Contents

We discuss the current minimisation strategies adopted by research projects involving the determination of parton distribution functions (PDFs) and fragmentation functions (FFs) through the training of neural networks. We present a short overview of a proton PDF determination obtained using the covariance matrix adaptation evolution strategy (CMA-ES) optimisation algorithm. We perform comparisons between the CMA-ES and the standard nodal genetic algorithm (NGA) adopted by the NNPDF collaboration

APFELgrid: A high performance tool for parton density determinations

We present a new software package designed to reduce the computational burden of hadron collider measurements in Parton Distribution Function (PDF) fits. The APFELgrid package converts interpolated weight tables provided by APPLgrid files into a more efficient format for PDF fitting by the combination with PDF and as evolution factors provided by APFEL. This combination significantly reduces the number of operations required to perform the calculation of hadronic observables in PDF fits and simplifies the structure of the calculation into a readily optimised scalar product. We demonstrate that our technique can lead to a substantial speed improvement when compared to existing methods without any reduction in numerical accuracy. Program Summary Program Title: APFELgrid Program Files doi: http://dx.doi.org/10.17632/mhwjt5nsg7.1 Licensing provisions: MIT license Programming language: C++ Nature of problem: Fast computation of hadronic observables under the variation of parton distribution functions. Solution method: Combination of interpolated weight grids from APPLgrid files and evolution factors from APFEL into efficient FastKernel tables. External routines/libraries: APPLgrid, APFE

Nanoantenna-enhanced ultrafast nonlinear spectroscopy of a single gold nanoparticle

Optical nanoantennas are a novel tool to investigate previously unattainable dimensions in the nanocosmos. Just like their radio-frequency equivalents, nanoantennas enhance the light-matter interaction in their feed gap. Antenna enhancement of small signals promises to open a new regime in linear and nonlinear spectroscopy on the nanoscale. Without antennas especially the nonlinear spectroscopy of single nanoobjects is very demanding. Here, we present for the first time antenna-enhanced ultrafast nonlinear optical spectroscopy. In particular, we utilize the antenna to determine the nonlinear transient absorption signal of a single gold nanoparticle caused by mechanical breathing oscillations. We increase the signal amplitude by an order of magnitude which is in good agreement with our analytical and numerical models. Our method will find applications in linear and nonlinear spectroscopy of nanoobjects, ranging from single protein binding events via nonlinear tensor elements to the limits of continuum mechanics

Sampling rate-corrected analysis of irregularly sampled time series

The analysis of irregularly sampled time series remains a challenging task requiring methods that account for continuous and abrupt changes of sampling resolution without introducing additional biases. The edit distance is an effective metric to quantitatively compare time series segments of unequal length by computing the cost of transforming one segment into the other. We show that transformation costs generally exhibit a nontrivial relationship with local sampling rate. If the sampling resolution undergoes strong variations, this effect impedes unbiased comparison between different time episodes. We study the impact of this effect on recurrence quantification analysis, a framework that is well suited for identifying regime shifts in nonlinear time series. A constrained randomization approach is put forward to correct for the biased recurrence quantification measures. This strategy involves the generation of a type of time series and time axis surrogates which we call sampling-rate-constrained (SRC) surrogates. We demonstrate the effectiveness of the proposed approach with a synthetic example and an irregularly sampled speleothem proxy record from Niue island in the central tropical Pacific. Application of the proposed correction scheme identifies a spurious transition that is solely imposed by an abrupt shift in sampling rate and uncovers periods of reduced seasonal rainfall predictability associated with enhanced El Niño-Southern Oscillation and tropical cyclone activity

Legionella pneumophila strain 130b possesses a unique combination of type IV secretion systems and novel Dot/Icm secretion system effector proteins

Legionella pneumophila is a ubiquitous inhabitant of environmental water reservoirs. The bacteria infect a wide variety of protozoa and, after accidental inhalation, human alveolar macrophages, which can lead to severe pneumonia. The capability to thrive in phagocytic hosts is dependent on the Dot/Icm type IV secretion system (T4SS), which translocates multiple effector proteins into the host cell. In this study, we determined the draft genome sequence of L. pneumophila strain 130b (Wadsworth). We found that the 130b genome encodes a unique set of T4SSs, namely, the Dot/Icm T4SS, a Trb-1-like T4SS, and two Lvh T4SS gene clusters. Sequence analysis substantiated that a core set of 107 Dot/Icm T4SS effectors was conserved among the sequenced L. pneumophila strains Philadelphia-1, Lens, Paris, Corby, Alcoy, and 130b. We also identified new effector candidates and validated the translocation of 10 novel Dot/Icm T4SS effectors that are not present in L. pneumophila strain Philadelphia-1. We examined the prevalence of the new effector genes among 87 environmental and clinical L. pneumophila isolates. Five of the new effectors were identified in 34 to 62% of the isolates, while less than 15% of the strains tested positive for the other five genes. Collectively, our data show that the core set of conserved Dot/Icm T4SS effector proteins is supplemented by a variable repertoire of accessory effectors that may partly account for differences in the virulences and prevalences of particular L. pneumophila strains. Copyright © 2010, American Society for Microbiology. All Rights Reserved

Direct Observation of Martensitic Phase-Transformation Dynamics in Iron by 4D Single-Pulse Electron Microscopy

The in situ martensitic phase transformation of iron, a complex solid-state transition involving collective atomic displacement and interface movement, is studied in real time by means of four-dimensional (4D) electron microscopy. The iron nanofilm specimen is heated at a maximum rate of ∼10^(11) K/s by a single heating pulse, and the evolution of the phase transformation from body-centered cubic to face-centered cubic crystal structure is followed by means of single-pulse, selected-area diffraction and real-space imaging. Two distinct components are revealed in the evolution of the crystal structure. The first, on the nanosecond time scale, is a direct martensitic transformation, which proceeds in regions heated into the temperature range of stability of the fcc phase, 1185−1667 K. The second, on the microsecond time scale, represents an indirect process for the hottest central zone of laser heating, where the temperature is initially above 1667 K and cooling is the rate-determining step. The mechanism of the direct transformation involves two steps, that of (barrier-crossing) nucleation on the reported nanosecond time scale, followed by a rapid grain growth typically in ∼100 ps for 10 nm crystallites

More than 18,000 effectors in the Legionella genus genome provide multiple, independent combinations for replication in human cells.

The genus Legionella comprises 65 species, among which Legionella pneumophila is a human pathogen causing severe pneumonia. To understand the evolution of an environmental to an accidental human pathogen, we have functionally analyzed 80 Legionella genomes spanning 58 species. Uniquely, an immense repository of 18,000 secreted proteins encoding 137 different eukaryotic-like domains and over 200 eukaryotic-like proteins is paired with a highly conserved type IV secretion system (T4SS). Specifically, we show that eukaryotic Rho- and Rab-GTPase domains are found nearly exclusively in eukaryotes and Legionella Translocation assays for selected Rab-GTPase proteins revealed that they are indeed T4SS secreted substrates. Furthermore, F-box, U-box, and SET domains were present in >70% of all species, suggesting that manipulation of host signal transduction, protein turnover, and chromatin modification pathways are fundamental intracellular replication strategies for legionellae. In contrast, the Sec-7 domain was restricted to L. pneumophila and seven other species, indicating effector repertoire tailoring within different amoebae. Functional screening of 47 species revealed 60% were competent for intracellular replication in THP-1 cells, but interestingly, this phenotype was associated with diverse effector assemblages. These data, combined with evolutionary analysis, indicate that the capacity to infect eukaryotic cells has been acquired independently many times within the genus and that a highly conserved yet versatile T4SS secretes an exceptional number of different proteins shaped by interdomain gene transfer. Furthermore, we revealed the surprising extent to which legionellae have coopted genes and thus cellular functions from their eukaryotic hosts, providing an understanding of how dynamic reshuffling and gene acquisition have led to the emergence of major human pathogens

Physics at a 100 TeV pp collider: Higgs and EW symmetry breaking studies

This report summarises the physics opportunities for the study of Higgs bosons and the dynamics of electroweak symmetry breaking at the 100 TeV pp collider.Comment: 187 pages, 94 figures. Chapter 2 of the "Physics at the FCC-hh" Repor

Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis

Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process