Search for Sterile Neutrinos Mixing with Muon Neutrinos in MINOS

We report results of a search for oscillations involving a light sterile neutrino over distances of 1.04 and 735 km in a νμ-dominated beam with a peak energy of 3 GeV. The data, from an exposure of 10.56 × 10^20 protons on target, are analyzed using a phenomenological model with one sterile neutrino. We constrain the mixing parameters θ24 and Δm41^2 and set limits on parameters of the four-dimensional Pontecorvo-Maki- Nakagawa-Sakata matrix, |Uμ4|2 and |Uτ4|2, under the assumption that mixing between νe and νs is negligible (|Ue4|^2 = 0). No evidence for νμ → νs transitions is found and we set a world-leading limit on θ24 for values of Δm41^2 ≲ 1 eV^2

Measurement of the multiple-muon charge ratio in the MINOS Far Detector

The charge ratio, Rμ=Nμ+/Nμ−, for cosmogenic multiple-muon events observed at an underground depth of 2070 mwe has been measured using the magnetized MINOS Far Detector. The multiple-muon events, recorded nearly continuously from August 2003 until April 2012, comprise two independent data sets imaged with opposite magnetic field polarities, the comparison of which allows the systematic uncertainties of the measurement to be minimized. The multiple-muon charge ratio is determined to be Rμ=1.104±0.006(stat)+0.009−0.010(syst). This measurement complements previous determinations of single-muon and multiple-muon charge ratios at underground sites and serves to constrain models of cosmic-ray interactions at TeV energies

Search for flavor-changing nonstandard neutrino interactions using nu(e) appearance in MINOS

We report new constraints on flavor-changing nonstandard neutrino interactions from the MINOS long-baseline experiment using νe and ¯νe appearance candidate events from predominantly νμ and ¯νμ beams. We used a statistical selection algorithm to separate νe candidates from background events, enabling an analysis of the combined MINOS neutrino and antineutrino data. We observe no deviations from standard neutrino mixing, and thus place constraints on the nonstandard interaction matter effect, |ϵeτ|, and phase, (δCP+δeτ), using a 30-bin likelihood fit

Precision measurement of the speed of propagation of neutrinos using the MINOS detectors

We report a two-detector measurement of the propagation speed of neutrinos over a baseline of 734 km. The measurement was made with the NuMI beam at Fermilab between the near and far MINOS detectors. The fractional difference between the neutrino speed and the speed of light is determined to be (v/c−1)=(1.0±1.1)×10−6, consistent with relativistic neutrinos

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Clinicopathological features and outcome in advanced colorectal cancer patients with synchronous vs metachronous metastases

Contains fulltext : 88999.pdf (publisher's version ) (Open Access)BACKGROUND: Synchronous metastases of colorectal cancer (CRC) are considered to be of worse prognostic value compared with metachronous metastases, but only few and conflicting data have been reported on this issue. METHODS: We retrospectively investigated patient demographics, primary tumour characteristics and overall survival (OS) in 550 advanced CRC patients with metachronous vs synchronous metastases, who participated in the phase III CAIRO study. For this purpose only patients with a prior resection of the primary tumour were considered. RESULTS: The clinical and pathological characteristics associated with poor prognosis that we observed more often in patients with synchronous metastases (n=280) concerned an abnormal serum lactate dehydrogenase (LDH) concentration (P=0.01), a worse WHO performance status (P=0.02), primary tumour localisation in the colon (P=0.002) and a higher T stage (P=0.0006). No significant difference in median OS was observed between patients with synchronous metastases and metachronous metastases (17.6 vs 18.5 months, respectively, P=0.24). CONCLUSION: Despite unfavourable clinicopathological features in patients with synchronous metastases with a resected primary tumour compared to patients with metachronous metastases, no difference in the median OS was observed. Possible explanations include a (partial) chemoresistance in patients with metachronous disease because of previous adjuvant treatment, whereas differences between the two groups in screening procedures resulting in a lead time bias to diagnosis or in prognostic molecular markers remain speculative

Probing Molecular Mechanisms of the Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators of Functional Dynamics

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based “conformational selection” of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be a rather general functional requirement encoded across molecular chaperones. The obtained insights may be useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein interfaces with co-chaperones and protein binding clients

Iota-Carrageenan Is a Potent Inhibitor of Influenza A Virus Infection

The 2009 flu pandemic and the appearance of oseltamivir-resistant H1N1 influenza strains highlight the need for treatment alternatives. One such option is the creation of a protective physical barrier in the nasal cavity. In vitro tests demonstrated that iota-carrageenan is a potent inhibitor of influenza A virus infection, most importantly also of pandemic H1N1/2009 in vitro. Consequently, we tested a commercially available nasal spray containing iota-carrageenan in an influenza A mouse infection model. Treatment of mice infected with a lethal dose of influenza A PR8/34 H1N1 virus with iota-carrageenan starting up to 48 hours post infection resulted in a strong protection of mice similar to mice treated with oseltamivir. Since alternative treatment options for influenza are rare, we conclude that the nasal spray containing iota-carrageenan is an alternative to neuraminidase inhibitors and should be tested for prevention and treatment of influenza A in clinical trials in humans