Microwave-assisted automated glycan assembly

Automated synthesis of DNA, RNA, and peptides provides quickly and reliably important tools for biomedical research. Automated glycan assembly (AGA) is significantly more challenging as highly branched carbohydrates require strict regio- and stereocontrol during synthesis. A new AGA synthesizer enables rapid temperature adjustment from -40 °C to +100 °C to control glycosylations at low temperature and accelerates capping, protecting group removal, and glycan modifications by using elevated temperatures. Thereby, the temporary protecting group portfolio is extended from two to four orthogonal groups that give rise to oligosaccharides with up to four branches. In addition, sulfated glycans and unprotected glycans can be prepared. The new design reduces the typical coupling cycles from 100 min to 60 min while expanding the range of accessible glycans. The instrument drastically shorten and generalizes the synthesis of carbohydrates for use in biomedical and material science

VaporSPOT : parallel synthesis of oligosaccharides on membranes

Automated chemical synthesis has revolutionized synthetic access to biopolymers in terms of simplicity and speed. While automated oligosaccharide synthesis has become faster and more versatile, the parallel synthesis of oligosaccharides is not yet possible. Here, a chemical vapor glycosylation strategy (VaporSPOT) is described that enables the simultaneous synthesis of oligosaccharides on a cellulose membrane solid support. Different linkers allow for flexible and straightforward cleavage, purification, and characterization of the target oligosaccharides. This method is the basis for the development of parallel automated glycan synthesis platforms

STABILIZATION OF NON ISOTHERMAL CHEMICAL REACTORS USING TWO THERMODYNAMIC LYAPUNOV FUNCTIONS

The main goal of this paper is to introduce a link between the thermodynamics and control systems theory. More precisely, the paper focuses on Lyapunov based control of process systems, specially the non isothermal Continuous Stirred Tank Reactors in a thermodynamic framework, using either the jacket temperature or the inlet molar flow rate as the only control input. As soon as the constraint on the total mass is considered and the reaction kinetics is a Lipschitz continuous function with respect to the temperature, it shows that the stabilization of thermal solicitations reciprocally entails the one of matter using La Salle’s invariance principle. As a consequence, these control problems can be solved if the closed loop Lyapunov functions are chosen to be proportional to the thermal part or material part of the so called thermodynamic availability function. Some numerical simulations for a first order chemical reaction with multiple steady states are given to validate our theoretical developments. The performance of the obtained nonlinear controllers with regard to the conversion rate is also discussed.The main goal of this paper is to introduce a link between the thermodynamics and control systems theory. More precisely, the paper focuses on Lyapunov based control of process systems, specially the non isothermal Continuous Stirred Tank Reactors in a thermodynamic framework, using either the jacket temperature or the inlet molar flow rate as the only control input. As soon as the constraint on the total mass is considered and the reaction kinetics is a Lipschitz continuous function with respect to the temperature, it shows that the stabilization of thermal solicitations reciprocally entails the one of matter using La Salle’s invariance principle. As a consequence, these control problems can be solved if the closed loop Lyapunov functions are chosen to be proportional to the thermal part or material part of the so called thermodynamic availability function. Some numerical simulations for a first order chemical reaction with multiple steady states are given to validate our theoretical developments. The performance of the obtained nonlinear controllers with regard to the conversion rate is also discussed

A 25-Year-Old Male with Orogenital Ulcers, Rash, and Difficulty Swallowing

A 25-year-old otherwise healthy male presented with new-onset odynophagia, rash, and orogenital ulcers. Despite treatment with antibiotics for presumed bacterial pharyngitis, the patient remained symptomatic, with abnormal vital signs and laboratory values. Upon dermatology consultation and histopathologic correlation, he was diagnosed with Behçet disease. Behçet disease is a rare rheumatologic condition that presents with recurrent oral ulcers and varying degrees of ophthalmic, neurologic, cardiac, and vascular disease. Given its protean nature, the treatment of Behçet disease is tailored to the patient's presentation and severity of organ involvement. Following treatment with colchicine and prednisone, the patient's symptoms improved rapidly

Dynamical chaos and power spectra in toy models of heteropolymers and proteins

The dynamical chaos in Lennard-Jones toy models of heteropolymers is studied by molecular dynamics simulations. It is shown that two nearby trajectories quickly diverge from each other if the heteropolymer corresponds to a random sequence. For good folders, on the other hand, two nearby trajectories may initially move apart but eventually they come together. Thus good folders are intrinsically non-chaotic. A choice of a distance of the initial conformation from the native state affects the way in which a separation between the twin trajectories behaves in time. This observation allows one to determine the size of a folding funnel in good folders. We study the energy landscapes of the toy models by determining the power spectra and fractal characteristics of the dependence of the potential energy on time. For good folders, folding and unfolding trajectories have distinctly different correlated behaviors at low frequencies.Comment: 8 pages, 9 EPS figures, Phys. Rev. E (in press

Glycoside hydrolase from the GH76 family indicates that marine Salegentibacter sp. Hel_I_6 consumes alpha-mannan from fungi

Microbial glycan degradation is essential to global carbon cycling. The marine bacterium Salegentibacter sp. Hel_I_6 (Bacteroidota) isolated from seawater off Helgoland island (North Sea) contains an α-mannan inducible gene cluster with a GH76 family endo-α-1,6-mannanase (ShGH76). This cluster is related to genetic loci employed by human gut bacteria to digest fungal α-mannan. Metagenomes from the Hel_I_6 isolation site revealed increasing GH76 gene frequencies in free-living bacteria during microalgae blooms, suggesting degradation of α-1,6-mannans from fungi. Recombinant ShGH76 protein activity assays with yeast α-mannan and synthetic oligomannans showed endo-α-1,6-mannanase activity. Resolved structures of apo-ShGH76 (2.0 Å) and of mutants co-crystalized with fungal mannan-mimicking α-1,6-mannotetrose (1.90 Å) and α-1,6-mannotriose (1.47 Å) retained the canonical (α/α)6 fold, despite low identities with sequences of known GH76 structures (GH76s from gut bacteria: <27%). The apo-form active site differed from those known from gut bacteria, and co-crystallizations revealed a kinked oligomannan conformation. Co-crystallizations also revealed precise molecular-scale interactions of ShGH76 with fungal mannan-mimicking oligomannans, indicating adaptation to this particular type of substrate. Our data hence suggest presence of yet unknown fungal α-1,6-mannans in marine ecosystems, in particular during microalgal blooms

Genome-wide association mapping for root traits in a panel of rice accessions from Vietnam

Background: Despite recent sequencing efforts, local genetic resources remain underexploited, even though they carry alleles that can bring agronomic benefits. Taking advantage of the recent genotyping with 22,000 single-nucleotide polymorphism markers of a core collection of 180 Vietnamese rice varieties originating from provinces from North to South Vietnam and from different agrosystems characterized by contrasted water regimes, we have performed a genome-wide association study for different root parameters. Roots contribute to water stress avoidance and are a still underexploited target for breeding purpose due to the difficulty to observe them. Results: The panel of 180 rice varieties was phenotyped under greenhouse conditions for several root traits in an experimental design with 3 replicates. The phenotyping system consisted of long plastic bags that were filled with sand and supplemented with fertilizer. Root length, root mass in different layers, root thickness, and the number of crown roots, as well as several derived root parameters and shoot traits, were recorded. The results were submitted to association mapping using a mixed model involving structure and kinship to enable the identification of significant associations. The analyses were conducted successively on the whole panel and on its indica (115 accessions) and japonica (64 accessions) subcomponents. The two associations with the highest significance were for root thickness on chromosome 2 and for crown root number on chromosome 11. No common associations were detected between the indica and japonica subpanels, probably because of the polymorphism repartition between the subspecies. Based on orthology with Arabidopsis, the possible candidate genes underlying the quantitative trait loci are reviewed. Conclusions: Some of the major quantitative trait loci we detected through this genome-wide association study contain promising candidate genes encoding regulatory elements of known key regulators of root formation and development

Apocrine-Eccrine Carcinomas: Molecular and Immunohistochemical Analyses

Apocrine-eccrine carcinomas are rare and associated with poor prognosis. Currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. However, studies on genetic alterations and EGFR and Her2 status of apocrine-eccrine carcinomas are few in number. In addition, hormonal studies have not been comprehensive and performed only on certain subsets of apocrine-eccrine carcinomas. To investigate whether apocrine-eccrine carcinomas express hormonal receptors or possess activation of oncogenic pathways that can be targeted by available chemotherapeutic agent we performed immunohistochemistry for AR, PR, ER, EGFR, and HER2 expression; fluorescence in situ hybridization (FISH) for EGFR and ERBB2 gene amplification; and molecular analyses for recurrent mutations in 15 cancer genes including AKT-1, EGFR, PIK3CA, and TP53 on 54 cases of apocrine-eccrine carcinomas. They include 10 apocrine carcinomas, 7 eccrine carcinomas, 9 aggressive digital papillary adenocarcinomas, 10 hidradenocarcinomas, 11 porocarcinomas, 1 adenoid cystic carcinoma, 4 malignant chondroid syringomas, 1 malignant spiradenoma, and 1 malignant cylindroma. AR, ER, PR, EGFR and HER2 expression was seen in 36% (19/53), 27% (14/51), 16% (8/51), 85% (44/52) and 12% (6/52), respectively. Polysomy or trisomy of EGFR was detected by FISH in 30% (14/46). Mutations of AKT-1, PIK3CA, and TP53 were detected in 1, 3, and 7 cases, respectively (11/47, 23%). Additional investigation regarding the potential treatment of rare cases of apocrine-eccrine carcinomas with PI3K/Akt/mTOR pathway inhibitors, currently in clinical testing, may be of clinical interest