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1.
Bassilana M  Damiano E  Leblanc G 《Biochemistry》1984,23(22):5288-5294
Modifications of the kinetic properties of the Escherichia coli (RA11) Na(+) - H(+) antiport system by imposed pH gradients (deltapH, interior alkaline) and membrane potential(delta(psi), interior negative) were studied by looking at the accelerating effects of deltapH and delta on downhill Na(+) efflux from membrane vesicles incubated at different external pHs. First,variations of the Na(+) efflux rate ( VNa) as a function of imposed delta pH appear to be strongly dependent on the external pH value.The individual VN, vs. deltapH relationships observed between pH 5.5 and pH 6.6 are all nonlinear and indicate the existence of a threshold deltapH above which V(Na) increases steeply as the deltapH magnitude increases; threshold deltapH values progressively decrease as the pH is raised from 5.5 to 6.6. In contrast, at or above neutrality, V(Na) acceleration is linearly related to deltapH amplitude. Strikingly, it is shown that the deltapH-dependent variations in the Na(+) efflux rate measured in vesicles incubated at different external pHs can be accounted for by variations of internal pH; the observed relationship suggests that a high internal H(+) concentration inhibits the Na(+) -H(+) antiport activity.This inhibition results from a drastic increase in the apparent K(m), of the Na(+) efflux reaction as the internal H(+) concentration increases. On the other hand, imposed Δ increases the Na(+) efflux rate linearly by a selective modification of the V(max) value of the Na(+) efflux. Together, these data indicate that the internal H(+) concentration controls the Na(+)-H(+) antiport activity and that the chemical and electrical proton gradients affect two different kinetic steps of the Na(+)-H(+) exchange reaction.  相似文献   
2.
While campaigns of vaccination against SARS-CoV-2 are underway across the world, communities face the challenge of a fair and effective distribution of a limited supply of doses. Current vaccine allocation strategies are based on criteria such as age or risk. In the light of strong spatial heterogeneities in disease history and transmission, we explore spatial allocation strategies as a complement to existing approaches. Given the practical constraints and complex epidemiological dynamics, designing effective vaccination strategies at a country scale is an intricate task. We propose a novel optimal control framework to derive the best possible vaccine allocation for given disease transmission projections and constraints on vaccine supply and distribution logistics. As a proof-of-concept, we couple our framework with an existing spatially explicit compartmental COVID-19 model tailored to the Italian geographic and epidemiological context. We optimize the vaccine allocation on scenarios of unfolding disease transmission across the 107 provinces of Italy, from January to April 2021. For each scenario, the optimal solution significantly outperforms alternative strategies that prioritize provinces based on incidence, population distribution, or prevalence of susceptibles. Our results suggest that the complex interplay between the mobility network and the spatial heterogeneities implies highly non-trivial prioritization strategies for effective vaccination campaigns. Our work demonstrates the potential of optimal control for complex and heterogeneous epidemiological landscapes at country, and possibly global, scales.  相似文献   
3.
Chemical fingerprinting of commercial Pelargonium capitatum (Geraniaceae) essential oil samples of south African origin was performed by GC, GC/MS, and (13) C- and (1) H-NMR. Thirty-seven compounds were identified, among which citronellol (32.71%) and geraniol (19.58%) were the most abundant. NMR Spectra of characteristic chemicals were provided. Broad-spectrum bioactivity properties of the oil were evaluated and compared with those of commercial Thymus vulgaris essential oil with the aim to obtain a functional profile in terms of efficacy and safety. P. capitatum essential oil provides a good performance as antimicrobial, with particular efficacy against Candida albicans strains. Antifungal activity performed against dermatophyte and phytopathogen strains revealed the latter as more sensitive, while antibacterial activity was not remarkable against both Gram-positive and Gram-negative bacteria. P. capitatum oil provided a lower antioxidant activity (IC(50) ) than that expressed by thyme essential oil, both in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and β-carotene bleaching tests. Results in photochemiluminescence (PCL) assay were negligible. To test the safety aspects of P. capitatum essential oil, mutagenic and toxicity properties were assayed by Ames test, with and without metabolic activation. Possible efficacy of P. capitatum essential oil as mutagenic protective agent against NaN(3) , 2-nitrofluorene, and 2-aminoanthracene was also assayed, providing interesting and significant antigenotoxic properties.  相似文献   
4.

Context

Medical centers worldwide report an increased frequency of Hashimoto''s thyroiditis (HT) and thyroid cancer (TC), two environmentally influenced diseases. In Sicily, data on HT are available for the province of Messina (1975–2005); data on TC are available for the whole island (2002–2004), with the volcanic province of Catania having the highest incidence.

Objective

To replicate in Catania, on comparable years, the HT data of Messina.

Design, Methods, Setting

Review of the clinical records of patients in years 1995–2005 to compare presentation and yearly changes of HT. During 1995–2005, records were computer stored in the Endocrine Divisions of the University Hospitals of Catania and Messina, two tertiary referral centers.

Results

Catania is outnumbered by Messina (742 vs. 3,409 HT patients). Similar were the linear increase in the yearly number of HT patients, rates of thyroid dysfunctions though with different proportions of subclinical and overt hypothyroidism, and rates of positiveness for TgAb or TPOAb. Different were age and its yearly trend; gender distribution and rates of the sonography variants, though yearly trends were similar.

Conclusion

The HT epidemics is smaller in Catania, with changes in presentation overlapping partially those in Messina. Whatever environmental factors might be involved, they (and/or their intensity) were not necessarily the same in these provinces. Intriguingly, the expected number of TC in HT patients with thyroid nodules in Catania is congruent with that of the general population of this province, but it is far less than in the Messina province. Thus, TC and HT incidences could be influenced by distinct environmental factors.  相似文献   
5.
The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19.This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020).During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis.In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.  相似文献   
6.
A key challenge for bioprocess engineering is the identification of the optimum process conditions for the production of biochemical and biopharmaceutical compounds using prokaryotic as well as eukaryotic cell factories. Shake flasks and bench-scale bioreactor systems are still the golden standard in the early stage of bioprocess development, though they are known to be expensive, time-consuming, and labor-intensive as well as lacking the throughput for efficient production optimizations. To bridge the technological gap between bioprocess optimization and upscaling, we have developed a microfluidic bioreactor array to reduce time and costs, and to increase throughput compared with traditional lab-scale culture strategies. We present a multifunctional microfluidic device containing 12 individual bioreactors (Vt = 15 µl) in a 26 mm × 76 mm area with in-line biosensing of dissolved oxygen and biomass concentration. Following initial device characterization, the bioreactor lab-on-a-chip was used in a proof-of-principle study to identify the most productive cell line for lactic acid production out of two engineered yeast strains, evaluating whether it could reduce the time needed for collecting meaningful data compared with shake flasks cultures. Results of the study showed significant difference in the strains' productivity within 3 hr of operation exhibiting a 4- to 6-fold higher lactic acid production, thus pointing at the potential of microfluidic technology as effective screening tool for fast and parallelizable industrial bioprocess development.  相似文献   
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9.
Objectives:Peroneal nerves Schwannomas are rare benign tumors. Literature is still poor of studies about clinical and functional outcomes after surgical treatment. We evaluated the pre-operative presentation of the disease and assessed clinical and functional outcomes after surgery.Methods:We collected all the cases of peroneal nerves’ neurinoma treated surgically between June 2016 and June 2020. We analyzed each patients’ personal data and carried out accurate clinical examinations before and after surgery. MRI was performed both pre-operatively and post-operatively.Results:We reported 9 cases of peroneal nerves schwannomas: five arising from the common peroneal nerve and four arising from the deep or superficial branches alone. Their mean size was 22.6 mm. Each patient showed sensation deficits before surgery; pre-operative MRC score was 4.2. Pre-Operative MSTS and LEFS scores were 23.6 and 64.4. Surgery was successful in each case. No local recurrence nor major complication occurred. Tumor size was significantly associated with both diagnostic delay and development of pre-operative deficits. Surgery was proven to be globally successful: post-operative evaluations highlighted a marked reduction of neurological signs and overall functional limitations.Conclusions:Surgical treatment at early stages of the disease represents a reliable and relatively safe therapeutic option.  相似文献   
10.
This paper describes a convenient synthesis of protected hydrazine derivatives, i.e. 1,2-bis-Boc-hydrazinoacetic acid, and its application for hydrazone ligation techniques in convergent template assembled synthetic protein (TASP) synthesis.  相似文献   
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