57 research outputs found
Searching edges in the overlap of two plane graphs
Consider a pair of plane straight-line graphs, whose edges are colored red
and blue, respectively, and let n be the total complexity of both graphs. We
present a O(n log n)-time O(n)-space technique to preprocess such pair of
graphs, that enables efficient searches among the red-blue intersections along
edges of one of the graphs. Our technique has a number of applications to
geometric problems. This includes: (1) a solution to the batched red-blue
search problem [Dehne et al. 2006] in O(n log n) queries to the oracle; (2) an
algorithm to compute the maximum vertical distance between a pair of 3D
polyhedral terrains one of which is convex in O(n log n) time, where n is the
total complexity of both terrains; (3) an algorithm to construct the Hausdorff
Voronoi diagram of a family of point clusters in the plane in O((n+m) log^3 n)
time and O(n+m) space, where n is the total number of points in all clusters
and m is the number of crossings between all clusters; (4) an algorithm to
construct the farthest-color Voronoi diagram of the corners of n axis-aligned
rectangles in O(n log^2 n) time; (5) an algorithm to solve the stabbing circle
problem for n parallel line segments in the plane in optimal O(n log n) time.
All these results are new or improve on the best known algorithms.Comment: 22 pages, 6 figure
Crossover from mesoscopic to universal phase for electron transmission in quantum dots
Measuring phase in coherent electron systems (mesoscopic systems) provides
ample information not easily revealed by conductance measurements. Phase
measurements in relatively large quantum dots (QDs) recently demonstrated a
universal like phase evolution independent of dot size, shape, and occupancy.
Explicitly, in Coulomb blockaded QDs the transmission phase increased
monotonically by pi throughout each conductance peak, thereafter, in the
conductance valleys the phase returned sharply to its base value. Expected
mesoscopic features in the phase, related to spin degeneracy or to exchange
effects, were never observed. Presently, there is no satisfactory full
explanation for the observed phase universality. Unfortunately, the phase in a
few-electron QDs, where it can be better understood was never measured. Here we
report on such measurements on a small QD that occupy only 1-20 electrons. Such
dot was embedded in one arm of a two path electron interferometer, with an
electron counter near the dot. Unlike the repetitive behavior found in larger
dots we found now mesoscopic features for dot occupation of less than some 10
electrons. An unexpected feature in this regime is a clear observation of the
occupation of two different orbital states by the first two electrons -
contrary to the recent publications. As the occupation increased the phase
evolved and turned universal like for some 14 electrons and higher. The present
measurements allowed us to determine level occupancy and parity. More
importantly, they suggest that QDs go through a phase transition, from
mesoscopic to universal like behavior, as the occupancy increases. These
measurements help in singling out potential few theoretical models among the
many proposed.Comment: 12 pages, 6 figure
An Efficient Coding Hypothesis Links Sparsity and Selectivity of Neural Responses
To what extent are sensory responses in the brain compatible with first-order principles? The efficient coding hypothesis projects that neurons use as few spikes as possible to faithfully represent natural stimuli. However, many sparsely firing neurons in higher brain areas seem to violate this hypothesis in that they respond more to familiar stimuli than to nonfamiliar stimuli. We reconcile this discrepancy by showing that efficient sensory responses give rise to stimulus selectivity that depends on the stimulus-independent firing threshold and the balance between excitatory and inhibitory inputs. We construct a cost function that enforces minimal firing rates in model neurons by linearly punishing suprathreshold synaptic currents. By contrast, subthreshold currents are punished quadratically, which allows us to optimally reconstruct sensory inputs from elicited responses. We train synaptic currents on many renditions of a particular bird's own song (BOS) and few renditions of conspecific birds' songs (CONs). During training, model neurons develop a response selectivity with complex dependence on the firing threshold. At low thresholds, they fire densely and prefer CON and the reverse BOS (REV) over BOS. However, at high thresholds or when hyperpolarized, they fire sparsely and prefer BOS over REV and over CON. Based on this selectivity reversal, our model suggests that preference for a highly familiar stimulus corresponds to a high-threshold or strong-inhibition regime of an efficient coding strategy. Our findings apply to songbird mirror neurons, and in general, they suggest that the brain may be endowed with simple mechanisms to rapidly change selectivity of neural responses to focus sensory processing on either familiar or nonfamiliar stimuli. In summary, we find support for the efficient coding hypothesis and provide new insights into the interplay between the sparsity and selectivity of neural responses
Quantitative determination of vitamin D metabolites in plasma using UHPLC-MS/MS
Vitamin D is an important determinant of bone health at all ages. The plasma concentrations of 25-hydroxy vitamin D (25-OH D) and other metabolites are used as biomarkers for vitamin sufficiency and function. To allow for the simultaneous determination of five vitamin D metabolites, 25-OH D3, 25-OH D2, 24,25-(OH)2 D3, 1,25-(OH)2 D3, and 1,25-(OH)2 D2, in low volumes of human plasma, an assay using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was established. Plasma samples were spiked with isotope-labeled internal standards and pretreated using protein precipitation, solid-phase extraction (SPE) and a Diels–Alder derivatization step with 4-phenyl-1,2,4-triazoline-3,5-dione. The SPE recovery rates ranged from 55% to 85%, depending on the vitamin D metabolite; the total sample run time was <5 min. Mass spectrometry was conducted using positive ion electrospray ionization in the multiple reaction monitoring mode on a quadrupole–quadrupole-linear ion trap instrument after pre-column addition of methylamine to increase the ionization efficiency. The intra- and inter-day relative standard deviations were 1.6–4.1% and 3.7–6.8%, respectively. The limit of quantitation for these compounds was determined to be between 10 and 20 pg/mL. The 25-OH D results were compared with values obtained for reference materials (DEQAS). In addition, plasma samples were analyzed with two additional Diasorin antibody assays. All comparisons with conventional methods showed excellent correlations (r2 = 0.9738) for DEQAS samples, demonstrating the high degree of comparability of the new UHPLC-MS/MS technique to existing methods
First-principles quantum transport modeling of spin-transfer and spin-orbit torques in magnetic multilayers
We review a unified approach for computing: (i) spin-transfer torque in
magnetic trilayers like spin-valves and magnetic tunnel junction, where
injected charge current flows perpendicularly to interfaces; and (ii)
spin-orbit torque in magnetic bilayers of the type
ferromagnet/spin-orbit-coupled-material, where injected charge current flows
parallel to the interface. Our approach requires to construct the torque
operator for a given Hamiltonian of the device and the steady-state
nonequilibrium density matrix, where the latter is expressed in terms of the
nonequilibrium Green's functions and split into three contributions. Tracing
these contributions with the torque operator automatically yields field-like
and damping-like components of spin-transfer torque or spin-orbit torque
vector, which is particularly advantageous for spin-orbit torque where the
direction of these components depends on the unknown-in-advance orientation of
the current-driven nonequilibrium spin density in the presence of spin-orbit
coupling. We provide illustrative examples by computing spin-transfer torque in
a one-dimensional toy model of a magnetic tunnel junction and realistic
Co/Cu/Co spin-valve, both of which are described by first-principles
Hamiltonians obtained from noncollinear density functional theory calculations;
as well as spin-orbit torque in a ferromagnetic layer described by a
tight-binding Hamiltonian which includes spin-orbit proximity effect within
ferromagnetic monolayers assumed to be generated by the adjacent monolayer
transition metal dichalcogenide.Comment: 22 pages, 9 figures, PDFLaTeX; prepared for Springer Handbook of
Materials Modeling, Volume 2 Applications: Current and Emerging Material
Reduced costs with bisoprolol treatment for heart failure - An economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II)
Background
Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II).
Methods
Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K.
Results
Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results.
Interpretation
Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure
Dissecting mechanisms of resistance to targeted drug combination therapy in human colorectal cancer.
Genomic alterations in cancer cells result in vulnerabilities that clinicians can exploit using molecularly targeted drugs, guided by knowledge of the tumour genotype. However, the selective activity of these drugs exerts an evolutionary pressure on cancers that can result in the outgrowth of resistant clones. Use of rational drug combinations can overcome resistance to targeted drugs, but resistance may eventually develop to combinatorial therapies. We selected MAPK- and PI3K-pathway inhibition in colorectal cancer as a model system to dissect out mechanisms of resistance. We focused on these signalling pathways because they are frequently activated in colorectal tumours, have well-characterised mutations and are clinically relevant. By treating a panel of 47 human colorectal cancer cell lines with a combination of MEK- and PI3K-inhibitors, we observe a synergistic inhibition of growth in almost all cell lines. Cells with KRAS mutations are less sensitive to PI3K inhibition, but are particularly sensitive to the combined treatment. Colorectal cancer cell lines with inherent or acquired resistance to monotherapy do not show a synergistic response to the combination treatment. Cells that acquire resistance to an MEK-PI3K inhibitor combination treatment still respond to an ERK-PI3K inhibitor regimen, but subsequently also acquire resistance to this combination treatment. Importantly, the mechanisms of resistance to MEK and PI3K inhibitors observed, MEK1/2 mutation or loss of PTEN, are similar to those detected in the clinic. ERK inhibitors may have clinical utility in overcoming resistance to MEK inhibitor regimes; however, we find a recurrent active site mutation of ERK2 that drives resistance to ERK inhibitors in mono- or combined regimens, suggesting that resistance will remain a hurdle. Importantly, we find that the addition of low concentrations of the BCL2-family inhibitor navitoclax to the MEK-PI3K inhibitor regimen improves the synergistic interaction and blocks the acquisition of resistance
Modeling 2T937 Bipolar Transistors Based on Experimental Static and Frequency Characteristics
Effect of Physical Rehabilitation on Echocardiographic Parameters in Patients with Acute Coronary Syndrome
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