bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient dynamics of an elastic Hele-Shaw cell due to external forces with application to impact mitigation
Authors: Tulchinsky A. , Gat A. D.
Published: July 2016

We study the transient dynamics of a viscous liquid contained in a narrow gap between a rigid surface and a parallel elastic plate. The elastic plate is deformed due to an externally applied time-varying pressure field. We model the flow field via the lubrication approximation and the plate deformation by the Kirchhoff–Love plate theory. We obtain a self-similarity solution for the case of an external point force acting on the elastic plate. The pressure and deformation field during and after the application of the external force are derived and presented by closed-form expressions. We examine a distributed external pressure, spatially uniform and linearly increasing with time, acting on the elastic plate over a finite region and during a finite time period, similar to the viscous–elastic interaction time-scale. The interaction between elasticity and viscosity is shown to reduce by an order of magnitude the pressure within the Hele-Shaw cell compared with the externally applied pressure. The results thus suggest that elastic Hele-Shaw configurations may be used to achieve significant impact mitigation.
Use of Lightweight Lime Mortar in the Construction of the West Church of Umm el-Jimal, Jordan: Radiocarbon Dating and Characterization
Authors: Al-Bashaireh Khaled
Published: July 2016

Lightweight concrete was widely used and mainly spread during the Roman period. This technology was used in the West Church, Umm el-Jimal, Jordan. The date of construction of the West Church is debated and different dates have been suggested based on its architectural styles and comparisons with other churches. This research aims to radiocarbon date the construction of the dome (church), archaeometrically characterize the mortar, and determine the source of the scoria. Three charcoals and two broken pieces comprising scoria from the mortar of the fallen dome and six large scoria samples from Quais cone were collected. The research used different analytical methods including accelerator mass spectrometry14C, X-ray diffraction, petrographic microscopy, inductively coupled plasma mass spectrometry, and scanning electron microscopy-energy dispersive X-ray spectroscopy.14C determinations dated the dome (church) to the Late Roman–Early Byzantine periods, which contradicted the archaeological data. Analytical results showed that the mortar is lime-based and hydraulic. The similarities in the mineralogical composition, macroscopic and microscopic features, and chemical composition (compared statistically) of the scoria samples and the short distance between Umm el-Jimal and the Quais volcanic cone very likely indicate that the Quais volcanic cone is the source of the scoria used in the fallen dome.
Extreme values and crossings for the X 2-Process and Other Functions of Multidimensional Gaussian Processes, by Reliability Applications
Authors: Lindgren Georg
Published: July 2016

Extreme values of non-linear functions of multivariate Gaussian processes are of considerable interest in engineering sciences dealing with the safety of structures. One then seeks thesurvivalprobability

whereX(t) = (X1(t), …,Xn(t)) is a stationary, multivariate Gaussianloadprocess, andSis asafe region.In general, the asymptotic survival probability for largeT-values is the most interesting quantity.

By considering the point process formed by the extreme points of the vector processX(t), and proving a general Poisson convergence theorem, we obtain the asymptotic survival probability for a large class of safe regions, including those defined by the level curves of any second- (or higher-) degree polynomial in (x1, …,xn). This makes it possible to give an asymptotic theory for the so-called Hasofer-Lind reliability index, β = inf>x∉S||x||, i.e. the smallest distance from the origin to an unsafe point.
Psychological processes underlying the association between childhood trauma and psychosis in daily life: an experience sampling study
Authors: Reininghaus U. , Gayer-Anderson C. , Valmaggia L. , Kempton M. J. , Calem M. , Onyejiaka A. , Hubbard K. , Dazzan P. , Beards S. , Fisher H. L. , Mills J. G. , McGuire P. , Craig T. K. J. , Garety P. , van Os J. , Murray R. M. , Wykes T. , Myin-Germeys I. , Morgan C.
Published: July 2016

Background

Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.

Method

We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.

Results

Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.

Conclusions

Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.
In Defense of Cooper v. Aaron: Distinguishing among Judicial Supremacy Claims
Authors: Harriger Katy J.
Published: July 2016

In the debate about the legitimacy of judicial supremacy, Cooper v. Aaron, the Little Rock desegregation case, is identified by both sides as critical to their argument. Defenders insist that Cooper exemplifies the need for a final authority in matters constitutional. Critics argue that the Court was wrong as a matter of democratic theory or empirical reality. In this article I argue that while it is true as a matter of empirical reality that the Court's interpretation is not the final word, the Court's assertion can be defended nonetheless. Relying on archival sources from the case, I explore the conditions under which the Court made the claim. To defend Cooper, however, does not require the defense of all assertions of judicial supremacy. I conclude by offering a preliminary analysis of how we might distinguish between more legitimate assertions of judicial supremacy and less legitimate ones.
Anthropology on trial: exploring the laws of anthropological expertise
Authors: Zenker Olaf
Published: July 2016

This paper explores the role of anthropological expertise in shaping the outcome of legal proceedings under conditions of cultural diversity. Taking the state-driven land-restitution process in post-apartheid South Africa as its point of reference, the text reflects upon the work of anthropological experts in a number of cases and shows how their theoretical and political stances shaped the trajectories of their legal engagements. Pointing towards frictions that emerge in acts of translation between the seemingly objectivist rhetoric evoked in court and more relativist and subjectivist stances within the academy, the paper revisits and problematises debates around strategic essentialism. Sketching instead the contours of a ‘recursive anthropology’ that expresses itself in terms of a post-positivist universalism, the paper turns on the author's use of his own expertise in support of a White land claim, probing – and critically reflecting upon – the practical potential of a form of expertise grounded in such a recursive anthropology.
Distraction of Mental Arithmetic by Background Speech
Authors: Perham Nick , Marsh John E. , Clarkson Martin , Lawrence Rosie , Sörqvist Patrik
Published: July 2016

Abstract. When solving mental arithmetic problems, one can easily be distracted by someone speaking in the background and this distraction is greater if the speech comprises numbers. We explored the basis of this disruption by asking participants to solve mental addition problems (e.g., “45 + 17 = ?”) in three different conditions: background speech comprising numbers in ascending order (e.g., “61, 62, 63, 64, 65”), background speech comprising numbers in descending order (e.g., “65, 64, 63, 62, 61”), and quiet. Performance was best in quiet, worse in the descending numbers condition, and poorest in the ascending numbers condition. In view of these findings, we suggest that disruption arises as a by-product of preventing the primed, but inaccurate, candidate responses from assuming the control of action. Alternative explanations are also discussed.
Eye Movement Patterns Characteristic of Cognitive Style
Authors: Nitzan-Tamar Ortal , Kramarski Bracha , Vakil Eli
Published: July 2016

Abstract. Various tools have been designed to classify the wholistic/analytic cognitive style, based mostly on behavioral data that reveals little about how these processes function. The main goal of this study is to characterize patterns of eye movements (EM) that are typical of learners with tendencies toward wholistic/analytic styles. Forty students completed the E-CSA-W/A test, while their EM were simultaneously monitored. The results revealed that the overall response time of the wholist group was lower in both tasks. The differences in response time between the groups are interpreted as being influenced by impulsive/reflective styles. While the behavioral data provide us with the end result and quantitative differences between the groups, EM provide us with the qualitative information about the process that led to the response. The study showed that the wholist group is characterized by less fixations and transitions than the analytic group, which is interpreted as reflecting use of whole/partial strategy.
Spacing and Presentation Modes Affect the Unit-Decade Compatibility Effect During Number Comparison
Authors: Pletzer Belinda , Scheuringer Andrea , Harris TiAnni
Published: July 2016

Abstract. The unit-decade compatibility effect has challenged the model of holistic number magnitude processing, suggesting decomposed processing of multi-digit numbers. Recent evidence confirms that decomposed processing of decade and unit magnitudes occurs in parallel. However, the mode of presentation of multi-digit numbers may affect the processing mode (holistic vs. decomposed, parallel vs. sequential). We therefore investigated in two studies, whether presentation mode (vertical, horizontal, or consecutive) or the distance between two vertically presented numbers affects the unit-decade compatibility effect during number comparison. We found that the compatibility effect did not differ significantly between vertical and horizontal presentation, adding to previous results on perceptual generality, but was nonsignificant with consecutive presentation. However, the compatibility effect was significantly smaller, if numbers are spaced further apart. Thus, stimulus size and distance between numbers affect the processing of multi-digit numbers and should be reported in future studies.
Closing the Air Quality Data Gap in the Developing World
Authors: Pierce Kathleen
Published: July 2016

How a husband-and-wife team created the world's first open access, open source international air quality data hub—a global resource for health organizations, policy makers, and others.
Tougher Guidelines Issued for Alaska Offshore Drilling
Authors: Showstack Randy
Published: July 2016

The regulations will reinforce safety mechanisms and provide stronger planning efforts and enhanced regulatory certainty, according to the Department of the Interior.
Nuclear localization of platelet-activating factor receptor controls retinal neovascularization
Authors: K Bhosle Vikrant , Rivera José Carlos , Zhou Tianwei , Omri Samy , Sanchez Melanie , Hamel David , Zhu Tang , Rouget Raphael , Rabea Areej Al , Hou Xin , Lahaie Isabelle , Ribeiro-da-Silva Alfredo , Chemtob Sylvain
Published: July 2016

Platelet-activating factor (PAF) is a pleiotropic phospholipid with proinflammatory, procoagulant and angiogenic actions on the vasculature. We and others have reported the presence of PAF receptor (Ptafr) at intracellular sites such as the nucleus. However, mechanisms of localization and physiologic functions of intracellular Ptafr remain poorly understood. We hereby identify the importance of C-terminal motif of the receptor and uncover novel roles of Rab11a GTPase and importin-5 in nuclear translocation of Ptafr in primary human retinal microvascular endothelial cells. Nuclear localization of Ptafr is independent of exogenous PAF stimulation as well as intracellular PAF biosynthesis. Moreover, nuclear Ptafr is responsible for the upregulation of unique set of growth factors, including vascular endothelial growth factor, in vitro and ex vivo. We further corroborate the intracrine PAF signaling, resulting in angiogenesis in vivo, using Ptafr antagonists with distinct plasma membrane permeability. Collectively, our findings show that nuclear Ptafr translocates in an agonist-independent manner, and distinctive functions of Ptafr based on its cellular localization point to another dimension needed for pharmacologic selectivity of drugs.
Human islets contain four distinct subtypes of β cells
Authors: Dorrell Craig , Schug Jonathan , Canaday Pamela S. , Russ Holger A. , Tarlow Branden D. , Grompe Maria T. , Horton Tamara , Hebrok Matthias , Streeter Philip R. , Kaestner Klaus H. , Grompe Markus
Published: July 2016

Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human β cells, which we refer to as β1–4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the β cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined β cell heterogeneity is functionally and likely medically relevant.
Bottom-up synthesis of chiral covalent organic frameworks and their bound capillaries for chiral separation
Authors: Qian Hai-Long , Yang Cheng-Xiong , Yan Xiu-Ping
Published: July 2016

Covalent organic frameworks (COFs) are a novel class of porous materials, and offer great potential for various applications. However, the applications of COFs in chiral separation and chiral catalysis are largely underexplored due to the very limited chiral COFs available and their challenging synthesis. Here we show a bottom-up strategy to construct chiral COFs and an in situ growth approach to fabricate chiral COF-bound capillary columns for chiral gas chromatography. We incorporate the chiral centres into one of the organic ligands for the synthesis of the chiral COFs. We subsequently in situ prepare the COF-bound capillary columns. The prepared chiral COFs and their bound capillary columns give high resolution for the separation of enantiomers with excellent repeatability and reproducibility. The proposed strategy provides a promising platform for the synthesis of chiral COFs and their chiral separation application.
Treatment of ongoing autoimmune encephalomyelitis with activated B-cell progenitors maturing into regulatory B cells
Authors: Korniotis Sarantis , Gras Christophe , Letscher Hélène , Montandon Ruddy , Mégret Jérôme , Siegert Stefanie , Ezine Sophie , Fallon Padraic G. , Luther Sanjiv A. , Fillatreau Simon , Zavala Flora
Published: July 2016

The influence of signals perceived by immature B cells during their development in bone marrow on their subsequent functions as mature cells are poorly defined. Here, we show that bone marrow cells transiently stimulated in vivo or in vitro through the Toll-like receptor 9 generate proB cells (CpG-proBs) that interrupt experimental autoimmune encephalomyelitis (EAE) when transferred at the onset of clinical symptoms. Protection requires differentiation of CpG-proBs into mature B cells that home to reactive lymph nodes, where they trap T cells by releasing the CCR7 ligand, CCL19, and to inflamed central nervous system, where they locally limit immunopathogenesis through interleukin-10 production, thereby cooperatively inhibiting ongoing EAE. These data demonstrate that a transient inflammation at the environment, where proB cells develop, is sufficient to confer regulatory functions onto their mature B-cell progeny. In addition, these properties of CpG-proBs open interesting perspectives for cell therapy of autoimmune diseases.
Claspin recruits Cdc7 kinase for initiation of DNA replication in human cells
Authors: Yang Chi-Chun , Suzuki Masahiro , Yamakawa Shiori , Uno Syuzi , Ishii Ai , Yamazaki Satoshi , Fukatsu Rino , Fujisawa Ryo , Sakimura Kenji , Tsurimoto Toshiki , Masai Hisao
Published: July 2016

Claspin transmits replication stress signal from ATR to Chk1 effector kinase as a mediator. It also plays a role in efficient replication fork progression during normal growth. Here we have generated conditional knockout of Claspin and show that Claspin knockout mice are dead by E12.5 and Claspin knockout mouse embryonic fibroblast (MEF) cells show defect in S phase. Using the mutant cell lines, we report the crucial roles of the acidic patch (AP) near the C terminus of Claspin in initiation of DNA replication. Cdc7 kinase binds to AP and this binding is required for phosphorylation of Mcm. AP is involved also in intramolecular interaction with a N-terminal segment, masking the DNA-binding domain and a newly identified PIP motif, and Cdc7-mediated phosphorylation reduces the intramolecular interaction. Our results suggest a new role of Claspin in initiation of DNA replication during normal S phase through the recruitment of Cdc7 that facilitates phosphorylation of Mcm proteins.
Dynamic polarization vision in mantis shrimps
Authors: Daly Ilse M. , How Martin J. , Partridge Julian C. , Temple Shelby E. , Marshall N. Justin , Cronin Thomas W. , Roberts Nicholas W.
Published: July 2016

Gaze stabilization is an almost ubiquitous animal behaviour, one that is required to see the world clearly and without blur. Stomatopods, however, only fix their eyes on scenes or objects of interest occasionally. Almost uniquely among animals they explore their visual environment with a series pitch, yaw and torsional (roll) rotations of their eyes, where each eye may also move largely independently of the other. In this work, we demonstrate that the torsional rotations are used to actively enhance their ability to see the polarization of light. Both Gonodactylus smithii and Odontodactylus scyllarus rotate their eyes to align particular photoreceptors relative to the angle of polarization of a linearly polarized visual stimulus, thereby maximizing the polarization contrast between an object of interest and its background. This is the first documented example of any animal displaying dynamic polarization vision, in which the polarization information is actively maximized through rotational eye movements.
Golgi membrane fission requires the CtBP1-S/BARS-induced activation of lysophosphatidic acid acyltransferase δ
Authors: Pagliuso Alessandro , Valente Carmen , Giordano Lucia Laura , Filograna Angela , Li Guiling , Circolo Diego , Turacchio Gabriele , Marzullo Vincenzo Manuel , Mandrich Luigi , Zhukovsky Mikhail A. , Formiggini Fabio , Polishchuk Roman S. , Corda Daniela , Luini Alberto
Published: July 2016

Membrane fission is an essential cellular process by which continuous membranes split into separate parts. We have previously identified CtBP1-S/BARS (BARS) as a key component of a protein complex that is required for fission of several endomembranes, including basolateral post-Golgi transport carriers. Assembly of this complex occurs at the Golgi apparatus, where BARS binds to the phosphoinositide kinase PI4KIIIβ through a 14-3-3γ dimer, as well as to ARF and the PKD and PAK kinases. We now report that, when incorporated into this complex, BARS binds to and activates a trans-Golgi lysophosphatidic acid (LPA) acyltransferase type δ (LPAATδ) that converts LPA into phosphatidic acid (PA); and that this reaction is essential for fission of the carriers. LPA and PA have unique biophysical properties, and their interconversion might facilitate the fission process either directly or indirectly (via recruitment of proteins that bind to PA, including BARS itself).
Host genotype and age shape the leaf and root microbiomes of a wild perennial plant
Authors: Wagner Maggie R. , Lundberg Derek S , del Rio Tijana G. , Tringe Susannah G. , Dangl Jeffery L. , Mitchell-Olds Thomas
Published: July 2016

Bacteria living on and in leaves and roots influence many aspects of plant health, so the extent of a plant’s genetic control over its microbiota is of great interest to crop breeders and evolutionary biologists. Laboratory-based studies, because they poorly simulate true environmental heterogeneity, may misestimate or totally miss the influence of certain host genes on the microbiome. Here we report a large-scale field experiment to disentangle the effects of genotype, environment, age and year of harvest on bacterial communities associated with leaves and roots ofBoechera stricta(Brassicaceae), a perennial wild mustard. Host genetic control of the microbiome is evident in leaves but not roots, and varies substantially among sites. Microbiome composition also shifts as plants age. Furthermore, a large proportion of leaf bacterial groups are shared with roots, suggesting inoculation from soil. Our results demonstrate how genotype-by-environment interactions contribute to the complexity of microbiome assembly in natural environments.
Homologous recombination-dependent repair of telomeric DSBs in proliferating human cells
Authors: Mao Pingsu , Liu Jingfan , Zhang Zepeng , Zhang Hong , Liu Haiying , Gao Song , Rong Yikang S. , Zhao Yong
Published: July 2016

Telomeres prevent chromosome ends from being recognized as double-stranded breaks (DSBs). Meanwhile, G/C-rich repetitive telomeric DNA is susceptible to attack by DNA-damaging agents. How cells balance the need to protect DNA ends and the need to repair DNA lesions in telomeres is unknown. Here we show that telomeric DSBs are efficiently repaired in proliferating cells, but are irreparable in stress-induced and replicatively senescent cells. Using the CRISPR-Cas9 technique, we specifically induce DSBs at telomeric or subtelomeric regions. We find that DSB repair (DSBR) at subtelomeres occurs in an error-prone manner resulting in small deletions, suggestive of NHEJ. However, DSBR in telomeres involves ‘telomere-clustering’, 3′-protruding C-rich telomeric ssDNA, and HR between sister-chromatid or interchromosomal telomeres. DSBR in telomeres is suppressed by deletion or inhibition of Rad51. These findings reveal proliferation-dependent DSBR in telomeres and suggest that telomeric HR, which is normally constitutively suppressed, is activated in the context of DSBR.
Cavity-enhanced Raman microscopy of individual carbon nanotubes
Authors: Hümmer Thomas , Noe Jonathan , Hofmann Matthias S. , Hänsch Theodor W. , Högele Alexander , Hunger David
Published: July 2016

Raman spectroscopy reveals chemically specific information and provides label-free insight into the molecular world. However, the signals are intrinsically weak and call for enhancement techniques. Here, we demonstrate Purcell enhancement of Raman scattering in a tunable high-finesse microcavity, and utilize it for molecular diagnostics by combined Raman and absorption imaging. Studying individual single-wall carbon nanotubes, we identify crucial structural parameters such as nanotube radius, electronic structure and extinction cross-section. We observe a 320-times enhanced Raman scattering spectral density and an effective Purcell factor of 6.2, together with a collection efficiency of 60%. Potential for significantly higher enhancement, quantitative signals, inherent spectral filtering and absence of intrinsic background in cavity-vacuum stimulated Raman scattering render the technique a promising tool for molecular imaging. Furthermore, cavity-enhanced Raman transitions involving localized excitons could potentially be used for gaining quantum control over nanomechanical motion and open a route for molecular cavity optomechanics.
ERRα mediates metabolic adaptations driving lapatinib resistance in breast cancer
Authors: Deblois Geneviève , Smith Harvey W. , Tam Ingrid S. , Gravel Simon-Pierre , Caron Maxime , Savage Paul , Labbé David P. , Bégin Louis R. , Tremblay Michel L. , Park Morag , Bourque Guillaume , St-Pierre Julie , Muller William J. , Giguère Vincent
Published: July 2016

Despite the initial benefits of treating HER2-amplified breast cancer patients with the tyrosine kinase inhibitor lapatinib, resistance inevitably develops. Here we report that lapatinib induces the degradation of the nuclear receptor ERRα, a master regulator of cellular metabolism, and that the expression of ERRα is restored in lapatinib-resistant breast cancer cells through reactivation of mTOR signalling. Re-expression of ERRα in resistant cells triggers metabolic adaptations favouring mitochondrial energy metabolism through increased glutamine metabolism, as well as ROS detoxification required for cell survival under therapeutic stress conditions. An ERRα inverse agonist counteracts these metabolic adaptations and overcomes lapatinib resistance in a HER2-induced mammary tumour mouse model. This work reveals a molecular mechanism by which ERRα-induced metabolic reprogramming promotes survival of lapatinib-resistant cancer cells and demonstrates the potential of ERRα inhibition as an effective adjuvant therapy in poor outcome HER2-positive breast cancer.
Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution
Authors: Luo Bangwei , Wang Jinsong , Liu Zongwei , Shen Zigang , Shi Rongchen , Liu Yu-Qi , Liu Yu , Jiang Man , Wu Yuzhang , Zhang Zhiren
Published: July 2016

Inflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental and of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia and macrophage erythropoietin signalling. Macrophage-specific erythropoietin receptor-deficient mice and chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, and exogenous erythropoietin enhances this resolution in WT and CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARγ, promotes macrophage removal of debris and enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions.
Highly stable and self-repairing membrane-mimetic 2D nanomaterials assembled from lipid-like peptoids
Authors: Jin Haibao , Jiao Fang , Daily Michael D. , Chen Yulin , Yan Feng , Ding Yan-Huai , Zhang Xin , Robertson Ellen J. , Baer Marcel D. , Chen Chun-Long
Published: July 2016

An ability to develop sequence-defined synthetic polymers that both mimic lipid amphiphilicity for self-assembly of highly stable membrane-mimetic 2D nanomaterials and exhibit protein-like functionality would revolutionize the development of biomimetic membranes. Here we report the assembly of lipid-like peptoids into highly stable, crystalline, free-standing and self-repairing membrane-mimetic 2D nanomaterials through a facile crystallization process. Both experimental and molecular dynamics simulation results show that peptoids assemble into membranes through an anisotropic formation process. We further demonstrated the use of peptoid membranes as a robust platform to incorporate and pattern functional objects through large side-chain diversity and/or co-crystallization approaches. Similar to lipid membranes, peptoid membranes exhibit changes in thickness upon exposure to external stimuli; they can coat surfaces in single layers and self-repair. We anticipate that this new class of membrane-mimetic 2D nanomaterials will provide a robust matrix for development of biomimetic membranes tailored to specific applications.
The molecular landscape of high-risk early breast cancer: comprehensive biomarker analysis of a phase III adjuvant population
Authors: Wilson Timothy R , Yu Jianjun , Lu Xuyang , Spoerke Jill M , Xiao Yuanyuan , O’Brien Carol , Savage Heidi M , Huw Ling-Yuh , Zou Wei , Koeppen Hartmut , Forrest William F , Fridlyand Jane , Fu Ling , Tam Rachel , Schleifman Erica B , Sumiyoshi Teiko , Molinero Luciana , Hampton Garret M , O’Shaughnessy Joyce A , Lackner Mark R
Published: July 2016

Breast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. We sought to characterize the molecular landscape of high-risk breast cancer patients enrolled onto an adjuvant chemotherapy study to understand how disease subsets and tumor immune status impact survival. DNA and RNA were extracted from 861 breast cancer samples from patients enrolled onto the United States Oncology trial 01062. Samples were characterized using multiplex gene expression, copy number, and qPCR mutation assays. HR+patients with aPIK3CAmutant tumor had a favorable disease-free survival (DFS; HR 0.66,P=0.05), however, the prognostic effect was specific to luminal A patients (Luminal A: HR 0.67,P=0.1; Luminal B: HR 1.01,P=0.98). Molecular subtyping of triple-negative breast cancers (TNBCs) suggested that the mesenchymal subtype had the worst DFS, whereas the immunomodulatory subtype had the best DFS. Profiling of immunologic genes revealed that TNBC tumors (n=280) displaying an activated T-cell signature had a longer DFS following adjuvant chemotherapy (HR 0.59,P=0.04), while a distinct set of immune genes was associated with DFS in HR+cancers. Utilizing a discovery approach, we identified genes associated with a high risk of recurrence in HR+patients, which were validated in an independent data set. Molecular classification based on PAM50 and TNBC subtyping stratified clinical high-risk patients into distinct prognostic subsets. Patients with high expression of immune-related genes showed superior DFS in both HR+and TNBC. These results may inform patient management and drug development in early breast cancer.
Correction: Corrigendum: Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development
Authors: Liu Yu-Fan , Chiang Shang-Lun , Lin Chien-Yu , Chang Jan-Gowth , Chung Chia-Min , Ko Albert Min-Shan , Lin You-Zhe , Lee Chien-Hung , Lee Ka-Wo , Chen Mu-Kuan , Hua Chun-Hung , Tsai Ming-Hsui , Chen Yuan-Chien , Ko Ying-Chin
Published: July 2016

Scientific Reports 6: Article number: 24014; published online: 01 April 2016; updated: 11 July 2016 This Article contains errors in Table 1, where the column headings ‘Without SMs (n = 105)’ and ‘With SMs (n = 23) are inverted. The correct Table 1 appears below.
Footprints reveal direct evidence of group behavior and locomotion in Homo erectus
Authors: Hatala Kevin G. , Roach Neil T. , Ostrofsky Kelly R. , Wunderlich Roshna E. , Dingwall Heather L. , Villmoare Brian A. , Green David J. , Harris John W. K. , Braun David R. , Richmond Brian G.
Published: July 2016

Bipedalism is a defining feature of the human lineage. Despite evidence that walking on two feet dates back 6–7 Ma, reconstructing hominin gait evolution is complicated by a sparse fossil record and challenges in inferring biomechanical patterns from isolated and fragmentary bones. Similarly, patterns of social behavior that distinguish modern humans from other living primates likely played significant roles in our evolution, but it is exceedingly difficult to understand the social behaviors of fossil hominins directly from fossil data. Footprints preserve direct records of gait biomechanics and behavior but they have been rare in the early human fossil record. Here we present analyses of an unprecedented discovery of 1.5-million-year-old footprint assemblages, produced by 20+ Homo erectus individuals. These footprints provide the oldest direct evidence for modern human-like weight transfer and confirm the presence of an energy-saving longitudinally arched foot in H. erectus. Further, print size analyses suggest that these H. erectus individuals lived and moved in cooperative multi-male groups, offering direct evidence consistent with human-like social behaviors in H. erectus.
A Rational Approach for the Identification of Non-Hydroxamate HDAC6-Selective Inhibitors
Authors: Goracci Laura , Deschamps Nathalie , Randazzo Giuseppe Marco , Petit Charlotte , Dos Santos Passos Carolina , Carrupt Pierre-Alain , Simões-Pires Claudia , Nurisso Alessandra
Published: July 2016

The human histone deacetylase isoform 6 (HDAC6) has been demonstrated to play a major role in cell motility and aggresome formation, being interesting for the treatment of multiple tumour types and neurodegenerative conditions. Currently, most HDAC inhibitors in preclinical or clinical evaluations are non-selective inhibitors, characterised by a hydroxamate zinc-binding group (ZBG) showing off-target effects and mutagenicity. The identification of selective HDAC6 inhibitors with novel chemical properties has not been successful yet, also because of the absence of crystallographic information that makes the rational design of HDAC6 selective inhibitors difficult. Using HDAC inhibitory data retrieved from the ChEMBL database and ligand-based computational strategies, we identified 8 original new non-hydroxamate HDAC6 inhibitors from the SPECS database, with activity in the low μM range. The most potent and selective compound, bearing a hydrazide ZBG, was shown to increase tubulin acetylation in human cells. No effects on histone H4 acetylation were observed. To the best of our knowledge, this is the first report of an HDAC6 selective inhibitor bearing a hydrazide ZBG. Its capability to passively cross the blood-brain barrier (BBB), as observed through PAMPA assays and its low cytotoxicity in vitro, suggested its potential for drug development.
Sox transcription in sarcosine utilization is controlled by Sigma54 and SoxR in Bacillus thuringiensis HD73
Authors: Peng Qi , Liu Chunxia , Wang Bo , Yang Min , Wu Jianbo , Zhang Jie , Song Fuping
Published: July 2016

Sarcosine oxidase catalyzes the oxidative demethylation of sarcosine to yield glycine, formaldehyde and hydrogen peroxide. In this study, we analyzed the transcription and regulation of the sox locus, including the sarcosine oxidase-encoding genes in Bacillus thuringiensis (Bt). RT-PCR analysis revealed that the sox locus forms two opposing transcriptional units: soxB (soxB/E/F/G/H/I) and soxR (soxR/C/D/A). The typical −12/−24 consensus sequence was located 15 bp and 12 bp from the transcriptional start site (TSS) of soxB and soxC, respectively. Promoter-lacZ fusion assays showed that the soxB promoter is controlled by the Sigma54 factor and is activated by the Sigma54-dependent transcriptional regulator SoxR. SoxR also inhibits its own expression. Expression from the PsoxCR promoter, which is responsible for the transcription of soxC, soxD, and soxA, is Sigma54-dependent and requires SoxR. An 11-bp inverted repeat sequence was identified as SoxR binding site upstream of the soxB TSS. Purified SoxR specifically bound a DNA fragment containing this region. Mutation or deletion of this sequence abolished the transcriptional activities of soxB and soxC. Thus, SoxR binds to the same sequence to activate the transcription of soxB and soxC. Sarcosine utilization was abolished in soxB and soxR mutants, suggesting that the sox locus is essential for sarcosine utilization.
Correction: Corrigendum: Synthesis of Reduced Graphene Oxide-Modified LiMn0.75Fe0.25PO4 Microspheres by Salt-Assisted Spray Drying for High-Performance Lithium-Ion Batteries
Authors: Kim Myeong-Seong , Kim Hyun-Kyung , Lee Suk-Woo , Kim Dong-Hyun , Ruan Dianbo , Chung Kyung Yoon , Lee Sang Hyun , Roh Kwang Chul , Kim Kwang-Bum
Published: July 2016

Scientific Reports 6: Article number: 26686; published online: 25 May 2016; updated: 11 July 2016 The Acknowledgements section in this Article is incomplete. “This work was supported by the energy efficiency and resources grant (No: 20122010100140) of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) funded by the Ministry of Knowledge Economy, Korean government.
A novel quantitation approach for maximizing detectable targets for offensive/volatile odorants with diverse functional groups by thermal desorption-gas chromatography-mass spectrometry
Authors: Kim Yong-Hyun , Kim Ki-Hyun
Published: July 2016

A multitude of analytical systems are needed to analyze diverse odorants with various functionalities. In this study, an experimental method was developed to assess the maximum covering range of odorants using a single experimental setup consisting of a thermal desorber-gas chromatography-mass spectrometry system. To this end, a total of 20 offensive odorants (aldehyde, ketone, ester, alcohol, aromatic, sulfide, amine, and carboxyl) were selected and tested by a single system. The analytical results of standards and environmental samples were evaluated in a number of respects. In the analysis of the standards, all targets were quantified via Carbopack (C + B + X) tube sampling while operating the thermal desorber at −25 °C. The method detection limits of 18 targets (exception of 2 out of the 20 targets: acetaldehyde and methanethiol) were excellent (mean 0.04 ± 0.03 ppb) in terms of their odor threshold values (74.7 ± 140 ~ 624 ± 1,729 ppb). The analysis of organic fertilizer plant samples at a pig farm (slurry treatment facility, compost facility, and ambient air) confirmed the presence of 18 odorants from 0.03 ppb (dimethyldisulfide, ambient sample) to 522 ppb (methyl ethyl ketone, slurry treatment facility). As such, our method allowed simultaneous quantitation of most key odorants with sufficient reliability and sensitivity.
The In-Plane Anisotropy of WTe2 Investigated by Angle-Dependent and Polarized Raman Spectroscopy
Authors: Song Qingjun , Pan Xingchen , Wang Haifeng , Zhang Kun , Tan Qinghai , Li Pan , Wan Yi , Wang Yilun , Xu Xiaolong , Lin Miaoling , Wan Xiangang , Song Fengqi , Dai Lun
Published: July 2016

Tungsten ditelluride (WTe2) is a semi-metallic layered transition metal dichalcogenide with a stable distorted 1T phase. The reduced symmetry of this system leads to in-plane anisotropy in various materials properties. We have systemically studied the in-plane anisotropy of Raman modes in few-layer and bulk WTe2 by angle-dependent and polarized Raman spectroscopy (ADPRS). Ten Raman modes are clearly resolved. Their intensities show periodic variation with sample rotating. We identify the symmetries of the detected modes by quantitatively analyzing the ADPRS results based on the symmetry selection rules. Material absorption effect on the phonon modes with high vibration frequencies is investigated by considering complex Raman tensor elements. We also provide a rapid and nondestructive method to identify the crystallographic orientation of WTe2. The crystallographic orientation is further confirmed by the quantitative atomic-resolution force image. Finally, we find that the atomic vibrational tendency and complexity of detected modes are also reflected in the shrinkage degree defined based on ADPRS, which is confirmed by corresponding density functional calculation. Our work provides a deep understanding of the interaction between WTe2 and light, which will benefit in future studies about the anisotropic physical properties of WTe2 and other in-plane anisotropic materials.
Oxidative Stress Induced by Pt(IV) Pro-drugs Based on the Cisplatin Scaffold and Indole Carboxylic Acids in Axial Position
Authors: Tolan Dina , Gandin Valentina , Morrison Liam , El-Nahas Ahmed , Marzano Cristina , Montagner Diego , Erxleben Andrea
Published: July 2016

The use of Pt(IV) complexes as pro-drugs that are activated by intracellular reduction is a widely investigated approach to overcome the limitations of Pt(II) anticancer agents. A series of ten mono- and bis-carboxylated Pt(IV) complexes with axial indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) ligands were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, 1H and 195Pt NMR spectroscopy. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. All the complexes are able to overcome cisplatin-resistance and the most potent complex, cis,cis,trans-[Pt(NH3)2Cl2(IPA)(OH)] was on average three times more active than cisplatin. Mechanistic studies revealed that the trend in cytotoxicity of the Pt(IV) complexes is primarily consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which in turn results in the loss of mitochondrial membrane potential and apoptosis induction. The role of the indole acid ligand as a redox modulator is discussed.
Potent response of QS-21 as a vaccine adjuvant in the skin when delivered with the Nanopatch, resulted in adjuvant dose sparing
Authors: Ng Hwee-Ing , Fernando Germain J. P. , Depelsenaire Alexandra C. I. , Kendall Mark A. F.
Published: July 2016

Adjuvants play a key role in boosting immunogenicity of vaccines, particularly for subunit protein vaccines. In this study we investigated the induction of antibody response against trivalent influenza subunit protein antigen and a saponin adjuvant, QS-21. Clinical trials of QS-21 have demonstrated the safety but, also a need of high dose for optimal immunity, which could possibly reduce patient acceptability. Here, we proposed the use of a skin delivery technology – the Nanopatch – to reduce both adjuvant and antigen dose but also retain its immune stimulating effects when compared to the conventional needle and syringe intramuscular (IM) delivery. We have demonstrated that Nanopatch delivery to skin requires only 1/100th of the IM antigen dose to induce equivalent humoral response. QS-21 enhanced humoral response in both skin and muscle route. Additionally, Nanopatch has demonstrated 30-fold adjuvant QS-21 dose sparing while retaining immune stimulating effects compared to IM. QS-21 induced localised, controlled cell death in the skin, suggesting that the danger signals released from dead cells contributed to the enhanced immunogenicity. Taken together, these findings demonstrated the suitability of reduced dose of QS-21 and the antigen using the Nanopatch to enhance humoral responses, and the potential to increase patient acceptability of QS-21 adjuvant.
Disrupted topological organization of structural and functional brain connectomes in clinically isolated syndrome and multiple sclerosis
Authors: Shu Ni , Duan Yunyun , Xia Mingrui , Schoonheim Menno M. , Huang Jing , Ren Zhuoqiong , Sun Zheng , Ye Jing , Dong Huiqing , Shi Fu-Dong , Barkhof Frederik , Li Kuncheng , Liu Yaou
Published: July 2016

The brain connectome of multiple sclerosis (MS) has been investigated by several previous studies; however, it is still unknown how the network changes in clinically isolated syndrome (CIS), the earliest stage of MS, and how network alterations on a functional level relate to the structural level in MS disease. Here, we investigated the topological alterations of both the structural and functional connectomes in 41 CIS and 32 MS patients, compared to 35 healthy controls, by combining diffusion tensor imaging and resting-state functional MRI with graph analysis approaches. We found that the structural connectome showed a deviation from the optimal pattern as early as the CIS stage, while the functional connectome only showed local changes in MS patients, not in CIS. When comparing two patient groups, the changes appear more severe in MS. Importantly, the disruptions of structural and functional connectomes in patients occurred in the same direction and locally correlated in sensorimotor component. Finally, the extent of structural network changes was correlated with several clinical variables in MS patients. Together, the results suggested early disruption of the structural brain connectome in CIS patients and provided a new perspective for investigating the relationship of the structural and functional alterations in MS.
Biochemical and proteomic characterization of retrovirus Gag based microparticles carrying melanoma antigens
Authors: Kurg Reet , Reinsalu Olavi , Jagur Sergei , Õunap Kadri , Võsa Liisi , Kasvandik Sergo , Padari Kärt , Gildemann Kiira , Ustav Mart
Published: July 2016

Extracellular vesicles are membraneous particles released by a variety of cells into the extracellular microenvironment. Retroviruses utilize the cellular vesiculation pathway for virus budding/assembly and the retrovirus Gag protein induces the spontaneous formation of microvesicles or virus-like particles (VLPs) when expressed in the mammalian cells. In this study, five different melanoma antigens, MAGEA4, MAGEA10, MART1, TRP1 and MCAM, were incorporated into the VLPs and their localization within the particles was determined. Our data show that the MAGEA4 and MAGEA10 proteins as well as MCAM are expressed on the surface of VLPs. The compartmentalization of exogenously expressed cancer antigens within the VLPs did not depend on the localization of the protein within the cell. Comparison of the protein content of VLPs by LC-MS/MS-based label-free quantitative proteomics showed that VLPs carrying different cancer antigens are very similar to each other, but differ to some extent from VLPs without recombinant antigen. We suggest that retrovirus Gag based virus-like particles carrying recombinant antigens have a potential to be used in cancer immunotherapy.