bluuebunny/crossref_metadata_2025 huggingface dataset:
Low resistivity contact on n-type Ge using low work-function Yb with a thin TiO2 interfacial layer
Authors: Dev Sachin , Remesh Nayana , Rawal Yaksh , Manik Prashanth Paramahans , Wood Bingxi , Lodha Saurabh
Published: March 2016

This work demonstrates the benefit of a lower contact barrier height, and hence reduced contact resistivity (ρc), using a low work-function metal (Yb) in unpinned metal-interfacial layer-semiconductor (MIS) contacts on n-type Ge. Fermi-level unpinning in MIS contacts on n-Ge is first established by introducing a 2 nm TiO2−x interfacial layer between various contact metals (Yb, Ti, Ni, Pt) and n-Ge. Further, Yb/TiO2−x/n-Ge MIS contact diodes exhibit higher current densities (up to 100×) and lower effective contact barrier height (up to 30%) versus Ti/TiO2−x control devices over a wide range of TiO2−x thickness (1–5 nm). Finally, low work-function Yb combined with doped TiO2−x having a low conduction band offset with Ge and high substrate doping (n+-Ge: 2.5×1019 cm−3) is shown to result in an ultra-low ρc value of 1.4 × 10−8 Ω cm2, 10 × lower than Ti/TiO2−x control devices.
Characterization of the magnetization reversal of perpendicular Nanomagnetic Logic clocked in the ns-range
Authors: Ziemys Grazvydas , Trummer Christian , Gamm Stephan Breitkreutz-v. , Eichwald Irina , Schmitt-Landsiedel Doris , Becherer Markus
Published: March 2016

We have investigated the magnetization reversal of fabricated Co/Pt nanomagnets with perpendicular anisotropy within a wide range of magnetic field pulse widths. This experiment covers the pulse lengths from 700 ms to 20 ns. We observed that the commonly used Arrhenius model fits very well the experimental data with a single parameter set for pulse times above 100 ns (tp > 100 ns). However, below 100 ns (tp < 100 ns), a steep increase of the switching field amplitude is observed and the deviation from the Arrhenius model becomes unacceptable. For short pulse times the model can be adjusted by the reversal time term for the dynamic switching field which is only dependent on the pulse amplitude and not on temperature anymore. Precise modeling of the magnetization reversal in the sub-100 ns-range is crucially important to ensure reliable operation in the favored GHz-range as well as to explore and design new kinds of Nanomagnetic Logic circuits and architectures.
Large-scale micromagnetics simulations with dipolar interaction using all-to-all communications
Authors: Tsukahara Hiroshi , Lee S.-J. , Iwano Kaoru , Inami Nobuhito , Ishikawa Tadashi , Mitsumata Chiharu , Yanagihara Hideto , Kita Eiji , Ono Kanta
Published: March 2016

We implement on our micromagnetics simulator low-complexity parallel fast-Fourier-transform algorithms, which reduces the frequency of all-to-all communications from six to two times. Almost all the computation time of micromagnetics simulation is taken up by the calculation of the magnetostatic field which can be calculated using the fast Fourier transform method. The results show that the simulation time is decreased with good scalability, even if the micromagentics simulation is performed using 8192 physical cores. This high parallelization effect enables large-scale micromagentics simulation using over one billion to be performed. Because massively parallel computing is needed to simulate the magnetization dynamics of real permanent magnets composed of many micron-sized grains, it is expected that our simulator reveals how magnetization dynamics influences the coercivity of the permanent magnet.
Evaluation of stress distribution due to shearing in non-oriented electrical steel by using synchrotron radiation
Authors: Zaizen Yoshiaki , Omura Takeshi , Fukumura Masaru , Senda Kunihiro , Toda Hiroaki
Published: March 2016

The influence of the shearing process on the iron loss of non-oriented electrical steels with grain sizes of 10 μm-150 μm was investigated. The deterioration ratio of iron loss was clearly smaller in sample with small grain sizes. The droop height, reflecting the amount of plastic deformation, displayed a good relationship with the deterioration of iron loss under the effect of the material grain size. To clarify the strain distribution around the sheared edge, the elastic strain in a sheet sample with the thickness of 0.30 mm and grain size of 10 μm was evaluated by using synchrotron radiation. The width of the region of elastic strain due to shearing was two or three times of the material thickness. The results of the plastic strain distribution obtained by the measurements were then used to estimate the iron loss deterioration rate in 5 mm width sheared samples. The estimated loss deteriotation coincided with the actual measured iron loss.
Tailoring Curie temperature and magnetic anisotropy in ultrathin Pt/Co/Pt films
Authors: Parakkat Vineeth Mohanan , Ganesh K. R. , Anil Kumar P. S.
Published: March 2016

The dependence of perpendicular magnetization and Curie temperature (Tc) of Pt/Co/Pt thin films on the thicknesses of Pt seed (Pts) and presence of Ta buffer layer has been investigated in this work. Pt and Co thicknesses were varied between 2 to 8 nm and 0.35 to 1.31 nm (across the spin reorientation transition thickness) respectively and the Tc was measured using SQUID magnetometer. We have observed a systematic dependence of Tc on the thickness of Pts. For 8nm thickness of Pts the Co layer of 0.35nm showed ferromagnetism with perpendicular anisotropy at room temperature. As the thickness of the Pts was decreased to 2nm, the Tc went down below 250K. XRD data indicated polycrystalline growth of Pts on SiO2. On the contrary Ta buffer layer promoted the growth of Pt(111). As a consequence Ta(5nm)/Pt(3nm)/Co(0.35nm)/Pt(2nm) had much higher Tc (above 300K) with perpendicular anisotropy when compared to the same stack without the Ta layer. Thus we could tune the ferromagnetic Tc and anisotropy by varying the Pts thickness and also by introducing Ta buffer layer. We attribute these observations to the micro-structural evolution of Pts layer which hosts the Co layer.
Two-dimensional chiral asymmetry in unidirectional magnetic anisotropy structures
Authors: Perna P. , Ajejas F. , Maccariello D. , Cuñado J. L. , Guerrero R. , Niño M. A. , Muñoz M. , Prieto J. L. , Miranda R. , Camarero J.
Published: March 2016

We investigate the symmetry-breaking effects of magnetic nanostructures that present unidirectional (one-fold) magnetic anisotropy. Angular and field dependent transport and magnetic properties have been studied in two different exchange-biased systems, i.e. ferromagnetic (FM)/ antiferromagnetic (AFM) bilayer and spin-valve structures. We experimentally show the direct relationships between the magnetoresistance (MR) response and the magnetization reversal pathways for any field value and direction. We demonstrate that even though the MR signals are related to different transport phenomena, namely anisotropic magnetoresistance (AMR) and giant magnetoresistance (GMR), chiral asymmetries are found around the magnetization hard-axis direction, in both cases originated from the one-fold symmetry of the interfacial exchange coupling. Our results indicate that the chiral asymmetry of transport and magnetic behaviors are intrinsic of systems with an unidirectional contribution.
Demonstration of efficient spin injection and detection in various systems using Fe3O4 based spin injectors
Authors: Bhat Shwetha G. , Anil Kumar P. S.
Published: March 2016

Half-metal based spin injector devices for spin injection and detection application have proven to be efficient owing to their enhanced injection and detection efficiency. In this study, we extend the all-electrical spin injection and detection studies into different systems like Si and GaAs using half-metal Fe3O4 as a spin injector in the presence and absence of tunnel barrier MgO. Injection into GaAs is verified using conventional Fe/MgO/GaAs devices. Room temperature spin injection into both p-type and n-type Si is achieved and the spin injection could be observed down to 100K. Obtained spin relaxation time for these n-type and p-type Si at different temperatures agree well with the existing reports. Further, the temperature dependent spin injection and detection is also successfully achieved in Fe3O4/GaAs (n-type) Schottky devices, and a comparison study of the results with control experiment using Fe/MgO/GaAs (n-type) devices confirm the relaxation to be similar in the GaAs substrate, as expected. Hence, even Fe3O4 material can be effectively used as an efficient spin injector as well as detector, making it an attractive candidate for the room temperature spintronics device applications.
Effects of viscous dissipation on MHD boundary layer flow of Sisko fluid over a stretching cylinder
Authors: Malik M. Y. , Hussain Arif , Salahuddin T. , Awais M.
Published: March 2016

The present study concentrates on the analysis of magnetohydrodynamic boundary layer flow of Sisko fluid over continuously stretching cylinder. The viscous dissipation effect is assumed in heat equation. To modify the governing equations first boundary layer approximations are applied. After this simultaneous partial differential equations are converted into the ordinary differential equations by applying proper similarity transformations. To find the numerical solution of this system of ordinary differential equations shooting method is utilized. Graphs are plotted to figure out the characteristics of physical parameters on momentum and heat equations. The variations of all physical parameters on skin friction coefficient and local Nusselt number are displayed via figures and tables.
Calculation of core loss and copper loss in amorphous/nanocrystalline core-based high-frequency transformer
Authors: Liu Xiaojing , Wang Youhua , Zhu Jianguo , Guo Youguang , Lei Gang , Liu Chengcheng
Published: March 2016

Amorphous and nanocrystalline alloys are now widely used for the cores of high-frequency transformers, and Litz-wire is commonly used as the windings, while it is difficult to calculate the resistance accurately. In order to design a high-frequency transformer, it is important to accurately calculate the core loss and copper loss. To calculate the core loss accurately, the additional core loss by the effect of end stripe should be considered. It is difficult to simulate the whole stripes in the core due to the limit of computation, so a scale down model with 5 stripes of amorphous alloy is simulated by the 2D finite element method (FEM). An analytical model is presented to calculate the copper loss in the Litz-wire, and the results are compared with the calculations by FEM.
Structure, magnetism, and electron-transport properties of Mn2CrGa-based nanomaterials
Authors: Zhang Wenyong , Kharel Parashu , Skomski Ralph , Valloppilly Shah , Li Xingzhong , Sellmyer David J.
Published: March 2016

Mn2CrGa in the disordered cubic structure has been synthesized using rapid quenching and subsequent annealing. The cubic phase transforms to a stable tetragonal phase when a fraction of Cr or Ga is replaced by Pt or Al, respectively. All samples are ferrimagnetic with high Curie temperatures (Tc); Mn2CrGa exhibits the highest Tc of about 813 K. The tetragonal samples have appreciable values of magnetocrystalline anisotropy energy, which leads to an increase in coercivity (Hc) that approaches about 10 kOe in the Pt-doped sample. The Hc linearly increases with a decrease of temperature, concomitant with the anisotropy change with temperature. All samples are metallic and show negative magnetoresistance with room-temperature resistivities on the order of 1 mΩcm. The magnetic properties including high Tc and low magnetic moment suggest that these tetragonal materials have potential for spin-transfer-torque-based devices.
The influence of interface on spin pumping effect in Ni80Fe20 /Tb bilayer
Authors: Yue Jinjin , Jiang Sheng , Zhang Dong , Yuan Honglei , Wang Yukun , Lin Lin , Zhai Ya , Du Jun , Zhai Hongru
Published: March 2016

Focusing on the interface effect of the Ni80Fe20 (Py)/terbium (Tb) bilayer, the influence of interface on the magnetization dynamic damping is investigated systematically. Two series of Py (12 nm)/Tb (d nm) films with and without copper (Cu) (1 nm) interlayer are deposited on silicon (Si) substrates by DC magnetron sputtering at room temperature. From vibrating sample magnetometer (VSM) measurements, the saturation magnetization (Ms) decreases with increasing Tb thickness in Py/Tb bilayer while the decrease of Ms is suppressed efficiently by inserting a Cu layer with even 1 nm of thickness. From the frequency dependence of ferromagnetic resonance (FMR) linewidth, we can obtain the Gilbert damping coefficient (α), α is found to exhibit an extreme enhancement in comparison to the single Py layer and shows an increasing trend with increasing Tb thickness. By inserting the Cu layer, α decreases significantly. From theoretical fitting, the spin diffusion length (λSD) and spin mixing conductance (g↑↓) are determined. It shows that the interface structure influences the spin mixing conductance but not the spin diffusion length.
Magnetic and structural properties of MnRh thin films
Authors: Chaturvedi Anurag , Suzuki Takao
Published: March 2016

A systematic study of magnetic and structural properties of MnRh thin films fabricated onto MgO substrates and amorphous SiO2 has been conducted. All the MnRh thin films thus fabricated are found to be of the CsCl type structure, and exhibit the ferromagnetism at room temperature. The coercivity of about 1.1 kOe was observed at 5 K for films grown onto SiO2 substrates, while coercivity measured at 300 K in all the films were less than 200 Oe. The temperature dependence of magnetization shows thermal hysteresis for all the samples ranging from 150 K to 250 K that varies with the substrates used. The maximum of exchange bias field of 270 Oe and unidirectional magnetic anisotropy constant of 0.35 erg/cm2 at 5K was observed for films grown onto SiO2 substrates better than that observed for the films grown onto MgO substrates. This enhanced exchange bias and unidirectional magnetic anisotropy constant in film grown onto SiO2 is attributed to the strong lattice distortion in such a case.
Kinesin-12 motors cooperate to suppress microtubule catastrophes and drive the formation of parallel microtubule bundles
Authors: Drechsler Hauke , McAinsh Andrew D.
Published: March 2016

Significance

During cell division, molecular motors from the kinesin superfamily, in particular Kinesin-12 (Kif15) and Kinesin-5 (Eg5), play a crucial role in formation of the spindle—a bipolar microtubule array that is essential for accurate chromosome segregation. While Eg5 is well studied, the mechanism by which Kif15 maintains spindle bipolarity in the absence of Eg5 is unknown. In this work we reconstitute Kif15 motors on dynamic microtubules in vitro. We reveal that Kif15 is a multi-function motor that cross-links microtubules and drives transport of one along the other, which results in the formation of parallel microtubule bundles. Additionally, motors track the microtubule tips, maintaining them in a growing state, which can synchronize microtubule dynamics within a bundle.
Hierarchy and extremes in selections from pools of randomized proteins
Authors: Boyer Sébastien , Biswas Dipanwita , Kumar Soshee Ananda , Scaramozzino Natale , Nizak Clément , Rivoire Olivier
Published: March 2016

Significance

Evolution by natural selection requires populations to be sufficiently diverse, but merely counting the number of different individuals provides a poor indication of the potential of a population to satisfy a new selective constraint. To achieve a more relevant characterization of this selective potential, we performed in vitro experiments of selection with populations of partially randomized proteins and analyzed the results quantitatively by high-throughput sequencing. We find that selective potentials in these populations follow simple statistical laws, which can be interpreted with extreme value theory (the mathematical theory of extreme events—here, the rare finding of a protein meeting the selective constraints). Our results provide an approach to quantitatively measure the selective potential of a population.
Sp5 and Sp8 recruit β-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription
Authors: Kennedy Mark W. , Chalamalasetty Ravindra B. , Thomas Sara , Garriock Robert J. , Jailwala Parthav , Yamaguchi Terry P.
Published: March 2016

Significance

Deciphering the mechanisms that underlie stem cell growth and differentiation is key to understanding how embryos develop and will lead to important applications in regenerative medicine. Wnt proteins are powerful regulators of stem cells. We have determined that the Sp1-like transcription factors, Sp5 and Sp8, are components of the Wnt/β-catenin signaling pathway. Sp5/8 promote the differentiation of pluripotent progenitors into the multipotent mesoderm progenitors that largely generate the trunk musculoskeletal system. Unexpectedly, Sp5/8 functions to recruit the transcriptional coactivator β-catenin to select enhancers to stimulate expression of a subset of Wnt target genes. This study reveals a more refined level of Wnt/β-catenin target gene regulation and suggests previously unidentified ways to manipulate the expression of specific Wnt targets.
No difference in the competitive ability of introduced and native Trifolium provenances when grown with soil biota from their introduced and native ranges
Authors: Shelby Natasha , Hulme Philip E. , van der Putten Wim H. , McGinn Kevin J. , Weser Carolin , Duncan Richard P.
Published: March 2016

The evolution of increased competitive ability (EICA) hypothesis could explain why some introduced plant species perform better outside their native ranges. The EICA hypothesis proposes that introduced plants escape specialist pathogens or herbivores leading to selection for resources to be reallocated away from defence and towards greater competitive ability. We tested the hypothesis that escape from soil-borne enemies has led to increased competitive ability in three non-agricultural Trifolium (Fabaceae) species native to Europe that were introduced to New Zealand in the 19th century. Trifolium performance is intimately tied to rhizosphere biota. Thus, we grew plants from one introduced (New Zealand) and two native (Spain and the UK) provenances for each of three species in pots inoculated with soil microbiota collected from the rhizosphere beneath conspecifics in the introduced and native ranges. Plants were grown singly and in competition with conspecifics from a different provenance in order to compare competitive ability in the presence of different microbial communities. In contrast to the predictions of the EICA hypothesis, we found no difference in the competitive ability of introduced and native provenances when grown with soil microbiota from either the native or introduced range. Although plants from introduced provenances of two species grew more slowly than native provenances in native-range soils, as predicted by the EICA hypothesis, plants from the introduced provenance were no less competitive than native conspecifics. Overall, the growth rate of plants grown singly was a poor predictor of their competitive ability, highlighting the importance of directly quantifying plant performance in competitive scenarios, rather than relying on surrogate measures such as growth rate.
IL-15 boosts the function and migration of human terminally differentiated CD8+ T cells by inducing a unique gene signature
Authors: Setoguchi Ruka
Published: March 2016

Human CCR7lowCD45RAhigh effector memory CD8+ T cells (terminally differentiated TEMRA) are reportedly a functionally compromised population with characteristics of cellular senescence when examined ex vivo. Although their frequencies are increased in elderly subjects in association with declined immune competence, however, it remains unclear whether their impaired functions can be reversed so that they contribute to immune responses in vivo. Here, I show that, in contrast to TCR stimulation, stimulation of TEMRA with IL-15 induced a unique transcriptional signature, promoted IFN-γ production and cell cycle entry, and reduced chemotaxis toward sphingosine-1-phosphate (S1P). TEMRA preferentially accumulated in non-lymphoid tissues when transferred into IL-15-treated NOD.SCID.γc-deficient mice compared with non-treated mice. This accumulation was impaired by S1P receptor 1 over-expression. These results suggest that TEMRA act as functional effector T cells in non-lymphoid tissues when IL-15 is abundant and that IL-15 treatment may be beneficial in enhancing vaccine efficacy in elderly people.
Alignments of radio galaxies in deep radio imaging of ELAIS N1
Authors: Taylor A. R. , Jagannathan P.
Published: March 2016

We present a study of the distribution of radio jet position angles of radio galaxies over an area of 1 square degree in the ELAIS N1 field. ELAIS N1 was observed with the Giant Metrewave Radio Telescope at 612 MHz to an rms noise level of 10 μJy and angular resolution of 6 arcsec × 5 arcsec. The image contains 65 resolved radio galaxy jets. The spatial distribution reveals a prominent alignment of jet position angles along a ‘filament’ of about 1°. We examine the possibility that the apparent alignment arises from an underlying random distribution and find that the probability of chance alignment is less than 0.1 per cent. An angular covariance analysis of the data indicates the presence of spatially coherence in position angles on scales >0 $_{.}^{\circ}$5. This angular scales translates to a comoving scale of >20 Mpc at a redshift of 1. The implied alignment of the spin axes of massive black holes that give rise to the radio jets suggest the presence of large-scale spatial coherence in angular momentum. Our results reinforce prior evidence for large-scale spatial alignments of quasar optical polarization position angles.
Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men
Authors: Turner Samuel S. , Gianella Sara , Yip Marcus J-S. , van Seggelen Wouter O. , Gillies Robert D. , Foster Andrew L. , Barbati Zachary R. , Smith Davey M. , Fierer Daniel S.
Published: March 2016

Background.  The epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) has been documented for over a decade. Despite this, there is no consensus as to the risk factors for sexual acquisition of HCV in these men.

Methods.  We obtained paired semen and blood samples at 2-week intervals from HIV-infected MSM with recent and chronic HCV infection and quantified HCV in semen.

Results.  Hepatitis C virus was quantified in 59 semen specimens from 33 men. Hepatitis C virus was shed in 16 (27%) of semen specimens from 11 (33%) of the men. Median HCV viral load (VL) in semen was 1.49 log10 IU/mL. Hepatitis C virus VL in blood was significantly higher at the time of HCV shedding in semen than when HCV shedding in semen was not detected (P = .002). Furthermore, there was a significant correlation between the HCV VL in blood and semen overall (rs = 0.41; P = .001), and in the subgroup with recent HCV infection (rs = 0.37; P = .02), but not in the subgroup with chronic HCV infection (rs = 0.34; P = .1).

Conclusions.  One third of HIV-infected MSM coinfected with HCV shed HCV into their semen. Based on the HCV VL in semen in this study, an average ejaculate would deliver up to 6630 IU of virus into the rectum of the receptive partner. Therefore, our data strongly support that condoms should be used during anal intercourse among MSM to prevent transmission of HCV.
Infectious Diseases (ID) Learning Unit: How Rapidly to Evaluate for Active Tuberculosis Disease in Low-Prevalence Settings
Authors: Chida Natasha , Shah Maunank
Published: March 2016

With declining tuberculosis (TB) incidence in low-prevalence settings, many clinicians are likely unaware that the approach to diagnosing active TB is evolving with newer technologies. Rapid molecular assays are commercially available, and more are likely to enter the market in the coming years. These tests, such as the Xpert MTB/RIF, which can detect TB and drug-resistance in 2 hours, are increasingly used in settings with higher TB prevalence; however, uptake has been slower in low-prevalence settings. Newer algorithms incorporating rapid TB diagnostics have the ability to alter current clinical and infection control practice patterns. In this learning unit, we review current and newly available tests for the detection of active TB disease and their usage in low-prevalence settings.
Combining multiple tools outperforms individual methods in gene set enrichment analyses
Authors: Alhamdoosh Monther , Ng Milica , Wilson Nicholas J. , Sheridan Julie M. , Huynh Huy , Wilson Michael J. , Ritchie Matthew E.
Published: March 2016

Gene set enrichment (GSE) analysis allows researchers to efficiently extract biological insight from long lists of differentially expressed genes by interrogating them at a systems level. In recent years, there has been a proliferation of GSE analysis methods and hence it has become increasingly difficult for researchers to select an optimal GSE tool based on their particular data set. Moreover, the majority of GSE analysis methods do not allow researchers to simultaneously compare gene set level results between multiple experimental conditions.

Results:The ensemble of genes set enrichment analyses (EGSEA) is a method developed for RNA-sequencing data that combines results from twelve algorithms and calculates collective gene set scores to improve the biological relevance of the highest ranked gene sets. redEGSEA’s gene set database contains around 25,000 gene sets from sixteen collections. It has multiple visualization capabilities that allow researchers to view gene sets at various levels of granularity. EGSEA has been tested on simulated data and on a number of human and mouse data sets and, based on biologists' feedback, consistently outperforms the individual tools that have been combined. Our evaluation demonstrates the superiority of the ensemble approach for GSE analysis, and its utility to effectively and efficiently extrapolate biological functions and potential involvement in disease processes from lists of differentially regulated genes.

Availability and Implementation:EGSEA is available as an R package athttp://www.bioconductor.org/packages/EGSEA/. The gene sets collections are available in the R package EGSEAdata fromhttp://www.bioconductor.org/packages/EGSEA/.
Exploratory analysis and error modeling of a sequencing technology
Authors: Inouye Michael , Small Kerrin S. , Teo Yik Y. , Li Heng , Whiteford Nava , Skelly Tom , Abnizova Irina , Turner Daniel J. , Deloukas Panos , Kwiatkowski Dominic P. , Brown Clive G. , Clark Taane G.
Published: March 2016

Next generation DNA sequencing methods have created an unprecedented leap in sequence data generation, thus novel computational tools and statistical models are required to optimize and assess the resulting data. In this report, we explore underlying causes of error for the Illumina Genome Analyzer (IGA) sequencing technology and attempt to quantify their effects using a human bacterial artificial chromosome sequenced to 60,000 fold coverage. Seven potential error predictors are considered:Phredscore, read entropy, tile coordinates, local tile density, base position within read, nucleotide call, and lane. With these parameters, logistic regression and log-linear models are constructed and used to show that each of the potential predictors contributes to error (P<1×10−4). With this additional information, we apply the logistic model and achieve a 3% improvement in both the sensitivity and specificity to detect IGA errors. Further, we demonstrate that these modeling approaches can be used as a feedback loop to inform laboratory methods and identify specific machine or run bias.
Metabolic adaptations in a range expanding arthropod
Authors: Van Petegem Katrien H. P. , Renault David , Stoks Robby , Bonte Dries
Published: March 2016

Despite an increasing number of studies documenting life-history evolution during range expansions or shifts, we lack a mechanistic understanding of the underlying physiological processes. In this explorative study, we used a metabolomics approach to study physiological changes associated with the recent range expansion of the two-spotted spider mite (Tetranychus urticae). Mite populations were sampled along a latitudinal gradient from range core to edge and reared under benign common garden conditions for two generations. Using Gas Chromatography-Mass Spectrometry (GC-MS), we obtained metabolic population profiles, which showed a gradual differentiation along the latitudinal gradient, indicating (epi)genetic changes in the metabolome in association with range expansion. These changes seemed not related with shifts in the mites’ energetic metabolism, but rather with differential use of amino acids. Particularly, more dispersive northern populations showed lowered concentrations of several essential and non-essential amino acids, suggesting a potential downregulation of metabolic pathways associated with protein synthesis.
Comprehensive discovery of subsample gene expression components by information explanation: therapeutic implications in cancer
Authors: Pepke S. , Ver Steeg G.
Published: March 2016

Background

De novoinference of clinically relevant gene function relationships from tumor RNA-seq remains a challenging task. Current methods typically either partition patient samples into a few subtypes or rely upon analysis of pairwise gene correlations (co-expression) that will miss some groups in noisy data. Leveraging higher dimensional information can be expected to increase the power to discern targetable pathways, but this is commonly thought to be an intractable computational problem.

Methods

In this work we adapt a recently developed machine learning algorithm, CorEx, that efficiently optimizes over multivariate mutual information for sensitive detection of complex gene relationships. The algorithm can be iteratively applied to generate a hierarchy of latent factors. Patients are stratified relative to each factor and combinatoric survival analyses are performed and interpreted in the context of biological function annotations and protein network interactions that might be utilized to match patients to multiple therapies.

Results

Analysis of ovarian tumor RNA-seq samples demonstrates the algorithm’s power to infer well over one hundred biologically interpretable gene cohorts, several times more than standard methods such as hierarchical clustering and k-means. The CorEx factor hierarchy is also informative, with related but distinct gene clusters grouped by upper nodes. Some latent factors correlate with patient survival, including one for a pathway connected with the epithelial-mesenchymal transition in breast cancer that is regulated by a potentially druggable microRNA. Further, combinations of factors lead to a synergistic survival advantage in some cases.

Conclusions

In contrast to studies that attempt to partition patients into a small number of subtypes (typically 4 or fewer) for treatment purposes, our approach utilizes subgroup information for combinatoric transcriptional phenotyping. Considering only the 66 gene expression groups that are both found to have significant Gene Ontology enrichment and are small enough to indicate specific drug targets implies a computational phenotype for ovarian cancer that allows for 366possible patient profiles, enabling truly personalized treatment. The findings here demonstrate a new technique that sheds light on the complexity of gene expression dependencies in tumors and could eventually enable the use of patient RNA-seq profiles for selection of personalized and effective cancer treatments.
Comparative analysis of dengue and Zika outbreaks reveals differences by setting and virus
Authors: Funk Sebastian , Kucharski Adam J. , Camacho Anton , Eggo Rosalind M. , Yakob Laith , Murray Lawrence M. , Edmunds W. John
Published: March 2016

The pacific islands of Micronesia have experienced several outbreaks of mosquito-borne diseases over the past decade. In outbreaks on small islands, the susceptible population is usually well defined, and there is no co-circulation of pathogens. Because of this, analysing such outbreaks can be useful for understanding the transmission dynamics of the pathogens involved, and particularly so for yet understudied pathogens such as Zika virus. Here, we compared three outbreaks of dengue and Zika virus in two different island settings in Micronesia, the Yap Main Islands and Fais, using a mathematical model of transmission dynamics, making full use of commonalities in disease and setting between the outbreaks. We found that the estimated reproduction numbers for Zika and dengue were similar when considered in the same setting, but that, conversely, reproduction number for the same disease can vary considerably by setting. On the Yap Main Islands, we estimated a reproduction number of 8.0–16 (95% Credible Interval (CI)) for the dengue outbreak and 4.8–14 (95% CI) for the Zika outbreak, whereas for the dengue outbreak on Fais our estimate was 28–102 (95% CI). We further found that the proportion of cases of Zika reported was smaller (95% CI 1.4%–1.9%) than that of dengue (95% CI 47%–61%). We confirmed these results in extensive sensitivity analysis. They suggest that models for dengue transmission can be useful for estimating the predicted dynamics of Zika transmission, but care must be taken when extrapolating findings from one setting to another.

Author Summary

Dengue and Zika are related viruses and are both transmitted by mosquitoes. Dengue is well described and affects people around the world. Zika, on the other hand has only recently caused outbreak in human populations, and it has been suggested that its behaviour might similar dengue. To investigate this, we compared three outbreaks of dengue and Zika in island populations of the pacific: two dengue outbreaks and one Zika outbreak. Island outbreaks are useful laboratories for understanding the spread of infections because they are usually short, well-identified episodes, whereas elsewhere it can be difficult to identify the properties of outbreaks when different viruses spread at the same time. In our investigation of the outbreaks in Micronesia we found that dengue and Zika virus did, indeed, behave similar in outbreaks they caused on the Yap Main Islands. A dengue outbreak on the smaller island of Fais, on the other hand, was different from the dengue outbreak on Yap in that transmission seems to have been more efficient. We conclude that dengue outbreaks are indeed a good model for Zika outbreaks when considered in the same setting, but that one must be careful when comparing outbreaks in different settings.
Understanding melanopsin using bayesian generative models – an Introduction
Authors: Ehinger Benedikt V. , Eickelbeck Dennis , Spoida Katharina , Herlitze Stefan , König Peter
Published: March 2016

1.

Understanding biological processes implies a quantitative description. In recent years a new tool set, Bayesian hierarchical modeling, has seen rapid development. We use these methods to model kinetics of a specific protein in a neuroscience context: melanopsin. Melanopsin is a photoactive protein in retinal ganglion cells. Due to its photoactivity, melanopsin is widely used in optogenetic experiments and an important component in the elucidation of neuronal interactions. Thus it is important to understand the relevant processes and develop mechanistic models. Here, with a focus on methodological aspects, we develop, implement, fit and discuss Bayesian generative models of melanopsin dynamics.

We start with a sketch of a basic model and then translate it into formal probabilistic language. As melanopsin occurs in at least two states, a resting and a firing state, a basic model is defined by a non-stationary two state hidden Markov process. Subsequently we add complexities in the form of (1) a hierarchical extension to fit multiple cells; (2) a wavelength dependency, to investigate the response at different color of light stimulation; (3) an additional third state to investigate whether melanopsin is bi‐ or tri-stable; (4) differences between different sub-types of melanopsin as found in different species. This application of modeling melanopsin dynamics demonstrates several benefits of Bayesian methods. They directly model uncertainty of parameters, are flexible in the distributions and relations of parameters in the modeling, and allow including prior knowledge, for example parameter values based on biochemical data.
Cerebrospinal Fluid and Interstitial Fluid Motion via the Glymphatic Pathway Modelled by Optimal Mass Transport
Authors: Ratner Vadim , Gao Yi , Lee Hedok , Nedergaard Maikan , Benveniste Helene , Tannenbaum Allen
Published: March 2016

It was recently shown that the brain-wide cerebrospinal fluid (CSF) and interstitial fluid exchange system designated the ‘glymphatic pathway’ plays a key role in removing waste products from the brain, similarly to the lymphatic system in other body organs1,2. It is therefore important to study the flow patterns of glymphatic transport through the live brain in order to better understand its functionality in normal and pathological states. Unlike blood, the CSF does not flow rapidly through a network of dedicated vessels, but rather through peri-vascular channels and brain parenchyma in a slower time-domain, and thus conventional fMRI or other blood-flow sensitive MRI sequences do not provide much useful information about the desired flow patterns. We have accordingly analyzed a series of MRI images, taken at different times, of the brain of a live rat, which was injected with a paramagnetic tracer into the CSF via the lumbar intrathecal space of the spine. Our goal is twofold: (a) find glymphatic (tracer) flow directions in the live rodent brain; and (b) provide a model of a (healthy) brain that will allow the prediction of tracer concentrations given initial conditions. We model the liquid flow through the brain by the diffusion equation. We then use the Optimal Mass Transfer (OMT) approach3to model the glymphatic flow vector field, and estimate the diffusion tensors by analyzing the (changes in the) flow. Simulations show that the resulting model successfully reproduces the dominant features of the experimental data.
An oscillating tragedy of the commons in replicator dynamics with game-environment feedback
Authors: Weitz Joshua S. , Eksin Ceyhun , Paarporn Keith , Brown Sam P. , Ratcliff William C.
Published: March 2016

A tragedy of the commons occurs when individuals take actions to maximize their payoffs even as their combined payoff is less than the global maximum had the players coordinated. The originating example is that of over-grazing of common pasture lands. In game theoretic treatments of this example there is rarely consideration of how individual behavior subsequently modifies the commons and associated payoffs. Here, we generalize evolutionary game theory by proposing a class of replicator dynamics with feedback-evolving games in which environment-dependent payoffs and strategies coevolve. We initially apply our formulation to a system in which the payoffs favor unilateral defection and cooperation, given replete and depleted environments respectively. Using this approach we identify and characterize a new class of dynamics: an oscillatory tragedy of the commons in which the system cycles between deplete and replete environmental states and cooperation and defection behavior states. We generalize the approach to consider outcomes given all possible rational choices of individual behavior in the depleted state when defection is favored in the replete state. In so doing we find that incentivizing cooperation when others defect in the depleted state is necessary to avert the tragedy of the commons. In closing, we propose new directions for the study of control and influence in games in which individual actions exert a substantive effect on the environmental state.
ALADIN is Required for the Production of Fertile Mouse Oocytes
Authors: Carvalhal Sara , Stevense Michelle , Koehler Katrin , Naumann Ronald , Huebner Angela , Jessberger Rolf , Griffis Eric R.
Published: March 2016

Asymmetric cell divisions depend upon the precise placement of the mitotic spindle. In mammalian oocytes, spindles assemble close to the cell’s centre but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphases. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently, we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygous deficient for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is impaired in a majority of oocytes due to problems in spindle orientation prior to the first meiotic anaphase. Those few oocytes that can mature far enough to be fertilized in vitro are unable to support embryonic development beyond the twocell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions.
Nature lessons: the whitefly bacterial endosymbiont is a minimal amino acid factory with unusual energetics
Authors: Calle-Espinosa Jorge , Ponce-de-Leon Miguel , Santos-Garcia Diego , Silva Francisco J. , Montero Francisco , Peretó Juli
Published: March 2016

Bacterial lineages that establish obligate symbiotic associations with insect hosts are known to possess highly reduced genomes with streamlined metabolic functions that are commonly focused on amino acid and vitamin synthesis. We constructed a genome-scale metabolic model of the whitefly bacterial endosymbiontCandidatusPortiera aleyrodidarum to study the energy production capabilities using stoichiometric analysis. Strikingly, the results suggest that the energetic metabolism of the bacterial endosymbiont relies on the use of pathways related to the synthesis of amino acids and carotenoids. A deeper insight showed that the ATP production via carotenoid synthesis may also have a potential role in the regulation of amino acid production. The coupling of energy production to anabolism suggest that minimization of metabolic networks as a consequence of genome size reduction does not necessarily limit the biosynthetic potential of obligate endosymbionts.
Clinicopathological study of crateriform verruca: Crateriform epithelial lesions histopathologically distinct from keratoacanthoma
Authors: Ogita Azusa , Ansai Shin‐ichi , Misago Noriyuki , Anan Takashi , Fukumoto Takaya , Saeki Hidehisa
Published: March 2016

Keratoacanthoma (KA) is a distinct clinicopathological entity, but it is often confused with other crateriform tumors. This study re‐examined the clinicopathological features of 380 crateriform epithelial tumors with a central keratin plug. Seventy‐six tumors (20%) had histopathological features that differed from solitary KA and were more verruca‐like, and we designated these lesions as crateriform verruca (CFV). We performed clinicopathological re‐examination of these neoplasms with a crateriform architecture and epithelial lip‐like structures similar to KA, which also displayed histopathological features reminiscent of verruca vulgaris, such as finger‐like exophytic projections with hyperkeratosis and acanthosis, focal hypergranulosis and arborization. Clinical data on CFV were also summarized. The main histopathological differences from KA were that CFV showed proliferation of keratinocytes with a similar size and regular arrangement, and the base of CFV was well demarcated without endophytic growth. Interestingly, some CFV were partly composed of epithelial cells with large pink cytoplasm in the upper malpighian layer between papillomatous projections. Furthermore, areas of trichilemmal‐like keratinization without formation of the granular layer were seen in some lesions. These types of CFV were hardly distinguishable from KA, unless it is recognized that CFV may contain trichilemmal keratinization‐like areas accompanied by large epithelial cells with eosinophilic cytoplasm. We have proposed the term CFV for these verrucous neoplasms to differentiate them from KA.
Case of paraneoplastic pemphigus with immunoglobulin (Ig)G and IgA antibodies to various antigens
Authors: Otsuka Yohei , Ueno Takashi , Yamase Aya , Ito Michiko , Osada Shinichi , Kawana Seiji , Funasaka Yoko , Teye Kwesi , Ishii Norito , Hashimoto Takashi , Saeki Hidehisa
Published: March 2016

A 63‐year‐old Japanese man with non‐Hodgkin B‐cell lymphoma presented with erythematous skin lesions on his entire body, with oral, ocular and anal mucosal lesions. The patient was diagnosed with paraneoplastic pemphigus. Immunofluorescence showed both immunoglobulin (Ig)G and IgA antibodies to keratinocyte cell surfaces. Various immunoblot and enzyme‐linked immunosorbent assays showed both IgG and IgA antibodies to various autoantigens, including desmogleins, desmocollins, envoplakin, periplakin and bullous pemphigoid antigens. This was a unique case with a very rare autoantibody profile in paraneoplastic pemphigus.
Phylogenetics of family Enterobacteriaceae and proposal to reclassify Escherichia hermannii and Salmonella subterranea as Atlantibacter hermannii and Atlantibacter subterranea gen. nov., comb. nov.
Authors: Hata Hiroyuki , Natori Tatsuya , Mizuno Takuya , Kanazawa Izumi , Eldesouky Ibrahim , Hayashi Masahiro , Miyata Machiko , Fukunaga Hajime , Ohji Shoko , Hosoyama Akira , Aono Eiji , Yamazoe Atsushi , Tsuchikane Keiko , Fujita Nobuyuki , Ezaki Takayuki
Published: March 2016

Multilocus sequence analysis based on hypervariable housekeeping proteins was utilized to differentiate closely related species in the family Enterobacteriaceae. Of 150 housekeeping proteins, the top 10 hypervariable proteins were selected and concatenated to obtain distance data. Distances between concatenated proteins within the family were 0.9–41.2%, whereas the 16S rRNA and atpD‐gyrB‐infB‐rpoB concatenated sequence (4MLSA) distances were 0.8–6.0% and 0.9–22.1%, respectively. These data indicate that phylogenetic analysis by concatenation of hypervariable proteins is a powerful tool for discriminating species in the family Enterobacteriaceae. To confirm the discriminatory power of the 10 chosen concatenated hypervariable proteins (C10HKP), phylogenetic trees based on C10HKP, 4MLSA, and the 16S rRNA gene were constructed. Comparison of average bootstrap values among C10HKP, 4MLSA and 16S rRNA genes indicated that the C10HKP tree was the most reliable. Location via the C10HKP tree was consistent with existing assignments for almost all species in the family Enterobacteriaceae. However, the C10HKP tree suggested that several species (including Enterobacter massiliensis, Escherichia vulneris, Escherichia hermannii, and Salmonella subterranea) should be reassigned to different clusters than those defined in previous analyses. Furthermore, E. hermannii and S. subterranea appeared to fall onto a branch independent from those occupied by the other Enterobacteriaceae. Therefore, we propose Atlantibacter gen. nov., such that E. hermannii and S. subterranea would be transferred to genus Atlantibacter as Atlantibacter hermannii, comb. nov. and Atlantibacter subterranea. comb. nov., respectively.