The surface accessibility of α-bungarotoxin monitored by a novel paramagnetic probe

The surface accessibility of {alpha}-bungarotoxin has been investigated by using Gd2L7, a newly designed paramagnetic NMR probe. Signal attenuations induced by Gd2L7 on {alpha}-bungarotoxin C{alpha}H peaks of 1H-13C HSQC spectra have been analyzed and compared with the ones previously obtained in the presence of GdDTPA-BMA. In spite of the different molecular size and shape, for the two probes a common pathway of approach to the {alpha}-bungarotoxin surface can be observed with an equally enhanced access of both GdDTPA-BMA and Gd2L7 towards the protein surface side where the binding site is located. Molecular dynamics simulations suggest that protein backbone flexibility and surface hydration contribute to the observed preferential approach of both gadolinium complexes specifically to the part of the {alpha}-bungarotoxin surface which is involved in the interaction with its physiological target, the nicotinic acetylcholine receptor

Analytical Modeling of a New Compliant Microsystem for Atherectomy Operations

This work offers a new alternative tool for atherectomy operations, with the purpose of minimizing the risks for the patients and maximizing the number of clinical cases for which the system can be used, thanks to the possibility of scaling its size down to lumen reduced to a few tenths of mm. The development of this microsystem has presented a certain theoretical work during the kinematic synthesis and the design stages. In the first stage a new multi-loop mechanism with a Stephenson’s kinematic chain (KC) was found and then adopted as the so-called pseudo-rigid body mechanism (PRBM). Analytical modeling was necessary to verify the synthesis requirements. In the second stage, the joint replacement method was applied to the PRBM to obtain a corresponding and equivalent compliant mechanism with lumped compliance. The latter presents two loops and six elastic joints and so the evaluation of the microsystem mechanical advantage (MA) had to be calculated by taking into account the accumulation of elastic energy in the elastic joints. Hence, a new closed form expression of the microsystem MA was found with a method that presents some new aspects in the approach. The results obtained with Finite Element Analysis (FEA) were compared to those obtained with the analytical model. Finally, it is worth noting that a microsystem prototype can be fabricated by using MEMS Technology classical methods, while the microsystem packaging could be a further development for the present investigation

Aggregation induced phosphorescent N-oxyde-2,2′-bipyridine bismuth complexes and polymorphism-dependent emission

Unprecedented bismuth complexes, based on the rarely used ditopic ligand N-oxide-2,2′-bipyridine (bp2mo), crystallizing as three polymorphs, α- (1), β- (2) and γ-[BiBr3(bp2mo)2] (3), exhibit phosphorescence with a quantum yield up to 17% for the crystal phase (1), while the complex displays a weak fluorescence in solution. A study of the luminescence properties combined with DFT/TDDFT calculations reveals that the lighting phenomenon originated by aggregation induced phosphorescence correlated with the weak intermolecular interactions present in the different crystal phases

Bismuth-Based Coordination Polymers with Efficient Aggregation-Induced Phosphorescence and Reversible Mechanochromic Luminescence

Two bismuth coordination polymers (CPs), (TBA)[BiBr4(bp4mo)] (TBA=tetrabutylammonium) and [BiBr3(bp4mo)2], which are based on the rarely used simple ditopic ligand N-oxide-4,4′-bipyridine (bp4mo), show mechanochromic luminescence (MCL). High solid-state phosphorescence quantum yields of up to 85 % were determined for (TBA)[BiBr4(bp4mo)] (λem=540 nm). Thorough investigations of the luminescence properties combined with DFT and TDDFT calculations revealed that the emission is due to aggregation-induced phosphorescence (AIP). Upon grinding, both samples became amorphous, and their luminescence changed from yellow to orange and red, respectively. Heating or exposure to water vapor led to the recovery of the initial luminescence. These materials are the first examples of mechanochromic phosphors based on bismuth(III)

Asymptotic adaptive methods for multi-scale problems in fluid mechanics

This paper reports on the results of a three-year research effort aimed at investigating and exploiting the role of physically motivated asymptotic analysis in the design of numerical methods for singular limit problems in fluid mechanics. Such problems naturally arise, among others, in combustion, magneto-hydrodynamics and geophysical fluid mechanics. Typically, they are characterized by multiple space and/or time scales and by the disturbing fact that standard computational techniques fail entirely, are unacceptably expensive, or both. The challenge here is to construct numerical methods which are robust, uniformly accurate, and efficient through different asymptotic regimes and over a wide range of relevant applications. Summaries of multiple scales asymptotic analyses for low Mach number flows, magnetohydrodynamics at small Mach and Alfv´en numbers, and of multiple scales atmospheric flows are provided. These reveal singular balances between selected terms in the respective governing equations within the considered flow regimes. These singularities give rise to problems of severe stiffness, stability, or to dynamic range issues in straightforward numerical discretizations. Aformal mathematical framework for the multiple scales asymptotics is then summarized using the example of multiple length scale – single time scale asymptotics for low Mach number flows. The remainder of the paper focuses on the construction of numerical discretizations for the respective full governing equation systems. These discretizations avoid the pitfalls of singular balances by exploiting the asymptotic results. Importantly, the asymptotics are not used here to derive simplified equation systems, which are then solved numerically. Rather, we aim at numerically integrating the full equation sets and at using the asymptotics only to construct discretizations that do not deteriorate as a singular limit is approached. One important ingredient of this strategy is the numerical identification of a singular limit regime given a set of discrete numerical state variables. This problem is addressed in an exemplary fashion for multiple length – single time scale low Mach number flows in one space dimension. The strategy allows a dynamic determination of an instantaneous relevant Mach number, and it can thus be used to drive the appropriate adjustment of the numerical discretizations when the singular limit regime is approached

Effect of GnRH on scrotal surface temperature, testicular volume and spern parameters of bulls with poor semen quality.

Spermatogenesis is coordinated by the hypothalamic-pituitary-gonadal axis, mainly by GnRH secretion.Edição dos Proceedings of the 32nd Annual Meeting of the Brazilian Embryo Technology Society (SBTE)

A retrospective analysis of pegylated liposomal doxorubicin in ovarian cancer: Do we still need it?

Background: Ovarian cancer (OC) is the sixth most common cancer in women. Currently, carboplatin/ paclitaxel bevacizumab is the cornerstone of front-line treatment. Conversely, the therapeutic options for recurrent or progressive disease are not well defined. For platinum-sensitive patients the best therapeutic approach is still a re-challenge with a platinum-based regimen. Pegylated liposomal doxorubicin (PLD), is considered one of the most active therapeutic options for recurrent or progressive OC. In this retrospective mono-institutional analysis, we evaluated the impact of PLD on the outcome of OC patients. Patients and methods: We performed the retrospective study on a cohort of 108 patients with histologically confirmed serous papillary OC, followed at our Institution between 2001 and 2011. 80 patients were in stage III/IV and 55 of them received a second-line treatment. Thirty patients were treated with PLD. Both groups (PLD-treated versus PLD-untreated) underwent a median of 3 treatment lines and were prognostically balanced. The median follow-up was 60 months. Survival endpoints, toxicity and correlations between patients' baseline characteristics and treatment efficacy were evaluated. Results: Patients who had undergone PLD treatment (PLD group) showed a median overall survival (OS) of 45 months as compared to 65 months of patients not treated with PLD (PLD-free group) (HR 2.50 [0.95-6.67; p = 0.06]). Moreover, the median progression-free survival was 6 months in the PLD group versus 10 months in the PLD-free group (HR 1.75 [0.94-3.34; p = 0.07]). The overall objective response rate in II line treatment was 43% (13% in PLD group versus 57% in PLD-free group). Furthermore, we investigated survival endpoints in platinum-refractory patients who received PLD at least once during the course of disease. No OS advantage was achieved by PLD administration when compared to other therapeutic options (30 versus 32 months; HR 1.16 [0.31-4.34; p = 0.81]). No difference in term of toxicity was observed among different groups. Conclusions: No evidence of superiority if PLD was compared to alternative agents was found in this analysis, particularly in the platinum-refractory setting. Our findings indicate a modest therapeutic activity of PLD in OC. Analysis of cost/benefit of PLD in OC is eagerly awaited

Mapping the Genetic Regions Responsible for Key Phenology-Related Traits in the European Hazelnut

An increasing interest in the cultivation of (European) hazelnut (Corylus avellana) is driving a demand to breed cultivars adapted to non-conventional environments, particularly in the context of incipient climate change. Given that plant phenology is so strongly determined by genotype, a rational approach to support these breeding efforts will be to identify quantitative trait loci (QTLs) and the genes underlying the basis for adaptation. The present study was designed to map QTLs for phenology-related traits, such as the timing of both male and female flowering, dichogamy, and the period required for nuts to reach maturity. The analysis took advantage of an existing linkage map developed from a population of F(1) progeny bred from the cross “Tonda Gentile delle Langhe” × “Merveille de Bollwiller,” consisting in 11 LG. A total of 42 QTL-harboring regions were identified. Overall, 71 QTLs were detected, 49 on the TGdL map and 22 on the MB map; among these, 21 were classified as major; 13 were detected in at least two of the seasons (stable-major QTL). In detail, 20 QTLs were identified as contributing to the time of male flowering, 15 to time of female flowering, 25 to dichogamy, and 11 to time of nut maturity. LG02 was found to harbor 16 QTLs, while 15 QTLs mapped to LG10 and 14 to LG03. Many of the QTLs were clustered with one another. The major cluster was located on TGdL_02 and consisted of mainly major QTLs governing all the analyzed traits. A search of the key genomic regions revealed 22 candidate genes underlying the set of traits being investigated. Many of them have been described in the literature as involved in processes related to flowering, control of dormancy, budburst, the switch from vegetative to reproductive growth, or the morphogenesis of flowers and seeds

Fingerprinting the impacts of global change on tropical forests

Recent observations of widespread changes in mature tropical forests such as increasing tree growth, recruitment and mortality rates and increasing above-ground biomass suggest that 'global change' agents may be causing predictable changes in tropical forests. However, consensus over both the robustness of these changes and the environmental drivers that may be causing them is yet to emerge. This paper focuses on the second part of this debate. We review (i) the evidence that the physical, chemical and biological environment that tropical trees grow in has been altered over recent decades across large areas of the tropics, and (ii) the theoretical, experimental and observational evidence regarding the most likely effects of each of these changes on tropical forests. Ten potential widespread drivers of environmental change were identified: temperature, precipitation, solar radiation, climatic extremes (including El Niño Southern Oscillation events), atmospheric CO2 concentrations, nutrient deposition, O3/acid depositions, hunting, land-use change and increasing liana numbers. We note that each of these environmental changes is expected to leave a unique 'fingerprint' in tropical forests, as drivers directly force different processes, have different distributions in space and time and may affect some forests more than others (e.g. depending on soil fertility). Thus, in the third part of the paper we present testable a priori predictions of forest responses to assist ecologists in attributing particular changes in forests to particular causes across multiple datasets. Finally, we discuss how these drivers may change in the future and the possible consequences for tropical forests