Mutations in genes encoding the laminin-5 heterotrimer, a key component of the epidermal-dermal junction, cause junctional epidermolysis bullosa (JEB), a severe and often fatal skin adhesion defect. ...Epidermal stem cells isolated from patients affected by β3 chain-deficient JEB were transduced with a retroviral vector expressing a β3 cDNA, and used to generate uniformly transduced cultured skin implants. The transgene was steadily expressed for >160 cell doublings in culture, leading to restoration of normal laminin 5 levels, assembly of functional hemidesmosomes, and full phenotypic correction. Cloning and sequencing of vector integrations showed that <20 stem cells are responsible for long-term maintenance of a transplantable skin culture. A phase-I clinical trial started in October 2005, aimed at proving the safety of the transduction/transplantation procedure, and analyzing persistence of transgene expression and long-term survival of transduced stem cells. The first patient was a 30-yr-old male affected by non-lethal JEB, carrying a null mutation in one LAMB3 allele and a point mutation (E212K) in the other one. The mutation affects the assembly of the laminin-5 heterotrimer, present at residual levels (<5%) in vitro and in vivo. Six genetically modified, cultured epidermal sheets of 100 sq cm were transplanted on both legs after removal of the outer skin layer using a minimally invasive technique. The procedure was well tolerated, and the patient discharged after five days. Engraftment was completed after 10 days, and transplanted skin remained stable on both legs in the absence of blistering or inflammation for the duration of the follow-up (4 months at the time of writing). 3-mm punch biopsies were taken 1 and 3 months after transplantation, and analyzed for vector presence by quantitative PCR and for protein expression by immunohistochemistry. A vector signal compatible with full transduction of the transplanted epidermis was observed at both time points. Synthesis and assembly of normal levels of heterotrimeric laminin-5 and α6β4 integrin was observed at the level of the basal lamina in all biopsies, together with the development of a firmly adherent, fully differentiated epidermis. Epidermal stem cells (p64 + ) were detected in the basal layer of the transplanted skin in normal numbers. These data show that gene therapy of JEB by transplantation of genetically corrected stem cells is feasible, and leads to full phenotypic correction of the adhesion defect in vivo. Safety studies are under way, which include detection or humoral or cytotoxic immune responses against laminin-5, and ex vivo cloning and sequencing of the integrated proviruses.
This paper presents a practical application of an opportunistic technique for the estimation of rainfall intensity and accumulated precipitation. The proposed technique is based upon signal strength ...measurements made by commercial-grade interactive satellite terminals. By applying some processing, the rain-induced attenuation on the microwave downlink from the satellite is first evaluated; then the rain attenuation is eventually mapped into a rainfall rate estimate via a tropospheric model. This methodology has been applied to a test area of 30 ×30 km 2 around the city of Dortmund (North Rhine-Westphalia, upper basin of Ermscher river), for the heavy rain event that devastated western Germany in July, 2021. A rainfall map on this area is obtained from the measurements collected by a set of satellite terminals deployed in the region, and successfully compared with a map obtained with a conventional weather radar.
Pathogenetic mechanisms of atopic dermatitis Pastore, S; Mascia, F; Giustizieri, M L ...
Archivum Immunologiae et Therapiae Experimentalis,
2000, Volume:
48, Issue:
6
Journal Article
Peer reviewed
Atopic dermatitis (AD) is a chronic inflammatory disease which results from complex interactions between genetic and environmental mechanisms. An altered lipid composition of the stratum corneum is ...responsible for the xerotic aspect of the skin and determines a higher permeability to allergens and irritants. Keratinocytes of AD patients exhibit a propensity to an exaggerated production of cytokines and chemokines, a phenomenon that can have a major role in promoting and maintaining inflammation. Specific immune responses against a variety of environmental allergens are also implicated in AD pathogenesis, with a bias towards Th2 immune responses. In particular, dendritic cells expressing membrane IgE receptors play a critical role in the amplification of allergen-specific T cell responses. Cross-linkage of specific IgE receptors on dermal mast cells provokes the release and synthesis of a vast series of mediators. Following their recruitment and activation into the skin, eosinophils are also thought to contribute relevantly to tissue damage. Thus, a complex network of cytokines and chemokines contributes to establishing a local milieu that favors the permanence of inflammation in AD skin.
In this paper, we first rely on small area techniques to derive from EU-SILC survey new indicators of compensatory and investment policies at regional level. While compensatory policies have mainly ...the goal of protecting individuals from “old” risks (e.g. old-age), investment-related social policies tend to focus more on "new social risks" (i.e. skill deficits). We rely on these new indicators to perform a data-driven SVAR analysis to investigate the casual relationships between youth labour market outcomes and these two types of spending. Our results support the view that investment policies are more effective for tackling new social challenges.
Ahstract- In the NEFOCAST project we aim at estimating rainfall by the opportunistic use of the signal attenuation due to the propagation channel in satellite communications. The estimation is ...performed by reverse engineering the effects of the various propagation phenomena on the satellite signal. However, the accuracy of the estimation is affected by several factors: in first place the rapid fluctuations in signal amplitude caused by small-scale irregularities in the tropospheric refractive index; secondly, the perturbations of the orbit of GEO satellites, such as the gravitational effects of the moon and the sun, which, even if periodically counteracted by correction maneuvers, nevertheless cause residual orbit inclinations. The problem with all these factors is that they can cause large deviations in the clear-sky measurements that can be misinterpreted as rain events. In this paper we address these problems by employing two Kalman filters designed to track slow and fast changes of the received signal energy, so that the rain events can be reliably estimated.
In the cuprates, the opening of a d-wave superconducting (SC) gap is accompanied by a redistribution of spectral weight at energies two orders of magnitude larger than this gap. This indicates the ...importance to the pairing mechanism of on-site electronic excitations, such as orbital transitions or charge transfer excitations. Here, we resort to a three-pulse pump-probe scheme to study the broadband non-equilibrium dielectric function in optimally-doped \(Bi_2Sr_2Ca_{0.92}Y_{0.08}Cu_2O_{8+{\delta}}\) and we identify two distinct dynamical responses: i) a blueshift of the central energy of an interband excitation peaked at 2 eV and ii) a change in spectral weight in the same energy range. Photoexcitation with near-IR and mid-IR pulses, with photon energies respectively above and below the SC gap, reveals that the transient changes in the central energy are not modified by the onset of superconductivity and do not depend on the pump photon energy. Conversely, the spectral weight dynamics strongly depends on the pump photon energy and has a discontinuity at the critical temperature. The picture that emerges is that, while high-energy pulses excite quasiparticles in both nodal and thermally inaccessible antinodal states, photoexcitation by low-energy pulses mostly accelerates the condensate and creates excitations predominantly at the nodes of the SC gap. These results, rationalized by kinetic equations for d-wave superconducting gaps, indicate that dynamical control of the momentum-dependent distribution of non-thermal quasiparticles may be achieved by the selective tuning of the photoexcitation.
An immediate tooth replantation is the treatment of choice following avulsion, although it may not always be possible. The therapeutic approach is more complicated in patients that are still growing, ...as it must not interfere with normal cranial-facial growth processes. This case report
evaluates the effectiveness of implant-prosthesis rehabilitation in a growing patient using mini-implants, following a failed post-avulsion tooth replantation. The accurate pre-surgical evaluation employed in this protocol, including the growth expectation assessment, made it possible to place
the mini implants without interfering with subsequent sagittal and transversal growth of the maxillary bones. Two years of follow-up in the present case allowed us to confirm that this protocol resulted in a fast rehabilitation of the frontal section, with immediate aesthetic and functional
success and patient's satisfaction.
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