Enzyme self-label-bound ATTO700 in single-molecule and super-resolution microscopy

Herein, we evaluate near-infrared ATTO700 as an acceptor in SNAP- and Halo-tag protein labelling for Förster Resonance Energy Transfer (FRET) by ensemble and single molecule measurements. Microscopy of cell surface proteins in live cells is perfomed including super-resolution stimulated emission by depletion (STED) nanoscopy

Identification of disease-relevant modulators of the SHH pathway in the developing brain

Pathogenic gene variants in humans that affect the sonic hedgehog (SHH) pathway lead to severe brain malformations with variable penetrance due to unknown modifier genes. To identify such modifiers, we established novel congenic mouse models. LRP2-deficient C57BL/6N mice suffer from heart outflow tract defects and holoprosencephaly caused by impaired SHH activity. These defects are fully rescued on a FVB/N background, indicating a strong influence of modifier genes. Applying comparative transcriptomics, we identified Pttg1 and Ulk4 as candidate modifiers upregulated in the rescue strain. Functional analyses showed that ULK4 and PTTG1, both microtubule-associated proteins, are positive regulators of SHH signaling, rendering the pathway more resilient to disturbances. In addition, we characterized ULK4 and PTTG1 as previously unidentified components of primary cilia in the neuroepithelium. The identification of genes that powerfully modulate the penetrance of genetic disturbances affecting the brain and heart is likely relevant to understanding the variability in human congenital disorders

Pan-claudin family interactome analysis reveals shared and specific interactions

Claudins are a family of transmembrane proteins expressed in epithelial tissues and are the major components of tight junctions (TJs), which define barrier properties in epithelia and maintain cell polarity. How claudins regulate the formation of TJs and which functions they exert outside of them is not entirely understood. Although the long and unstructured C-terminal tail is essential for regulation, it is unclear how it is involved in these functions beyond interacting with TJ-associated proteins such as TJ protein ZO-1 (TJP1). Here, we present an interactome study of the pan-claudin family in Madin-Darby canine kidney (MDCK)-C7 cells by combining two complementary mass spectrometry-based pull-down techniques creating an interaction landscape of the entire claudin family. The interaction partners of the claudins' C termini reveal their possible implications in localized biological processes in epithelial cells and their regulation by post-translational modifications (PTMs)

Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}=2.76 TeV

The elliptic, $v_2$, triangular, $v_3$, and quadrangular, $v_4$, azimuthal anisotropic flow coefficients are measured for unidentified charged particles, pions and (anti-)protons in Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV with the ALICE detector at the Large Hadron Collider. Results obtained with the event plane and four-particle cumulant methods are reported for the pseudo-rapidity range $|\eta|<0.8$ at different collision centralities and as a function of transverse momentum, $p_{\rm T}$, out to $p_{\rm T}=20$ GeV/$c$. The observed non-zero elliptic and triangular flow depends only weakly on transverse momentum for $p_{\rm T}>8$ GeV/$c$. The small $p_{\rm T}$ dependence of the difference between elliptic flow results obtained from the event plane and four-particle cumulant methods suggests a common origin of flow fluctuations up to $p_{\rm T}=8$ GeV/$c$. The magnitude of the (anti-)proton elliptic and triangular flow is larger than that of pions out to at least $p_{\rm T}=8$ GeV/$c$ indicating that the particle type dependence persists out to high $p_{\rm T}$.Comment: 16 pages, 5 captioned figures, authors from page 11, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186

Ks0^0_sKs0^0_s correlations in pp collisions at s=7\sqrt{s}=7 TeV from the LHC ALICE experiment

Identical neutral kaon pair correlations are measured in $\sqrt{s}=7$ TeV pp collisions in the ALICE experiment. One-dimensional K$^0_s$K$^0_s$ correlation functions in terms of the invariant momentum difference of kaon pairs are formed in two multiplicity and two transverse momentum ranges. The femtoscopic parameters for the radius and correlation strength of the kaon source are extracted. The f${\rm i}$t includes quantum statistics and final-state interactions of the a$_0$/f$_0$ resonance. K$^0_s$K$^0_s$ correlations show an increase in radius for increasing multiplicity and a slight decrease in radius for increasing transverse mass, $m_{\rm T}$, as seen in $\pi\pi$ correlations in the pp system and in heavy-ion collisions. Transverse mass scaling is observed between the K$^0_s$K$^0_s$ and $\pi\pi$ radii. Also, the f${\rm i}$rst observation is made of the decay of the f$_2'$(1525) meson into the K$^0_s$K$^0_s$ channel in pp collisions.Comment: 17 pages, 7 captioned figures, 2 tables, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/310

Measurement of charm production at central rapidity in proton-proton collisions at 1as = 2.76 TeV

The pt-differential production cross sections of the prompt (B feed-down subtracted) charmed mesons D0, D+, and D+ in the rapidity range |y| K 12\u3c0+, D+ -> K 12\u3c0+\u3c0+, D+ -> D0\u3c0+, and their charge conjugates, and was performed on a Lint = 1.1 nb 121 event sample collected in 2011 with a minimum-bias trigger. The total charm production cross section at ps = 2.76 TeV and at 7 TeV was evaluated by extrapolating to the full phase space the pt-differential production cross sections at ps = 2.76 TeV and our previous measurements at ps = 7 TeV. The results were compared to existing measurements and to perturbative-QCD calculations. The fraction of cd(bar) D mesons produced in a vector state was also determined

Trennen mit Festkoerperlasern. Teilvorhaben: Trennen von Leichtmetallen, Superlegierungen und keramischen Werkstoffen Abschlussbericht

Conventional machining processes for cutting of ceramic materials due to the material are very time consuming and expensive, while some of them have limited geometrical flexibility. Laser beam cutting offers itself as an alternative, while the ND:YAG laser, contrary to CO_2 lasers, warrants expectations of reduced thermal impact and hence improved machining qualities. Similarly foreseeable are advantages for the cutting of light metals and super alloys using the Nd:YAG laser, which among others are due to their wavelengths and high pulse powers. Only little experience with regard to solid state laser cutting is available for the above materials. The objective of this project is to develop fundamental knowledge concerning the suitability of various Nd:YAG laser systems for the cutting of light metals, super alloys and ceramics, and concerning their influence on process efficiency and machining quality. For this purpose, extensive cutting tests were carried out using representative materials, and the results were assessed with regard to the objectives stated. Improved absorption of the Nd:YAG radiation for TiAl6V4 and various aluminum alloys of small sheet thicknesses observed during laser beam cutting using Nd:YAG lasers was due to the shorter wavelength as compared to the CO_2 laser. With an optimized ratio of the Rayleigh length to the sheet thickness and with an identical cutting gap width, the Nd:YAG laser produces high cutting speeds in the sheet thickness range up to 2 mm. The stated cutting method produces lower cutting surface roughnesses in the cw mode than it does in the pulsed mode. The cutting efficiency, i.e. the maximum achievable cutting speed as a function of mean laser power, can be optimized by adaptation of the laser/optical fiber system. The applicable variation ranges of process parameters were determined for the ceramics under investigation. Purposeful adaptation of these parameters permits a sufficient cutting quality for almost all engineering ceramics in pulsed mode of operation under the condition that fixed lens systems are used for beam guidance. The degraded beam quality associated with the use of optical fibers having a core diameter of 600 #mu#m limits the cuttability to tough ceramics such as Si_3N_4. Similarly, the high thermal load during cw operation limits the range of cuttable materials. Laser induced crack damage can be reduced by appropriate adjustment of the pulse parameters. The results with regard to industrial application show the capabilities and limitations of Nd:YAG laser cutting with different beam guidance systems for the materials under investigation. (orig.)SIGLEAvailable from TIB Hannover: F95B203+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman