An automated treatment planning strategy for highly noncoplanar radiotherapy arc trajectories

Radiation therapy is a technology-driven cancer treatment modality that has experienced significant advances over the last decades, due to multidisciplinary contributions that include engineering and computing. Recent technological developments allow the use of noncoplanar volumetric modulated arc therapy (VMAT), one of the most recent photon treatment techniques, in clinical practice. In this work, an automated noncoplanar arc trajectory optimization framework designed in two modular phases is presented. First, a noncoplanar beam angle optimization algorithm is used to obtain a set of noncoplanar irradiation directions. Then, anchored in these directions, an optimization strategy is proposed to compute an optimal arc trajectory. The computational experiments considered a pool of twelve difficult head-and-neck tumor cases. It was possible to observe that, for some of these cases, the optimized noncoplanar arc trajectories led to significant treatment planning quality improvements, when compared with coplanar VMAT treatment plans. Although these experiments were done in a research environment treatment planning software (matRad), the conclusions can be of interest for a clinical setting: automated procedures can simplify the current treatment workflow, produce high-quality treatment plans, making better use of human resources and allowing for unbiased comparisons between different treatment techniques.     

Impact of high-intensity ultrasound on physical properties and degree of oxidation of lipase modified menhaden oil with caprylic acid and/or stearic acid

The purpose of this research was to determine the effect of high-intensity ultrasound (HIU) on physical properties, degree of oxidation, and oxidative stability of structured lipids (SLs). Caprylic acid (C) and stearic acid (S) were incorporated into menhaden oil using Lipozyme® 435 lipase to obtain five samples: (1) LC 20 (menhaden oil with 20% of C), (2) LC 30 (menhaden oil with 30% C), (3) LS 20 (menhaden oil with 20% S), (4) LS 30 (menhaden oil with 30% S), and (5) Blend C (menhaden oil with 16.24% C and 13.04% S). Samples were crystallized for 90 min at the following temperatures: (1) LC 20 at 15.5°C, (2) LC 30 at 17.5°C, (3) LS 20 at 24°C, (4) LS 30 at 30°C, and (5) Blend C at 18.0°C, and HIU was applied at the onset of crystallization. Physical properties, degree of oxidation, and oxidative stability were evaluated in sonicated and nonsonicated samples. All SLs had statistically higher G′ after sonication. Sonicated LS 30, LC 30, and Blend C had a higher melting enthalpy than the nonsonicated ones, while enthalpy values in sonicated LS 20 and LC 20 samples were not statistically different than the nonsonicated ones. No significant difference between sonicated and nonsonicated samples was observed in peroxide values (1.2 ± 0.1 meq/kg, p > 0.05) and in the oxidative stability index (6.3 ± 0.2 h, p > 0.05). These results showed that HIU was effective at changing physical properties without affecting the oxidation of the samples.     

Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

Collective institutional work: the case of Airbnb in Amsterdam,London and New York

ABSTRACT

Given that online platforms disrupt established industries and challenge existing institutions, they can only be successful if their innovation becomes both legal and legitimate. This requires ‘institutional work’ that changes perceptions and regulations within society. Rather than only focussing on the online platform as the sole agent engaging in institutional work, our study analyses institutional work as a collective process. We investigate the case of home-sharing platform Airbnb and the process of institutional change its introduction prompted regarding short-term rental in Amsterdam, London and New York. We find, contrary to the popular view of online platforms as disruptive entrepreneurs, that the platform mainly focusses on creating new institutions rather than disrupting existing ones, and that users and non-users undertake most of the institutional work activities. We also show that different types of actors carry out different types of institutional work suggesting that the process of institutional work is highly distributed.     

The generalized discrete ‐centroid problem

The ‐centroid problem or leader–follower problem is generalized considering different customer choice rules where a customer may use facilities belonging to different firms, if the difference in travel distance (or time) is small enough. Assuming essential goods, some particular customer choice rules are analyzed. Linear programming formulations for the generalized ‐medianoid and ‐centroid problems are presented and an exact solution approach is applied. Some computational examples are included.     

5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late-Stage Functionalization

This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare S-adenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Second, innovative methods to regenerate SAM cofactors by enzymatic cascades is reported. Finally, future opportunities towards establishing a generalized platform for late-stage alkylation are described.     

Potential of renewable energy system utilisation at decentralised level in the state of Uttarakhand in India

ABSTRACT

Design and implementation of an effective dissemination programme for decentralised renewable energy system necessitate an accurate estimate of its utilisation potential. Hence, in this study, an attempt has been made to develop frameworks to estimate the utilisation potential of decentralised renewable energy systems in the state of Uttarakhand in India. Estimations imply large resource, technical and economic potentials of the domestic solar water heater, solar home system, solar lantern, family size biogas plant and improved biomass cookstove in Uttarakhand. With higher impact on the purchasing power of households, prevailing soft loan scheme has been found to be more appropriate than a capital subsidy for promoting the usage of decentralised renewable energy systems.