bluuebunny/crossref_metadata_2025 huggingface dataset:
Demonstration of a time-integrated short line of sight neutron imaging system for inertial confinement fusion
Authors: Simpson R. , Christensen K. , Danly C. , Fatherley V. E. , Fittinghoff D. , Grim G. P. , Izumi N. , Jedlovec D. , Merrill F. E. , Skulina K. , Volegov P. , Wilde C.
Published: December 2015

The Neutron Imaging System (NIS) is an important diagnostic for understanding implosions of deuterium-tritium capsules at the National Ignition Facility. While the detectors for the existing system must be positioned 28 m from the source to produce sufficient imaging magnification and resolution, recent testing of a new short line of sight neutron imaging system has shown sufficient resolution to allow reconstruction of the source image with quality similar to that of the existing NIS on a 11.6 m line of sight. The new system used the existing pinhole aperture array and a stack of detectors composed of 2 mm thick high-density polyethylene converter material followed by an image plate. In these detectors, neutrons enter the converter material and interact with protons, which recoil and deposit energy within the thin active layer of the image plate through ionization losses. The described system produces time-integrated images for all neutron energies passing through the pinhole. We present details of the measurement scheme for this novel technique to produce energy-integrated neutron images as well as source reconstruction results from recent experiments at NIF.
Steady and transient analysis of anisotropic swelling in fibered gels
Authors: Nardinocchi P. , Pezzulla M. , Teresi L.
Published: December 2015

The swelling–induced mechanical response of homogeneous anisotropic gels under free conditions and uniaxial loading is investigated. Semi–analytical and numerical analyses show that fibers hamper solvent uptake regardless of their orientation, causing the several changes in shape that occur. Finally, we verified that fibers do not significantly alter relaxation time, which determines the steady state under free–swelling conditions.
Enhanced interlayer exchange coupling in antiferromagnetically coupled ultrathin (Co70Fe30/Pd) multilayers
Authors: Meng Zhaoliang , Qiu Jinjun , Han Guchang , Teo Kie Leong
Published: December 2015

We report the studies of magnetization reversal and magnetic interlayer coupling in synthetic antiferromagnetic (SAF) [Pd/Co70Fe30]9/Ru(tRu)/Pd(tPd)/[Co70Fe30/Pd]9 structure as functions of inserted Pd layer (tPd) and Ru layer (tRu) thicknesses. We found the exchange coupling field (Hex) and perpendicular magnetic anisotropy (PMA) can be controlled by both the tPd and tRu, The Hex shows a Ruderman-Kittel-Kasuya-Yosida-type oscillatory decay dependence on tRu and a maximum interlayer coupling strength Jex = 0.522 erg/cm2 is achieved at tPd + tRu ≈ 0.8 nm in the as-deposited sample. As it is known that a high post-annealing stability of SAF structure is required for magnetic random access memory applications, the dependence of Hex and PMA on the post-annealing temperature (Ta) is also investigated. We found that both high PMA of the top Co70Fe30/Pd multilayer is maintained and Hex is enhanced with increasing Ta up to 350 °C for tRu > 0.7 nm in our SAF structure.
Anomalous photoconductive behavior of a single InAs nanowire photodetector
Authors: Li Junshuai , Yan Xin , Sun Fukuan , Zhang Xia , Ren Xiaomin
Published: December 2015

We report on a bare InAs nanowire photodetector which exhibits an anomalous photoconductive behavior. Under low-power illumination, the current is smaller than the dark current, and monotonously decreases as the excitation power increases. When the excitation power is high enough, the current starts to increase normally. The phenomenon is attributed to different electron mobilities in the “core” and “shell” of a relatively thick nanowire originating from the surface effect, which result in a quickly dropped “core current” and slowly increased “shell current” under illumination.
Electric-field-temperature phase diagram of Mn-doped Bi0.5(Na0.9K0.1)0.5TiO3 ceramics
Authors: Ehara Yoshitaka , Novak Nikola , Yasui Shintaro , Itoh Mitsuru , Webber Kyle G.
Published: December 2015

An electric field–temperature (E-T) phase diagram for a lead-free 0.5 mol. % Mn-doped Bi(Na0.1K0.9)TiO3 ceramics was investigated. The x-ray diffraction, dielectric and polarization measurements revealed relaxor behavior and were used to characterize the stability regions of the non-ergodic relaxor, ergodic relaxor and electric field induced ferroelectric states. As indicated by the polarization–current density profiles, transformation between two electric fields, induced ferroelectric states with opposite polarization direction arise via a two-step process through an intermediate relaxor state. Interplay between the ferroelectric state conversion and intermediate relaxor state is governed by the dynamics of polarization relaxation. The presented E-T phase diagram revealed the effects of the applied electric field and temperature on stability regions. This is of special interest since the Bi0.5(Na0.1K0.9)0.5TiO3 ceramics were proposed as a potential piezoceramic material.
Electronic structure and insulating gap in epitaxial VO2 polymorphs
Authors: Lee Shinbuhm , Meyer Tricia L. , Sohn Changhee , Lee Donghwa , Nichols John , Lee Dongkyu , Seo Sung S. Ambrose , Freeland John W. , Noh Tae Won , Lee Ho Nyung
Published: December 2015

Determining the origin of the insulating gap in the monoclinic V O2(M1) is a long-standing issue. The difficulty of this study arises from the simultaneous occurrence of structural and electronic transitions upon thermal cycling. Here, we compare the electronic structure of the M1 phase with that of single crystalline insulating V O2(A) and V O2(B) thin films to better understand the insulating phase of VO2. As these A and B phases do not undergo a structural transition upon thermal cycling, we comparatively study the origin of the gap opening in the insulating VO2 phases. By x-ray absorption and optical spectroscopy, we find that the shift of unoccupied t2g orbitals away from the Fermi level is a common feature, which plays an important role for the insulating behavior in VO2 polymorphs. The distinct splitting of the half-filled t2g orbital is observed only in the M1 phase, widening the bandgap up to ∼0.6 eV. Our approach of comparing all three insulating VO2 phases provides insight into a better understanding of the electronic structure and the origin of the insulating gap in VO2.
Fishbone activity in experimental advanced superconducting tokamak neutral beam injection plasma
Authors: Xu Liqing , Zhang Jizong , Chen Kaiyun , Hu Liqun , Li Erzhong , Lin Shiyao , Shi Tonghui , Duan Yanmin , Zhu Yubao
Published: December 2015

Repetitive fishbones near the trapped ion procession frequency were observed for the first time in the neutral beam injection high confinement plasmas in Experimental Advanced Superconducting Tokamak (EAST) tokamak, and diagnosed using a solid-state neutral particle analyzer based on a compact silicon photodiode together with an upgraded high spatial-temporal-resolution multi-arrays soft X-ray (SX) system. This 1/1 typical internal kink mode propagates in the ion-diamagnetism direction with a rotation speed faster than the bulk plasma in the plasma frame. From the SX measurements, this mode frequency is typical of chirping down and the energetic particle effect related to the twisting mode structure. This ion fishbone was found able to trigger a multiple core sawtooth crashes with edge-2/1 sideband modes, as well as to lead to a transition from fishbone to long lived saturated kink mode to fishbone. Furthermore, using SX tomography, a correlation between mode amplitude and mode frequency was found. Finally, a phenomenological prey–predator model was found to reproduce the fishbone nonlinear process well.
Use of molecular beacons for the rapid analysis of DNA damage induced by exposure to an atmospheric pressure plasma jet
Authors: Kurita Hirofumi , Miyachika Saki , Yasuda Hachiro , Takashima Kazunori , Mizuno Akira
Published: December 2015

A rapid method for evaluating the damage caused to DNA molecules upon exposure to plasma is demonstrated. Here, we propose the use of a molecular beacon for rapid detection of DNA strand breaks induced by atmospheric pressure plasma jet (APPJ) irradiation. Scission of the molecular beacon by APPJ irradiation leads to separation of the fluorophore-quencher pair, resulting in an increase in fluorescence that directly correlates with the DNA strand breaks. The results show that the increase in fluorescence intensity is proportional to the exposure time and the rate of fluorescence increase is proportional to the discharge power. This simple and rapid method allows the estimation of DNA damage induced by exposure to a non-thermal plasma.
Note: Gratings on low absorbing substrates for x-ray phase contrast imaging
Authors: Koch F. J. , Schröter T. J. , Kunka D. , Meyer P. , Meiser J. , Faisal A. , Khalil M. I. , Birnbacher L. , Viermetz M. , Walter M. , Schulz J. , Pfeiffer F. , Mohr J.
Published: December 2015

Grating based X-ray phase contrast imaging is on the verge of being applied in clinical settings. To achieve this goal, compact setups with high sensitivity and dose efficiency are necessary. Both can be increased by eliminating unwanted absorption in the beam path, which is mainly due to the grating substrates. Fabrication of gratings via deep X-ray lithography can address this issue by replacing the commonly used silicon substrate with materials with lower X-ray absorption that fulfill certain boundary conditions. Gratings were produced on both graphite and polymer substrates without compromising on structure quality. These gratings were tested in a three-grating setup with a source operated at 40 kVp and lead to an increase in the detector photon count rate of almost a factor of 4 compared to a set of gratings on silicon substrates. As the visibility was hardly affected, this corresponds to a significant increase in sensitivity and therefore dose efficiency.
Hepatitis C virus utilizes VLDLR as a novel entry pathway
Authors: Ujino Saneyuki , Nishitsuji Hironori , Hishiki Takayuki , Sugiyama Kazuo , Takaku Hiroshi , Shimotohno Kunitada
Published: December 2015

Significance

Hepatitis C virus (HCV) utilizes various host factors to enter host cells. During the process of HCV entry, cell surface-residing lipoprotein receptors such as scavenger receptor class B member 1 (SR-BI) play important roles through interactions with virus envelope protein E2 and virus-associated apolipoproteins such as apolipoprotein E (ApoE). CD81 plays a crucial role during this process in association with HCV. Here, we identified another pathway for HCV entry that does not use CD81. This pathway involves an association with the very-low-density lipoprotein receptor (VLDLR) and does not require previously reported host factors such as claudin, occludin, or CD81. This finding may shed new light on the process of HCV entry.
A linear relationship between wave power and erosion determines salt-marsh resilience to violent storms and hurricanes
Authors: Leonardi Nicoletta , Ganju Neil K. , Fagherazzi Sergio
Published: December 2015

Significance

In recent years, there has been a flurry of restoration projects aimed at mitigating the impact of coastal storms using salt marshes and vegetated surfaces (called “living shorelines”). Based on a large dataset of salt marsh erosion and wave measurements collected all around the world, we find that erosion rates of marsh boundaries and incident wave energy collapse into a unique linear relationship. Our result clearly shows that long-term salt marsh deterioration is dictated by average wave conditions, and it is, therefore, predictable. Violent storms and hurricanes contribute less than 1% to long-term salt marsh erosion rates. This result is of high value for coastal restoration projects and the use of living shorelines to mitigate storms effect.
Surface expression, peptide repertoire, and thermostability of chicken class I molecules correlate with peptide transporter specificity
Authors: Tregaskes Clive A. , Harrison Michael , Sowa Anna K. , van Hateren Andy , Hunt Lawrence G. , Vainio Olli , Kaufman Jim
Published: December 2015

Significance

Major histocompatibility complex (MHC) molecules play crucial roles in the immune response to pathogens and tumors by presenting protein fragments (peptides) to T lymphocytes. Recently, it has become clear that the breadth of peptide presentation by MHC class I molecules is inversely correlated with the level of cell surface expression, a relationship that is correlated with resistance to Marek’s disease in chickens and with progression to AIDS in humans. In this article, evidence is presented that class I molecules vary in a suite of correlated properties, including thermostability, that are influenced, at least in part, by the breadth of peptide translocation by the transporters for antigen presentation (TAPs) that pump peptides to be loaded.
Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs
Authors: Marsden Clare D. , Ortega-Del Vecchyo Diego , O’Brien Dennis P. , Taylor Jeremy F. , Ramirez Oscar , Vilà Carles , Marques-Bonet Tomas , Schnabel Robert D. , Wayne Robert K. , Lohmueller Kirk E.
Published: December 2015

Significance

Dogs have an integral role in human society, and recent evidence suggests they have a unique bond that elicits a beneficial hormonal response in both dogs and human handlers. Here, we show this relationship has a dark side. Small population size during domestication and strong artificial selection for breed-defining traits has unintentionally increased the numbers of deleterious genetic variants. Our findings question the overly typological practice of breeding individuals that best fit breed standards, a Victorian legacy. This practice does not allow selection to remove potentially deleterious variation associated with genes responsible for breed-specific traits.
Transplantation of human embryonic stem cell-derived retinal tissue in two primate models of retinal degeneration
Authors: Shirai Hiroshi , Mandai Michiko , Matsushita Keizo , Kuwahara Atsushi , Yonemura Shigenobu , Nakano Tokushige , Assawachananont Juthaporn , Kimura Toru , Saito Koichi , Terasaki Hiroko , Eiraku Mototsugu , Sasai Yoshiki , Takahashi Masayo
Published: December 2015

Significance

We first confirmed the ability of human embryonic stem cell-derived retina (hESC-retina) to form structured mature photoreceptor layers after transplantation into nude rats. We then developed two monkey models of retinal degeneration and evaluated their utility as host models for transplantation studies. Finally, we performed a pilot study of hESC-retina transplantation in the developed models and conducted in vivo monitoring studies using clinical devices and subsequently confirmed structured graft maturation and the potential formation of synaptic contacts between graft and host cells. This study demonstrates the competency of hESC-retina as a graft source and the eligibility of two newly developed monkey models that may be useful in future, long-term, functional studies of retinal transplantation.
Nuclear deformability and telomere dynamics are regulated by cell geometric constraints
Authors: Makhija Ekta , Jokhun D. S. , Shivashankar G. V.
Published: December 2015

Significance

Physical properties of the cell nucleus are important for various cellular functions. However, the role of cell geometry and active cytoskeletal forces in regulating nuclear dynamics and chromatin dynamics is not well understood. Our results show cells with reduced matrix constraints have short actomyosin structures. These dynamic structures together with lower lamin A/C levels, resulting in softer nuclei, may provide the driving force for nuclear fluctuations. Furthermore, we observed increased dynamics of heterochromatin and telomere structures under such reduced cell–matrix interactions. We conclude that extracellular matrix signals alter cytoskeletal organization and lamin A/C expression levels, which together lead to nuclear and chromatin dynamics. These results highlight the importance of matrix constraints in regulating gene expression and maintaining genome integrity.
Sea spray aerosol as a unique source of ice nucleating particles
Authors: DeMott Paul J. , Hill Thomas C. J. , McCluskey Christina S. , Prather Kimberly A. , Collins Douglas B. , Sullivan Ryan C. , Ruppel Matthew J. , Mason Ryan H. , Irish Victoria E. , Lee Taehyoung , Hwang Chung Yeon , Rhee Tae Siek , Snider Jefferson R. , McMeeking Gavin R. , Dhaniyala Suresh , Lewis Ernie R. , Wentzell Jeremy J. B. , Abbatt Jonathan , Lee Christopher , Sultana Camille M. , Ault Andrew P. , Axson Jessica L. , Diaz Martinez Myrelis , Venero Ingrid , Santos-Figueroa Gilmarie , Stokes M. Dale , Deane Grant B. , Mayol-Bracero Olga L. , Grassian Vicki H. , Bertram Timothy H. , Bertram Allan K. , Moffett Bruce F. , Franc Gary D.
Published: December 2015

Ice nucleating particles (INPs) are vital for ice initiation in, and precipitation from, mixed-phase clouds. A source of INPs from oceans within sea spray aerosol (SSA) emissions has been suggested in previous studies but remained unconfirmed. Here, we show that INPs are emitted using real wave breaking in a laboratory flume to produce SSA. The number concentrations of INPs from laboratory-generated SSA, when normalized to typical total aerosol number concentrations in the marine boundary layer, agree well with measurements from diverse regions over the oceans. Data in the present study are also in accord with previously published INP measurements made over remote ocean regions. INP number concentrations active within liquid water droplets increase exponentially in number with a decrease in temperature below 0 °C, averaging an order of magnitude increase per 5 °C interval. The plausibility of a strong increase in SSA INP emissions in association with phytoplankton blooms is also shown in laboratory simulations. Nevertheless, INP number concentrations, or active site densities approximated using “dry” geometric SSA surface areas, are a few orders of magnitude lower than corresponding concentrations or site densities in the surface boundary layer over continental regions. These findings have important implications for cloud radiative forcing and precipitation within low-level and midlevel marine clouds unaffected by continental INP sources, such as may occur over the Southern Ocean.
Cold season emissions dominate the Arctic tundra methane budget
Authors: Zona Donatella , Gioli Beniamino , Commane Róisín , Lindaas Jakob , Wofsy Steven C. , Miller Charles E. , Dinardo Steven J. , Dengel Sigrid , Sweeney Colm , Karion Anna , Chang Rachel Y.-W. , Henderson John M. , Murphy Patrick C. , Goodrich Jordan P. , Moreaux Virginie , Liljedahl Anna , Watts Jennifer D. , Kimball John S. , Lipson David A. , Oechel Walter C.
Published: December 2015

Significance

Arctic ecosystems are major global sources of methane. We report that emissions during the cold season (September to May) contribute ≥50% of annual sources of methane from Alaskan tundra, based on fluxes obtained from eddy covariance sites and from regional fluxes calculated from aircraft data. The largest emissions were observed at the driest site (<5% inundation). Emissions of methane in the cold season are linked to the extended “zero curtain” period, where soil temperatures are poised near 0 °C, indicating that total emissions are very sensitive to soil climate and related factors, such as snow depth. The dominance of late season emissions, sensitivity to soil conditions, and importance of dry tundra are not currently simulated in most global climate models.
The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function
Authors: Gu Yue , Jones Amanda E. , Yang Wei , Liu Shanrun , Dai Qian , Liu Yudong , Swindle C. Scott , Zhou Dewang , Zhang Zhuo , Ryan Thomas M. , Townes Tim M. , Klug Christopher A. , Chen Dongquan , Wang Hengbin
Published: December 2015

Significance

Polycomb repressive complex 1 (PRC1) represents an important epigenetic regulator, which exerts its effect on gene expression via histone H2A ubiquitination (ubH2A). We developed a conditional
Usp16
knockout mouse model and demonstrated that
Usp16
is indispensable for hematopoiesis and hematopoietic stem cell (HSC) lineage commitment. We identified Usp16 to be a H2A deubiquitinase that counterbalances the PRC1 ubiquitin ligase to control ubH2A level in the hematopoietic system. Conditional
Usp16
deletion led to altered expression of many regulators of chromatin organization and hematopoiesis. In addition, Usp16 maintains normal HSC cell cycle status via repressing the expression of
Cdkn1a
, which encodes p21cip1, an inhibitor of cell cycle entry. This study provides novel insights into the epigenetic mechanism that regulates hematopoiesis and HSC function.
Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in
Mob1a/1b
-deficient mice
Authors: Nishio Miki , Sugimachi Keishi , Goto Hiroki , Wang Jia , Morikawa Takumi , Miyachi Yosuke , Takano Yusuke , Hikasa Hiroki , Itoh Tohru , Suzuki Satoshi O. , Kurihara Hiroki , Aishima Shinichi , Leask Andrew , Sasaki Takehiko , Nakano Toru , Nishina Hiroshi , Nishikawa Yuji , Sekido Yoshitaka , Nakao Kazuwa , Shin-ya Kazuo , Mimori Koshi , Suzuki Akira
Published: December 2015

Significance

Patients with intrahepatic cholangiocellular carcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (cHC-CC) have worse prognoses than those with hepatocellular carcinoma and rarely show clinical responses to drugs. Our analyses of mice with liver-specific deletions of Mps One Binder Kinase Activator (MOB)1A/1B reveal that MOB1A/1B constitute the most important hub of Hippo signaling in mammalian liver. MOB1A/1B maintain hepatocyte stem/progenitor cell quiescence and are potent tumor suppressors, especially in cHC-CCs and ICCs. Because these functions depend on the Hippo target
Yap1
/
Taz
and the
Yap1/Taz
targets
Tgfb
s, our data point to a new therapeutic approach for liver cancer based on inhibition of MOB1-YAP1/TAZ and/or TGF-βs–SMADs signaling. Our demonstration that well-tolerated and already-approved antiparasitic drugs inhibit YAP1 signaling may point to a new route of treatment for these cancers that can be rapidly tested and implemented.
Modeling the status, trends, and impacts of wild bee abundance in the United States
Authors: Koh Insu , Lonsdorf Eric V. , Williams Neal M. , Brittain Claire , Isaacs Rufus , Gibbs Jason , Ricketts Taylor H.
Published: December 2015

Significance

In 2014, a presidential memorandum called for an assessment of the nation’s pollinators, in response to growing awareness of their economic importance and recent declines. We assess, for the first time to our knowledge, the status and trends of wild bee abundance and their potential impacts on pollination services across the United States. We develop national maps of wild bee abundance, report land-use–driven changes over time, and relate them to trends in agricultural demand for pollination. We estimate uncertainty in the findings, so future research can target the least-understood regions and topics. Our findings can also help focus conservation efforts where declines in bee abundance are most certain, especially where agricultural demand for pollination services is growing.
From convection rolls to finger convection in double-diffusive turbulence
Authors: Yang Yantao , Verzicco Roberto , Lohse Detlef
Published: December 2015

Significance

Double-diffusive convection occurs in many natural flows with fluid density determined by two scalar components, such as the thermohaline convection in the ocean. It plays a crucial role in mixing and scalar transport. Here we report a systematic study of such flow under a destabilizing salinity gradient and a stabilizing temperature gradient. Counterintuitively, applying an extra stabilizing temperature gradient may enhance the salinity transfer even though the velocity becomes smaller. This happens when large-scale convection rolls are replaced by well-organized salt fingers. We identify the parameter ranges for different flow regimes and demonstrate that the Grossmann–Lohse theory can accurately predict the salinity transfer rate for a wide range of control parameters.
Limitations of GCTA as a solution to the missing heritability problem
Authors: Krishna Kumar Siddharth , Feldman Marcus W. , Rehkopf David H. , Tuljapurkar Shripad
Published: December 2015

Significance

The genetic contribution to a phenotype is frequently measured by heritability, the fraction of trait variation explained by genetic differences. Hundreds of publications have found DNA polymorphisms that are statistically associated with diseases or quantitative traits [genome-wide association studies (GWASs)]. Genome-wide complex trait analysis (GCTA), a recent method of analyzing such data, finds high heritabilities for such phenotypes. We analyze GCTA and show that the heritability estimates it produces are highly sensitive to the structure of the genetic relatedness matrix, to the sampling of phenotypes and subjects, and to the accuracy of phenotype measurements. Plausible modifications of the method aimed at increasing stability yield much smaller heritabilities. It is essential to reevaluate the many published heritability estimates based on GCTA.
Age, Growth, and Reproduction in Two Coastal Populations of Longnose Gars
Authors: Smylie Meredith , Shervette Virginia , McDonough Chris
Published: December 2015

Measurements of age, growth, and reproduction are excellent tools for determining the ecological role and impact of a species within an ecosystem. Longnose Gar Lepisosteus osseus is a large, ubiquitous top predator in fresh and saline waters of the eastern United States. Even though the species is common, their basic biology has been largely uncharacterized in brackish and marine waters. Specimens were collected from two estuaries: Winyah Bay and Charleston Harbor, South Carolina, from May 2012 through July 2013 to examine age, growth, and reproduction in tidally influenced systems. This species is fairly long‐lived, with maximum ages of 17 and 25 years for males and females, respectively. The von Bertalanffy growth model yielded significantly higher growth rates for males than for females. Reproductive histology and the gonadosomatic index indicated that Longnose Gars exhibit determinate fecundity and spawn in late spring following a long development period during fall and winter. These life history parameters provide valuable insight into the basic biology of Longnose Gars and into how they function in estuarine environments. Further research on the precise timing and location of spawning movement, as well as daily movement patterns of this species, would provide a more comprehensive knowledge of Longnose Gar reproductive biology.
Endosomal Na+/H+exchanger NHE5 influences MET recycling and cell migration
Authors: Fan Steven Hung-Yi , Numata Yuka , Numata Masayuki
Published: December 2015

Increased recycling and elevated cell surface expression of receptors serve as a mechanism for persistent receptor-mediated signaling. We show that the neuron-enriched Na+/H+exchanger NHE5 is abundantly expressed in C6 glioma cells and plays an important part in regulating cell surface expression of the receptor tyrosine kinases MET and EGF receptor. NHE5 is associated with transferrin receptor (TfR)- and Rab11-positive recycling endosomal membranes, and NHE5 knockdown by short hairpin RNA significantly elevates pH of TfR-positive recycling endosomes. We present evidence that NHE5 facilitates MET recycling to the plasma membrane, protects MET from degradation, and modulates HGF-induced phosphatidylinositol-3-kinase and mitogen-activated protein kinase signaling. Moreover, NHE5 depletion abrogates Rac1 and Cdc42 signaling and actin cytoskeletal remodeling. We further show that NHE5 knockdown impairs directed cell migration and causes loss of cell polarity. Our study highlights a possible role of recycling endosomal pH in regulating receptor-mediated signaling through vesicular trafficking.
Abnormal intermediate filament organization alters mitochondrial motility in giant axonal neuropathy fibroblasts
Authors: Lowery Jason , Jain Nikhil , Kuczmarski Edward R. , Mahammad Saleemulla , Goldman Anne , Gelfand Vladimir I. , Opal Puneet , Goldman Robert D.
Published: December 2015

Giant axonal neuropathy (GAN) is a rare disease caused by mutations in the GAN gene, which encodes gigaxonin, an E3 ligase adapter that targets intermediate filament (IF) proteins for degradation in numerous cell types, including neurons and fibroblasts. The cellular hallmark of GAN pathology is the formation of large aggregates and bundles of IFs. In this study, we show that both the distribution and motility of mitochondria are altered in GAN fibroblasts and this is attributable to their association with vimentin IF aggregates and bundles. Transient expression of wild-type gigaxonin in GAN fibroblasts reduces the number of IF aggregates and bundles, restoring mitochondrial motility. Conversely, silencing the expression of gigaxonin in control fibroblasts leads to changes in IF organization similar to that of GAN patient fibroblasts and a coincident loss of mitochondrial motility. The inhibition of mitochondrial motility in GAN fibroblasts is not due to a global inhibition of organelle translocation, as lysosome motility is normal. Our findings demonstrate that it is the pathological changes in IF organization that cause the loss of mitochondrial motility.
Conformational states of syntaxin-1 govern the necessity of N-peptide binding in exocytosis of PC12 cells and Caenorhabditis elegans
Authors: Park Seungmee , Bin Na-Ryum , Michael Rajah Maaran , Kim Byungjin , Chou Ting-Chieh , Kang Soo-young Ann , Sugita Kyoko , Parsaud Leon , Smith Matthew , Monnier Philippe P. , Ikura Mitsuhiko , Zhen Mei , Sugita Shuzo
Published: December 2015

Syntaxin-1 is the central SNARE protein for neuronal exocytosis. It interacts with Munc18-1 through its cytoplasmic domains, including the N-terminal peptide (N-peptide). Here we examine the role of the N-peptide binding in two conformational states (“closed” vs. “open”) of syntaxin-1 using PC12 cells and Caenorhabditis elegans. We show that expression of “closed” syntaxin-1A carrying N-terminal single point mutations (D3R, L8A) that perturb interaction with the hydrophobic pocket of Munc18-1 rescues impaired secretion in syntaxin-1–depleted PC12 cells and the lethality and lethargy of unc-64 ( C. elegans orthologue of syntaxin-1)-null mutants. Conversely, expression of the “open” syntaxin-1A harboring the same mutations fails to rescue the impairments. Biochemically, the L8A mutation alone slightly weakens the binding between “closed” syntaxin-1A and Munc18-1, whereas the same mutation in the “open” syntaxin-1A disrupts it. Our results reveal a striking interplay between the syntaxin-1 N-peptide and the conformational state of the protein. We propose that the N-peptide plays a critical role in intracellular trafficking of syntaxin-1, which is dependent on the conformational state of this protein. Surprisingly, however, the N-peptide binding mode seems dispensable for SNARE-mediated exocytosis per se, as long as the protein is trafficked to the plasma membrane.
The State of Medical Student Performance Evaluations: Improved Transparency or Continued Obfuscation?
Authors: Hom Jason , Richman Ilana , Hall Philip , Ahuja Neera , Harman Stephanie , Harrington Robert , Witteles Ronald
Published: December 2015

Purpose

The medical student performance evaluation (MSPE), a letter summarizing academic performance, is included in each medical student’s residency application. The extent to which medical schools follow Association of American Medical Colleges (AAMC) recommendations for comparative and transparent data is not known. This study’s purpose was to describe the content, interpretability, and transparency of MSPEs.

Method

This cross-sectional study examined one randomly selected MSPE from every Liaison Committee on Medical Education–accredited U.S. medical school from which at least one student applied to the Stanford University internal medical residency program during the 2013–2014 application cycle. The authors described the number, distribution, and range of key words and clerkship grades used in the MSPEs and the proportions of schools with missing or incomplete data.

Results

The sample included MSPEs from 117 (89%) of 131 medical schools. Sixty schools (51%) provided complete information about clerkship grade and key word distributions. Ninety-six (82%) provided comparative data for clerkship grades, and 71 (61%) provided complete key word data. Key words describing overall performance were extremely heterogeneous, with a total of 72 used and great variation in the assignment of the top designation (median: 24% of students; range: 1%–60%). There was also great variation in the proportion of students awarded the top internal medicine clerkship grade (median: 29%; range: 2%–90%).

Conclusions

The MSPE is a critical component of residency applications, yet data contained within MSPEs are incomplete and variable. Approximately half of U.S. medical schools do not follow AAMC guidelines for MSPEs.
OPTOMAP WIDEFIELD IMAGING OF THE ARGUS II RETINAL PROSTHESIS IN PATIENTS WITH RETINITIS PIGMENTOSA
Authors: Israelsen Paul E. , Sadda SriniVas R. , Dorn Jessy D. , Humayun Mark S. , Olmos de Koo Lisa C.
Published: December 2015

Purpose:

To explore the utility of using ultra-widefield imaging to visualize the Argus II implant in the eyes of three patients with retinitis pigmentosa.

Methods:

Case series of three patients with retinitis pigmentosa who were implanted with the Argus II Retinal Prosthesis System; two of whom were enrolled in the Argus II clinical trial and one received the implant after the commercial release of the device. Optomap widefield fundus autofluorescence and color images of both eyes were taken in all three patients by an experienced technician using the Optos 200Tx imaging system. Analysis focused on fundus autofluorescence images of the implanted eyes and consisted of assessing the location and configuration of the Argus II electrode array and cable, and also the condition of the surrounding retina. Analysis was led by an experienced vitreoretinal surgeon.

Results:

Optos fundus autofluorescence images of the implanted eyes in all 3 patients gave a wide-angle view of the retina, with the electrode array and cable clearly visible. The status of the array and cable was able to be determined without difficulty. All 3 cases showed an appropriate mild-to-moderate bowing of the cable, and also the electrode array being positioned on or near the macula with a superotemporal tilt. Other features, such as “bone spicules,” were also clearly seen. Optos color images were not as useful in the analysis because of an exaggerated green light artifact seen in the implanted versus the nonimplanted eyes.

Conclusion:

Optomap fundus autofluorescence widefield images are useful in determining the configuration of the Argus II cable and the position of the electrode array on the retina and therefore are a useful component of the postoperative surveillance of patients implanted with the device. Using autofluorescence avoids the generation of a light reflection artifact often seen with Optos color imaging.
Absence of Maternal Microchimerism in Regional Lymph Nodes of Children With Biliary Atresia
Authors: Engelmann Carsten , Maelzer Madeleine , Kreyenberg Hermann
Published: December 2015

Objective:

Maternal lymphocytes have been cited as a potential cause of infantile biliary atresia (BA). When hepatoportoenterostomy is performed, locoregional lymphadenopathy is frequently encountered.

Methods:

We screened enlarged nodes from 6 consecutive nonsyndromatic BA patients (age: 68 days ± 18.9 days) for maternal elements using DNA fingerprinting with short tandem repeat analysis and quantitative real‐time polymerase chain reaction for allelic (single nucleotide) sequence polymorphisms.

Results:

Although being partly positive in infants’ peripheral blood, no maternal microchimerism could be demonstrated in any of the lymph nodes.

Conclusion:

This result challenges the hypothesis that maternal cells play a role in hilar lymphadenopathy of children with BA.
Universal remote quantum computation assisted by the cavity input–output process
Authors: Luo Ming-Xing , Wang Xiaojun
Published: December 2015

Quantum computing may provide potential superiority to solve some difficult problems. We propose a scheme for scalable remote quantum computation based on an interface between the photon and the spin of an electron confined in a quantum dot embedded in a microcavity. By successively interacting auxiliary photon pulses with spins charged in optical cavities, a prototypical quantum controlled–controlled flip gate (Toffoli gate) is achieved on a remote three-spin system using only one Einstein–Podolsky–Rosen entanglement, and local operations and classical communication. Our proposed model is shown to be robust to practical noise and experimental imperfections in current cavity–quantum electrodynamics techniques.
Weightlifting and the actomyosin cycle
Authors: Cohen C. , Texier B. Darbois , Laffaye G. , Auvray L. , Clanet C.
Published: December 2015

How does a human lift a weight? Can we relate the dynamics of the lift to the molecular actin–myosin interactions responsible for muscle contraction? We address these questions with bench press experiments that we analyse with a theoretical model, based on the sliding filament theory. The agreement is fair, and we discuss its possible extension to medical diagnostics.
Vibrations of thin plates with small clamped patches
Authors: Lindsay A. E. , Hao W. , Sommese A. J.
Published: December 2015

Eigenvalues of fourth-order elliptic operators feature prominently in stability analysis of elastic structures. This paper considers out-of-plane modes of vibration of a thin elastic plate perforated by a collection of small clamped patches. As the radius of each patch shrinks to zero, apoint constraint eigenvalue problemis derived in which each patch is replaced by a homogeneous Dirichlet condition at its centre. The limiting problem is consequently not the eigenvalue problem with no patches, but a new type of spectral problem. The discrepancy between the eigenvalues of the patch-free and point constraint problems is calculated. The dependence of the point constraint eigenvalues on the location(s) of clamping is studied numerically using techniques from numerical algebraic geometry. The vibrational frequencies are found to depend very sensitively on the number and centre(s) of the clamped patches. For a range of number of punctures, we find spatial clamping patterns that correspond to local maxima of the base vibrational frequency of the plate.
Mixed-mode dynamics of certain bistable oscillators: behavioural mapping, approximations for motion and links with van der Pol oscillators
Authors: Kovacic Ivana , Cartmell Matthew , Zukovic Miodrag
Published: December 2015

This study is concerned with a new generalized mathematical model for single degree-of-freedom bistable oscillators with harmonic excitation of low-frequency, linear viscous damping and a restoring force that contains a negative linear term and a positive nonlinear term which is a power-form function of the generalized coordinate. Comprehensive numerical mapping of the range of bifurcatory behaviour shows that such non-autonomous systems can experience mixed-mode oscillations, including bursting oscillations (fast flow oscillations around the outer curves of a slow flow), and relaxation oscillations like a classical (autonomous) van der Pol oscillator. After studying the global system dynamics the focus of the investigations is on cubic oscillators of this type. Approximate techniques are presented to quantify their response, i.e. to determine approximations for both the slow and fast flows. In addition, a clear analogy between the behaviour of two archetypical oscillators—the non-autonomous bistable oscillator operating at low frequency and the strongly damped autonomous van der Pol oscillator—is established for the first time.
Deviated linear cyclic pursuit
Authors: Mukherjee Dwaipayan , Ghose Debasish
Published: December 2015

This paper analyses deviated linear cyclic pursuit in which an agent pursues its leader with an angle of deviation in both the continuous- and discrete-time domains, while admitting heterogeneous gains and deviations for the agents. Sufficient conditions for the stability of such systems, in both the domains, are presented in this paper along with the derivation of the reachable set, which is a set of points where the agents may converge asymptotically. The stability conditions are derived based on Gershgorin's theorem. Simulations validating the theoretical results presented in this paper are provided.
State aggregation for fast likelihood computations in molecular evolution
Authors: Davydov Iakov I. , Robinson-Rechavi Marc , Salamin Nicolas
Published: December 2015

Motivation

Codon models are widely used to identify the signature of selection at the molecular level and to test for changes in selective pressure during the evolution of genes encoding proteins. The large size of the state space of the Markov processes used to model codon evolution makes it difficult to use these models with large biological datasets. We propose here to use state aggregation to reduce the state space of codon models and, thus, improve the computational performance of likelihood estimation on these models.

Results

We show that this heuristic speeds up the computations of the M0 and branch-site models up to 6.8 times. We also show through simulations that state aggregation does not introduce a detectable bias. We analysed a real dataset and show that aggregation provides highly correlated predictions compared to the full likelihood computations. Finally, state aggregation is a very general approach and can be applied to any continuous-time Markov process-based model with large state space, such as amino acid and coevolution models. We therefore discuss different ways to apply state aggregation to Markov models used in phylogenetics.

Availability

The heuristic is implemented in thegodonpackage (https://bitbucket.org/Davydov/godon) and in a version of FastCodeML (https://gitlab.isb-sib.ch/phylo/fastcodeml).
Lipocalin‐2 exacerbates psoriasiform skin inflammation by augmenting T‐helper 17 response
Authors: Hau Carren S. , Kanda Naoko , Tada Yayoi , Shibata Sayaka , Uozaki Hiroshi , Fukusato Toshio , Sato Shinichi , Watanabe Shinichi
Published: December 2015

Lipocalin‐2 (LCN2) is an antimicrobial protein and adipokine associated with insulin resistance, obesity and atherosclerotic disease. Psoriasis is a T‐helper (Th)1/Th17‐mediated, chronic inflammatory dermatosis related to metabolic syndromes and serum LCN2 levels are elevated in psoriatic patients. We examined the in vivo effects of LCN2 on topical imiquimod (IMQ)‐induced psoriasiform skin in BALB/c mice and in vitro on human keratinocytes (KC). Clinically, i.p. injected LCN2 exacerbated erythema and scaling in IMQ‐treated murine skin compared with phosphate‐buffered saline injection alone, and it augmented interleukin (IL)‐17A, IL‐17F, IL‐22, IL‐23p19, IL‐12p40, CCL20, tumor necrosis factor‐α, chemokine (C‐X‐C motif) ligand (CXCL)1, CXCL2, DEFB4, DEFB14, LCN2 and S100A7 mRNA levels of IMQ‐treated murine skin while it did not increase the mRNA levels of interferon‐γ, IL‐12p35 or CXCL10. LCN2 in synergy with IL‐17 increased mRNA levels of CCL20, LCN2 and DEFB4A but not of CXCL10 in human KC in vitro. These results suggest that LCN2 enhances the expression of Th17 cytokines/chemokines and antimicrobial peptides in murine IMQ‐treated psoriatic skin and KC. LCN2 may potentiate the development of psoriasis via the enhancement of Th17‐ and antimicrobial peptide‐mediated inflammation.
Mast cell chymase in experimentally induced psoriasis
Authors: Suttle Mireille‐Maria , Harvima Ilkka T.
Published: December 2015

Mast cell chymase can have a pro‐inflammatory or an immunosuppressive function in psoriasis, but the outcome may depend on the level of chymase activity. Therefore, mast cells showing chymase activity (Chyact) and immunoreactivity (Chyprot) were studied during the Köbner reaction (0 days, 2 h, 1 day, 3 days and 7 days) of psoriasis induced by the tape‐stripping technique. Also, the effect of recombinant human chymase (rh‐chymase) or human LAD2 mast cells (LAD2) on the 3H‐thymidine uptake of psoriatic peripheral blood mononuclear cells (PBMC) or total T cells was studied. The Chyact/Chyprot ratio tended to be higher in all time‐point biopsies in the Köbner‐negative (n = 10) than ‐positive (n = 8) group (P = 0.073), although chymase activity decreased significantly at 2 h to 1 day only in the Köbner‐negative group. rh‐chymase (0.05–0.5 μg/mL) stimulated to a varying extent PBMC in eight out of nine cultures, but in all cultures 5 μg/mL rh‐chymase turned the stimulation towards inhibition. The effect of rh‐chymase on T cells varied from stimulation to inhibition, but in 11 of 15 cultures rh‐chymase, at least at 5 μg/mL, produced a change to inhibition. In co‐cultures, LAD2 inhibited PBMC in the absence of soybean trypsin inhibitor (SBTI). In the presence of SBTI, LAD2 stimulated PBMC in the majority of seven cultures. In summary, the psoriatic immunopathogenesis may be promoted at low, but controlled at high, activity status of chymase.
Microorganisms inhabiting follicular contents of facial acne are not only Propionibacterium but also Malassezia spp.
Authors: Akaza Narifumi , Akamatsu Hirohiko , Numata Shigeki , Yamada Shunji , Yagami Akiko , Nakata Satoru , Matsunaga Kayoko
Published: December 2015

To clarify the relationship between major cutaneous microorganisms (Propionibacterium, Staphylococcus and Malassezia spp.) and acne vulgaris (acne), we examined the microbiota quantitatively in the follicular contents of inflammatory acne and on the facial skin of patients with acne. Fifteen Japanese untreated acne outpatients were studied. The follicular contents from inflammatory acne lesions of the face were collected using a comedo extractor. The skin surface samples were obtained by the swab method from 10 cm2 of facial skin. The microbiota was analyzed using polymerase chain reaction. The microbiota in follicular contents was similar to that on the skin surface, namely, there were large populations of Propionibacterium spp., Staphylococcus spp. and Malassezia spp. Moreover, the number of Malassezia spp. on the skin surface was correlated with that of inflammatory acne and that in follicular contents. This study clarified that there are large populations of Propionibacterium spp., Staphylococcus spp. and Malassezia spp. in follicular contents. These results suggest the possibility that not only Propionibacterium acnes but also other cutaneous resident microorganisms are related to acne. Particularly, we considered that Malassezia spp. is closely related.