Output Feedback Linearization of Turbidostats After Time Scaling

Turbidostats are a class of bioreactors gaining interest due to the recent availability of microscale and small-scale devices for characterization and scalingup of the biotechnological systems relevant in the biotech and pharma industries. The goal is to keep cell density constant in continuous operation. Thus, the control law, i.e., the substrate feeding strategy, must guarantee global or semiglobal convergence to an equilibrium point. However, their control is difficult due to the uncertain, time varying, and nonlinear nature of the processes involved. In this brief, we propose an adaptive control law that globally stabilizes the desired biomass setpoint. Furthermore, in a certain region of the state space, the controller linearizes the dynamic behavior after some time scaling. By this way, the orbits of the closed-loop system are imposed by the designer. The intrinsic integral action of the gain adaptation rejects the parameter uncertainties. Moreover, the controller implementation only assumes the biomass concentration to be measured. Both the simulated and experimental results show the performance of the controller.Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señale

Adsorption of peroxidase from Raphanus sativus L onto alginateguar gum matrix: Kinetic, equilibrium and thermodynamic analysis

This work explores the kinetics, equilibrium and thermodynamics of peroxidase adsorption onto spherical guar gumalginate matrices. The effect of contact time, solution pH, initial protein concentration and temperature was studied in batch experiments. The results show that peroxidase adsorption increased with rising contact time and initial enzyme concentration, and was higher at pH 4.0. The kinetic processes can be predicted by both the pseudo-first-order rate kinetics and the pseudo-second-order rate kinetics. Equilibrium adsorption data were analyzed with different isotherm models. The experimental data fitted to the Freundlich model in agreement with the low energy activation, demonstrating the presence of a high physical and unspecific interaction between the enzyme and the matrix.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: FonCyT, Projects PICT 2013–271 – Argentina Innovator 2020 and Biotechnologies to Valorize the regional food Biodiversity in Latin America – Marie Curie Actions – IRSES Project number 611493 – European Community.info:eu-repo/semantics/publishedVersio

Optimizing NANOS OpenMP for the IBM Cyclops multithreaded architecture

In this paper, we present two approaches to improve the execution of OpenMP applications on the IBM Cyclops multithreaded architecture. Both solutions are independent and they are focused to obtain better performance through a better management of the cache locality. The first solution is based on software modifications to the OpenMP runtime library to balance stack accesses across all data caches. The second solution is a small hardware modification to change the data cache mapping behavior, with the same goal. Both solutions help parallel applications to improve scalability and obtain better performance in this kind of architectures. In fact, they could also be applied to future multi-core processors. We have executed (using simulation) some of the NAS benchmarks to prove these proposals. They show how, with small changes in both the software and the hardware, we achieve very good scalability in parallel applications. Our results also show that standard execution environments oriented to multiprocessor architectures can be easily adapted to exploit multithreaded processors.Peer ReviewedPostprint (author's final draft

Novel intravesical bacterial immunotherapy induces rejection of BCG-unresponsive established bladder tumors

Background Intravesical BCG is the gold-standard therapy for non-muscle invasive bladder cancer (NMIBC); however, it still fails in a significant proportion of patients, so improved treatment options are urgently needed. Methods Here, we compared BCG antitumoral efficacy with another live attenuated mycobacteria, MTBVAC, in an orthotopic mouse model of bladder cancer (BC). We aimed to identify both bacterial and host immunological factors to understand the antitumoral mechanisms behind effective bacterial immunotherapy for BC. Results We found that the expression of the BCG-absent proteins ESAT6/CFP10 by MTBVAC was determinant in mediating bladder colonization by the bacteria, which correlated with augmented antitumoral efficacy. We further analyzed the mechanism of action of bacterial immunotherapy and found that it critically relied on the adaptive cytotoxic response. MTBVAC enhanced both tumor antigen-specific CD4 + and CD8 + T-cell responses, in a process dependent on stimulation of type 1 conventional dendritic cells. Importantly, improved intravesical bacterial immunotherapy using MBTVAC induced eradication of fully established bladder tumors, both as a monotherapy and specially in combination with the immune checkpoint inhibitor antiprogrammed cell death ligand 1 (anti PD-L1). Conclusion These results contribute to the understanding of the mechanisms behind successful bacterial immunotherapy against BC and characterize a novel therapeutic approach for BCG-unresponsive NMIBC cases. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Brazilian melon landraces resistant to Podosphaera xanthii are unique germplasm resources

"This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] Podosphaera xanthii is the most important causal agent of powdery mildew in melon, a crop ranked within the most economically important species worldwide. The best strategy to face this fungus disease, which causes important production losses, is the development of genetically resistant cultivars. Genetic breeding programmes require sources of resistance, and a few ones have been reported in melon, mostly in Momordica and Acidulus horticultural groups. However, the existence of many races that reduces the durability of the resistance makes necessary to find new resistant genotypes with different genetic backgrounds. In this work, Brazilian germplasm, together with a set of Indian landraces, and the COMAV¿s (Institute for the Conservation and Breeding of Agricultural Biodiversity) melon core collection, representing the whole variability of the species, were assessed for resistance against some common races in Spain and Brazil and genotyped with a 123-SNP (single nucleotide polymorphisms) genotyping platform to study the molecular relationships of the resistant accessions. In the first experiment, carried out in Valencia (Spain) in 2013, seventy-nine melon accessions were evaluated using artificial inoculation. Five accessions selected as resistant were also evaluated against races 1, 3, and 5 in Mossoró (Brazil, 2015) and against race 3.5 in Valencia (2016) under greenhouse conditions, and under four field conditions in Brazil. The accessions, AL-1, BA-3, CE-3, and RN-2, within the Brazilian collection, presented resistance against all the races of P. xanthii assayed in all conditions tested. AL-1, CE-3 and RN-2 were molecularly more similar to wild agrestis and Acidulus melons from Asia and Africa, while BA-3 grouped with Momordica types. Molecular analysis also confirmed that these new Brazilian sources of resistance differ from those previously reported, constituting interesting materials to encourage genetic breeding programmes, especially in Brazil and Spain.This work was supported by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq ( Processes: 485739/2013-5; 312315/2013-9) and CAPES-DPGU (294/2013) and by the projects funded by the Ministerio de Economia y Competitividad AGL2014-53398-C2-1-R and AGL2014-53398-C2-2-R (jointly funded by FEDER). We also thank Sakata Seed Sudamerica Ltda for the inoculum source for the different P. xanthii races employed.Nunes, EWLP.; Esteras Gómez, C.; Ricarte, AO.; Martínez-Pérez, EM.; Gómez-Guillamon, ML.; Nunes, GHS.; Picó Sirvent, MB. (2017). Brazilian melon landraces resistant to Podosphaera xanthii are unique germplasm resources. Annals of Applied Biology. 171(2):214-228. https://doi.org/10.1111/aab.12370S214228171

Artroplastia total de codo tras fractura de húmero distal en ancianos. Revisión de casos.

Osteosynthesis is the gold standard in most distal humerus fractures but in elderly patients, arthroplasty may be a better option. The aim of the study was to assess our results with total elbow arthroplasty after acute distal humerus fracture in the elderly. Retrospective study to evaluate clinical and functional results plus complications of all patients from our hospital with a total elbow arthroplasty performed for acute distal humeral fracture. 18 patients were included with a mean age of 77 years (63-87). The mean postoperative range of motion was 89º and the average MEPS and DASH score 80 and 26 respectively. There were 4 complications (22%) and no reoperations. Total elbow arthroplasty can be a good choice for distal humerus fracture, as long as they are indicated in patients with complex fractures, difficult to synthesize due to osteoporotic or severe comminution and with a low functional demand

Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile

In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also

Recovery from depressive symptoms, state anxiety and post-traumatic stress disorder in women exposed to physical and psychological, but not to psychological intimate partner violence alone: A longitudinal study

<p>Abstract</p> <p>Background</p> <p>It is well established that intimate male partner violence (IPV) has a high impact on women's mental health. It is necessary to further investigate this impact longitudinally to assess the factors that contribute to its recovery or deterioration. The objective of this study was to assess the course of depressive, anxiety and post-traumatic stress disorder (PTSD) symptoms and suicidal behavior over a three-year follow-up in female victims of IPV.</p> <p>Methods</p> <p>Women (n = 91) who participated in our previous cross-sectional study, and who had been either physically/psychologically (n = 33) or psychologically abused (n = 23) by their male partners, were evaluated three years later. A nonabused control group of women (n = 35) was included for comparison. Information about mental health status and lifestyle variables was obtained through face-to-face structured interviews.</p> <p>Results</p> <p>Results of the follow-up study indicated that while women exposed to physical/psychological IPV recovered their mental health status with a significant decrease in depressive, anxiety and PTSD symptoms, no recovery occurred in women exposed to psychological IPV alone. The evolution of IPV was also different: while it continued across both time points in 65.21% of psychologically abused women, it continued in only 12.12% of physically/psychologically abused women while it was reduced to psychological IPV in 51.5%. Hierarchical multiple regression analyses indicated that cessation of physical IPV and perceived social support contributed to mental health recovery, while a high perception of lifetime events predicted the continuation of PTSD symptoms.</p> <p>Conclusion</p> <p>This study shows that the pattern of mental health recovery depends on the type of IPV that the women had been exposed to. While those experiencing physical/psychological IPV have a higher likelihood of undergoing a cessation or reduction of IPV over time and, therefore, could recover, women exposed to psychological IPV alone have a high probability of continued exposure to the same type of IPV with a low possibility of recovery. Thus, women exposed to psychological IPV alone need more help to escape from IPV and to recuperate their mental health. Longitudinal studies are needed to improve knowledge of factors promoting or impeding health recovery to guide the formulation of policy at individual, social and criminal justice levels.</p

Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation. Methods: Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease. Results: The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001), mostly due to variants of unknown significance (VUS) in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3%) had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN. Conclusions: A small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM

The effectiveness of sewage treatment processes to remove faecal pathogens and antibiotic residues

Pathogens and antibiotics enter the aquatic environment via sewage effluents and may pose a health risk to wild life and humans. The aim of this study was to determine the levels of faecal bacteria, and selected antibiotic residues in raw wastewater and treated sewage effluents from three different sewage treatment plants in the Western Cape, South Africa. Sewage treatment plant 1 and 2 use older technologies, while sewage treatment plant 3 has been upgraded and membrane technologies were incorporated in the treatment processes. Coliforms and Escherichia coli (E. coli) were used as bioindicators for faecal bacteria. A chromogenic test was used to screen for coliforms and E. coli. Fluoroquinolones and sulfamethoxazole are commonly used antibiotics and were selected to monitor the efficiency of sewage treatment processes for antibiotic removal. Enzyme Linked Immunosorbent Assays (ELISAs) were used to quantitate antibiotic residues in raw and treated sewage. Raw intake water at all treatment plants contained total coliforms and E. coli. High removal of E. coli by treatment processes was evident for treatment plant 2 and 3 only. Fluoroquinolones and sulfamethoxazole were detected in raw wastewater from all sewage treatment plants. Treatment processes at plant 1 did not reduce the fluoroquinolone concentration in treated sewage effluents. Treatment processes at plant 2 and 3 reduced the fluoroquinolone concentration by 21% and 31%, respectively. Treatment processes at plant 1 did not reduce the sulfamethoxazole concentration in treated sewage effluents. Treatment processes at plant 2 and 3 reduced sulfamethoxazole by 34% and 56%, respectively. This study showed that bacteria and antibiotic residues are still discharged into the environment. Further research needs to be undertaken to improve sewage treatment technologies, thereby producing a better quality treated sewage effluent