Mass migrations by Odonata, although less studied than those of Monarch butterflies and plague locusts, have provoked comment and study for many years. Relatively recently, increasing interest in ...dragonflies, supported by new technologies, has resulted in more detailed knowledge of the species involved, behavioral mechanisms, and geographic extent. In this paper we examine, in four independent but complementary studies, how larval habitat and emergence phenology interact with climate to shape the evolution of migratory strategy in Anax junius, a common species throughout much of the eastern United States and southern Canada. In brief, we argue that fish predation on larvae, coupled with the need for ample emergent vegetation for oviposition and adult eclosion, dictates that larval development and survival is optimal in ponds that are neither permanent nor extremely ephemeral. Coupled with annual variation in regional weather and winters in much of their range too cold for adult survival, conditions facing newly emerged A. junius may unpredictably favor either local reproduction or long-distance movement to more favorable areas. Both temperature and hydroperiod tend to favor local reproduction early in the adult activity period and migration later, so late emerging adults are more likely to migrate. No single pond is always predictably suitable or unsuitable, however, so ovipositing females also may spread the risk to their offspring by ovipositing at multiple sites that, for migrants, may be distributed over very long distances.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stretchable electronics provide a foundation for applications that exceed the scope of conventional wafer and circuit board technologies due to their unique capacity to integrate with soft materials ...and curvilinear surfaces. The range of possibilities is predicated on the development of device architectures that simultaneously offer advanced electronic function and compliant mechanics. Here we report that thin films of hard electronic materials patterned in deterministic fractal motifs and bonded to elastomers enable unusual mechanics with important implications in stretchable device design. In particular, we demonstrate the utility of Peano, Greek cross, Vicsek and other fractal constructs to yield space-filling structures of electronic materials, including monocrystalline silicon, for electrophysiological sensors, precision monitors and actuators, and radio frequency antennas. These devices support conformal mounting on the skin and have unique properties such as invisibility under magnetic resonance imaging. The results suggest that fractal-based layouts represent important strategies for hard-soft materials integration.
Increased Number of Islet-Associated Macrophages in Type 2 Diabetes
Jan A. Ehses 1 ,
Aurel Perren 2 ,
Elisabeth Eppler 3 ,
Pascale Ribaux 4 ,
John A. Pospisilik 5 ,
Ranit Maor-Cahn 1 ,
Xavier ...Gueripel 2 ,
Helga Ellingsgaard 1 ,
Marten K.J. Schneider 6 ,
Gregoire Biollaz 7 ,
Adriano Fontana 7 ,
Manfred Reinecke 3 ,
Francoise Homo-Delarche 8 and
Marc Y. Donath 1
1 Division of Endocrinology and Diabetes and Center for Integrated Human Physiology, University Hospital of Zürich, Zürich,
Switzerland
2 Department of Pathology, University Hospital of Zürich, Zürich, Switzerland
3 Division of Neuroendocrinology, Institute of Anatomy, University of Zürich, Zürich, Switzerland
4 Department of Genetic Medicine and Development, University Medical Center, Geneva, Switzerland
5 Institute of Molecular Biotechnology, Austrian Academy of Science, Vienna, Austria
6 Laboratory for Transplantation Immunology, University Hospital of Zürich, Zürich, Switzerland
7 Division of Clinical Immunology, University Hospital of Zürich, Zürich, Switzerland
8 Unité mixte de recherches 7059, National Center for Scientific Research, Paris 7 University/D. Diderot, Paris, France
Address correspondence and reprint requests to Dr. Jan A. Ehses, Division of Endocrinology and Diabetes, University Hospital
of Zürich, Rämistrasse 100, Zürich 8091, Switzerland. E-mail: jan.ehses{at}usz.ch . Or to Dr. Marc Y. Donath, Division of Endocrinology and Diabetes, University Hospital of Zürich, Rämistrasse 100, Zürich
8091, Switzerland. E-mail: marc.donath{at}usz.ch
Abstract
Activation of the innate immune system in obesity is a risk factor for the development of type 2 diabetes. The aim of the
current study was to investigate the notion that increased numbers of macrophages exist in the islets of type 2 diabetes patients
and that this may be explained by a dysregulation of islet-derived inflammatory factors. Increased islet-associated immune
cells were observed in human type 2 diabetic patients, high-fat–fed C57BL/6J mice, the GK rat, and the db/db mouse. When cultured islets were exposed to a type 2 diabetic milieu or when islets were isolated from high-fat–fed mice,
increased islet-derived inflammatory factors were produced and released, including interleukin (IL)-6, IL-8, chemokine KC,
granulocyte colony-stimulating factor, and macrophage inflammatory protein 1α. The specificity of this response was investigated
by direct comparison to nonislet pancreatic tissue and β-cell lines and was not mimicked by the induction of islet cell death.
Further, this inflammatory response was found to be biologically functional, as conditioned medium from human islets exposed
to a type 2 diabetic milieu could induce increased migration of monocytes and neutrophils. This migration was blocked by IL-8
neutralization, and IL-8 was localized to the human pancreatic α-cell. Therefore, islet-derived inflammatory factors are regulated
by a type 2 diabetic milieu and may contribute to the macrophage infiltration of pancreatic islets that we observe in type
2 diabetes.
AEC, 3-amino-9-ethylcarbazole
ECM, extracellular matrix
FITC, fluorescein isothiocyanate
G-CSF, granulocyte colony-stimulating factor
IL, interleukin
IP-10, interferon-inducible protein 10
MHC, major histocompatibility complex
MIP, macrophage inflammatory protein
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 19 June 2007. DOI: 10.2337/db06-1650.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted May 21, 2007.
Received November 26, 2006.
DIABETES
Purpose
The purpose of this educational report is to provide an overview of the present state‐of‐the‐art PET auto‐segmentation (PET‐AS) algorithms and their respective validation, with an emphasis on ...providing the user with help in understanding the challenges and pitfalls associated with selecting and implementing a PET‐AS algorithm for a particular application.
Approach
A brief description of the different types of PET‐AS algorithms is provided using a classification based on method complexity and type. The advantages and the limitations of the current PET‐AS algorithms are highlighted based on current publications and existing comparison studies. A review of the available image datasets and contour evaluation metrics in terms of their applicability for establishing a standardized evaluation of PET‐AS algorithms is provided. The performance requirements for the algorithms and their dependence on the application, the radiotracer used and the evaluation criteria are described and discussed. Finally, a procedure for algorithm acceptance and implementation, as well as the complementary role of manual and auto‐segmentation are addressed.
Findings
A large number of PET‐AS algorithms have been developed within the last 20 years. Many of the proposed algorithms are based on either fixed or adaptively selected thresholds. More recently, numerous papers have proposed the use of more advanced image analysis paradigms to perform semi‐automated delineation of the PET images. However, the level of algorithm validation is variable and for most published algorithms is either insufficient or inconsistent which prevents recommending a single algorithm. This is compounded by the fact that realistic image configurations with low signal‐to‐noise ratios (SNR) and heterogeneous tracer distributions have rarely been used. Large variations in the evaluation methods used in the literature point to the need for a standardized evaluation protocol.
Conclusions
Available comparison studies suggest that PET‐AS algorithms relying on advanced image analysis paradigms provide generally more accurate segmentation than approaches based on PET activity thresholds, particularly for realistic configurations. However, this may not be the case for simple shape lesions in situations with a narrower range of parameters, where simpler methods may also perform well. Recent algorithms which employ some type of consensus or automatic selection between several PET‐AS methods have potential to overcome the limitations of the individual methods when appropriately trained. In either case, accuracy evaluation is required for each different PET scanner and scanning and image reconstruction protocol. For the simpler, less robust approaches, adaptation to scanning conditions, tumor type, and tumor location by optimization of parameters is necessary. The results from the method evaluation stage can be used to estimate the contouring uncertainty. All PET‐AS contours should be critically verified by a physician. A standard test, i.e., a benchmark dedicated to evaluating both existing and future PET‐AS algorithms needs to be designed, to aid clinicians in evaluating and selecting PET‐AS algorithms and to establish performance limits for their acceptance for clinical use. The initial steps toward designing and building such a standard are undertaken by the task group members.
A new gradient-based method for segmenting FDG-PET images is described and validated.
The proposed method relies on the watershed transform and hierarchical cluster analysis. To allow a better ...estimation of the gradient intensity, iteratively reconstructed images were first denoised and deblurred with an edge-preserving filter and a constrained iterative deconvolution algorithm. Validation was first performed on computer-generated 3D phantoms containing spheres, then on a real cylindrical Lucite phantom containing spheres of different volumes ranging from 2.1 to 92.9 ml. Moreover, laryngeal tumours from seven patients were segmented on PET images acquired before laryngectomy by the gradient-based method and the thresholding method based on the source-to-background ratio developed by Daisne (Radiother Oncol 2003;69:247-50). For the spheres, the calculated volumes and radii were compared with the known values; for laryngeal tumours, the volumes were compared with the macroscopic specimens. Volume mismatches were also analysed.
On computer-generated phantoms, the deconvolution algorithm decreased the mis-estimate of volumes and radii. For the Lucite phantom, the gradient-based method led to a slight underestimation of sphere volumes (by 10-20%), corresponding to negligible radius differences (0.5-1.1 mm); for laryngeal tumours, the segmented volumes by the gradient-based method agreed with those delineated on the macroscopic specimens, whereas the threshold-based method overestimated the true volume by 68% (p=0.014). Lastly, macroscopic laryngeal specimens were totally encompassed by neither the threshold-based nor the gradient-based volumes.
The gradient-based segmentation method applied on denoised and deblurred images proved to be more accurate than the source-to-background ratio method.
Remission durability following single-antigen targeted chimeric antigen receptor (CAR) T-cells is limited by antigen modulation, which may be overcome with combinatorial targeting. Building upon our ...experiences targeting CD19 and CD22 in B-cell acute lymphoblastic leukemia (B-ALL), we report on our phase 1 dose-escalation study of a novel murine stem cell virus (MSCV)-CD19/CD22-4-1BB bivalent CAR T-cell (CD19.22.BBζ) for children and young adults (CAYA) with B-cell malignancies. Primary objectives included toxicity and dose finding. Secondary objectives included response rates and relapse-free survival (RFS). Biologic correlatives included laboratory investigations, CAR T-cell expansion and cytokine profiling. Twenty patients, ages 5.4 to 34.6 years, with B-ALL received CD19.22.BBζ. The complete response (CR) rate was 60% (12 of 20) in the full cohort and 71.4% (10 of 14) in CAR-naïve patients. Ten (50%) developed cytokine release syndrome (CRS), with 3 (15%) having ≥ grade 3 CRS and only 1 experiencing neurotoxicity (grade 3). The 6- and 12-month RFS in those achieving CR was 80.8% (95% confidence interval CI: 42.4%-94.9%) and 57.7% (95% CI: 22.1%-81.9%), respectively. Limited CAR T-cell expansion and persistence of MSCV-CD19.22.BBζ compared with EF1α-CD22.BBζ prompted laboratory investigations comparing EF1α vs MSCV promoters, which did not reveal major differences. Limited CD22 targeting with CD19.22.BBζ, as evaluated by ex vivo cytokine secretion and leukemia eradication in humanized mice, led to development of a novel bicistronic CD19.28ζ/CD22.BBζ construct with enhanced cytokine production against CD22. With demonstrated safety and efficacy of CD19.22.BBζ in a heavily pretreated CAYA B-ALL cohort, further optimization of combinatorial antigen targeting serves to overcome identified limitations (www.clinicaltrials.gov #NCT03448393).
•CD19.22.BBζ CAR T cells were well tolerated and effective in pediatric B-ALL, but persistence and CD22 targeting were limited.•A novel bicistronic CD19.28ζ/CD22.BBζ CAR T-cell enhanced dual-targeting efficacy and cytokine production in preclinical models.
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We report the use of a small concentration of ethanol in addition to ethylene as the carbon source for growth of dense vertically aligned “forests” of few-walled carbon nanotubes (CNTs). Through a ...detailed comparison of CNTs grown with and without ethanol added to the C2H4/H2 feedstock, we quantify several important effects of the ethanol addition. We show that ethanol selectively reduces the number of CNT walls without changing the outer diameter, increases the catalyst lifetime more than 3-fold, and increases the rate of carbon conversion more than 5-fold. Online dewpoint and mass spectrometry measurements of the exhaust stream suggest that ethanol decomposes into active carbon species that enhance growth, and into H2O, which counteracts the accumulation of amorphous carbon and thus prolongs the catalyst lifetime. We performed a systematic study of the effect of the catalyst film thickness, and identify a set of conditions that provides growth of millimeter-tall double-walled CNT forests. Importantly, our study reveals that the chemistry of the CVD atmosphere alone plays a critical role in controlling the structure of CNTs, and that addition of ethanol results in few-walled CNTs over a broad range of growth conditions. These findings are an important step toward the ultimate goal of control of CNT chirality during synthesis as well as toward realization of important large-scale applications of aligned CNT films having high monodispersity and structural quality.
Adaptive Radiotherapy of Head and Neck Cancer Castadot, Pierre, MD; Lee, John A., Eng, PhD; Geets, Xavier, MD, PhD ...
Seminars in radiation oncology,
04/2010, Letnik:
20, Številka:
2
Journal Article
Recenzirano
Intensity-modulated radiation therapy (IMRT) in head and neck (H&N) cancer has the capability to generate steep dose gradients, leading to an improved therapeutic index. IMRT plans are typically ...based on a pretreatment computed tomography scan that provides a snapshot of the patient's anatomy. Nevertheless, interfractional patient variations may occur because of setup error and anatomical modifications. Therefore, the accuracy of IMRT delivery for H&N cancer may be compromised during the treatment course, potentially affecting the therapeutic index. In this framework, adaptive radiotherapy is a potential solution, which consists of “the explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy.” Adaptive radiotherapy has brought an additional dimension to the management of patients with H&N cancer and has the potential to counteract the effects of positioning errors and anatomical changes. This article reviews the causes and discusses potential solutions to circumvent the discrepancies between the planned dose and the actual dose received by patients treated for H&N malignancies.
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