400 research outputs found
Etched distributed Bragg reflectors as three-dimensional photonic crystals: photonic bands and density of states
The photonic band dispersion and density of states (DOS) are calculated for
the three-dimensional (3D) hexagonal structure corresponding to a distributed
Bragg reflector patterned with a 2D triangular lattice of circular holes.
Results for the Si/SiO and GaAs/AlGaAs systems determine the optimal
parameters for which a gap in the 2D plane occurs and overlaps the 1D gap of
the multilayer. The DOS is considerably reduced in correspondence with the
overlap of 2D and 1D gaps. Also, the local density of states (i.e., the DOS
weighted with the squared electric field at a given point) has strong
variations depending on the position. Both results imply substantial changes of
spontaneous emission rates and patterns for a local emitter embedded in the
structure and make this system attractive for the fabrication of a 3D photonic
crystal with controlled radiative properties.Comment: 8 pages, 5 figures; to appear in Phys. Rev.
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A Semiconductor Microlaser for Intracavity Flow Cytometry
Semiconductor microlasers are attractive components for micro-analysis systems because of their ability to emit coherent intense light from a small aperture. By using a surface-emitting semiconductor geometry, we were able to incorporate fluid flow inside a laser microcavity for the first time. This confers significant advantages for high throughput screening of cells, particulates and fluid analytes in a sensitive microdevice. In this paper we discuss the intracavity microfluidics and present preliminary results with flowing blood and brain cells
An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib
BACKGROUND: Olaparib is poorly soluble, requiring advanced drug delivery technologies for adequate bioavailability. Sixteen capsules/day are required for the approved 400 mg twice-daily dose; a tablet formulation was developed to reduce pill burden. This clinical trial evaluated the optimal dose and administration schedule of the tablet formulation.
PATIENTS AND METHODS: Two stages of sequentially enrolled cohorts: stage 1, pharmacokinetic properties of tablet and capsule formulations were compared in patients with advanced solid tumours; stage 2, tablet dose escalation with expansion cohorts at doses/schedules of interest in patients with solid tumours and BRCAm breast/ovarian cancers.
RESULTS: Olaparib 200 mg tablets displayed similar Cmax,ss, but lower AUCss and Cmin,ss than 400 mg capsules. Following multiple dosing, steady-state exposure with tablets ≥300 mg matched or exceeded that of 400 mg capsules. After dose escalation, while 400 mg twice daily was the tablet maximum tolerated dose based on haematological toxicity, 65 % of patients in the randomized expansion phase eventually required dose reduction to 300 mg. Intermittent tablet administration did not significantly improve tolerability. Tumour shrinkage was similar for 300 and 400 mg tablet and 400 mg capsule cohorts.
CONCLUSIONS: The recommended monotherapy dose of olaparib tablet for Phase III trials was 300 mg twice daily, simplifying drug administration from 16 capsules to four tablets per day.
CLINICAL TRIAL NUMBER: NCT00777582 (ClinicalTrials.gov
Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1
The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development
Effect of the GaAsP shell on optical properties of self-catalyzed GaAs nanowires grown on silicon
We realize growth of self-catalyzed core-shell GaAs/GaAsP nanowires (NWs) on
Si substrates using molecular-beam epitaxy. Transmission electron microscopy
(TEM) of single GaAs/GaAsP NWs confirms their high crystal quality and shows
domination of the zinc-blende phase. This is further confirmed in optics of
single NWs, studied using cw and time-resolved photoluminescence (PL). A
detailed comparison with uncapped GaAs NWs emphasizes the effect of the GaAsP
capping in suppressing the non-radiative surface states: significant PL
enhancement in the core-shell structures exceeding 2000 times at 10K is
observed; in uncapped NWs PL is quenched at 60K whereas single core-shell
GaAs/GaAsP NWs exhibit bright emission even at room temperature. From analysis
of the PL temperature dependence in both types of NW we are able to determine
the main carrier escape mechanisms leading to the PL quench
Quantum saturation and condensation of excitons in CuO: a theoretical study
Recent experiments on high density excitons in CuO provide evidence for
degenerate quantum statistics and Bose-Einstein condensation of this nearly
ideal gas. We model the time dependence of this bosonic system including
exciton decay mechanisms, energy exchange with phonons, and interconversion
between ortho (triplet-state) and para (singlet-state) excitons, using
parameters for the excitonic decay, the coupling to acoustic and low-lying
optical phonons, Auger recombination, and ortho-para interconversion derived
from experiment. The single adjustable parameter in our model is the
optical-phonon cooling rate for Auger and laser-produced hot excitons. We show
that the orthoexcitons move along the phase boundary without crossing it (i.e.,
exhibit a ``quantum saturation''), as a consequence of the balance of entropy
changes due to cooling of excitons by phonons and heating by the non-radiative
Auger two-exciton recombination process. The Auger annihilation rate for
para-para collisions is much smaller than that for ortho-para and ortho-ortho
collisions, explaining why, under the given experimental conditions, the
paraexcitons condense while the orthoexcitons fail to do so.Comment: Revised to improve clarity and physical content 18 pages, revtex,
figures available from G. Kavoulakis, Physics Department, University of
Illinois, Urban
The two types of 3-dehydroquinase have distinct structures but catalyze the same overall reaction
The structures of enzymes catalyzing the reactions in central
metabolic pathways are generally well conserved as are their
catalytic mechanisms. The two types of 3-dehydroquinate
dehydratase (DHQase) are therefore most unusual since they
are unrelated at the sequence level and they utilize completely
different mechanisms to catalyze the same overall reaction.
The type I enzymes catalyze a cis-dehydration of 3-dehydroquinate
via a covalent imine intermediate, while the type II
enzymes catalyze a trans-dehydration via an enolate intermediate.
Here we report the three-dimensional structures of a
representative member of each type of biosynthetic DHQase.Both enzymes function as part of the shikimate pathway,
which is essential in microorganisms and plants for the
biosynthesis of aromatic compounds including folate,
ubiquinone and the aromatic amino acids. An explanation for
the presence of two different enzymes catalyzing the same
reaction is presented. The absence of the shikimate pathway in
animals makes it an attractive target for antimicrobial agents.
The availability of these two structures opens the way for the
design of highly specific enzyme inhibitors with potential
importance as selective therapeutic agents
Stability Analysis of a Reaction–Diffusion Equation with Spatiotemporal Delay and Dirichlet Boundary Condition
Validation of Individual Computerized Sow Feeding Systems in Lactation
Two experiments evaluated the accuracy of individual computerized feed delivery systems for lactating sows (GESTAL Solo, JYGA Technologies Inc., St-Lambert-de-Lauzon, Quebec, Canada). The feeders volumetrically dispense feed based on rotations of a screw auger. In Experiment 1, 29 prototype feeders were used across 3 farrowing groups. On d 0, 1 feeder was selected to calibrate the computer system to the bulk density of the lactation diet. Feeders were programmed for 5 feeding periods per day with feeding period allowing up to 4 feed drops triggered by the sow. Sows activate a trigger within the feed bowl to receive a targeted amount of feed (1.5 lb) and the computerized feeder records the delivery amount based on calibration values. In addition, total lactation feed intake was recorded by weighing the quantity of feed provided to the feeding system for each sow throughout lactation. Feed delivered by a single trigger activation on d 0, d 10, and d of weaning was collected and weighed with a scale and compared to the computer record. Additionally, total feed delivered over the lactation period was compared between the recorded computer measurement and scale weight. Average percentage difference between the two measurements ranged from 0.01 to 36.6% for a single trigger event. Computer-recorded total lactation feed intake was marginally less (P \u3c 0.089) than the actual weight of feed delivered (230.3 vs. 239.9 lb; SEM 5.43). Individual feeders had recorded total feed delivery ranging from 77 to 122% of actual weight delivered. Based on these results, a new feeder design, identical to the commercially marketed GESTAL Solo (plastic hopper manufactured with injection mold instead of rotational mold), was tested in Experiment 2. In Experiment 2, 29 feeders were used in a single farrowing group to evaluate the new sow feeders. Feeders were calibrated and data were collected using the same procedures as Experiment 1, except individual feed drops were collected 8 times per feeder throughout lactation. Average percentage difference across all feeders ranged from 3.8 to 13.4%. There was no evidence (P \u3c 0.542) of difference between the computer-recorded total lactation feed and actual weight of feed delivered (279.6 vs. 272.8 lb; SEM 4.03). Individual feeders had recorded total feed delivery ranging from 90.4 to 106.4% of actual weight delivered. Overall, this study shows the new feeder model was less variable in feed drops and total feed delivery than the old prototype
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