Why are scientists not managers!?:the importance of interdisciplinary skills in business and science

Research is the translation from money to knowledge. Innovation is the metamorphosis of knowledge to money. Thus, business management and science are interdependent. That is no big news. But, in an ever faster changing economy, companies need a new type of scientist. Someone who knows not only science, but also business administration and management. Can the educational system satisfy those needs? In our opinion more work needs to be done – especially in the minds of scientists and managers alike

A Phase I Dose Escalation Study of the Triple Angiokinase Inhibitor Nintedanib Combined with Low-Dose Cytarabine in Elderly Patients with Acute Myeloid Leukemia

Nintedanib (BIBF 1120), a potent multikinase inhibitor of VEGFR-1/-2/-3, FGFR-1/-2/-3 and PDGFR-α/-β, exerts growth inhibitory and pro-apoptotic effects in myeloid leukemic cells, especially when used in combination with cytarabine. This phase I study evaluated nintedanib in combination with low-dose cytarabine (LDAC) in elderly patients with untreated or relapsed/refractory acute myeloid leukemia (AML) ineligible for intensive chemotherapy in a 3+3 design. Nintedanib (dose levels 100, 150, and 200 mg orally twice daily) and LDAC (20 mg subcutaneous injection twice daily for 10 days) were administered in 28-day cycles. Dose-limiting toxicity (DLT) was defined as non-hematological severe adverse reaction CTC grade ≥ 4 with possible or definite relationship to nintedanib. Between April 2012 and October 2013, 13 patients (median age 73 [range: 62–86] years) were enrolled. One patient did not receive study medication and was replaced. Nine (69%) patients had relapsed or refractory disease and 6 (46%) patients had unfavorable cytogenetics. The most frequently reported treatment-related adverse events (AE) were gastrointestinal events. Twelve SAEs irrespective of relatedness were reported. Two SUSARs were observed, one fatal hypercalcemia and one fatal gastrointestinal infection. Two patients (17%) with relapsed AML achieved a complete remission (one CR, one CRi) and bone marrow blast reductions without fulfilling PR criteria were observed in 3 patients (25%). One-year overall survival was 33%. Nintedanib combined with LDAC shows an adequate safety profile and survival data are promising in a difficult-to-treat patient population. Continuation of this trial with a phase II recommended dose of 2 x 200 mg nintedanib in a randomized, placebo-controlled phase II study is planned. The trial is registered to EudraCT as 2011-001086-41

Neutrinos and Cosmic Rays Observed by IceCube

The core mission of the IceCube Neutrino observatory is to study the origin and propagation of cosmic rays. IceCube, with its surface component IceTop, observes multiple signatures to accomplish this mission. Most important are the astrophysical neutrinos that are produced in interactions of cosmic rays, close to their sources and in interstellar space. IceCube is the first instrument that measures the properties of this astrophysical neutrino flux, and constrains its origin. In addition, the spectrum, composition and anisotropy of the local cosmic-ray flux are obtained from measurements of atmospheric muons and showers. Here we provide an overview of recent findings from the analysis of IceCube data, and their implications on our understanding of cosmic rays.Comment: Review article, to appear in Advances in Space Research, special issue "Origins of Cosmic Rays

Search for astrophysical sources of neutrinos using cascade events in IceCube

The IceCube neutrino observatory has established the existence of a flux of high-energy astrophysical neutrinos inconsistent with the expectation from atmospheric backgrounds at a significance greater than $5\sigma$. This flux has been observed in analyses of both track events from muon neutrino interactions and cascade events from interactions of all neutrino flavors. Searches for astrophysical neutrino sources have focused on track events due to the significantly better angular resolution of track reconstructions. To date, no such sources have been confirmed. Here we present the first search for astrophysical neutrino sources using cascades interacting in IceCube with deposited energies as small as 1 TeV. No significant clustering was observed in a selection of 263 cascades collected from May 2010 to May 2012. We show that compared to the classic approach using tracks, this statistically-independent search offers improved sensitivity to sources in the southern sky, especially if the emission is spatially extended or follows a soft energy spectrum. This enhancement is due to the low background from atmospheric neutrinos forming cascade events and the additional veto of atmospheric neutrinos at declinations $\lesssim-30^\circ$.Comment: 14 pages, 9 figures, 1 tabl

The contribution of Fermi-2LAC blazars to the diffuse TeV-PeV neutrino flux

The recent discovery of a diffuse cosmic neutrino flux extending up to PeV energies raises the question of which astrophysical sources generate this signal. One class of extragalactic sources which may produce such high-energy neutrinos are blazars. We present a likelihood analysis searching for cumulative neutrino emission from blazars in the 2nd Fermi-LAT AGN catalogue (2LAC) using an IceCube neutrino dataset 2009-12 which was optimised for the detection of individual sources. In contrast to previous searches with IceCube, the populations investigated contain up to hundreds of sources, the largest one being the entire blazar sample in the 2LAC catalogue. No significant excess is observed and upper limits for the cumulative flux from these populations are obtained. These constrain the maximum contribution of the 2LAC blazars to the observed astrophysical neutrino flux to be $27 \%$ or less between around 10 TeV and 2 PeV, assuming equipartition of flavours at Earth and a single power-law spectrum with a spectral index of $-2.5$. We can still exclude that the 2LAC blazars (and sub-populations) emit more than $50 \%$ of the observed neutrinos up to a spectral index as hard as $-2.2$ in the same energy range. Our result takes into account that the neutrino source count distribution is unknown, and it does not assume strict proportionality of the neutrino flux to the measured 2LAC $\gamma$-ray signal for each source. Additionally, we constrain recent models for neutrino emission by blazars.Comment: 18 pages, 22 figure

All-sky search for time-integrated neutrino emission from astrophysical sources with 7 years of IceCube data

Since the recent detection of an astrophysical flux of high energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over seven years from 2008--2015. The discovery potential of the analysis in the northern sky is now significantly below $E_\nu^2d\phi/dE_\nu=10^{-12}\:\mathrm{TeV\,cm^{-2}\,s^{-1}}$, on average $38\%$ lower than the sensitivity of the previously published analysis of four years exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.Comment: 19 pages, 17 figures, 3 tables; ; submitted to The Astrophysical Journa

The IceCube Neutrino Observatory: Instrumentation and Online Systems

The IceCube Neutrino Observatory is a cubic-kilometer-scale high-energy neutrino detector built into the ice at the South Pole. Construction of IceCube, the largest neutrino detector built to date, was completed in 2011 and enabled the discovery of high-energy astrophysical neutrinos. We describe here the design, production, and calibration of the IceCube digital optical module (DOM), the cable systems, computing hardware, and our methodology for drilling and deployment. We also describe the online triggering and data filtering systems that select candidate neutrino and cosmic ray events for analysis. Due to a rigorous pre-deployment protocol, 98.4% of the DOMs in the deep ice are operating and collecting data. IceCube routinely achieves a detector uptime of 99% by emphasizing software stability and monitoring. Detector operations have been stable since construction was completed, and the detector is expected to operate at least until the end of the next decade.Comment: 83 pages, 50 figures; updated with minor changes from journal review and proofin

Improved limits on dark matter annihilation in the Sun with the 79-string IceCube detector and implications for supersymmetry

We present an improved event-level likelihood formalism for including neutrino telescope data in global fits to new physics. We derive limits on spin-dependent dark matter-proton scattering by employing the new formalism in a re-analysis of data from the 79-string IceCube search for dark matter annihilation in the Sun, including explicit energy information for each event. The new analysis excludes a number of models in the weak-scale minimal supersymmetric standard model (MSSM) for the first time. This work is accompanied by the public release of the 79-string IceCube data, as well as an associated computer code for applying the new likelihood to arbitrary dark matter models.Comment: 24 pages, 8 figs, 1 table. Contact authors: Pat Scott & Matthias Danninger. Likelihood tool available at http://nulike.hepforge.org. v2: small updates to address JCAP referee repor

Atmospheric and Astrophysical Neutrinos above 1 TeV Interacting in IceCube

The IceCube Neutrino Observatory was designed primarily to search for high-energy (TeV--PeV) neutrinos produced in distant astrophysical objects. A search for $\gtrsim 100$~TeV neutrinos interacting inside the instrumented volume has recently provided evidence for an isotropic flux of such neutrinos. At lower energies, IceCube collects large numbers of neutrinos from the weak decays of mesons in cosmic-ray air showers. Here we present the results of a search for neutrino interactions inside IceCube's instrumented volume between 1~TeV and 1~PeV in 641 days of data taken from 2010--2012, lowering the energy threshold for neutrinos from the southern sky below 10 TeV for the first time, far below the threshold of the previous high-energy analysis. Astrophysical neutrinos remain the dominant component in the southern sky down to 10 TeV. From these data we derive new constraints on the diffuse astrophysical neutrino spectrum, $\Phi_{\nu} = 2.06^{+0.4}_{-0.3} \times 10^{-18} \left({E_{\nu}}/{10^5 \,\, \rm{GeV}} \right)^{-2.46 \pm 0.12} {\rm {GeV^{-1} \, cm^{-2} \, sr^{-1} \, s^{-1}} }$, as well as the strongest upper limit yet on the flux of neutrinos from charmed-meson decay in the atmosphere, 1.52 times the benchmark theoretical prediction used in previous IceCube results at 90\% confidence.Comment: 18 pages, 12 figure