Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

TOF-Brho Mass Measurements of Very Exotic Nuclides for Astrophysical Calculations at the NSCL

Atomic masses play a crucial role in many nuclear astrophysics calculations. The lack of experimental values for relevant exotic nuclides triggered a rapid development of new mass measurement devices around the world. The Time-of-Flight (TOF) mass measurements offer a complementary technique to the most precise one, Penning trap measurements, the latter being limited by the rate and half-lives of the ions of interest. The NSCL facility provides a well-suited infrastructure for TOF mass measurements of very exotic nuclei. At this facility, we have recently implemented a TOF-Brho technique and performed mass measurements of neutron-rich nuclides in the Fe region, important for r-process calculations and for calculations of processes occurring in the crust of accreting neutron stars.Comment: 8 pages, 4 figures, submitted to Journal of Physics G, proceedings of Nuclear Physics in Astrophysics II

Parametric generation of second sound in superfluid helium: linear stability and nonlinear dynamics

We report the experimental studies of a parametric excitation of a second sound (SS) by a first sound (FS) in a superfluid helium in a resonance cavity. The results on several topics in this system are presented: (i) The linear properties of the instability, namely, the threshold, its temperature and geometrical dependencies, and the spectra of SS just above the onset were measured. They were found to be in a good quantitative agreement with the theory. (ii) It was shown that the mechanism of SS amplitude saturation is due to the nonlinear attenuation of SS via three wave interactions between the SS waves. Strong low frequency amplitude fluctuations of SS above the threshold were observed. The spectra of these fluctuations had a universal shape with exponentially decaying tails. Furthermore, the spectral width grew continuously with the FS amplitude. The role of three and four wave interactions are discussed with respect to the nonlinear SS behavior. The first evidence of Gaussian statistics of the wave amplitudes for the parametrically generated wave ensemble was obtained. (iii) The experiments on simultaneous pumping of the FS and independent SS waves revealed new effects. Below the instability threshold, the SS phase conjugation as a result of three-wave interactions between the FS and SS waves was observed. Above the threshold two new effects were found: a giant amplification of the SS wave intensity and strong resonance oscillations of the SS wave amplitude as a function of the FS amplitude. Qualitative explanations of these effects are suggested.Comment: 73 pages, 23 figures. to appear in Phys. Rev. B, July 1 st (2001

Optical, Magnetic and Magneto-Transport Properties of Nd 1-xAxMn0.5Fe0.5O3-δ (A=Ca, Sr, Ba; x=0, 0.25)

The effect of A-site doping by alkaline earth metals (A = Ca, Sr and Ba) on optical, magnetic, and electrical properties of Nd1-xAxMn0.5Fe0·5O3-δ (x = 0, 0.25) has been investigated. The UV–vis absorption spectra show that the A-site doping decreases the absorption. Two values of optical band-gap energy (Eg) can be estimated for each studied sample: the higher Eg value is associated with the charge transfer involving iron cations and the lower Eg value – with the charge transfer via manganese cations. Partial substitution of neodymium by alkaline earth metals decreases the Néel temperature (TN) and induces significant irreversibility between the zero-field cooled (ZFC) and field-cooled (FC) data below TN. The field-dependent magnetization at 3 K indicates antiferromagnetic ordering with a spin canting. Temperature dependencies of resistivity demonstrate the change from metallic to semiconductor-type conduction (with increasing temperature) at T = Tp < TN. The Tp temperature significantly decreases with doping. The introduction of alkaline earth metals in Nd1-xAxMn0.5Fe0·5O3-δ noticeably reduces the resistivity in the semiconducting region. The small polaron hopping (SPH) mechanism of conduction is suggested at T > TN. Within the range of Tp < T < TN, the resistivity data are interpreted by the variable range hopping (VRH) mechanism. A significant value of magnetoresistance (∼44%) is observed only for Nd0.75Sr0·25Mn0·5Fe0·5O3-δ at 120 K. © 2020 Elsevier B.V.A. S. acknowledges, the financial support provided by the Department of Science and Technology (DST), Government of India (Indo-Russian project (INT/RUS/RFBR/P-239); A.R.G and V.A.C. acknowledge the financial support from Indo-Russian project (RFBR grant No 16-53-45010); and A.H. acknowledges financial support obtained from the Government of the Russian Federation by Act 211 agreement 02.A03.21.0006

Bond-disordered spin systems: Theory and application to doped high-Tc compounds

We examine the stability of magnetic order in a classical Heisenberg model with quenched random exchange couplings. This system represents the spin degrees of freedom in high-$T_\textrm{c}$ compounds with immobile dopants. Starting from a replica representation of the nonlinear $\sigma$-model, we perform a renormalization-group analysis. The importance of cumulants of the disorder distribution to arbitrarily high orders necessitates a functional renormalization scheme. From the renormalization flow equations we determine the magnetic correlation length numerically as a function of the impurity concentration and of temperature. From our analysis follows that two-dimensional layers can be magnetically ordered for arbitrarily strong but sufficiently diluted defects. We further consider the dimensional crossover in a stack of weakly coupled layers. The resulting phase diagram is compared with experimental data for La$_{2-x}$Sr$_x$CuO$_4$.Comment: 12 pages, 5 figure

LEDGF/p75 Proteins with Alternative Chromatin Tethers Are Functional HIV-1 Cofactors

LEDGF/p75 can tether over-expressed lentiviral integrase proteins to chromatin but how this underlies its integration cofactor role for these retroviruses is unclear. While a single integrase binding domain (IBD) binds integrase, a complex N-terminal domain ensemble (NDE) interacts with unknown chromatin ligands. Whether integration requires chromatin tethering per se, specific NDE-chromatin ligand interactions or other emergent properties of LEDGF/p75 has been elusive. Here we replaced the NDE with strongly divergent chromatin-binding modules. The chimeras rescued integrase tethering and HIV-1 integration in LEDGF/p75-deficient cells. Furthermore, chromatin ligands could reside inside or outside the nucleosome core, and could be protein or DNA. Remarkably, a short Kaposi's sarcoma virus peptide that binds the histone 2A/B dimer converted GFP-IBD from an integration blocker to an integration cofactor that rescues over two logs of infectivity. NDE mutants were corroborative. Chromatin tethering per se is a basic HIV-1 requirement and this rather than engagement of particular chromatin ligands is important for the LEDGF/p75 cofactor mechanism

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE