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Showing papers by "University of Erlangen-Nuremberg published in 2014"


Journal ArticleDOI
Keith A. Olive1, Kaustubh Agashe2, Claude Amsler3, Mario Antonelli  +222 moreInstitutions (107)
TL;DR: The review as discussed by the authors summarizes much of particle physics and cosmology using data from previous editions, plus 3,283 new measurements from 899 Japers, including the recently discovered Higgs boson, leptons, quarks, mesons and baryons.
Abstract: The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 Japers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that are new or heavily revised including those on: Dark Energy, Higgs Boson Physics, Electroweak Model, Neutrino Cross Section Measurements, Monte Carlo Neutrino Generators, Top Quark, Dark Matter, Dynamical Electroweak Symmetry Breaking, Accelerator Physics of Colliders, High-Energy Collider Parameters, Big Bang Nucleosynthesis, Astrophysical Constants and Cosmological Parameters.

7,337 citations


Journal ArticleDOI
Stephan Ripke1, Stephan Ripke2, Benjamin M. Neale1, Benjamin M. Neale2  +351 moreInstitutions (102)
24 Jul 2014-Nature
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

6,809 citations


Journal ArticleDOI
TL;DR: The role of cytokines produced by innate and adaptive immune cells, as well as their relevance to the future therapy of IBD are discussed.
Abstract: Erroneous communication between the innate and adaptive immune systems through cytokines results in exaggerated or attenuated immune response. It is not known whether the pathologic immune response in inflammatory bowel disease has its origin in a dysbalance of pro- and anti-inflammatory cytokine release or whether it is secondary in subsequence of a defective intestinal barrier or the destructive power of aggressive microbiota in the gut lumen.

1,938 citations


Proceedings ArticleDOI
01 Jan 2014
TL;DR: DREBIN is proposed, a lightweight method for detection of Android malware that enables identifying malicious applications directly on the smartphone and outperforms several related approaches and detects 94% of the malware with few false alarms.
Abstract: Malicious applications pose a threat to the security of the Android platform. The growing amount and diversity of these applications render conventional defenses largely ineffective and thus Android smartphones often remain unprotected from novel malware. In this paper, we propose DREBIN, a lightweight method for detection of Android malware that enables identifying malicious applications directly on the smartphone. As the limited resources impede monitoring applications at run-time, DREBIN performs a broad static analysis, gathering as many features of an application as possible. These features are embedded in a joint vector space, such that typical patterns indicative for malware can be automatically identified and used for explaining the decisions of our method. In an evaluation with 123,453 applications and 5,560 malware samples DREBIN outperforms several related approaches and detects 94% of the malware with few false alarms, where the explanations provided for each detection reveal relevant properties of the detected malware. On five popular smartphones, the method requires 10 seconds for an analysis on average, rendering it suitable for checking downloaded applications directly on the device.

1,905 citations


Journal ArticleDOI
TL;DR: This data set provides quantum chemical properties for a relevant, consistent, and comprehensive chemical space of small organic molecules that may serve the benchmarking of existing methods, development of new methods, such as hybrid quantum mechanics/machine learning, and systematic identification of structure-property relationships.
Abstract: Computational de novo design of new drugs and materials requires rigorous and unbiased exploration of chemical compound space. However, large uncharted territories persist due to its size scaling combinatorially with molecular size. We report computed geometric, energetic, electronic, and thermodynamic properties for 134k stable small organic molecules made up of CHONF. These molecules correspond to the subset of all 133,885 species with up to nine heavy atoms (CONF) out of the GDB-17 chemical universe of 166 billion organic molecules. We report geometries minimal in energy, corresponding harmonic frequencies, dipole moments, polarizabilities, along with energies, enthalpies, and free energies of atomization. All properties were calculated at the B3LYP/6-31G(2df,p) level of quantum chemistry. Furthermore, for the predominant stoichiometry, C7H10O2, there are 6,095 constitutional isomers among the 134k molecules. We report energies, enthalpies, and free energies of atomization at the more accurate G4MP2 level of theory for all of them. As such, this data set provides quantum chemical properties for a relevant, consistent, and comprehensive chemical space of small organic molecules. This database may serve the benchmarking of existing methods, development of new methods, such as hybrid quantum mechanics/machine learning, and systematic identification of structure-property relationships.

1,272 citations


Journal ArticleDOI
Kestutis Aidas1, Celestino Angeli2, Keld L. Bak3, Vebjørn Bakken4, Radovan Bast5, Linus Boman6, Ove Christiansen3, Renzo Cimiraglia2, Sonja Coriani7, Pål Dahle8, Erik K. Dalskov, Ulf Ekström4, Thomas Enevoldsen9, Janus J. Eriksen3, Patrick Ettenhuber3, Berta Fernández10, Lara Ferrighi, Heike Fliegl4, Luca Frediani, Kasper Hald11, Asger Halkier, Christof Hättig12, Hanne Heiberg13, Trygve Helgaker4, Alf C. Hennum14, Hinne Hettema15, Eirik Hjertenæs16, Stine Høst3, Ida-Marie Høyvik3, Maria Francesca Iozzi17, Brannislav Jansik18, Hans-Jørgen Aa. Jensen9, Dan Jonsson, Poul Jørgensen3, Johanna Kauczor19, Sheela Kirpekar, Thomas Kjærgaard3, Wim Klopper20, Stefan Knecht21, Rika Kobayashi22, Henrik Koch16, Jacob Kongsted9, Andreas Krapp, Kasper Kristensen3, Andrea Ligabue23, Ola B. Lutnæs24, Juan Ignacio Melo25, Kurt V. Mikkelsen26, Rolf H. Myhre16, Christian Neiss27, Christian B. Nielsen, Patrick Norman19, Jeppe Olsen3, Jógvan Magnus Haugaard Olsen9, Anders Osted, Martin J. Packer9, Filip Pawłowski28, Thomas Bondo Pedersen4, Patricio Federico Provasi29, Simen Reine4, Zilvinas Rinkevicius5, Torgeir A. Ruden, Kenneth Ruud, Vladimir V. Rybkin20, Paweł Sałek, Claire C. M. Samson20, Alfredo Sánchez de Merás30, Trond Saue31, Stephan P. A. Sauer26, Bernd Schimmelpfennig20, Kristian Sneskov11, Arnfinn Hykkerud Steindal, Kristian O. Sylvester-Hvid, Peter R. Taylor32, Andrew M. Teale33, Erik I. Tellgren4, David P. Tew34, Andreas J. Thorvaldsen3, Lea Thøgersen35, Olav Vahtras5, Mark A. Watson36, David J. D. Wilson37, Marcin Ziółkowski38, Hans Ågren5 
TL;DR: Dalton is a powerful general‐purpose program system for the study of molecular electronic structure at the Hartree–Fock, Kohn–Sham, multiconfigurational self‐consistent‐field, Møller–Plesset, configuration‐interaction, and coupled‐cluster levels of theory.
Abstract: Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, confi ...

1,212 citations


Journal ArticleDOI
M. G. Aartsen1, Markus Ackermann, Jenni Adams2, Juanan Aguilar3  +299 moreInstitutions (41)
TL;DR: Results from an analysis with a third year of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm-2 s-1 sr-1 per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7σ.
Abstract: A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm(-2) s(-1) sr(-1) per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7 sigma. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.

1,183 citations


Journal ArticleDOI
TL;DR: In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC or UICCTNM classification.
Abstract: The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

1,128 citations



Journal ArticleDOI
TL;DR: The present review tries to give a comprehensive and most up to date view to the field, with an emphasis on the currently most investigated anodic TiO2 nanotube arrays.
Abstract: In the present review we try to give a comprehensive and most up to date view to the field, with an emphasis on the currently most investigated anodic TiO2 nanotube arrays. We will first give an overview of different synthesis approaches to produce TiO2 nanotubes and TiO2 nanotube arrays, and then deal with physical and chemical properties of TiO2 nanotubes and techniques to modify them. Finally, we will provide an overview of the most explored and prospective applications of nanotubular TiO2.

984 citations


Journal ArticleDOI
TL;DR: An overview of SWIPT systems with a particular focus on the hardware realization of rectenna circuits and practical techniques that achieveSWIPT in the domains of time, power, antennas, and space is provided.
Abstract: Energy harvesting for wireless communication networks is a new paradigm that allows terminals to recharge their batteries from external energy sources in the surrounding environment. A promising energy harvesting technology is wireless power transfer where terminals harvest energy from electromagnetic radiation. Thereby, the energy may be harvested opportunistically from ambient electromagnetic sources or from sources that intentionally transmit electromagnetic energy for energy harvesting purposes. A particularly interesting and challenging scenario arises when sources perform simultaneous wireless information and power transfer (SWIPT), as strong signals not only increase power transfer but also interference. This article provides an overview of SWIPT systems with a particular focus on the hardware realization of rectenna circuits and practical techniques that achieve SWIPT in the domains of time, power, antennas, and space. The article also discusses the benefits of a potential integration of SWIPT technologies in modern communication networks in the context of resource allocation and cooperative cognitive radio networks.

Journal ArticleDOI
20 Mar 2014-Nature
TL;DR: The increased immunity found in mice lacking IL-35 production by B cells was associated with a higher activation of macrophages and inflammatory T cells, as well as an increased function of B cells as antigen-presenting cells (APCs).
Abstract: B lymphocytes have critical roles as positive and negative regulators of immunity. Their inhibitory function has been associated primarily with interleukin 10 (IL-10) because B-cell-derived IL-10 can protect against autoimmune disease and increase susceptibility to pathogens. Here we identify IL-35-producing B cells as key players in the negative regulation of immunity. Mice in which only B cells did not express IL-35 lost their ability to recover from the T-cell-mediated demyelinating autoimmune disease experimental autoimmune encephalomyelitis (EAE). In contrast, these mice displayed a markedly improved resistance to infection with the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as shown by their superior containment of the bacterial growth and their prolonged survival after primary infection, and upon secondary challenge, compared to control mice. The increased immunity found in mice lacking IL-35 production by B cells was associated with a higher activation of macrophages and inflammatory T cells, as well as an increased function of B cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and IL-10-producing B cells corresponded to two largely distinct sets of surface-IgM(+)CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressing the transcription factor Blimp1 (also known as Prdm1). During EAE, CD138(+) plasma cells were also the main source of B-cell-derived IL-35 and IL-10. Collectively, our data show the importance of IL-35-producing B cells in regulation of immunity and highlight IL-35 production by B cells as a potential therapeutic target for autoimmune and infectious diseases. This study reveals the central role of activated B cells, particularly plasma cells, and their production of cytokines in the regulation of immune responses in health and disease.

Journal ArticleDOI
TL;DR: This poster presents a meta-analyses of the literature review conducted at the 2015 American College of Cardiology Annual Meeting and presented as a “roadmap for future studies” to improve the quality of care for patients with high-risk hearts.

Journal ArticleDOI
TL;DR: In this article, a review of the state-of-the-art for the chemical functionalization of graphite, graphene, graphite oxide, and graphite-based nanomaterials is presented.
Abstract: The chemical production of graphene as well as its controlled wet chemical modification is a challenge for synthetic chemists. Furthermore, the characterization of reaction products requires sophisticated analytical methods. In this Review we first describe the structure of graphene and graphene oxide and then outline the most important synthetic methods that are used for the production of these carbon-based nanomaterials. We summarize the state-of-the-art for their chemical functionalization by noncovalent and covalent approaches. We put special emphasis on the differentiation of the terms graphite, graphene, graphite oxide, and graphene oxide. An improved fundamental knowledge of the structure and the chemical properties of graphene and graphene oxide is an important prerequisite for the development of practical applications.

Journal ArticleDOI
TL;DR: It is reported that neutrophils recruited to sites of inflammation undergo oxidative burst and form neutrophil extracellular traps (NETs), and aggregated NETs promote the resolution of neutrophilic inflammation by degrading cytokines and chemokines and disrupting neutrophIL recruitment and activation.
Abstract: Gout is characterized by an acute inflammatory reaction and the accumulation of neutrophils in response to monosodium urate (MSU) crystals. Inflammation resolves spontaneously within a few days, although MSU crystals can still be detected in the synovial fluid and affected tissues. Here we report that neutrophils recruited to sites of inflammation undergo oxidative burst and form neutrophil extracellular traps (NETs). Under high neutrophil densities, these NETs aggregate and degrade cytokines and chemokines via serine proteases. Tophi, the pathognomonic structures of chronic gout, share characteristics with aggregated NETs, and MSU crystals can induce NETosis and aggregation of NETs. In individuals with impaired NETosis, MSU crystals induce uncontrolled production of inflammatory mediators from neutrophils and persistent inflammation. Furthermore, in models of neutrophilic inflammation, NETosis-deficient mice develop exacerbated and chronic disease that can be reduced by adoptive transfer of aggregated NETs. These findings suggest that aggregated NETs promote the resolution of neutrophilic inflammation by degrading cytokines and chemokines and disrupting neutrophil recruitment and activation.

Journal ArticleDOI
Sofia Khan1, Dario Greco2, Dario Greco1, Kyriaki Michailidou3  +158 moreInstitutions (54)
12 Nov 2014-PLOS ONE
TL;DR: Five miRNA binding site SNPs associated significantly with breast cancer risk are located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively, which belongs to miRNA machinery genes and has a central role in initial miRNA processing.
Abstract: Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

Journal ArticleDOI
TL;DR: Interleukin (IL)-10 expression by macrophages is identified as the critical mediator of this phenotype and expression of IL12A and cytotoxic effector molecules were predictive of pathological complete response rates to paclitaxel in human breast cancer.

Journal ArticleDOI
TL;DR: The findings suggest that solely MOF-derived heteroatom-doped carbon materials can be a promising alternative for Pt-based catalysts in fuel cells.
Abstract: Nitrogen-doped graphitic porous carbons (NGPCs) have been synthesized by using a zeolite-type nanoscale metal–organic framework (NMOF) as a self-sacrificing template, which simultaneously acts as both the carbon and nitrogen sources in a facile carbonization process. The NGPCs not only retain the nanopolyhedral morphology of the parent NMOF, but also possess rich nitrogen, high surface area and hierarchical porosity with well-conducting networks. The promising potential of NGPCs as metal-free electrocatalysts for oxygen reduction reactions (ORR) in fuel cells is demonstrated. Compared with commercial Pt/C, the optimized NGPC-1000-10 (carbonized at 1000 °C for 10 h) catalyst exhibits comparable electrocatalytic activity via an efficient four-electron-dominant ORR process coupled with superior methanol tolerance as well as cycling stability in alkaline media. Furthermore, the controlled experiments reveal that the optimum activity of NGPC-1000-10 can be attributed to the synergetic contributions of the abundant active sites with high graphitic-N portion, high surface area and porosity, and the high degree of graphitization. Our findings suggest that solely MOF-derived heteroatom-doped carbon materials can be a promising alternative for Pt-based catalysts in fuel cells.

Journal ArticleDOI
Oliver Kepp1, Laura Senovilla1, Ilio Vitale, Erika Vacchelli1, Sandy Adjemian2, Patrizia Agostinis3, Lionel Apetoh4, Fernando Aranda1, Vincenzo Barnaba5, Norma Bloy1, Laura Bracci6, Karine Breckpot7, David Brough8, Aitziber Buqué1, Maria G. Castro9, Mara Cirone5, María Isabel Colombo10, Isabelle Cremer11, Sandra Demaria12, Luciana Dini13, Aristides G. Eliopoulos14, Alberto Faggioni5, Silvia C. Formenti12, Jitka Fucikova15, Lucia Gabriele6, Udo S. Gaipl16, Jérôme Galon11, Abhishek D. Garg3, François Ghiringhelli4, Nathalia A. Giese17, Zong Sheng Guo18, Akseli Hemminki19, Martin Herrmann16, James W. Hodge20, Stefan Holdenrieder21, Jamie Honeychurch8, Hong-Min Hu22, Xing Huang1, Timothy M Illidge8, Koji Kono23, Mladen Korbelik, Dmitri V. Krysko24, Sherene Loi, Pedro R. Lowenstein9, Enrico Lugli25, Yuting Ma1, Frank Madeo26, Angelo A. Manfredi, Isabelle Martins27, Domenico Mavilio25, Laurie Menger28, Nicolò Merendino29, Michael Michaud1, Grégoire Mignot, Karen L. Mossman30, Gabriele Multhoff31, Rudolf Oehler32, Fabio Palombo5, Theocharis Panaretakis33, Jonathan Pol1, Enrico Proietti6, Jean-Ehrland Ricci34, Chiara Riganti35, Patrizia Rovere-Querini, Anna Rubartelli, Antonella Sistigu, Mark J. Smyth36, Juergen Sonnemann, Radek Spisek15, John Stagg37, Abdul Qader Sukkurwala38, Eric Tartour39, Andrew Thorburn40, Stephen H. Thorne18, Peter Vandenabeele24, Francesca Velotti29, Samuel T Workenhe30, Haining Yang41, Wei-Xing Zong42, Laurence Zitvogel1, Guido Kroemer43, Lorenzo Galluzzi43 
TL;DR: Strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative I CD inducers are outlined, based on a high-content, high-throughput platform that was recently developed.
Abstract: Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

Journal ArticleDOI
TL;DR: In this paper, the authors provided a high-resolution view of the lipid organization of a plasma membrane at an unprecedented level of complexity by combining 14 types of headgroups and 11 types of tails asymmetrically distributed across the two leaflets, closely mimicking an idealized mammalian plasma membrane.
Abstract: The detailed organization of cellular membranes remains rather elusive. Based on large-scale molecular dynamics simulations, we provide a high-resolution view of the lipid organization of a plasma membrane at an unprecedented level of complexity. Our plasma membrane model consists of 63 different lipid species, combining 14 types of headgroups and 11 types of tails asymmetrically distributed across the two leaflets, closely mimicking an idealized mammalian plasma membrane. We observe an enrichment of cholesterol in the outer leaflet and a general non-ideal lateral mixing of the different lipid species. Transient domains with liquid-ordered character form and disappear on the microsecond time scale. These domains are coupled across the two membrane leaflets. In the outer leaflet, distinct nanodomains consisting of gangliosides are observed. Phosphoinositides show preferential clustering in the inner leaflet. Our data provide a key view on the lateral organization of lipids in one of life's fundamental structures, the cell membrane.

Journal ArticleDOI
TL;DR: Optical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD and provides more distinct vascular network patterns that were less obscured by subretinal hemorrhage.

Journal ArticleDOI
TL;DR: Optical coherence tomography angiography, generated by the new SSADA, repeatably measures optic disc perfusion and may be useful in the evaluation of glaucoma and glAUcoma progression.

Journal ArticleDOI
TL;DR: It is shown that the efficiency at maximum power increases with the degree of squeezing, surpassing the standard Carnot limit and approaching unity exponentially for large squeezing parameters.
Abstract: We consider a quantum Otto cycle for a time-dependent harmonic oscillator coupled to a squeezed thermal reservoir. We show that the efficiency at maximum power increases with the degree of squeezing, surpassing the standard Carnot limit and approaching unity exponentially for large squeezing parameters. We further propose an experimental scheme to implement such a model system by using a single trapped ion in a linear Paul trap with special geometry. Our analytical investigations are supported by Monte Carlo simulations that demonstrate the feasibility of our proposal. For realistic trap parameters, an increase of the efficiency at maximum power of up to a factor of 4 is reached, largely exceeding the Carnot bound.

Journal ArticleDOI
S. Chatrchyan, Khachatryan1, Albert M. Sirunyan, Armen Tumasyan  +2384 moreInstitutions (207)
26 May 2014
TL;DR: In this paper, a description of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices is provided.
Abstract: A description is provided of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices. Despite the very hostile environment at the LHC, the performance obtained with these algorithms is found to be excellent. For tt events under typical 2011 pileup conditions, the average track-reconstruction efficiency for promptly-produced charged particles with transverse momenta of p_T > 0.9GeV is 94% for pseudorapidities of |η| < 0.9 and 85% for 0.9 < |η| < 2.5. The inefficiency is caused mainly by hadrons that undergo nuclear interactions in the tracker material. For isolated muons, the corresponding efficiencies are essentially 100%. For isolated muons of p_T = 100GeV emitted at |η| < 1.4, the resolutions are approximately 2.8% in p_T, and respectively, 10μm and 30μm in the transverse and longitudinal impact parameters. The position resolution achieved for reconstructed primary vertices that correspond to interesting pp collisions is 10–12μm in each of the three spatial dimensions. The tracking and vertexing software is fast and flexible, and easily adaptable to other functions, such as fast tracking for the trigger, or dedicated tracking for electrons that takes into account bremsstrahlung.

01 Mar 2014
TL;DR: In this paper, the authors compared optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc percutaneous changes.
Abstract: Purpose To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma. Design Observational, cross-sectional study. Participants Twenty-four normal subjects and 11 patients with glaucoma were included. Methods One eye of each subject was scanned by a high-speed 1050-nm–wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute 3-dimensional optic disc angiography. A disc flow index was computed from 4 registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc (C/D) ratios. Wide-field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. Main Outcome Measures Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations among disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. Results In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in subjects with glaucoma. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV, respectively. The disc flow index was reduced by 25% in the glaucoma group ( P = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation ( R 2 = 0.752, P = 0.001). These correlations were significant even after accounting for age, C/D area ratio, NFL, and rim area. Conclusions Optical coherence tomography angiography, generated by the new SSADA, repeatably measures optic disc perfusion and may be useful in the evaluation of glaucoma and glaucoma progression.

Journal ArticleDOI
TL;DR: The focus of this work is on the coarse-grained MARTINI force field, for which mapping definitions are written to allow conversion to and from the higher-resolution force fields GROMOS, CHARMM, and AMBER, and to andFrom a simplified three-bead lipid model.
Abstract: The conversion of coarse-grained to atomistic models is an important step in obtaining insight about atomistic scale processes from coarse-grained simulations. For this process, called backmapping or reverse transformation, several tools are available, but these commonly require libraries of molecule fragments or they are linked to a specific software package. In addition, the methods are usually restricted to specific molecules and to a specific force field. Here, we present an alternative method, consisting of geometric projection and subsequent force-field based relaxation. This method is designed to be simple and flexible, and offers a generic solution for resolution transformation. For simple systems, the conversion only requires a list of particle correspondences on the two levels of resolution. For special cases, such as nondefault protonation states of amino acids and virtual sites, a target particle list can be specified. The mapping uses simple building blocks, which list the particles on the di...

Journal ArticleDOI
05 Mar 2014
TL;DR: A subspace projection to improve channel estimation in massive multi-antenna systems is proposed and analyzed and can mitigate the pilot contamination problem without the need for coordination among cells.
Abstract: A subspace projection to improve channel estimation in massive multi-antenna systems is proposed and analyzed. Together with power-controlled hand-off, it can mitigate the pilot contamination problem without the need for coordination among cells. The proposed method is blind in the sense that it does not require pilot data to find the appropriate subspace. It is based on the theory of large random matrices that predicts that the eigenvalue spectra of large sample covariance matrices can asymptotically decompose into disjoint bulks as the matrix size grows large. Random matrix and free probability theory are utilized to predict under which system parameters such a bulk decomposition takes place. Simulation results are provided to confirm that the proposed method outperforms conventional linear channel estimation if bulk separation occurs.

01 Mar 2014
TL;DR: In this article, the authors used OCT angiograms to detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography.
Abstract: Purpose To detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography. Design Observational, cross-sectional study. Participants A total of 5 normal subjects and 5 subjects with neovascular AMD were included. Methods A total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3×3-mm area and comprised 200×200×8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. Main Outcome Measures The CNV angiogram, CNV area, and CNV flow index. Results En face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV. Conclusions Optical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.

Journal ArticleDOI
TL;DR: How technologies such as deformable mirrors and spatial light modulators, which compensate for aberrations by locally controlling the wavefront of a light wave, are now improving the performance of multiphoton, confocal, widefield and super-resolution microscopes are reviewed.
Abstract: Adaptive optics is becoming a valuable tool for high resolution microscopy, providing correction for aberrations introduced by the refractive index structure of specimens. This is proving particularly promising for applications that require images from deep within biological tissue specimens. We review recent developments in adaptive microscopy, including methods and applications. A range of advances in different microscope modalities is covered and prospects for the future are discussed. Adaptive optics is used to improve image quality across a wide range of microscopy techniques. Martin Booth from the University of Oxford in the UK reviews how technologies such as deformable mirrors and spatial light modulators, which compensate for aberrations by locally controlling the wavefront of a light wave, are now improving the performance of multiphoton, confocal, widefield and super-resolution microscopes. The benefits of such improvements are especially appealing for images captured from within biological tissue (focal distances of tens to hundreds of micrometres), where low-order aberrations associated with smooth phase variations occur. One future challenge is the development of efficient measurement and correction schemes for higher-order phase variations.

Journal ArticleDOI
TL;DR: In this article, the authors studied the design of a resource allocation algorithm minimizing the total transmit power for the case when the legitimate receivers are able to harvest energy from radio frequency signals and proposed a suboptimal resource allocation scheme with low computational complexity for providing communication secrecy and facilitating efficient energy transfer.
Abstract: This paper considers a multiuser multiple-input single-output (MISO) downlink system with simultaneous wireless information and power transfer. In particular, we focus on secure communication in the presence of passive eavesdroppers and potential eavesdroppers (idle legitimate receivers). We study the design of a resource allocation algorithm minimizing the total transmit power for the case when the legitimate receivers are able to harvest energy from radio frequency signals. Our design advocates the dual use of both artificial noise and energy signals in providing secure communication and facilitating efficient wireless energy transfer. The algorithm design is formulated as a non-convex optimization problem. The problem formulation takes into account artificial noise and energy signal generation for protecting the transmitted information against both considered types of eavesdroppers when imperfect channel state information (CSI) of the potential eavesdroppers and no CSI of the passive eavesdroppers are available at the transmitter. Besides, the problem formulation also takes into account different quality of service (QoS) requirements: a minimum required signal-to-interference-plus-noise ratio (SINR) at the desired receiver; maximum tolerable SINRs at the potential eavesdroppers; a minimum required outage probability at the passive eavesdroppers; and minimum required heterogeneous amounts of power transferred to the idle legitimate receivers. In light of the intractability of the problem, we reformulate the considered problem by replacing a non-convex probabilistic constraint with a convex deterministic constraint. Then, a semi-definite programming (SDP) relaxation approach is adopted to obtain the optimal solution for the reformulated problem. Furthermore, we propose a suboptimal resource allocation scheme with low computational complexity for providing communication secrecy and facilitating efficient energy transfer. Simulation results demonstrate the close-to-optimal performance of the proposed schemes and significant transmit power savings by optimization of the artificial noise and energy signal generation.