Toxicology and efficacy of tumor-targeting Salmonella typhimurium A1-R compared to VNP 20009 in a syngeneic mouse tumor model in immunocompetent mice.

Salmonella typhimurium A1-R (S. typhimurium A1-R) attenuated by leu and arg auxotrophy has been shown to target multiple types of cancer in mouse models. In the present study, toxicologic and biodistribution studies of tumor-targeting S. typhimurium A1-R and S. typhimurium VNP20009 (VNP 20009) were performed in a syngeneic tumor model growing in immunocompetent BALB/c mice. Single or multiple doses of S. typhimurium A1-R of 2.5 × 105 and 5 × 105 were tolerated. A single dose of 1 × 106 resulted in mouse death. S. typhimurium A1-R (5 × 105 CFU) was eliminated from the circulation, liver and spleen approximately 3-5 days after bacterial administration via the tail vein, but remained in the tumor in high amounts. S. typhimurium A1-R was cleared from other organs much more rapidly. S. typhimurium A1-R and VNP 20009 toxicity to the spleen and liver was minimal. S. typhimurium A1-R showed higher selective targeting to the necrotic areas of the tumors than VNP20009. S. typhimurium A1-R inhibited the growth of CT26 colon carcinoma to a greater extent at the same dose of VNP20009. In conclusion, we have determined a safe dose and schedule of S. typhimurium A1-R administration in BALB/c mice, which is also efficacious against tumor growth. The results of the present report indicate similar toxicity of S. typhimurium A1-R and VNP20009, but greater antitumor efficacy of S. typhimurium A1-R in an immunocompetent animal. Since VNP2009 has already proven safe in a Phase I clinical trial, the present results indicate the high clinical potential of S. typhimurium A1-R

Synthesis of cyclopropyl-substituted furans by Brønsted acid promoted cascade reactions

Chloroacetic acid promotes an efficient and diastereoselective intramolecular cascade reaction of electron-deficient ynenones to deliver products featuring a 2,3,5-trisubstituted furan bearing a fused cyclopropyl substituent at the 5-position. Synthetically relevant polycyclic building blocks featuring rings of various sizes and heteroatoms have been synthesized in high yield using this mild acid-catalyzed reaction

Correlations and the Cross Section of Exclusive (e,e′pe,e'p) Reactions for 16^{16}O

The reduced cross section for exclusive ($e,e'p$) reactions has been studied in DWIA for the example of the nucleus $^{16}$O using a spectral function containing effects of correlations. The spectral function is evaluated directly for the finite nucleus starting from a realistic nucleon-nucleon interaction within the framework of the Green's function approach. The emphasis is focused on the correlations induced by excitation modes at low energies described within a model-space of shell-model configurations including states up to the $sdg$ shell. Cross sections for the $p$-wave quasi-hole transitions at low missing energies are presented and compared with the most recent experimental data. In the case of the so-called perpendicular kinematics the reduced cross section derived in DWIA shows an enhancement at high missing momenta as compared to the PWIA result. Furthermore the cross sections for the $s$- and $d$-wave quasi-hole transitions are presented and compared to available data at low missing momenta. Also in these cases, which cannot be described in a model without correlations, a good agreement with the experiment is obtained.Comment: 12 pages, LaTeX, 4 figures include

Long-Range Correlations and the Momentum Distribution in Nuclei

The influence of correlations on the momentum distribution of nucleons in nuclei is evaluated starting from a realistic nucleon-nucleon interaction. The calculations are performed directly for the finite nucleus $\,^{16}$O making use of the Green's function approach. The emphasis is focused on the correlations induced by the excitation modes at low energies described within a model-space of shell-model configurations including states up to the sdg shell. Our analysis demonstrates that these long-range correlations do not produce any significant enhancement of the momentum distribution at high missing momenta and low missing energies. This is in agreement with high resolution $(e,e'p)$ experiments for this nucleus. We also try to simulate the corresponding effects in large nuclei by quenching the energy-spacing between single-particle orbits. This yields a sizable enhancement of the spectral function at large momenta and small energy. Such behavior could explain the deviation of the momentum distribution from the mean field prediction, which has been observed in $(e,e'p)$ experiments on heavy nuclei like $^{208}$Pb

Description of nuclear systems within the relativistic Hartree-Fock method with zero range self-interactions of the scalar field

An exact method is suggested to treat the nonlinear self-interactions (NLSI) in the relativistic Hartree-Fock (RHF) approach for nuclear systems. We consider here the NLSI constructed from the relativistic scalar nucleon densities and including products of six and eight fermion fields. This type of NLSI corresponds to the zero range limit of the standard cubic and quartic self-interactions of the scalar field. The method to treat the NLSI uses the Fierz transformation, which enables one to express the exchange (Fock) components in terms of the direct (Hartree) ones. The method is applied to nuclear matter and finite nuclei. It is shown that, in the RHF formalism, the NLSI, which are explicitly isovector-independent, generate scalar, vector and tensor nucleon self-energies strongly density-dependent. This strong isovector structure of the self-energies is due to the exchange terms of the RHF method. Calculations are carried out with a parametrization containing five free parameters. The model allows a description of both types of systems compatible with experimental data.Comment: 23 pages, 14 figures (v2: major quantitative changes

Temperatures of Exploding Nuclei

Breakup temperatures in central collisions of 197Au + 197Au at bombarding energies E/A = 50 to 200 MeV were determined with two methods. Isotope temperatures, deduced from double ratios of hydrogen, helium, and lithium isotopic yields, increase monotonically with bombarding energy from 5 MeV to 12 MeV, in qualitative agreement with a scenario of chemical freeze-out after adiabatic expansion. Excited-state temperatures, derived from yield ratios of states in 4He, 5Li, 6Li, and 8Be, are about 5 MeV, independent of the projectile energy, and seem to reflect the internal temperature of fragments at their final separation from the system. PACS numbers: 25.70.Mn, 25.70.Pq, 25.75.-qComment: 10 pages, RevTeX with 4 included figures; Also available from http://www-kp3.gsi.de/www/kp3/aladin_publications.htm

Kidney Transplantation Group of the Spanish Society of Nephrology

Document publicat també en castellàThe Board of Directors of the Spanish Society of Nephrology (S.E.N.) approved at its ordinary meeting of 18 December 2012 the creation of a Transplantation Working Group (SENTRA). In accordance with the Regulations of the S.E.N. Working Groups, in promoting the establishment of a working group, four priority aspects must be addressed..

H-ATLAS: a candidate high redshift cluster/protocluster of star-forming galaxies

We investigate the region around the Planck-detected z=3.26 gravitationally lensed galaxy HATLAS J114637.9-001132 (hereinafter HATLAS12-00) using both archival Herschel data from the H-ATLAS survey and using submm data obtained with both LABOCA and SCUBA2. The lensed source is found to be surrounded by a strong overdensity of both Herschel-SPIRE sources and submm sources. We detect 17 bright (S870 >~7 mJy) sources at >4sigma closer than 5 arcmin to the lensed object at 850/870 microns. Ten of these sources have good cross-identifications with objects detected by Herschel-SPIRE which have redder colours than other sources in the field, with 350 micron flux > 250 micron flux, suggesting that they lie at high redshift. Submillimeter Array (SMA) observations localise one of these companions to ~1 arcsecond, allowing unambiguous cross identification with a 3.6 and 4.5 micron Spitzer source. The optical/near-IR spectral energy distribution (SED) of this source is measured by further observations and found to be consistent with z>2, but incompatible with lower redshifts. We conclude that this system may be a galaxy cluster/protocluster or larger scale structure that contains a number of galaxies undergoing starbursts at the same time

Design and performance of the first IceAct demonstrator at the South Pole

In this paper we describe the first results of IceAct, a compact imaging air-Cherenkov telescope operating in coincidence with the IceCube Neutrino Observatory (IceCube) at the geographic South Pole. An array of IceAct telescopes (referred to as the IceAct project) is under consideration as part of the IceCube-Gen2 extension to IceCube. Surface detectors in general will be a powerful tool in IceCube-Gen2 for distinguishing astrophysical neutrinos from the dominant backgrounds of cosmic-ray induced atmospheric muons and neutrinos: the IceTop array is already in place as part of IceCube, but has a high energy threshold. Although the duty cycle will be lower for the IceAct telescopes than the present IceTop tanks, the IceAct telescopes may prove to be more effective at lowering the detection threshold for air showers. Additionally, small imaging air-Cherenkov telescopes in combination with IceTop, the deep IceCube detector or other future detector systems might improve measurements of the composition of the cosmic ray energy spectrum. In this paper we present measurements of a first 7-pixel imaging air Cherenkov telescope demonstrator, proving the capability of this technology to measure air showers at the South Pole in coincidence with IceTop and the deep IceCube detector

Combined sensitivity to the neutrino mass ordering with JUNO, the IceCube Upgrade, and PINGU

The ordering of the neutrino mass eigenstates is one of the fundamental open questions in neutrino physics. While current-generation neutrino oscillation experiments are able to produce moderate indications on this ordering, upcoming experiments of the next generation aim to provide conclusive evidence. In this paper we study the combined performance of the two future multi-purpose neutrino oscillation experiments JUNO and the IceCube Upgrade, which employ two very distinct and complementary routes toward the neutrino mass ordering. The approach pursued by the 20 kt medium-baseline reactor neutrino experiment JUNO consists of a careful investigation of the energy spectrum of oscillated νe produced by ten nuclear reactor cores. The IceCube Upgrade, on the other hand, which consists of seven additional densely instrumented strings deployed in the center of IceCube DeepCore, will observe large numbers of atmospheric neutrinos that have undergone oscillations affected by Earth matter. In a joint fit with both approaches, tension occurs between their preferred mass-squared differences Δm312=m32-m12 within the wrong mass ordering. In the case of JUNO and the IceCube Upgrade, this allows to exclude the wrong ordering at >5σ on a timescale of 3-7 years - even under circumstances that are unfavorable to the experiments' individual sensitivities. For PINGU, a 26-string detector array designed as a potential low-energy extension to IceCube, the inverted ordering could be excluded within 1.5 years (3 years for the normal ordering) in a joint analysis