and evaluated for their VEGFR2 inhibitory activity as well as their antiproliferative properties against four cancer cell lines (MCF‐7, HeLa, HepG2, and A549). In vitro biological evaluations against these human tumor cell lines indicate that most of the prepared compounds have antiproliferative activities; compound 3 a (3β‐hydroxy‐30‐(4‐phenyl‐1‐piperazinyl)olean‐12‐ene‐11,30‐dione) exhibited the best inhibitory activity against MCF‐7 cells, with an IC50 value of 1.08 μm. Compound 3 a also showed the most potent inhibitory activity against VEGFR2 tyrosine kinase, with an IC50 value of 0.35 μm. Docking simulations were performed with the aim of discovering the binding mode of compound 3 a, and the results indicate that 3 a could bind at the VEGFR2 active site.
Searching for Novel Inhibitors of the S. aureus NorA Efflux Pump: Synthesis and Biological Evaluation of the 3‐Phenyl‐1,4‐benzothiazine Analogues
Authors: Felicetti Tommaso , Cannalire Rolando , Burali Maria Sole , Massari Serena , Manfroni Giuseppe , Barreca Maria Letizia , Tabarrini Oriana , Schindler Bryan D. , Sabatini Stefano , Kaatz Glenn W. , Cecchetti Violetta
Published: June 2017

Bacterial resistance to antimicrobial agents has become an increasingly serious health problem in recent years. Among the strategies by which resistance can be achieved, overexpression of efflux pumps such as NorA of Staphylococcus aureus leads to a sub‐lethal concentration of the antibacterial agent at the active site that in turn may predispose the organism to the development of high‐level target‐based resistance. With an aim to improve both the chemical stability and potency of our previously reported 3‐phenyl‐1,4‐benzothiazine NorA inhibitors, we replaced the benzothiazine core with different nuclei. None of the new synthesized compounds showed any appreciable intrinsic antibacterial activity, and, in particular, 2‐(3,4‐dimethoxyphenyl)quinoline (6 c) was able to decrease, in a concentration‐dependent manner, the ciprofloxacin MIC against the norA‐overexpressing strains S. aureus SA‐K2378 (norA++) and SA‐1199B (norA+/A116E GrlA).
Synthesis and Antibacterial Activity of Polymerizable Acryloyloxyalkyltriethyl Ammonium Salts
Authors: Mancuso Raffaella , Amuso Roberta , Armentano Biagio , Grasso Giuseppe , Rago Vittoria , Cappello Anna Rita , Galiano Francesco , Figoli Alberto , De Luca Giorgio , Hoinkis Jan , Gabriele Bartolo
Published: June 2017

This study reports an efficient and practical synthetic approach for the synthesis of a particularly important class of polymerizable quaternary ammonium salts (PQASs), that is, acryloxyalkyltriethylammonium bromides (AATEABs), which may find application as antimicrobial coatings for commercial membranes with antifouling and anti‐biofouling properties, to be used for wastewater treatment. The synthetic method is based on a simple two‐step procedure from commercially available substrates, entirely carried out under air and without any need for chromatographic purification. All the newly synthesized AATEABs were tested for their antimicrobial activity, and the results showed that AATEABs bearing an alkyl chain of 11 and particularly 12 carbon atoms possessed significant activity against Gram positive bacteria and yeast strains.
Digitizing Medicines for Remote Capture of Oral Medication Adherence Using Co‐encapsulation
Authors: Browne SH , Peloquin C , Santillo F , Haubrich R , Muttera L , Moser K , Savage GM , Benson CA , Blaschke TF
Published: June 2017

High‐resolution measurement of medication adherence is essential to personalized drug therapy. A US Food and Drug Administration (FDA)‐cleared device, using an edible ingestion sensor (IS), external wearable patch, and paired mobile device can detect and record ingestion events. Oral medications must be combined with an IS to generate precise “digitized‐medication” ingestion records. We developed a Good Manufacturing Practice protocol to repackage oral medications with the IS within certified Capsugel capsules, termed co‐encapsulation (CoE). A randomized bioequivalence study of CoE‐IS‐Rifamate (Isoniazid/Rifampin 150/300 mg) vs. native‐Rifamate was conducted in 12 patients with active Mycobacterium tuberculosis and demonstrated bioequivalence using the population method ratio test (95% confidence interval). Subsequently, CoE‐IS‐medications across all biopharmaceutical classes underwent in vitro dissolution testing utilizing USP and FDA guidelines. CoE‐IS medications tested met USP dissolution specifications and were equivalent to their native formulations. CoE combines oral medications with the IS without altering the quality of the native formulation, generating “digitized” medications for remote capture of dosing histories.
Preoperative evaluation of bone quality for dental implantation using an ultrasound axial transmission device in an ex vivo model
Authors: Okada Shinsuke , Kawano Akira , Oue Hiroshi , Takeda Yosuke , Yokoi Miyuki , Koretake Katsunori , Tsuga Kazuhiro
Published: June 2017

This study investigated the clinical utility of an ultrasound axial transmission device in preoperative evaluation of bone quality for dental implantation, by clarifying the relationship between cortical bone speed of sound (cSOS), insertion torque values (ITV), and implant stability quotient (ISQ) in porcine femur bone. Eleven fresh porcine femurs, without soft tissue, were prepared. The cSOS of these bones were measured using the axial transmission device. Bone mineral density (BMD) and porosity (Po) were measured in cortical bone samples obtained from the region of ultrasound measurements by X‐ray microcomputed tomography. Thirty‐three implants were inserted into these samples (three implants per bone sample), and ITV and ISQ were measured for all implants. Then, cortical bone thickness (CbTh) of the area for implantation was measured for all implants using a micrometer. The mean cSOS was 3962 m/s; mean BMD and Po were 0.822 g/cm2 and 0.185%, respectively. cSOS and BMD values were positively correlated, and cSOS values and Po values were negatively correlated. Mean ITV, ISQ, and CbTh were 37.95 Ncm, 71.172, and 2.869 mm, respectively. There was a positive correlation between cSOS values and ISQ values. The cSOS of each bone did not correlate with ITV for all of the bone samples. However, when the CbTh ranges from 3.0 to 3.5 mm, ITV are correlated with cSOS. These findings suggest that cSOS, which reflects the cortical bone quality, may be clinical utility as a preoperative diagnosis of the implant.
Evolutionary implications of Liebig's law of the minimum: Selection under low concentrations of two nonsubstitutable nutrients
Authors: Warsi Omar M. , Dykhuizen Daniel E.
Published: June 2017

Interactions between different axes of an organism's niche determine the evolutionary trajectory of a population. An extreme case of these interactions is predicted from ecological theory in Liebig's law of the minimum. This law states that in environments where multiple nutrients are in relatively low concentrations, only one nutrient will affect the growth of the organism. This implies that the evolutionary response of the population would be dictated by the most growth‐limiting nutrient. Alternatively, it is possible that an initial adaptation to the most limiting nutrient results in other nutrients present in low concentration affecting the evolutionary dynamics of the population. To test these hypotheses, we conducted twelve evolution experiments in chemostats using Escherichia coli populations: four under nitrogen limitation, four under magnesium limitation, and four in which both nitrogen and magnesium are in low concentrations. In the last environment, only magnesium seems to limit growth (Low Nitrogen Magnesium Limited environment, LNML). We observe a decrease in nitrogen concentration in the LNML environment over the course of our evolution experiment indicating that nitrogen might become limiting in these environments. Genetic reconstruction results show that clones adapted to magnesium limitation have genes involved in nitrogen starvation, that is, glnG (nitrogen starvation transcriptional regulator) and amtB (transport protein) to be upregulated only in the LNML environment as compared to magnesium‐limiting environments. Together, our results highlights that in low‐nutrient environments, adaptation to the growth‐limiting nutrient results in other nutrients at low concentrations to play a role in the evolutionary dynamics of the population.
Sociality influences thermoregulation and roost switching in a forest bat using ephemeral roosts
Authors: Russo Danilo , Cistrone Luca , Budinski Ivana , Console Giulia , Della Corte Martina , Milighetti Claudia , Di Salvo Ivy , Nardone Valentina , Brigham R. Mark , Ancillotto Leonardo
Published: June 2017

In summer, many temperate bat species use daytime torpor, but breeding females do so less to avoid interferences with reproduction. In forest‐roosting bats, deep tree cavities buffer roost microclimate from abrupt temperature oscillations and facilitate thermoregulation. Forest bats also switch roosts frequently, so thermally suitable cavities may be limiting. We tested how barbastelle bats (Barbastella barbastellus), often roosting beneath flaking bark in snags, may thermoregulate successfully despite the unstable microclimate of their preferred cavities. We assessed thermoregulation patterns of bats roosting in trees in a beech forest of central Italy. Although all bats used torpor, females were more often normothermic. Cavities were poorly insulated, but social thermoregulation probably overcomes this problem. A model incorporating the presence of roost mates and group size explained thermoregulation patterns better than others based, respectively, on the location and structural characteristics of tree roosts and cavities, weather, or sex, reproductive or body condition. Homeothermy was recorded for all subjects, including nonreproductive females: This probably ensures availability of a warm roosting environment for nonvolant juveniles. Homeothermy may also represent a lifesaver for bats roosting beneath loose bark, very exposed to predators, because homeothermic bats may react quickly in case of emergency. We also found that barbastelle bats maintain group cohesion when switching roosts: This may accelerate roost occupation at the end of a night, quickly securing a stable microclimate in the newly occupied cavity. Overall, both thermoregulation and roost‐switching patterns were satisfactorily explained as adaptations to a structurally and thermally labile roosting environment.
Seasonally contrasting responses of evapotranspiration to warming and elevated CO2 in a semiarid grassland
Authors: Sorokin Y. , Zelikova T. J. , Blumenthal D. , Williams D. G. , Pendall E.
Published: June 2017

Global climate change is expected to alter seasonal patterns and rates of evapotranspiration in dry regions. Although climate change will involve elevated CO2 and increased temperatures, independently, these factors may have different impacts on actual evapotranspiration (AET) due to their opposing effects on transpiration. We used canopy gas exchange chambers to quantify AET in a semiarid grassland experimentally altered by elevated CO2 and warming over 3 years with contrasting ambient precipitation. Seasonal and interannual variations in AET due to background climate variability were larger than the effects of climate manipulation treatments. However, in a year with average precipitation, cumulative growing season AET was suppressed by warming by 23%. Across years, warming increased AET early in the growing season and suppressed it later in the growing season. By contrast, elevated CO2 suppressed AET early in the growing season and enhanced it later, but only in years with average or above‐average precipitation. Vegetation greenness (a proxy for photosynthetically active leaf area) was consistently the strongest predictor of AET, whereas soil moisture and vapor pressure deficit were secondary drivers. Our research demonstrates that effects of increased atmospheric CO2 and temperature on AET will be mediated by plant phenological development and seasonal climatic conditions.
Reactivity of the 2‐Chloroazaborolyl Anion
Authors: Chen Peixing , Cui Chunming
Published: June 2017

The reactivity of the 2‐chloroazaborolyl anion (LBCl)[K(THF)] {1; L = [ArNC(R)CHC(R)]–; Ar = 2,6‐Me2C6H3, R = tBu} was investigated. Treatment of 1 with a diazomethane resulted in the formation of a donor‐stabilized iminoborane featuring an intramolecular donor‐stabilized B=N bond. Compound 1 readily reacted with chlorotriphenyltin to afford the new 1,2‐azaborolyl complex 3, whereas reactions with ortho‐quinone, azobenzene, and diphenyl disulfide led to the oxidative cycloaddition and cleavage of the disulfide S–S bond, with elimination of KCl.
Pesticides, environment, and food safety
Authors: Carvalho Fernando P.
Published: June 2017

Agrochemicals have enabled to more than duplicate food production during the last century, and the current need to increase food production to feed a rapid growing human population maintains pressure on the intensive use of pesticides and fertilizers. However, worldwide surveys have documented the contamination and impact of agrochemical residues in soils, and terrestrial and aquatic ecosystems including coastal marine systems, and their toxic effects on humans and nonhuman biota. Although persistent organic chemicals have been phased out and replaced by more biodegradable chemicals, contamination by legacy residues and recent residues still impacts on the quality of human food, water, and environment. Current and future increase in food production must go along with production of food with better quality and with less toxic contaminants. Alternative paths to the intensive use of crop protection chemicals are open, such as genetically engineered organisms, organic farming, change of dietary habits, and development of food technologies. Agro industries need to further develop advanced practices to protect public health, which requires more cautious use of agrochemicals through prior testing, careful risk assessment, and licensing, but also through education of farmers and users in general, measures for better protection of ecosystems, and good practices for sustainable development of agriculture, fisheries, and aquaculture. Enhanced scientific research for new developments in food production and food safety, as well as for environmental protection, is a necessary part of this endeavor. Furthermore, worldwide agreement on good agriculture practices, including development of genetically modified organisms (GMOs) and their release for international agriculture, may be urgent to ensure the success of safe food production.
Control‐Oriented Modeling of Non‐Adiabatic Solid Oxide Fuel Cell Stacks
Authors: Marra D. , Sorrentino M. , Pianese C. , Jensen K. J. N. L.
Published: June 2017

The paper presents a lumped zero dimensional (0D) model for the simulation of solid oxide fuel cell (SOFC) stack thermal dynamics. Particularly, a dedicated sub‐model is developed, via a mixed gray/black‐box modeling approach, to suitably treat the heat exchange mechanisms between the stack and its surrounding environment. Such a sub‐model was embedded into an existing 0D simulator and then tested via comparison with temperature sensor measurements. The hardware sensor is indeed particularly critical, due to its location and the typically high operating temperature characterizing SOFC. Therefore, suitable experimental transients were performed at Topsoe fuel cell test‐bench, thus allowing verifying the accuracy and generalization granted by the 0D model in reproducing stack outlet temperature trajectories, both in steady‐state and dynamic operations. As a result, the modeling approach here proposed is proven effective either to replace the hardware temperature sensor at stack outlet or for redundancy purposes to improve reliability. Moreover, the 0D model can be deployed for offline design of SOFC systems' control strategies, as well as for real‐time diagnostic and control applications.
SrCo0.85Fe0.15O2.62 – Oxygen Deficient “314‐type” Perovskite; a Highly Efficient Cathode for Solid Oxide Fuel Cells
Authors: Marik S. , Nicollet C. , Channabasappa M. , Fourcade S. , Wattiaux A. , Duttine M. , Decourt R. , Bassat J.‐M. , Toulemonde O.
Published: June 2017

Structure, electrical conductivity and electrochemical performance for a new oxygen deficient perovskite material with composition SrCo0.85Fe0.15O2.62 is explored here. It crystallizes in a “314‐type” oxygen‐vacancy ordered structure (Space Group: I4/mmm) with 2ap × 2ap × 4ap unit cell, and contains alternate oxygen replete [Co2/Fe2‐O] and oxygen deficient [Co1/Fe1‐O] planes along c‐direction. Room temperature Mössbauer spectroscopy and room temperature neutron powder diffraction confirm the presence of mixed valence states (3+ and 4+) for both Fe and Co. Polaronic behavior in the electrical conductivity is observed below 400 °C, and attributed to the presence of Co4+ and Fe3+ cations in the structure. The electrical conductivity at 600 °C is high enough (∼200 S cm−1) to act as a cathode material. At the same time, the polarization resistance measurements show an excellent value of 0.1 Ω cm2 at 600 °C. These results suggest that at 600 °C, this material is a mixed oxide‐ion and electronic conductor exhibiting excellent activity for the oxygen reduction reaction, making it a promising cathode material for an intermediate temperature solid oxide fuel cell.
Bioelectrochemical Dechlorination of 1,2‐DCA with an AQDS‐Functionalized Cathode Serving as Electron Donor
Authors: Leitão P. , Nouws H. , Danko A. S. , Aulenta F.
Published: June 2017

In the present study we describe a simple method to immobilize the redox mediator anthraquinone‐2,6‐disulfonate (AQDS) at the surface of graphite electrodes, by means of a commercial anion exchange membrane. Cyclic voltammetry experiments confirmed the efficacy of the immobilization protocol and the long‐term (over 70 days) electrochemical stability of the AQDS‐functionalized electrode. Potentiostatic (–300 mV vs. SHE) batch experiments proved the capability of the electrode in accelerating the bioelectrochemical reductive dechlorination of the groundwater contaminant 1,2‐dichloroethane (1,2‐DCA) to harmless ethene by a mixed microbial culture, by serving as electron donor in the process. Considering the reported broad range of anodic and cathodic reactions catalyzed by AQDS, the herein described functionalized electrode has a remarkable potential for application in the environmental and industrial sector.
Significant association between FOXP3 gene polymorphism and steroid‐resistant acute rejection in living donor liver transplantation
Authors: Verma Sapana , Tanaka Yuka , Shimizu Seiichi , Tanimine Naoki , Ohdan Hideki
Published: June 2017

Previous studies have found that preferential accumulation of regulatory T (Treg) cells in liver allografts during acute cellular rejection (ACR) is associated with less severe rejection, suggesting a role of Treg cells in preventing excessive progress of ACR. We investigated the impact of single nucleotide polymorphisms (SNPs) in the Forkhead box P3 (FOXP3) gene, a master regulator gene of Treg cells, on ACR severity in liver transplant (LT) recipients. In total, 102 living donor LT patients were enrolled in this study and categorized into no rejection (n = 86), steroid‐sensitive acute rejection (SSAR; n = 11), and steroid‐resistant acute rejection (SRAR; n = 5). FOXP3 SNPs –3499 A/G (rs3761547), –3279 A/C (rs3761548), and –924 A/G (rs2232365) were genotyped using the polymerase chain reaction restriction fragment length polymorphism technique. T‐cell responses to allostimulation were evaluated by the mixed lymphocyte reaction assay. We found no statistical association between the FOXP3 SNP genotype frequencies and ACR incidence. However, significantly higher incidence of SRAR was observed in LT patients with the FOXP3 rs3761548 A/C+A/A genotype than in those with the C/C genotype (A/C+A/A versus C/C; no rejection, SSAR, SRAR, 85.71%, 0%, 14.29% versus 83.58%, 16.42%, 0%, respectively; P =  0.0005). The mixed lymphocyte reaction assay performed at the time of ACR diagnosis showed higher anti‐donor CD4+ T‐cell responses in patients carrying rs3761548 A/C+A/A than in those with the C/C genotype (P =  0.019). No significant association was observed between the incidence of SRAR and either rs3761547A/G or rs2232365 A/G. Infectious complications and overall survival were not related to FOXP3 SNPs.

Conclusion: Our findings indicate that FOXP3 SNP rs3761548 A/C might be a predisposing factor for SRAR after liver transplantation. (Hepatology Communications 2017;1:406–420)
The challenge of complex drug use: Associated use of codeine‐containing medicines and new psychoactive substances in a European cross‐sectional online population
Authors: Kimergård Andreas , Foley Michelle , Davey Zoe , Wadsworth Elle , Drummond Colin , Deluca Paolo
Published: June 2017

Objective

Misuse of codeine‐containing medicines in combination with new psychoactive substances (NPS) is inadequately described. This study characterises codeine consumption amongst NPS users and non‐NPS users to provide warning of health issues.

Methods

Online survey conducted between July 2015 and March 2016.

Results

Out of 340 respondents, residing in a country in Europe and using codeine recently, 63.8% were female. Mean age: 34.9 years (SD = 12.4). Substance use included NPS (18.5%) and illicit controlled drugs (55.9%). Factors relating to codeine use found to significantly predict NPS use were consuming codeine extracted from combination tablets (OR = 16.79, 95% CI [8.67, 32.51]), obtaining codeine from friends, family, and acquaintances (OR = 3.98, 95% CI [1.82, 8.7]), use of illicit controlled drugs (OR = 34.99, 95% CI [8.39, 145.94]) and use of codeine to experience euphoria (OR = 6.41, 95% CI [3.42, 12.04]).

Conclusions

Amongst NPS users, codeine is less likely to be used daily but more likely to be used for recreational purposes. Smaller populations engaging in high‐risk use exist who take multiple drugs in high doses. Combinations of misused codeine and NPS highlight the need for policy to respond to a more complex drug situation.
Precision oncology based on omics data: The NCT Heidelberg experience
Authors: Horak Peter , Klink Barbara , Heining Christoph , Gröschel Stefan , Hutter Barbara , Fröhlich Martina , Uhrig Sebastian , Hübschmann Daniel , Schlesner Matthias , Eils Roland , Richter Daniela , Pfütze Katrin , Geörg Christina , Meißburger Bettina , Wolf Stephan , Schulz Angela , Penzel Roland , Herpel Esther , Kirchner Martina , Lier Amelie , Endris Volker , Singer Stephan , Schirmacher Peter , Weichert Wilko , Stenzinger Albrecht , Schlenk Richard F. , Schröck Evelin , Brors Benedikt , von Kalle Christof , Glimm Hanno , Fröhling Stefan
Published: June 2017

Precision oncology implies the ability to predict which patients will likely respond to specific cancer therapies based on increasingly accurate, high‐resolution molecular diagnostics as well as the functional and mechanistic understanding of individual tumors. While molecular stratification of patients can be achieved through different means, a promising approach is next‐generation sequencing of tumor DNA and RNA, which can reveal genomic alterations that have immediate clinical implications. Furthermore, certain genetic alterations are shared across multiple histologic entities, raising the fundamental question of whether tumors should be treated by molecular profile and not tissue of origin. We here describe MASTER (Molecularly Aided Stratification for Tumor Eradication Research), a clinically applicable platform for prospective, biology‐driven stratification of younger adults with advanced‐stage cancer across all histologies and patients with rare tumors. We illustrate how a standardized workflow for selection and consenting of patients, sample processing, whole‐exome/genome and RNA sequencing, bioinformatic analysis, rigorous validation of potentially actionable findings, and data evaluation by a dedicated molecular tumor board enables categorization of patients into different intervention baskets and formulation of evidence‐based recommendations for clinical management. Critical next steps will be to increase the number of patients that can be offered comprehensive molecular analysis through collaborations and partnering, to explore ways in which additional technologies can aid in patient stratification and individualization of treatment, to stimulate clinically guided exploratory research projects, and to gradually move away from assessing the therapeutic activity of targeted interventions on a case‐by‐case basis toward controlled clinical trials of genomics‐guided treatments.
Retrospective study of the prognostic significance of neutrophil‐to‐lymphocyte ratio for postsurgical outcomes of patients with endometrial carcinoma
Authors: Ding Ling , Ding Yi , Mao Xiao‐hua , Zhao Jian‐fei , Zhou Huai‐jun
Published: June 2017

Objective

To evaluate the significance of postoperative inflammatory system response markers in predicting the prognosis of patients with endometrial cancer undergoing surgery.

Methods

The present retrospective study included patients who underwent surgical treatment for pathology‐confirmed endometrial cancer between January 1, 2007, and June 30, 2013, at the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. Potential prognostic factors were investigated by Cox proportional hazards analysis and survival rates were compared using Kaplan‐Meier analyses.

Results

There were 185 patients with surgically treated endometrial cancer included. Multivariate analyses demonstrated that a preoperative neutrophil‐to‐lymphocyte ratio (NLR) above 1.81 (P=0.010) and a postoperative NLR above 7.54 (P=0.008) were both independently associated with lower disease free survival. Elevated preoperative and postoperative NLRs were associated with higher tumor stage (P=0.021 and P=0.009, respectively), and only elevated preoperative NLR was associated with lymph node involvement (P=0.023).

Conclusion

Preoperative and postoperative NLRs were independently associated with inflammatory system response markers and could be combined to evaluate the prognosis of patients with endometrial cancer following surgery.
Loss functions for predicted click‐through rates in auctions for online advertising
Authors: Hummel Patrick , McAfee R. Preston
Published: June 2017

We characterize the optimal loss functions for predicted click‐through rates in auctions for online advertising. Whereas standard loss functions such as mean squared error or log likelihood severely penalize large mispredictions while imposing little penalty on smaller mistakes, a loss function reflecting the true economic loss from mispredictions imposes significant penalties for small mispredictions and only slightly larger penalties on large mispredictions. We illustrate that when the model is misspecified using such a loss function can improve economic efficiency, but the efficiency gain is likely to be small.
Pharmacokinetic Characterization and Dose Selection of a Novel Sumatriptan Nasal Spray Formulation, DFN‐02
Authors: Pal Arindam , Gautam Anirudh , Munjal Sagar
Published: June 2017

This 3‐way, single‐dose, randomized crossover study evaluated the pharmacokinetics (PK) and dose proportionality of 5‐, 10‐, and 15‐mg doses of intranasal sumatriptan (DFN‐02) coformulated with a permeation enhancer (DDM) in 18 healthy adults. The objective was to determine which DFN‐02 dose approximates the PK of a 6‐mg dose of sumatriptan delivered via subcutaneous injection in the deltoid muscle of the arm. Sumatriptan plasma concentrations peaked with DFN‐02 between 10 and 15 minutes postdose, declining thereafter, with a t1/2 of about 2.5 hours; mean Cmax and AUC0–∞ values increased linearly across doses. After DFN‐02 doses of 5, 10, and 15 mg, mean Cmax was 40.7 ± 14.2, 71.2  ±  22.1, and 101.0  ±  49.5 ng/mL, and mean AUC0–∞ was 49.9  ±  20.6, 87.1  ± 31.2, and 120.5  ± 53.3 ng·h/mL, respectively. The increase in sumatriptan bioavailability was less than dose‐proportional among the DFN‐02 doses studied. Based on the established PK of a 6‐mg subcutaneous sumatriptan injection (mean Tmax,  12 minutes; mean Cmax,  74  ± 15 ng/mL in the deltoid area of the arm) and the peak and time to peak sumatriptan concentrations of the DFN‐02 doses tested, a 10‐mg dose of DFN‐02 was found to be the closest match. Overall, DFN‐02 was well tolerated at doses of 5 to 15 mg, and no new safety concerns were identified.
Morphological Variation in Anuran Limbs: Constraints and Novelties
Authors: Fabrezi Marissa , Goldberg Javier , Chuliver Pereyra Mariana
Published: June 2017

Anurans have three primary types of locomotion: walking, jumping, and swimming. Additionally, they may dig, climb, grasp, etc. All adult anurans have four limbs, with four fingers on the hands and five toes on the feet. We summarized and updated knowledge on the interspecific variation within anuran limbs, then discuss how developmental constraints (e.g., in size) and novelties may have influenced anuran diversification through the locomotion. We analyze morphological variation from limb bud stages up to the final limb form resulting from certain skeletal organization and growth. We find limited morphometric variations in the skeleton of different developmental modules (i.e., skull, trunk, urostyle, limbs) indicate that the anuran body shape is largely constrained. We identify specializations of the stylopodium, zeugopodium, and proximal carpals/tarsals that have evolved to facilitiate saltatorial locomotion. We show that the anuran prepollex and prehallux are not vestigial digits and that they have come to serve specialized function. Medial rotation of the manus in anurans appears to have evolved to help distribute the force of impact upon landing at the end of a jump. Additional skeletal elements in anuran limbs are intercalary elements and sesamoids. The intercalary elements appear within neobatrachians and are integrated with digital pads in lineages capable of locomotion on smooth vertical surfaces. They have allowed arboreal anurans to occupy a wide range of arboreal habitats.
“Very much in love”: The letters of Magda Arnold and Father John Gasson
Authors: Rodkey Elissa N.
Published: June 2017

Magda Arnold (1903–2002), best known for her pioneering appraisal theory of emotion, belonged to the second generation of women in psychology who frequently experienced institutional sexism and career barriers. Following her religious conversion, Arnold had to contend with the additional challenge of being an openly Catholic woman in psychology at a time when Catholic academics were stigmatized. This paper announces the discovery of and relies upon a number of previously unknown primary sources on Magda Arnold, including approximately 150 letters exchanged by Arnold and Father John Gasson. This correspondence illuminates both the development of Arnold's thought and her navigation of the career challenges posed by her conversion. I argue that Gasson's emotional and intellectual support be considered as resources that helped Arnold succeed despite the discrimination she experienced. Given the romantic content of the correspondence, I also consider Arnold and Gasson in the context of other academic couples in psychology in this period and argue that religious belief ought to be further explored as a potential contributor to the resilience of women in psychology's history.
Novel 4‐arylaminoquinoline‐3‐carbonitriles as Inhibitors of HIV‐1 Reverse Transcriptase
Authors: Melo Beatriz C. L. , Bernardino Alice M. R. , Polillo Gustavo , Pereira Helena S. , Paixão Izabel C. P. , Ribeiro Michele S. , Borges Julio C.
Published: June 2017

This paper describes the synthesis of several new 4‐arylaminoquinoline‐3‐carbonitriles derivatives. These were evaluated on the activity reverse transcriptase (RT) of HIV‐1. Most of the synthesized compounds showed significant in vitro inhibition of RT enzyme, especially derivative 3h (IC50 = <8 μM). The derivatives showed low‐level cytotoxicity.
PTR‐MS volatile profiling of Pinot Noir wines for the investigation of differences based on vineyard site
Authors: Schueuermann C. , Bremer P. , Silcock P.
Published: June 2017

This study investigated the effect of vineyard site on the volatile profiles of Pinot Noir wines using proton‐transfer reaction mass spectrometry with prior headspace dilution. The ANOVA and PCA enabled discrimination of wine based on vineyard site. Sample separation was due to differences in the ratios of a mixture of compounds, including higher alcohols, ethyl, and acetate esters. Proton‐transfer reaction mass spectrometry appears to be a useful technique for rapidly discriminating wines based on vineyard site. The similarities and differences expressed in the wines' volatile profiles may help winemakers to reveal the potential of individual vineyard sites to produce wines of certain character. Copyright © 2017 John Wiley & Sons, Ltd.
Development of overuse tendinopathy: A new descriptive model for the initiation of tendon damage during cyclic loading
Authors: Herod Tyler W. , Veres Samuel P.
Published: June 2017

Tendinopathic tissue has long been characterized by changes to collagen microstructure. However, initial tendon damage from excessive mechanical loading—a hallmark of tendinopathy development—could occur at the nanoscale level of collagen fibrils. Indeed, it is on this scale that tenocytes interact directly with tendon matrix, and excessive collagen fibril damage not visible at the microscale could trigger a degenerative cascade. In this study, we explored whether initiation of tendon damage during cyclic loading occurs via a longitudinal compression‐induced buckling mechanism of collagen fibrils leading to nanoscale kinkband development. Two groups of tendons were cyclically loaded to equivalent peak stresses. In each loading cycle, tendons in one group were unloaded to the zero displacement mark, while those in the other group were unloaded to a nominal level of tension, minimizing the potential for fibril buckling. Tendons that were unloaded to the zero displacement mark ruptured significantly sooner during cyclic loading (1,446 ± 737 vs. 4,069 ± 1,129 cycles), indicating that significant fatigue damage is accrued in the low stress, toe region of the load‐deformation response. Ultrastructural analysis using scanning electron microscopy of tendons stopped after 1,000 cycles showed that maintaining a nominal tension slowed the accumulation of kinkbands, supporting a longitudinal compression‐induced buckling mechanism as the basis for kinkband development. Based on our results, we present a new descriptive model for the initiation of tendon damage during cyclic loading. The so‐called Compression of Unrecovered Elongation or CUE Model may provide useful insight into the development of tendinopathy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:467–476, 2018.