This book enables scientists to tackle the fundamental issues of chemical change in the archaeological materials, in order to advance the study of the past.
Central release of vasopressin (VP) by the magnocellular neuroendocrine cells (MNCs) responsible for systemic VP release is believed to be important in modulating the activity of these neurons during ...dehydration. Central VP release from MNC somata and dendrites is stimulated by both dehydration and pituitary adenylate cyclase activating polypeptide (PACAP). Although PACAP is expressed in MNCs, its potential role in the magnocellular response to dehydration is unexplored. The current study demonstrates that prolonged dehydration increases immunoreactivity for PACAP-27, PACAP-38, and the type I PACAP receptor in the supraoptic nucleus (SON) of the rat. In addition, PACAP stimulates local VP release in the euhydrated rat SON in vitro, and this effect is reduced by the PACAP receptor antagonist PAC6–27 (100 nm), suggesting the participation of PACAP receptors. Concomitant with its effects on local VP release, PACAP also reduces basal glutamate and aspartate release in the euhydrated rat SON. Furthermore, somatodendritic VP release elicited by acute dehydration is blocked by PAC6–27, suggesting that endogenous PACAP participates in this response. Consistent with this, RIA revealed that local PACAP-38 release within the SON is significantly elevated during acute dehydration. These results suggest that prolonged activation of hypothalamic MNCs is accompanied by up-regulation of PACAP and the type I PACAP receptor in these cells and that somatodendritic VP release in response to acute dehydration is mediated by activation of PACAP receptors by endogenous PACAP released within the SON. A potential role for PACAP in promoting efficient, but not exhaustive, systemic release of VP from MNCs during physiological challenge is discussed.
The development of interferon-free regimens for the treatment of chronic HCV infection constitutes a preferred option that is expected in the future to provide patients with improved efficacy, better ...tolerability, and reduced risk for emergence of drug-resistant virus. We have pursued non-nucleoside NS5B polymerase allosteric inhibitors as combination partners with other direct acting antivirals (DAAs) having a complementary mechanism of action. Herein, we describe the discovery of a potent follow-up compound (BI 207524, 27) to the first thumb pocket 1 NS5B inhibitor to demonstrate antiviral activity in genotype 1 HCV infected patients, BILB 1941 (1). Cell-based replicon potency was significantly improved through electronic modulation of the pK a of the carboxylic acid function of the lead molecule. Subsequent ADME-PK optimization lead to 27, a predicted low clearance compound in man. The preclinical profile of inhibitor 27 is discussed, as well as the identification of a genotoxic metabolite that led to the discontinuation of the development of this compound.
An explicit analysis of the retrodirective mechanism of a flattened dihedral using periodic arrays is proposed. Once flattened, a corner dihedral requires a phasing mechanism to restore its ...retrodirective behaviour. This can be achieved by equipping each of the panels with passive phase-shifting cells that obey a global retrodirective phase law. The challenge is to have a trade-off between two steering mechanisms on each side such that this global phase law is achieved. In this work, an analytical study of the reflection phenomenon between the two panels is presented and sufficient information are provided to predict the retrodirective performance affected by the dihedral geometrical configuration itself. The analytical formulation of the global phase law is thus defined along with other complementary formulations to provide a better understanding of the reflection phenomenon involved. Based on these analysis and comprehension, guidelines are suggested in terms of the cell design and the dihedral geometrical configuration so that to efficiently engineer the retrodirective profile of the dihedral. A simple method utilizing these guidelines is proposed to enhance the flattened dihedral performances. And an experimental validation of this design is finally proposed at 24 GHz.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Anoperianal lesions affect up to 30% of patients with Crohn’s disease (CD). Long-term fistula healing is challenging with conventional biotherapies. Although recent studies ...demonstrated the efficacy of local injections of adipose tissue-derived stem cells with 50 % of fistulae closure without abscess at one year, this treatment is not available in routine.
The primary aim of this study was to evaluate the safety and the feasibility of the injection of bone marrow-derived mesenchymal stem cells isolated and prepared in a local university laboratory of cell therapy for perianal fistulizing CD. The second aim was to evaluate the efficacy of this treatment and his impact on the quality of life of the patients.
Methods
A prospective observational study was performed in the CHU of Liège from October 2019 till October 2021. All CD patients with perianal fistula and seton placement for at least 6 months were eligible. PRO, clinical examination, CRP, fecal calprotectine, CDAI, Short health scale (SHS) and MRI were performed at weeks 0, 12 and 48. PDAI was calculated at inclusion and at Week 48. Efficacy was defined as closure of all treated external openings at clinical examination without abscess at MRI.
Results
Sixteen patients with a median age of 49 years old and a median duration of perianal CD of 8 years were included. Eleven (69%) patients were on anti-TNF. CDAI and PDAI at inclusion were 97,5 ± 48,8 et 5 ± 4,4 respectively. Four (25%) patients reported adverse events the week after the injection (local pain 3/16, mild bleeding 1/16), all of them quickly resolutive. Ten (63%) and 8 (50%) patients had a closure of all the external opening at week 12 and 48 respectively. Five out of 6 patients with 2 external openings had at least 1 opening closed at Week 48. One abscess was observed during the follow-up. The median PDAI was numerically lower at the end of the study (3 versus 5 at the inclusion). The quality of life improved with a regression of the SHS from 10 to 7.5 at the end of the follow-up. At MRI, MAGNIFI-CD score and Van Assche index were similar for each patients at the inclusion and at the end of the study.
Conclusion
Injection of locally prepared bone marrow-derived mesenchymal stem cells seems safe and effective in refractory perianal fistulae in Crohn’s disease with 50% of closure at 1 year. The treatment is associated with an improvement of the perianal activity scores and the quality of life scores but not with the MRI scores.
A new design of circularly polarised slot fed dielectric resonator antenna (DRA) is presented. The dissymmetry of the design enabling circular polarisation relies on a metallic strip printed on top ...of the resonator. Simulations are compared with measurements for a single antenna as well as a four DRA sequential rotation array.
In this letter, the new Multistructure fast computation technique based on the Method of Moments (MSMoM) is combined with a genetic algorithm (GA). The MSMoM/GA optimizer is applied to the bandwidth ...and axial ratio optimization of an antenna fed by electromagnetic coupling with a microstrip-line. Computation time is greatly reduced as compared to the direct MoM/GA implementation
This letter investigates the potential of additive manufacturing for the fabrication of complex antenna geometries with enhanced performance at K-band. Stereolithography is here used to ...three-dimensionally (3D) print a novel topology of dual-polarized leaky-wave antenna that allows for the control of its aperture illumination both in phase and magnitude. The antenna consists of a modulated triple-ridge square waveguide perforated on its top wall with crossed slots of different sizes. An orthomode-transducer is integrated within the structure for dual-mode operation. Monolithic implementation of this compound 3D structure is only possible thanks to additive manufacturing. In addition, low weight and compactness are attained compared to classical milling. The present proposal is validated through the manufacturing of a low-sidelobe-levels prototype suitable for intersatellite links. The corresponding measured results are in a very good agreement with full-wave predictions.
PDF
