76 results on '"N. Daniele"'
Search Results
2. Muscle‐specific, liver‐detargeted <scp>adeno‐associated virus</scp> gene therapy rescues Pompe phenotype in adult and neonate <scp>Gaa−/−</scp> mice
- Author
-
P. Sellier, P. Vidal, B. Bertin, E. Gicquel, E. Bertil‐Froidevaux, C. Georger, L. van Wittenberghe, A. Miranda, N. Daniele, I. Richard, D. A. Gross, F. Mingozzi, F. Collaud, and G. Ronzitti
- Subjects
Genetics ,Genetics (clinical) - Published
- 2023
- Full Text
- View/download PDF
3. Use of Domain-Swapping to Identify Candidate Amino Acids Involved in Differential Interactions between Two Allelic Variants of Type-1 S-Locus F-Box Protein and S3-RNase in Petunia inflata
- Author
-
Wu, Lihua, Williams, Justin S, Wang, Ning, Khatri, Wasi A, San Rom[REPLACEMENT CHARACTER]n, Daniele, and Kao, Teh-hui
- Published
- 2018
- Full Text
- View/download PDF
4. Marble Wastes Recycling: Design and Synthesis of Low-Temperature Calcium Silicate Hydrate Under Various CaO:SiO 2 Ratio and Alkalinity
- Author
-
Cristina Leonelli, Alberto Mariani, Roberto Rosa, David Sanna, Elie Kamseu, N Daniele, and A Valeria
- Subjects
Materials science ,Alkalinity ,Pozzolan ,law.invention ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,law ,Calcination ,Orthosilicate ,Particle size ,Calcium silicate hydrate ,Dissolution ,BET theory - Abstract
Marble sludge wastes (MSW) are investigated as solid precursor for the production of low-temperature calcium silicate hydrate (CSH). Calcined powder of MSW is ball-milled with rice husk ash (RHA) and the slurries are treated in oven at 100C for 24 hours in a context where water evaporation is minimized. The initial CaO:SiO2 molar ratio varies from 1 to 3 (CS, C2S and C3S) and the solution used for the preparation of the calcium silicate hydrate presents NaOH with concentration of 0, 1, 2 and 3 N. FTIR, XRD, Particle size distribution, BET surface area and Environmental Scanning Electron Microscope (ESEM) permitted to confirm the formation of CxS (x = 1, 2, 3) and CSH at 100C through pozzolanic reactions. The increase of the alkalinity of the solution improved the silica dissolution and enhances the formation of CxS and CSH up to 2N. Further increase of the alkalinity affected the silica polymerization, the particle size and the concentration of CxS and CSH into the final matrix. Precursor with CaO:SiO2 = 1 seem to promote more monomers while 2CaO:SiO2 and 3CaO:SiO2 resulted in orthosilicate chains and interlayer respectively. The high reactivity and fine particles (ϕ < 32 nm) of CSH obtained appeared promising for the design of low-cost, environmentally-friendly and sustainable binders as well as others engineering applications including refractory precursors, hydroceramics, insulating matrices, filtration and catalysis.
- Published
- 2021
- Full Text
- View/download PDF
5. Marble Wastes Recycling: Design and Synthesis of Low-Temperature Calcium Silicate Hydrate Under Various CaO:SiO 2 Ratio and Alkalinity
- Author
-
Kamseu, Elie, primary, A., Valeria, additional, Rosa, Roberto, additional, N., Daniele, additional, Sanna, David, additional, Mariani, Alberto, additional, and Leonelli, Cristina, additional
- Published
- 2021
- Full Text
- View/download PDF
6. On the Amplify-and-Forward Cooperative Diversity with Time-Hopping Ultra-Wideband Communications
- Author
-
Jean-Claude Belfiore, Chadi Abou-Rjeily, and N. Daniele
- Subjects
Channel code ,Computer science ,Rake ,Time-hopping ,Full Rate ,law.invention ,Cooperative diversity ,Amplitude modulation ,Relay ,law ,Modulation ,Pulse-amplitude modulation ,Pulse-position modulation ,Electronic engineering ,Fading ,Electrical and Electronic Engineering ,Communication channel - Abstract
In this paper, we extend the Amplify-and-Forward cooperative diversity scheme to the context of impulse radio ultra wideband (IR-UWB). In particular, we present the construction of three families of minimal-delay and totally-real distributed algebraic space-time (ST) codes suitable for IR-UWB. The first family encodes adjacent symbols and is based on totally-real cyclic division algebras. The second family encodes the pulses used to transmit one information symbol and permits to achieve high performance levels with lower complexity. Both families of codes achieve full rate, full diversity with non-vanishing determinants for various number of relays. These schemes can be associated with pulse position modulation (PPM), pulse amplitude modulation (PAM) and hybrid pulse position and amplitude modulation (PPM-PAM). The third family of codes is information-lossless and does not require any pulse repetitions. It is specific to M-PPM-M'-PAM with M ges 3 and for all values of M'. Simulations performed over realistic indoor UWB channels are provided to verify the theoretical results.
- Published
- 2008
- Full Text
- View/download PDF
7. Distributed Algebraic Space-Time Codes for Ultra-Wideband Communications
- Author
-
Chadi Abou-Rjeily, N. Daniele, and Jean-Claude Belfiore
- Subjects
Computer science ,business.industry ,Rake ,Ultra-wideband ,Context (language use) ,Full Rate ,Topology ,Computer Science Applications ,Cooperative diversity ,Scheme (mathematics) ,Algebraic space ,Electrical and Electronic Engineering ,Algebraic number ,Telecommunications ,business ,Computer Science::Information Theory - Abstract
In this paper, we extend the Amplify-and-Forward cooperative diversity scheme to the context of impulse radio ultra-wideband. In particular, we present the construction of two families of distributed algebraic space-time codes. The first family is based on totally real cyclic division algebras. The second family encodes the pulses used to transmit one information symbol and permits to achieve high-performance levels with lower complexity. Both families of codes achieve full rate, full diversity with non-vanishing determinants with various numbers of relays. Simulations performed over realistic indoor UWB channel models show important performance gains.
- Published
- 2006
- Full Text
- View/download PDF
8. UWB SIMO channel measurements and simulations
- Author
-
J. Keignart, C. Delaveaud, Chadi Abou-Rjeily, and N. Daniele
- Subjects
Radiation ,Computer science ,business.industry ,MIMO ,Channel sounding ,Electrical engineering ,Ultra-wideband ,Data_CODINGANDINFORMATIONTHEORY ,Condensed Matter Physics ,Antenna diversity ,Antenna array ,Bit error rate ,Electronic engineering ,Rake receiver ,Electrical and Electronic Engineering ,business ,Communication channel - Abstract
Ultra-wideband (UWB) technology has recently attracted the entire wireless community with its great potential for short-range and high data-rate communications. On the other hand, multiantenna (or multiple-input multiple-output) techniques are considered as an effective way to improve the link reliability and transmission rate. In this paper, both aspects are studied through a complete UWB single-input multiple-output (SIMO) channel sounding campaign. The time-domain channel sounder with its antenna array is firstly detailed. Secondly, measurement results will be used to describe interesting antenna array effects and channel behavior (like correlation results and underlying spatial diversity). Finally, in order to show the utility of spatial diversity in UWB systems, the performance of a SIMO system with a Rake receiver will be presented through bit error rate simulations based on measurement results.
- Published
- 2006
- Full Text
- View/download PDF
9. L'étalement de spectre par séquence directe Une solution pour les communications radio en milieu perturbé
- Author
-
J.R. Lequepeys, A Leroy, D Lattard, A Merle, N Daniele, R. Lionti, C Boulanger, and L. Ouvry
- Subjects
Physics ,Automotive Engineering ,Transportation ,Humanities - Abstract
Resume La necessite de faire communiquer des robots en environnement hostile (de type centrale nucleaire) a conduit le cea-letl a valoriser ses connaissances de l'etalement de spectre par sequence directe. Cette technique permet en effet de tirer profit des trajets multiples qui ne manquent pas d'affecter les transmissions radio classiques, grâce a une structure de reception originale et un traitement de diversite. D'abord realisees a partir d'un filtre a ondes acoustiques de surface, les recepteurs mis au point ont ensuite utilise des circuits numeriques dedies prenant en compte tout le traitement bande de base, La souplesse apportee permet des lors d'envisager des structures de reception multiutilisateurs orientees haut debit(jusqu'a 10 Mbits/s). Toutes ces recherches trouvent ainsi leurs applications dans des domaines varies: la video-surveillance et les communications sol-train dans le metro, les communications tete queue pour les trains hyper-lourds en sont quelques exemples.
- Published
- 1999
- Full Text
- View/download PDF
10. A 2 x 2 antennas ultra-wideband system with biorthogonal pulse position modulation
- Author
-
Chadi Abou-Rjeily, Jean-Claude Belfiore, and N. Daniele
- Subjects
Computer science ,business.industry ,MIMO ,Ultra-wideband ,Full Rate ,Topology ,Coding gain ,Computer Science Applications ,Modeling and Simulation ,Biorthogonal system ,Pulse-position modulation ,Electrical and Electronic Engineering ,Telecommunications ,business ,Data transmission - Abstract
The Golden code is a 2/spl times/2 space-time code that achieves the best known performance with all constellations carved from /spl Zopf/[i]. In this letter, we present the construction of a new coding scheme for 2M-ary biorthogonal pulse position modulations (BPPM) with M/spl ges/4. The proposed code satisfies all of the construction constraints of the Golden code and it has the additional advantage of being totally real making it suitable for low cost carrier-less ultra-wideband terminals. Namely, this totally real construction achieves full rate and full diversity with the best known coding gain and without any shaping losses for 2M-BPPM with M/spl ges/4.
- Published
- 2006
- Full Text
- View/download PDF
11. Recent results for the Raytheon RELI program
- Author
-
David M. Filgas, David Mordaunt, Andrew N. Daniele, Matt Cashen, Todd O. Clatterbuck, and Steve Hughes
- Subjects
Single beam ,business.industry ,Computer science ,Amplifier ,Electrical engineering ,Physics::Optics ,Laser ,Waveguide (optics) ,Line (electrical engineering) ,law.invention ,Planar ,law ,Scalability ,Laser beam quality ,business - Abstract
We describe our approach and latest results for Raytheon's RELI (Robust Electric Laser Initiative) program. Our architecture leverages a slab-based, Master Oscillator / Power Amplifier (MOPA) architecture based on Raytheon's unique planar waveguide amplifier. Technical objectives for this effort are to demonstrate > 25 kW output with excellent beam quality and an electrical to optical efficiency > 30%. The planar waveguide architecture provides compact packaging and is inherently scalable to 100 kW or greater in a single beam line. We report on the latest progress and test results for the program.
- Published
- 2012
- Full Text
- View/download PDF
12. Diversity-Multiplexing Tradeoff of Single-Antenna and Multi-Antenna Indoor Ultra-Wideband Channels
- Author
-
Chadi Abou-Rjeily, N. Daniele, and Jean-Claude Belfiore
- Subjects
Engineering ,business.industry ,Diversity gain ,Electronic engineering ,Ultra-wideband ,Statistical model ,Antenna (radio) ,business ,Multiplexing ,WiMAX ,Energy (signal processing) ,Expression (mathematics) ,Computer Science::Information Theory - Abstract
In this paper, we study the achievable diversity-multiplexing gain (D-MG) tradeoffs over the IEEE 802.15.3a channel model. In particular, we give an exact expression of the D-MG tradeoff for single antenna systems. This expression is based on a statistical model of the integrated energy of the considered channels. At a second time, we evaluate lower and upper bounds on the D-MG tradeoffs of multi-antenna systems. This formulation gives us more insights on the real potential of multi-antenna techniques with UWB systems. It is shown that even though the asymptotical diversity gain has an infinite value, the multi-antenna techniques can be very beneficial in the practical range of signal-to-noise ratios.
- Published
- 2006
- Full Text
- View/download PDF
13. MIMO UWB Communications Using Modified Hermite Pulses
- Author
-
Chadi Abou-Rjeily, N. Daniele, and Jean-Claude Belfiore
- Subjects
Transmit diversity ,Hermite polynomials ,Computer science ,business.industry ,Pulse-amplitude modulation ,Pulse-position modulation ,MIMO ,Electronic engineering ,Data_CODINGANDINFORMATIONTHEORY ,Full Rate ,Telecommunications ,business ,Computer Science::Information Theory - Abstract
In this paper, we present a new full rate scheme for exploiting diversity in multi-antenna ultra-wideband (UWB) systems. The independent data streams that are transmitted simultaneously from the different antennas are rendered orthogonal by the use of modified Hermite pulses. At a second time, appropriate real rotations enhance the transmit diversity level. We also consider, for the first time, the problem of Maximum Likelihood (ML) detection with multi-dimensional PPM and hybrid PPM-PAM constellations that can be used in conjunction with the proposed scheme.
- Published
- 2006
- Full Text
- View/download PDF
14. Amplify-and-Forward Cooperative Diversity with Space-Time Coded UWB Systems
- Author
-
Chadi Abou-Rjeily, N. Daniele, and Jean-Claude Belfiore
- Subjects
Engineering ,business.industry ,Space time ,Data_CODINGANDINFORMATIONTHEORY ,Antenna diversity ,Modulation coding ,Cooperative diversity ,Ultra wideband antennas ,Computer engineering ,Electronic engineering ,Amplify and forward ,business ,Computer Science::Information Theory ,Coding (social sciences) ,Constellation - Abstract
In this paper, we examine the impact of spatial diversity on ultra-wideband (UWB) systems. This diversity is exploited by deploying two antennas at the UWB terminals. For single-antenna systems, spatial diversity is exploited in a distributed manner where a neighboring node can help the source in delivering its message to a destination. In particular, two space-time (ST) coding schemes are proposed. The first one is optimal among all totally-real codes having a constant transmitted energy per antenna. Unlike the classical approach of constructing ST codes over infinite fields, the second construction takes the structure of 2-dimensional constellations into consideration in order to propose an appropriate modulation-specific code. These schemes are associated with multi-antenna arrays and with virtual arrays based on the amplify-and-forward (AF) strategy.
- Published
- 2006
- Full Text
- View/download PDF
15. Distributed Space-Time Coding with Ultra-Wideband Systems
- Author
-
Chadi Abou-Rjeily, N. Daniele, and Jean-Claude Belfiore
- Subjects
Amplitude modulation ,Pulse-amplitude modulation ,Computer science ,business.industry ,Pulse-position modulation ,Electronic engineering ,Ultra-wideband ,Space–time code ,Telecommunications ,business ,Diversity scheme - Abstract
In this paper, we extend the Amplify-and-Forward (AF) co-operative diversity scheme to the context of impulse radio ultra wideband (IR-UWB). In particular, we apply a space-time (ST) coding scheme based on totally-real cyclic division algebras in order to achieve full diversity with no data rate losses. At a second time, the pulse repetitions are exploited in order to enhance the performance of the first scheme and to propose a new scheme that achieves comparable performance with lower complexity. These schemes are associated with pulse position modulation (PPM), pulse amplitude modulation (PAM) and hybrid pulse position and amplitude modulation (PPM-PAM).
- Published
- 2006
- Full Text
- View/download PDF
16. An Optimal 2 × 2 Space-Time Code for Time-Hopping Ultra-Wideband Systems with binary Pulse Position Modulation
- Author
-
Chadi Abou-Rjeily, N. Daniele, and Jean-Claude Belfiore
- Subjects
Amplitude modulation ,business.industry ,Computer science ,Pulse-position modulation ,Time-hopping ,Code (cryptography) ,Baseband ,Ultra-wideband ,Constant-weight code ,Telecommunications ,business ,Topology ,Space–time code - Abstract
The golden code (Belfiore, 2005) is a 2 x 2 space-time (ST) code that achieves the best known performance with all constellations carved from Zopf[i]. On the other hand, impulse radio (IR) time-hopping (TH) ultra wideband (UWB) is a carrier-less baseband transmission technique. Therefore, being complex-valued, the golden code can not be associated with IR-UWB systems. In this paper, we propose a new ST code that satisfies all of the construction constraints of the golden code and that has the additional advantage of being totally real making it suitable for low cost carrier-less UWB terminals. Unlike the golden code that can be associated with all constellations carved from Zopf[i], the proposed code is optimal with binary pulse position modulation (PPM) which is a popular modulation scheme for TH-UWB. Moreover, the proposed scheme permits to achieve full transmit diversity with hybrid pulse position and amplitude modulations (PPAM) having two modulation positions.
- Published
- 2006
- Full Text
- View/download PDF
17. On the Decode-and-Forward Cooperative Diversity with Coherent and Non-Coherent UWB Systems
- Author
-
Chadi Abou-Rjeily, Jean-Claude Belfiore, and N. Daniele
- Subjects
Diversity combining ,Exploit ,Wireless network ,Computer science ,Electronic engineering ,Data_CODINGANDINFORMATIONTHEORY ,Antenna diversity ,Decoding methods ,Coding (social sciences) ,Diversity scheme ,Cooperative diversity - Abstract
In this paper, we extend the Decode-and-Forward cooperative diversity scheme to the context of impulse radio ultra-wideband (IR-UWB). We develop coherent and non-coherent schemes that exploit the spatial diversity in a distributed manner among the different terminals of a wireless network. These schemes are specific to IR-UWB and they take advantage of the pulse repetitions used to convey each information symbol. If Nf is the number of pulses per symbol, the coherent scheme is based on joint symbol and pulse coding and it achieves full diversity with any number of relays for Nf > 1. The non-coherent scheme is based on pulse coding and it achieves full diversity with a maximum number of Nf ? 1 relays.
- Published
- 2006
- Full Text
- View/download PDF
18. A New Full Rate Full Diversity ST Code with Nonvanishing Determinant for TH-UWB Systems
- Author
-
Jean-Claude Belfiore, Chadi Abou-Rjeily, and N. Daniele
- Subjects
Cyclic division algebras ,business.industry ,Space time ,Time-hopping ,Variable-length code ,Ultra-wideband ,Data_CODINGANDINFORMATIONTHEORY ,Full Rate ,Topology ,Coding gain ,Telecommunications ,business ,Computer Science::Information Theory ,Coding (social sciences) ,Mathematics - Abstract
In this paper, we propose a new space time (ST) coding scheme for time hopping (TH) ultra wideband (UWB) systems. The proposed scheme encodes the pulses used to transmit one information symbol. This permits to achieve full rate and full diversity with a non-vanishing coding gain for all number of transmit antennas. The proposed code shows to be the optimal extension of the codes constructed from cyclic division algebras when inter-pulse coding is performed
- Published
- 2006
- Full Text
- View/download PDF
19. 50_015
- Author
-
C. Abou-Rjeily, N. Daniele, and J.-C. Belfiore
- Published
- 2006
- Full Text
- View/download PDF
20. A New Family of Space-Time Codes for Pulse Amplitude and Position Modulated UWB Systems
- Author
-
Chadi Abou-Rjeily, N. Daniele, and Jean-Claude Belfiore
- Subjects
Amplitude modulation ,Physics ,Amplitude ,Pulse-amplitude modulation ,business.industry ,Space time ,Pulse-position modulation ,Fading ,Full Rate ,Topology ,Telecommunications ,business ,Pulse-width modulation - Abstract
This paper presents the construction of new totally-real space-time coding schemes suited for carrier-less ultra-wideband transmissions. These schemes are associated with pulse position modulation and with hybrid pulse amplitude and position modulation where the input data is modulated onto both the pulse amplitudes and positions. The new schemes have a uniform average transmitted energy per antenna and achieve full rate and full diversity with hybrid M-PPM-M'-PAM for all values of M' and for M ges 3, M ges 5 and {M = 5, M ges 7} with n = 2, 3 and 4 transmit antennas respectively
- Published
- 2006
- Full Text
- View/download PDF
21. On High Data Rate Space-Time Codes For Ultra-Wideband Systems
- Author
-
Jean-Claude Belfiore, Chadi Abou-Rjeily, and N. Daniele
- Subjects
Multidimensional signal processing ,Engineering ,Pulse-amplitude modulation ,business.industry ,Transmitter ,Pulse-position modulation ,Electronic engineering ,Ultra-wideband ,Data_CODINGANDINFORMATIONTHEORY ,Full Rate ,business ,Coding gain ,Decoding methods - Abstract
In this paper, the advantage of applying space-time (ST) coding on ultra wideband (UWB) systems is discussed. In order to achieve very high data rates and important performance gains combined pulse position modulation (PPM) and pulse amplitude modulation (PAM) constellations along with full diversity and full rate ST codes are used at the transmitter side. The proposed coding-decoding scheme takes into account the nature of the highly frequency selective channel and the multi-dimensional constellation. Furthermore, the coding gain is optimized over different constellations and the possibility of compromising performance to lower peak-to-average power ratios (PAPR) is discussed. Moreover, for simplified receiver structures, V-BLAST decoding scheme was adapted to multi-dimensional signals. Results show considerable performance gains and better immunity against inter symbol interference (ISI) and multi user interference (MUI).
- Published
- 2006
- Full Text
- View/download PDF
22. Performance analysis of space-time coding over ultra wideband channels
- Author
-
C.A. Rjeily and N. Daniele
- Subjects
Channel code ,Computer science ,business.industry ,ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS ,Rake ,Radio receiver ,Ultra-wideband ,Data_CODINGANDINFORMATIONTHEORY ,law.invention ,Transmit diversity ,law ,Computer Science::Networking and Internet Architecture ,Electronic engineering ,Code (cryptography) ,Antenna (radio) ,Space–time code ,business ,Computer Science::Information Theory ,Communication channel ,Computer network - Abstract
In this paper, we propose two transmit diversity schemes for ultra-wideband time-hopping (UWB-TH) communications. The performance of these schemes is evaluated for binary antipodal signalling over real UWB channels. The first proposed scheme assigns orthogonal codes to the M transmit antennas and is capable of achieving the maximum transmit diversity of M with no data rate loss compared to single antenna UWB systems. The second scheme is the extension of Alamouti's space-time (ST) code to UWB communications. Simulations and semi-analytical evaluations of the error probability show that giving rise to both spatial and multipath diversity by associating these schemes with partial or selective combining Rake receivers (PRake or SRake) can result in considerable performance gains.
- Published
- 2005
- Full Text
- View/download PDF
23. Effect of supplementation of calcium and Vitamin D on bone mineral density and bone mineral content in peri- and post-menopause women: A double-blind, randomized, controlled trial
- Author
-
N DANIELE, M CARBONELLI, N CANDELORO, L IACOPINO, A DELORENZO, and A ANDREOLI
- Subjects
Pharmacology ,perimenopause ,bone mineral content ,bone mineral density ,calcium ,peri-menopause ,post-menopause ,vitamin D ,analysis of variance ,middle aged ,postmenopause ,female ,osteoporosis, postmenopausal ,double-blind method ,calcium, dietary ,bone density ,drug combinations ,dietary supplements ,postmenopausal ,osteoporosis ,Calcium, Dietary ,Humans ,dietary ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,Osteoporosis, Postmenopausal - Abstract
Osteoporosis is a serious global health problem for the future, that is why improving diagnostic methods and prevention of this disease could be helpful.To assess the effects of calcium supplementations combined with Vitamin D on bone mineral density (BMD) and bone mineral content (BMC) in a representative sample of peri- and post-menopausal women in a double-blind, a randomized, controlled trial was untaken.A total of 120 women aged over 45 were included in a randomised placebo-controlled, double-blind trial on the effect of a daily dietary supplementation of calcium and Vitamin D on bone mineral density and bone mineral content; over a 30-month period.Dietary intake assessment; dual-energy X-ray absorptiometry to measure total body and segmental bone mineral density and bone mineral content at beginning of the study and every 15 months were undertaken.There was no significant change in dietary calcium or Vitamin D intakes in either of the treatment groups during the 30-month intervention period. The change in total BMD in the calcium group was significantly different from that in the placebo group (P0.005). The placebo group lost a total BMD at a rate of about 0.4% per year. There was an inverse correlation between BMD and age.The effect of calcium and Vitamin D supplementation on bone mineral density of calcium has been demonstrated in this group of young adult women. Our results showed the positive effect of calcium and Vitamin D supplementation in women both peri- and post-menopausal status; for this reason a supplementation of calcium and Vitamin D should be recommended as a strategic option in helping to prevent early postmenopausal bone loss.
- Published
- 2004
24. Rhythm perception and production predict reading abilities in developmental dyslexia
- Author
-
Flaugnacco, Elena, primary, Lopez, Luisa, additional, Terribili, Chiara, additional, Zoia, Stefania, additional, Buda, Sonia, additional, Tilli, Sara, additional, Monasta, Lorenzo, additional, Montico, Marcella, additional, Sila, Alessandra, additional, Ronfani, Luca, additional, and Schön, Daniele, additional
- Published
- 2014
- Full Text
- View/download PDF
25. Subnanosecond UWB channel sounding in frequency and temporal domain
- Author
-
J. Keignart and N. Daniele
- Subjects
Engineering ,Intersymbol interference ,business.industry ,Frequency domain ,Bandwidth (signal processing) ,Performance prediction ,Electronic engineering ,Channel sounding ,Data_CODINGANDINFORMATIONTHEORY ,Oscilloscope ,Communications system ,business ,Multipath propagation - Abstract
The performance prediction and simulation of new communication and positioning systems based on UWB technology require an important effort to reach a deep knowledge of the physical channel. The multipath nature of the indoor channel is the limiting factor for positioning accuracy and communication capabilities of UWB systems in real environments, in particular ISI for high data rate applications. Most of the measurement performed to characterise the UWB channel have been performed in the time-domain by using a sampling oscilloscope with resolution greater than 1 ns. This paper describes a frequency approach based on a vector network analyser with a subnanosecond resolution in accordance with usually UWB pulse width. After an introduction the measurement technique is described and the performances of the sounding chain evaluated. Then an experimental methodology is proposed in order to assess the channel characteristics at different scale levels (small, medium, large). Finally the statistical post-processing for the future measurements is described.
- Published
- 2003
- Full Text
- View/download PDF
26. Modires: a programmable single component for spread spectrum receiver
- Author
-
D. Lattard, J.R. Lequepeys, and N. Daniele
- Subjects
Spread spectrum ,Engineering ,Application-specific integrated circuit ,business.industry ,Matched filter ,Electronic engineering ,Electrical engineering ,Demodulation ,Digital radio ,Direct-sequence spread spectrum ,business ,Clock recovery ,Multipath propagation - Abstract
LETI, a laboratory of the French Atomic Energy Commission, has built several direct sequence spread spectrum systems using SAW devices, the binary data rate of these systems goes from 256 kbit/s up to 8 Mbits/s and the frequency range is large (from 900 MHz up to 60 GHz). Taking into account its knowledge of this particular field of radio communications in multipath environments, LETI has designed a powerful programmable single chip that is able to perform as the matched filter of a direct spread spectrum receiver, the delay line of a differential demodulator, the demodulation, the data generation and the clock recovery.
- Published
- 2002
- Full Text
- View/download PDF
27. CESSIUM: a single component for implementing high data rates DSSS/CDMA interference cancellation receivers
- Author
-
L. Ouvry, D. Varreau, C. Boulanger, B. Piaget, D. Lattard, J.R. Lequepeys, and N. Daniele
- Subjects
Spread spectrum ,Computer Science::Hardware Architecture ,Parallel processing (DSP implementation) ,Single antenna interference cancellation ,Application-specific integrated circuit ,Computer science ,Code division multiple access ,Detector ,Electronic engineering ,Detection theory ,Direct-sequence spread spectrum ,Computer Science::Information Theory - Abstract
Different code division multiple access (CDMA) receiver architectures have already been proposed such as the maximum-likelihood or the decorrelating detectors. However these architectures are too complex to be implemented. Some other solutions based on subtractive interference cancellation (IC), which meanwhile have better performance than conventional detectors, are particularly attractive for hardware implementation. After a description and comparison of different IC methods, this article focuses on the implementation of a parallel interference cancellation receiver. A dedicated integrated component (ASIC), called CESSIUM, which integrates, in a single chip, all the required functions for such architecture is then described.
- Published
- 2002
- Full Text
- View/download PDF
28. Wireless transmissions in multipath environments benefit from direct sequence spread spectrum techniques
- Author
-
D. Chagnot-Auclair, R. Lionti, N. Daniele, and D. Noguet
- Subjects
Engineering ,business.industry ,ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS ,Electrical engineering ,Direct-sequence spread spectrum ,Spread spectrum ,Cognitive radio ,Interference (communication) ,Electronic engineering ,Wireless ,Fading ,business ,Multipath propagation ,Radio wave - Abstract
Presents recent radio communications research work carried out by LETI (Laboratoire d'Electronique, de Technologie et d'Instrumentation), which is a laboratory belonging to the French Atomic Energy Commission. At the outset, a team from the LETI was involved in a programme to develop robot intervention in hostile environments. One of the first problems to be solved was to find a reliable and robust radio modulation technique for multi-path environments. In this type of situation, conventional radio solutions are unsuccessful and provide only extremely low data rates. The performance of wireless transmissions is much poorer than conventional communications using cables and they have to cope with a transmission channel that is subject to much more interference. In particular, multi-path transmission of radio waves leads to interference phenomena such as widening of the channel impulse response, fading and Doppler noise, which reduce the quality of the transmission. A novel reception structure, implementing direct-sequence spread-spectrum techniques combined with a diversity system, actually benefits from the multi-path phenomena which usually damage conventional radio transmissions. The first receivers developed were based on a surface acoustic wave filter and were subsequently replaced by dedicated digital circuits that perform all the base band processing. The resulting flexibility has made the design of CDMA and high-data-rate wireless systems possible. This research has potential applications in a wide variety of areas, e.g. video surveillance and track-to-train communications in underground systems and factory communications for machine synchronisation.
- Published
- 2002
- Full Text
- View/download PDF
29. VICASSO: a new flexible base-band transceiver ASIC for a wide range of DSSS communication applications
- Author
-
R. Lionti, N. Daniele, D. Noguet, and Jean-Rene Lequepeys
- Subjects
Spread spectrum ,Intersymbol interference ,Application-specific integrated circuit ,Robustness (computer science) ,Computer science ,Electronic engineering ,Keying ,Spectral efficiency ,Direct-sequence spread spectrum ,Transceiver - Abstract
Direct sequence spread spectrum (DSSS) modulations have been widely used in different application fields over the past few years. Their main assets are now well known : reliability, robustness, communication privacy. The main drawback is a low spectrum efficiency due to spectrum spreading. This paper addresses a new base-band transceiver dedicated to point to point DSSS communications. This ASIC called VICASSO (Versatile Integrated Circuit for Advanced Spread Spectrum mOdulations) can be configured in many ways to suit a broad range of applications. First, in order to improve spectrum efficiency, M-ary orthogonal keying (MOK) and multi codes (MC) techniques have been implemented. Then, to face out inter symbol interference (ISI), a code hopping (CH) technique has been used. Many configurations mixing these modulations are available leading to a very flexible approach. VICASSO enables the end user to choose the best trade-off between data rate, robustness and spectrum efficiency for a given application. The functional description of the ASIC, its hardware features and its performance are detailed in this paper.
- Published
- 2002
- Full Text
- View/download PDF
30. ICARE, VICASSO, ACCELAN, MUSYCA: an innovative family of DSSS/CDMA ASICs for implementing DSSS/CDMA transceivers
- Author
-
Jean-Rene Lequepeys, Didier Varreau, M. Des Noes, D. Lattard, N. Daniele, D. Noguet, R. Lionti, B. Piaget, Marc Laugeois, and Laurent Ouvry
- Subjects
Engineering ,Synchronous CDMA ,business.industry ,Code division multiple access ,Direct-sequence spread spectrum ,Spread spectrum ,Computer Science::Hardware Architecture ,Diversity combining ,Application-specific integrated circuit ,Computer architecture ,Single antenna interference cancellation ,Electronic engineering ,Transceiver ,business ,Computer Science::Information Theory - Abstract
The direct sequence spread spectrum (DSSS) modulation technique has been widely used for a number of years. For point-to-point applications, LETI has proposed the concept of a matched filter receiver able to take into account all the propagation path signals implementing a diversity combining method. The proven interest, in different kinds of environments, of this original architecture had led to the development of a family of flexible ASICs. First this paper describes two ASICs (ICARE and VICASSO), developed in 1999. Then, special attention will be given to the implementation of an asynchronous code division multiple access (CDMA) receiver. The advanced CDMA architecture developed is based on co-channel interference cancellation (IC) schemes, which meanwhile have better performance than conventional detectors and are particularly attractive for hardware implementation. Finally, this article will focus on a synchronous CDMA receiver architecture.
- Published
- 2002
- Full Text
- View/download PDF
31. Clinical evaluation of hard tissue proliferations in the mouth
- Author
-
N, Piera-Navarro, N, Daniele-Rios, and D, Villalain-Blanco
- Subjects
Adult ,Male ,Mouth ,Adolescent ,Child, Preschool ,Humans ,Female ,Middle Aged ,Child ,Mouth Diseases ,Aged - Abstract
This work shows the results of a study of the proliferation of bone tissue in the mouth.It was carried out on a sample of 530 persons who were natives of Central American countries, 179 males and 154 females, evaluating the rate of appearance of these formations depending on age, sex, racial group, and their location within the jaw.It was observed that 38% of the total sample showed hard tissue proliferation in the mouth. Of these cases, 158 (80%) were located in the superior maxilla and 48 (20%) of the cases in the jaw. Of which, 52 were men (25%) and 154 women (75%). This proliferation has greater incidence in the black race, in university students and liberal professions. The most frequent are torus palatinus and bilateral torus mandibularis.The Central American population shows a high incidence of hard tissue proliferations in the mouth; a radiological study is sufficient for their detection.
- Published
- 2002
32. Role of phosphatidylinositol-3 kinase (PI3K) in the inhibition of glucose-6 phosphatase in the postprandial situation
- Author
-
Gilles Mithieux, N. Daniele, C. Zitoun, B. Payrastre, and Revues Inra, Import
- Subjects
medicine.medical_specialty ,Kinase ,0402 animal and dairy science ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,04 agricultural and veterinary sciences ,Biology ,040201 dairy & animal science ,3. Good health ,chemistry.chemical_compound ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,Endocrinology ,Postprandial ,chemistry ,Biochemistry ,Internal medicine ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,medicine ,biology.protein ,Phosphatidylinositol ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,PI3K/AKT/mTOR pathway ,Glucose 6-phosphatase ,ComputingMilieux_MISCELLANEOUS ,[SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology - Abstract
International audience
- Published
- 1998
33. Role of the abundance of messenger RNA in the expression of hepatic and renal glucose-6 phosphatase in fasted and diabetic rats
- Author
-
Gilles Mithieux, C. Zitoun, Hubert Vidal, C. Minassian, N. Daniele, and Revues Inra, Import
- Subjects
medicine.medical_specialty ,Messenger RNA ,Biology ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,Endocrinology ,Biochemistry ,Abundance (ecology) ,Internal medicine ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,medicine ,biology.protein ,Glucose 6-phosphatase ,ComputingMilieux_MISCELLANEOUS ,[SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology - Published
- 1996
34. Role of unsaturated fatty acids in the in vitro inhibition of glucose-6 phosphatase by glycogen
- Author
-
JC Bordet, Gilles Mithieux, N. Daniele, and Revues Inra, Import
- Subjects
medicine.medical_specialty ,biology ,Glycogen ,In vitro ,chemistry.chemical_compound ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,Endocrinology ,Biochemistry ,chemistry ,Internal medicine ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,biology.protein ,medicine ,Glucose 6-phosphatase ,[SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology - Published
- 1996
35. Liver glucose-6 phosphatase activity is inhibited by refeeding in rats
- Author
-
C, Minassian, N, Daniele, J C, Bordet, C, Zitoun, and G, Mithieux
- Subjects
Blood Glucose ,Male ,Rats, Sprague-Dawley ,Eating ,Glucose ,Time Factors ,Liver ,Glucose Clamp Technique ,Glucose-6-Phosphatase ,Animals ,Insulin ,Rats - Abstract
This study was conducted to determine whether inhibition of hepatic glucose-6 phosphatase is involved in the mechanism of suppression of hepatic glucose production during the postprandial period. We studied the time course of changes in the enzyme activity by refeeding food-deprived rats with nonpurified diet. The Vmax of the enzyme, assayed in homogenates from livers freeze-clamped in situ in anesthetized 48-h unfed rats (12.3 +/- 0.15 U/g wet liver, mean +/- SEM, n = 6) was progressively decreased upon refeeding: 11.1 +/- 0.5, 8.5 +/- 0.4 and 7.9 +/- 0.5 U/g, in rats refed for 90, 180 (P0.01) and 360 min (P0.01), respectively. The Km of the enzyme was not affected by refeeding. No inhibition of the enzyme was observed in microsomes purified from these homogenates, suggesting a metabolite-induced inhibition mechanism. To assess the role of insulin in the inhibition, we assayed the glucose-6 phosphatase activity in similarly processed liver homogenates from food-deprived rats perfused with insulin at physiological and supraphysiological concentrations, whereas plasma glucose was maintained at the basal level by adapted glucose perfusion (euglycemic clamps). No inhibition of glucose-6 phosphatase was found under these conditions, suggesting that insulin cannot by itself account for the inhibition observed in the refeeding experiments. These data constitute the first demonstration of the inhibition of glucose-6 phosphatase activity during the postprandial period.
- Published
- 1995
36. Global and local music perception in children with Williams syndrome
- Author
-
Deruelle, Christine, primary, Sch??n, Daniele, additional, Rondan, C??cilie, additional, and Mancini, Josette, additional
- Published
- 2005
- Full Text
- View/download PDF
37. An fMRI study of music sight-reading
- Author
-
Sch??n, Daniele, primary, Anton, Jean Luc, additional, Roth, Muriel, additional, and Besson, Mireille, additional
- Published
- 2002
- Full Text
- View/download PDF
38. Outdoor millimetre-wave propagation measurements with line of sight obstructed by natural elements
- Author
-
C. Fort, D. Chagnot, and N. Daniele
- Subjects
Physics ,Line-of-sight ,business.industry ,Wave propagation ,Frequency band ,Cumulative distribution function ,Delay spread ,Radio propagation ,Optics ,Electrical and Electronic Engineering ,Wideband ,business ,Multipath propagation ,Computer Science::Information Theory - Abstract
The authors present wideband measurements of outdoor radio channels operating within a 2 GHz frequency band around a 60 GHz carrier. Statistical analyses such as the RMS delay spread and cumulative distribution function (CDF) of the received signal envelope are presented. Investigations into the multipath effect and data rate limitation are discussed.
- Published
- 1994
- Full Text
- View/download PDF
39. Differential space-time ultra-wideband communications
- Author
-
Jean-Claude Belfiore, Chadi Abou-Rjeily, and N. Daniele
- Subjects
Engineering ,business.industry ,Transmitter ,Rake ,Ultra-wideband ,Keying ,Data_CODINGANDINFORMATIONTHEORY ,Differential phase ,Permutation ,Channel state information ,Electronic engineering ,business ,Computer Science::Information Theory ,Constellation - Abstract
In this paper, we present two space-time schemes for exploiting diversity in multi-antenna impulse radio ultra wide-band (IR-UWB) systems when neither the transmitter nor the receiver has access to channel state information. The first scheme encodes the pulses of the same data symbol by a combination of differential phase shift keying and permutation codes and can be associated with any number of transmit and receive antennas. The second scheme encodes different symbols with two transmit antennas. These schemes are associated with Rake receivers and achieve full spatial and multi-path diversity with no data rate loss for constant-modulus multi-dimensional constellations. Adaptive versions of these schemes are also presented and shown to approach the performance of coherent receivers in stationary indoor channels.
40. A functional mini-GDE transgene corrects impairment in models of glycogen storage disease type III.
- Author
-
Gardin A, Rouillon J, Montalvo-Romeral V, Rossiaud L, Vidal P, Launay R, Vie M, Krimi Benchekroun Y, Cosette J, Bertin B, La Bella T, Dubreuil G, Nozi J, Jauze L, Fragnoud R, Daniele N, Van Wittenberghe L, Esque J, André I, Nissan X, Hoch L, and Ronzitti G
- Subjects
- Humans, Mice, Rats, Animals, Muscle, Skeletal metabolism, Glycogen metabolism, Transgenes, Glycogen Storage Disease Type III genetics, Glycogen Storage Disease Type III therapy, Glycogen Debranching Enzyme System genetics
- Abstract
Glycogen storage disease type III (GSDIII) is a rare inborn error of metabolism affecting liver, skeletal muscle, and heart due to mutations of the AGL gene encoding for the glycogen debranching enzyme (GDE). No curative treatment exists for GSDIII. The 4.6 kb GDE cDNA represents the major technical challenge toward the development of a single recombinant adeno-associated virus-derived (rAAV-derived) vector gene therapy strategy. Using information on GDE structure and molecular modeling, we generated multiple truncated GDEs. Among them, an N-terminal-truncated mutant, ΔNter2-GDE, had a similar efficacy in vivo compared with the full-size enzyme. A rAAV vector expressing ΔNter2-GDE allowed significant glycogen reduction in heart and muscle of Agl-/- mice 3 months after i.v. injection, as well as normalization of histology features and restoration of muscle strength. Similarly, glycogen accumulation and histological features were corrected in a recently generated Agl-/- rat model. Finally, transduction with rAAV vectors encoding ΔNter2-GDE corrected glycogen accumulation in an in vitro human skeletal muscle cellular model of GSDIII. In conclusion, our results demonstrated the ability of a single rAAV vector expressing a functional mini-GDE transgene to correct the muscle and heart phenotype in multiple models of GSDIII, supporting its clinical translation to patients with GSDIII.
- Published
- 2024
- Full Text
- View/download PDF
41. Muscle-specific, liver-detargeted adeno-associated virus gene therapy rescues Pompe phenotype in adult and neonate Gaa -/- mice.
- Author
-
Sellier P, Vidal P, Bertin B, Gicquel E, Bertil-Froidevaux E, Georger C, van Wittenberghe L, Miranda A, Daniele N, Richard I, Gross DA, Mingozzi F, Collaud F, and Ronzitti G
- Subjects
- Mice, Humans, Animals, Infant, Newborn, Genetic Vectors genetics, Mice, Knockout, alpha-Glucosidases genetics, alpha-Glucosidases therapeutic use, Liver metabolism, Muscle, Skeletal pathology, Glycogen metabolism, Genetic Therapy, Phenotype, Dependovirus genetics, Dependovirus metabolism, Glycogen Storage Disease Type II genetics, Glycogen Storage Disease Type II therapy, Glycogen Storage Disease Type II pathology
- Abstract
Pompe disease (PD) is a neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency. Reduced GAA activity leads to pathological glycogen accumulation in cardiac and skeletal muscles responsible for severe heart impairment, respiratory defects, and muscle weakness. Enzyme replacement therapy with recombinant human GAA (rhGAA) is the standard-of-care treatment for PD, however, its efficacy is limited due to poor uptake in muscle and the development of an immune response. Multiple clinical trials are ongoing in PD with adeno-associated virus (AAV) vectors based on liver- and muscle-targeting. Current gene therapy approaches are limited by liver proliferation, poor muscle targeting, and the potential immune response to the hGAA transgene. To generate a treatment tailored to infantile-onset PD, we took advantage of a novel AAV capsid able to increase skeletal muscle targeting compared to AAV9 while reducing liver overload. When combined with a liver-muscle tandem promoter (LiMP), and despite the extensive liver-detargeting, this vector had a limited immune response to the hGAA transgene. This combination of capsid and promoter with improved muscle expression and specificity allowed for glycogen clearance in cardiac and skeletal muscles of Gaa
-/- adult mice. In neonate Gaa-/- , complete rescue of glycogen content and muscle strength was observed 6 months after AAV vector injection. Our work highlights the importance of residual liver expression to control the immune response toward a potentially immunogenic transgene expressed in muscle. In conclusion, the demonstration of the efficacy of a muscle-specific AAV capsid-promoter combination for the full rescue of PD manifestation in both neonate and adult Gaa-/- provides a potential therapeutic avenue for the infantile-onset form of this devastating disease., (© 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)- Published
- 2024
- Full Text
- View/download PDF
42. Co-Administration of Simvastatin Does Not Potentiate the Benefit of Gene Therapy in the mdx Mouse Model for Duchenne Muscular Dystrophy.
- Author
-
Bourg N, Vu Hong A, Lostal W, Jaber A, Guerchet N, Tanniou G, Bordier F, Bertil-Froidevaux E, Georger C, Daniele N, Richard I, and Israeli D
- Subjects
- Animals, Disease Models, Animal, Genetic Therapy methods, Male, Mice, Mice, Inbred mdx, Muscle, Skeletal drug effects, Muscular Dystrophy, Duchenne drug therapy, Muscular Dystrophy, Duchenne therapy, Simvastatin administration & dosage
- Abstract
Duchenne muscular dystrophy (DMD) is the most common and cureless muscle pediatric genetic disease, which is caused by the lack or the drastically reduced expression of dystrophin. Experimental therapeutic approaches for DMD have been mainly focused in recent years on attempts to restore the expression of dystrophin. While significant progress was achieved, the therapeutic benefit of treated patients is still unsatisfactory. Efficiency in gene therapy for DMD is hampered not only by incompletely resolved technical issues, but likely also due to the progressive nature of DMD. It is indeed suspected that some of the secondary pathologies, which are evolving over time in DMD patients, are not fully corrected by the restoration of dystrophin expression. We recently identified perturbations of the mevalonate pathway and of cholesterol metabolism in DMD patients. Taking advantage of the mdx model for DMD, we then demonstrated that some of these perturbations are improved by treatment with the cholesterol-lowering drug, simvastatin. In the present investigation, we tested whether the combination of the restoration of dystrophin expression with simvastatin treatment could have an additive beneficial effect in the mdx model. We confirmed the positive effects of microdystrophin, and of simvastatin, when administrated separately, but detected no additive effect by their combination. Thus, the present study does not support an additive beneficial effect by combining dystrophin restoration with a metabolic normalization by simvastatin.
- Published
- 2022
- Full Text
- View/download PDF
43. Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates.
- Author
-
Costa-Verdera H, Collaud F, Riling CR, Sellier P, Nordin JML, Preston GM, Cagin U, Fabregue J, Barral S, Moya-Nilges M, Krijnse-Locker J, van Wittenberghe L, Daniele N, Gjata B, Cosette J, Abad C, Simon-Sola M, Charles S, Li M, Crosariol M, Antrilli T, Quinn WJ 3rd, Gross DA, Boyer O, Anguela XM, Armour SM, Colella P, Ronzitti G, and Mingozzi F
- Subjects
- Animals, Autophagy, Enzyme Replacement Therapy, Female, Glycogen Storage Disease Type II therapy, Liver enzymology, Male, Mice, alpha-Glucosidases genetics, Glycogen Storage Disease Type II enzymology, alpha-Glucosidases metabolism
- Abstract
Pompe disease (PD) is a severe neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). PD is currently treated with enzyme replacement therapy (ERT) with intravenous infusions of recombinant human GAA (rhGAA). Although the introduction of ERT represents a breakthrough in the management of PD, the approach suffers from several shortcomings. Here, we developed a mouse model of PD to compare the efficacy of hepatic gene transfer with adeno-associated virus (AAV) vectors expressing secretable GAA with long-term ERT. Liver expression of GAA results in enhanced pharmacokinetics and uptake of the enzyme in peripheral tissues compared to ERT. Combination of gene transfer with pharmacological chaperones boosts GAA bioavailability, resulting in improved rescue of the PD phenotype. Scale-up of hepatic gene transfer to non-human primates also successfully results in enzyme secretion in blood and uptake in key target tissues, supporting the ongoing clinical translation of the approach., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
44. The authors reply.
- Author
-
Santoro F, Núñez-Gil IJ, and Daniele Brunetti N
- Abstract
Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.
- Published
- 2021
- Full Text
- View/download PDF
45. Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back.
- Author
-
Buscara L, Gross DA, and Daniele N
- Abstract
Neuromuscular disorders are a large group of rare pathologies characterised by skeletal muscle atrophy and weakness, with the common involvement of respiratory and/or cardiac muscles. These diseases lead to life-long motor deficiencies and specific organ failures, and are, in their worst-case scenarios, life threatening. Amongst other causes, they can be genetically inherited through mutations in more than 500 different genes. In the last 20 years, specific pharmacological treatments have been approved for human usage. However, these "à-la-carte" therapies cover only a very small portion of the clinical needs and are often partially efficient in alleviating the symptoms of the disease, even less so in curing it. Recombinant adeno-associated virus vector-mediated gene transfer is a more general strategy that could be adapted for a large majority of these diseases and has proved very efficient in rescuing the symptoms in many neuropathological animal models. On this solid ground, several clinical trials are currently being conducted with the whole-body delivery of the therapeutic vectors. This review recapitulates the state-of-the-art tools for neuron and muscle-targeted gene therapy, and summarises the main findings of the spinal muscular atrophy (SMA), Duchenne muscular dystrophy (DMD) and X-linked myotubular myopathy (XLMTM) trials. Despite promising efficacy results, serious adverse events of various severities were observed in these trials. Possible leads for second-generation products are also discussed.
- Published
- 2020
- Full Text
- View/download PDF
46. Chronic thromboembolic pulmonary hypertension mimicking coronary artery disease.
- Author
-
Correale M, Fortunato M, Magnesa M, Varricchione G, Campanale G, Gravina M, Di Biase M, and Daniele Brunetti N
- Abstract
We report the case of 63-year-old man, complaining of dyspnea and with abnormal systolic motion of the interventricular septum at echocardiography, referred for coronary angiography and suspect coronary artery disease. In the presence of normal coronary angio, a specific work-up showed chronic thromboembolic pulmonary hypertension requiring pulmonary endarterectomy. The case highlights the need for a global cardiovascular and imaging approach in presence of poorly specific symptoms and signs of coronary artery disease., (© The Author(s) 2020.)
- Published
- 2020
- Full Text
- View/download PDF
47. Gene therapy with secreted acid alpha-glucosidase rescues Pompe disease in a novel mouse model with early-onset spinal cord and respiratory defects.
- Author
-
Colella P, Sellier P, Gomez MJ, Biferi MG, Tanniou G, Guerchet N, Cohen-Tannoudji M, Moya-Nilges M, van Wittenberghe L, Daniele N, Gjata B, Krijnse-Locker J, Collaud F, Simon-Sola M, Charles S, Cagin U, and Mingozzi F
- Subjects
- Alleles, Animals, Dependovirus genetics, Disease Models, Animal, Gene Expression, Gene Transfer Techniques, Genetic Vectors administration & dosage, Genetic Vectors genetics, Glycogen metabolism, Glycogen Storage Disease Type II diagnosis, Homozygote, Immunohistochemistry, Male, Mice, Mice, Knockout, Motor Neurons metabolism, Muscle Strength genetics, Muscle, Skeletal, Prognosis, Spinal Cord physiopathology, Transduction, Genetic, Treatment Outcome, alpha-Glucosidases metabolism, Genetic Therapy methods, Glycogen Storage Disease Type II genetics, Glycogen Storage Disease Type II therapy, Phenotype, Spinal Cord metabolism, alpha-Glucosidases genetics
- Abstract
Background: Pompe disease (PD) is a neuromuscular disorder caused by deficiency of acidalpha-glucosidase (GAA), leading to motor and respiratory dysfunctions. Available Gaa knock-out (KO) mouse models do not accurately mimic PD, particularly its highly impaired respiratory phenotype., Methods: Here we developed a new mouse model of PD crossing Gaa KO
B6;129 with DBA2/J mice. We subsequently treated Gaa KODBA2/J mice with adeno-associated virus (AAV) vectors expressing a secretable form of GAA (secGAA)., Findings: Male Gaa KODBA2/J mice present most of the key features of the human disease, including early lethality, severe respiratory impairment, cardiac hypertrophy and muscle weakness. Transcriptome analyses of Gaa KODBA2/J , compared to the parental Gaa KOB6;129 mice, revealed a profoundly impaired gene signature in the spinal cord and a similarly deregulated gene expression in skeletal muscle. Muscle and spinal cord transcriptome changes, biochemical defects, respiratory and muscle function in the Gaa KODBA2/J model were significantly improved upon gene therapy with AAV vectors expressing secGAA., Interpretation: These data show that the genetic background impacts on the severity of respiratory function and neuroglial spinal cord defects in the Gaa KO mouse model of PD. Our findings have implications for PD prognosis and treatment, show novel molecular pathophysiology mechanisms of the disease and provide a unique model to study PD respiratory defects, which majorly affect patients., Funding: This work was supported by Genethon, the French Muscular Dystrophy Association (AFM), the European Commission (grant nos. 667751, 617432, and 797144), and Spark Therapeutics., Competing Interests: Declaration of Competing Interest P.C. and F.M. are inventors in patent applications describing the secGAA technology and concerning the treatment of Pompe disease by AAV licensed to Spark Therapeutics (F.M.: WO2018046774, WO2018046775; P.C: WO2018046775). P.C and F.M. are inventors in a patent application describing the use of tandem promoters (WO2019154939A1). F.M. is employee and equity holder of Spark Therapeutics, Inc., a Roche company. U.C. received salary from the Marie Skłodowska-Curie Actions Individual Fellowship (MSCA-IF) grant agreement no. 797144. All other authors declare no conflict of interest. This work was partially supported by Spark Therapeutics under a sponsored research agreement (to Genethon)., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
48. Rescue of Advanced Pompe Disease in Mice with Hepatic Expression of Secretable Acid α-Glucosidase.
- Author
-
Cagin U, Puzzo F, Gomez MJ, Moya-Nilges M, Sellier P, Abad C, Van Wittenberghe L, Daniele N, Guerchet N, Gjata B, Collaud F, Charles S, Sola MS, Boyer O, Krijnse-Locker J, Ronzitti G, Colella P, and Mingozzi F
- Subjects
- Animals, Dependovirus genetics, Disease Models, Animal, Genetic Vectors administration & dosage, Glycogen metabolism, Glycogen Storage Disease Type II genetics, Lysosomes metabolism, Male, Mice, Mice, Knockout, Muscle, Skeletal metabolism, Phenotype, Signal Transduction genetics, Transcriptome, Treatment Outcome, alpha-Glucosidases genetics, Genetic Therapy methods, Glycogen Storage Disease Type II metabolism, Glycogen Storage Disease Type II therapy, Liver metabolism, Secretory Pathway genetics, Transfection methods, alpha-Glucosidases metabolism
- Abstract
Pompe disease is a neuromuscular disorder caused by disease-associated variants in the gene encoding for the lysosomal enzyme acid α-glucosidase (GAA), which converts lysosomal glycogen to glucose. We previously reported full rescue of Pompe disease in symptomatic 4-month-old Gaa knockout (Gaa
-/- ) mice by adeno-associated virus (AAV) vector-mediated liver gene transfer of an engineered secretable form of GAA (secGAA). Here, we showed that hepatic expression of secGAA rescues the phenotype of 4-month-old Gaa-/- mice at vector doses at which the native form of GAA has little to no therapeutic effect. Based on these results, we then treated severely affected 9-month-old Gaa-/- mice with an AAV vector expressing secGAA and followed the animals for 9 months thereafter. AAV-treated Gaa-/- mice showed complete reversal of the Pompe phenotype, with rescue of glycogen accumulation in most tissues, including the central nervous system, and normalization of muscle strength. Transcriptomic profiling of skeletal muscle showed rescue of most altered pathways, including those involved in mitochondrial defects, a finding supported by structural and biochemical analyses, which also showed restoration of lysosomal function. Together, these results provide insight into the reversibility of advanced Pompe disease in the Gaa-/- mouse model via liver gene transfer of secGAA., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
49. [The biological resources and molecule archives organization: turn a need into an opportunity for the Smart Specialization Strategy of the Lazio region.]
- Author
-
Bravo E, Franchin T, Santoro F, Conti L, Carrara S, Marino M, Di Caro A, Cigliana G, Mandoj C, Baselice S, Daniele N, Giampaoli S, Quintarelli C, Salerno M, Zinno F, Russo G, Errico MC, Minghetti L, Ricciardi W, and Napolitano M
- Subjects
- Biological Specimen Banks standards, Biomedical Research standards, Biotechnology standards, Humans, Italy, Specimen Handling standards, Biological Specimen Banks organization & administration, Biomedical Research organization & administration, Biotechnology organization & administration
- Abstract
Smart Specialization Strategy (S3) of Lazio defines smart specialization strategies to bring out the excellence of the territory with prospects of success on the global market. Chemical-pharmaceutical, biomedical and biotechnological field is one of the 7 sectors considered of greatest interest for the S3. Key engine of biotechnology development are biological materials and associated data, stored in biobanks. However, to ensure that the research and product development carried out with that resources gives statistically significant and reproducible results, it is essential that they are collected, manipulated and stored using standardized and traced methods. Implementation of the recent published standard ISO 20387- "Biotechnology-Biobanking-General requirements for biobanking" is bridging biobanks toward to storage and distribution of qualified biological material only. Human biobanks are also an essential part of the assistance and care of the citizen and constitute an unavoidable cost of the regional health system. However, biobanks organization, rationalization of their territorial distribution, completion of the process of recognition and regional accreditation, parallel to the implementation of the offer of remunerated services for biobanking, can turn the cost of the necessary preservation of the samples, into an opportunity of territorial development. The paper describes the necessity, shared by a working group represented by several Lazio biobanks, of including biobank activities in the virtuous circle designed by the S3,concretizing the framework prefigured by the S3 document on infrastructures for research, innovation and technology transfer. To allow inclusion of biobank activities in the virtuous circle, we underline the need to quickly start the process of recognition of the territorial research biobanks, to implement at regional level the process of optimization and rationalization of the management of biological samples, in accordance with the international harmonization standards and with the territorial indications of sustainability.
- Published
- 2019
- Full Text
- View/download PDF
50. AAV Gene Transfer with Tandem Promoter Design Prevents Anti-transgene Immunity and Provides Persistent Efficacy in Neonate Pompe Mice.
- Author
-
Colella P, Sellier P, Costa Verdera H, Puzzo F, van Wittenberghe L, Guerchet N, Daniele N, Gjata B, Marmier S, Charles S, Simon Sola M, Ragone I, Leborgne C, Collaud F, and Mingozzi F
- Abstract
Hepatocyte-restricted, AAV-mediated gene transfer is being used to provide sustained, tolerogenic transgene expression in gene therapy. However, given the episomal status of the AAV genome, this approach cannot be applied to pediatric disorders when hepatocyte proliferation may result in significant loss of therapeutic efficacy over time. In addition, many multi-systemic diseases require widespread expression of the therapeutic transgene that, when provided with ubiquitous or tissue-specific non-hepatic promoters, often results in anti-transgene immunity. Here we have developed tandem promoter monocistronic expression cassettes that, packaged in a single AAV, provide combined hepatic and extra-hepatic tissue-specific transgene expression and prevent anti-transgene immunity. We validated our approach in infantile Pompe disease, a prototype disease caused by lack of the ubiquitous enzyme acid-alpha-glucosidase (GAA), presenting multi-systemic manifestations and detrimental anti-GAA immunity. We showed that the use of efficient tandem promoters prevents immune responses to GAA following systemic AAV gene transfer in immunocompetent Gaa-/- mice. Then we demonstrated that neonatal gene therapy with either AAV8 or AAV9 in Gaa-/- mice resulted in persistent therapeutic efficacy when using a tandem liver-muscle promoter (LiMP) that provided high and persistent transgene expression in non-dividing extra-hepatic tissues. In conclusion, the tandem promoter design overcomes important limitations of AAV-mediated gene transfer and can be beneficial when treating pediatric conditions requiring persistent multi-systemic transgene expression and prevention of anti-transgene immunity.
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.