96 research outputs found
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Origins of observed reactivity and specificity in the addition of B2Cl4 and analogues to unsaturated compounds
In 1954 Schlesinger and co-workers observed the direct reaction of diboron tetrachloride with simple organic compounds under mild conditions, the 1,2 addition product being formed with either ethylene or acetylene. In the following 25 years a series of addition reactions to simple alkenes, alkynes and dienes was demonstrated. B2F4 was shown to react in similar manner, albeit under more forcing conditions. Crucially, it was demonstrated that the addition to (E)- or (Z)-but-2-ene occurred with cis-stereospecificity. Only sporadic interest was shown in this field thereafter until catalysed addition reactions of diboron reagents were realized. Encouraged by this revival of interest through the discovery of transition-metal and nucleophilic catalysis of diboryl additions, DFT analysis of uncatalysed additions of B2X4 has been carried out and interpreted. This includes the relative reactivity of several B–B reagents with ethene, and that of B2Cl4vs. B2F4 additions, including benzene, naphthalene and C60 as reactants. This allows the analysis of relative reactivity vis-à-vis substitution on boron, and also direct comparison with hydroboration by HBCl2. [4 + 2] Addition of diboron reagents to dienes with B–B cleavage competes with direct [2 + 2] addition, favourably so for B2F4. The computational results demonstrate that the stereospecific addition to isomeric but-2-enes is a rare concerted [2σs + 2πs] proces
Proyecto SHE: School and Home Emotions
Hoy en día, la inteligencia no garantiza la felicidad en nuestro entorno, trabajo o vida
social. El éxito personal y profesional no se vincula únicamente a los conocimientos académicamente adquiridos, sino también al dominio de competencias emocionales, cuyo desarrollo ayuda a gestionar las diferentes situaciones estresantes que se dan en el día a día. En este trabajo se describe un programa en educación emocional (SHE) –diseñado e implementado como estudio piloto–, basado en modelos científicos ampliamente conocidos sobre inteligencia (Salovey &y Mayer, 1997) y regulación emocional (Gross &y John, 2003). Mediante dicho programa se pretende poner al alcance de los niños las sinergias creadas por una educación emocional global: niños, profesores y padres. Para ello, se seleccionaron tres muestras de participantes: niños/niñas de 4º de primaria, padres y madres, y profesorado del mismo centro escolar. La intervención consistió en desarrollar e impartir sesiones bi-quincenales sobre educación emocional. Los resultados mostraron efectos significativos sobre el uso de estrategias de regulación emocional –en la muestra
de estudiantes y progenitores–, con una disminución de la supresión emocional y un
aumento de la reevaluación cognitiva. En el caso de los profesores, disminuyeron las
puntuaciones en afecto negativo. Los valores de funcionamiento familiar permanecieron estables tras la intervención. Por último, no se observaron cambios significativos en las habilidades de inteligencia emocional en ninguno de los tres grupos a estudio.Today, intelligence does not guarantee happiness in our environment, work or social life. Personal and professional success is not only related to academic knowledge but also to the domain of emotional competences, whose development helps to manage the different stressful situations that occur on a daily basis. In this paper we describe a program in emotional education (SHE), designed and implemented as a pilot study, based on well-known scientific models of intelligence (Salovey &and Mayer, 1997) and emotional regulation (Gross &and John, 2003). This program aims to make available to children the synergies created by a global emotional education: children, teachers and parents. For this purpose, three samples of participants were selected: children from 4th grade primary, a group of parents of 4th grade and a group of teachers from the same school. The intervention consisted of developing and imparting bi-fortnightly sessions on emotional education. The results showed significant effects on the use of emotional regulation strategies - in student
and parent samples - with a decrease in emotional suppression and an increase in cognitive reevaluation. In the case of teachers, the scores on negative affection decreased. The values of family functioning remained stable after the intervention. Finally, no significant changes in emotional intelligence skills were observed in any of the three study groups
Optimization of flucloxacillin dosing regimens in critically ill patients using population pharmacokinetic modelling of total and unbound concentrations
Background: Initial appropriate anti-infective therapy is associated with improved outcomes in patients with severe infections. In critically ill patients, altered pharmacokinetic (PK) behaviour is common and known to influence the achievement of PK/pharmacodynamic targets. Objectives: To describe population PK and optimized dosing regimens for flucloxacillin in critically ill patients. Methods: First, we developed a population PK model, estimated between-patient variability (BPV) and identified covariates that could explain BPV through non-linear mixed-effects analysis, using total and unbound concentrations obtained from 35 adult critically ill patients treated with intermittent flucloxacillin. Second, we validated the model using external datasets from two different countries. Finally, frequently prescribed dosing regimens were evaluated using Monte Carlo simulations. Results: A two-compartment model with non-linear protein binding was developed and validated. BPV of the maximum binding capacity decreased from 42.2% to 30.4% and BPV of unbound clearance decreased from 88.1% to 71.6% upon inclusion of serumalbumin concentrations and estimated glomerular filtration rate (eGFR; by CKD-EPI equation), respectively. PTA (target of 100%fT(>MIC)) was 91% for patients with eGFR of 33mL/min and 1 g q6h, 87% for patients with eGFR of 96 mL/min and 2 g q4h and 71% for patients with eGFR of 153 mL/min and 2 g q4h. Conclusions: For patients with high creatinine clearance who are infected with moderately susceptible pathogens, therapeutic drug monitoring is advised since there is a risk of underexposure to flucloxacillin. Due to the non-linear protein binding of flucloxacillin and the high prevalence of hypoalbuminaemia in critically ill patients, dose adjustments should be based on unbound concentrations
Sonogashira diversification of unprotected halotryptophans, halotryptophan containing tripeptides; and generation of a new to nature bromo-natural product and its diversification in water
The blending together of synthetic chemistry with natural product biosynthesis represents a potentially powerful approach to synthesis; to enable this, further synthetic tools and methodologies are needed. To this end, we have explored the first Sonogashira cross-coupling to halotryptophans in water. Broad reaction scope is demonstrated and we have explored the limits of the scope of the reaction. We have demonstrated this methodology to work excellently in the modification of model tripeptides. Furthermore, through precursor directed biosynthesis, we have generated for the first time a new to nature brominated natural product bromo-cystargamide, and demonstrated the applicability of our reaction conditions to modify this novel metabolite
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An expedient, mild and aqueous method for Suzuki–Miyaura diversification of (hetero)aryl halides or (poly)chlorinated pharmaceuticals
The development of mild, aqueous conditions for the cross-coupling of highly functionalized (hetero)aryl chlorides or bromides is attractive, enabling their functionalization and diversification. Herein, we report a general method for Suzuki–Miyaura cross-coupling at 37 °C in aqueous media in the presence of air. We demonstrate application of this general methodology for derivatisation of (poly)chlorinated, medicinally active compounds and halogenated amino acids. The approach holds the potential to be a useful tool for late-stage functionalization or analogue generation
Heck diversification of indole‐based substrates under aqueous conditions : from indoles to unprotected halo‐tryptophans and halo‐tryptophans in natural product derivatives
The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013/ERC grant agreement no 614779 GenoChemetics (to R.J.M.G). P. C. is supported by the European Union's Horizon 2020 research and innovation program through the SponGES project (grant agreement No. 679849). C.P-U. was supported by the Marie Sklodowska-Curie Fellowship C-XAq.The blending of synthetic chemistry with biosynthetic processes provides a powerful approach to synthesis. Biosynthetic halogenation and synthetic cross‐coupling have great potential to be used together, for small molecule generation, access to natural product analogues and as a tool for chemical biology. However, to enable enhanced generality of this approach, further synthetic tools are needed. Though considerable research has been invested in the diversification of phenylalanine and tyrosine, functionalisation of tryptophans thorough cross‐coupling has been largely neglected. Tryptophan is a key residue in many biologically active natural products and peptides; in proteins it is key to fluorescence and dominates protein folding. To this end, we have explored the Heck cross‐coupling of halo‐indoles and halo‐tryptophans in water, showing broad reaction scope. We have demonstrated the ability to use this methodology in the functionalisation of a brominated antibiotic (bromo‐pacidamycin), as well as a marine sponge metabolite, barettin.Publisher PDFPeer reviewe
Buchwald Hartwig diversification of unprotected halotryptophans, halotryptophan containing tripeptides and the natural product barettin in aqueous conditions
The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013/ERC grant agreement no 614779 GenoChemetics (to R.J.M.G) P. Cárdenas received support from the European Union's Horizon 2020 research and innovation program through the SponGES project (grant agreement No. 679849).Blending synthetic chemistry and biology is synthetically powerful. To further enable this, compatible synthetic tools are needed. We report the first Buchwald Hartwig amination reactions with unprotected halotryptophans in aqueous systems and demonstrate this methodology applicable to the modification of unprotected halotryptophans, simple tripeptides and the natural product barettin.Publisher PDFPeer reviewe
Combination antibiotic therapy for community-acquired pneumonia
Community-acquired pneumonia (CAP) is a common and potentially serious illness that is associated with morbidity and mortality. Although medical care has improved during the past decades, it is still potentially lethal. Streptococcus pneumoniae is the most frequent microorganism isolated. Treatment includes mandatory antibiotic therapy and organ support as needed. There are several antibiotic therapy regimens that include β-lactams or macrolides or fluoroquinolones alone or in combination. Combination antibiotic therapy achieves a better outcome compared with monotherapy and it should be given in the following subset of patients with CAP: outpatients with comorbidities and previous antibiotic therapy, nursing home patients with CAP, hospitalized patients with severe CAP, bacteremic pneumococcal CAP, presence of shock, and necessity of mechanical ventilation. Better outcome is associated with combination therapy that includes a macrolide for wide coverage of atypical pneumonia, polymicrobial pneumonia, or resistant Streptococcus pneumoniae. Macrolides have shown different properties other than antimicrobial activity, such as anti-inflammatory properties. Although this evidence comes from observational, most of them retrospective and nonblinded studies, the findings are consistent. Ideally, a prospective, multicenter, randomized trial should be performed to confirm these findings
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