Biosynthesis of 2-hydroxyisobutyric acid (2-HIBA) from renewable carbon

Nowadays a growing demand for green chemicals and cleantech solutions is motivating the industry to strive for biobased building blocks. We have identified the tertiary carbon atom-containing 2-hydroxyisobutyric acid (2-HIBA) as an interesting building block for polymer synthesis. Starting from this carboxylic acid, practically all compounds possessing the isobutane structure are accessible by simple chemical conversions, e. g. the commodity methacrylic acid as well as isobutylene glycol and oxide. During recent years, biotechnological routes to 2-HIBA acid have been proposed and significant progress in elucidating the underlying biochemistry has been made. Besides biohydrolysis and biooxidation, now a bioisomerization reaction can be employed, converting the common metabolite 3-hydroxybutyric acid to 2-HIBA by a novel cobalamin-dependent CoA-carbonyl mutase. The latter reaction has recently been discovered in the course of elucidating the degradation pathway of the groundwater pollutant methyl tert-butyl ether (MTBE) in the new bacterial species Aquincola tertiaricarbonis. This discovery opens the ground for developing a completely biotechnological process for producing 2-HIBA. The mutase enzyme has to be active in a suitable biological system producing 3-hydroxybutyryl-CoA, which is the precursor of the well-known bacterial bioplastic polyhydroxybutyrate (PHB). This connection to the PHB metabolism is a great advantage as its underlying biochemistry and physiology is well understood and can easily be adopted towards producing 2-HIBA. This review highlights the potential of these discoveries for a large-scale 2-HIBA biosynthesis from renewable carbon, replacing conventional chemistry as synthesis route and petrochemicals as carbon source

Coarse Graining of Nonbonded Inter-particle Potentials Using Automatic Simplex Optimization to Fit Structural Properties

We implemented a coarse-graining procedure to construct mesoscopic models of complex molecules. The final aim is to obtain better results on properties depending on slow modes of the molecules. Therefore the number of particles considered in molecular dynamics simulations is reduced while conserving as many properties of the original substance as possible. We address the problem of finding nonbonded interaction parameters which reproduce structural properties from experiment or atomistic simulations. The approach consists of optimizing automatically nonbonded parameters using the simplex algorithm to fit structural properties like the radial distribution function as target functions. Moreover, any mix of structural and thermodynamic properties can be included in the target function. Different spherically symmetric inter-particle potentials are discussed. Besides demonstrating the method for Lennard--Jones liquids, it is applied to several more complex molecular liquids such as diphenyl carbonate, tetrahydrofurane, and monomers of poly(isoprene).Comment: 24 pages, 3 tables, 14 figures submitted to the Journal of Chemical Physics (JCP

Terabyte-scale supervised 3D training and benchmarking dataset of the mouse kidney

The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training datasets, which require state-of-the-art imaging facilities, domain experts for annotation and large computational and personal resources. The HR-Kidney dataset presented in this work bridges this gap by providing 1.7 TB of artefact-corrected synchrotron radiation-based X-ray phase-contrast microtomography images of whole mouse kidneys and validated segmentations of 33 729 glomeruli, which corresponds to a one to two orders of magnitude increase over currently available biomedical datasets. The image sets also contain the underlying raw data, threshold- and morphology-based semi-automatic segmentations of renal vasculature and uriniferous tubules, as well as true 3D manual annotations. We therewith provide a broad basis for the scientific community to build upon and expand in the fields of image processing, data augmentation and machine learning, in particular unsupervised and semi-supervised learning investigations, as well as transfer learning and generative adversarial networks

Terabyte-scale supervised 3D training and benchmarking dataset of the mouse kidney

The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training datasets, which require state-of-the-art imaging facilities, domain experts for annotation and large computational and personal resources. The HR-Kidney dataset presented in this work bridges this gap by providing 1.7 TB of artefact-corrected synchrotron radiation-based X-ray phase-contrast microtomography images of whole mouse kidneys and validated segmentations of 33 729 glomeruli, which corresponds to a one to two orders of magnitude increase over currently available biomedical datasets. The image sets also contain the underlying raw data, threshold- and morphology-based semi-automatic segmentations of renal vasculature and uriniferous tubules, as well as true 3D manual annotations. We therewith provide a broad basis for the scientific community to build upon and expand in the fields of image processing, data augmentation and machine learning, in particular unsupervised and semi-supervised learning investigations, as well as transfer learning and generative adversarial networks

Statistical anisotropy of magnetohydrodynamic turbulence

Direct numerical simulations of decaying and forced magnetohydrodynamic (MHD) turbulence without and with mean magnetic field are analyzed by higher-order two-point statistics. The turbulence exhibits statistical anisotropy with respect to the direction of the local magnetic field even in the case of global isotropy. A mean magnetic field reduces the parallel-field dynamics while in the perpendicular direction a gradual transition towards two-dimensional MHD turbulence is observed with $k^{-3/2}$ inertial-range scaling of the perpendicular energy spectrum. An intermittency model based on the Log-Poisson approach, $\zeta_p=p/g^2 +1 -(1/g)^{p/g}$, is able to describe the observed structure function scalings.Comment: 4 pages, 3 figures. To appear in Phys.Rev.

Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis

In hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis, high transplant-related mortality after busulfan-based myeloablative regimens has been observed. Conditioning regimens with reduced toxicity based on melphalan or treosulfan are promising alternatives. We retrospectively analyzed hematopoietic stem cell transplantations in 19 hemophagocytic lymphohistiocytosis patients after conditioning with fludarabine, treosulfan, alemtuzumab, with or without thiotepa. Overall and disease-free survivals were 100% (follow up 7-31 months). Two patients required second transplant (1 after haploidentical transplantation). In 6 patients, overall donor chimerism dropped below 75% and prompted donor lymphocyte infusions. Administration of donor lymphocytes or second transplantation were significantly more frequent after transplantation from a human leukocyte antigen mismatched (9/10) versus matched (10/10) donor (P=0.018). The toxicity profile was favorable, with one veno-occlusive disease, one grade 3 graft-versus-host disease after donor lymphocyte infusion, and 2 severe viral infections (1 influenza, 1 Epstein Barr virus). In conclusion, the treosulfan-based regimen in hemophagocytic lymphohistiocytosis is effective with low toxicity and gives excellent overall and disease-free survival rates. In the future, the incidence of mixed chimerism, particularly after human leukocyte antigen mismatched donor transplants, needs to be addressed

Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis

In hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis, high transplant-related mortality after busulfan-based myeloablative regimens has been observed. Conditioning regimens with reduced toxicity based on melphalan or treosulfan are promising alternatives. We retrospectively analyzed hematopoietic stem cell transplantations in 19 hemophagocytic lymphohistiocytosis patients after conditioning with fludarabine, treosulfan, alemtuzumab, with or without thiotepa. Overall and disease-free survivals were 100% (follow up 7-31 months). Two patients required second transplant (1 after haploidentical transplantation). In 6 patients, overall donor chimerism dropped below 75% and prompted donor lymphocyte infusions. Administration of donor lymphocytes or second transplantation were significantly more frequent after transplantation from a human leukocyte antigen mismatched (9/10) versus matched (10/10) donor (P=0.018). The toxicity profile was favorable, with one veno-occlusive disease, one grade 3 graft-versus-host disease after donor lymphocyte infusion, and 2 severe viral infections (1 influenza, 1 Epstein Barr virus). In conclusion, the treosulfan-based regimen in hemophagocytic lymphohistiocytosis is effective with low toxicity and gives excellent overall and disease-free survival rates. In the future, the incidence of mixed chimerism, particularly after human leukocyte antigen mismatched donor transplants, needs to be addressed

Recent results in relativistic heavy ion collisions: from ``a new state of matter'' to "the perfect fluid"

Experimental Physics with Relativistic Heavy Ions dates from 1992 when a beam of 197Au of energy greater than 10A GeV/c first became available at the Alternating Gradient Synchrotron (AGS) at Brookhaven National Laboratory (BNL) soon followed in 1994 by a 208Pb beam of 158A GeV/c at the Super Proton Synchrotron (SPS) at CERN (European Center for Nuclear Research). Previous pioneering measurements at the Berkeley Bevalac in the late 1970's and early 1980's were at much lower bombarding energies (~ 1 A GeV/c) where nuclear breakup rather than particle production is the dominant inelastic process in A+A collisions. More recently, starting in 2000, the Relativistic Heavy Ion Collider (RHIC) at BNL has produced head-on collisions of two 100A GeV beams of fully stripped Au ions, corresponding to nucleon-nucleon center-of-mass energy, sqrt(sNN)=200 GeV, total c.m. energy 200A GeV. The objective of this research program is to produce nuclear matter with extreme density and temperature, possibly resulting in a state of matter where the quarks and gluons normally confined inside individual nucleons (r < 1 fm) are free to act over distances an order of magnitude larger. Progress from the period 1992 to the present will be reviewed, with reference to previous results from light ion and proton-proton collisions where appropriate. Emphasis will be placed on the measurements which formed the basis for the announcements by the two major laboratories: "A new state of matter", by CERN on Feb 10, 2000 and "The perfect fluid", by BNL on April 19, 2005.Comment: 62 pages, 39 figures. Review article published in Reports on Progress in Physics on June 23, 2006. In this published version, mistakes, typographical errors, and citations have been corrected and a subsection has been adde

Using 81Kr and Noble Gases to Characterize and Date Groundwater and Brines in the Baltic Artesian Basin on the One-Million-Year Timescale

Analyses for $^{81}$Kr and noble gases on groundwater from the deepest aquifer system of the Baltic Artesian Basin (BAB) were performed to determine groundwater ages and uncover the flow dynamics of the system on a timescale of several hundred thousand years. We find that the system is controlled by mixing of three distinct water masses: Interglacial or recent meteoric water (\delta^{18}\text{O} \approx -10.4\unicode{x2030}) with a poorly evolved chemical and noble gas signature, glacial meltwater (\delta^{18}\text{O} \leq -18\unicode{x2030}) with elevated noble gas concentrations, and an old, high-salinity brine component (\delta^{18}\text{O} \geq -4.5\unicode{x2030}, \geq 90 \text{g Cl}^{-}/\text{L}) with strongly depleted atmospheric noble gas concentrations. The $^{81}$Kr measurements are interpreted within this mixing framework to estimate the age of the end-members. Deconvoluted $^{81}$Kr ages range from 300 ka to 1.3 Ma for interglacial or recent meteoric water and glacial meltwater. For the brine component, ages exceed the dating range of the ATTA 3 instrument of 1.3 Ma. The radiogenic noble gas components $^{4}$He* and $^{40}$Ar* are less conclusive but also support an age of > 1 Ma for the brine. Based on the chemical and noble gas concentrations and the dating results, we conclude that the brine originates from evaporated seawater that has been modified by later water-rock interaction. As the obtained tracer ages cover several glacial cycles, we discuss the impact of the glacial cycles on flow patterns in the studied aquifer system.Comment: Accepted for publication in Geochimica et Cosmochimica Act