Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450_(BM3) demethylases

Polysaccharides comprise an extremely important class of biopolymers that play critical roles in a wide range of biological processes, but the synthesis of these compounds is challenging because of their complex structures. We have developed a chemoenzymatic method for regioselective deprotection of monosaccharide substrates using engineered Bacillus megaterium cytochrome P450 (P450_(BM3)) demethylases that provides a highly efficient means to access valuable intermediates, which can be converted to a wide range of substituted monosaccharides and polysaccharides. Demethylases displaying high levels of regioselectivity toward a number of protected monosaccharides were identified using a combination of protein and substrate engineering, suggesting that this approach ultimately could be used in the synthesis of a wide range of substituted mono- and polysaccharides for studies in chemistry, biology, and medicine

High-Frequency InAIAs/InGaAs Metal-Insulator-Doped Semiconductor Field-Effect Transistors (MIDFET's) for Telecommunications

Contains report on one research project.Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAALO3-89-C-0001

A survey to investigate the association of pain, foot disability and quality of life with corns

Background Corns are a common foot problem affecting a large proportion of the population. This study describes the characteristics of corns experienced by 201 participants taking part in a randomised controlled trial to investigate associations between demographic and corn parameters on pain, foot related disability and quality of life (QoL). Methods Pain from the main (index) corn was measured using a visual analogue scale (VAS); foot related disability was assessed with the Foot Disability Questionnaire (now known as the Manchester Foot Pain and Disability Index) and quality of life was recorded with the EQ-5D questionnaire. The effect of demographic and corn parameters on the pain and quality of life outcomes was assessed with analysis of variance (ANOVA) methods. The effect of the same factors on a linear combination of the foot-related disability outcome measures was assessed using multivariate ANOVA methods. Pain was also tested for its mediating properties on the causal pathway between the independent variables and quality of life. Results The mean pain score was 5.29 points on a 10 cm VAS, with females reporting substantively higher pain levels than males. Age affected foot-related disability, with lower levels on all domains of the MFPDI reported in older participants; each year of advancing age was associated with falls of: 0.009 points on the Concern about Appearance (CA) domain; 0.047 points on the Functional Limitation (FL) domain and 0.048 points on the Pain Intensity (PI) domain. Sex and corn type also affected disability, with higher scores reported by females and participants with plantar corns. Conclusions The effect of pain was shown to mediate the relationship between sex and foot-related disability. The presence of plantar corns has a more detrimental effect on QoL than dorsal/inter-digital corns

Taken by strum: ukuleles and participatory music-making in Hamilton, Aotearoa/New Zealand

Ethnographic study of ukulele playing in Hamilton, N

Charge Conjugation Invariance of the Vacuum and the Cosmological Constant Problem

We propose a method of field quantization which uses an indefinite metric in a Hilbert space of state vectors. The action for gravity and the standard model includes, as well as the positive energy fermion and boson fields, negative energy fields. The Hamiltonian for the action leads through charge conjugation invariance symmetry of the vacuum to a cancellation of the zero-point vacuum energy and a vanishing cosmological constant in the presence of a gravitational field. To guarantee the stability of the vacuum, we introduce a Dirac sea `hole' theory of quantization for gravity as well as the standard model. The vacuum is defined to be fully occupied by negative energy particles with a hole in the Dirac sea, corresponding to an anti-particle. We postulate that the negative energy bosons in the vacuum satisfy a para-statistics that leads to a para-Pauli exclusion principle for the negative energy bosons in the vacuum, while the positive energy bosons in the Hilbert space obey the usual Bose-Einstein statistics. This assures that the vacuum is stable for both fermions and bosons. Restrictions on the para-operator Hamiltonian density lead to selection rules that prohibit positive energy para-bosons from being observable. The problem of deriving a positive energy spectrum and a consistent unitary field theory from a pseudo-Hermitian Hamiltonian is investigated.Comment: 15 pages, Latex file, no figures. Typos corrected. To be published in Physics Letters

Sisyphus cooling and amplification by a superconducting qubit

Laser cooling of the atomic motion paved the way for remarkable achievements in the fields of quantum optics and atomic physics, including Bose-Einstein condensation and the trapping of atoms in optical lattices. More recently superconducting qubits were shown to act as artificial two-level atoms, displaying Rabi oscillations, Ramsey fringes, and further quantum effects. Coupling such qubits to resonators brought the superconducting circuits into the realm of quantum electrodynamics (circuit QED). It opened the perspective to use superconducting qubits as micro-coolers or to create a population inversion in the qubit to induce lasing behavior of the resonator. Furthering these analogies between quantum optical and superconducting systems we demonstrate here Sisyphus cooling of a low frequency LC oscillator coupled to a near-resonantly driven superconducting qubit. In the quantum optics setup the mechanical degrees of freedom of an atom are cooled by laser driving the atom's electronic degrees of freedom. Here the roles of the two degrees of freedom are played by the LC circuit and the qubit's levels, respectively. We also demonstrate the counterpart of the Sisyphus cooling, namely Sisyphus amplification. Parallel to the experimental demonstration we analyze the system theoretically and find quantitative agreement, which supports the interpretation and allows us to estimate system parameters.Comment: 7 pages, 4 figure

A Texture Bestiary

Textures are topologically nontrivial field configurations which can exist in a field theory in which a global symmetry group $G$ is broken to a subgroup $H$, if the third homotopy group \p3 of $G/H$ is nontrivial. We compute this group for a variety of choices of $G$ and $H$, revealing what symmetry breaking patterns can lead to texture. We also comment on the construction of texture configurations in the different models.Comment: 34 pages, plain Tex. (Minor corrections to an old paper.

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

Acknowledgements The authors would like to thank Petter S. Woll, MSc, PhD, Karolinska Institutet, Stockholm, Sweden, for the kind and generous supervision of the LTC-IC experiments. We thank the FACS Core Facility at Aarhus University for access to the cell sorter and Pia S. Kristensen, Department of Haematology, Aarhus University Hospital for her excellent technical assistance conducting the FISH experiments. The Karen Elise Jensen Foundation, The Meyer Foundation, The Wellcome Trust and the Danish Cancer Society supported the study.Peer reviewedPublisher PD

Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle.

Migration through 3D constrictions can cause nuclear rupture and mislocalization of nuclear proteins, but damage to DNA remains uncertain, as does any effect on cell cycle. Here, myosin II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent block in cell cycle appears unaffected. Co-overexpression of multiple DNA repair factors or antioxidant inhibition of break formation also exert partial effects, independently of rupture. Combined treatments completely rescue cell cycle suppression by DNA damage, revealing a sigmoidal dependence of cell cycle on excess DNA damage. Migration through custom-etched pores yields the same damage threshold, with ∼4-µm pores causing intermediate levels of both damage and cell cycle suppression. High curvature imposed rapidly by pores or probes or else by small micronuclei consistently associates nuclear rupture with dilution of stiff lamin-B filaments, loss of repair factors, and entry from cytoplasm of chromatin-binding cGAS (cyclic GMP-AMP synthase). The cell cycle block caused by constricted migration is nonetheless reversible, with a potential for DNA misrepair and genome variation

Differing clinical features between Japanese and Caucasian patients with myelodysplastic syndromes:Analysis from the International Working Group for Prognosis of MDS

Clinical features of myelodysplastic syndromes (MDS) could be influenced by many factors, such as disease intrinsic factors (e.g., morphologic, cytogenetic, molecular), extrinsic factors (e.g, management, environment), and ethnicity. Several previous studies have suggested such differences between Asian and European/USA countries. In this study, to elucidate potential differences in primary untreated MDS between Japanese (JPN) and Caucasians (CAUC), we analyzed the data from a large international database collected by the International Working Group for Prognosis of MDS (300 and 5838 patients, respectively). JPN MDS were significantly younger with more severe cytopenias, and cytogenetic differences: less del(5q) and more +1/+1q, -1/del(1p), der(1;7), -9/del(9q), del(16q), and del(20q). Although differences in time to acute myeloid leukemia transformation did not occur, a significantly better survival in JPN was demonstrated, even after the adjustment for age and FAB subtypes, especially in lower, but not in higher prognostic risk categories. Certain clinical factors (cytopenias, blast percentage, cytogenetic risk) had different impact on survival and time to transformation to leukemia between the two groups. Although possible confounding events (e.g., environment, diet, and access to care) could not be excluded, our results indicated the existence of clinically relevant ethnic differences regarding survival in MDS between JPN and CAUC patients. The good performance of the IPSS-R in both CAUC and JP patients underlines that its common risk model is adequate for CAUC and JP