Homologous recombination (HR) is an evolutionarily conserved process that plays a pivotal role in the equilibrium between genetic stability and diversity. HR is commonly considered to be error-free, ...but several studies have shown that HR can be error-prone. Here, we discuss the actual accuracy of HR. First, we present the product of genetic exchanges (gene conversion, GC, and crossing over, CO) and the mechanisms of HR during double strand break repair and replication restart. We discuss the intrinsic capacities of HR to generate genome rearrangements by GC or CO, either during DSB repair or replication restart. During this process, abortive HR intermediates generate genetic instability and cell toxicity. In addition to genome rearrangements, HR also primes error-prone DNA synthesis and favors mutagenesis on single stranded DNA, a key DNA intermediate during the HR process. The fact that cells have developed several mechanisms protecting against HR excess emphasize its potential risks. Consistent with this duality, several pro-oncogenic situations have been consistently associated with either decreased or increased HR levels. Nevertheless, this versatility also has advantages that we outline here. We conclude that HR is a double-edged sword, which on one hand controls the equilibrium between genome stability and diversity but, on the other hand, can jeopardize the maintenance of genomic integrity. Therefore, whether non-homologous end joining (which, in contrast with HR, is not intrinsically mutagenic) or HR is the more mutagenic process is a question that should be re-evaluated. Both processes can be "Dr. Jekyll" in maintaining genome stability/variability and "Mr. Hyde" in jeopardizing genome integrity.
A wavelet neural control scheme for a quadrotor unmanned aerial vehicle Jurado, F.; Lopez, S.
Philosophical transactions - Royal Society. Mathematical, Physical and engineering sciences/Philosophical transactions - Royal Society. Mathematical, physical and engineering sciences,
08/2018, Letnik:
376, Številka:
2126
Journal Article
Recenzirano
Odprti dostop
Wavelets are designed to have compact support in both time and frequency, giving them the ability to represent a signal in the two-dimensional time-frequency plane. The Gaussian, the Mexican hat and ...the Morlet wavelets are crude wavelets that can be used only in continuous decomposition. The Morlet wavelet is complex-valued and suitable for feature extraction using the continuous wavelet transform. Continuous wavelets are favoured when high temporal and spectral resolution is required at all scales. In this paper, considering the properties from the Morlet wavelet and based on the structure of a recurrent high-order neural network model, a novel wavelet neural network structure, here called a recurrent Morlet wavelet neural network, is proposed in order to achieve a better identification of the behaviour of dynamic systems. The effectiveness of our proposal is explored through the design of a decentralized neural backstepping control scheme for a quadrotor unmanned aerial vehicle. The performance of the overall neural identification and control scheme is verified via simulation and real-time results.
This article is part of the theme issue 'Redundancy rules: the continuous wavelet transform comes of age'.
To characterize the clinical phenotype of myelin oligodendrocyte glycoprotein antibody (MOG-IgG) optic neuritis.
Observational case series.
Setting: Multicenter. Patient/Study Population: Subjects ...meeting inclusion criteria: (1) history of optic neuritis; (2) seropositivity (MOG-IgG binding index > 2.5); 87 MOG-IgG-seropositive patients with optic neuritis were included (Mayo Clinic, 76; other medical centers, 11). MOG-IgG was detected using full-length MOG-transfected live HEK293 cells in a clinically validated flow cytometry assay. Main Outcome Measures: Clinical and radiologic characteristics and visual outcomes.
Fifty-seven percent were female and median age at onset was 31 (range 2–79) years. Median number of optic neuritis attacks was 3 (range 1–8), median follow-up 2.9 years (range 0.5–24 years), and annualized relapse rate 0.8. Average visual acuity (VA) at nadir of worst attack was count fingers. Average final VA was 20/30; for 5 patients (6%) it was ≤20/200 in either eye. Optic disc edema and pain each occurred in 86% of patients. Magnetic resonance imaging showed perineural enhancement in 50% and longitudinally extensive involvement in 80%. Twenty-six patients (30%) had recurrent optic neuritis without other neurologic symptoms, 10 (12%) had single optic neuritis, 14 (16%) had chronic relapsing inflammatory optic neuropathy, and 36 (41%) had optic neuritis with other neurologic symptoms (most neuromyelitis optica spectrum disorder–like phenotype or acute disseminated encephalomyelitis). Only 1 patient was diagnosed with MS (MOG-IgG-binding index 2.8; normal range ≤ 2.5). Persistent MOG-IgG seropositivity occurred in 61 of 62 (98%). A total of 61% received long-term immunosuppressant therapy.
Manifestations of MOG-IgG-positive optic neuritis are diverse. Despite recurrent attacks with severe vision loss, the majority of patients have significant recovery and retain functional vision long-term.
Background
Anastomotic leakage of pancreaticojejunostomy (PJ) remains the single most important source of morbidity after pancreaticoduodenectomy (PD). The primary aim of this randomized clinical ...trial comparing PG with PJ after PD was to test the hypothesis that invaginated PG would result in a lower rate and severity of pancreatic fistula.
Methods
Patients undergoing PD were randomized to receive either a duct‐to‐duct PJ or a double‐layer invaginated PG. The primary endpoint was the rate of pancreatic fistula, using the definition of the International Study Group on Pancreatic Fistula. Secondary endpoints were the evaluation of severe abdominal complications (Clavien–Dindo grade IIIa or above), endocrine and exocrine function.
Results
Of 123 patients randomized, 58 underwent PJ and 65 had PG. The incidence of pancreatic fistula was significantly higher following PJ than for PG (20 of 58 versus 10 of 65 respectively; P = 0·014), as was the severity of pancreatic fistula (grade A: 2 versus 5 per cent; grade B–C: 33 versus 11 per cent; P = 0·006). The hospital readmission rate for complications was significantly lower after PG (6 versus 24 per cent; P = 0·005), weight loss was lower (P = 0·025) and exocrine function better (P = 0·022).
Conclusion
The rate and severity of pancreatic fistula was significantly lower with this PG technique compared with that following PJ. Registration number: ISRCTN58328599 (http://www.controlled-trials.com).
This pancreaticogastrostomy technique is superior
DNA double-strand breaks (DSB) are very harmful lesions that can generate genome rearrangements. In this study, we used intrachromosomal reporters to compare both the efficiency and accuracy of ...end-joining occurring with close (34 bp apart) vs. distant DSBs (3200 bp apart) in human fibroblasts. We showed that a few kb between two intrachromosomal I-SceI-induced DSBs are sufficient to foster deletions and capture/insertions at the junction scar. Captured sequences are mostly coupled to deletions and can be partial duplications of the reporter (i.e., sequences adjacent to the DSB) or insertions of ectopic chromosomal sequences (ECS). Interestingly, silencing 53BP1 stimulates capture/insertions with distant but not with close double-strand ends (DSEs), although deletions were stimulated in both case. This shows that 53BP1 protects both close and distant DSEs from degradation and that the association of unprotection with distance between DSEs favors ECS capture. Reciprocally, silencing CtIP lessens ECS capture both in control and 53BP1-depleted cells. We propose that close ends are immediately/rapidly tethered and ligated, whereas distant ends first require synapsis of the distant DSEs prior to ligation. This "spatio-temporal" gap gives time and space for CtIP to initiate DNA resection, suggesting an involvement of single-stranded DNA tails for ECS capture. We therefore speculate that the resulting single-stranded DNA copies ECS through microhomology-mediated template switching.
The integration between solar energy systems and building components is highly critical in sensitive heritage contexts. On the one hand there is the need for finding a balance between the ...preservation of the aesthetic appearance and the historical values, but on the other hand, finding the space where to effectively integrate the systems might be quite challenging. The solar systems can be divided in photovoltaic (PV) and solar thermal (ST) systems. Building Integrated Photovoltaics (BIPV) and Building Integrated Solar Thermal (BIST) are PV or ST panels integrated into the building envelope, combining the energy generation with other functions, such as noise, weather protection, thermal insulation, sun shadow, and other aspects. Nowadays, the dynamism of the market allows to design highly compatible products which look like traditional architecture materials. This situation fosters the integration of these products in the BIPV and BIST systems within the heritage sites, especially thanks to the use of advanced customisation processes, special and low-reflecting glasses, and innovative cost-competitive coatings. There is a limited number of studies on the application of these technologies in heritage contexts, due to the presence of architectonic, conservative, and cultural barriers. This paper aims to conduct a comprehensive review of the available literature on the integration of renewable energy sources (RES) in heritage sites and buildings, which would foster the preservation of their cultural and natural values as well as reducing primary energy consumption, increasing comfort levels, minimizing environmental impacts, and improving technical quality and economical outlays. A common framework will thus defined to support restorers, historic conservators, and energy experts and to facilitate the diffusion and application of RES in heritage contexts. This conceptual framework will provide industries and academics with operative strategies and will encourage their diffusion and application in sensible contexts.
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•Novel theoretical Fe-based binaries predicted by an Adaptive Genetic Algorithm.•Computational high-throughput screening of magnetocrystalline anisotropy.•Theoretical and experimental ...data of intrinsic and extrinsic magnetic properties.•Friendly Graphical User Interface with advanced search and plotting tools.
This paper describes the open Novamag database that has been developed for the design of novel Rare-Earth free/lean permanent magnets. Its main features as software technologies, friendly graphical user interface, advanced search mode, plotting tool and available data are explained in detail. Following the philosophy and standards of Materials Genome Initiative, it contains significant results of novel magnetic phases with high magnetocrystalline anisotropy obtained by three computational high-throughput screening approaches based on a crystal structure prediction method using an Adaptive Genetic Algorithm, tetragonally distortion of cubic phases and tuning known phases by doping. Additionally, it also includes theoretical and experimental data about fundamental magnetic material properties such as magnetic moments, magnetocrystalline anisotropy energy, exchange parameters, Curie temperature, domain wall width, exchange stiffness, coercivity and maximum energy product, that can be used in the study and design of new promising high-performance Rare-Earth free/lean permanent magnets. The results therein contained might provide some insights into the ongoing debate about the theoretical performance limits beyond Rare-Earth based magnets. Finally, some general strategies are discussed to design possible experimental routes for exploring most promising theoretical novel materials found in the database.
To evaluate the performance of the Finnish Diabetes Risk Score (FINDRISC) and a simplified FINDRISC score (MADRISC) in screening for undiagnosed type 2 diabetes mellitus (UT2DM) and dysglycaemia.
A ...population-based, cross-sectional, descriptive study was carried out with participants with UT2DM, ranged between 45-74 years and lived in two districts in the north of metropolitan Madrid (Spain). The FINDRISC and MADRISC scores were evaluated using the area under the receiver operating characteristic curve method (ROC-AUC). Four different gold standards were used for UT2DM and any dysglycaemia, as follows: fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), HbA1c, and OGTT or HbA1c. Dysglycaemia and UT2DM were defined according to American Diabetes Association criteria.
The study population comprised 1,426 participants (832 females and 594 males) with a mean age of 62 years (SD = 6.1). When HbA1c or OGTT criteria were used, the prevalence of UT2DM was 7.4% (10.4% in men and 5.2% in women; p<0.01) and the FINDRISC ROC-AUC for UT2DM was 0.72 (95% CI, 0.69-0.74). The optimal cut-off point was ≥13 (sensitivity = 63.8%, specificity = 65.1%). The ROC-AUC of MADRISC was 0.76 (95% CI, 0.72-0.81) with ≥13 as the optimal cut-off point (sensitivity = 84.8%, specificity = 54.6%). FINDRISC score ≥12 for detecting any dysglycaemia offered the best cut-off point when HbA1c alone or OGTT and HbA1c were the criteria used.
FINDRISC proved to be a useful instrument in screening for dysglycaemia and UT2DM. In the screening of UT2DM, the simplified MADRISC performed as well as FINDRISC.
Rapid degradation of fresh‐cut papaya limits its marketability. Hydrothermal treatments in combination with a calcium dip, applied to whole fruit before slicing, and also the application of chitosan ...as a coating film, have been found to have very good results in maintaining the quality of fresh‐cut fruits. Based on these considerations, the aim of this study was to evaluate the effect of hydrothermal treatment (HT; 49 °C, 25 min) containing calcium chloride (Ca; 1%, w/v) followed by dipping in chitosan (Chit; 1%, w/v, 3 min) on the physical, chemical, and microbial qualities of papaya slices stored at 5 °C for 10 d. Pulp color, firmness, ascorbic acid, total phenolics, β‐carotene, and lycopene were evaluated every 2 d while the microbial quality (mesophilics, psychrophilics, molds, and yeasts) was evaluated every 5 d. Fruit treated with HT‐Ca and HT‐Ca + Chit showed better color and firmness retention than Control and Chit. Papaya slices treated with HT‐Ca + Chit had higher nutritional content and lower microbial growth at the end of storage. The application of the HT‐Ca + Chit could be used to reduce deterioration processes, maintaining physical, chemical, and microbial qualities and increasing the shelf life of fresh‐cut papaya stored at 5 °C.
Practical Application
The application of hydrothermal‐calcium chloride, combined with chitosan coatings, reduced deterioration processes and presented antimicrobial activity, thus increasing the shelf life and showing its potential use in food preservation. Also, it can constitute an alternative for the natural preservation of fresh‐cut papaya for which the use of synthetic chemicals is objectionable.
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