This work aimed to develop a real-time test platform for systems associated with the tactile internet area. The proposal comprises a master device, a communication channel and a slave device. The ...master device is a tactile glove (wearable technology) that works as a tactile interface based on vibratory feedback. The master device can interact with virtual elements (local or remote). The Matlab/Simulink environment and a robotics toolbox form the communication channel and the slave device. The communication channel introduces a bidirectional connection of variable latency, and the slave device is defined as a robotic phantom omni manipulator emulated in Matlab/Simulink. The virtual robotic manipulator, the slave device, can generate different types of tactile sensations in the tactile glove, that is, in the master device. The platform can model tactile sensations such as coarse roughness, fine roughness, smoothness, dripping and softness. The proposed platform presented adequate results and can be used to test various algorithms and methods correlated to the tactile internet.
Introduction: Gene therapy is a promising approach to be applied in cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies. However, cardiomyocytes are ...crucial cell types that are considered hard-to- transfect. The entrapment of nucleic acids in non-viral vectors, such as lipid nanoparticles (LNPs), is an attractive approach for safe and effective delivery. Methods: Here, a mini-library of engineered LNPs was developed for pDNA delivery in cardiomyocytes. LNPs were characterized and screened for pDNA delivery in cardiomyocytes and identified a lead LNP formulation with enhanced transfection efficiency. Results: By varying lipid molar ratios, the LNP formulation was optimized to deliver pDNA in cardiomyocytes with enhanced gene expression in vitro and in vivo, with negligible toxicity. In vitro, our lead LNP was able to reach a gene expression greater than 80%. The in vivo treatment with lead LNPs induced a twofold increase in GFP expression in heart tissue compared to control. In addition, levels of circulating myeloid cells and inflammatory cytokines remained without significant changes in the heart after LNP treatment. It was also demonstrated that cardiac cell function was not affected after LNP treatment. Conclusion: Collectively, our results highlight the potential of LNPs as an efficient delivery vector for pDNA to cardiomyocytes. This study suggests that LNPs hold promise to improve gene therapy for treatment of cardiovascular disease. Keywords: lipid nanoparticles, ionizable lipids, pDNA delivery, heart, cardiomyocytes
Purpose: Solid tumors harboring tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb) received agnostic approval for pembrolizumab. This work aims to analyze the somatic mutational ...profile’s influence on the outcomes of patients with TMB-high tumors treated with immune checkpoint inhibitors (ICIs). Methods: This post-hoc analysis evaluated clinical and molecular features of patients with solid tumors treated with ICIs that could be either monoclonal antibody directed against programmed cell death protein-1 or monoclonal antibody directed against programmed cell death ligand 1 (anti-PD-1/anti-PD-L1), monoclonal antibody directed against cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) or a combined treatment regimen including one anti-PD-1/anti-PD-L1 and one anti-CTLA-4 (ICIs combination). We performed OS analysis for TMB thresholds of ≥10, ≥20, and <10 mut/Mb. We assessed OS according to the mutational profile for a TMB ≥ 10 mut/Mb cutoff. For genes correlated with OS at the univariate assessment, we conducted a Cox multivariate analysis adjusted by median TMB, sex, age, microsatellite instability (MSI), and histology. Results: A total of 1661 patients were investigated; 488 with a TMB ≥10 mut/Mb (29.4%). The median OS was 42 months for TMB ≥10 or 20 mut/Mb, and 15 months for TMB <10 mut/Mb (p < 0.005). Among TMB ≥10 mut/Mb patients, mutations in E2F3 or STK11 correlated with worse OS, and mutations in NTRK3, PTPRD, RNF43, TENT5C, TET1, or ZFHX3 with better OS. These associations were confirmed with univariate and multivariate analyses (p < 0.05). Melanoma histology and TMB above the median endowed patients with better OS (p < 0.05), while MSI status, age, and gender did not have a statistically significant effect on OS. Conclusion: Combining TMB and mutation profiles in key cancer genes can better qualify patients for ICI treatment and predict their OS.
Generating streams of true random numbers is a critical component of many electronic and information systems. The design of fully integrated, area and power efficient true random number generators ...(TRNGs) is a challenge. We propose a fully integrated, lightweight implementation that uses the random telegraph noise (RTN) of standard MOSFET as entropy source. It is not analog-intensive, and without traditional post-processing algorithms, the generated random bit sequence passes the National Institute of Standards and Technology (NIST) tests.
Farmers of the Franca region in Brazil observed that Bidens sulphurea was able to eliminate the Panicum maximum weed, which infected coffee plantations, without affecting the crop. In an effort to ...determine if the inhibitory effects observed were due to the presence of phytotoxic compounds from leaves and roots, a biodirected isolation and spectroscopic characterization has been carried out. The leaf dichloromethane and root acetone extracts were the most active, and the former appeared to be more phytotoxic to the target species, including four weeds. A total of 26 compounds were isolated from leaves and roots, and four of them are described here for the first time. The major compounds in the leaf extract are the sesquiterpene lactones costunolide, reynosin, and santamarine, and these showed marked inhibition. Amaranthus viridis and Panicum maximum were the most sensitive species of the weeds tested. These three phytotoxic lactones were also evaluated on A. viridis and P. maximum under hydroponic conditions. A. viridis was the most affected species with the three lactones, and santamarine was the most phytotoxic compound on both. This is the first time that the phytotoxicity of sesquiterpene lactones has been evaluated on hydroponic culture. The work described here is a preliminary approach for the use of B. sulphurea for weed control in agriculture, both as a cover crop and by use of its components as natural herbicide leads.
The ability to select, isolate, and manipulate micron-sized particles or small clusters has made optical tweezers one of the emergent tools for modern biotechnology. In conventional setups, the ...classification of the trapped specimen is usually achieved through the acquired image, the scattered signal, or additional information such as Raman spectroscopy. In this work, we propose a solution that uses the temporal data signal from the scattering process of the trapping laser, acquired with a quadrant photodetector. Our methodology rests on a pre-processing strategy that combines Fourier transform and principal component analysis to reduce the dimension of the data and perform relevant feature extraction. Testing a wide range of standard machine learning algorithms, it is shown that this methodology allows achieving accuracy performances around 90%, validating the concept of using the temporal dynamics of the scattering signal for the classification task. Achieved with 500 millisecond signals and leveraging on methods of low computational footprint, the results presented pave the way for the deployment of alternative and faster classification methodologies in optical trapping technologies.
We assess whether a Payments for Ecosystem Services (PES) programme met its objectives of reducing soil erosion and yielding water in an environmental protected area, the Guariroba River Basin, ...Midwestern Brazil. We measured rainfall and water discharge throughout 2012 and 2016. During the same period, soil and water conservation practices were performed in the basin, such as: building level terraces and riparian vegetation recovery. We separated streamflow into baseflow and direct runoff, then we evaluted the baseflow index that indicated that groundwater significantly contributes to total flow. Therefore, to investigate the effects on streamflow, we performed a trend analysis in the baseflow time series using the Mann-Kendall test. In addition, we analysed the efficiency of soil erosion regulation practices over time, considering the total payment and the trends found in the baseflow. Whereas precipitation records present a decreasing trend (1 mm month−1), baseflow tends to increase by 0.018 m3 s−1 in the same period. Our findings show that soil conservation practices performed in the basin increase baseflow and also provide a better resilience to endure extreme events such as drought based on an increase in forest areas and soil conservation practices such as level terrace.
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•We assessed the effects of Payment for Ecosystem Services on water provisioning and sediment transport using observed data.•Baseflow tends to increase by 0.018 m3 s−1 in five years;•Soil conservation practices reduced soil erosion by a quarter.
The coronavirus disease 2019 (COVID-19) pandemic unfolded due to the widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission reinforced the urgent need for affordable ...molecular diagnostic alternative methods for massive testing screening. We present the clinical validation of a pH-dependent colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) for SARS-CoV-2 detection. The method revealed a limit of detection of 19.3 ± 2.7 viral genomic copies/μL when using RNA extracted samples obtained from nasopharyngeal swabs collected in guanidine-containing viral transport medium. Typical RT-LAMP reactions were performed at 65°C for 30 min. When compared to reverse transcriptase–quantitative polymerase chain reaction (RT-qPCR), up to cycle-threshold (Ct) value 32, RT-LAMP presented 98% 95% confidence interval (CI) = 95.3–99.5% sensitivity and 100% (95% CI = 94.5–100%) specificity for SARS-CoV-2 RNA detection targeting
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genes. No cross-reactivity was detected when testing other non–SARS-CoV virus, confirming high specificity. The test is compatible with primary RNA extraction–free samples. We also demonstrated that colorimetric RT-LAMP can detect SARS-CoV-2 variants of concern and variants of interest, such as variants occurring in Brazil named gamma (P.1), zeta (P.2), delta (B.1.617.2), B.1.1.374, and B.1.1.371. The method meets point-of-care requirements and can be deployed in the field for high-throughput COVID-19 testing campaigns, especially in countries where COVID-19 testing efforts are far from ideal to tackle the pandemics. Although RT-qPCR is considered the gold standard for SARS-CoV-2 RNA detection, it requires expensive equipment, infrastructure, and highly trained personnel. In contrast, RT-LAMP emerges as an affordable, inexpensive, and simple alternative for SARS-CoV-2 molecular detection that can be applied to massive COVID-19 testing campaigns and save lives.
BIOREDUCTIVE ANTINEOPLASIC AGENTS: ADVANCES AND CHALLENGES AFTER 20 YEARS. Solid tumors are frequently affected by the presence of hypoxic cells, originating anomalous and disordered cell growth. ...This subpopulation presents resistance to conventional chemotherapy agents and radiotherapy, due to the difficulties of reaching the target region, the permanence in the G0 phase of cell cycle and the low local concentration of oxygen. The use of hypoxia activated prodrugs becomes, in this scenario, an effective and selective alternative in cancer therapy, though not yet available for clinical use in solid tumor treatment. Twenty years after the publication of the paper intitled “Agentes Antineoplásicos Biorredutíveis: Uma Nova Alternativa para o Tratamento de Tumores Sólidos” in the Química Nova journal (2002), the current essay aims to identify the advances in the pre-clinical and clinical studies regarding the development of new hypoxia-directed drugs and the improvement of the molecules previously studied. Moreover, to clarify the main challenges for the implementation and success of this drug class, in order to identify the hindrances for the preparation of a bioavailable, safe and selective drug.
Damaged yacon roots, often discarded, are a rich source of sweet carbohydrates. In this context, yacon roots from the Hualqui and Crespo varieties were characterized and processed into low-calorie ...and low-glycemic syrups for sugar reduction in foods. Syrups were obtained using, as technological adjuvants, lemon juice and its most relevant components: citric acid and ascorbic acid. The Hualqui variety was found to be mostly composed of fructose (210 g/kg), while the Crespo variety was rich in inulin (352 g/kg). The use of lemon juice during syrup production promoted the hydrolysis of inulin to fructooligosaccharides and fructose, yielding syrups with competitive relative sweetness (0.52–0.91), glycemic index (0.21–0.40), and caloric values (186–263 kcal/100 g) to commercial syrups. The increase in citric acid concentrations promoted inulin hydrolysis, yielding, at the highest concentration, syrups with higher fructose (333–445 g/kg) and kesto-type fructooligosaccharides (11–85 g/kg) content and lower surface stickiness and stringiness. The addition of ascorbic acid, as an antioxidant agent, decreased by 10% the free sugar content, negatively impacting the sweetness level. These results evidence that fructooligosaccharides-rich syrup can be obtained from yacon-damaged roots with tailored sweetness and low glycemic and caloric properties.
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