bluuebunny/crossref_metadata_2025 huggingface dataset:
Near-field speckle imaging of light localization in disordered photonic systems
Authors: Caselli Niccolò , Intonti Francesca , La China Federico , Biccari Francesco , Riboli Francesco , Gerardino Annamaria , Li Lianhe , Linfield Edmund H. , Pagliano Francesco , Fiore Andrea , Gurioli Massimo
Published: February 2017

Optical localization in strongly disordered photonic media is an attractive topic for proposing novel cavity-like structures. Light interference can produce random modes confined within small volumes, whose spatial distribution in the near-field is predicted to show hot spots at the nanoscale. However, these near-field speckles have not yet been experimentally investigated due to the lack of a high spatial resolution imaging techniques. Here, we study a system where the disorder is induced by random drilling air holes in a GaAs suspended membrane with internal InAs quantum dots. We perform deep-subwavelength near-field experiments in the telecom window to directly image the spatial distribution of the electric field intensity of disordered-induced localized optical modes. We retrieve the near-field speckle patterns that extend over few micrometers and show several single speckles of the order of λ/10 size. The results are compared with the numerical calculations and with the recent findings in the literature of disordered media. Notably, the hot spots of random modes are found in proximity of the air holes of the disordered system.
Interface band gap narrowing behind open circuit voltage losses in Cu2ZnSnS4 solar cells
Authors: Crovetto Andrea , Palsgaard Mattias L. N. , Gunst Tue , Markussen Troels , Stokbro Kurt , Brandbyge Mads , Hansen Ole
Published: February 2017

We present evidence that bandgap narrowing at the heterointerface may be a major cause of the large open circuit voltage deficit of Cu2ZnSnS4/CdS solar cells. Bandgap narrowing is caused by surface states that extend the Cu2ZnSnS4 valence band into the forbidden gap. Those surface states are consistently found in Cu2ZnSnS4, but not in Cu2ZnSnSe4, by first-principles calculations. They do not simply arise from defects at surfaces but are an intrinsic feature of Cu2ZnSnS4 surfaces. By including those states in a device model, the outcome of previously published temperature-dependent open circuit voltage measurements on Cu2ZnSnS4 solar cells can be reproduced quantitatively without necessarily assuming a cliff-like conduction band offset with the CdS buffer layer. Our first-principles calculations indicate that Zn-based alternative buffer layers are advantageous due to the ability of Zn to passivate those surface states. Focusing future research on Zn-based buffers is expected to significantly improve the open circuit voltage and efficiency of pure-sulfide Cu2ZnSnS4 solar cells.
Increased absorption in InAsSb nanowire clusters through coupled optical modes
Authors: Svensson Johannes , Chen Yang , Anttu Nicklas , Pistol Mats-Erik , Wernersson Lars-Erik
Published: February 2017

Nanowires can act as efficient light absorbers where waveguide modes are resonant to specific wavelengths. This resonant wavelength can easily be tuned by the nanowire dimensions, but the absorption of infrared radiation requires diameters of hundreds of nm, which is difficult to achieve using epitaxial growth. Here, we demonstrate that infrared absorption in InAsSb nanowires with the diameters of only 140 nm grown on Si substrates can be enhanced resonantly by placing them closely packed in clusters of different sizes. We find that coating the nanowires with a dielectric to optically connect them results in an efficient absorption diameter far exceeding the diameter of the constituent nanowires and that the cut-off wavelength is redshifted with an increasing cluster diameter. Numerical simulations are in agreement with the experimental results and demonstrate that if nanowires are positioned in clusters, a peak absorptance of 20% is possible at 5.6 μm with only 3% surface coverage. This absorptance is 200 times higher than for wires placed in an equidistant pattern. Our findings have direct implications for the design of efficient nanowire based photodetectors and solar cells.
Evaluation of disposable microfluidic chip design for automated and fast Immunoassays
Authors: Wang Guochun , Das Champak , Ledden Bradley , Sun Qian , Nguyen Chien , Kumar Sai
Published: February 2017

We report here, the design and development of a disposable immunoassay chip for protein biomarker detection within ∼1 h. The unique design allows for real-time dynamic calibration of immunoassay for multiple biomarker detections on the chip. The limit of detection achieved for this test chip is 10 pg/ml for IL6, and 50 pg/ml for GFAP with a detection time of 1 h. The prototype instrument used for flowing the reagents through the chip can be easily assembled from off-the-shelf components with the final chemiluminescent detection carried out in a commercial plate reader. Optimization of different aspects of chip design, fabrication, and assay development is discussed in detail.
Fast-type high-accuracy universal polarimeter using charge-coupled device spectrometer
Authors: Takanabe Akifumi , Koshima Hideko , Asahi Toru
Published: February 2017

A fast, high-accuracy universal polarimeter was developed using a charge-coupled device (CCD) spectrometer (CCD-HAUP), to carry out simultaneous optical anisotropic (linear birefringence, LB; linear dichroism, LD) and chiroptical (circular birefringence, CB; circular dichroism, CD) measurements on single crystals without any pretreatment, in the visible region between 400–680 nm. The principle of the HAUP method is to measure the intensities of emergent light passing through a polarizer, a crystal sample, and then an analyzer, as the azimuth angles of the polarizer and analyzer are independently altered. The CCD-HAUP has the unique feature that white transmitted light intensity can be measured using a CCD spectrometer, compared with the generalized HAUP (G-HAUP) system in which monochromatic transmitted light is measured using a photomultiplier. The CCD-HAUP measurements across the entire wavelength region are completed within the G-HAUP measurement time for a single wavelength. The CCD-HAUP drastically reduces the measurement time for a dataset to only 1.5 h, from the 24 h required for the G-HAUP system. LB, LD, CB, and CD measurements of single crystals of α-quartz and enantiomeric photomechanical salicylidenephenylethylamines before, during, and after ultraviolet light irradiation show results comparable to those obtained using the G-HAUP system. The newly developed system is very effective for samples susceptible to degradation induced by external stimuli, such as light and heat.
Spatially varying constraints of human-caused fire occurrence in British Columbia, Canada
Authors: Camp Philip E. , Krawchuk Meg A.
Published: February 2017

Human-caused wildfires are controlled by human and natural influences, and determining their key drivers is critical for understanding spatial patterns of wildfire and implementing effective fire management. We examined an array of explanatory variables that account for spatial controls of human-caused fire occurrence from 1990 to 2013 among six ecosystem zones that vary in human footprint and environmental characteristics in British Columbia, Canada. We found that long-term patterns of human-caused fire in ecosystem zones with a larger human footprint were strongly controlled by biophysical variables explaining conditions conducive to burning, whereas fire occurrence in remote ecosystem zones was controlled by various metrics of human activity. A metric representing the wildland–urban interface was a key factor explaining human-caused fire occurrence regardless of ecosystem zone. Our results contribute to the growing body of research on the varying constraints of spatial patterns of fire occurrence by explicitly examining human-caused fire and the heterogeneity of constraints based on human development.
Selective autophagy limits cauliflower mosaic virus infection by NBR1-mediated targeting of viral capsid protein and particles
Authors: Hafrén Anders , Macia Jean-Luc , Love Andrew J. , Milner Joel J. , Drucker Martin , Hofius Daniel
Published: February 2017

Significance

Autophagy contributes to innate immune responses in metazoans by targeted elimination of intracellular pathogens, including viruses, in a process termed “xenophagy.” Whether autophagy has a similar role in plant immunity is unknown. Here we demonstrate that the selective autophagy receptor NEIGHBOR OF BRCA1 (NBR1) binds the viral capsid protein and particles of cauliflower mosaic virus (CaMV) and mediates their autophagic degradation. We further demonstrate that this antiviral xenophagy is counteracted by protective functions of autophagy-resistant CaMV inclusion bodies. Finally, we show that a second, nonselective NBR1-independent autophagy pathway promotes plant viability during infection and serves as a proviral mechanism to extend the timespan for virus production and potential CaMV transmission. Thus autophagy exhibits important pro- and antiviral roles in compatible plant–virus interactions.
Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer
Authors: Adhikary Suraj , Deredge Daniel J. , Nagarajan Anu , Forrest Lucy R. , Wintrode Patrick L. , Singh Satinder K.
Published: February 2017

Significance

Most studies of neurotransmitter:sodium symporter (NSS) function and dynamics have been carried out in detergent even though the activity of these integral membrane proteins is heavily modulated by surrounding lipids. Here, we reconstituted the prokaryotic homolog LeuT into nanodiscs and subjected the preparation to hydrogen–deuterium exchange mass spectrometry to reveal a global view of the hallmarks of the transporter in two disparate conformations. The data were interpreted with the aid of molecular dynamics simulations, allowing unprecedented atomic-level insights into the dynamics of an unmodified, unlabeled NSS in a native-like lipid bilayer environment.
EHD2 restrains dynamics of caveolae by an ATP-dependent, membrane-bound, open conformation
Authors: Hoernke Maria , Mohan Jagan , Larsson Elin , Blomberg Jeanette , Kahra Dana , Westenhoff Sebastian , Schwieger Christian , Lundmark Richard
Published: February 2017

Significance

The EHD2 protein controls the association of membrane pits termed caveolae to cell surfaces. Caveolae are implicated in muscle, pulmonary, and lipid disorders. We establish functionally, and structurally, how EHD2 cycles between an active, membrane-bound state and an inactive state in solution. We present an approach to resolve the structure of proteins in their membrane-bound state, which is difficult to obtain otherwise. A dramatic conformational change of EHD2 upon membrane binding is demonstrated. ATP binding is required for partial membrane insertion and subsequent oligomerization. In solution, internal regulatory regions inhibit the conformational change. This stringently regulated mechanistic cycle might be prototypical for a large family of proteins involved in membrane fission and may open avenues to control the process in vivo.
Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain
Authors: Li Zhe , Tseng Pang-Yen , Tiwari Vinod , Xu Qian , He Shao-Qiu , Wang Yan , Zheng Qin , Han Liang , Wu Zhiping , Blobaum Anna L. , Cui Yiyuan , Tiwari Vineeta , Sun Shuohao , Cheng Yingying , Huang-Lionnet Julie H. Y. , Geng Yixun , Xiao Bo , Peng Junmin , Hopkins Corey , Raja Srinivasa N. , Guan Yun , Dong Xinzhong
Published: February 2017

Significance

Chronic pain is a major health and economic problem worldwide with an estimated prevalence reaching epidemic levels of >25% of the population. Most drugs on the market for chronic pain have undesired side effects because their targets exist both inside and outside the pain pathways. Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target of novel pain inhibitors, mainly because of its restricted expression in primary nociceptive neurons. Our humanized mouse model expressing MRGPRX1 in native nociceptive neurons allowed us to examine physiological roles of MRGPRX1 and to develop therapeutic agents for pain treatment in patients. Our studies suggest that both agonists and positive allosteric modulators of MRGPRX1 may be promising novel drug candidates for managing persistent pain conditions.
Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection
Authors: Lyke Kirsten E. , Ishizuka Andrew S. , Berry Andrea A. , Chakravarty Sumana , DeZure Adam , Enama Mary E. , James Eric R. , Billingsley Peter F. , Gunasekera Anusha , Manoj Anita , Li Minglin , Ruben Adam J. , Li Tao , Eappen Abraham G. , Stafford Richard E. , KC Natasha , Murshedkar Tooba , Mendoza Floreliz H. , Gordon Ingelise J. , Zephir Kathryn L. , Holman LaSonji A. , Plummer Sarah H. , Hendel Cynthia S. , Novik Laura , Costner Pamela J. M. , Saunders Jamie G. , Berkowitz Nina M. , Flynn Barbara J. , Nason Martha C. , Garver Lindsay S. , Laurens Matthew B. , Plowe Christopher V. , Richie Thomas L. , Graham Barney S. , Roederer Mario , Sim B. Kim Lee , Ledgerwood Julie E. , Hoffman Stephen L. , Seder Robert A.
Published: February 2017

Significance

A highly effective malaria vaccine capable of long-term protection against genetically diverse strains is urgently needed. Here, we demonstrate that a three-dose regimen of a live attenuated whole-parasite malaria vaccine conferred durable sterile protection through 33 weeks in ∼50% of subjects against a controlled human malaria infection strain that is heterologous to the vaccine strain. Prior studies by others and us have shown that T cells are critical to mediating sterile protection after live-attenuated malaria vaccination. Here, we provide evidence that this
Plasmodium falciparum
sporozoite vaccine (PfSPZ Vaccine) induces antigen-specific IFN-γ-producing CD8 and CD4 T cells that recognize both the homologous and the heterologous Pf strain.
On the shape of giant soap bubbles
Authors: Cohen Caroline , Darbois Texier Baptiste , Reyssat Etienne , Snoeijer Jacco H. , Quéré David , Clanet Christophe
Published: February 2017

Significance

Surface tension dictates the spherical cap shape of small sessile drops, whereas gravity flattens larger drops into millimeter-thick flat puddles. In contrast with drops, soap bubbles remain spherical at much larger sizes. However, we demonstrate experimentally and theoretically that meter-sized bubbles also flatten under their weight, and we compute their shapes. We find that mechanics does not impose a maximum height for large soap bubbles, but, in practice, the physicochemical properties of surfactants limit the access to this self-similar regime where the height grows as the radius to the power 2/3. An exact analogy shows that the shape of giant soap bubbles is nevertheless realized by large inflatable structures.
Large nonsaturating magnetoresistance and signature of nondegenerate Dirac nodes in ZrSiS
Authors: Singha Ratnadwip , Pariari Arnab Kumar , Satpati Biswarup , Mandal Prabhat
Published: February 2017

Significance

Topological semimetals provide the opportunity to explore the fundamental physics of relativistic particles and offer the possibility of technological applications. However, finding robust systems with a sufficiently large range of linearly dispersing bands remains elusive. Recently discovered Dirac semimetal ZrSiS hosts multiple Dirac cones with the largest reported energy range of linear band dispersion (

∼

2 eV). In this work, we report transport measurements on ZrSiS, exploring extreme and anisotropic magnetoresistance with distinct quantum oscillations, enabling us to quantitatively analyze the Fermi surface properties. We have also observed the unique signature of chiral anomaly in longitudinal magnetoresistance. Our work comprehensively confirms the recent theoretical and angle-resolved photoemission spectroscopy results on ZrSiS and suggests a large family of materials as potential topological semimetals.
Differential TOR activation and cell proliferation in
Arabidopsis
root and shoot apexes
Authors: Li Xiaojuan , Cai Wenguo , Liu Yanlin , Li Hui , Fu Liwen , Liu Zengyu , Xu Lin , Liu Hongtao , Xu Tongda , Xiong Yan
Published: February 2017

Significance

The modulation of growth and development is central to sessile plants. Shoot and root meristems share almost identical molecular machineries but are responsible for different types of aboveground and underground organogenesis. How two such highly similar biological systems respond to different environmental cues and regulate distinct developmental programs remains largely unknown. We report that, in harmony with nature, the shoot, but not the root, demands light for the activation of cell proliferation during organogenesis. We decipher the underlying mechanism that light is necessary for continuous auxin biosynthesis only in the shoot, but not the root, to activate target of rapamycin (TOR) kinase signaling. We further elucidate an auxin-Rho-related protein 2 (ROP2)-TOR-transcription factors E2Fa,b signaling cascade that integrates different environmental signals to orchestrate plant growth and development.
Activation of contact-dependent antibacterial tRNase toxins by translation elongation factors
Authors: Jones Allison M. , Garza-Sánchez Fernando , So Jaime , Hayes Christopher S. , Low David A.
Published: February 2017

Significance

Contact-dependent growth inhibition (CDI) systems enable cells to bind competing bacteria and deliver toxins that cleave nucleic acids or form membrane pores. Here, we characterize a CDI toxin that specifically cleaves transfer RNA (tRNA), thereby blocking protein synthesis and inhibiting bacterial growth. Remarkably, two highly conserved and essential translation factors, EF-Ts and EF-Tu, are critical for this toxic nuclease activity. The toxin binds EF-Tu with high affinity and only cleaves tRNA in complex with the translation factor. EF-Ts appears to increase the rate of tRNA turnover. The activities of two other distinct CDI toxins are also regulated by EF-Ts. We propose that the regulation of toxin activity by the protein synthesis apparatus may play a role in intercellular communication.
Rps3/uS3 promotes mRNA binding at the 40S ribosome entry channel and stabilizes preinitiation complexes at start codons
Authors: Dong Jinsheng , Aitken Colin Echeverría , Thakur Anil , Shin Byung-Sik , Lorsch Jon R. , Hinnebusch Alan G.
Published: February 2017

Significance

In the initiation of protein synthesis, a preinitiation complex (PIC) of the 40S ribosomal subunit, initiation factors, and initiator tRNA
i
scans the mRNA leader for an AUG codon in favorable context; and AUG recognition evokes a closed conformation of the PIC with more tightly bound tRNA
i
. uS3 (Rps3 in yeast) is a protein in the 40S mRNA entry channel, whose function during initiation was unknown. Substituting uS3 arginine residues in contact with mRNA reduces initiation at suboptimal start codons (UUG and AUG in poor context), weakens ribosome–mRNA interaction specifically at the entry channel, and destabilizes tRNA
i
binding selectively at UUG codons. Thus, uS3 promotes mRNA:40S interaction at the entry channel to enhance initiation accuracy.
Imaging mRNA and protein interactions within neurons
Authors: Eliscovich Carolina , Shenoy Shailesh M. , Singer Robert H.
Published: February 2017

Significance

Gene expression is regulated by interactions between mRNAs and RNA-binding proteins. This functionality depends on their ability to specifically recognize and bind RNAs within the cell. Thus, elucidation of RNA–protein interactions is an area of active research. Technological developments allowed the study of these associations in living cells by ensemble biochemistry approaches. However, these traditional methods to investigate RNA–protein association may report adventitious associations and importantly, lack information about cellular spatial information. In this work, we provide an approach that can integrate information from biochemical interactions with visualization of these physical contacts within neurons.
Rhythmic brain stimulation reduces anxiety-related behavior in a mouse model based on meditation training
Authors: Weible Aldis P. , Piscopo Denise M. , Rothbart Mary K. , Posner Michael I. , Niell Cristopher M.
Published: February 2017

Significance

Meditation training has been shown to reduce anxiety, lower stress hormones, improve attention and cognition, and increase rhythmic electrical activity in brain areas related to emotional control. We describe how artificially inducing rhythmic activity influenced mouse behavior. We induced rhythms in mouse anterior cingulate cortex activity for 30 min/d over 20 d, matching protocols for studying meditation in humans. Rhythmic cortical stimulation was followed by lower scores on behavioral measures of anxiety, mirroring the reductions in stress hormones and anxiety reported in human meditation studies. No effects were observed in preference for novelty. This study provides support for the use of a mouse model for studying changes in the brain following meditation and potentially other forms of human cognitive training.
Cryo-EM structure of the replisome reveals multiple interactions coordinating DNA synthesis
Authors: Kulczyk Arkadiusz W. , Moeller Arne , Meyer Peter , Sliz Piotr , Richardson Charles C.
Published: February 2017

Significance

The antiparallel nature of the two strands in duplex DNA poses a topological problem for their simultaneous synthesis. The “trombone” model of the replication fork postulates that the lagging-strand forms a loop such that the leading- and lagging-strand replication proteins contact one another. The replisome then can move in one direction along the DNA while synthesizing both strands. Physical interactions between the replication proteins and DNA coordinate processive synthesis of the leading and lagging strands. Here, we present the structure of a functional replisome from bacteriophage T7. Our structural and biochemical analyses provide an explanation of the mechanisms governing coordination of leading- and lagging-strand synthesis.
Transcriptome-wide microRNA and target dynamics in the fat body during the gonadotrophic cycle of
Aedes aegypti
Authors: Zhang Xiufeng , Aksoy Emre , Girke Thomas , Raikhel Alexander S. , Karginov Fedor V.
Published: February 2017

Significance

A potential avenue to control the spread of mosquito disease vectors lies in reproductive events that follow a blood meal. A key component is the massive production of yolk proteins in the fat body tissue, governed by regulatory networks triggered by the available nutrients. MicroRNAs play a critical role in mosquito egg maturation, and deciphering their dynamics and targets is necessary to fully realize these regulatory processes. We carried out a tissue-specific and time-resolved characterization of microRNA expression in the
Aedes aegypti
fat body and integrated these results with transcriptome-wide determination of their mRNA targets, followed by validation. This extensive analysis lays the groundwork for a systemic understanding of the gene regulation that underpins reproductive events in the female mosquito.
Distinct conformations of GPCR–β-arrestin complexes mediate desensitization, signaling, and endocytosis
Authors: Cahill Thomas J. , Thomsen Alex R. B. , Tarrasch Jeffrey T. , Plouffe Bianca , Nguyen Anthony H. , Yang Fan , Huang Li-Yin , Kahsai Alem W. , Bassoni Daniel L. , Gavino Bryant J. , Lamerdin Jane E. , Triest Sarah , Shukla Arun K. , Berger Benjamin , Little John , Antar Albert , Blanc Adi , Qu Chang-Xiu , Chen Xin , Kawakami Kouki , Inoue Asuka , Aoki Junken , Steyaert Jan , Sun Jin-Peng , Bouvier Michel , Skiniotis Georgios , Lefkowitz Robert J.
Published: February 2017

Significance

β-Arrestins (βarrs) interact with G protein-coupled receptors (GPCRs) to desensitize G protein signaling, initiate signaling on their own, and mediate receptor endocytosis. Using a panel of GPCRs believed to couple differently to βarrs, we demonstrate how distinct conformations of GPCR–βarr complexes are specialized to perform different subsets of these cellular functions. Our results thus provide a new signaling paradigm for the understanding of GPCRs, whereby a specific GPCR–βarr conformation mediates receptor desensitization, and another drives internalization and some forms of signaling.
Survey Methods for Estimating Red Snapper Landings in a High-Effort Recreational Fishery Managed with a Small Annual Catch Limit
Authors: Sauls Beverly J. , Cody Richard P. , Strelcheck Andrew J.
Published: February 2017

Before the Red Snapper Lutjanus campechanus stock in the southeastern U.S. Atlantic was formally assessed, recreational harvest was permitted year-round. However, in 2010, all sectors of the fishery were closed to immediately end overfishing. In recent years, the recreational fishery for Red Snapper in the region has been managed with a substantially reduced catch limit and an annual harvest season ranging from 0 to 8 d. To obtain a precise estimate of recreational harvest over this reduced time scale, a new creel survey method was developed in Florida, where the majority of Red Snapper landings in the region occur. The fishery was intensely monitored during the short sample window when the harvest season was open, and the survey design took advantage of choke points at ocean inlets that restrict recreational boat access to offshore fishing grounds. Landings estimates from this specialized survey were more precise than the general survey that has historically been used in the region to monitor saltwater recreational fisheries over larger spatial and temporal scales. Fishing effort was highly concentrated, and the fishery was capable of reaching the small annual catch limit over the short time periods allowed. Fishing effort and landings were highest between Ponce Inlet and Cape Canaveral, and the majority of Red Snapper were harvested from shallow depths (<29 m). Fish from shallow depths were approximately equally distributed among younger (1–5 years) and older age-classes. However, as fishing moved into deeper waters (≥29 m), a greater proportion of fish were older than 5 years. Precise landings estimates from the survey enabled managers to monitor the recreational fishery against a small annual catch limit, and the survey also revealed spatial patterns of effort and CPUE in the region's private boat segment of the recreational fishery, which had been poorly understood.

Received May 13, 2016; accepted November 5, 2016 Published online February 22, 2017
DNA Vaccination Partially Protects Muskellunge against Viral Hemorrhagic Septicemia Virus (VHSV-IVb)
Authors: Millard Elena V. , Bourke Ashley M. , LaPatra Scott E. , Brenden Travis O. , Fitzgerald Scott D. , Faisal Mohamed
Published: February 2017

A DNA vaccine containing the glycoprotein (G) gene of the North American viral hemorrhagic septicemia virus (VHSV) genotype IVb was developed to evaluate the immune response of fish following vaccination and evaluate its efficacy in protecting a susceptible species, the Muskellunge Esox masquinongy, against VHSV-IVb challenge. Seven weeks (539 degree-days) following vaccination with 10 μg of either pVHSivb-G or a control plasmid, Muskellunge were challenged by immersion with 105 plaque-forming units (pfu)/mL of VHSV-IVb. Fish vaccinated with pVHSivb-G had a relative percent survival (RPS) of 45%. Vaccinated fish also had significantly lower mean viral titers in tissues (4.2 × 102 pfu/g) and viral prevalence (4%) than fish receiving the plasmid control vaccine (3.3 × 105 pfu/g; 82%). Neutralizing antibodies were detected 28 d (308 degree-days) postchallenge (11 weeks postvaccination) in 100% of Muskellunge vaccinated with pVHSivb-G compared with only 12% of plasmid-control-vaccinated Muskellunge, suggesting robust induction of a secondary, adaptive immune response. In addition, pVHSivb-G–vaccinated Rainbow Trout Oncorhynchus mykiss challenged 7 d (100 degree-days) postvaccination with the heterologous novirhabdovirus, infectious hematopoietic necrosis virus (IHNV), experienced an RPS of 61%, compared to control fish, suggesting induction of an early and transient nonspecific antiviral immune response. This study provides an important starting point for VHSV-IVb vaccine development and useful information about the antiviral immune response elicited by DNA vaccination in a nondomesticated fish species.

Received May 1, 2016; accepted September 1, 2016
Competition, Product Safety, and Product Liability
Authors: Chen Yongmin , Hua Xinyu
Published: February 2017

A firm’s incentive to invest in product safety is affected by both market environment and product liability. We investigate the relationship between competition and product liability in a spatial model of oligopoly, where reputation provides a market incentive for safety investment and higher liability may distort consumers’ incentive for product care. We find that partial liability, together with reputation concerns, can motivate firms to make safety investment. Increased competition due to less product differentiation diminishes a firm’s gain from maintaining reputation and raises the socially desired product liability. On the other hand, an increase in the number of competitors reduces the benefit from maintaining reputation, but has a non-monotonic effect on the potential gain from cutting back safety investment; consequently, the optimal liability may vary non-monotonically with the number of competitors. In general, therefore, the relationship between competition and product liability is subtle, depending on how competition is measured. (JEL L13, L15, K13)
Discrimination as a Self-Fulfilling Prophecy: Evidence from French Grocery Stores*
Authors: Glover Dylan , Pallais Amanda , Pariente William
Published: February 2017

Examining the performance of cashiers in a French grocery store chain, we find that manager bias negatively affects minority job performance. In the stores studied, cashiers work with different managers on different days and their schedules are determined quasi-randomly. When minority cashiers, but not majority cashiers, are scheduled to work with managers who are biased (as determined by an implicit association test), they are absent more often, spend less time at work, scan items more slowly, and take more time between customers. This appears to be because biased managers interact less with minorities, leading minorities to exert less effort. Manager bias has consequences for the average performance of minority workers: while on average minority and majority workers perform equivalently, on days where managers are unbiased, minorities perform significantly better than do majority workers. The findings are consistent with statistical discrimination in hiring whereby because minorities underperform when assigned to biased managers, the firm sets a higher hiring standard for minorities to get similar average performance from minority and nonminority workers.
The Plant-Dependent Life Cycle of Thecaphora thlaspeos: A Smut Fungus Adapted to Brassicaceae
Authors: Frantzeskakis Lamprinos , Courville Kaitlyn J. , Plücker Lesley , Kellner Ronny , Kruse Julia , Brachmann Andreas , Feldbrügge Michael , Göhre Vera
Published: February 2017

Smut fungi are globally distributed plant pathogens that infect agriculturally important crop plants such as maize or potato. To date, molecular studies on plant responses to smut fungi are challenging due to the genetic complexity of their host plants. Therefore, we set out to investigate the known smut fungus of Brassicaceae hosts, Thecaphora thlaspeos. T. thlaspeos infects different Brassicaceae plant species throughout Europe, including the perennial model plant Arabis alpina. In contrast to characterized smut fungi, mature and dry T. thlaspeos teliospores germinated only in the presence of a plant signal. An infectious filament emerges from the teliospore, which can proliferate as haploid filamentous cultures. Haploid filaments from opposite mating types mate, similar to sporidia of the model smut fungus Ustilago maydis. Consistently, the a and b mating locus genes are conserved. Infectious filaments can penetrate roots and aerial tissues of host plants, causing systemic colonization along the vasculature. Notably, we could show that T. thlaspeos also infects Arabidopsis thaliana. Exploiting the genetic resources of A. thaliana and Arabis alpina will allow us to characterize plant responses to smut infection in a comparative manner and, thereby, characterize factors for endophytic growth as well as smut fungi virulence in dicot plants.
A man with a productive cough
Authors: Pavlik Daniel , Laxton Mary , Felker Lori
Published: February 2017

The clinical presentation of active tuberculosis is nonspecific. This article describes a patient whose chronic cough was eventually diagnosed as reactivation tuberculosis.
An update on the pharmacologic management and treatment of neuropathic pain
Authors: Wright Megan E. , Rizzolo Denise
Published: February 2017

Neuropathic pain results directly from a lesion or disease of the somatosensory nervous system and can be central or peripheral in origin. Epidemiologic research suggests that 7% to 10% of the general population suffers from neuropathic pain, although the prevalence may be underestimated. Patients with neuropathic pain may experience anxiety, depression, insomnia, disability, and reduced quality of life. Treatment remains suboptimal because traditional drugs provide only modest pain relief. This article reviews the causes of neuropathic pain, patient presentation, diagnosis, and management strategies.
Which dosing of furosemide is better in acute decompensated heart failure?
Authors: Jalaba Stephanie , Palermo Jennifer , Budavari Adriane I.
Published: February 2017

Continuous versus bolus dosing of furosemide has been a longstanding debate for clinicians treating patients with acute decompensated heart failure. This article discusses the efficacy and safety of both options, and reviews several meta-analyses examining this topic.
Early introduction of peanuts
Authors: Rickman Shelley , Duby Desiree , Peters Michelle , Freigeh Carla , Archambault Mark E.
Published: February 2017

Peanut allergy is the most common food allergy and the leading cause of anaphylaxis and death due to food allergy. Despite previous guidelines created by the American Academy of Pediatrics in 2003, peanut allergy has continued to significantly increase over the past decade. Therefore, further research has been done to help clinicians provide more evidence-based recommendations about the timing of introduction of peanuts. The LEAP study, published in February 2015, demonstrated the value of much earlier introduction of peanuts to nonallergic patients than previously suggested. These findings have altered current practice, and recommendations supported by the American Academy of Pediatrics now allow the introduction of peanuts as early as age 4 months to reduce the likelihood of developing peanut allergy.
Building school health partnerships to improve pediatric asthma care: the School-based Asthma Management Program
Authors: Kakumanu Sujani , Antos Nicholas , Szefler Stanley J. , Lemanske Robert F.
Published: February 2017

Purpose of review

Children with asthma require care that is seamlessly coordinated so that asthma symptoms are recognized and managed at home and at school. The purpose of this review is to discuss recent consensus recommendations in school-based asthma care.

Recent findings

The School-based Asthma Management Program (SAMPRO) provides a widely endorsed framework to coordinate care with schools and consists of four components: establishing a circle of support around the child with asthma; facilitating bidirectional communication between clinicians and schools; comprehensive asthma education for schools; and assessment and remediation of environmental asthma triggers at school. SAMPRO standardizes recommendations for school-based asthma care coordination and provides a toolkit with websites and resources useful for the care of children with asthma in the school setting.

The review will discuss the need for coordinated school asthma partnerships, the inception and development of SAMPRO, and its vision to improve pediatric asthma care coordination within the circle of support, comprising clinicians, school nurses, families, and communities.
Progress with Structure–Activity Relationship modelling of occupational chemical respiratory sensitizers
Authors: Seed Martin J. , Agius Raymond M.
Published: February 2017

Purpose of review

This appraises currently available computer-based (‘in silico’) models relating the molecular structure of low molecular weight compounds to their respiratory sensitization hazard. The present review places focus on the two main applications of such structure--activity relationship (SAR) models: hypotheses on disease mechanisms and toxicological prediction.

Recent findings

Analyses of the chemical structures of low molecular weight organic compounds known to have caused occupational asthma has led to the development of mechanistic alerts usually based on electrophilic reaction chemistry and protein cross-linking potential. Protein cross-linking potential has also been found to be a consistent feature of chemicals that have caused human cases of hypersensitivity pneumonitis. Stepwise iteration of quantitative SAR (QSAR) modelling has shown appreciable improvements in predictivity for occupational asthma hazard and useful prospects for practical application. A good case has also been made for the potential use of structural alert-based mechanistic SARs in predictive toxicology.

Further understanding of the molecular interactions between chemical respiratory sensitizers and components of human proteins have been obtained from in-vitro and in-silico techniques. There have been developments in both qualitative (mechanistic) SARs and QSARs, which offer potential for use in a predictive algorithm for the toxicological screening of industrial chemicals for respiratory sensitization potential.
It Is Time to Cancel Medicine’s Social Contract Metaphor
Authors: Harris John M.
Published: February 2017

There is agreement that the complex relationship between medicine and society is best described as a metaphorical social contract and that professionalism is the medical profession’s contribution to this contract. Metaphors can help clarify abstract concepts, but they can also be abused if the counterfactual attributes of a metaphor become attributed to its subject. This seems to be happening with medical professionalism, which has sometimes been reduced to a contracted deliverable and a bargaining chip. The undesirable attributes of the social contract metaphor may be hindering efforts to understand and teach medical professionalism.

Despite its theoretical weaknesses, the social contract metaphor has historical credibility because of its alleged association with the 1847 Code of Medical Ethics and the subsequent ascension of regular (allopathic) medicine in the early 20th century. However, the record does not support an argument that the intended purpose of the 1847 Code was to create a social contract or that one ever arose. The alternative account that a contract did arise, but physicians were poor partners, is neither satisfying nor explanatory.

As now used, medicine’s social contract metaphor has serious theoretical and historic weaknesses. Medical educators should remove this narrow and overworked metaphor from their discussions of professionalism. By doing this, educators and the profession in general would only lose the ability to threaten themselves with the cancellation of their social contract. In return they would open the door to a more complex and fruitful consideration of medical professionalism and medicine’s relationship with society.
Beyond Selection: The Use of Situational Judgement Tests in the Teaching and Assessment of Professionalism
Authors: Goss Barbara D. , Ryan Anna T. , Waring Joshua , Judd Terry , Chiavaroli Neville G. , O’Brien Richard Charles , Trumble Stephen C. , McColl Geoffrey J.
Published: February 2017

Problem

Professionalism is a critical attribute of medical graduates. Its measurement is challenging. The authors sought to assess final-year medical students’ knowledge of appropriate professional behavior across a broad range of workplace situations.

Approach

Situational judgement tests (SJTs) are used widely in applicant selection to assess judgement or decision making in work-related settings as well as attributes such as empathy, integrity, and resilience. In 2014, the authors developed three 40-item SJTs with scenarios relevant to interns (first-year junior doctors) and delivered the tests to final-year medical students to assess aspects of professionalism. As preparation, students discussed SJT-style scenarios; after the tests they completed an evaluation. The authors applied the Angoff method for the standard-setting process, delivered electronic individualized feedback reports to students post test, and provided remediation for students failing to meet the cut score.

Outcomes

Evaluation revealed that the tests positively affected students’ learning and that students accepted them as an assessment tool. Validity and reliability were acceptable. Implementation costs were initially high but will be recouped over time.

Next Steps

Recent improvements include changes to pass requirements, question revision based on reliability testing, and provision of detailed item-level feedback. Work is currently under way to expand the item bank and to introduce tests earlier in the course. Future research will explore correlation of SJT performance with other measures of professionalism and focus on the impact of SJTs on professionalism and interns’ ability to deal with challenging workplace situations.
A Patient-Centered Approach to Developing Entrustable Professional Activities
Authors: El-Haddad Carlos , Damodaran Arvin , McNeil H. Patrick , Hu Wendy
Published: February 2017

Purpose

The medical education community is rapidly accepting the use of entrustable professional activities (EPAs) as a means of assessing residents. Stakeholder engagement is advised in developing EPAs, but no studies have investigated the role of patient input. In this qualitative study, the authors investigated what patient input may add to designing a patient-centered EPA.

Method

The authors chose “management of acute low back pain (LBP)” as a common, important clinical task on which to base the patient-centered EPA. In 2015, 14 patients who presented to a teaching hospital with acute LBP participated in semistructured interviews exploring their illness experience and expectations of doctors. Clinicians representing multiple disciplines participated in a focus group. The authors used the Framework Method to analyze data, identifying and developing themes, similarities, and differences between patient and clinician input. They used the findings to develop the EPA. Through an iterative procedure of data review and tracking data sources, they determined how patient and clinician input informed each EPA descriptor.

Results

Drawing from their firsthand experience of LBP, patients described unique expectations of trainees which directly informed EPA descriptors. For example, the authors primarily used patients’ detailed descriptions of desirable and observable trainee behaviors to inform the required attitudes descriptor.

Conclusions

Patients can provide unique contributions, complementary to those of clinicians, to EPAs. Consultations with patients led to the development of a patient-centered EPA, which aligned best clinical practice with patient expectations. Educators seeking to apply patient-centered care to EPA development could adopt a similar approach.
The Use of Social Media in Graduate Medical Education: A Systematic Review
Authors: Sterling Madeline , Leung Peggy , Wright Drew , Bishop Tara F.
Published: February 2017

Purpose

Despite the growing presence of social media in graduate medical education (GME), few studies have attempted to characterize their effect on residents and their training. The authors conducted a systematic review of the peer-reviewed literature to understand the effect of social media on resident (1) education, (2) recruitment, and (3) professionalism.

Method

The authors identified English-language peer-reviewed articles published through November 2015 using Medline, Embase, Cochrane, PubMed, Scopus, and ERIC. They extracted and synthesized data from articles that met inclusion criteria. They assessed study quality for quantitative and qualitative studies through, respectively, the Medical Education Research Study Quality Instrument and the Consolidated Criteria for Reporting Qualitative Studies.

Results

Twenty-nine studies met inclusion criteria. Thirteen (44.8%) pertained to residency education. Twitter, podcasts, and blogs were frequently used to engage learners and enhance education. YouTube and wikis were more commonly used to teach technical skills and promote self-efficacy. Six studies (20.7%) pertained to the recruitment process; these suggest that GME programs are transitioning information to social media to attract applicants. Ten studies (34.5%) pertained to resident professionalism. Most were exploratory, highlighting patient and resident privacy, particularly with respect to Facebook. Four of these studies surveyed residents about their social network behavior with respect to their patients, while the rest explored how program directors use it to monitor residents’ unprofessional online behavior.

Conclusions

The effect of social media platforms on residency education, recruitment, and professionalism is mixed, and the quality of existing studies is modest at best.
Doctors Without Borders
Authors: Wass Val , Southgate Lesley
Published: February 2017

The unprecedented demands of patient and population priorities created by globalization and escalating health and social inequities will not be met unless medical education changes. Educators have failed to move fast enough to create an education framework that meets current population needs. A new common set of professional values around global social accountability is necessary. Education borders must be broken down at three levels—societal-institutional, interpersonal, and individual.

At a societal-institutional level, global health must be embraced as part of a philosophy of population needs, human rights, equity, and justice. A move from informative acquisition of knowledge and skills to formative learning where students socialize around values, develop leadership attributes, and become agents for change is needed. At an interpersonal level, radical changes in curriculum delivery, which move away from the well-defined borders of specialty rotations, are required. Students must develop an integrated understanding of the future of health care and the patient’s journey through health care delivery, within the context of population needs. At an individual level, doctors need to understand the boundaries of the professional values they hold within themselves and develop a deeper understanding of their own internal prejudices and conflicts. Opening the borders between the sciences and humanities is essential. Fostering and mentoring that emphasize that resilience, leadership, flexibility, and the ability to cope with uncertainty are needed to tackle the complexities of current, as well as future, health care. Doctors need to understand the restraints within themselves to work effectively without borders.