The KATRIN Pre-Spectrometer at reduced Filter Energy

The KArlsruhe TRItium Neutrino experiment, KATRIN, will determine the mass of the electron neutrino with a sensitivity of 0.2 eV (90% C.L.) via a measurement of the beta-spectrum of gaseous tritium near its endpoint of E_0 =18.57 keV. An ultra-low background of about b = 10 mHz is among the requirements to reach this sensitivity. In the KATRIN main beam-line two spectrometers of MAC-E filter type are used in a tandem configuration. This setup, however, produces a Penning trap which could lead to increased background. We have performed test measurements showing that the filter energy of the pre-spectrometer can be reduced by several keV in order to diminish this trap. These measurements were analyzed with the help of a complex computer simulation, modeling multiple electron reflections both from the detector and the photoelectric electron source used in our test setup.Comment: 22 pages, 12 figure

Kassiopeia: A Modern, Extensible C++ Particle Tracking Package

The Kassiopeia particle tracking framework is an object-oriented software package using modern C++ techniques, written originally to meet the needs of the KATRIN collaboration. Kassiopeia features a new algorithmic paradigm for particle tracking simulations which targets experiments containing complex geometries and electromagnetic fields, with high priority put on calculation efficiency, customizability, extensibility, and ease of use for novice programmers. To solve Kassiopeia's target physics problem the software is capable of simulating particle trajectories governed by arbitrarily complex differential equations of motion, continuous physics processes that may in part be modeled as terms perturbing that equation of motion, stochastic processes that occur in flight such as bulk scattering and decay, and stochastic surface processes occuring at interfaces, including transmission and reflection effects. This entire set of computations takes place against the backdrop of a rich geometry package which serves a variety of roles, including initialization of electromagnetic field simulations and the support of state-dependent algorithm-swapping and behavioral changes as a particle's state evolves. Thanks to the very general approach taken by Kassiopeia it can be used by other experiments facing similar challenges when calculating particle trajectories in electromagnetic fields. It is publicly available at https://github.com/KATRIN-Experiment/Kassiopei

What happened to anti-malarial markets after the Affordable Medicines Facility-malaria pilot? Trends in ACT availability, price and market share from five African countries under continuation of the private sector co-payment mechanism

BACKGROUND: The private sector supplies anti-malarial treatment for large proportions of patients in sub-Saharan Africa. Following the large-scale piloting of the Affordable Medicines Facility-malaria (AMFm) from 2010 to 2011, a private sector co-payment mechanism (CPM) provided continuation of private sector subsidies for quality-assured artemisinin combination therapies (QAACT). This article analyses for the first time the extent to which improvements in private sector QAACT supply and distribution observed during the AMFm were maintained or intensified during continuation of the CPM through 2015 in Kenya, Madagascar, Nigeria, Tanzania and Uganda using repeat cross-sectional outlet survey data. RESULTS: QAACT market share in all five countries increased during the AMFm period (p < 0.001). According to the data from the last ACTwatch survey round, in all study countries except Madagascar, AMFm levels of private sector QAACT availability were maintained or improved. In 2014/15, private sector QAACT availability was greater than 70% in Nigeria (84.3%), Kenya (70.5%), Tanzania (83.0%) and Uganda (77.1%), but only 11.2% in Madagascar. QAACT market share was maintained or improved post-AMFm in Nigeria, Tanzania and Uganda, but statistically significant declines were observed in Kenya and Madagascar. In 2014/5, QAACT market share was highest in Kenya and Uganda (48.2 and 47.5%, respectively) followed by Tanzania (39.2%), Nigeria (35.0%), and Madagascar (7.0%). Four of the five countries experienced significant decreases in median QAACT price during the AMFm period. Private sector QAACT prices were maintained or further reduced in Tanzania, Nigeria and Uganda, but prices increased significantly in Kenya and Madagascar. SP prices were consistently lower than those of QAACT in the AMFm period, with the exception of Kenya and Tanzania in 2011, where they were equal. In 2014/5 QAACT remained two to three times more expensive than the most popular non-artemisinin therapy in all countries except Tanzania. CONCLUSIONS: Results suggest that a private sector co-payment mechanism for QAACT implemented at national scale for 5 years was associated with positive and sustained improvements in QAACT availability, price and market share in Nigeria, Tanzania and Uganda, with more mixed results in Kenya, and few improvements in Madagascar. The subsidy mechanism as implemented over time across countries was not sufficient on its own to achieve optimal QAACT uptake. Supporting interventions to address continued availability and distribution of non-artemisinin therapies, and to create demand for QAACT among providers and consumers need to be effectively implemented to realize the full potential of this subsidy mechanism. Furthermore, there is need for comprehensive market assessments to identify contemporary market barriers to high coverage with both confirmatory testing and appropriate treatment

Do anti-malarials in Africa meet quality standards? The market penetration of non quality-assured artemisinin combination therapy in eight African countries

BACKGROUND: Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector. RESULTS: In 2014/15, non-QAACT were most commonly available in Kinshasa (83%), followed by Katanga (53%), Nigeria (48%), Kenya (42%), and Uganda (33%). Non-QAACT accounted for 20% of the market share in the private sector in Kenya, followed by Benin and Uganda (19%), Nigeria (12%) and Zambia (8%); this figure was 27% in Katanga and 40% in Kinshasa. Public sector non-QAACT availability and distribution was much lower, with the exception of Zambia (availability, 85%; market share, 32%). Diverse generics and formulations were available, but non-QAACT were most commonly artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA PPQ), in tablet formulation, imported, and distributed in urban areas at either pharmacies or drug stores. The number of unique manufacturers supplying non-QAACT to each country ranged from 9 in Uganda to 92 in Nigeria. CONCLUSIONS: Addressing the availability and distribution of non-QAACT will require effective private sector engagement and evidence-based strategies to address provider and consumer demand for these products. Given the variation in non-QAACT markets observed across the eight study countries, active efforts to limit registration, importation and distribution of non-QAACT must be tailored to the country context, and will involve addressing complex and challenging aspects of medicine registration, private sector pharmaceutical regulation, local manufacturing and drug importation. These efforts may be critical not only to patient health and safety, but also to effective malaria control and protection of artemisinin drug efficacy in the face of spreading resistance

Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).</p> <p>Methods</p> <p>Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)</p> <p>Results</p> <p>HNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.</p> <p>Conclusions</p> <p>The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.</p

Dead layer on silicon p–i–n diode charged-particle detectors

Semiconductor detectors in general have a dead layer at their surfaces that is either a result of natural or induced passivation, or is formed during the process of making a contact. Charged particles passing through this region produce ionization that is incompletely collected and recorded, which leads to departures from the ideal in both energy deposition and resolution. The silicon p-i-n diode used in the KATRIN neutrinomass experiment has such a dead layer. We have constructed a detailed Monte Carlo model for the passage of electrons from vacuum into a silicon detector, and compared the measured energy spectra to the predicted ones for a range of energies from 12 to 20 keV. The comparison provides experimental evidence that a substantial fraction of the ionization produced in the "dead" layer evidently escapes by diffusion, with 46% being collected in the depletion zone and the balance being neutralized at the contact or by bulk recombination. The most elementary model of a thinner dead layer from which no charge is collected is strongly disfavored

Search for PeV gamma-ray emission from the southern hemisphere with 5 Yr of data from the IceCube observatory

The measurement of diffuse PeV gamma-ray emission from the Galactic plane would provide information about the energy spectrum and propagation of Galactic cosmic rays, and the detection of a pointlike source of PeV gamma-rays would be strong evidence for a Galactic source capable of accelerating cosmic rays up to at least a few PeV. This paper presents several unbinned maximum-likelihood searches for PeV gamma-rays in the Southern Hemisphere using 5 yr of data from the IceTop air shower surface detector and the in-ice array of the IceCube Observatory. The combination of both detectors takes advantage of the low muon content and deep shower maximum of gamma-ray air showers and provides excellent sensitivity to gamma-rays between similar to 0.6 and 100 PeV. Our measurements of pointlike and diffuse Galactic emission of PeV gamma-rays are consistent with the background, so we constrain the angle-integrated diffuse gamma-ray flux from the Galactic plane at 2 PeV to 2.61 x 10(-19) cm(-2) s(-1) TeV-1 at 90% confidence, assuming an E-3 spectrum, and we estimate 90% upper limits on pointlike emission at 2 PeV between 10(-21) and 10(-20) cm(-2) s(-1) TeV-1 for an E-2 spectrum, depending on decl. Furthermore, we exclude unbroken power-law emission up to 2 PeV for several TeV gamma-ray sources observed by the High Energy Spectroscopic System and calculate upper limits on the energy cutoffs of these sources at 90% confidence. We also find no PeV gamma-rays correlated with neutrinos from IceCube's high-energy starting event sample. These are currently the strongest constraints on PeV gamma-ray emission