bluuebunny/crossref_metadata_2025 huggingface dataset:
Ginsenoside Rg3 stereoisomers differentially inhibit vascular smooth muscle cell proliferation and migration in diabetic atherosclerosis
Authors: Guo Mengqi , Guo Guanlun , Xiao Jie , Sheng Xi , Zhang Xinyu , Tie Yuanyuan , Cheng Yuen‐Kit , Ji Xiaoping
Published: March 2018

Ginsenoside 20(R/S)‐Rg3, as a natural peroxisome proliferator‐activated receptor gamma (PPARγ) ligand, has been reported to exhibit differential biological effects. It is of great interest to understand the stereochemical selectivity of 20(R/S)‐Rg3 and explore whether differential PPARγ activation by Rg3 stereoisomers, if it exists, could lead to differential physiological outcome and therapeutic effects in diabetic atherosclerosis. Here, we investigated the binding modes of 20(R/S)‐Rg3 stereoisomers in the PPARγ ligand‐binding domain (PPARγ‐LBD) using molecular modelling and their effects on smooth muscle cell proliferation and migration induced by advanced glycation end products (AGEs). The results revealed that 20(S)‐Rg3 exhibited stronger antiproliferative and antimigratory effects due to stronger PPARγ activation. To validate the in vitro results, we used a mice model with diabetic atherosclerosis and obtained that 20(S)‐Rg3 markedly reduced the plaque size secondary to reducing the proliferation and migration of VSMCs, while the plaques were more stable due to improvements in other plaque compositions. The results shed light on the structural difference between Rg3 stereoisomers that can lead to significant differential physiological outcome, and the (S)‐isomer seems to be the more potent isomer to be developed as a promising drug for diabetic atherosclerosis.
Effects of trimethoprim–sulfadiazine and detomidine on the function of equine Kv11.1 channels in a two‐electrode voltage‐clamp (TEVC) oocyte model
Authors: Trachsel D. S. , Tejada M. A. , Groesfjeld Christensen V. , Pedersen P. J. , Kanters J. K. , Buhl R. , Calloe K. , Klaerke D. A.
Published: March 2018

The long QT syndrome (LQTS) is a channelopathy that can lead to severe arrhythmia and sudden cardiac death. Pharmacologically induced LQTS is caused by interaction between drugs and potassium channels, especially the Kv11.1 channel. Due to such interactions, numerous drugs have been withdrawn from the market or are administered with precautions in human medicine. However, some compounds, such as trimethoprim–sulfonamide combinations are still widely used in veterinarian medicine. Therefore, we investigate the effect of trimethoprim–sulfadiazine (TMS), trimethoprim, sulfadiazine, and detomidine on equine‐specific Kv11.1 channels. Kv11.1 channels cloned from equine hearts were heterologously expressed in Xenopus laevis oocytes, and whole cell currents were measured by two‐electrode voltage‐clamp before and after drug application. TMS blocked equine Kv11.1 current with an IC50 of 3.74 mm (95% CI: 2.95–4.73 mm) and affected the kinetics of activation and inactivation. Similar was found for trimethoprim but not for sulfadiazine, suggesting the effect is due to trimethoprim. Detomidine did not affect equine Kv11.1 current. Thus, equine Kv11.1 channels are also susceptible to pharmacological block, indicating that some drugs may have the potential to affect repolarization in horse. However, in vivo studies are needed to assess the potential risk of these drugs to induce equine LQTS.
Pathotypes and phylogenetic variation determine downy mildew epidemics in Brassica spp. in Australia
Authors: Mohammed A. E. , You M. P. , Al‐lami H. F. D. , Barbetti M. J.
Published: March 2018

Isolates of Hyaloperonospora brassicae inoculated onto cotyledons of 28 diverse Brassicaceae genotypes, 13 from Brassica napus, two from B. juncea, five from B. oleracea, two from Eruca vesicaria, and one each from B. nigra, B. carinata, B. rapa, Crambe abyssinica, Raphanus sativus and R. raphanistrum, showed significant effects (P ≤ 0.001) of isolate, host and their interaction. Host responses ranged from no visible symptom or a hypersensitive response, to systemic spread and abundant pathogen sporulation. Isolates were generally most virulent on their host of origin. Using an octal classification, six host genotypes were identified as suitable host differentials to characterize pathotypes of H. brassicae and distinguished eight distinct pathotypes. There were fewer, but more virulent, pathotypes in 2015–2016 isolates than 2006–2008 pathogen populations, probably explaining the increase in severity of canola downy mildew over the past decade. Phylogenetic relationships determined across 20 H. brassicae isolates collected in 2006–2008 and 88 isolates collected in 2015–2016 showed seven distinct clades, with 70% of 2006–2008 isolates distributed within clade I (bootstrap value (BVs) of 100%) and the remaining 30% in clade V (BVs 83.3%). This is the first study to define phylogenetic relationships of H. brassicae isolates in Australia, setting a benchmark for understanding current and future genetic shifts within pathogen populations; it is also the first to use octal classification to characterize pathotypes of H. brassicae, providing a novel basis for standardizing phenotypic characterization and monitoring of pathotypes on B. napus and some crucifer species in Australia.
Effect of Foetal Bovine Serum on sperm motility, acrosome reaction and spermatic interaction to zona pellucida in alpacas (Vicugna pacos)
Authors: Bravo Z , Valdivia M
Published: March 2018

Contents

The use of foetal bovine serum (FBS) in cell culture media is quite common. However, little is known about the effect of FBS on sperm. The severe difficulties in alpaca reproduction demand the search of new methods for in vitro reproductive management. In the present study, we use for the first time FBS as a supplement in the culture medium for sperm in alpaca, and the effect of FBS on motility, acrosome reaction and sperm binding to the zona pellucida in this species was evaluated. A concentration of 10% v/v FBS was used. The sperm motility with FBS at the first hour was 32.8% (vs. control = 30.0%), whereas at the second hour sperm motility with FBS was 30.2% (vs. control = 28.8%). The acrosome reaction reached an average of 44.0% for treatment with FBS (vs. control = 30.1%). The sperm‐zona pellucida binding assay showed that the samples incubated with FBS had an average of 2.7 bound sperm (vs. control = 1.7). Only a significant difference was observed for sperm motility at the first hour and for the acrosome reaction. It is concluded that FBS favours the capacitation of sperm in alpaca.
Qualitative and quantitative ultrasound attributes of maternal‐foetal structures in pregnant ewes
Authors: da Silva PDA , Uscategui RAR , Santos VJC , Taira AR , Mariano RSG , Rodrigues MGK , Simões APR , Maronezi MC , Avante ML , Vicente WRR , Feliciano MAR
Published: March 2018

Contents

The aim of this study was to examine foetal organs and placental tissue to establish a correlation between the changes in the composition of these structures associated with their maturation and the ultrasonographic characteristics of the images. Twenty‐four pregnant ewes were included in the study. Ultrasonography assessments were performed in B‐mode, from the ninth gestational week until parturition. The lungs, liver and kidneys of foetuses and placentomes were located in transverse and longitudinal sections to evaluate the echogenicity (hypoechoic, isoechoic, hyperechoic or mixed) and echotexture (homogeneous and heterogeneous) of the tissues of interest. For quantitative evaluation of the ultrasonographic characteristics, it was performed a computerized image analysis using a commercial software (Image ProPlus®). Mean numerical pixel values (NPVs), pixel heterogeneity (standard deviation ofNPVs) and minimum and maximum pixel values were measured by selecting five circular regions of interest in each assessed tissue. All evaluated tissues presented significant variations in theNPVs, except for the liver. PulmonaryNPVmean,NPVmin andNPVmax decreased gradually through gestational weeks. The renal parameters gradually decreased with the advancement of the gestational weeks until the 17th week and later stabilized. The placentomeNPVmean,NPVmin andNPVmax decreased gradually over the course of weeks. The hepatic tissue did not show echogenicity and echotexture variations and presented medium echogenicity and homogeneous echotexture throughout the experimental period. It was concluded that pixels numerical evaluation of maternal‐foetal tissues was applicable and allowed the identification of quantitative ultrasonographic characteristics showing changes in echogenicity related to gestational age.
Out Through the Intake
Authors: Langston Lee S.
Published: March 2018

This article elaborates various challenges presented by stall and surge to the gas turbine research community and jet engine designers. The article also presents several examples of stall and surge faced by the pilots. Stall and surge emerge from basic physics: the behavior of the boundary layer on the compressor blades and stators; however, current technology has no means to completely eliminate it. Engine control systems, such as the Full Authority Digital Electric Control (FADEC), are programmed to keep the operating point of the compressor well away from the surge line. Researchers have been studying stall and surge for decades, looking for ways to predict and combat the phenomena. Meanwhile, there has been some success in using FADEC to either prevent a stall and surge or to limit the number of repetitions. FADEC can also step in during flights in heavy rain or hailstorms. In those conditions, extra fuel is needed to process and evaporate the water being swallowed by the engine. The electronic control system can sense the mismatch between the power setting and the fuel flow and take action to prevent possible engine instability.
A Kinetic Sculptor
Authors: O’Heir Jeff , Hegner Chehalis
Published: March 2018

This article highlights different mechanical engineering works of Arthur Ganson. The fundamentals of mechanical engineering inform every piece of Arthur Ganson’s moving sculptures. Ganson, who is as much an engineer as he is an artist, works with unpolished steel, found objects, homemade gears, and roughly soldered wires. Yet he assembles them with such care that their movements create an elegant and mesmerizing beauty. His permanent installations tick, whiz, and hum at the National Inventors Hall of Fame in Ohio and at the Smithsonian Institution’s Lemelson Center for the Study of Invention and Innovation. His work has been featured at numerous museums and galleries around the world, and he has even appeared in ‘Muffy’s Art Attack,’ an episode of the children’s cartoon Arthur. While most engineers spend their careers hiding the pieces that make their machines move, Ganson reveals his. To construct each sculpture and engineer its movement, he relies on the fundamentals of mechanical engineering and physics the same way that a painter uses color theory as a guide for creating a visual effect.
Efficiency is Easy to Hack
Authors: Johnson Brian David
Published: March 2018

This article focuses on the possible cyberattacks as the current generation go Internet-connected way. Connecting an appliance to the Internet provides not only the opportunity for added functions and efficiency, but also the potential for hackers to exploit security lapses. As the attack plain begins to expand and digital attacks spread and become individual, physical, or even kinetic in nature, the calculus will change. Cybersecurity experts have demonstrated that Internet-connected vehicles are vulnerable to attack by hackers. As more physical systems undergo a wave of artificial intelligence (AI)-driven automation with the driving factor being efficiency, those systems become increasingly vulnerable to attack. The article concludes that traditional engineering has long optimized for things like cost, efficiency, or simplicity. Internet-connected machines and IoT-enabled devices will allow systems to do amazing things, but they also create opportunities for bad actors to turn these systems against us.
Living in the Material World
Authors: Thilmany Jean
Published: March 2018

This article explores ways and solutions that could make computer-aided design (CAD) systems help engineers make a better choice of their design. CES Selector is a stand-alone library of material property data that helps engineers screen materials based on design objectives and constraints. The tool is useful for identifying potential materials during the conceptual design phase and when searching for a replacement for a material that is not working out. The MultiFab printer developed by MIT’s Science and Artificial Intelligence Lab enables engineers to print multiple materials at once and build objects whose segments have different properties. Research teams are looking for ways to enable engineers to design a part and the materials that comprise it at the same time, within a single software application. The approach will give engineers tools to customize those materials at the microscale and give them just the right properties for the design. By integrating this into CAD design systems, engineers could alter materials at the microscale to achieve specific physical properties needed for the shapes and structures they design at the macroscale.
Increasing Efficiency
Authors: Crawford Mark C. , Romer Thomas
Published: March 2018

This article discusses the technology used at the John W. Turk Jr. Power Plant in Fulton, Ark., to tackle the challenges of raising the pressure and temperature of the steam to new heights. The Turk plant is the first in the United States where the final steam conditions exceed both the critical pressure and a temperature of 1,100°F. Operating as an ultrasupercritical boiler, the Turk plant has the highest net plant efficiency of any solid fuel power plant in the United States. In this plant, Southwestern Electric Power Company tapped Babcock & Wilcox to design, supply, and erect the 600-MW advanced supercritical steam generator. To best optimize efficiency, the design team selected a single reheat cycle with elevated steam pressure and temperature. Babcock & Wilcox engineers also employed computational fluid dynamics modeling to place burners and overfire air ports to make the best use of low-sulfur coal.
Electric Enabler
Authors: Kosowatz John , Romer Thomas
Published: March 2018

This article explains how Tesla batteries are making electric vehicles (EVs) affordable for customers. Tesla’s battery revolution began when CEO Elon Musk declared that it would sell a mass-market EV for just $35,000. To produce battery packs cheaply enough to reach that price point, Tesla reengineered not only the production process, but also the factory in which the batteries are made. The Reno, Nev., Gigafactory is not yet operating at full capacity, but it is expected to produce 35 GW per year of lithium-ion batteries, about double the present-day global production. Tesla partnered with Panasonic to revamp the production process, and ended up redesigning the chemistry of the battery itself. The standard “18-650” cell format used thousands of less-expensive commodity cells, similar to lithium-ion batteries used in laptop computers. Tesla replaced individual safety systems built into each cell with an inexpensive fireproof system for the entire battery pack. Now, they have begun producing the new “2170” cell, which delivers higher density through an automated system developed with Panasonic to further reduce costs.
Seeing Beyond the Line of Site – Controlling Connected Automated Vehicles
Authors: Orosz Gábor , Ge Jin I. , He Chaozhe R. , Avedisov Sergei S. , Qin Wubing B. , Zhang Linjun
Published: March 2018

This article discusses past, present, and future research on connected automated vehicles and their impact on road transportation. From the 1980s, microcontrollers started to penetrate production vehicles through various subsystems such as engine control units, and anti-lock braking systems. Soon the need for different microcontrollers to communicate with each other led to the invention of the controller area network bus. In the 1990s, onboard sensors were introduced to monitor the environment and the motion of neighboring vehicles. These sensors, combined with more powerful computers, allowed vehicles to perform lateral and longitudinal control such as lane keeping and car following. Starting from the mid-2000s, wireless communication technologies such as WiFi and 4G/LTE have been adopted in order to facilitate vehicle-to-vehicle and vehicle-to-infrastructure communication. These are often referred to as vehicle-to-everything (V2X) communication, where X also includes pedestrians, bicyclists, etc. In particular, in the United States, dedicated short-range communication has been standardized based on IEEE 802.11p protocol, which allows low-latency, ad-hoc, and peer-to-peer communication with 10-Hz update frequency.
A Driver’s License Test for Driverless Vehicles
Authors: Abbas Houssam , O’Kelly Matthew E. , Rodionova Alena , Mangharam Rahul
Published: March 2018

This article elaborates the approaches that can be used to verify an autonomous vehicle (AV) before giving it a driver’s license. Formal methods applied to the problem of AV verification include theorem proving, reachability analysis, synthesis, and maneuver design. Theorem proving is an interactive technique in which the computer is largely responsible for demonstrating that the model satisfies the specification, with occasional help from the user. The latter provides lemmas and axioms that the tool leverages to advance the proof towards its conclusion. Reachability analysis is used to verify the operation of the AV during navigation. This provides an extension of onboard diagnostics to whole-AV operation, where the diagnosis does not concern one component’s requirements, but the safety of the entire AV. Another approach is to design correct-by-construction controllers from preverified maneuvers. The basic idea is that one builds a library of maneuvers, such as Left-Turn and Right-Turn, and verifies that the car can perform these maneuvers from any initial state.
The Proving Grounds
Authors: Brown Alan S.
Published: March 2018

This article focuses on the emerging supply chain of hardware, software, and engineers transforming warehouses to test bed of innovation for autonomous robots. Although warehouses are controlled environments, they are filled with changing obstacles, traffic, and unexpected surprises. Warehouses used to be the hub of a relatively simple logistics operation. They received and stored pallets of identical goods from manufacturers and importers, and then sent boxes via a conveyor belt or cart to trucks destined for retail outlets. Bruce Welty and his partner have built a world-class e-commerce fulfillment facility, Quiet Logistics, by deploying robots sold by Kiva Systems. The next-generation robots have master control systems to optimize their movements, as do the Kiva robots. However, these new robots are designed to collaborate with human workers rather than banishing them from the aisles, which means the robots must move briskly across the warehouse floor while avoiding people, forklifts, pallets, and boxes. Economics make warehouses a great proving ground for autonomous robots.
How to Train Your Robot?
Authors: Warrier Rahul B. , Devasia Santosh
Published: March 2018

This article explores the concept of inferring intent during human-in-the-loop robot learning for output tracking. The human-response dynamics can affect the precision achieved by the human during human-in-the-loop operation. Preview-based online inversion is a viable technique that allows for stable online inversion of complex linear controlled systems, even those for which stable causal inverses do not exist, such as non-minimum phase systems. The averaged motion can still be affected by the human-response dynamics and can therefore be still different from the user’s intent. Therefore, inferring the human intent is important and necessary in the context of human-robot shared control. The results of applying the inversion-based iterative learning scheme to the human-in-the-loop trajectory tracking task has also been presented in the article. Figures show that the output tracking performance improves with respect to the manual tracking performance when inverse control is applied. When the iterative learning control law is applied, further tracking improvement is achieved. Thus, the learned control input can successfully emulate the human intent. An advantage of the robot-learning framework is that it allows novice human operators, who may be experts in the task, but not in teaching a robot, to successfully achieve the task objectives, which can expand the usage and acceptability of robots in society.
Organ Banking
Authors: Rabin Yoed , Lewis Jedediah
Published: March 2018

This article focuses on various technological innovations in the field of cryopreservation of human tissues. In order to further explore how engineers from various disciplines can offer a broader and improved set of tools to tackle preservation challenges, ASME and the Organ Preservation Alliance are co-organizing the Summit on Organ Banking through Converging Technologies in Boston, Mass., in August 2017. Techniques for successful cryopreservation have been developed over the past five decades for several tissue types. To achieve vitrification, cryobiologists introduce glass-promoting solutions known as cryoprotective agents (CPAs) into the tissue. As researchers push the boundaries on the ability to cryopreserve bulky tissues and large organs, a new thermal challenge emerges called rapid cooling, which can potentially give rise to dangerous thermomechanical stress driven by the tendency of the material to contract with temperature.
AI and the Future of the Machine Design
Authors: Noor Ahmed K.
Published: March 2018

This article discusses advantages of artificially intelligent (AI) systems and future of machine design. Advances in AI, combined synergistically with other technologies such as cognitive computing, Internet of Things, 3D (or even 4D) printing, advanced robotics, virtual and mixed reality, and human–machine interfaces are transforming what, where, and how products are designed, manufactured, assembled, distributed, serviced, and upgraded. The research and related activities may ultimately result in the development of self-repairing, self-healing, self-adaptive, self-reconfiguring systems—and products that ‘operationally improve’ themselves. Instead of depreciating in value and capability, such products could improve over time. In time, the role of the human engineer may be that of a director rather than of a producer. Much of the technical aspect of engineering will be moved to the machine-based design system, just as one need not be able to operate a slide rule or complete an isometric drawing to be a successful engineer today.
Electrofuels
Authors: Todd Davidson F. , Nagasawa Kazunori , Webber Michael E.
Published: March 2018

This article explains the need for producing synthetic fuels in support of making a clean and reliable energy system. This production process is expected to solve several problems at once: stabilizing intermittent electricity supply while creating renewable fuels for use in power generation, transportation, and industry. The large-scale introduction of wind and solar power now makes the production of renewable fuels at least technically feasible. Policymakers should start to give electrofuels the attention they deserve. There are many tax credits or subsidies for renewable or low-carbon sources of electricity such as wind, solar, geothermal, and nuclear, but electrofuels are not yet prominent in the discussion. In addition, while states like California have mandates for energy storage, stakeholders often ignore the option of electrofuels despite the potential for them to be a more useful and affordable competitor to batteries. The article concludes that electrofuels may provide a unique solution to a number of challenges, and it is time our markets and policies recognize that possibility.
Re-engineering Houston
Authors: Mintz Testa Bridget
Published: March 2018

This article focuses on various engineering projects that are being undertaken to protect Houston and other cities from future storms. With so much activity in Houston, regional planners and government officials wanted to know exactly how much of an upgrade the region’s coastal defenses needed, that required advanced fluid dynamics models and time on state-of-the-art supercomputers. The model utilizes the latitude, longitude, and the elevation of the ground, both above and below the water. The model can simulate normal tides based on the phase of the moon and wind direction, showing how the water flows in and out of the complex geography of the bay, both above the surface and below. Storm Prediction, Education, and Evacuation from Disasters (SSPEED) Center now leans toward a multiple barrier system combining the mid-bay and lower-bay gate concepts. The combination plan would provide some protection to the towns along Galveston Bay’s coast, while providing additional protection to the Houston ship channel and its critical infrastructure, as well as to the heavily developed west side of the bay.
Energy Consumption and Tailpipe Emission Reductions by Personalized Control of Connected Vehicles
Authors: Wang Junmin
Published: March 2018

This article demonstrates several approaches to the vehicle energy consumption and tailpipe emission reduction opportunities. The article leverages the vehicle storage dynamics through smart and personalized optimization and control approaches in the context of connected vehicles. Recent advances in vehicle connectivity and automation have brought unprecedented information richness and new degrees of freedom that can be synergized with insightful understanding of vehicle powertrain and aftertreatment physical systems. Vehicle automation also provides new degrees of freedom that can be further leveraged by the vehicle control systems to improve vehicle energy efficiency and reduce tailpipe emissions. While vehicle automation levels probably will keep increasing, humans will still be involved in vehicle operations at various levels for the foreseeable future. The prediction of future vehicle’s power demand based on vehicle connectivity can significantly benefit tailpipe emission reductions and fuel economy.
Stephen Hawking, betting man
Authors: Clery Daniel
Published: March 2018

The famed cosmologist loved a wager on serious scientific topics, but he had a poor record for winning them.
Too much of a good thing?
Authors: Kaiser Jocelyn
Published: March 2018

Cancer experts debate whether there's a glut of immunotherapy trials.
A nonconjugated radical polymer glass with high electrical conductivity
Authors: Joo Yongho , Agarkar Varad , Sung Seung Hyun , Savoie Brett M. , Boudouris Bryan W.
Published: March 2018

Moving charges with radicals

Conducting polymers usually contain backbones with multiple bonds. After chemical doping to remove some of the electrons, charge carriers can move freely. These conjugated backbones can also make the polymers rigid and hard to process. Joo
et al.
synthesized a redox-active, nonconjugated radical polymer that exhibited high conductivity (see the Perspective by Lutkenhaus). The polymer has a low glass transition temperature, allowing it to form intermolecular percolation networks for electrons.

Science
, this issue p.
1391
; see also p.
1334
A single fungal MAP kinase controls plant cell-to-cell invasion by the rice blast fungus
Authors: Sakulkoo Wasin , Osés-Ruiz Miriam , Oliveira Garcia Ely , Soanes Darren M. , Littlejohn George R. , Hacker Christian , Correia Ana , Valent Barbara , Talbot Nicholas J.
Published: March 2018

Keeping the channels open

When the rice blast fungus enters a rice cell, the plasma membrane stays intact, so the rice cell remains viable. The fungus then moves to adjacent cells via plasmodesmata, the plant's intercellular channels. Sakulkoo
et al.
used a chemical genetic approach to selectively inhibit a single MAP (mitogen-activated protein) kinase, Pmk1, in the blast fungus. Inhibition of Pmk1 trapped the fungus within a rice cell. Pmk1 regulated the expression of a suite of effector genes involved in suppression of host immunity, allowing the fungus to manipulate plasmodesmal conductance. At the same time, Pmk1 regulated the fungus's hyphal constriction, which allows movement into new host cells.

Science
, this issue p.
1399
Two-billion-year-old evaporites capture Earth’s great oxidation
Authors: Blättler C. L. , Claire M. W. , Prave A. R. , Kirsimäe K. , Higgins J. A. , Medvedev P. V. , Romashkin A. E. , Rychanchik D. V. , Zerkle A. L. , Paiste K. , Kreitsmann T. , Millar I. L. , Hayles J. A. , Bao H. , Turchyn A. V. , Warke M. R. , Lepland A.
Published: March 2018

A strongly oxidizing Paleoproterozoic era

Two billion years ago, marine sulfate concentrations were around one-third as high as modern ones, constituting an oxidizing capacity equivalent to more than 20% of that of the modern ocean-atmosphere system. Blättler
et al.
found this by analyzing a remarkable evaporite succession more than 1 billion years older than the oldest comparable deposit discovered to date. These quantitative results, for a time when only more qualitative information was previously available, provide a constraint on the magnitude and timing of early Earth's response to the Great Oxidation Event 2.3 billion years ago.

Science
, this issue p.
320
Legacy nitrogen may prevent achievement of water quality goals in the Gulf of Mexico
Authors: Van Meter K. J. , Van Cappellen P. , Basu N. B.
Published: March 2018

Haunted by the past

Reducing the extent of hypoxia in the Gulf of Mexico will not be as easy as reducing agricultural nitrogen use. Van Meter
et al.
report that so much nitrogen from runoff has accumulated in the Mississippi River basin that, even if future agricultural nitrogen inputs are eliminated, it will still take 30 years to realize the 60% decrease in load needed to reduce eutrophication in the Gulf. This legacy effect means that a dramatic shift in land-use practices, which may not be compatible with current levels of agricultural production, will be needed to control hypoxia in the Gulf of Mexico.

Science
, this issue p.
427
Personalized vaccines for cancer immunotherapy
Authors: Sahin Ugur , Türeci Özlem
Published: March 2018

Cancer is characterized by an accumulation of genetic alterations. Somatic mutations can generate cancer-specific neoepitopes that are recognized by autologous T cells as foreign and constitute ideal cancer vaccine targets. Every tumor has its own unique composition of mutations, with only a small fraction shared between patients. Technological advances in genomics, data science, and cancer immunotherapy now enable the rapid mapping of the mutations within a genome, rational selection of vaccine targets, and on-demand production of a therapy customized to a patient’s individual tumor. First-in-human clinical trials of personalized cancer vaccines have shown the feasibility, safety, and immunotherapeutic activity of targeting individual tumor mutation signatures. With vaccination development being promoted by emerging innovations of the digital age, vaccinating a patient with individual tumor mutations may become the first truly personalized treatment for cancer.
Identification and Characterization of the Neisseria gonorrhoeae MscS-Like Mechanosensitive Channel
Authors: Wang Zhemin , Wang Xiaomin , Lu Ping , Ni Chunshan , Li Yuezhou , van der Veen Stijn
Published: March 2018

Mechanosensitive channels are ubiquitous in bacteria and provide an essential mechanism to survive sudden exposure to a hypo-osmotic environment by the sensing and release of increased turgor pressure. No mechanosensitive channels have thus far been identified and characterized for the human-specific bacterial pathogen
Neisseria gonorrhoeae
. In this study, we identified and characterized the
N. gonorrhoeae
MscS-like mechanosensitive channel (Ng-MscS). Electrophysiological analyses by the patch clamp method showed that Ng-MscS is stretch activated and contains pressure-dependent gating properties. Further mutagenesis studies of critical residues forming the hydrophobic vapor lock showed that gain-of-function mutations in Ng-MscS inhibited bacterial growth. Subsequent analysis of the function of Ng-MscS in
N. gonorrhoeae
by osmotic down-shock assays revealed that the survival of Ng-
mscS
deletion mutants was significantly reduced compared with that of wild-type strains, while down-shock survival was restored upon the ectopic complementation of
mscS
. Finally, to investigate whether Ng-MscS is important for
N. gonorrhoeae
during infections, competition assays were performed by using a murine vaginal tract infection model. Ng-
mscS
deletion mutants were outcompeted by
N. gonorrhoeae
wild-type strains for colonization and survival in this infection model, highlighting that Ng-MscS contributes to
in vivo
colonization and survival. Therefore, Ng-MscS might be a promising target for the future development of novel antimicrobials.
Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine
Authors: Daum L. T. , Konstantynovska O. S. , Solodiankin O. S. , Liashenko O. O. , Poteiko P. I. , Bolotin V. I. , Hrek I. I. , Rohozhyn A. V. , Rodriguez J. D. , Fischer G. W. , Chambers J. P. , Gerilovych A. P.
Published: March 2018

The Ukraine ranks among the top 20 countries with the highest number of multidrug-resistant (MDR) and extensively drug resistant (XDR)
Mycobacterium tuberculosis
cases in the world. However, little is known of the genetic diversity, i.e., resistance signatures, in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistance-conferring genes from clinical isolates (
n
= 75) collected from geographically diverse Ukrainian oblasts and the southern Crimean peninsula. Genomic analysis revealed that 6 (8%) were sensitive, 3 (4%) were resistant to at least one antibiotic but were not MDR, 40 (53%) were MDR, and 26 (35%) were XDR. The majority of isolates (81%) were of the Beijing-like lineage. This is the first study to use next-generation sequencing (NGS) of clinical isolates from the Ukraine to characterize mutations in genes conferring
M. tuberculosis
drug resistance. Several isolates harbored drug resistance signatures that have not been observed in other countries with high-burden tuberculosis. Most notably, the absence of
inhA
gene promoter mutations, a diversity of mutation types in the
rpoB
resistance-determining region, and detection of heteroresistance provide a broader understanding of MDR/XDR from this area of the world.
Frequency of Instrument, Environment, and Laboratory Technologist Contamination during Routine Diagnostic Testing of Infectious Specimens
Authors: Yarbrough Melanie L. , Kwon Jennie H. , Wallace Meghan A. , Hink Tiffany , Shupe Angela , Fraser Victoria J. , Dubberke Erik R. , Burnham Carey-Ann D.
Published: March 2018

Laboratory testing to support the care of patients with highly infectious diseases may pose a risk for laboratory workers. However, data on the risk of virus transmission during routine laboratory testing conducted using standard personal protective equipment (PPE) are sparse. Our objective was to measure laboratory contamination during routine analysis of patient specimens. Remnant specimens were spiked with the nonpathogenic bacteriophage MS2 at 1.0 × 10
7
PFU/ml, and contamination was assessed using reverse transcriptase PCR (RT-PCR) for MS2. Specimen containers were exteriorly coated with a fluorescent powder to enable the visualization of gross contamination using UV light. Testing was performed by two experienced laboratory technologists using standard laboratory PPE and sample-to-answer instrumentation. Fluorescence was noted on the gloves, bare hands, and laboratory coat cuffs of the laboratory technologist in 36/36 (100%), 13/36 (36%), and 4/36 (11%) tests performed, respectively. Fluorescence was observed in the biosafety cabinet (BSC) in 8/36 (22%) tests, on test cartridges/devices in 14/32 (44%) tests, and on testing accessory items in 29/32 (91%) tests. Fluorescence was not observed on or in laboratory instrumentation or adjacent surfaces. In contrast to fluorescence detection, MS2 detection was infrequent (3/286 instances [1%]) and occurred during test setup for the FilmArray instrument and on FilmArray accessory equipment. The information from this study may provide opportunities for the improvement of clinical laboratory safety practices so as to reduce the risk of pathogen transmission to laboratory workers.
New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five
Authors: Quan Chuansong , Shi Weifeng , Yang Yang , Yang Yongchun , Liu Xiaoqing , Xu Wen , Li Hong , Li Juan , Wang Qianli , Tong Zhou , Wong Gary , Zhang Cheng , Ma Sufang , Ma Zhenghai , Fu Guanghua , Zhang Zewu , Huang Yu , Song Houhui , Yang Liuqing , Liu William J. , Liu Yingxia , Liu Wenjun , Gao George F. , Bi Yuhai
Published: March 2018

H7N9 virus has caused five infection waves since it emerged in 2013. The highest number of human cases was seen in wave 5; however, the underlying reasons have not been thoroughly elucidated. In this study, the geographical distribution, phylogeny, and genetic evolution of 240 H7N9 viruses in wave 5, including 35 new isolates from patients and poultry in nine provinces, were comprehensively analyzed together with strains from first four waves. Geographical distribution analysis indicated that the newly emerging highly pathogenic (HP) and low-pathogenicity (LP) H7N9 viruses were cocirculating, causing human and poultry infections across China. Genetic analysis indicated that dynamic reassortment of the internal genes among LP-H7N9/H9N2/H6Ny and HP-H7N9, as well as of the surface genes, between the Yangtze and Pearl River Delta lineages resulted in at least 36 genotypes, with three major genotypes (G1 [A/chicken/Jiangsu/SC537/2013-like], G3 [A/Chicken/Zhongshan/ZS/2017-like], and G11 [A/Anhui/40094/2015-like]). The HP-H7N9 genotype likely evolved from G1 LP-H7N9 by the insertion of a KRTA motif at the cleavage site (CS) and then evolved into 15 genotypes with four different CS motifs, including PKG
KRTA
R/G, PKG
KRIA
R/G, PKR
KRAA
R/G, and PKR
KRTA
R/G. Approximately 46% (28/61) of HP strains belonged to G3. Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains. In summary, the enhanced prevalence and diverse genetic characteristics that occurred with mammalian-adapted and NAI-resistant mutations may have contributed to increased numbers of human infections in wave 5.

IMPORTANCE
The highest numbers of human H7N9 infections were observed during wave 5 from October 2016 to September 2017. Our results showed that HP-H7N9 and LP-H7N9 had spread virtually throughout China and underwent dynamic reassortment with different subtypes (H7N9/H9N2 and H6Ny) and lineages (Yangtze and Pearl River Delta lineages), resulting in totals of 36 and 3 major genotypes, respectively. Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections. The broad dissemination of LP- and HP-H7N9 with high levels of genetic diversity and host adaptation and drug-resistant mutations likely accounted for the sharp increases in the number of human infections during wave 5. Therefore, more strategies are needed against the further spread and damage of H7N9 in the world.
Full tendon medial transposition of lateral rectus with augmentation sutures in cases of complete third nerve palsy
Authors: Saxena Rohit , Sharma Medha , Singh Digvijay , Sharma Pradeep
Published: March 2018

Management options in third nerve palsy are limited as four of the six extraocular muscles are involved. Surgery has to be tailored on a case-to-case basis. Aim of this retrospective case series is to report 1-year outcomes of a modified surgical technique entailing full tendon transposition of lateral rectus to medial rectus augmented with posterior fixation sutures in four patients with complete third nerve palsy. All four cases showed significant improvement of vertical and horizontal deviation with long-term stability of correction. Choice of route of full tendon augmented transposition of lateral rectus to medial rectus can aid in achieving good correction of the vertical misalignment in addition to horizontal correction.
Concurrent drug use among methadone maintenance patients in mountainous areas in northern Vietnam
Authors: Tran Bach Xuan , Boggiano Victoria L , Thi Nguyen Huong Lan , Nguyen Long Hoang , Nguyen Hung Van , Hoang Canh Dinh , Le Huong Thi , Tran Tho Dinh , Le Hai Quan , Latkin Carl A , Thi Vu Thuc Minh , Zhang Melvyn WB , Ho Roger CM
Published: March 2018

Objectives

With the rise in methadone maintenance therapy (MMT) for drug users in Vietnam, there has been growing interest in understanding if and how often MMT patients engage in concurrent illicit drug use while on methadone therapy in various settings. This study examined factors associated with concurrent opioid use among patients on MMT in a mountainous area in Vietnam.

Setting

One urban and one rural MMT clinics in Tuyen Quang province.

Participants

Survey participants consisted of patients who were taking MMT at the selected study sites. A convenience sampling approach was used to recruit the participants.

Primary and secondary outcome measures

Participants were asked a series of questions about their socioeconomic status, current alcohol and tobacco use, health problems (measured by the EuroQol-Five Dimension-Five Level instrument), psychological distress (measured by Kessler score), and factors associated with current and/or previous drug use. Regression models were used to determine factors associated with concurrent drug use among MMT patients.

Results

Among the 241 male MMT patients included in the study, 13.4% reported concurrent opioid use. On average, the longer patients had been enrolled in MMT, the less likely they were to concurrently use drugs. Conversely, patients with higher levels of psychological distress were more likely to engage in concurrent drug use while on MMT.

Conclusion

Longer duration of MMT was significantly correlated with reduced illicit drug use among participants. Higher levels of psychological distress were associated with increased use of illicit drugs among MMT patients. Regardless of distance, long-term MMT is still effective and should be expanded in mountainous areas.
Association of socioeconomic status with financial burden of disease among elderly patients with cardiovascular disease: evidence from the China Health and Retirement Longitudinal Survey
Authors: Li Chunyan , Young Belinda-Rose , Jian Weiyan
Published: March 2018

Objectives

The prevalence of cardiovascular diseases (CVD) within low-income and middle-income countries has reached epidemic proportions. However, the association between out-of-pocket (OOP) payment and socioeconomic status (SES) of patients with CVD is not well studied. We aimed to understand the financial burden among Chinese middle-aged and older patients with CVD, and whether there was an association with SES.

Settings

A nationally representative survey—The China Health and Retirement Longitudinal Survey(CHARLS)—was conducted in 28 provinces of mainland China in 2011 and 2013.

Participants

Of the over 18 000 CHARLS respondents, eligible participants were those aged 45 years and over who had been previously diagnosed with CVD.

Outcome measures

Financial burden was measured byindividualOOP payment andhouseholdcatastrophic health expenditure (CHE) occurrence (ie, the annual household health expenditure was 40% or more of the total non-food household expenditure). Multilevel regression models were used to explore the association between financial burden and SES.

Results

Among CHARLS respondents, CVD prevalence increased from 14.7% in 2011 to 16.6% in 2013. Average annual CVD OOP payment increased from 5000 RMB (770 USD) to 6120 RMB (970 USD). Furthermore, CHE occurrence increased from 44.2% to 48.1%. Patients spent almost twice on outpatient as on inpatient services. Two of the three SES indicators (total household expenditure, occupation type) were found to be associated with CVD OOP payment amount, and the likelihood of CHE. Unemployed patients had a higher likelihood of CHE compared with agricultural workers. Rural-urban difference was associated with the likelihood of CHE in 2011 alone.

Conclusion

The Chinese health system should use this health expenditure pattern among patients with CVD to create more equitable health insurance schemes that financially balance between outpatient and inpatient care, and provide better financial risk protection to patients with low SES.
Preparation and electrochemical characterization of PANI/MnCo2O4 nanocomposite as supercapacitor electrode material
Authors: Panahi Saeid , Es’haghi Moosa
Published: March 2018

In this work, PANI/MnCo2O4 nanocomposite was prepared via in-situ chemical polymerization method. Materials synthesized were characterized by FTIR spectroscopy, X-ray diffraction, and scanning electron spectroscopy. In addition, surface characterization of samples such as specific surface area, pore volume, and pore size distribution was studied. Supercapacitor capability of materials was investigated in 1 mol L–1 Na2SO4 solution using cyclic voltammetry in different potential scan rates and electrochemical impedance spectroscopy (EIS). The specific capacitance of materials was calculated, and it was observed that the specific capacitance of PANI/MnCo2O4 nanocomposite was 185 F g−1, much larger than PANI. Moreover, the prepared nanocomposite exhibited better rate capability in scan rate of 100 mV s−1 with respect to PANI. The EIS experiments revealed that the nanocomposite has lower charge transfer resistance compared with pure PANI. Subsequently, it was shown that the nanocomposite cycling performance was superior to the PANI cycling performance.
Metallothionein expression in slow- vs. fast-twitch muscle fibers following 4 weeks of streptozotocin-induced type 1 diabetes
Authors: Mondragon Pamela , Bergdahl Andreas
Published: March 2018

Type 1 diabetes (T1DM) is known to cause an increase in reactive oxygen species (ROS) and elevated intracellular glucose levels. We investigated the metallothionein I and II (MT I+II) antioxidants expression in soleus (mainly slow-twitch) and plantaris (predominantly fast-twitch) skeletal muscle using a rodent model of streptozotocin-induced diabetes. The presence of oxidative stress was confirmed by the detection of increased levels of protein carbonyl formation in the diabetic tissues. DAB (3,3′-diaminobenzidine) immunostaining and Western blotting analyses demonstrated that MT I+II expression was significantly upregulated in the diabetic soleus and plantaris muscle tissues compared with their respective controls. Moreover, no significant difference was detected between the plantaris and soleus controls or between the plantaris and soleus diabetic tissues. These findings suggest that there is an increase in MT protein expression in the soleus and plantaris muscles associated with the induction of T1DM. A better understanding of the molecular mechanisms that allow MT to prevent the oxidative stress associated with diabetes could lead to a novel therapeutic strategy for this chronic disease and its associated complications.
Farey–Lorenz Permutations for Interval Maps
Authors: Geller William , Misiurewicz Michał
Published: March 2018

Lorenz-like maps arise in models of neuron activity, among other places. Motivated by questions about the pattern of neuron firing in such a model, we study periodic orbits and their itineraries for Lorenz-like maps with nondegenerate rotation intervals. We characterize such orbits for the simplest such case and gain substantial information about the general case.