bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular and Morphologic Correlates of the Alternative Lengthening of Telomeres Phenotype in High‐Grade Astrocytomas
Authors: Nguyen Doreen N. , Heaphy Christopher M. , de Wilde Roeland F. , Orr Brent A. , Odia Yazmin , Eberhart Charles G. , Meeker Alan K. , Rodriguez Fausto J.
Published: August 2012

Recent studies suggest that the telomere maintenance mechanism known as alternative lengthening of telomeres (ALT) is relatively more common in specific glioma subsets and strongly associated with ATRX mutations. We retrospectively examined 116 high‐grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas, 19 anaplastic astrocytomas) with known ALT status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and IDH1R132H mutant protein. EGFR amplification was evaluated by fluorescence in situ hybridization (FISH). Almost half of fibrillary and gemistocytic astrocytomas (44%) demonstrated ALT. Conversely all gliosarcomas (n = 4), epithelioid (n = 2), giant cell (n = 2) and adult small cell astrocytomas (n = 7) were ALT negative. The ALT phenotype was positively correlated with the presence of round cells (P = 0.002), microcysts (P < 0.0002), IDH1 mutant protein (P < 0.0001), ATRX protein loss (P < 0.0001), strong P53 immunostaining (P < 0.0001) and absence of EGFR amplification (P = 0.004). There was no significant correlation with DAXX expression. We conclude that ALT represents a specific phenotype in high‐grade astrocytomas with distinctive pathologic and molecular features. Future studies are required to clarify the clinical and biological significance of ALT in high‐grade astrocytomas.
Strengthening the case for saproxylic arthropod conservation: a call for ecosystem services research
Authors: Ulyshen Michael D.
Published: August 2012

While research on the ecosystem services provided by biodiversity is becoming widely embraced as an important tool in conservation, the services provided by saproxylic arthropods – an especially diverse and threatened assemblage dependent on dead or dying wood – remain unmeasured.

A conceptual model depicting the reciprocal relationships between dead wood and saproxylic arthropod biodiversity, wildfires, climate change, forest productivity and pest outbreaks is presented. This model suggests that the ecological influence of saproxylic arthropods may extend far beyond their effects on wood decay.

Several predictions arising from this view are briefly summarised with the hope of stimulating research that may ultimately help strengthen the argument for saproxylic arthropod conservation.
Astragaloside IV inhibited the activity of CYP1A2 in liver microsomes and influenced theophylline pharmacokinetics in rats
Authors: Zhang Yan-Hui , Zhang You-Jin , Guo Yan-Lei , Li Wen-Juan , Yu Chao
Published: August 2012

Objectives

With the growing popularity of herbal and natural medicinal products, attention has turned to possible interactions between these products and pharmaceutical drugs. In this study, we examined whether astragaloside IV (AGS-IV) could inhibit the activity of CYP1A2 in rat liver microsomes in vitro and in vivo.

Methods

The effect of AGS-IV on CYP1A2 activity was investigated using probe substrates: phenacetin in vitro and theophylline in vivo. Phenacetin was incubated in rat liver microsomes with or without AGS-IV, and the mechanism, kinetics and type of inhibition were determined. The inhibitory effect of AGS-IV on CYP1A2 activity in rats was also determined using theophylline in vivo. The pharmacokinetics of theophylline were observed after a single or week-long treatment with AGS-IV.

Key findings

AGS-IV was found to be a competitive inhibitor with a Ki value of 6.29 μm  in vitro. In the multiple-pretreatment rat group, it was found to have a significantly higher area under the concentration–time curve (AUC) for theophylline, as well as a lower apparent oral total body clearance value (CL/F). In contrast, no significant difference in metabolism of theophylline was found for the single pretreatment group.

Conclusions

These findings suggest that AGS-IV is a potent inhibitor of CYP1A2. This work offers a useful reference for the reasonable and safe use of clinically prescribed herbal or natural products to avoid unnecessary herb–drug interactions.
Ultrasound‐Guided Venous Access for Pacemakers and Defibrillators
Authors: SETO ARNOLD H. , JOLLY AARON , SALCEDO JONATHAN
Published: August 2012

Ultrasound‐Guided Lead Placement. Introduction: Ultrasound guidance is widely recommended to reduce the risk of complications during central venous catheter placement. However, ultrasound guidance is not commonly utilized for implanting leads for cardiac rhythm management devices.

Methods and Results: We describe our technique of ultrasound‐guided pacemaker implantation, including a novel pull‐through technique that allows percutaneous guidewire insertion prior to the first incision. We review the literature and recent advances in ultrasound imaging technology that may facilitate the adoption of ultrasound guidance.

Conclusions: Ultrasound guidance provides a safe and rapid technique for extrathoracic subclavian or axillary venous lead placement. (J Cardiovasc Electrophysiol, Vol. 24, pp. 370‐374, March 2013)
The N‐terminal domain of the myelin enzyme 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase: direct molecular interaction with the calcium sensor calmodulin
Authors: Myllykoski Matti , Itoh Kouichi , Kangas Salla M. , Heape Anthony M. , Kang Sung‐Ung , Lubec Gert , Kursula Inari , Kursula Petri
Published: August 2012

2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase) is a quantitatively major enzyme in myelin, where it localizes to the non‐compact regions and is bound to the membrane surface. Although its catalytic activity in vitro has been characterized, the physiological function and in vivo substrate of CNPase remain unknown. Especially the N‐terminal domain has been poorly characterized; previously, we have shown it is involved in CNPase dimerization and RNA binding. Here, we show that purified CNPase binds to the calcium sensor protein calmodulin (CaM) in a calcium‐dependent manner; the binding site is in the N‐terminal domain of CNPase. CaM does not affect the phosphodiesterase activity of CNPase in vitro, nor does it influence polyadenylic acid binding. The colocalization of CNPase and CaM during Schwann cell myelination in culture was observed, and CaM antagonists induced the colocalization of CNPase with microtubules in differentiated CG‐4 oligodendrocytes. An analysis of post‐translational modifications of CNPase from rat brain revealed the presence of two novel phosphorylation sites on Tyr110 and Ser169 within the N‐terminal domain. The results indicate a role for the N‐terminal domain of CNPase in mediating multiple molecular interactions and provide a starting point for detailed structure‐function studies on CNPase and its N‐terminal domain.
Differential neurite outgrowth is required for axon specification by cultured hippocampal neurons
Authors: Yamamoto Hideaki , Demura Takanori , Morita Mayu , Banker Gary A. , Tanii Takashi , Nakamura Shun
Published: August 2012

Formation of an axon is the first morphological evidence of neuronal polarization, visible as a profound outgrowth of the axon compared with sibling neurites. One unsolved question on the mechanism of axon formation is the role of axon outgrowth in axon specification. This question was difficult to assess, because neurons freely extend their neurites in a conventional culture. Here, we leveraged surface nano/micro‐modification techniques to fabricate a template substrate for constraining neurite lengths of cultured neurons. Using the template, we asked (i) Do neurons polarize even if all neurites cannot grow sufficiently long? (ii) Would the neurite be fated to become an axon if only one was allowed to grow long? A pattern with symmetrical short paths (20 μm) was used to address the former question, and an asymmetrical pattern with one path extended to 100 μm for the latter. Axon formation was evaluated by tau‐1/MAP2 immunostaining and live‐cell imaging of constitutively‐active kinesin‐1. We found that (1) neurons cannot polarize when extension of all neurites is restricted and that (2) when only a single neurite is permitted to grow long, neurons polarize and the longest neurite becomes the axon. These results provide clear evidence that axon outgrowth is required for its specification.
Intracellular BKCa (iBKCa) channels
Authors: Singh Harpreet , Stefani Enrico , Toro Ligia
Published: August 2012

Abstract  The large conductance calcium‐ and voltage‐activated potassium channel (BKCa) is widely expressed at the plasma membrane. This channel is involved in a variety of fundamental cellular functions including excitability, smooth muscle contractility, and Ca2+ homeostasis, as well as in pathological situations like proinflammatory responses in rheumatoid arthritis, and cancer cell proliferation. Immunochemical, biochemical and pharmacological studies from over a decade have intermittently shown the presence of BKCa in intracellular organelles. To date, intracellular BKCa (iBKCa) has been localized in the mitochondria, endoplasmic reticulum, nucleus and Golgi apparatus but its functional role remains largely unknown except for the mitochondrial BKCa whose opening is thought to play a role in protecting the heart from ischaemic injury. In the nucleus, pharmacology suggests a role in regulating nuclear Ca2+, membrane potential and eNOS expression. Establishing the molecular correlates of iBKCa, the mechanisms defining iBKCa organelle‐specific targeting, and their modulation are challenging questions. This review summarizes iBKCa channels, their possible functions, and efforts to identify their molecular correlates.
Synaptic integration in dendrites: exceptional need for speed
Authors: Golding Nace L. , Oertel Donata
Published: August 2012

Abstract  Some neurons in the mammalian auditory system are able to detect and report the coincident firing of inputs with remarkable temporal precision. A strong, low‐voltage‐activated potassium conductance (gKL) at the cell body and dendrites gives these neurons sensitivity to the rate of depolarization by EPSPs, allowing neurons to assess the coincidence of the rising slopes of unitary EPSPs. Two groups of neurons in the brain stem, octopus cells in the posteroventral cochlear nucleus and principal cells of the medial superior olive (MSO), extract acoustic information by assessing coincident firing of their inputs over a submillisecond timescale and convey that information at rates of up to 1000 spikes s−1. Octopus cells detect the coincident activation of groups of auditory nerve fibres by broadband transient sounds, compensating for the travelling wave delay by dendritic filtering, while MSO neurons detect coincident activation of similarly tuned neurons from each of the two ears through separate dendritic tufts. Each makes use of filtering that is introduced by the spatial distribution of inputs on dendrites.
Maternal corticosterone regulates nutrient allocation to fetal growth in mice
Authors: Vaughan Owen R. , Sferruzzi‐Perri Amanda N. , Fowden Abigail L.
Published: August 2012

Key points

Stress during pregnancy leads to fetal growth restriction.

Natural glucocorticoids, such as corticosterone, are elevated by maternal stress and, hence, may mediate the effects of stress on fetal growth.

This study shows that increasing corticosterone levels in pregnant mice limits fetal growth by reducing the amino acid supply and density of blood vessels in the placenta.

The findings suggest that excess corticosterone may act to defend maternal resources during times of stress by constraining the placental allocation of nutrients to the fetus.

The results also provide a potential mechanism by which stresses during pregnancy can program intrauterine growth and development with consequences in later life.

Abstract  Stresses during pregnancy that increase maternal glucocorticoids reduce birth weight in several species. However, the role of natural glucocorticoids in the mother in fetal acquisition of nutrients for growth remains unknown. This study aimed to determine whether fetal growth was reduced as a consequence of altered amino acid supply when mice were given corticosterone in their drinking water for 5 day periods in mid to late pregnancy (day, D, 11–16 or D14–19). Compared to controls drinking tap water, fetal weight was always reduced by corticosterone. At D16, corticosterone had no effect on materno‐fetal transfer of [14C]methylaminoisobutyric acid (MeAIB), although placental MeAIB accumulation and expression of the Slc38a1 and Slc38a2 transporters were increased. However, at D19, 3 days after treatment ended, materno‐fetal transfer of MeAIB was increased by 37% (P < 0.04). During treatment at D19, placental accumulation and materno‐fetal transfer of MeAIB were reduced by 40% (P < 0.01), although expression of Slc38a1 was again elevated. Permanent reductions in placental vascularity occurred during the earlier but not the later period of treatment. Placental Hsd11b2 expression, which regulates feto‐placental glucocorticoid bioavailability, was also affected by treatment at D19 only. Maternal corticosterone concentrations inversely correlated with materno‐fetal MeAIB clearance and fetal weight at D19 but not D16. On D19, weight gain of the maternal carcass was normal during corticosterone treatment but reduced in those mice treated from D11 to D16, in which corticosterone levels were lowest. Maternal corticosterone is, therefore, a physiological regulator of the amino acid supply for fetal growth via actions on placental phenotype.
Adverse cardiac remodelling in spontaneously hypertensive rats: acceleration by high aerobic exercise intensity
Authors: da Costa Rebelo Rui Manuel , Schreckenberg Rolf , Schlüter Klaus‐Dieter
Published: August 2012

Key points

Physical exercise is recommended as first line therapy for hypertensive patients. However, studies investigating long‐term effects of high intensity exercise on the progression of hypertensive heart disease have revealed conflicting results.

We show that high intensity aerobic exercise accelerates hypertensive heart disease and improves fibrosis.

Surprisingly, high intensity aerobic exercise in the presence of an angiotensin converting enzyme inhibitor not only attenuated training induced mal‐adaptation but exerts positive repair processes. These effects were independent of blood pressure effects.

The results of this study provide evidence that high physical activity in hypertensives must be considered as an important risk factor rather than a therapeutic intervention.

Abstract  In the present study it was hypothesized that voluntary aerobic exercise favours a pro‐fibrotic phenotype and promotes adverse remodelling in hearts from spontaneously hypertensive rats (SHRs) in an angiotensin II‐dependent manner. To test this, female SHRs at the age of 1 year were started to perform free running wheel exercise. Captopril was used to inhibit the renin–angiotensin system (RAS). Normotensive rats and SHRs kept in regular cages were used as sedentary controls. Training intensity, expressed as mean running velocity, was positively correlated with the left ventricular mRNA expression of TGF‐β1, collagen‐III and biglycan but negatively correlated with the ratio of sarcoplasmic reticulum Ca2+‐ATPase (SERCA)2a to Na+–Ca2+ exchanger (NCX). A pro‐fibrotic phenotype was verified by Picrosirius red staining. Sixty‐seven per cent of SHRs performing free running wheel exercise died either spontaneously or had to be killed during a 6 month follow‐up. In the presence of captopril, aerobic exercise did not show a similar positive correlation between training intensity and the expression of fibrotic markers. Moreover, in SHRs receiving captopril and performing free running wheel exercise, a training intensity‐dependent reverse remodelling of the SERCA2a‐to‐NCX ratio was observed. None of these rats died spontaneously or had to be killed. In captopril‐treated SHRs performing exercise, expression of mRNA for decorin, a natural inhibitor of TGF‐β1, was up‐regulated. Despite these differences between SHR‐training groups with and without captopril, positive training effects (lower resting heart rate and no progression of hypertension) were found in both groups. In conclusion, high aerobic exercise induces an angiotensin II‐dependent adverse remodelling in chronic pressure overloaded hearts. However, high physical activity can potentially induce reverse remodelling in the presence of RAS inhibition.
Zinc induces long‐term upregulation of T‐type calcium current in hippocampal neurons in vivo
Authors: Ekstein Dana , Benninger Felix , Daninos Moshe , Pitsch Julika , van Loo Karen M. J. , Becker Albert J. , Yaari Yoel
Published: August 2012

Key points

Zinc induces various acute and persistent effects in neurons and it acutely blocks T‐type voltage‐gated calcium current (ICaT).

I
CaT contributes to pilocarpine status epilepticus (SE)‐induced epileptogenesis (transformation of normal brain into epileptic) by mediating the increase in intrinsic excitability of CA1 hippocampal neurons. Therefore, since SE causes both zinc release into the extracellular space and long‐lasting increase in ICaT, zinc may actually upregulate ICaT on the long‐term.

We demonstrated that when injected into the lateral ventricles of rats zinc upregulated ICaT in a subset of CA1 hippocampal neurons for about 2 weeks.

This shows that zinc has a dual effect on ICaT, blocking it acutely while causing its long‐term upregulation.

This finding provides a possible explanation to the mechanism of epileptogenesis induced by pathological conditions associated with enhanced release of zinc, such as SE.

Abstract  Extracellular zinc can induce numerous acute and persistent physiological and toxic effects in neurons by acting at their plasma membrane or intracellularly following permeation or uptake into them. Zinc acutely and reversibly blocks T‐type voltage‐gated calcium current (ICaT), but the long‐term effect of zinc on this current has not been studied. Because chemically induced status epilepticus (SE) results in the release of zinc into the extracellular space, as well as in a long‐lasting increase in ICaT in CA1 pyramidal cells, we hypothesized that zinc may play a causative role in ICaT upregulation. We tested this hypothesis by monitoring for 18 days the effects of zinc and ibotenic acid (a neurotoxic agent serving as control for zinc), injected into the right lateral ventricle, on ICaT in rat CA1 pyramidal cells. Both zinc and ibotenic acid caused marked hippocampal lesions on the side of injection, but only minor damage to contralateral hippocampi. Zinc, but not ibotenic acid, caused upregulation of a nickel‐sensitive ICaT in a subset of contralateral CA1 pyramidal cells, appearing 2 days after injection and lasting for about 2 weeks thereafter. In contrast, acute application of zinc to CA1 pyramidal cells promptly blocked ICaT. These data indicate that extracellular zinc has a dual effect on ICaT, blocking it acutely while causing its long‐term upregulation. Through the latter effect, zinc may regulate the intrinsic excitability of principal neurons, particularly in pathological conditions associated with enhanced release of zinc, such as SE.
Optimization and Design of a Multipass Branching Microchannel Heat Sink for Electronics Cooling
Authors: Dede Ercan M.
Published: August 2012

This article is focused on the optimization and design of a multipass branching microchannel heat sink for high heat flux electronics cooling applications. A multiphysics topology optimization method is used to arrive at two different branching channel solutions for the cooling of a heated plate. These optimization results are combined and synthesized into a unique multipass manifold microchannel heat sink design that has both jet and channel based characteristics. Numerical experiments for a representative electronics package were completed to evaluate the heat sink thermal and fluid performance. It is found that the derived cold plate exhibits favorable heat transfer with low pressure drop due to multiple passes through the branching microchannels. In addition to numerical results, ongoing prototype development for concept validation is described.
Die Bonding of High Power 808 nm Laser Diodes With Nanosilver Paste
Authors: Yan Yi , Chen Xu , Liu Xingsheng , Mei Yunhui , Lu Guo-Quan
Published: August 2012

Conduction-cooled high power laser diodes have a variety of significant commercial, industrial, and military applications. For these devices to perform effectively, an appropriate die-attached material meeting specific requirements must be selected. In this study, nanosilver paste, a novel die-attached material, was used in packaging the 60 W 808 nm high power laser diodes. The properties of the laser diodes operating in the continuous wave (CW) mode, including the characteristics of power–current–voltage (LIV), spectrum, near field, far field, near field linearity, spatial spectrum, and thermal impedance, were determined. In addition, destructive tests, including the die shear test, scanning acoustic microscopy, and the thermal rollover test, were conducted to evaluate the reliability of the die bonding of the 60 W 808 nm high power semiconductor laser with nanosilver paste. Thermal analyses of the laser diodes operating at CW mode with different die-attached materials, indium solder, gold–tin solder and nanosilver paste, were conducted by finite element analysis (FEA). According to the result of the FEA, the nanosilver paste resulted in the lowest temperature in the laser diodes. The test results showed that the nanosilver paste was a very promising die-attached material in packaging high power semiconductor laser.
Predicted Thermal Stress in a Multileg Thermoelectric Module (TEM) Design
Authors: Suhir E. , Shakouri A.
Published: August 2012

A physically meaningful analytical (mathematical) model is developed for the prediction of the interfacial shearing thermal stress in an assembly comprised of two identical components, which are subjected to different temperatures. The bonding system is comprised of a plurality of identical columnlike supports located at equal distances (spaces) from each other. The model is developed in application to a thermoelectric module (TEM) design where bonding is provided by multiple thermoelectric material supports (legs). We show that thinner (dimension in the horizontal direction) and longer (dimension in the vertical direction) TEM legs could result in a significant stress relief, and that such a relief could be achieved even if shorter legs are employed, as long as they are thin and the spacing between them is significant. It is imperative, of course, that if thin legs are employed for lower stresses, there is still enough interfacial “real estate,” so that the adhesive strength of the assembly is not compromised. On the other hand, owing to a lower stress level in an assembly with thin legs and large spacing, assurance of its interfacial strength is less of a challenge than for a conventional assembly with stiff, thick, and closely positioned legs. We show also that the thermal stresses not only in conventional TEM designs (using Be2Te3 as the thermoelectric material, and Sn-Sb solder), but also in the future high-power (and high operating temperatures) TEM design (using Si or SiGe as the thermoelectric material and Gold100 as the appropriate solder), might be low enough, so that the short- and long-term reliability of the TEM structure could still be assured. We have found, however, that thin-and-long legs should be considered for lower stresses, but not to an extent that appreciable bending deformations of the legs become possible. Future work will include, but might not be limited to, the finite-element computations and to experimental evaluations (e.g., shear-off testing) of the stress-at-failure for the TEMs of interest.
Mechanically robust silica-like coatings deposited by microwave plasmas for barrier applications
Authors: Maria Coclite Anna , De Luca François , Gleason Karen K.
Published: August 2012

Dense and flexible silicon dioxide-like barrier coatings were deposited by microwave postdischarge (downstream plasma). The optical transparency, recyclability, and compatibility with microwave usage are some of the advantages of SiOx offers as compared to thin metallic coatings. Generally, porous silicon dioxide coatings with poor barrier properties are obtained by microwave downstream plasmas, because of limited ion bombardment. Here, we demonstrate that by using very high powers, mechanically robust, barrier coatings deposit both by pulsed and continuous microwave downstream discharges. These SiOx coatings exhibit hardness comparable to Al2O3, but have higher elasticity. Thus, the SiOx have superior cohesion and the ability to recover after cracking. The high critical tensile and compression strain for crack formation demonstrates that these coatings are very resistant and flexible. Correspondingly, a two orders of magnitude barrier improvement is obtained with 100-nm-thick-coating deposited by continuous discharge. The films deposited by pulsed discharges show better elasticity and flexibility but slightly lower barrier performances compared to the coatings deposited by continuous discharges.
Discrimination of gastric cancer from normal by serum RNA based on surface‐enhanced Raman spectroscopy (SERS) and multivariate analysis
Authors: Chen Yanping , Chen Gang , Zheng Xiongwei , He Cheng , Feng Shangyuan , Chen Yan , Lin Xiaoqian , Chen Rong , Zeng Haisan
Published: August 2012

Purpose:

Here, the authors explore the feasibility of discriminating cancer patients from healthy controls by serum RNA detection based on surface‐enhanced Raman spectroscopy (SERS) and multivariate analysis.

Methods:

MgSO4‐aggregated silver nanoparticles (Ag NP) as the SERS‐active substrate presented strong SERS signals to RNA. SERS measurements were performed on two groups of serum RNA samples: one group from patients (n = 31) with gastric cancer and the other group from healthy volunteers (n = 34).

Results:

Tentative assignments of the Raman bands in the normalized SERS spectra demonstrated that there are differential expressions of circulating RNA between the gastric cancer group and the control group. Principal component analysis (PCA) combined with linear discriminate analysis (LDA) was introduced to differentiate gastric cancer from normal and achieved sensitivity of 100% and specificity of 94.1%.

Conclusions:

This exploratory study demonstrated potential for developing serum RNA SERS analysis into a useful clinical tool for noninvasive screening and detection of cancer.
A novel segmentation method for breast ultrasound images based on neutrosophic l‐means clustering
Authors: Shan Juan , Cheng H. D. , Wang Yuxuan
Published: August 2012

Purpose:

Fully automatic and accurate breast lesion segmentation is an essential and challenging task. In this paper, the authors develop a novel, effective, and fully automatic method for breast ultrasound (BUS) image segmentation.

Methods:

The segmentation method utilizes a novel phase feature to improve the image quality, and a novel neutrosophic clustering approach to detect the accurate lesion boundary. First, a region of interest is generated to cut off complex background. After speckle reduction, an enhancement algorithm based on phase in max‐energy orientation (PMO) is developed to further improve the image quality. The PMO is a newly proposed 2D phase feature obtained by filtering the image in the frequency domain and calculating the phase accumulation in the orientation with maximum energy. Finally, the authors propose a novel clustering approach called neutrosophic l‐means (NLM) to detect the lesion boundary. NLM is a generalized clustering method that can be used to solve other clustering problems as well. In this paper, NLM is used to segment images with vague boundaries, and to deal with uncertainty better. To evaluate the performance of the proposed method, the authors compare it with the traditional fuzzy c‐means clustering, active contour, level set, and watershed‐based segmentation methods, using a common database. Radiologist's manual delineations are used as the golden standards. Five assessment metrics are utilized to evaluate the performance from different aspects. Both accuracy and efficiency are analyzed. Sensitivity analysis is also conducted to test the robustness of the proposed method.

Results:

Compared with the other methods, the proposed method generates the most similar boundaries to the radiologist's manual delineations (TP rate is 92.4%, FP rate is 7.2%, and similarity rate is 86.3%; Hausdorff distance is 22.5 pixels and mean absolute distance is 4.8 pixels), with efficient processing speed (averagely 9.8 s per image). Sensitivity analysis shows the robustness of the proposed method as well.

Conclusions:

The proposed method is a fully automatic segmentation method for BUS images that can generate accurate lesion boundaries even for complicated cases. The fast processing speed, robustness, and accuracy of the proposed method suggest its potential applications in clinics.
Target‐specific optimization of four‐dimensional cone beam computed tomography
Authors: Ahmad Moiz , Pan Tinsu
Published: August 2012

Purpose:

Under‐sampling artifacts are a major problem in four‐dimensional cone‐beam computed tomography (4D‐CBCT) and may compromise evaluation of target motion. Several studies have addressed scan parameter selection for minimizing under‐sampling artifacts; however, the role of the target characteristics in scan parameter selection has not been investigated. In this work, the authors evaluated 4D‐CBCT performance by assessing the accuracy of target motion measurements for various target sizes and motions. The results may serve as patient‐specific guidelines for scan parameters selection in 4D‐CBCT.

Methods:

The authors acquired 4D‐CBCT scans of a moving phantom consisting of six water‐filled sphere targets of sizes 10–37 mm, using various scan times ranging from 30 s to 3 min., setting the motion to 3‐s and 6‐s periods. The authors used automatic image registration to extract the target motion trajectories and evaluated these measurements for various target sizes and motions over various combinations of scan parameters including scan time, detector configuration, number of respiration phases, and reconstruction filters.

Results:

The most important object parameter to 4D‐CBCT performance was the period of motion. Measurements for the 6‐s motion were always systematically less accurate than measurements for the 3‐s motion for 34 of 36 objects of various sizes and periods of motion. The 6‐s motion required a greater scan time than the 3‐s motion for equivalent measurement accuracy. The second most influential parameter was the target size. For the 3‐s period of motion, objects larger than 13 mm were tracked with sub‐millimeter accuracy with a 1‐min scan time. For the 6‐s period of motion, objects larger than 22‐mm were tracked with sub‐millimeter accuracy with a 1.5‐min scan time. For all sizes and motions, temporal blurring was observed when the number of phases was fewer than 8. Offset detector configuration provided the same performance as centered detector except for small targets (20 mm.) at short scan times (≤1 min). Finally, reconstruction filtering and number of respiratory phases did not affect performance.

Conclusions:

Scan time should be set according to target size and motion. The authors have provided figures that provide the minimum scan time needed to achieve the particular motion measurement accuracy for a particular size and motion period.
The Stoichiometric Production of IL-2 and IFN-γ mRNA Defines Memory T Cells That Can Self-Renew After Adoptive Transfer in Humans
Authors: Wang Anran , Chandran Smita , Shah Syed A. , Chiu Yu , Paria Biman C. , Aghamolla Tamara , Alvarez-Downing Melissa M. , Lee Chyi-Chia Richard , Singh Sanmeet , Li Thomas , Dudley Mark E. , Restifo Nicholas P. , Rosenberg Steven A. , Kammula Udai S.
Published: August 2012

Cytokines can identify memory T cells used for cancer immunotherapy.
Tale of Reactive Oxygen Species Retold
Authors: Methe Heiko
Published: August 2012

Ataxia telangiectasia–mutated kinase regulates reactive oxygen signaling in new blood vessel formation.
A Silver Bullet for T Cell Malignancies?
Authors: Tanhehco Yvette
Published: August 2012

Inhibitors of Itk kinase may be useful for treating T cell malignancies.
Effects of Olympic-style taekwondo kicks on an instrumented head-form and resultant injury measures
Authors: Fife Gabriel P , O'Sullivan David M , Pieter Willy , Cook David P , Kaminski Thomas W
Published: August 2012

Objective

The objective of this study was to assess the effect of taekwondo kicks and peak foot velocity (FVEL) on resultant head linear acceleration (RLA), head injury criterion (HIC15) and head velocity (HVEL).

Methods

Each subject (n=12) randomly performed five repetitions of the turning kick (TK), clench axe kick (CA), front leg axe kick, jump back kick (JB) and jump spinning hook kick (JH) at the average standing head height for competitors in their weight division. A Hybrid II Crash Test Dummy head was fitted with a protective taekwondo helmet and instrumented with a triaxial accelerometer and fixed to a height-adjustable frame. Resultant head linear acceleration, HVEL, FVEL data were captured and processed using Qualysis Track Manager.

Results

The TK (130.11±51.67 g) produced a higher RLA than the CA (54.95±20.08 g, p<0.001, d=1.84) and a higher HIC15 than the JH (672.74±540.89 vs 300.19±144.35, p<0.001, ES=0.97). There was no difference in HVEL of the TK (4.73±1.67 m/s) and that of the JB (4.43±0.78 m/s; p=0.977, ES<0.01).

Conclusions

The TK is of concern because it is the most common technique and cause of concussion in taekwondo. Future studies should aim to understand rotational accelerations of the head.
Topical glyceryl trinitrate treatment of chronic patellar tendinopathy: a randomised, double-blind, placebo-controlled clinical trial
Authors: Steunebrink Mirjam , Zwerver Johannes , Brandsema Ruben , Groenenboom Petra , Akker-Scheek Inge van den , Weir Adam
Published: August 2012

Objectives

To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone.

Methods

Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN or placebo patch in combination with eccentric squats on a decline board. Measurements were performed at baseline, 6, 12 and 24 weeks. Primary outcome measure was the Victorian Institute of Sports Assessment-Patella (VISA-P) questionnaire. Secondary outcome measures were patient satisfaction and pain scores during sports. Generalised estimated equation was used to analyse the treatment, time and treatment×time effect. Analyses were performed following the intention-to-treat principle.

Results

VISA-P scores for both groups improved over the study period to 75.0±16.2 and 80.7±22.1 at 24 weeks. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.80). Mean Visual Analogue Scores pain scores during sports for both groups increased over the study period to 6.6±3 and 7.8±3.1. Results showed a significant effect for time (p<0.01) but no effect for treatment×time (p=0.38). Patient satisfaction showed no difference between GTN and placebo groups (p=0.25) after 24 weeks, but did show a significant difference over time (p=0.01). Three patients in the GTN group reported some rash.

Conclusion

It seems that continuous topical GTN treatment in addition to an eccentric exercise programme does not improve clinical outcome compared to placebo patches and an eccentric exercise programme in patients with chronic patellar tendinopathy.
The prevalence and clinicopathological profile of IgM nephropathy in children with steroid-resistant nephrotic syndrome at a single centre in Pakistan
Authors: Shakeel Shaheera , Mubarak Muhammed , Kazi Javed I , Lanewala Ali
Published: August 2012

Background

There is little information on the clinicopathological characteristics of IgM nephropathy (IgMN) in paediatric steroid-resistant nephrotic syndrome (SRNS) and its response to calcineurin inhibitors (CNI).

Material and Methods

This study was conducted at Sindh Institute of Urology and Transplantation, from January 2009 to August 2011. All SRNS children who received renal biopsies were included. Relevant data were compared among minimal change disease (MCD) and IgMN. The response to CNI was analysed in detail in IgMN by groups (group 1: complete or partial remission; group 2: no response).

Results

The frequency of IgMN in 147 children with SRNS was 13.6%. Compared with MCD, there was a male preponderance in IgMN. Blood urea and serum creatinine both at presentation and at last follow-up were significantly higher in IgMN. Regarding subgroups of IgMN, systolic blood pressure (SBP), blood urea and serum creatinine were significantly higher in group 2 at presentation, while at last follow-up, SBP, diastolic blood pressure and proteinuria were higher in group 2. The prevalence and degree of mesangial proliferation, global glomerulosclerosis, interstitial fibrosis and tubular atrophy were significantly higher in group 2.

Conclusions

IgMN is a common cause of paediatric SRNS and is significantly different from MCD. There is also a significant difference in clinical and laboratory parameters among responders and non-responders to CNI in IgMN.
Strategies and tools for studying the metabolism and function of γ-aminobutyrate in plants. II. Integrated analysis
Authors: Shelp Barry J. , Bozzo Gale G. , Zarei Adel , Simpson Jeffrey P. , Trobacher Christopher P. , Allan Wendy L.
Published: August 2012

γ-Aminobutyrate (GABA) is a ubiquitous nonprotein amino acid that accumulates in plants in response to abiotic and biotic stresses. In a companion paper, we discussed the origin of GABA from glutamate and subsequent catabolism to succinic semialdehyde and either succinate or γ-hydroxybutyrate (GHB), and the characteristics of genes and proteins responsible for GABA permease, glutamate decarboxylase, GABA transaminase, succinic semialdehyde dehydrogenase, and succinic semialdehyde reductase activities. In this paper, we explore gene expression and transcript–metabolite relationships during the response to abiotic stress, and describe phenotypes of genetic mutants and relationships of GABA metabolism to other plant functions. Evidence indicates that both gene-dependent and -independent processes are involved in the response of the GABA pathway to abiotic stresses. Study of stress-specific responses and their interplay with the C/N network and various signalling pathways would be more informative if circadian rhythms and light–dark transitions upon imposition of the stress were always taken into account, and relevant genes and metabolites simultaneously profiled in wild-type plants or genetic mutants.
Higher-order bud production increases tillering capacity in the perennial caespitose grass Scribner’s Panicum (Dichanthelium oligosanthes)
Authors: Ott Jacqueline P. , Hartnett David C.
Published: August 2012

The persistence and dynamics of perennial grass populations strongly depend on tiller recruitment from the bud bank. Because of the structural organization of grasses as populations of phytomers, bud production and tillering are constrained by morphology. An infrequent trait observed in only a few caespitose grasses is the branching of buds to produce higher-order buds prior to tiller development. We studied bud bank dynamics in Dichanthelium oligosanthes (Schult.) Gould a C3 perennial caespitose grass widely distributed in the eastern Great Plains. A hierarchy of bud development occurred in D. oligosanthes, with primary buds branching to produce secondary, tertiary, and quaternary buds. This higher-order bud production increased the overwintering propagule supply for spring recruitment by 4.5 times, and more than half of successful tiller recruits originated as higher-order buds. The temporal patterns of higher-order bud production and development suggest that growing season length may be an important factor determining the extent of higher-order bud production and subsequent year tiller natality in D. oligosanthes. Higher-order bud production likely has important consequences for the population dynamics of grasses. It may increase bud bank densities and tillering capacity, buffer population dynamics, and increase intraclonal tiller densities and resource consolidation in caespitose grasses.
Leaf epidermal characters of Brazilian species of Solanum section Torva as taxonomic evidence
Authors: Nurit-Silva Kiriaki , Costa-Silva Rafael , Basílio Ionaldo J.L.D. , Agra Maria de Fátima
Published: August 2012

To evaluate their taxonomic significance, the yet unknown epidermal characters of the leaves of 10 species of Solanum section Torva Nees (Solanaceae) from Brazil were determined using light and scanning electron microscopy. Our results indicated that the leaf epidermis showed epidermal cells of straight to wavy outlines. The curved pattern of anticlinal cell walls was predominant on the adaxial surface, and the wave pattern was predominant on the abaxial surface. Leaves are amphistomatic in six species ( Solanum acutilobum Dunal, Solanum bonariense L., Solanum guaraniticum A. St.-Hil., Solanum metrobotryon Dunal, Solanum scuticum M. Nee, and Solanum torvum Sw.) and hypostomatic in four species ( Solanum adspersum Witasek, Solanum paniculatum L., Solanum subumbellatum Vell., and Solanum variabile Mart.). Four different types of stomata (anisocytic, anomocytic, paracytic, and diacytic) were recognized, with the anisocytic type predominant on adaxial and abaxial surfaces. The combination of some micro-morphological characters such as density, distribution and type of stellate trichomes, the anticlinal walls of epidermal cells, and also the type and distribution of stomata proved to be the most useful and distinctive characters for the separation of species. This set of characters also may help as additional support in quality control of species having medicinal importance.
Randomized Controlled Pilot Study: Pain Intensity and Pressure Pain Thresholds in Patients with Neck and Low Back Pain Before and After Traditional East Asian "Gua Sha" Therapy
Authors: Lauche Romy , Wübbeling Klaus , Lüdtke Rainer , Cramer Holger , Choi Kyung-Eun , Rampp Thomas , Michalsen Andreas , Langhorst Jost , Dobos Gustav J.
Published: August 2012

Gua Sha is a traditional East Asian healing technique where the body surface is "press-stroked" with a smooth-edged instrument to raise therapeutic petechiae that last 2–5 days. The technique is traditionally used in the treatment of both acute and chronic neck and back pain. This study aimed to measure the effects of Gua Sha therapy on the pain ratings and pressure pain thresholds of patients with chronic neck pain (CNP) and chronic low back pain (CLBP). A total of 40 patients with either CNP or CLBP (mean age 49.23 ± 10.96 years) were randomized to either a treatment group (TG) or a waiting list control group (WLC). At baseline assessment (T1), all patients rated their pain on a 10 cm visual analog scale (VAS). Patients' pressure pain thresholds (PPT) at a site of maximal pain (pain-maximum) and an adjacent (pain-adjacent) site were also established. The treatment group then received a single Gua Sha treatment. Post-intervention measurements were taken for both groups at T2, seven days after baseline assessment (T1), using the same VAS and PPT measurements in precisely the same locations as at T1. Final analysis were conducted with 21 patients with CNP and 18 patients with CLBP. The study groups were equally distributed with regard to randomization. Patients in both the CNP and the CLBP treatment groups reported pain reduction (p < 0.05) and improved health status from their one Gua Sha treatment, as compared to the waiting list group. Pain sensitivity improved in the TG in CNP, but not in CLBP patients, possibly due to higher pressure sensitivity in the neck area. No adverse events were reported. These results suggest that Gua Sha may be an effective treatment for patients with chronic neck and low back pain. Further study of Gua Sha is warranted.
Differential Localization of Pain-Related Neural Responses During Acupuncture Stimulation Using Blood Oxygen Level Dependent (BOLD) fMRI in a Canine Model
Authors: Chang Suk-Ki , Jahng Geon-Ho , Lee Sung-Ho , Choi Il-Whan , Choi Chi-Bong , Choi Woo-Suk
Published: August 2012

The objective of this study was to differentiate the neuronal responses, which was related or unrelated, to pain associated with acupuncture stimulation, and to localize the brain regions with response to stimulation that is unrelated to pain by using Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). BOLD fMRI was performed in six normal healthy beagle dogs, during placebo and verum acupuncture stimulations, at the right side of BL60 (KunLun) acupoint before and after local anesthesia of the acupoint. The order of the four sessions was placebo; verum acupuncture stimulation; before local anesthesia; and followed by the same stimulation after local anesthesia. One-sample t-test analysis was performed to localize the activated or deactivated areas, during both pre-anesthesia and post-anesthesia. In order to compare the pre-anesthesia to post-anesthetic responses, and placebo to verum acupuncture stimulation, within-subject analysis was performed. The post-anesthetic verum acupuncture stimulation resulted in increased activations in the left somatic afferent area I and II, right visual and auditory association area, and the descending reticular activating system of the brainstem. In addition, differential areas during post-anesthesia compared to that of the pre-anesthesia were in the left olfactory peduncle and descending reticular activating system of the brainstem. These results indicate that the areas of specific neural pathway are considered to be unrelated to the pain response during acupuncture stimulation.
The Memory-Ameliorating Effects of Artemisia princeps var. orientalis Against Cholinergic Dysfunction in Mice
Authors: Liu Xiaotong , Kim Dong Hyun , Kim Jong Min , Park Se Jin , Cai Mudan , Jang Dae Sik , Ryu Jong Hoon
Published: August 2012

Artemisia princeps var. orientalis (Compositae) is widely distributed in China, Japan and Korea and is known to have anti-inflammatory and anti-oxidative activities. The ethyl acetate fraction of ethanolic extract of A. princeps var. orientalis (AEA) was found to inhibit acetylcholinesterase activity in a dose-dependent manner in vitro (IC50 value: 541.4 ± 67.5 μg/ml). Therefore, we investigated the effects of AEA on scopolamine-induced learning and memory impairment using the passive avoidance, the Y-maze, and the Morris water maze tasks in mice. AEA (100 or 200 mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairments in the passive avoidance and Y-maze tasks (p < 0.05). In the Morris water maze task, AEA (200 mg/kg, p.o.) significantly shortened escape latencies in training trials and increased both swimming time spent in the target zone and probe crossing numbers during the probe trial as compared with scopolamine-treated mice (p < 0.05). Additionally, the ameliorating effect of AEA on scopolamine-induced memory impairment was antagonized by a subeffective dose of MK-801. These results suggest that AEA could be an effective treatment against cholinergic dysfunction and its effect is mediated by the enhancement of the cholinergic neurotransmitter system via NMDA receptor signaling or acetylcholinesterase inhibition.