In vitro assessment of antimicrobial, antioxidant, and cytotoxic properties of Saccharin-Tetrazolyl and-Thiadiazolyl derivatives: the simple dependence of the pH value on antimicrobial activity

The antimicrobial, antioxidant, and cytotoxic activities of a series of saccharin-tetrazolyl and -thiadiazolyl analogs were examined. The assessment of the antimicrobial properties of the referred-to molecules was completed through an evaluation of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against Gram-positive and Gram-negative bacteria and yeasts. Scrutiny of the MIC and MBC values of the compounds at pH 4.0, 7.0, and 9.0 against four Gram-positive strains revealed high values for both the MIC and MBC at pH 4.0 (ranging from 0.98 to 125 µg/mL) and moderate values at pH 7.0 and 9.0, exposing strong antimicrobial activities in an acidic medium. An antioxidant activity analysis of the molecules was performed by using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, which showed high activity for the TSMT (N-(1-methyl-2H-tetrazol-5-yl)-N-(1,1-dioxo-1,2-benzisothiazol-3-yl) amine, 7) derivative (90.29% compared to a butylated hydroxytoluene positive control of 61.96%). Besides, the general toxicity of the saccharin analogs was evaluated in an Artemia salina model, which displayed insignificant toxicity values. In turn, upon an assessment of cell viability, all of the compounds were found to be nontoxic in range concentrations of 0-100 µg/mL in H7PX glioma cells. The tested molecules have inspiring antimicrobial and antioxidant properties that represent potential core structures in the design of new drugs for the treatment of infectious diseases.Funding Agency Portuguese Foundation for Science and Technology UID/QUI/00100/2019 UID/MULTI/04326/2019 -CCMAR Portuguese Foundation for Science and Technology SFRH/BPD/99851/2014 IST-ID/115/2018info:eu-repo/semantics/publishedVersio

CGIAR modeling approaches for resource constrained scenarios: IV Models for analyzing socio‐economic factors to improve policy recommendations

International crop-related research as conducted by the CGIAR uses crop modelingfor a variety of purposes. By linking crop models with economic models andapproaches, crop model outputs can be effectively used as inputs into socioeco-nomic modeling efforts for priority setting and policy advice using ex-ante impactassessment of technologies and scenario analysis. This requires interdisciplinarycollaboration and very often collaboration across a variety of research organizations.This study highlights the key topics, purposes, and approaches of socioeconomicanalysis within the CGIAR related to cropping systems. Although each CGIARcenter has a different mission, all CGIAR centers share a common strategy of strivingtoward a world free of hunger, poverty, and environmental degradation. This meansresearch is mostly focused toward resource-constrained smallholder farmers. Thereview covers global modeling efforts using the IMPACT model to farm householdbio-economic models for assessing the potential impact of new technologies onfarming systems and livelihoods. Although the CGIAR addresses all aspects of foodsystems, the focus of this review is on crop commodities and the economic analysislinked to crop-growth model results. This study, while not a comprehensive review,provides insights into the richness of the socioeconomic modeling endeavors withinthe CGIAR. The study highlights the need for interdisciplinary approaches to addressthe challenges this type of modeling faces

Carbenic nitrile imines: Properties and reactivity

Structures and properties of nitrile imines were investigated computationally at B3LYP and CCSD(T) levels. Whereas NBO analysis at the B3LYP DFT level invariably predicts a propargylic electronic structure, CCSD(T) calculations permit a clear distinction between propargylic, allenic, and carbenic structures. Nitrile imines with strong IR absorptions above ca. 2150 cm-1 have propargylic structures with a CN triple bond (RCNNSiMe 3 and R2BCNNBR2), and those with IR absorptions below ca. 2150 cm-1 are allenic (HCNNH, PhCNNH, and HCNNPh). Nitrile imines lacking significant cumulenic IR absorptions at 1900-2200 cm -1 are carbenic (R-(C:)-N=N-R′). Electronegative but lone pair-donating groups NR2, OR, and F stabilize the carbenic form of nitrile imines in the same way they stabilize "normal" singlet carbenes, including N-heterocyclic carbenes. NBO analyses at the CCSD(T) level confirm the classification into propargylic, allenic, and carbenic reactivity types. Carbenic nitrile imines are predicted to form azoketenes 21 with CO, to form [2+2] and [2+4] cycloadducts and borane adducts, and to cyclize to 1H-diazirenes of the type 24 in mildly exothermic reactions with activation energies in the range 29-38 kcal/mol. Such reactions will be readily accessible photochemically and thermally, e.g., under the conditions of matrix photolysis and flash vacuum thermolysis

Modelling generalized firms' restructuring using inverse DEA

The key consideration for firms’ restructuring is improving their operational efficiencies. Market conditions often offer opportunities or generate threats that can be handled by restructuring scenarios through consolidation, to create synergy, or through split, to create reverse synergy. A generalized restructuring refers to a move in a business market where a homogeneous set of firms, a set of pre-restructuring decision making units (DMUs), proceed with a restructuring to produce a new set of post-restructuring entities in the same market to realize efficiency targets. This paper aims to develop a novel inverse Data Envelopment Analysis based methodology, called GInvDEA (Generalized Inverse DEA), for modeling the generalized restructuring. Moreover, the paper suggests a linear programming model that allows determining the lowest performance levels, measured by efficiency that can be achieved through a given generalized restructuring. An application in banking operations illustrates the theory developed in the paper

Structural and functional insights into asymmetric enzymatic dehydration of alkenols

The asymmetric dehydration of alcohols is an important process for the direct synthesis of alkenes. We report the structure and substrate specificity of the bifunctional linalool dehydratase isomerase (LinD) from the bacterium Castellaniella defragrans that catalyzes in nature the hydration of β-myrcene to linalool and the subsequent isomerization to geraniol. Enzymatic kinetic resolutions of truncated and elongated aromatic and aliphatic tertiary alcohols (C5-C15) that contain a specific signature motif demonstrate the broad substrate specificity of LinD. The three-dimensional structure of LinD from Castellaniella defragrans revealed a pentamer with active sites at the protomer interfaces. Furthermore, the structure of LinD in complex with the product geraniol provides initial mechanistic insights into this bifunctional enzyme. Site-directed mutagenesis confirmed active site amino acid residues essential for its dehydration and isomerization activity. These structural and mechanistic insights facilitate the development of hydrating catalysts, enriching the toolbox for novel bond-forming biocatalysis

Pulmonary arterial hypertension in patients with sleep apnoea syndrome

BACKGROUND—Pulmonary arterial hypertension (PAH) in patients with sleep apnoea syndrome (SAS) is classically ascribed to associated chronic obstructive pulmonary disease (COPD). The aim of this retrospective study was to evaluate the possible occurrence of PAH as a complication of SAS in patients without COPD.
METHODS—Right heart catheterisation was performed in 44 patients with SAS and without COPD confirmed by polysomnography (apnoea index >5/h) admitted for the administration of nasal continuous positive airway pressure (CPAP).
RESULTS—Precapillary PAH, defined as mean pulmonary arterial pressure of >20 mm Hg with pulmonary capillary wedge pressure <15 mm Hg, was observed in 12/44 (27%) patients with SAS. There were no significant differences in apnoea index between patients with (PAH+) and those without PAH (PAH-) (42.6 (26.3) versus 35.8 (21.7) apnoeas/h). The PAH+ group differed significantly from the PAH- group in the following respects: lower daytime arterial oxygen tension (PaO(2)) (9.6 (1.1) versus 11.3 (1.5) kPa, p=0.0006); higher daytime arterial carbon dioxide tension (PaCO(2)) (5.8 (0.5) versus 5.3 (0.5) kPa, p=0.002); more severe nocturnal hypoxaemia with a higher percentage of total sleep time spent at SaO(2) <80% (32.2(28.5)% versus 10.7 (18.8)%, p=0.005); and higher body mass index (BMI) (37.4 (6) versus 30.3 (6.7) kg/m(2), p=0.002). The PAH+ patients had significantly lower values of vital capacity (VC) (87 (14)% predicted versus 105 (20)% predicted, p=0.005), forced expiratory volume in one second (FEV(1)) (82 (14)% predicted versus 101 (17)% predicted, p=0.001), expiratory reserve volume (40 (16)% predicted versus 77 (41)% predicted, p=0.003), and total lung capacity (87 (13)% predicted versus 98 (18)% predicted, p=0.04). Stepwise multiple regression analysis showed that mean pulmonary artery pressure (PAPm) was positively correlated with BMI and negatively with PaO(2).
CONCLUSION—Pulmonary arterial hypertension is frequently observed in patients with SAS, even when COPD is absent, and appears to be related to the severity of obesity and its respiratory mechanical consequences.