Reference, Preference, Convexity and Efficiency - Basic Notions in Multiobjective Decision Making

In commonly used Pareto optimality the notions reference, preference, convexity and efficiency are interrelated and of great importance. It is shown that the usual notion of convexity on the base of straight lines is not consistent with Pareto optimality. There are many possibilities to reach all efficient points by using a parameterized set of compromise criteria. Especially important for the decision maker's goal is to describe local wishes by corresponding reference points. It is useful to describe these reference points by preference levels or local utility fields. The method of direction diagrams helps to introduce the decision maker's imagination. The penalty scalarization method proves as a special case of direction diagrams. Direction diagrams serve for the design of good seeking procedures for efficient points expressed in terms of the control space

Efficient and precise CRISPR/Cas9-mediated MECP2 modifications in human-induced pluripotent stem cells

Patients with Rett syndrome (RTT) have severe mental and physical disabilities. The majority of RTT patients carry a heterozygous mutation in methyl-CpG binding protein 2 (MECP2), an X-linked gene encoding an epigenetic factor crucial for normal nerve cell function. No curative therapy for RTT syndrome exists, and cellular mechanisms are incompletely understood. Here, we developed a CRISPR/Cas9-mediated system that targets and corrects the disease relevant regions of the MECP2 exon 4 coding sequence. We achieved homologous recombination (HR) efficiencies of 20% to 30% in human cell lines and iPSCs. Furthermore, we successfully introduced a MECP2(R270X) mutation into the MECP2 gene in human induced pluripotent stem cells (iPSCs). Consequently, using CRISPR/Cas9, we were able to repair such mutations with high efficiency in human mutant iPSCs. In summary, we provide a new strategy for MECP2 gene targeting that can be potentially translated into gene therapy or for iPSCs-based disease modeling of RTT syndrome

A comprehensive study in efficacy of Vietnamese herbal extracts on whiteleg shrimp (<em>Penaeus vannamei</em>) against <em>Vibrio parahaemolyticus</em> causing acute hepatopancreatic necrosis disease (AHPND)

Traditional Vietnamese herbal species were examined for their antimicrobial activity and disease resistance in whiteleg shrimp. In-vitro screening, the extracts of ten herbs were conducted to test the inhibition ability against Vibrio parahaemolyticus, causing acute hepatopancreatic necrosis disease. The results showed that five out of ten herbal species, including Pithecellobium dulce, Melaleuca leucadendron, Eucalyptus globulus, Mimosa pirga, and Hibiscus sabdariffa displayed potent antibacterial activity. Besides, three types of extracts of H. sabdariffa, E. globulus, and M. pirga were coated to the pellet feed at a concentration of 1%. After 30 days of feeding, the whiteleg shrimp (Penaeus vannamei) were challenged by V. parahaemolyticus through immersion. The growth performance (such as growth rate in length and weight, survival rate), hematological parameters of total hemocytes (THC), hyaline hemocytes (HC), and granulocytes (GC), and hepatopancreas recovery under the treatments with herbal extracts of the whiteleg shrimp were significantly enhanced as compared with the control (without herbal extract). The mortality and the bacterial density in the hepatopancreas of shrimp decreased. Specifically, the mortality of shrimp in the treatment supplemented with the methanol extract of H. sabdariffa was the lowest, followed by M. pirga and E. globulus. The experimental results also indicated that H. sabdariffa, E. globulus, and M. pirga could improve immune parameters and disease resistance; therefore, they should be employed in sustainable shrimp, practical farming

Willingness to Pay for Improving Household Solid Waste Management in Vietnam

Management of solid waste is a major challenge in urban areas of most parts of the world, especially in developing countries. The study aimed to determine and estimate the willingness to pay (WTP) of the selected households for the improvement of solid waste management in Vietnam. The research evaluated WTP of household solid waste in case studies in Bien Hoa and My Tho cities using contingent valuation method (CVM). The data were collected through a closed-ended questionnaire survey and interviews with 200 households. The results showed that the most willingness to pay was equal to 10,000 and 15,000 VND per month. The respondents were willing to pay in Bien Hoa and My Tho with an average of 14,450 VND (0.63 USD) and 13,000 VND (0.56 USD) per month, respectively. Regression model identified influential factors on WTP of households in the two cities of Vietnam. The factors that significantly influence households’ WTP were monthly household income, education of respondents, age, occupation and solid waste volume (p<0.05). The results of this study can be used for the urban planning and implemented the sustainable development process in Bien Hoa and My Tho cities

Infection néonatale bactérienne précoce : Quand mettre sous antibiotique et quelle antibiothérapie ? Early bacterial neonatal infection: When to indicate antibiotic treatment and what antibiotic therapy ?

Objective. Propose a relevant management strategy that can identify newborns with a bacterial infectious risk and those under clinical monitoring alone or in combination with parenteral antibiotic therapy.Methods. Retrospective study carried out between SA &lt; 42, suspected of early bacterial infection and monitored in Maternity and in the Neonatology Unit of the Hospital Group Carnelle Portes of Oise [Val France]. The clinical-biological and bacteriological data, the therapeutic strategy and the evolution are analyzed. Results. Two hundred and forty newborns were eligible and divided into three groups: 120 asymptomatic newborns with antenatal criteria for bacterial infectious risk [G1NAS], 70 symptomatic newborns with antenatal criteria for bacterial infectious risk [G2NSCARIB] and 50 symptomatic newborns without antenatal criteria of bacterial infectious risk [G3NSSCARIB]. Inflammatory biology is limited tocolonized G1NAS newborns and symptomatic groups. The identified bacteria [Peripheral samples, gastric fluid, blood and cerebrospinal fluid] were mainly the Streptococcus of the group and the E Coli. Antibiotic therapy has been shown to be useful in asymptomatic&nbsp;newborns with inflammatory syndrome and bacteria identified on peripheral samples and gastric fluid, but&nbsp; also in all symptomatic newborns. Conclusion. In a early bacterial infection, an interventionist attitude is required, but early antibiotic therapy is only useful in the situation of symptomatic newborns. On the otherhand, in the asymptomatic newborns, antibiotic therapy will be reserved for those carrying both an identified bacteria and an inflammatory syndrome. Contexte et objectif. L‟infection néonatale bactérienne précoce est greffée d‟une forte mortalité et morbidité conduisant à une antibiothérapie probabiliste sans délai souvent à posteriori inutile. L‟objectif du présent travail était de proposer une stratégie de prise en charge pertinente susceptible de bien identifier les nouveau-nés à risque infectieux bactérien et ceux relevant d‟une surveillance clinique seule ou associée à une antibiothérapie parentérale.&nbsp; &nbsp; Méthodes. Etude documentaire menée entre janvier 2014 et janvier 2016 sur des nouveau-nés de 36≥SA&lt;42, suspects d‟infection bactérienne précoce et suivis en Maternité et dans l‟unité de Néonatologie du Groupe Hospitalier Carnelle Portes de l‟Oise [Val D‟Oise, France]. Les données clinico-biologiques et bactériologiques, la stratégie thérapeutique et l‟évolution sont analysées.&nbsp; Résultats. Deux cent quarante nouveau-nés [NNES] ont été éligibles et repartis en trois groupes : 120 NNES asymptomatiques avec critères anténatals de risque infectieux bactérien [G1NAS], 70 NNES symptomatiques avec critères anténatals de risque infectieux bactérien [G2NSCARIB] et 50 NNES symptomatiques sans critères anténatals de risque infectieux bactérien [G3NSSCARIB]. La biologie inflammatoire est limitée aux NNES du groupe G1NAS colonisés et aux groupes symptomatiques. Les germes identifiés [Prélèvements périphériques, liquide gastrique, sang et liquide céphalorachidien] ont été principalement le Streptocoque du groupe β et l‟E Coli. L‟antibiothérapie s‟est avérée utile chez les NNES asymptomatiques avec syndrome inflam-matoire et germes identifiés sur les prélèvements périphériques et liquide gastrique, mais aussi chez tous les NNES symptomatiques.&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; Conclusion. Chez un NNE âgé de ≥ 36SA et suspect d‟infection bactérienne précoce, une attitude interventionniste est de rigueur, mais l‟antibiothérapie sans délai n‟est utile que dans les situations des NNES symptomatiques. En revanche, chez les NNES asymptomatiques, l‟antibiothérapie sera réservée à ceux porteurs à la fois d‟un germe et d‟un syndrome inflammatoire

Polyphasic evaluation and cytotoxic investigation of isolated cyanobacteria with an emphasis on potent activities of a Scytonema strain

DATA AVAILABILITY STATEMENT : The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.Cyanobacteria are phototrophic organisms widely found in most types of natural habitats in the tropical regions of the world. In this study, we isolated and identified cyanobacterial strains from paddy soil in Hanoi (Vietnam) and investigated their cytotoxic activities. Five isolated cyanobacterial strains showed distinctive profiles of gene sequences (rRNA 16S and rbcL), phylogenetic placements, and morphological characteristics. Based on the polyphasic evaluation, they were classified as Scytonema bilaspurense NK13, Hapalosiphon welwitschii MD2411, Aulosira sp. XN1103, Desikacharya sp. NS2000, and Desmonostoc sp. NK1813. The cytotoxic screening revealed that the extract of strain Scytonema bilaspurense NK13 exhibited potent cytotoxic activities against four human cell lines of HeLa cells, OVCAR-8 cells, HaCaT cells, and HEK-293T cells, with IC50 values of 3.8, 34.2, 21.6, and 0.6μg/mL, respectively. This is the first time a well-classified Scytonema strain from tropical habitat in Southeast Asia has been recognized as a potential producer of cytotoxic compounds.The Vietnam National University, Hanoi (VNU).http://www.frontiersin.org/Microbiologyam2023BiochemistryGeneticsMicrobiology and Plant Patholog

The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28.

Anti-CD19 chimeric antigen receptor (CD19-CAR)-engineered T cells are approved therapeutics for malignancies. The impact of the hinge domain (HD) and the transmembrane domain (TMD) between the extracellular antigen-targeting CARs and the intracellular signaling modalities of CARs has not been systemically studied. In this study, a series of 19-CARs differing only by their HD (CD8, CD28, or IgG &lt;sub&gt;4&lt;/sub&gt; ) and TMD (CD8 or CD28) was generated. CARs containing a CD28-TMD, but not a CD8-TMD, formed heterodimers with the endogenous CD28 in human T cells, as shown by co-immunoprecipitation and CAR-dependent proliferation of anti-CD28 stimulation. This dimerization was dependent on polar amino acids in the CD28-TMD and was more efficient with CARs containing CD28 or CD8 HD than IgG &lt;sub&gt;4&lt;/sub&gt; -HD. The CD28-CAR heterodimers did not respond to CD80 and CD86 stimulation but had a significantly reduced CD28 cell-surface expression. These data unveiled a fundamental difference between CD28-TMD and CD8-TMD and indicated that CD28-TMD can modulate CAR T-cell activities by engaging endogenous partners

Clade-level Spatial Modelling of HPAI H5N1 Dynamics in the Mekong Region Reveals New Patterns and Associations with Agro-Ecological Factors.

The highly pathogenic avian influenza (HPAI) H5N1 virus has been circulating in Asia since 2003 and diversified into several genetic lineages, or clades. Although the spatial distribution of its outbreaks was extensively studied, differences in clades were never previously taken into account. We developed models to quantify associations over time and space between different HPAI H5N1 viruses from clade 1, 2.3.4 and 2.3.2 and agro-ecological factors. We found that the distribution of clades in the Mekong region from 2004 to 2013 was strongly regionalised, defining specific epidemiological zones, or epizones. Clade 1 became entrenched in the Mekong Delta and was not supplanted by newer clades, in association with a relatively higher presence of domestic ducks. In contrast, two new clades were introduced (2.3.4 and 2.3.2) in northern Viet Nam and were associated with higher chicken density and more intensive chicken production systems. We suggest that differences in poultry production systems in these different epizones may explain these associations, along with differences in introduction pressure from neighbouring countries. The different distribution patterns found at the clade level would not be otherwise apparent through analysis treating all outbreaks equally, which requires improved linking of disease outbreak records and genetic sequence data