Noether's Symmetry Theorem for Variational and Optimal Control Problems with Time Delay

We extend the DuBois-Reymond necessary optimality condition and Noether's symmetry theorem to the time delay variational setting. Both Lagrangian and Hamiltonian versions of Noether's theorem are proved, covering problems of the calculus of variations and optimal control with delays.Comment: This is a preprint of a paper whose final and definite form will appear in the international journal Numerical Algebra, Control and Optimization (NACO). Paper accepted for publication 15-March-201

Spectrum of the Nuclear Environment for GaAs Spin Qubits

Using a singlet-triplet spin qubit as a sensitive spectrometer of the GaAs nuclear spin bath, we demonstrate that the spectrum of Overhauser noise agrees with a classical spin diffusion model over six orders of magnitude in frequency, from 1 mHz to 1 kHz, is flat below 10 mHz, and falls as $1/f^2$ for frequency $f \! \gtrsim \! 1$ Hz. Increasing the applied magnetic field from 0.1 T to 0.75 T suppresses electron-mediated spin diffusion, which decreases spectral content in the $1/f^2$ region and lowers the saturation frequency, each by an order of magnitude, consistent with a numerical model. Spectral content at megahertz frequencies is accessed using dynamical decoupling, which shows a crossover from the few-pulse regime ($\lesssim \! 16$ $\pi$-pulses), where transverse Overhauser fluctuations dominate dephasing, to the many-pulse regime ($\gtrsim \! 32$ $\pi$-pulses), where longitudinal Overhauser fluctuations with a $1/f$ spectrum dominate.Comment: 6 pages, 4 figures, 8 pages of supplementary material, 5 supplementary figure

A clinical argument or an access constraint?

Funding Information: In the preparation of this article, the authors received collaboration from the medical writer Duarte Oliveira (W4Research) financially supported by Sanofi. Sanofi had no role in the preparation of the manuscript or in the decision to submit the manuscript for publication. All authors declare collaborating and receiving fees from Sanofi and other pharmaceutical companies either through participation in advisory boards or consultancy, congress symposia, conducting clinical trials, investigator-initiated trials or grants. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.proofpublishe

Intensity modulated radiotherapy for localized prostate cancer: rigid compliance to dose-volume constraints as a warranty of acceptable toxicity?

BACKGROUND: To report the toxicity after intensity modulated radiotherapy (IMRT) for patients with localized prostate cancer, as a sole treatment or after radical prostatectomy. METHODS: Between August 2001 and December 2003, 132 patients with prostate cancer were treated with IMRT and 125 were evaluable to acute and late toxicity analysis, after a minimum follow-up time of one year. Clinical and treatment data, including normal tissue dose-volume histogram (DVH) constraints, were reviewed. Gastro-intestinal (GI) and genito-urinary (GU) signs and symptoms were evaluated according to the Radiation Therapy Oncology Group (RTOG) toxicity scales. Median prescribed dose was 76 Gy. Median follow-up time was of 26.1 months. RESULTS: From the 125 patients, 73 (58.4%) presented acute Grade 1 or Grade 2 GI and 97 (77.2%) presented acute Grade 1 or Grade 2 GU toxicity. Grade 3 GI acute toxicity occurred in only 2 patients (1.6%) and Grade 3 GU acute toxicity in only 3 patients (2.4%). Regarding Grade 1 and 2 late toxicity, 26 patients (20.8%) and 21 patients (16.8%) presented GI and GU toxicity, respectively. Grade 2 GI late toxicity occurred in 6 patients (4.8%) and Grade 2 GU late toxicity in 4 patients (3.2%). None patient presented any Grade 3 or higher late toxicity. Non-conformity to DVH constraints occurred in only 11.2% of treatment plans. On univariate analysis, no significant risk factor was identified for Grade 2 GI late toxicity, but mean dose delivered to the PTV was associated to higher Grade 2 GU late toxicity (p = 0.042). CONCLUSION: IMRT is a well tolerable technique for routine treatment of localized prostate cancer, with short and medium-term acceptable toxicity profiles. According to the data presented here, rigid compliance to DHV constraints might prevent higher incidences of normal tissue complication

Highly specific blood-brain barrier transmigrating single-domain antibodies selected by an In Vivo phage display screening

Research Areas: Pharmacology & PharmacyA major bottleneck in the successful development of central nervous system (CNS) drugs is the discovery and design of molecules that can cross the blood-brain barrier (BBB). Nano-delivery strategies are a promising approach that take advantage of natural portals of entry into the brain such as monoclonal antibodies (mAbs) targeting endogenous BBB receptors. However, the main selected mAbs rely on targeting broadly expressed receptors, such as the transferrin and insulin receptors, and in selection processes that do not fully mimic the native receptor conformation, leading to mistargeting and a low fraction of the administered dose effectively reaching the brain. Thus, there is an urgent need to identify new BBB receptors and explore novel antibody selection approaches that can allow a more selective delivery into the brain. Considering that in vitro models fail to completely mimic brain structure complexity, we explored an in vivo cell immunization approach to construct a rabbit derived single-domain antibody (sdAb) library towards BBB endothelial cell receptors. The sdAb antibody library was used in an in vivo phage display screening as a functional selection of novel BBB targeting antibodies. Following three rounds of selections, next generation sequencing analysis, in vitro brain endothelial barrier (BEB) model screenings and in vivo biodistribution studies, five potential sdAbs were identified, three of which reaching >0.6% ID/g in the brain. To validate the brain drug delivery proof-of-concept, the most promising sdAb, namely RG3, was conjugated at the surface of liposomes encapsulated with a model drug, the pan-histone deacetylase inhibitor panobinostat (PAN). The translocation efficiency and activity of the conjugate liposome was determined in a dual functional in vitro BEB-glioblastoma model. The RG3 conjugated PAN liposomes enabled an efficient BEB translocation and presented a potent antitumoral activity against LN229 glioblastoma cells without influencing BEB integrity. In conclusion, our in vivo screening approach allowed the selection of highly specific nano-antibody scaffolds with promising properties for brain targeting and drug delivery.info:eu-repo/semantics/publishedVersio

Effects of Horizontal and Incline Bench Press on Neuromuscular Adaptations in Untrained Young Men

International Journal of Exercise Science 13(6): 859-872, 2020. The aim of the current study was to investigate the effects of horizontal and incline bench press as well as the combination of both exercises on neuromuscular adaptation in untrained young men. Forty-seven untrained men were randomly assigned to one of the three groups: 1) a horizontal bench press group (n= 15), 2) an incline bench press group (n= 15), and 3) a combination (horizontal + incline) group (n= 17). Training was conducted once a week for eight weeks, with equalized number of sets among groups. Muscle thickness, isometric strength and electromyography (EMG) amplitude of the pectoralis major were measured one week before and after the training period. There was no difference between groups for the change in horizontal bench press isometric strength (~ 10 kg increase, p=0.776) or incline bench press isometric strength (~ 11 kg increase, p=0.333). Changes in muscle thickness differed only in one of the three sites. The changes in the second intercostal space of the pectoralis major was greatest in the incline pressure group compared with the horizontal [mean difference (95% CI) of 0.62 (0.23, 1.0) cm, p=0.003] and combination groups [mean difference (95% CI) of 0.50 (0.14, 0.86) cm, p=0.008]. The change in EMG amplitude following training differed between groups in only one out of the four sites. The present results indicate that strength and conditioning professionals might consider that horizontal and incline bench press exercises, or a combination of both exercises can render similar change in general strength

The Halogen Effect on the Magnetic Behaviour of Dimethylformamide Solvates in [Fe(halide-salEen)2]BPh4

Funding Research was funded by Fundação para a Ciência e a Tecnologia (FCT): projects UIDB/00100/2020, UIDP/00100/2020, LA/P/0056/2020, UIDB/04046/2020, UIDP/04046/2020, UIDB/50006/2020, UIDP/50006/2020 and LA/P/0008/2020, UIDB/04378/2020, UIDP/04378/2020, and LA/P/0140/2020, PTDC/QUI-QFI/29236/2017, PTDCQUI-QIN0252_2021, CEECIND/00509/2017; Fonds de la Recherche Scientifique (FNRS): PDR T.0095.21); Portugal2020: CENTRO-01-0145-FEDER-000018; Royal Society of Chemistry (RSC): R21-7511142525. Acknowledgments Centro de Química Estrutural (CQE) and Institute of Molecular Sciences (IMS) acknowledge the financial support of Fundação para a Ciência e a Tecnologia (FCT): Projects UIDB/00100/2020, UIDP/00100/2020, and LA/P/0056/2020, respectively. BioISI acknowledges FCT for financial support (UIDB/04046/2020, UIDP/04046/2020). This work was supported by the FNRS (PDR T.0095.21). Clara S. B. Gomes acknowledges the Associate Laboratory for Green Chemistry—LAQV, the Applied Molecular Biosciences Unit—UCIBIO and Associated Laboratory i4HB, which are financed by national funds from FCT (UIDB/50006/2020, UIDP/50006/2020 and LA/P/0008/2020, UIDB/04378/2020 and UIDP/04378/2020, and LA/P/0140/2020, respectively). Sónia Barroso thanks project SmartBioR for financial support (CENTRO-01-0145-FEDER-000018)and Centro de Química Estrutural for the access to crystallography facilities. Nuno A. G. Bandeira gratefully acknowledges the NanoBioSolutions FCT grant PTDC/QUI-QFI/29236/2017 for the computational infrastructure. Paulo N. Martinho thanks FCT and RSC for financial support (grants PTDCQUI-QIN0252_2021 and R21-7511142525). Paulo N. Martinho also thanks FCT for the contract CEECIND/00509/2017.Complexes [Fe(X-salEen)2]BPh4·DMF, with X = Br (1), Cl (2), and F (3), were crystallised from N,N′-dimethylformamide with the aim of understanding the role of a high boiling point N,N′-dimethylformamide solvate in the spin crossover phenomenon. The counter ion was chosen for only being able to participate in weak intermolecular interactions. The compounds were structurally characterised by single crystal X-ray diffraction. Complex 1 crystallised in the orthorhombic space group P212121, and complexes 2 and 3 in the monoclinic space group P21/n. Even at room temperature, low spin was the predominant form, although complex 2 exhibited the largest proportion of the high-spin species according to both the magnetisation measurements and the Mössbauer spectra. Density Functional Theory calculations were performed both on the periodic solids and on molecular models for complexes 1–3 and the iodide analogue 4. While all approaches reproduced the experimental structures very well, the energy balance between the high-spin and low-spin forms was harder to reproduce, though some calculations pointed to the easier spin crossover of complex 2, as observed. Periodic calculations with the functional PBE led to very similar ΔEHS-LS values for all complexes but showed a preference for the low-spin form. However, the single-point calculations with B3LYP* showed, for the model without solvate, that the Cl complex should undergo spin crossover more easily. The molecular calculations also reflected this fact, which was more clearly defined when the cation–anion–solvate model was used. In the other models there was not much difference between the Cl, Br, and I complexes.publishersversionpublishe

Processing of Apeiba tibourbou Aubl. extract via spray drying

The effects of drying air inlet temperature (IT) and concentration of Aerosil® 200 (CA) on several properties of spray-dried Apeiba tibourbou extracts were investigated following a 32 full factorial design. Powder recovery varied from 9.83 to 46.95% and dried products showed moisture contents below 7%. Although the spray-dried products lost some of their polyphenols, they still present excellent antioxidant activity, opening perspectives for its use to medicinal purpose. CA exerted a key role on the properties of spray-dried extracts, while IT did not present a significative influence. Aerosil® 200 proved to be an interesting alternative as an excipient for the drying of the herbal extract, even at intermediate concentrations such as 15%. The best combination of conditions to use for obtaining dry A. tibourbou extracts with adequate physicochemical and functional properties involves an IT of 100 ºC and a CA of 15%.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Seasonal variation and antimicrobial activity of Myrcia myrtifolia essential oils

This work reports the seasonal variation of the composition of leaf volatile oils and the composition of volatile oils from flowers and fruits of Myrcia myrtifolia DC harvested in the sand dunes of Salvador, Bahia, northeastern region of Brazil between 2002 and 2003. The oils were analyzed by GC-FID and GC-MS so that 28 components were identified. alpha-Pinene was predominant in a range from 61.5 to 90.9% in all samples analyzed. The leaf oil collected in October 2002 had their antimicrobial properties tested against six bacteria, two yeasts and five filamentous fungi being active against Staphylococcus aureus, methicilin-resistant Staphylococcus aureus, Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, and showed strongest activity against Microsporum canis and Trichophyton rubrum. The oil displayed moderate toxicity against Artemia salina showing a LC50 of 479.16 µg mL-1

DNA Dosimetry Assessment for Sunscreen Genotoxic Photoprotection

Background: Due to the increase of solar ultraviolet radiation (UV) incidence over the last few decades, the use of sunscreen has been widely adopted for skin protection. However, considering the high efficiency of sunlight-induced DNA lesions, it is critical to improve upon the current approaches that are used to evaluate protection factors. An alternative approach to evaluate the photoprotection provided by sunscreens against daily UV radiation-induced DNA damage is provided by the systematic use of a DNA dosimeter. Methodology/Principal Findings: The Sun Protection Factor for DNA (DNA-SPF) is calculated by using specific DNA repair enzymes, and it is defined as the capacity for inhibiting the generation of cyclobutane pyrimidine dimers (CPD) and oxidised DNA bases compared with unprotected control samples. Five different commercial brands of sunscreen were initially evaluated, and further studies extended the analysis to include 17 other products representing various formulations and Sun Protection Factors (SPF). Overall, all of the commercial brands of SPF 30 sunscreens provided sufficient protection against simulated sunlight genotoxicity. In addition, this DNA biosensor was useful for rapidly screening the biological protection properties of the various sunscreen formulations. Conclusions/Significance: The application of the DNA dosimeter is demonstrated as an alternative, complementary, and reliable method for the quantification of sunscreen photoprotection at the level of DNA damage.Natura Inovacao e Tecnologia de Produtos LTDA (Sao Paulo, Brazil)Natura Inovacao e Tecnologia de Produtos LTDA (Sao Paulo, Brazil)FAPESP (Sao Paulo, Brazil)FAPESP (Sao Paulo, Brazil)CNPq (Brasilia, Brazil)CNPq (Brasilia, Brazil)Natura Inovacao e Tecnologia de Produtos LTDANatura Inovacao e Tecnologia de Produtos LTD