796 research outputs found

    De-excitation spectroscopy of strongly interacting Rydberg gases

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    We present experimental results on the controlled de-excitation of Rydberg states in a cold gas of Rb atoms. The effect of the van der Waals interactions between the Rydberg atoms is clearly seen in the de-excitation spectrum and dynamics. Our observations are confirmed by numerical simulations. In particular, for off-resonant (facilitated) excitation we find that the de-excitation spectrum reflects the spatial arrangement of the atoms in the quasi one-dimensional geometry of our experiment. We discuss future applications of this technique and implications for detection and controlled dissipation schemes.Comment: 6 pages, 5 figure

    Mice with cardiac-restricted angiotensin-converting enzyme (ACE) have atrial enlargement, cardiac arrhythmia, and sudden death

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    Journal ArticleTo investigate the local effects of angiotensin II on the heart, we created a mouse model with 100-fold normal cardiac angiotensin-converting enzyme (ACE), but no ACE expression in kidney or vascular endothelium. This was achieved by placing the endogenous ACE gene under the control of the α-myosin heavy chain promoter using targeted homologous recombination. These mice, called ACE 8/8, have cardiac angiotensin II levels that are 4.3-fold those of wild-type mice. Despite near normal blood pressure and a normal renal function, ACE 8/8 mice have a high incidence of sudden death. Both histological analysis and in vivo catheterization of the heart showed normal ventricular size and function. In contrast, both the left and right atria were three times normal size. ECG analysis showed atrial fibrillation and cardiac block. In conclusion, increased local production of angiotensin II in the heart is not sufficient to induce ventricular hypertrophy or fibrosis. Instead, it leads to atrial morphological changes, cardiac arrhythmia, and sudden death

    Targeted disruption of the even-skipped gene, evx1, causes early postimplantation lethality of the mouse conceptus.

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    Journal ArticleImplantation within the mammalian uterus elicits dramatic changes in the growth, differentiation, and morphogenesis of the conceptus. This process is interrupted in mice carrying a targeted disruption of the murine evx1 gene, a homolog of the Drosophila even-skipped (eve) gene. Upon implantation, presumptive evx1- homozygotes elicit a decidual response, invade the uterine epithelium, and attach to the basement membrane between uterine stroma and epithelium, but fail to differentiate extraembryonic tissues or to form egg cylinders prior to resorption. Retrograde analysis of embryo genotypes demonstrates that homozygotes could be isolated as free-floating blastocysts but not as gastrulating egg cylinders. Homozygous mutant blastocysts appeared normal and, when grown in vitro, attach, proliferate, and form trophoblastic giant cells surrounding a growing inner cell mass before rapidly degenerating. In situ hybridization analysis demonstrates evx1 gene expression within the visceral endoderm after implantation and prior to gastrulation, at a time in which the mutant phenotype is first detected

    Altered enzymes in drug-resistant variants of mammalian tissue culture cells.

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    Journal ArticleTwo selective procedures are compared in an effort to isolate variants of mouse L cells containing structural gene mutations. Among the resulting variant cloned cell lines are found two types of alterations in theenzyme hypoxanthine phosphoribosyl transferase (EC 2.4.2.8.) (1): enzyme with altered kinetic constants causing in vivo and in vitro resistance to 8-azaguanine; and (enzyme with altered heat sensitivity in vitro. These results support the view that tissue culture cell variantscan arise from structural gene mutations

    Epoxy/ graphene nanocomposites – processing and properties: a review

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    Graphene has recently attracted significant academic and industrial interest because of its excellent performance in mechanical, electrical and thermal applications. Graphene can significantly improve physical properties of epoxy at extremely small loading when incorporated appropriately. Herein, the structure, preparation and properties of epoxy/graphene nanocomposites are reviewed in general, along with detailed examples drawn from the key scientific literature. The modification of graphene and the utilization of these materials in the fabrication of nanocomposites with different processing methods have been explored. This review has been focused on the processing methods and mechanical, electrical, thermal, and fire retardant properties of the nanocomposites. The synergic effects of graphene and other fillers in epoxy matrix have been summarised as well

    Lignin nanoparticles as sustainable photoprotective carriers for sunscreen filters

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    Sunscreen filters may be degraded after prolonged UV exposure with loss of their shielding property and generation of harmful radical species. They are contained in cosmetic formulations in high concentrations, so the improvement of photostability is of relevance for safety concerns. We report here that lignin nanoparticles are sustainable carriers and photostabilizers of two common UV chemical filters, namely, avobenzone and octyl methoxycinnamate. These compounds have been encapsulated by nanoprecipitation into kraft lignin nanoparticles using eco-certified dimethyl isosorbide as a primary solvent and deionized water as an antisolvent. After the encapsulation, both compounds significantly prolonged the half-life stability against UV irradiation. The stabilizing properties of lignin nanoparticles were further improved by coencapsulation of avobenzone and octyl methoxycinnamate with hydroxytyrosol, a natural phenol with antioxidant activity recovered from olive oil wastes and characterized by skin regenerative properties

    Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation-assay based diagnostic kit

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    Pseudotype viruses (PVs) are chimeric, replication-deficient virions that mimic wild-type virus entry mechanisms and can be safely employed in neutralisation assays, bypassing the need for high biosafety requirements and performing comparably to established serological assays. However, PV supernatant necessitates -80°C long-term storage and cold-chain maintenance during transport, which limits the scope of dissemination and application throughout resource-limited laboratories. We therefore investigated the effects of lyophilisation on influenza, rabies and Marburg PV stability, with a view to developing a pseudotype virus neutralisation assay (PVNA) based kit suitable for affordable global distribution. Infectivity of each PV was calculated after lyophilisation and immediate reconstitution, as well as subsequent to incubation of freeze-dried pellets at varying temperatures, humidities and timepoints. Integrity of glycoprotein structure following treatment was also assessed by employing lyophilised PVs in downstream PVNAs. In the presence of 0.5M sucrose-PBS cryoprotectant, each freeze-dried pseudotype was stably stored for 4 weeks at up to 37°C and could be neutralised to the same potency as unlyophilised PVs when employed in PVNAs. These results confirm the viability of a freeze-dried PVNA-based kit, which could significantly facilitate low-cost serology for a wide portfolio of emerging infectious viruses

    Treatment strategy introducing immunosuppressive drugs with glucocorticoids ab initio or very early in giant cell arteritis: A multicenter retrospective controlled study

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    Objective: Glucocorticoids (GC) are associated with side effects in giant cell arteritis (GCA). Immunosuppressive therapies (ITs) have given conflicting results in GCA, regarding GC sparing effect. Primary endpoint is to evaluate whether very early introduction of ITs in GCA minimize the rate of GC-induced adverse events, in terms of infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures. Methods: A multicenter retrospective case-control study included 165 patients. One group included 114 patients who were treated with at least one IT given at diagnosis or within 3 months from the start of GC. A second group included 51 GCA who received only GC or an IT more than 3 months later. Results: The most frequently used ITs were: methotrexate (138 patients), cyclophosphamide (48 patients) and tocilizumab (27 patients). No difference was observed as concerns the follow-up time between groups [48.5 (IQR 26\u201372) vs 40 (IQR 24\u201369), p \u200b= \u200b0.3)]. The first group showed a significantly lower incidence of steroid-induced diabetes (8/114, 7% vs 12/51, 23.5%; p \u200b= \u200b0.003) and no differences for the rate of infections (p \u200b= \u200b0.64). The group was also exposed to lower doses of GC at first (p \u200b< \u200b0.0001) and third (p \u200b< \u200b0.0001, rank-sum test) month. Forty-four patients in the first group (38.6%) compared with 34 in the second one (66.7%) experienced at least one relapse (p \u200b= \u200b0.001). Conclusion: Very early introduction of IT in GCA lowered the incidence of steroid-induced diabetes, possibly due to the lower doses of GC in the first three months. Relapse rate was even lower

    FRI0216 STEROID SPARING EFFECT, LOWER INCIDENCE OF DISEASE RELAPSE AND DIABETES IN GIANT CELL ARTERITIS TREATED WITH IMMUNOSUPPRESSORS AB INITIO OR VERY EARLY: A MULTICENTER RETROSPECTIVE CASE-CONTROL STUDY

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    Background:Glucocorticoids (GC) are associated with serious side effects in giant cell arteritis (GCA). Immunosuppressive therapies (IT) gave conflicting results in GCA, regarding GC sparing effect. Recently, tocilizumab by blocking IL-6, has been licensed as first biologic treatment for GCA, being clinically effective and saving GC (1).Objectives:To evaluate the usefulness of IT for GCA in: 1) minimizing the rate of GC-induced adverse events (AEs) and 2) reducing the risk of relapse.Methods:A multicenter retrospective case-control study included 165 GCA was performed. The first group of patients (GCA-IT) included 114 patients who were treated with at least one IT given ab initio or within 3 months from the start of GC. The control group included 51 GCA who received only GC or an IT later than 3 months (GCA-steroid). The primary endpoints were the rate of GC-related side effects: infections, hospitalized infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures.Results:Methotrexate up to 20 mg/week (138 patients), followed by cyclophosphamide (48 patients) and tocilizumab (27 patients) were the most frequently used IT. No difference was observed as concerns the follow-up time between the two groups [48.5 (IQR 26-72) vs 40 (IQR 24-69), p=0,3, rank-sum test)]. The two groups were similar as concerns sex (p=0,13), while the first group (69±8 yrs) was slightly younger than the second one (72±7 yrs) (p=0,005). Comorbidity was similar between groups. Patients in the GCA-IT group showed a significant lower incidence of GC-induced diabetes (8/114, 7% vs 12/51, 23,5%; p=0,003, chi-square test), while no differences were documented for rate of infections (p=0,64), including hospitalized infections (p=0,44), new onset systemic arterial hypertension (p=0,68), or osteoporotic fractures (p=0,32). Forty-four patients in the GCA-IT group (38,6%), while 34 patients in the GCA-steroid group (66,7%) experienced at least one relapse (p=0,001, chi square test). There was no difference in terms of time to first relapse between the two groups (p=0,53, log-rank test). GCA-IT group was exposed to lower dose of GC at first (p<0,0001, rank-sum test) and third (p<0,0001, rank-sum test) month, while no differences were recorded at the other time points. Clinical outcomes were similar between the two groups.Conclusion:Very early introduction of IT in GCA provided a greater steroid sparing in the first 3 months of treatment, leading to a lower incidence of diabetes. Relapse rate was even lower. IT was usually well tolerated without an increase incidence of infections. A randomized prospective trial is required to support this strategy in the management of GCA.References:[1]Hellmich B, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79:19-30.Disclosure of Interests:Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Miriam Isola: None declared, Dario Bruno: None declared, Elena Treppo: None declared, Laura Gigante: None declared, Francesca Angelotti: None declared, Riccardo Capecchi: None declared, Gianfranco Vitiello: None declared, Elena Cavallaro: None declared, Antonio Tavoni: None declared, Silvia Laura Bosello: None declared, Daniele Cammelli: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UC
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