bluuebunny/crossref_metadata_2025 huggingface dataset:
Interbasis expansions in the Zernike system
Authors: Atakishiyev Natig M. , Pogosyan George S. , Wolf Kurt Bernardo , Yakhno Alexander
Published: October 2017

The differential equation with free boundary conditions on the unit disk that was proposed by Frits Zernike in 1934 to find Jacobi polynomial solutions (indicated as I) serves to define a classical system and a quantum system which have been found to be superintegrable. We have determined two new orthogonal polynomial solutions (indicated as II and III) that are separable and involve Legendre and Gegenbauer polynomials. Here we report on their three interbasis expansion coefficients: between the I–II and I–III bases, they are given by F23(⋯|1) polynomials that are also special su(2) Clebsch–Gordan coefficients and Hahn polynomials. Between the II–III bases, we find an expansion expressed by F34(⋯|1)’s and Racah polynomials that are related to the Wigner 6j coefficients.
Segal-Bargmann-Fock modules of monogenic functions
Authors: Peña Peña Dixan , Sabadini Irene , Sommen Franciscus
Published: October 2017

In this paper, we introduce the classical Segal-Bargmann transform starting from the basis of Hermite polynomials and extending it to Clifford algebra-valued functions. Then we apply the results to monogenic functions and prove that the Segal-Bargmann kernel corresponds to the kernel of the Fourier-Borel transform for monogenic functionals. This kernel is also the reproducing kernel for the monogenic Bargmann module.
A numerical analysis and experimental demonstration of a low degradation conductive bridge resistive memory device
Authors: Berco Dan , Chand Umesh , Fariborzi Hossein
Published: October 2017

This study investigates a low degradation metal-ion conductive bridge RAM (CBRAM) structure. The structure is based on placing a diffusion blocking layer (DBL) between the device's top electrode (TE) and the resistive switching layer (RSL), unlike conventional CBRAMs, where the TE serves as a supply reservoir for metallic species diffusing into the RSL to form a conductive filament (CF) and is kept in direct contact with the RSL. The properties of a conventional CBRAM structure (Cu/HfO2/TiN), having a Cu TE, 10 nm HfO2 RSL, and a TiN bottom electrode, are compared with a 2 nm TaN DBL incorporating structure (Cu/TaN/HfO2/TiN) for 103 programming and erase simulation cycles. The low and high resistive state values for each cycle are calculated and the analysis reveals that adding the DBL yields lower degradation. In addition, the 2D distribution plots of oxygen vacancies, O ions, and Cu species within the RSL indicate that oxidation occurring in the DBL-RSL interface results in the formation of a sub-stoichiometric tantalum oxynitride with higher blocking capabilities that suppresses further Cu insertion beyond an initial CF formation phase, as well as CF lateral widening during cycling. The higher endurance of the structure with DBL may thus be attributed to the relatively low amount of Cu migrating into the RSL during the initial CF formation. Furthermore, this isomorphic CF displays similar cycling behavior to neural ionic channels. The results of numerical analysis show a good match to experimental measurements of similar device structures as well.
Growth and characterization of high quality N-type GaSb/GaAs heterostructure by IMF growth mode using MOCVD for low power application
Authors: Hsiao Chih Jen , Kakkerla Ramesh Kumar , Chang Po Chun , Lumbantoruan Franky Juanda , Lee Tsu Ting , Lin Yueh Chin , Chang Shoou Jinn , Chang Edward Yi
Published: October 2017

In this study, we demonstrate the growth of a 150-nm-thick GaSb layer on a GaAs substrate with excellent film quality using the interfacial misfit dislocation growth mode by the Metal–Organic Chemical Vapor Deposition technique. The n-type GaSb epilayer grown on the GaAs substrate has a low threading dislocation density of 3.2 × 106 cm−2 and a surface roughness of approximately 0.8 nm. A high carrier mobility up to 4600 cm2 V−1 s−1 with a carrier concentration of 1.2 × 1017 cm−3 is achieved in this study. The fabricated Al2O3/GaSb/GaAs MOSCAP demonstrated excellent capacitance–voltage (C–V) characteristics with a small frequency dispersion of approximately 2.8%/decade. The results demonstrate the potential of high-mobility Sb-based materials on GaAs for p-type channel CMOS applications in the future.
Dye concentration dependence of spectral triplet in one-dimensional photonic crystal with cyanine dye J-aggregate in strong coupling regime
Authors: Suzuki Makoto , Sakata Tomohiro , Takenobu Ryouya , Uemura Shinobu , Miyagawa Hayato , Nakanishi Shunsuke , Tsurumachi Noriaki
Published: October 2017

We report on the dye concentration dependence of nonlinear transmission properties of one-dimensional photonic crystal microcavities containing cyanine dye J-aggregates. Using femtosecond nonlinear transmission spectroscopy, we observed a transition from a polariton doublet state to a spectral triplet state over the whole tested concentration range, even at room temperature. In these samples, changes in the dye concentration affected the Rabi splitting energy in the linear transmission measurements; however, we found that changes in the concentration did not greatly affect the triplet formation.
Protective effects of taurine on growth performance and intestinal epithelial barrier function in weaned piglets challenged without or with lipopolysaccharide
Authors: Tang Zhiru , Liu Jinyan , Sun Zhihong , Li Jinlong , Sun Weizhong , Mao Junxia , Wang Yao
Published: October 2017

We evaluated whether weaned piglets were protected from bacterial endotoxins by placing the animals on a taurine-supplemented diet. A total of 40 weaned Landrace × Yorkshire piglets (5.75 ± 0.58 kg, weaned at 21 days) were allocated to four groups with 10 barrows per group, following a 2 × 2 factorial design with two inclusion levels of lipopolysaccharide (LPS) (no or one time peritoneal injection by the dose of 100 µg/kg bodyweight on Day 7 of the trial) and two inclusion levels of dietary taurine (no or 0.1% taurine in a basal diet in the whole trial). There was a significant interaction between LPS and taurine with regard to growth and small intestinal mucosal membrane integrity, morphology, immune parameters, and antioxidant capacity (P < 0.05). Feed conversion, daily weight gain, daily feed intake, villus height, and the villus to crypt ratio, vascular endothelial growth factor, regenerating islet-derived protein 3 gamma, trefoil factor-3, transforming growth factor β-1 expression, number of goblet cells and the least amount of claudin-1, occludin, zonula occludens-1, serum glutathione peroxidase, nitrogen oxide synthase, superoxide dismutase, peroxidase, and total antioxidant was lowest in LPS-challenged animals. Furthermore, animals in the LPS group had the highest serum diamine oxidase concentration, number of lymphocytes, concentrations of calprotectin, sIgA, toll-like receptor-4, mRNA levels of interleukin-1β, interleukin-8, toll-like receptor-4, and tumour necrosis factor-α (P < 0.05). These data suggested that the peritoneal injection administration of LPS decreased growth performance and disrupted small intestinal mucosal membrane integrity and triggered an inflammatory response in the small intestinal mucosal membrane. Dietary administration of taurine improved growth performance, increased small intestinal villus height, stimulated immune and antioxidant function and improved small intestinal mucosal membrane integrity in weaned piglets challenged without or with LPS (P < 0.05). The beneficial effects of taurine were likely due to decreased stimulation of the immune response to LPS and an improvement in intestinal epithelial barrier function. Dietary administration of taurine could prevent weaned piglets from intestinal damage by LPS of Gram-negative bacteria.
Electron leak from NDUFA13 within mitochondrial complex I attenuates ischemia-reperfusion injury via dimerized STAT3
Authors: Hu Hengxun , Nan Jinliang , Sun Yong , Zhu Dan , Xiao Changchen , Wang Yaping , Zhu Lianlian , Wu Yue , Zhao Jing , Wu Rongrong , Chen Jinghai , Yu Hong , Hu Xinyang , Zhu Wei , Wang Jian’an
Published: October 2017

Significance

Reactive oxygen species (ROS) generation due to electron leak from the mitochondria may be involved in physiological or pathological processes. NDUFA13 is an accessory subunit of mitochondria complex I with a unique molecular structure and is located close to FeS clusters with low electrochemical potentials. Here, we generated cardiac-specific conditional NDUFA13 heterozygous knockout mice. At the basal state, a moderate down-regulation of NDUFA13 created a leak within complex I, resulting in a mild increase in cytoplasm localized H
2
O
2
, but not superoxide. The resultant ROS served as a second messenger and was responsible for the STAT3 dimerization and, hence, the activation of antiapoptotic signaling, which eventually significantly suppressed the superoxide burst and decreased the infarct size during the ischemia-reperfusion process.
Squaw Teats*, Harney Peak, and Negrohead Creek*: A Corpus-Linguistic Investigation of Proposals to Change Official US Toponymy to (Dis)honor Indigenous US Americans
Authors: Nick I. M.
Published: October 2017

Each year, the US Government receives hundreds of petitions to alter the official name of a geographical feature. Since the nineteenth century, the US Board on Geographic Names (USBGN) has had the task of assessing these requests with a view toward standardizing the nation’s toponymic inventory. During its decision-making, the Board seeks to maximize consistency in the formation, selection, and application of official toponyms, while minimizing potential public injury. The challenges in this regulatory balancing act are particularly apparent with regard to indigenous place names. Using an original corpus compiled from 10 years of USBGN petitions, this empirical study identified patterns in the type, motivation, and argumentation used to (dis)honor Native American identities, histories, and cultures via names and naming. After introducing the UsBGN's policies and practices, these findings are presented with several illustrative examples. The article ends by contextualizing the findings within the broader PC debate and offering future research suggestions.
Suffixation as a Place Naming Strategy in the Central Pacific and its Implications for Prehistory
Authors: Geraghty Paul
Published: October 2017

This article uses comparative linguistic data to arrive at some generalizations about the place naming practices of the early inhabitants of the Central Pacific (Fiji, Rotuma, and Polynesia) who are believed to have arrived there some three thousand years ago. In particular it focuses on a pair of suffixes, -(C)a and -(C)aga, that had similar functions of nominalization and were therefore used quite extensively in various types of derivation, including place naming. Many place names so formed are indicators of the environment that prevailed when the place was named, so have great potential value in the reconstruction of prehistory.
CE–MS-based metabolomics reveals the metabolic profile of maitake mushroom (Grifola frondosa) strains with different cultivation characteristics
Authors: Sato Mayumi , Miyagi Atsuko , Yoneyama Shozo , Gisusi Seiki , Tokuji Yoshihiko , Kawai-Yamada Maki
Published: October 2017

Maitake mushroom (Grifola frondosa [Dicks.] Gray) is generally cultured using the sawdust of broadleaf trees. The maitake strain Gf433 has high production efficiency, with high-quality of fruiting bodies even when 30% of the birch sawdust on the basal substrate is replaced with conifer sawdust. We performed metabolome analysis to investigate the effect of different cultivation components on the metabolism of Gf433 and Mori52 by performing CE–MS on their fruiting bodies in different cultivation conditions to quantify the levels of amino acids, organic acids, and phosphorylated organic acids. We found that amino acid and organic acid content in Gf433 were not affected by the kind of sawdust. However, Gf433 contained more organic acids and less amino acids than Mori52, and Gf433 also contained more chitin compared with Mori52. We believe that these differences in the metabolome contents of the two strains are related to the high production efficiency of Gf433.
Recent development of antiSMASH and other computational approaches to mine secondary metabolite biosynthetic gene clusters
Authors: Blin Kai , Kim Hyun Uk , Medema Marnix H , Weber Tilmann
Published: October 2017

Many drugs are derived from small molecules produced by microorganisms and plants, so-called natural products. Natural products have diverse chemical structures, but the biosynthetic pathways producing those compounds are often organized as biosynthetic gene clusters (BGCs) and follow a highly conserved biosynthetic logic. This allows for the identification of core biosynthetic enzymes using genome mining strategies that are based on the sequence similarity of the involved enzymes/genes. However, mining for a variety of BGCs quickly approaches a complexity level where manual analyses are no longer possible and require the use of automated genome mining pipelines, such as the antiSMASH software. In this review, we discuss the principles underlying the predictions of antiSMASH and other tools and provide practical advice for their application. Furthermore, we discuss important caveats such as rule-based BGC detection, sequence and annotation quality and cluster boundary prediction, which all have to be considered while planning for, performing and analyzing the results of genome mining studies.
A fast fiducial marker tracking model for fully automatic alignment in electron tomography
Authors: Han Renmin , Zhang Fa , Gao Xin
Published: October 2017

Motivation

Automatic alignment, especially fiducial marker-based alignment, has become increasingly important due to the high demand of subtomogram averaging and the rapid development of large-field electron microscopy. Among the alignment steps, fiducial marker tracking is a crucial one that determines the quality of the final alignment. Yet, it is still a challenging problem to track the fiducial markers accurately and effectively in a fully automatic manner.

Results

In this paper, we propose a robust and efficient scheme for fiducial marker tracking. Firstly, we theoretically prove the upper bound of the transformation deviation of aligning the positions of fiducial markers on two micrographs by affine transformation. Secondly, we design an automatic algorithm based on the Gaussian mixture model to accelerate the procedure of fiducial marker tracking. Thirdly, we propose a divide-and-conquer strategy against lens distortions to ensure the reliability of our scheme. To our knowledge, this is the first attempt that theoretically relates the projection model with the tracking model. The real-world experimental results further support our theoretical bound and demonstrate the effectiveness of our algorithm. This work facilitates the fully automatic tracking for datasets with a massive number of fiducial markers.

Availability and implementation

The C/C ++ source code that implements the fast fiducial marker tracking is available at https://github.com/icthrm/gmm-marker-tracking. Markerauto 1.6 version or later (also integrated in the AuTom platform at http://ear.ict.ac.cn/) offers a complete implementation for fast alignment, in which fast fiducial marker tracking is available by the ‘-t’ option.

Supplementary information

Supplementary data are available at Bioinformatics online.
ARCS: scaffolding genome drafts with linked reads
Authors: Yeo Sarah , Coombe Lauren , Warren René L , Chu Justin , Birol Inanç
Published: October 2017

Motivation

Sequencing of human genomes is now routine, and assembly of shotgun reads is increasingly feasible. However, assemblies often fail to inform about chromosome-scale structure due to a lack of linkage information over long stretches of DNA—a shortcoming that is being addressed by new sequencing protocols, such as the GemCode and Chromium linked reads from 10 × Genomics.

Results

Here, we present ARCS, an application that utilizes the barcoding information contained in linked reads to further organize draft genomes into highly contiguous assemblies. We show how the contiguity of an ABySS H.sapiens genome assembly can be increased over six-fold, using moderate coverage (25-fold) Chromium data. We expect ARCS to have broad utility in harnessing the barcoding information contained in linked read data for connecting high-quality sequences in genome assembly drafts.

Availability and implementation

https://github.com/bcgsc/ARCS/

Supplementary information

Supplementary data are available at Bioinformatics online.
PESTO: Parameter EStimation TOolbox
Authors: Stapor Paul , Weindl Daniel , Ballnus Benjamin , Hug Sabine , Loos Carolin , Fiedler Anna , Krause Sabrina , Hroß Sabrina , Fröhlich Fabian , Hasenauer Jan
Published: October 2017

PESTO is a widely applicable and highly customizable toolbox for parameter estimation in MathWorks MATLAB. It offers scalable algorithms for optimization, uncertainty and identifiability analysis, which work in a very generic manner, treating the objective function as a black box. Hence, PESTO can be used for any parameter estimation problem, for which the user can provide a deterministic objective function in MATLAB.

Availability and implementation

PESTO is a MATLAB toolbox, freely available under the BSD license. The source code, along with extensive documentation and example code, can be downloaded from https://github.com/ICB-DCM/PESTO/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Wach Modules, Regulator Maps, and $\varepsilon$-Isomorphisms in Families
Authors: Bellovin Rebecca , Venjakob Otmar
Published: October 2017

We prove the “local $\varepsilon$-isomorphism” conjecture of Fukaya and Kato [13] for certain crystalline families of $G_{{\mathbf{Q}_p}}$-representations. This conjecture can be regarded as a local analog of the Iwasawa main conjecture for families. Our work extends earlier work of Kato for rank-$1$ modules (cf. [33]), of Benois and Berger for crystalline $G_{{\mathbf{Q}_p}}$-representations with respect to the cyclotomic extension (cf. [1]), as well as of Loeffler et al. (cf. [21]) for crystalline $G_{{\mathbf{Q}_p}}$-representations with respect to abelian $p$-adic Lie extensions of ${\mathbf{Q}_p}$. Nakamura [24, 25] has also formulated a version of Kato’s $\varepsilon$-conjecture for affinoid families of $(\varphi,\Gamma)$-modules over the Robba ring, and proved his conjecture in the rank-$1$ case. He used this case to construct an $\varepsilon$-isomorphism for families of trianguline $(\varphi,\Gamma)$-modules, depending on a fixed triangulation. Our results imply that this $\varepsilon$-isomorphism is independent of the chosen triangulation for certain crystalline families. The main ingredient of our proof consists of the construction of families of Wach modules generalizing work of Wach and Berger [6] and following Kisin’s approach to the construction of potentially semi-stable deformation rings [18].
CLAMP – a toolkit for efficiently building customized clinical natural language processing pipelines
Authors: Soysal Ergin , Wang Jingqi , Jiang Min , Wu Yonghui , Pakhomov Serguei , Liu Hongfang , Xu Hua
Published: October 2017

Existing general clinical natural language processing (NLP) systems such as MetaMap and Clinical Text Analysis and Knowledge Extraction System have been successfully applied to information extraction from clinical text. However, end users often have to customize existing systems for their individual tasks, which can require substantial NLP skills. Here we present CLAMP (Clinical Language Annotation, Modeling, and Processing), a newly developed clinical NLP toolkit that provides not only state-of-the-art NLP components, but also a user-friendly graphic user interface that can help users quickly build customized NLP pipelines for their individual applications. Our evaluation shows that the CLAMP default pipeline achieved good performance on named entity recognition and concept encoding. We also demonstrate the efficiency of the CLAMP graphic user interface in building customized, high-performance NLP pipelines with 2 use cases, extracting smoking status and lab test values. CLAMP is publicly available for research use, and we believe it is a unique asset for the clinical NLP community.
Handwritten digit recognition using neural networks and dynamic zoning with stroke-based descriptors
Authors: Álvarez-León David , Fernández-Díaz Ramón-Ángel , Sánchez-Gonzalez Lidia , Alija-Pérez José-Manuel
Published: October 2017

This article presents an Off-line handwritten digit recognition approach based on neural networks. We define a numeric character as a composition of vertical and horizontal strokes. After the preprocessing, we use dynamic zoning to retrieve the positions where vertical strokes – the main strokes — are joined to horizontal strokes. These features are recorded into a representative string and verified using a custom matching pattern. Finally, a multilayer perceptron neural network is fed with the previous data to raise the learning process. The results gathered from the experiments performed on the well-known MNIST handwritten database are compared against other proposals providing promising results.
Predictive Factors for Corneal Clearance After Descemetorhexis Without Endothelial Keratoplasty
Authors: Davies Emma , Jurkunas Ula , Pineda Roberto
Published: October 2017

Purpose:

To study preoperative factors that possibly contribute to corneal clearance after Descemetorhexis without endothelial keratoplasty (DWEK) and to determine the most successful surgical technique for the procedure.

Methods:

Retrospective chart review of 17 eyes of 13 patients with Fuchs corneal endothelial dystrophy that underwent central 4-mm DWEK.

Results:

Baseline age, pachymetry, and endothelial cell count were not statistically significantly different between eyes that cleared 0 to 2 months, 3 to 5 months, 6 to 8 months, or that failed to clear. All eyes that failed to clear had DWEK performed using scoring followed by the stripping technique. Postoperative endothelial cell counts steadily increased over time after the procedure, even in eyes that failed to clear.

Conclusions:

DWEK when performed with a Descemetorhexis technique results in corneal clearance in the majority of cases regardless of baseline demographics, with clearance typically 3 months after the procedure. Further studies are needed to investigate environmental factors, such as possible growth factors in the anterior chamber, that may influence clearing in these cases.
Vaccinia virus protein A49 activates Wnt signalling by targetting the E3 ligase β-TrCP
Authors: Maluquer de Motes Carlos , Smith Geoffrey L.
Published: October 2017

Vaccinia virus (VACV) encodes multiple proteins inhibiting the NF-κB signalling pathway. One of these, A49, targets the E3 ubiquitin ligase β-TrCP, which is responsible for the ubiquitylation and consequential proteosomal degradation of IκBα and the release of the NF-κB heterodimer. β-TrCP is a pleiotropic enzyme ubiquitylating multiple cellular substrates, including the transcriptional activator β-catenin. Here we demonstrate that A49 can activate the Wnt signalling pathway, a critical pathway that is involved in cell cycle and cell differentiation, and is controlled by β-catenin. The data presented show that the expression of A49 ectopically or during VACV infection causes accumulation of β-catenin, and that A49 triggering of Wnt signalling is dependent on binding β-TrCP. This is consistent with A49 blocking the ability of β-TrCP to recognise β-catenin and IκBα, and possibly other cellular targets. Thus, A49 targetting of β-TrCP affects multiple cellular pathways, including the NF-κB and Wnt signalling cascades.
Postoperative Tropheryma whipplei endophthalmitis – a case report highlighting the additive value of molecular testing
Authors: Dick Julia , Krauß Patrizia , Hillenkamp Jost , Kohlmorgen Britta , Schoen Christoph
Published: October 2017

Introduction.
Tropheryma whipplei is the causative agent of Whipple’s disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms.

Case presentation. A 74-year-old Caucasian female presented with blurred vision in the right eye over a period of 1–2 months, accompanied by stinging pain and conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was hand motion in the affected eye. Ophthalmological examination showed typical signs of intraocular inflammation. Diagnostic and therapeutic pars plana vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin and amikacin was performed within hours of initial presentation. Both microscopic analysis and microbial cultures of the vitreous biopsy remained negative for bacteria and fungi. The postoperative antibiotic regime included intravenous administration of ceftriaxone in combination with topical tobramycin and ofloxacin. Due to the empirical therapy the inflammation ceased and the patient was discharged after 5 days with cefpodoxime orally and local antibiotic and steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the PCR product revealed a specific sequence of T. whipplei.

Conclusion. In our patient, endophthalmitis was the first and only symptom of Morbus Whipple, while most patients with Whipple’s disease suffer from severe gastrointestinal symptoms. 16S rDNA PCR should be considered for any intraocular infection when microscopy and standard culture methods remain negative.
Signatures of Selection in the Human Antibody Repertoire: Selective Sweeps, Competing Subclones, and Neutral Drift
Authors: Horns Felix , Vollmers Christopher , Dekker Cornelia L. , Quake Stephen R.
Published: October 2017

Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with the ability to recognize and eliminate diverse pathogens. However, the evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show that the molecular signatures of evolution are evident in human B cell lineages and reveal how antibodies evolve somatically. We measured the dynamics and genetic diversity of B cell responses of five adults longitudinally before and after influenza vaccination using high-throughput antibody repertoire sequencing. We identified vaccine-responsive B cell lineages that carry signatures of selective sweeps driven by positive selection, and discovered that they often display evidence for selective sweeps favoring multiple subclones. We also found persistent B cell lineages that exhibit stable population dynamics and carry signatures of neutral drift. By exploiting the linkage between B cell fitness and antibody binding affinity, we demonstrated the potential for using signatures of selection to identify antibodies with high binding affinity. This quantitative characterization reveals that antibody repertoires are shaped by an unexpectedly broad spectrum of evolutionary processes and shows how signatures of evolutionary history can be harnessed for antibody discovery and engineering.

One Sentence Summary

Molecular signatures of somatic evolution reveal that diverse evolutionary processes ranging from strong positive selection to neutral drift sculpt human antibodies.
Blind estimation and correction of microarray batch effect
Authors: Varma Sudhir
Published: October 2017

Microarray batch effect (BE) has been the primary bottleneck for large-scale integration of data from multiple experiments. Current BE correction methods either need known batch identities (ComBat)or have the potential to overcorrect, by removing true but unknown biological differences (SVA).Even though the effects of technical differences on measured expression have been published, there are no BE correction algorithms that take the approach of predicting technical effects from parameters computed from a fixed reference sample set. We show that a set of signatures, each of which is a vector the length of the number of probes, calculated on a Reference set of microarray samples can predict much of the batch effect in other Validation sets. We present a rationale of selecting a Reference set of samples designed to estimate technical differences without removing biological differences. Putting both together, we introduce the Batch Effect Signature Correction (BESC) algorithm that uses the BES calculated on the Reference set to efficiently predict and remove BE. Using two independent Validation sets, we show that BESC is capable of removing batch effect without removing unknown but true biological differences. Much of the variations due to batch effect is shared between different microarray datasets. That shared information can be used to predict signatures (i.e. directions of perturbation) due to batch effect in new datasets. The correction is blind (without needing to re-compute the parameters on new samples to be corrected), single sample, (each sample is corrected independently of each other) and conservative (only those perturbations known to be likely to be due to technical differences are removed ensuring that unknown but important biological differences are maintained). Those three characteristics make it ideal for high-throughput correction of samples for a microarray data repository. An R Package besc implementing the algorithm is available from http://explainbio.com.
Raising the stakes: Loss of efflux-pump regulation decreases meropenem susceptibility in Burkholderia pseudomallei
Authors: Sarovich Derek S. , Webb Jessica R. , Pitman Matthew C. , Viberg Linda T. , Mayo Mark , Baird Robert W. , Robson Jennifer M. , Currie Bart J. , Price Erin P.
Published: October 2017

Burkholderia pseudomallei, the causative agent of the high-mortality disease melioidosis, is a Gram-negative bacterium that is naturally resistant to many antibiotics. There is no vaccine for melioidosis, and effective eradication is reliant on biphasic and prolonged antibiotic administration. The carbapenem drug, meropenem, is the current gold-standard option for treating severe melioidosis. Intrinsic B. pseudomallei resistance towards meropenem has not yet been documented; however, resistance could conceivably develop over the course of infection, leading to prolonged sepsis and treatment failure. Here, we document 11 melioidosis cases in which B. pseudomallei isolates developed decreased susceptibility towards meropenem during treatment, including two cases not treated with this antibiotic. Meropenem minimum inhibitory concentrations increased over time from 0.5-0.75 to 3-8 μg/mL. Using comparative genomics, we identified multiple mutations affecting multidrug resistance-nodulation-division (RND) efflux pump regulators, leading to over-expression of their corresponding pumps. The most commonly affected pump was AmrAB-OprA, although alterations in the local regulators of BpeEF-OprC or BpeAB-OprB were observed in three cases. This study confirms the role of RND efflux pumps in decreased meropenem susceptibility in B. pseudomallei. Further, we document two concerning examples of severe melioidosis where the reduced treatment efficacy of meropenem was associated with a fatal outcome.

Significance Statement

The bacterium Burkholderia pseudomallei, which causes the often-fatal tropical disease melioidosis, is difficult to eradicate. Due to high levels of intrinsic antibiotic resistance, only a handful of antibiotics are effective against this pathogen. One of these, meropenem, is commonly used in the treatment of melioidosis patients who are unresponsive to other treatments or are critically ill. Here, we describe 11 melioidosis cases whereby patients exhibited prolonged or repeated infections that were associated with the development of decreased meropenem susceptibility. We identified the molecular basis for this decreased susceptibility in latter B. pseudomallei isolates obtained from these patients, and functionally confirmed the mechanism conferring this phenotype. Our findings have important ramifications for the diagnosis, treatment and management of life-threatening melioidosis cases.
Pathways-wide genetic risks in Chlamydial infections overlap between tissue tropisms: A genome-wide association scan
Authors: Roberts Chrissy h. , Ouberg Sander , Preston Mark D. , de Vries Henry J.C. , Holland Martin J , Morre Servaas
Published: October 2017

Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection and can lead to tubal factor infertility, a disease characterised by fibrosis of the fallopian tubes. Genetic polymorphisms in molecular pathways involving G protein coupled receptor signalling, the Akt/PI3K cascade, the mitotic cell cycle and immune response have been identified in association with the development of trachomatous scarring, an ocular form of chlamydia-related fibrotic pathology. In this case control study, we performed genome-wide association and pathways based analysis in a sample of 71 Dutch women who attended an STI clinic who were seropositive for Chlamydia trachomatis antibodies and 169 high risk Dutch women who sought similar health services but who were seronegative. We identified two regions of within-gene SNP association with Chlamydia trachomatis serological response and found that GPCR signalling and cell cycle pathways were also associated with the trait. These pathway level associations appear to be common to immunological sequelae of Chlamydial infections in both ocular and urogenital tropisms. These pathways may be central mediators of human refractoriness to chlamydial diseases.
The Polycomb-dependent epigenome controls β-cell dysfunction, dedifferentiation and diabetes
Authors: Lu Tess Tsai-Hsiu , Heyne Steffen , Dror Erez , Casas Eduard , Leonhardt Laura , Boenke Thorina , Yang Chih-Hsiang , Sagar  , Arrigoni Laura , Dalgaard Kevin , Teperino Raffaele , Enders Lennart , Selvaraj Madhan , Ruf Marius , Raja Sunil Jayaramaiah , Xie Huafeng , Boenisch Ulrike , Orkin Stuart H. , Lynn Francis C , Hoffman Brad G. , Grün Dominic , Vavouri Tanya , Lempradl Adelheid , Pospisilik J. Andrew
Published: October 2017

Chromatin is the physical template that stabilizes and specifies transcriptional programs. To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combined deep epigenome mapping with single cell transcriptomics to mine for evidence of chromatin dysregulation in type-2 diabetes. We identify two chromatin-state signatures that track the trajectory of β-cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-domains and a loss of expression at a subclass of highly active domains containing key lineage-defining genes. β-cell specific deletion of Polycomb (Eed/PRC2) triggers parallel transcriptional signatures. Intriguingly, these β-cell Eed-knockouts also exhibit highly penetrant hyperglycemia-independent dedifferentiation indicating that Polycomb dysregulation sensitizes the β-cell for dedifferentiation. These findings provide novel resources for exploring transcriptional and epigenetic control of β-cell (dys)function. They identify PRC2 as necessary for long-term maintenance of β-cell identity. The data suggest a two-hit model for loss of β-cell identity in diabetes and highlight epigenetic therapeutic potential to block dedifferentiation.
HuD is a neural enhancer of global translation acting on mTORC1-responsive genes and sponged by the Y3 small non-coding RNA
Authors: Zuccotti Paola , Tebaldi Toma , Peroni Daniele , Köhn Marcel , Gasperini Lisa , Potrich Valentina , Dudnakova Tatiana , Sanguinetti Guido , Conti Luciano , Macchi Paolo , Tollervey David , Hüttelmaier Stefan , Quattrone Alessandro
Published: October 2017

The RNA-binding protein HuD promotes neurogenesis and favors recovery from peripheral axon injury. HuD interacts with many mRNAs, altering both stability and translation efficiency. UV-crosslinking and analysis of cDNA (CRAC) generated a nucleotide resolution map of the HuD RNA interactome in motor neuron-like cells. HuD target sites were identified in 1304 mRNAs, predominantly in the 3’UTR, with enrichment for genes involved in protein synthesis and axonogenesis. HuD bound many mRNAs encoding mTORC1-responsive ribosomal proteins and translation factors. Altered HuD expression correlated with the translational efficiency of these mRNAs and overall protein synthesis, in a mTORC1-independent fashion. The predominant HuD target was the abundant, small non-coding RNA Y3, which represented 70% of HuD interaction signal. Y3 functions as a molecular sponge for HuD, dynamically limiting its activity. These findings uncover an alternative route to the mTORC1 pathway for translational control in motor neurons that is tunable by a small non-coding RNA.

Graphical abstract
Long-Term Leisure-Time Physical Activity and Other Health Habits as Predictors of Objectively Monitored Late-Life Physical Activity – A 40-Year Twin Study
Authors: Waller Katja , Vähä-Ypyä Henri , Törmäkangas Timo , Hautasaari Pekka , Lindgren Noora , Iso-Markku Paula , Heikkilä Kauko , Rinne Juha , Kaprio Jaakko , Sievänen Harri , Kujala Urho M.
Published: October 2017

IMPORTANCE

Moderate-to-vigorous physical activity (MVPA) in old age is an important indicator of good health and functional capacity enabling independent living.

OBJECTIVE

To investigate whether physical activity and other health habits at ages 31-48 years predict objectively measured MVPA decades later.

DESIGN, SETTING, AND PARTICIPANTS

This prospective twin cohort study in Finland comprised 616 individuals (197 complete twin pairs, including 91 monozygotic pairs, born 1940-1944), who responded to baseline questionnaires in 1975, 1981, and 1990, and participated in accelerometer monitoring at follow-up (mean age, 73 years).

EXPOSURES

Primary exposure was long-term leisure-time physical activity, 1975-1990 (LT-mMET index). Covariates were body mass index (BMI), work-related physical activity, smoking, heavy alcohol use and health status in 1990, and socioeconomic status.

MAIN OUTCOMES AND MEASURES

Physical activity was measured with a waist-worn triaxial accelerometer (at least 10 hours per day for at least 4 days) to obtain daily mean MVPA values.

RESULTS

High baseline LT-mMET index predicted higher amounts of MVPA (increase in R2 of 6.9% after age and sex adjustment, P<.001) at follow-up. After addition of BMI to the regression model, the R2 value of the whole multivariate model was 17.2%, and with further addition of baseline smoking, socioeconomic status, and health status, the R2 increased to 20.3%. In pairwise analyses, differences in MVPA amount were seen only among twin pairs who were discordant at baseline for smoking (n=40 pairs, median follow-up MVPA 25 vs. 35 min, P=.037) or for health status (n=69 pairs, 30 vs. 44 min, P=.014). For smoking, the difference in MVPA also was seen for monozygotic pairs, but for health status, it was seen only for dizygotic pairs. Mediation analysis showed that shared genetic factors explained 82% of the correlation between LT-mMET and MVPA.

CONCLUSIONS AND RELEVANCE

Low leisure-time physical activity at younger age, overweight, smoking, low socioeconomic status, and health problems predicted low MVPA in old age in individual-based analyses. However, based on the pairwise analyses and quantitative trait modeling, genetic factors and smoking seem to be important determinants of later-life MVPA.
Normative Brain Size Variation and the Remodeling of Brain Shape in Humans
Authors: Reardon P. K. , Vandekar Simon N. , Liu Siyuan , Patel Raihaan , Park Min Tae M. , Alexander-Bloch Aaron , Seidlitz Jakob , Clasen Liv S. , Blumenthal Jonathan D. , Giedd Jay N. , Gur Ruben C. , Gur Raquel E. , Lerch Jason P. , Chakravarty M. Mallar , Satterthwaite Theodore D. , Shinohara Russel T. , Raznahan Armin
Published: October 2017

Evolutionary and developmental increases in primate brain size have been accompanied by systematic shifts in the proportionality of different primate brain systems. However, it remains unknown if and how brain patterning varies across the more than 2-fold inter-individual variation in brain size that occurs amongst typically-developing humans. Using in vivo neuroimaging data from 2 independent cohorts totaling nearly 3000 individuals, we find that larger-brained humans show preferential areal expansion within specific fronto-parietal cortical networks (default mode, dorsal attentional) and related subcortical regions, at the expense of primary sensory/motor systems. This targeted areal expansion recapitulates cortical remodeling across evolution, manifests by early childhood and is linked to molecular signatures of heightened metabolic cost. Our results define a new organizing principle in human brain patterning which governs the highly-coordinated remodeling of human brain shape as a function of naturally-occurring variations in brain size.

One Sentence Summary

A hodologically and metabolically expensive brain network is preferentially expanded in larger-brained humans.
Demographic fluctuation of community-acquired antibiotic-resistant Staphylococcus aureus lineages: potential role of flimsy antibiotic exposure
Authors: Gustave Claude-Alexandre , Tristan Anne , Martins-Simoes Patricia , Stegger Marc , Benito Yvonne , Andersen Paal Skytt , Bes Michèle , Glaser Philippe , Laurent Frédéric , Wirth Thierry , Vandenesch François
Published: October 2017

Community-acquired (CA) -as opposed to hospital acquired- methicillin-resistant Staphylococcus aureus (MRSA) lineages arose worldwide during the 1990s. To determine which factors, including selective antibiotic pressure, govern the expansion of two major lineages of CA-MRSA, namely “USA300” in Northern America and the “European ST80” in North Africa, Europe and the Middle East, we explored virulence factor expression, and fitness levels with or without antibiotics. The sampled strains were collected in a temporal window representing various steps of the epidemics, reflecting predicted effective population size as inferred from whole genome analysis. In addition to slight variations in virulence factor expression and biofilm production that might influence the ecological niches of theses lineages, competitive fitness experiments revealed that the biological cost of resistance to methicillin, fusidic-acid and fluoroquinolone is totally reversed in the presence of trace amount of antibiotics. Our results suggest that low-level antibiotics exposure in human and animal environments contributed to the expansion of both European-ST80 and USA300 lineages in community setting. This surge was likely driven by antibiotic (ab)use promoting the accumulation of antibiotics as environmental pollutants. The current results provide a novel link between effective population size increase of a pathogen and a selective advantage conferred by antibiotic resistance.
Memory consolidation is linked to spindle-mediated information processing during sleep
Authors: Cairney S.A. , Guttesen A. , El Marj N. , Staresina B.P.
Published: October 2017

How are brief encounters transformed into lasting memories? Previous research has established the role of non-rapid eye movement (NREM) sleep, along with its electrophysiological signatures of slow oscillations (SOs) and spindles, for memory consolidation. More recently, experimental manipulations have demonstrated that NREM sleep provides a window of opportunity to selectively strengthen particular memory traces via the delivery of sensory cues. It has remained unclear, however, whether experimental memory cueing triggers the brain’s endogenous consolidation mechanisms (linked to SOs and/or spindles) and whether those mechanisms in turn mediate effective processing of the cue information. Here we devised a novel paradigm in which associative memories (adjective-object and adjective-scene pairs) were selectively cued during a post-learning nap, successfully stabilising next-day retention relative to non-cued memories. First, we found that compared to novel control adjectives, memory cues were accompanied by an increase in fast spindles coupled to SO up states. Critically, EEG pattern decodability of the associated memory category (object vs. scene) was temporally linked to cue-induced spindles and predicted next-day retrieval performance across participants. These results provide highly controlled empirical evidence for an information processing role of sleep spindles in service of memory consolidation.
Verbal paired associates and the hippocampus: The role of scenes
Authors: Clark Ian A. , Kim Misun , Maguire Eleanor A.
Published: October 2017

It is widely agreed that patients with bilateral hippocampal damage are impaired at binding pairs of words together. Consequently, the verbal paired associates (VPA) task has become emblematic of hippocampal function. This VPA deficit is not well understood, and is particularly difficult for hippocampal theories with a visuospatial bias to explain (e.g., cognitive map and scene construction theories). Resolving the tension among hippocampal theories concerning the VPA could be important for leveraging a fuller understanding of hippocampal function. Notably, VPA tasks typically use high imagery concrete words and so conflate imagery and binding. To determine why VPA engages the hippocampus, we devised an fMRI encoding task involving closely matched pairs of scene words, pairs of object words and pairs of very low imagery abstract words. We found that the anterior hippocampus was engaged during processing of both scene and object word pairs in comparison to abstract word pairs, despite binding occurring in all conditions. This was also the case when just subsequently remembered stimuli were considered. Moreover, for object word pairs, fMRI activity patterns in anterior hippocampus were more similar to those for scene imagery than object imagery. This was especially evident in participants who were high imagery users, and not in mid and low imagery users. Overall, our results show that hippocampal engagement during VPA, even when object word pairs are involved, seems to be evoked by scene imagery rather than binding. This may help to resolve the issue that visuospatial hippocampal theories have in accounting for verbal memory.
Roosting in exposed microsites by a nocturnal bird, the rufous-cheeked nightjar: implications for water balance under current and future climate conditions
Authors: O’Connor Ryan S. , Brigham R. Mark , McKechnie Andrew E.
Published: October 2017

Nocturnally active birds roosting in exposed diurnal microsites with intense solar radiation can experience operative temperatures (Te) that markedly differ from air temperature (Ta). Quantifying Tethus becomes important for accurately modeling energy and water balance. We measured Teat roost and nest sites used by Rufous-cheeked Nightjars (Caprimulgus rufigena) with three-dimensionally printed biophysical models covered with the integument and plumage of a bird. Additionally, we estimated site-specific diurnal water requirements for evaporative cooling by integrating Teand Taprofiles with evaporative water loss (EWL) data for Rufous-cheeked Nightjars. Between 12:00 and 15:00 hrs, average Teat roost sites varied from 33.1 to 49.9 °C, whereas at the single nest site Teaveraged 51.4 °C. Average diurnal EWL, estimated using Te, was as high as 10.5 and 11.3 g at roost and nest sites, respectively, estimates 3.8- and 4.0-fold greater, respectively, than when calculated with Taprofiles. These data illustrate that under current climatic conditions, Rufous-cheeked Nightjars can experience EWL potentially approaching their limits of dehydration tolerance. In the absence of microsite changes, climate change during the 21stcentury could perhaps create thermal conditions under which Rufous-cheeked Nightjars exceed dehydration tolerance limits before the onset of their nocturnal active phase.