This study analysed genomic variation of the translation elongation factor 1α (TEF‐1α) and the intergenic spacer region (IGS) of the nuclear ribosomal operon of Fusarium oxysporum f. sp. cubense ...(Foc) isolates, from different banana production areas, representing strains within the known races, comprising 20 vegetative compatibility groups (VCG). Based on two single nucleotide polymorphisms present in the IGS region, a PCR‐based diagnostic tool was developed to specifically detect isolates from VCG 01213, also called tropical race 4 (TR4), which is currently a major concern in global banana production. Validation involved TR4 isolates, as well as Foc isolates from 19 other VCGs, other fungal plant pathogens and DNA samples from infected tissues of the Cavendish banana cultivar Grand Naine (AAA). Subsequently, a multiplex PCR was developed for fungal or plant samples that also discriminated Musa acuminata and M. balbisiana genotypes. It was concluded that this diagnostic procedure is currently the best option for the rapid and reliable detection and monitoring of TR4 to support eradication and quarantine strategies.
This paper deals with the Open-Pit-Mining Operational Planning problem with dynamic truck allocation. The objective is to optimize mineral extraction in the mines by minimizing the number of mining ...trucks used to meet production goals and quality requirements. According to the literature, this problem is NP-hard, so a heuristic strategy is justified. We present a hybrid algorithm that combines characteristics of two metaheuristics: Greedy Randomized Adaptive Search Procedures and General Variable Neighborhood Search. The proposed algorithm was tested using a set of real-data problems and the results were validated by running the
CPLEX optimizer with the same data. This solver used a mixed integer programming model also developed in this work. The computational experiments show that the proposed algorithm is very competitive, finding near optimal solutions (with a gap of less than 1%) in most instances, demanding short computing times.
In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed–platinum) significantly improved overall survival (OS) and progression-free ...survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed–platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed–platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab.
Eligible patients were randomized 2 : 1 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks (for up to 35 cycles, ∼2 years) plus four cycles of pemetrexed (500 mg/m2) and investigators’ choice of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg·min/ml) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed–platinum could cross over to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS.
After a median follow-up of 31.0 months, pembrolizumab plus pemetrexed–platinum continued to improve OS hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.46-0.69 and PFS (HR, 0.49; 95% CI, 0.41-0.59) over placebo plus pemetrexed–platinum regardless of programmed death-ligand 1 expression. Objective response rate (ORR) (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41-0.61) were improved in patients who received pembrolizumab plus pemetrexed–platinum. Eighty-four patients (40.8%) from the placebo plus pemetrexed–platinum group crossed over to pembrolizumab on-study. Grade 3-5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed–platinum and 66.8% of patients receiving placebo plus pemetrexed–platinum. Fifty-six patients completed 35 cycles (∼2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cut-off.
Pembrolizumab plus pemetrexed–platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed–platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed–platinum in patients with previously untreated metastatic nonsquamous NSCLC.
•KEYNOTE-189 evaluated the efficacy and safety of pembrolizumab + pemetrexed–platinum versus placebo + pemetrexed–platinum in NSCLC.•Pembrolizumab + pemetrexed–platinum improved OS (HR, 0.56; 95% CI, 0.46-0.69) versus placebo + pemetrexed–platinum.•Pembrolizumab + pemetrexed–platinum improved PFS (HR, 0.49; 95% CI, 0.41-0.59) versus placebo + pemetrexed–platinum.•ORR was 85.7% in patients who completed 35 cycles (2 years) of pembrolizumab therapy.•Pembrolizumab + pemetrexed–platinum had manageable toxicity.
The antimicrobial activity of four labdane-type diterpenes isolated from the oleoresin of Copaifera langsdorffii as well as of two commercially available diterpenes (sclareol and manool) was ...investigated against a representative panel of microorganisms responsible for periodontitis. Among all the evaluated compounds, (-)-copalic acid (CA) was the most active, displaying a very promising MIC value (3.1 µg mL-1; 10.2 µM) against the key pathogen (Porphyromonas gingivalis) involved in this infectious disease. Moreover, CA did not exhibit cytotoxicity when tested in human fibroblasts. Time-kill curve assays performed with CA against P. gingivalis revealed that this compound only inhibited the growth of the inoculums in the first 12 h (bacteriostatic effect). However, its bactericidal effect was clearly noted thereafter (between 12 and 24 h). It was also possible to verify an additive effect when CA and chlorhexidine dihydrochloride (CHD, positive control) were associated at their MBC values. The time curve profile resulting from this combination showed that this association needed only six hours for the bactericidal effect to be noted. In summary, CA has shown to be an important metabolite for the control of periodontal diseases. Moreover, the use of standardized extracts based on copaiba oleoresin with high CA contents can be an important strategy in the development of novel oral care products.
In a previous study, we reported the identification and synthesis of a male-specific sex pheromone component of the stink bug,
Pellaea stictica
, as the alcohol 2,4,8,13-tetramethyltetradecan-1-ol (
...1
). To establish the correlation between the stereochemistry of the pheromone and its bioactivity, it first was necessary to determine its absolute configuration. For this purpose, a series of syntheses were designed to: (a) furnish a mixture of all possible stereoisomers; (b) a narrowed down group of diastereomers, and (c) one specific enantiomer. A crucial step in the syntheses involved a coupling reaction between two key intermediates: a phosphonium salt and an aldehyde, through a Wittig olefination. Nuclear magnetic resonance data of a mixture of the synthetic pheromone diastereomers and further comparison of GC retention times with that of the natural product by gas chromatography suggested that the methyl branches at C2 and C4 were in a
syn
relationship, reducing the possibilities to only four of the eight possible stereoisomers. Employing GC analysis, chiral derivatization reagents and synthetic (8
R
)-2,4-
syn
-
1
it was possible to confirm the configuration of the methyl branch at C8 as
R
, reducing the number of possible stereoisomers to two. After enantioselective synthesis of (2
R
,4
R
,8
R
)-
1
, the absolute configurations of all methyl branches of the natural compound were confirmed as
R
, fully identifying the male-produced sex pheromone of
P. stictica
as (2
R
,4
R
,8
R
)-2,4,8,13-tetramethyltetradecan-1-ol.
Recent studies have recognised the importance of pulmonary hypertension (PH) in sickle cell disease (SCD). The aim of this study was to determine the prevalence and prognostic impact of PH and its ...features in patients with SCD. 80 patients with SCD underwent baseline clinical evaluation, laboratory testing, 6-min walk tests (6MWTs) and echocardiography. Patients with a peak tricuspid regurgitant jet velocity (TRV) of ≥ 2.5 m·s(-1) were further evaluated through right heart catheterisation (RHC) to assure the diagnosis of PH. Our study evidenced a 40% prevalence of patients with elevated TRV at echocardiography. RHC (performed in 25 out of 32 patients) confirmed PH in 10% (95% CI 3.4-16.5%) of all patients, with a prevalence of post-capillary PH of 6.25% (95% CI 0.95-11.55%) and pre-capillary PH of 3.75% (95% CI -0.4-7.9%). Patients with PH were older, had worse performance in 6MWTs, and more pronounced anaemia, haemolysis and renal dysfunction. Survival was shorter in patients with PH. Our study reinforced the use of echocardiography as a screening tool for PH in SCD and the mandatory role of RHC for proper diagnosis. Our findings confirmed the prognostic significance of PH in SCD as its association to pronounced haemolytic profile.
Light amplification by stimulated emission of radiation (laser) sources has many advantages for use in high-data-rate optical wireless communications (OWCs). In particular, the low-cost and ...high-bandwidth properties of laser sources, such as vertical-cavity surface-emitting lasers (VCSELs), make them attractive for future indoor OWCs. In order to be integrated into future indoor networks, such lasers should conform to eye safety regulations determined by the International Electrotechnical Commission (IEC) standards for laser safety. In this article, we provide a detailed study of beam propagation to evaluate the received power of various laser sources, based on which and the maximum permissible exposure (MPE) defined by the IEC 60825-1:2014 Standard, we establish a comprehensive framework for eye safety analyses. This framework allows us to calculate the maximum allowable transmit power, which is crucial in the design of a reliable and safe laser-based wireless communication system. Initially, we consider a single-mode Gaussian beam and calculate the maximum permissible transmit power. Subsequently, we generalize this approach for higher mode beams. It is shown that the <inline-formula> <tex-math notation="LaTeX">M </tex-math></inline-formula>-squared-based approach for analysis of multimode lasers ensures the IEC eye safety limits; however, in some scenarios, it can be too conservative compared to the precise beam decomposition method. Laser safety analyses with consideration of optical elements, such as lens and diffuser, as well as for the VCSEL array, have been also presented. Skin safety, as another significant factor of laser safety, has also been investigated in this article. We have studied the impacts of various parameters, such as wavelength, exposure duration, and the divergence angle of laser sources on the safety analysis by presenting insightful results.
Type 1 diabetes (T1D) is a multifactorial disease that has a strong genetic component. The HLA-G is a nonclassical HLA class I locus that is associated with immunomodulatory functions, including ...downregulation of innate and adaptive immune responses and induction of immune tolerance. However, there is currently limited information about the involvement of HLA-G in T1D susceptibility. This case-control study aims to investigate the T1D susceptibility association of alleles and genotypes of a widely investigated 14-bp insertion/deletion polymorphism in the HLA-G and to provide further evidence of the frequency distribution of class II HLA-DR-DQ-risk genotypes in T1D children and adolescents in the Brazilian population. The deletion allele and the homozygous deletion genotype are associated with susceptibility to T1D and the insertion allele and the heterozygous deletion/insertion genotype are associated with protection from T1D. We also confirm that genetic susceptibility to T1D is associated with the DRB1*03:01-DQA1*05:01-DQB1*02:01 and DRB1*04-DQA1*03:01-DQB1*03:02 haplotypes in Brazilian northeast region. The DR3-DQ2/DR4-DQ8 genotype conferred the highest detected risk for T1D. Our results identify a novel association of the 14-bp deletion allele and the homozygous deletion genotype with T1D development and provide additional evidence of the importance of HLA class II heterozygous DR3-DQ2/DR4-DQ8 genotype in T1D susceptibility.
K. Schum (Sterculiaceae), commonly known in Brazil as 'pitó', is traditionally used by indigenous peoples as insecticides and repellents. The present work reports on the the phytoconstituents from ...aerial parts of
and evaluation of the larvicidal potential of its extract. The compounds were isolated using chromatographic techniques and identified by NMR, IR and LC-HRMS. This study led to the isolation of a fatty acid, one aliphatic alcohol, four chlorophyll derivatives, one steroid, triterpenes, a lignan, and flavonoids, highlighting the new compounds in the literature, 5,4'-di-hydroxy-7-methoxy-8-
-sulphate flavone (mariahine) (
) and 5,3'-di-hydroxy-7,4'-dimethoxy-8-
-sulphate flavone (condadine) (
). The work presented here contributes to the chemotaxonomic knowledge of the Sterculiaceae family by describing the occurrence of sulphated flavonoids in this family for the first time. The crude ethanolic extract of
featured robust larvicidal activity against
larvae, showing that the extract can be useful as a domestic larvicide, just as indicated by traditional use, to combat
, a vector insect of severe viral diseases, such as dengue and Zika.
The article delves into the intricate phenomenon of deposition in heat exchangers and how a piece of equipment known as the benchtop heat exchanger test instrument (BHETI) has been developed to ...expedite the examination of this phenomenon. The BHETI subjects samples to substantial stress, facilitating the assessment of an oil’s tendency to generate deposits. Tests were conducted on two crude oil blends referred to as blend A and blend B using a BHETI unit. This equipment permits testing under various controlled conditions, including temperature, pressure, and volumetric flow rate. The results indicated that blend A exhibited a higher susceptibility to deposition compared to blend B due to its elevated concentration of light hydrocarbons. The wall temperature exerted a significant influence on the deposition rate, with higher temperatures leading to elevated deposition rates. Conversely, lower oil flow rates resulted in increased deposition rates. Furthermore, extended-term tests unveiled fluctuations in deposition rates over time when blending the two oil samples, suggesting intermittent fouling processes, possibly attributable to thermodynamic imbalances induced by mixing, rendering the oil’s asphaltenes less stable. The outcomes were subjected to analysis employing the Colloidal Instability Index (CII), which indicated that the majority of samples exhibited values exceeding 0.9, signifying asphaltene instability. Additionally, the examination of saturated, aromatic, and NSO (nitrogen, sulfur, oxygen) fractions revealed decreased saturation and increased aromatics after the deposition tests.
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