In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment ...of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plant Artemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
KM3NeT will be a network of deep-sea neutrino telescopes in the Mediterranean Sea. The KM3NeT/ARCA detector, to be installed at the Capo Passero site (Italy), is optimised for the detection of ...high-energy neutrinos of cosmic origin. Thanks to its geographical location on the Northern hemisphere, KM3NeT/ARCA can observe upgoing neutrinos from most of the Galactic Plane, including the Galactic Centre. Given its effective area and excellent pointing resolution, KM3NeT/ARCA will measure or significantly constrain the neutrino flux from potential astrophysical neutrino sources. At the same time, it will test flux predictions based on gamma-ray measurements and the assumption that the gamma-ray flux is of hadronic origin. Assuming this scenario, discovery potentials and sensitivities for a selected list of Galactic sources and to generic point sources with an E−2 spectrum are presented. These spectra are assumed to be time independent. The results indicate that an observation with 3σ significance is possible in about six years of operation for the most intense sources, such as Supernovae Remnants RX J1713.7-3946 and Vela Jr. If no signal will be found during this time, the fraction of the gamma-ray flux coming from hadronic processes can be constrained to be below 50% for these two objects.
Letter of intent for KM3NeT 2.0 Adrián-Martínez, S; Aharonian, F; Aiello, S ...
Journal of physics. G, Nuclear and particle physics,
08/2016, Letnik:
43, Številka:
8
Journal Article, Publication
Recenzirano
Odprti dostop
The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of ...neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and complementary field of view, including the galactic plane. One building block will be densely configured to precisely measure atmospheric neutrino oscillations.
The Protvino accelerator facility located in the Moscow region, Russia, is in a good position to offer a rich experimental research program in the field of neutrino physics. Of particular interest is ...the possibility to direct a neutrino beam from Protvino towards the KM3NeT/ORCA detector, which is currently under construction in the Mediterranean Sea 40 km offshore Toulon, France. This proposal is known as P2O. Thanks to its baseline of 2595 km, this experiment would yield an unparalleled sensitivity to matter effects in the Earth, allowing for the determination of the neutrino mass ordering with a high level of certainty after only a few years of running at a modest beam intensity of
≈
90
kW
. With a prolonged exposure (
≈
1500
kW
year
), a
2
σ
sensitivity to the leptonic CP-violating Dirac phase can be achieved. A second stage of the experiment, comprising a further intensity upgrade of the accelerator complex and a densified version of the ORCA detector (Super-ORCA), would allow for up to a
6
σ
sensitivity to CP violation and a
10
∘
-
17
∘
resolution on the CP phase after 10 years of running with a 450 kW beam, competitive with other planned experiments. The initial composition and energy spectrum of the neutrino beam would need to be monitored by a near detector, to be constructed several hundred meters downstream from the proton beam target. The same neutrino beam and near detector set-up would also allow for neutrino-nucleus cross section measurements to be performed. A short-baseline sterile neutrino search experiment would also be possible.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The gSeaGen code is a GENIE-based application developed to efficiently generate high statistics samples of events, induced by neutrino interactions, detectable in a neutrino telescope. The gSeaGen ...code is able to generate events induced by all neutrino flavours, considering topological differences between track-type and shower-like events. Neutrino interactions are simulated taking into account the density and the composition of the media surrounding the detector. The main features of gSeaGen are presented together with some examples of its application within the KM3NeT project.
Program Title: gSeaGen
CPC Library link to program files:http://dx.doi.org/10.17632/ymgxvy2br4.1
Licensing provisions: GPLv3
Programming language: C++
External routines/libraries: GENIE 1 and its external dependencies. Linkable to MUSIC 2 and PROPOSAL 3.
Nature of problem: Development of a code to generate detectable events in neutrino telescopes, using modern and maintained neutrino interaction simulation libraries which include the state-of-the-art physics models. The default application is the simulation of neutrino interactions within KM3NeT 4.
Solution method: Neutrino interactions are simulated using GENIE, a modern framework for Monte Carlo event generators. The GENIE framework, used by nearly all modern neutrino experiments, is considered as a reference code within the neutrino community.
Additional comments including restrictions and unusual features: The code was tested with GENIE version 2.12.10 and it is linkable with release series 3. Presently valid up to 5 TeV. This limitation is not intrinsic to the code but due to the present GENIE valid energy range.
References:
1 C. Andreopoulos at al., Nucl. Instrum. Meth. A614 (2010) 87.
2 P. Antonioli et al., Astropart. Phys. 7 (1997) 357.
3 J. H. Koehne et al., Comput. Phys. Commun. 184 (2013) 2070.
4 S. Adrián-Martínez et al., J. Phys. G: Nucl. Part. Phys. 43 (2016) 084001.
The KM3NeT Collaboration is currently constructing a multi-site high-energy neutrino telescope in the Mediterranean Sea consisting of matrices of pressure-resistant glass spheres, each holding a set ...of 31 small-area photomultipliers. The main goals of the telescope are the observation of neutrino sources in the Universe and the measurement of the neutrino oscillation parameters with atmospheric neutrinos. A relative time synchronisation between photomultipliers of the nanosecond order needed to guarantee the required angular resolution of the detector. Due to the large detector volumes to be instrumented by KM3NeT, a cost reduction of the different systems is a priority. To this end, the inexpensive Nanobeacon has been designed and developed by the KM3NeT Collaboration to be used for detector time-calibration studies. At present, more than 600 Nanobeacons have been already produced. The characterisation of the optical pulse and the wavelength emission profile of the devices is critical for the time calibration. The optical pulse rise time has been quantified as less than 3 ns, while the Full Width Half Maximum is less than 6 ns. The wavelength drift, due to a variation of the supply voltage, has also been qualified as lower than 10 nm for the full range of the Nanobeacon. In this paper, more details about the main features of the Nanobeacon design, production and operation, together with the main properties of the light pulse generated are described.
The KM3NeT multi-PMT optical module Alshamsi, M.; Alves Garre, S.; Aly, Z. ...
Journal of instrumentation,
07/2022, Letnik:
17, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Abstract
The optical module of the KM3NeT neutrino telescope is an
innovative multi-faceted large area photodetection module. It
contains 31 three-inch photomultiplier tubes in a single 0.44 m
...diameter pressure-resistant glass sphere. The module is a sensory
device also comprising calibration instruments and electronics for
power, readout and data acquisition. It is capped with a
breakout-box with electronics for connection to an electro-optical
cable for power and long-distance communication to the onshore
control station. The design of the module was qualified for the
first time in the deep sea in 2013. Since then, the technology has
been further improved to meet requirements of scalability,
cost-effectiveness and high reliability. The module features a
sub-nanosecond timing accuracy and a dynamic range allowing the
measurement of a single photon up to a cascade of thousands of
photons, suited for the measurement of the Cherenkov radiation
induced in water by secondary particles from interactions of
neutrinos with energies in the range of GeV to PeV. A distributed
production model has been implemented for the delivery of more than
6000 modules in the coming few years with an average production rate
of more than 100 modules per month. In this paper a review is
presented of the design of the multi-PMT KM3NeT optical module with
a proven effective background suppression and signal recognition and
sensitivity to the incoming direction of photons.
The KM3NeT Collaboration runs a multi-site neutrino observatory in the Mediterranean Sea. Water Cherenkov particle detectors, deep in the sea and far off the coasts of France and Italy, are already ...taking data while incremental construction progresses. Data Acquisition Control software is operating off-shore detectors as well as testing and qualification stations for their components. The software, named Control Unit, is highly modular. It can undergo upgrades and reconfiguration with the acquisition running. Interplay with the central database of the Collaboration is obtained in a way that allows for data taking even if Internet links fail. In order to simplify the management of computing resources in the long term, and to cope with possible hardware failures of one or more computers, the KM3NeT Control Unit software features a custom dynamic resource provisioning and failover technology, which is especially important for ensuring continuity in case of rare transient events in multi-messenger astronomy. The software architecture relies on ubiquitous tools and broadly adopted technologies and has been successfully tested on several operating systems.
The KM3NeT research infrastructure is under construction in the Mediterranean Sea. It consists of two water Cherenkov neutrino detectors, ARCA and ORCA, aimed at neutrino astrophysics and oscillation ...research, respectively. Instrumenting a large volume of sea water with
∼
6200
optical modules comprising a total of
∼
200
,
000
photomultiplier tubes, KM3NeT will achieve sensitivity to
∼
10
MeV
neutrinos from Galactic and near-Galactic core-collapse supernovae through the observation of coincident hits in photomultipliers above the background. In this paper, the sensitivity of KM3NeT to a supernova explosion is estimated from detailed analyses of background data from the first KM3NeT detection units and simulations of the neutrino signal. The KM3NeT observational horizon (for a
5
σ
discovery) covers essentially the Milky-Way and for the most optimistic model, extends to the Small Magellanic Cloud (
∼
60
kpc
). Detailed studies of the time profile of the neutrino signal allow assessment of the KM3NeT capability to determine the arrival time of the neutrino burst with a few milliseconds precision for sources up to 5–8 kpc away, and detecting the peculiar signature of the
standing accretion shock instability
if the core-collapse supernova explosion happens closer than 3–5 kpc, depending on the progenitor mass. KM3NeT’s capability to measure the neutrino flux spectral parameters is also presented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
KM3NeT is a research infrastructure located in the Mediterranean Sea, that will consist of two deep-sea Cherenkov neutrino detectors. With one detector (ARCA), the KM3NeT Collaboration aims at ...identifying and studying TeV–PeV astrophysical neutrino sources. With the other detector (ORCA), the neutrino mass ordering will be determined by studying GeV-scale atmospheric neutrino oscillations. The first KM3NeT detection units were deployed at the Italian and French sites between 2015 and 2017. In this paper, a description of the detector is presented, together with a summary of the procedures used to calibrate the detector in-situ. Finally, the measurement of the atmospheric muon flux between 2232–3386 m seawater depth is obtained.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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