Ratio Of Target Research Articles

Current Trends in Radio-Pharmaceuticals

The development of radiotraces with defined affinities for specific receptor systems is a potentially useful approach to the design of radio pharmaceuticals for nuclear medicine. Radio labeled ligands, such as hormones and neurotransmitters, are being synthesized and evaluated as diagnostic tools for diseases which can be characterized either by changes in receptor concentration or by novel receptor expression. Since the utility of a radio pharmaceutical is dependent upon the achievement of adequate ratios of target to non-target accumulation of radio activity, design of radio traces via the receptor approach attempts to exploit those systems in which receptor is present in significantly higher concentration at potential target sites such as tumors. Receptormediated radio tracers are also currently being used in animal models to investigate the normal tissue distribution of drug and hormone receptors and the in-vivo pharmacokinetics of receptor binding. The successful development of receptor-avid radiopharmaceuticals will depend upon the ability to synthesize ligands of high specific radio activity which retain the high affinity and binding specifically for the receptor after radio labeling.

Dual-energy CT virtual non-calcium technique for detection of bone marrow edema in patients with vertebral fractures: A prospective feasibility study on a single- source volume CT scanner

ObjectivesDual-energy computed tomography (DECT) is a recent development for detecting bone marrow edema (BME) in patients with vertebral compression fractures. The aim of this pilot study was to determine the reliability of single-source DECT in detecting vertebral BME using magnetic resonance imaging (MRI) as standard of reference. Materials and methodsNine patients with radiographic thoracic or lumbar vertebral compression fractures underwent both, DECT on a 320-row single-source scanner and 1.5T MRI. Virtual non-calcium (VNC) images were reconstructed from the DECT volume datasets. Three blinded readers independently scored images for the presence of BME. Only vertebrae with loss of height in radiography (target vertebrae) were included in the analysis. A vertebra was counted as positive if two readers agreed on the presence of BME. Cohen’s kappa was calculated for interrater comparison. Intervertebral ratios of target and the reference vertebra were compared for CT attenuation and MR signal intensity in a reference vertebra using Spearman correlation. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. ResultsFourteen target vertebrae with a radiographic height loss were identified; eight of them showed BME on MRI, while DECT identified BME in 7 instances. There were no false positive virtual non-calcium images, resulting in a sensitivity of 0.88 (0.75–1.0 among all readers) and specificity of 1.0 (0.81–1.0). Interrater agreement was inferior for DECT (κ=0.63–0.89) compared to MRI (κ=0.9–1.0). Intervertebral ratio in VNC images strongly correlated with short-tau inversion recovery (r=0.87) and inversely with T1 (-0.89). SNR (0.2+/− 0.2 in VNC and 16.7+/− 7.3 in STIR) and CNR (0.2+/− 0.3 and 7.1+/− 6.3) values were inferior in VNC. ConclusionsDetecting BME with single-source DECT is feasible and allows detection of vertebral compression fractures with reasonably high sensitivity and specificity. However, image quality of VNC reconstructions has to be improved to achieve better interrater agreement. Nonetheless, DECT might accelerate the diagnostic work-flow in patients with vertebral compression fractures in the future and reduce the number of additional MRI examinations.

Effects of Scutellaria Barbata on VEGF Expression in K562 Cells

To investigate the anti-angiogenesis effect of Scutellaria barbata extract(SBE) on chronic myeloid leukemia(CML) K562 cell line in vitro. The proliferating activity after treating K562 cells with 0.5,1.0,2.0 and 4.0 g/ml SB for 24, 36, 48 hours were assessed by MTT assay. The level of vascular endothelial growth factor(VEGF) in the culture supematant of K562 cells was determined by ELISA; and the expression of VEGF mRNA was detected by RT-PCR. MTT assay showed that SBE could inhibit the proliferation of K562 cells in a dose-dependent manner (r=0.56); ELISA displayed that the concentration of VEGF in K562 cells in blank-control group was most high; after intervention of K562 cells by SBE (0.5,1.0,2.0 and 4.0 g/ml) for 48 h, the concentration of VEGF decreased, the comparison between different groups showed significant differences (P<0.05); after treatment with SBE for 48 h, the expression of VEGF mRNA in K562 cells decreased, the gray scale ratio of target gene/β-actin declined, and the difference between various groups was statistically significant (P<0.05). Conclution: SBE can inhibit K562 cell proliferation, its action mechanism may related with the VEGF level concentration in K562 cells and down-regulation of VEGF mRNA expression.

The annealing effects on the micro-structure and properties of RuMoC films as seedless barrier for advanced Cu metallization

100 nm thick RuMoC films and 5 nm thick RuMoC films with Cu capping have been deposited on Si(111) by magnetron co-sputtering with Ru and MoC confocal targets. The samples were subsequently annealed at temperatures ranging from 450 to 650 °C in vacuum at a pressure of 3 × 10−4 Pa to study the annealing effects on the microstructures and properties of RuMoC films for advanced seedless Cu metallization applications. The sheet resistances, residual oxygen contents, and microstructures of the RuMoC films have close correlation with the doping contents of Mo and C, which can be easily controlled by the deposition power ratio of MoC versus Ru targets (DPR). When DPR was 0.5, amorphous RuMoC film (marked as RuMoC II) with low sheet resistances and residual oxygen contents was obtained. The fundamental relationship between the annealing temperatures with the microstructures and properties of the RuMoC films was investigated, and a critical temperature point was revealed at about 550 °C where the components and microstructures of the RuMoC II films changed obviously. Results indicated that below 550 °C, the RuMoC II films remained amorphous due to the well-preserved C-Ru and C-Mo bonds. However, above 550 °C, the microstructures of RuMoC II films transformed from amorphous to nano-composite structure due to the breakage of Ru-C bonds, while the supersaturated solid solution MoC segregated out along the grain boundaries of Ru, thus hindering the diffusion of Cu and O atoms. This is the main mechanism of the excellent thermal stability of the RuMoC films after annealing at high temperatures. The results indicated great prospects of amorphous RuMoC films in advanced seedless Cu metallization applications.

Full Dose-Reduction Potential of Statistical Iterative Reconstruction for Head CT Protocols in a Predominantly Pediatric Population.

A statistical iterative reconstruction algorithm provides an effective approach to reduce patient dose by compensating for increased image noise in CT due to reduced radiation output. However, after a point, the degree to which a statistical iterative algorithm is used for image reconstruction changes the image appearance. Our aim was to determine the maximum level of statistical iterative reconstruction that can be used to establish dose-reduced head CT protocols in a primarily pediatric population while maintaining similar appearance and level of image noise in the reconstructed image. Select head examinations (brain, orbits, sinus, maxilla, and temporal bones) were investigated. Dose-reduced head protocols using an adaptive statistical iterative reconstruction were compared for image quality with the original filtered back-projection reconstructed protocols in a phantom by using the following metrics: image noise frequency (change in perceived appearance of noise texture), image noise magnitude, contrast-to-noise ratio, and spatial resolution. Dose-reduction estimates were based on CT dose index values. Patient volume CT dose index and image noise magnitude were assessed in 737 pre- and post-dose-reduced examinations. Image noise texture was acceptable for up to 60% adaptive statistical iterative reconstruction for the soft reconstruction kernel (at both 100 and 120 kV[peak]) and up to 40% adaptive statistical iterative reconstruction for the standard reconstruction kernel. Implementation of 40% and 60% adaptive statistical iterative reconstruction led to an average reduction in the volume CT dose index of 43% for brain, 41% for orbit, 30% for maxilla, 43% for sinus, and 42% for temporal bone protocols for patients between 1 month and 26 years of age, while maintaining an average noise magnitude difference of 0.1% (range, -3% to 5%), improving the contrast-to-noise ratio of low-contrast soft-tissue targets and the spatial resolution of high-contrast bony anatomy, compared with filtered back-projection. The methodology in this study demonstrates maximizing patient dose reduction and maintaining image quality by using statistical iterative reconstruction for a primarily pediatric population undergoing head CT examinations.

Onset of normal and inverse homoclinic bifurcation in a double plasma system near a plasma fireball

Plasma fireballs are generated due to a localized discharge and appear as a luminous glow with a sharp boundary, which suggests the presence of a localized electric field such as electrical sheath or double layer structure. The present work reports the observation of normal and inverse homoclinic bifurcation phenomena in plasma oscillations that are excited in the presence of fireball in a double plasma device. The controlling parameters for these observations are the ratio of target to source chamber (nT/nS) densities and applied electrode voltage. Homoclinic bifurcation is noticed in the plasma potential fluctuations as the system evolves from narrow to long time period oscillations and vice versa with the change of control parameter. The dynamical transition in plasma fireball is demonstrated by spectral analysis, recurrence quantification analysis (RQA), and statistical measures, viz., skewness and kurtosis. The increasing trend of normalized variance reflects that enhancing nT/nS induces irregularity in plasma dynamics. The exponential growth of the time period is strongly indicative of homoclinic bifurcation in the system. The gradual decrease of skewness and increase of kurtosis with the increase of nT/nS also reflect growing complexity in the system. The visual change of recurrence plot and gradual enhancement of RQA variables DET, Lmax, and ENT reflects the bifurcation behavior in the dynamics. The combination of RQA and spectral analysis is a clear evidence that homoclinic bifurcation occurs due to the presence of plasma fireball with different density ratios. However, inverse bifurcation takes place due to the change of fireball voltage. Some of the features observed in the experiment are consistent with a model that describes the dynamics of ionization instabilities.

⁶⁸Ga-NOTA-UBI-29-41 as a PET Tracer for Detection of Bacterial Infection.

The cationic peptide (68)Ga-NOTA-UBI-29-41 was synthesized and characterized. Biodistribution and PET/CT examinations were performed for evaluation of its biologic behavior. Differentiation of infection from sterile inflammation was investigated using microbiology methods at the sites of bacterial infections. Labeling of UBI-29-41 conjugated with NOTA with (68)Ga was optimized at 20°C-100°C and pH 3.5-5.5. Radiochemical purity, stability up to 260 min, and binding to serum proteins were determined. In vitro binding to Staphylococcus aureus was evaluated from 9.14 × 10(7) to 1.17 × 10(10) cfu/mL. Of 3 groups of Mus musculus Swiss male mice, the first was inoculated intramuscularly with 1.2 × 10(8) cfu of S. aureus to provoke infection, and the second, with 1.2 × 10(8) cfu of heat shock-treated S. aureus to generate sterile inflammation. The third mouse was not treated and served as a control. After 24 h, (68)Ga-NOTA-UBI-29-41 was administrated intravenously, and biodistribution was performed at 30, 60, and 120 min. PET/CT dynamic studies (120 min) were acquired. Sinograms were reconstructed using 3D maximum-likelihood expectation maximization and analyzed with software. Infected or inflamed muscles were dissected, homogenized, and cultured in tryptic soy agar medium. Recovered S. aureus was calculated as cfu/g. (68)Ga-NOTA-UBI-29-41 showed high renal excretion (83.2% ± 7.3%) of injected dose and rapid blood clearance. More than 95% was bound in vitro to 5 × 10(9) cfu/mL. A significantly higher (P< 0.05) accumulation of (68)Ga-NOTA-UBI-29-41 was observed at sites of S. aureus inoculation in infected mice (ratio of target to nontarget, 5.0 at 60 min and 4.1 at 120 min) compared with animals with inflammation (ratio of target to nontarget, 1.6 at 60 min and 1.2 at 120 min). The difference in uptake of (68)Ga-NOTA-UBI-29-41 in the infected muscles compared with the inflamed muscles was clearly observed in the PET/CT images and positively correlated with the degree of infection.

A novel approach to the island of stability of super-heavy elements search

It is expected that the cross section for super-heavy nuclei production of Z > 118 is dropping into the region of tens of femto barns. This creates a serious limitation for the complete fusion technique that is used so far. Moreover, the available combinations of the neutron to proton ratio of stable projectiles and targets are quite limited and it can be difficult to reach the island of stability of super heavy elements using complete fusion reactions with stable projectiles. In this context, a new experimental investigation of mechanisms other than complete fusion of heavy nuclei and a novel experimental technique are invented for our search of super- and hyper-nuclei. This contribution is focused on that technique.

C3-P-06Structome analysis of freeze-substituted virulentMycobacterium tuberculosisbased on direct enumeration of the serial ultrathin sections with TEM

Serial ultrathin sections of virulent Mycobacterium tuberculosis H37Rv (ATCC 27294) were examined by transmission electron microscope and “structome” analysis (i.e., the quantitative three-dimensional structural analysis of a whole cell through direct enumeration and measurement at the electron microscopic level) was performed [ 1 ]. Five M. tuberculosis cells were cut into 24, 36, 69, 55, and 63 serial ultrathin cross sections, respectively. On average, the cells were 2.71 ± 1.05 μm in length, and the average diameter of the cell was 0.345 ± 0.029 μm. The outer membrane and plasma membrane surface areas were 3.04 ± 1.33 μm 2 and 2.67 ± 1.19 μm 2 , respectively. The cell and cytoplasm volumes were 0.293 ± 0.113 fl (= μm 3 ) and 0.210 ± 0.091 fl, respectively. The average total ribosome number per cell was 1,672 ± 568, and the ribosome density was 716.5 ± 171.4/0.1 fl. This is the first report of a structome analysis of M. tuberculosis cells prepared as serial ultrathin sections following cryofixation and rapid freeze substitution. These data are based on the direct measurement and enumeration of exquisitely preserved single-cell structures in transmission electron microscopy images rather than calculations or assumptions from indirect biochemical or molecular biological data, and may explain the slow growth of M. tuberculosis and enhance understanding of the structural properties related to the expression of antigenicity, acid-fastness, and the mechanism of drug resistance, particularly in regard to the ratio of target to drug concentrations.

Heat stress inhibits proliferation, promotes growth, and induces apoptosis in cultured Lantang swine skeletal muscle satellite cells.

Proliferation suppression and apoptosis are the prominent characteristics induced by heat stress (HS) in cells, whereas the effects of HS on cell growth (mass accumulation) are unknown. In this study, Lantang swine (an indigenous breed of China) skeletal muscle satellite cells (SCs) were pre-cultured at 37 °C for 24 h. The HS group was subjected to HS at 41 °C, while the control group was maintained at 37 °C. Heat shock protein 70 (HSP70) expression and SC size are significantly increased (P<0.05) by HS, but cell proliferation is suppressed (P<0.05) and apoptosis is induced (P<0.05). HS led to a lower percentage of SCs in the G0/G1 phase (P<0.05) together with a higher percentage of SCs in the S phase (P<0.05). However, the percentage of SCs in the G2/M phase was decreased (P<0.05) at 48 h but then increased (P<0.05) at 72 h with HS. In addition, the phosphorylation ratios of protein kinase b (Akt), ribosomal protein S6 kinase (S6K), and ribosomal protein S6 were increased (P<0.05) by HS. Nevertheless, the phosphorylation ratios of the 4E binding protein 1 and the eukaryotic initiation factor-4E were indistinguishable (P>0.05) from those of the control group. The phosphorylation ratio of the mammalian target of rapamycin (mTOR) (Ser(2448)) increased (P<0.05) within 48 h, and apparent differences were abrogated at 72 h (P>0.05). Moreover, cleaved caspase-3 expression was increased at 72 h (P<0.05). These findings indicate that HS induces apoptosis and disrupts cell cycle distribution to decrease the number of cells. Additionally, HS can promote SC growth via an activated Akt/mTOR/S6K signaling pathway.

How best to study the function of consciousness?

How best to study the function of consciousness?

Rmax: A systematic approach to evaluate instrument sort performance using center stream catch

Sorting performance can be evaluated with regard to Purity, Yield and/or Recovery of the sorted fraction. Purity is a check on the quality of the sample and the sort decisions made by the instrument. Recovery and Yield definitions vary with some authors regarding both as how efficient the instrument is at sorting the target particles from the original sample, others distinguishing Recovery from Yield, where the former is used to describe the accuracy of the instrument’s sort count. Yield and Recovery are often neglected, mostly due to difficulties in their measurement. Purity of the sort product is often cited alone but is not sufficient to evaluate sorting performance. All of these three performance metrics require re-sampling of the sorted fraction. But, unlike Purity, calculating Yield and/or Recovery calls for the absolute counting of particles in the sorted fraction, which may not be feasible, particularly when dealing with rare populations and precious samples. In addition, the counting process itself involves large errors.Here we describe a new metric for evaluating instrument sort Recovery, defined as the number of particles sorted relative to the number of original particles to be sorted. This calculation requires only measuring the ratios of target and non-target populations in the original pre-sort sample and in the waste stream or center stream catch (CSC), avoiding re-sampling the sorted fraction and absolute counting. We called this new metric Rmax, since it corresponds to the maximum expected Recovery for a particular set of instrument parameters. Rmax is ideal to evaluate and troubleshoot the optimum drop-charge delay of the sorter, or any instrument related failures that will affect sort performance. It can be used as a daily quality control check but can be particularly useful to assess instrument performance before single-cell sorting experiments. Because we do not perturb the sort fraction we can calculate Rmax during the sort process, being especially valuable to check instrument performance during rare population sorts.

Structome analysis of virulent Mycobacterium tuberculosis, which survives with only 700 ribosomes per 0.1 fl of cytoplasm.

We previously reported the exquisite preservation of the ultrastructures of virulent Mycobacterium tuberculosis cells processed through cryofixation and rapid freeze substitution. Here, we report the “structome” analysis (i.e., the quantitative three-dimensional structural analysis of a whole cell at the electron microscopic level) of virulent M. tuberculosis using serial ultrathin sections prepared after cryofixation and rapid freeze substitution and analyzed by transmission electron microscopy. Five M. tuberculosis cells, which were contained in the serial ultrathin cross sections encompassing from one end to the other, were cut into 24, 36, 69, 55, and 63 serial ultrathin sections, respectively. On average, the cells were 2.71 ± 1.05 μm in length, and the average diameter of the cell was 0.345 ± 0.029 μm. The outer membrane and plasma membrane surface areas were 3.04 ± 1.33 μm2 and 2.67 ± 1.19 μm2, respectively. The cell, outer membrane, periplasm, plasma membrane, and cytoplasm volumes were 0.293 ± 0.113 fl (= μm3), 0.006 ± 0.003 fl, 0.060 ± 0.021 fl, 0.019 ± 0.008 fl, and 0.210 ± 0.091 fl, respectively. The average total ribosome number was 1,672 ± 568, and the ribosome density was 716.5 ± 171.4/0.1 fl. This is the first report of a structome analysis of M. tuberculosis cells prepared as serial ultrathin sections following cryofixation and rapid freeze substitution and examined by transmission electron microscopy. These data are based on the direct measurement and enumeration of exquisitely preserved single-cell structures in transmission electron microscopy images rather than calculations or assumptions from indirect biochemical or molecular biological data. In addition, these data may explain the slow growth of M. tuberculosis and enhance understanding of the structural properties related to the expression of antigenicity, acid-fastness, and the mechanism of drug resistance, particularly in regard to the ratio of target to drug concentrations.

Statistical Angular Resolution Limit for Ultrawideband MIMO Noise Radar

The two-dimensional angular resolution limit (ARL) of elevation and azimuth for MIMO radar with ultrawideband (UWB) noise waveforms is investigated using statistical resolution theory. First, the signal model of monostatic UWB MIMO noise radar is established in a 3D reference frame. Then, the statistical angular resolution limits (SARLs) of two closely spaced targets are derived using the detection-theoretic and estimation-theoretic approaches, respectively. The detection-theoretic approach is based on the generalized likelihood ratio test (GLRT) with given probabilities of false alarm and detection, while the estimation-theoretic approach is based on Smith’s criterion which involves the Cramér-Rao lower bound (CRLB). Furthermore, the relationship between the two approaches is presented, and the factors affecting the SARL, that is, detection parameters, transmit waveforms, array geometry, signal-to-noise ratio (SNR), and parameters of target (i.e., radar cross section (RCS) and direction), are analyzed. Compared with the conventional radar resolution theory defined by the ambiguity function, the SARL reflects the practical resolution ability of radar and can provide an optimization criterion for radar system design.

Effective Symbology: Searching for Salient Symbols

We present the results of an experiment designed to explore the effectiveness of different combinations of symbol features in facilitating participants’ ability to extract important global information in visually-cluttered displays. Participants were presented with arrays of visual symbols consisting of a number of visual targets amidst distractor symbols. The participants had to decide as quickly and accurately as possible whether there were more targets or more distractors present in the array. Combinations of symbol features (color-fill, color-letter, color-shape, and fill-shape) were varied on a block-to-block basis, while set size and ratio of targets to distractors (easy/20:80 or difficult/40:60) were varied on a trial-by-trial basis. The results of this experiment revealed that the combination of color and shape and specific shapes and fill led to worse performance compared to the combinations of color and fill. These results suggest that the combination of colors and fill can be used to facilitate the identification of display elements in a complex visual array.

Multipath ghost suppression for through-the-wall radar

When through-the-wall ultra-wideband (UWB) synthetic aperture radar (SAR) is applied to imaging, the interference of multipath spreading between targets will introduce ghosts into the SAR image. This paper proposes a hidden Markov model (HMM)–based method for suppressing ghosts in the SAR images. Simulations show that the method proposed can improve the peak value ratio of real targets to ghosts by about 15 dB.

Improvement and Simulation of THOR Formula with Yaw Angle

The THOR formula is widely used in the investigation of vulnerability and effectiveness of weapon system, however, its application was limited by the small slenderness ratio and limited materials of target. In order to investigate the damage effect of KE-rod warhead, this paper, basing on the classic THOR formula, focused on improving the formula of residual velocity and residual mass. The improved THOR model could predict the residual velocity and residual mass of KE-rod penetration in the complex conditions, and the predictions were found to be consistent with the experimental numerical results in the literatures. As the experimental data is limited, for the better validation of the improved formula, the paper investigated further research and verification of the improvement THOR formula with numerical simulation. Since the experimental data are limited for hypervelocity impact, comparisons of results between M-THOR with experimental and numerical data were widely preceded. The error is less than 4.8% for the predicted residual velocity while 5.4% for predicted residual velocity. The effect of yaw angle in the modified THOR formula was also found to agree quite well with the reference.

Abstract 189: STAR: CT and MR Perfusion Imaging and Good Outcomes in Endovascular Stroke Treatment

Background: Perfusion imaging may be used to select stroke patients for endovascular treatment, although few data are available on studies of CT and MRI, as used in Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), a prospective, multicenter, single-arm trial. Methods: The CT/MRI core lab processed available CT and MR perfusion source images with Olea Sphere 2.2 to measure volumes of infarct core and hypoperfusion. Established definitions for CT and MRI (core: rCBF &lt; 31% (CT); ADC &lt; 600х10 -6 mm 2 /s (MRI); hypoperfusion: Tmax &gt; 6s (CT and MRI)) were used to provide equivalent measures. Core and hypoperfusion volumes, mismatch ratio and DEFUSE-2 categories of target and malignant profile were used to define the relationship of perfusion imaging with clinical outcomes. Results: 87 of 202 cases in STAR (mean age 68.7 ± 12.5 years; 57% women; median baseline NIHSS 15 (8-25)) had CT (60/87 or 69%) or MRI (27/87 or 31%) perfusion imaging processed. This cohort was similar to other STAR cases with mean time to treatment of 263 ± 95 min and IV tPA before thrombectomy in 55%. Infarct core volume was mean 11.2 ± 19.7 (0-116.9) cc with hypoperfusion volume of mean 70.6 ± 46.0 (0-182.2) cc. Mismatch ratio was mean 17.8 ± 53.7. 75/87 (86%) cases were categorized as target mismatch and only 5/87 (6%) as malignant profile. 58/87 patients (67%) had a mRS of 0, 1, or 2 at 90 days and 39/87 (45%) with a mRS of 0 or 1. Multivariate logistic regression identified that age (OR 0.91, p=0.010), time to treatment (OR 0.23, p=0.001), and Tmax &gt; 10 s volume (OR 0.96, p=0.003) were associated with good outcomes (mRS 0-2 at 90 days). Only 2/87 (2.3%) patients had symptomatic ICH. Target mismatch exhibited a trend for good outcomes (p=0.149). Conclusions: STAR enrolled subjects with small infarct cores and extensive mismatch, achieving good clinical outcomes in a majority of cases treated with endovascular therapy. Randomized trials using CT and MR perfusion imaging are warranted to assess the impact of current endovascular stroke treatments.

Capture-Induced, Fast, Distributed, Splitting Based Selection with Imperfect Power Control

Opportunistic selection selects the node that improves the overall system performance the most. Selecting the best node is challenging as the nodes are geographically distributed and have only local knowledge. Yet, selection must be fast to allow more time to be spent on data transmission, which exploits the selected node's services. We analyze the impact of imperfect power control on a fast, distributed, splitting based selection scheme that exploits the capture effect by allowing the transmitting nodes to have different target receive powers and uses information about the total received power to speed up selection. Imperfect power control makes the received power deviate from the target and, hence, affects performance. Our analysis quantifies how it changes the selection probability, reduces the selection speed, and leads to the selection of no node or a wrong node. We show that the effect of imperfect power control is primarily driven by the ratio of target receive powers. Furthermore, we quantify its effect on the net system throughput.

Preclinical studies on intestinal administration of antisense oligonucleotides as a model for oral delivery for treatment of duchenne muscular dystrophy.

Antisense oligonucleotides (AONs) used to reframe dystrophin mRNA transcripts for Duchenne muscular dystrophy (DMD) patients are tested in clinical trials. Here, AONs are administered subcutaneously and intravenously, while the less invasive oral route would be preferred. Oral delivery of encapsulated AONs supplemented with a permeation enhancer, sodium caprate, has been successfully used to target tumor necrosis factor (TNF)-α expression in liver. To test the feasibility of orally delivered AONs for DMD, we applied 2′-O-methyl phosphorothioate AONs (with or without sodium caprate supplementation) directly to the intestine of mdx mice and compared pharmacokinetics and -dynamics with intravenous, intraperitoneal, and subcutaneous delivery. Intestinally infused AONs were taken up, but resulted in lower plasma levels compared to other delivery routes, although bioavailability could be largely improved by supplementation of sodium caprate. After intestinal infusion, AON levels in all tissues were lower than for other administration routes, as were the ratios of target versus nontarget organ levels, except for diaphragm and heart where comparable levels and ratios were observed. For each administration route, low levels of exon skipping in triceps was observed 3 hours post-AON administration. These data suggest that oral administration of naked 2′-O-methyl phosphorothioate AONs may be feasible, but only when high AON concentrations are used in combination with sodium caprate.