Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms

Remarks on the KLS conjecture and Hardy-type inequalities

We generalize the classical Hardy and Faber-Krahn inequalities to arbitrary functions on a convex body $\Omega \subset \mathbb{R}^n$, not necessarily vanishing on the boundary $\partial \Omega$. This reduces the study of the Neumann Poincar\'e constant on $\Omega$ to that of the cone and Lebesgue measures on $\partial \Omega$; these may be bounded via the curvature of $\partial \Omega$. A second reduction is obtained to the class of harmonic functions on $\Omega$. We also study the relation between the Poincar\'e constant of a log-concave measure $\mu$ and its associated K. Ball body $K_\mu$. In particular, we obtain a simple proof of a conjecture of Kannan--Lov\'asz--Simonovits for unit-balls of $\ell^n_p$, originally due to Sodin and Lata{\l}a--Wojtaszczyk.Comment: 18 pages. Numbering of propositions, theorems, etc.. as appeared in final form in GAFA seminar note

Probing two-electron multiplets in bilayer graphene quantum dots

Understanding how the electron spin is coupled to orbital degrees of freedom, such as a valley degree of freedom in solid-state systems is central to applications in spin-based electronics and quantum computation. Recent developments in the preparation of electrostatically-confined quantum dots in gapped bilayer graphene (BLG) enables to study the low-energy single-electron spectra in BLG quantum dots, which is crucial for potential spin and spin-valley qubit operations. Here, we present the observation of the spin-valley coupling in a bilayer graphene quantum dot in the single-electron regime. By making use of a highly-tunable double quantum dot device we achieve an energy resolution allowing us to resolve the lifting of the fourfold spin and valley degeneracy by a Kane-Mele type spin-orbit coupling of $\approx 65~\mu$eV. Also, we find an upper limit of a potentially disorder-induced mixing of the $K$ and $K'$ states below $20~\mu$eV.Comment: 5 Pages 5 Figure

In Situ Spatiotemporal Mapping of Flow Fields around Seeded Stem Cells at the Subcellular Length Scale

A major hurdle to understanding and exploiting interactions between the stem cell and its environment is the lack of a tool for precise delivery of mechanical cues concomitant to observing sub-cellular adaptation of structure. These studies demonstrate the use of microscale particle image velocimetry (μ-PIV) for in situ spatiotemporal mapping of flow fields around mesenchymal stem cells, i.e. murine embryonic multipotent cell line C3H10T1/2, at the subcellular length scale, providing a tool for real time observation and analysis of stem cell adaptation to the prevailing mechanical milieu. In the absence of cells, computational fluid dynamics (CFD) predicts flow regimes within 12% of μ-PIV measures, achieving the technical specifications of the chamber and the flow rates necessary to deliver target shear stresses at a particular height from the base of the flow chamber. However, our μ-PIV studies show that the presence of cells per se as well as the density at which cells are seeded significantly influences local flow fields. Furthermore, for any given cell or cell seeding density, flow regimes vary significantly along the vertical profile of the cell. Hence, the mechanical milieu of the stem cell exposed to shape changing shear stresses, induced by fluid drag, varies with respect to proximity of surrounding cells as well as with respect to apical height. The current study addresses a previously unmet need to predict and observe both flow regimes as well as mechanoadaptation of cells in flow chambers designed to deliver precisely controlled mechanical signals to live cells. An understanding of interactions and adaptation in response to forces at the interface between the surface of the cell and its immediate local environment may be key for de novo engineering of functional tissues from stem cell templates as well as for unraveling the mechanisms underlying multiscale development, growth and adaptation of organisms

Novel explant model to study mechanotransduction and cell–cell communication

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6–12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 µM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1687–1698, 2006Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55788/1/20207_ftp.pd

Kondo effect and spin-orbit coupling in graphene quantum dots

The Kondo effect is a cornerstone in the study of strongly correlated fermions. The coherent exchange coupling of conduction electrons to local magnetic moments gives rise to a Kondo cloud that screens the impurity spin. Whereas complete Kondo screening has been explored widely, realizations of the underscreened scenario - where only some of several Kondo channels participate in the screening - remain rare. Here we report the observation of fully screened and underscreened Kondo effects in quantum dots in bilayer graphene. More generally, we introduce a unique platform for studying Kondo physics. In contrast to carbon nanotubes, whose curved surfaces give rise to strong spin-orbit coupling breaking the SU(4) symmetry of the electronic states relevant for the Kondo effect, we study a nominally flat carbon material with small spin-orbit coupling. Moreover, the unusual two-electron triplet ground state in bilayer graphene dots provides a route to exploring the underscreened spin-1 Kondo effect

Fluid flow in the osteocyte mechanical environment : a fluid-structure interaction approach

Osteocytes are believed to be the primary sensor of mechanical stimuli in bone, which orchestrate osteoblasts and osteoclasts to adapt bone structure and composition to meet physiological loading demands. Experimental studies to quantify the mechanical environment surrounding bone cells are challenging, and as such, computational and theoretical approaches have modelled either the solid or fluid environment of osteocytes to predict how these cells are stimulated in vivo. Osteocytes are an elastic cellular structure that deforms in response to the external fluid flow imposed by mechanical loading. This represents a most challenging multi-physics problem in which fluid and solid domains interact, and as such, no previous study has accounted for this complex behaviour. The objective of this study is to employ fluid–structure interaction (FSI) modelling to investigate the complex mechanical environment of osteocytes in vivo. Fluorescent staining of osteocytes was performed in order to visualise their native environment and develop geometrically accurate models of the osteocyte in vivo. By simulating loading levels representative of vigorous physiological activity (3,000με compression and 300 Pa pressure gradient), we predict average interstitial fluid velocities (∼60.5μ m/s ) and average maximum shear stresses (∼11 Pa ) surrounding osteocytes in vivo. Interestingly, these values occur in the canaliculi around the osteocyte cell processes and are within the range of stimuli known to stimulate osteogenic responses by osteoblastic cells in vitro. Significantly our results suggest that the greatest mechanical stimulation of the osteocyte occurs in the cell processes, which, cell culture studies have indicated, is the most mechanosensitive area of the cell. These are the first computational FSI models to simulate the complex multi-physics mechanical environment of osteocyte in vivo and provide a deeper understanding of bone mechanobiology

Facile route to conformal hydrotalcite coatings over complex architectures:a hierarchically ordered nanoporous base catalyst for FAME production

An alkali- and nitrate-free hydrotalcite coating has been grafted onto the surface of a hierarchically ordered macroporous-mesoporous SBA-15 template via stepwise growth of conformal alumina adlayers and their subsequent reaction with magnesium methoxide. The resulting low dimensional hydrotalcite crystallites exhibit excellent per site activity for the base catalysed transesterification of glyceryl triolein with methanol for FAME production