High-Level Teleoperation System for Aerial Exploration of Indoor Environments.

Exploration of challenging indoor environments is a demanding task. While automation with aerial robots seems a promising solution, fully autonomous systems still struggle with high-level cognitive tasks and intuitive decision making. To facilitate automation, we introduce a novel teleoperation system with an aerial telerobot that is capable of handling all demanding low-level tasks. Motivated by the typical structure of indoor environments, the system creates an interactive scene topology in real-time that reduces scene details and supports affordances. Thus, difficult high-level tasks can be effectively supervised by a human operator. To elaborate on the effectiveness of our system during a real-world exploration mission, we conducted a user study. Despite being limited by real-world constraints, results indicate that our system better supports operators with indoor exploration, compared to a baseline system with traditional joystick control.

Drone-Augmented Human Vision: Exocentric Control for Drones Exploring Hidden Areas.

Drones allow exploring dangerous or impassable areas safely from a distant point of view. However, flight control from an egocentric view in narrow or constrained environments can be challenging. Arguably, an exocentric view would afford a better overview and, thus, more intuitive flight control of the drone. Unfortunately, such an exocentric view is unavailable when exploring indoor environments. This paper investigates the potential of drone-augmented human vision, i.e., of exploring the environment and controlling the drone indirectly from an exocentric viewpoint. If used with a see-through display, this approach can simulate X-ray vision to provide a natural view into an otherwise occluded environment. The user's view is synthesized from a three-dimensional reconstruction of the indoor environment using image-based rendering. This user interface is designed to reduce the cognitive load of the drone's flight control. The user can concentrate on the exploration of the inaccessible space, while flight control is largely delegated to the drone's autopilot system. We assess our system with a first experiment showing how drone-augmented human vision supports spatial understanding and improves natural interaction with the drone.

How Biobanks Are Assessing and Measuring Their Financial Sustainability.

As guest editors of this sustainability issue of Biopreservation and Biobanking focused on business planning, utilization, and marketing, we invited a number of experts from different sectors of the biobanking arena to provide their views on business planning issues. Each expert was asked to provide a brief background statement on their biobanks, to build a context to understand their answers to the sustainability questions. We hope that these insights and experiences can provide valuable considerations and ideas for other biobanks who wish to develop or refine their own business plans, measure their utilization rates, and work toward financial sustainability. In addition, after the expert input was gathered, the guest editors invited an additional expert to provide summary comments and observations on cost and operational optimization strategies. The broad experiences from all of the experts included and scope of the biobanks they represent should provide a level of relevant representation for all interested parties.

Stable myoelectric control of a hand prosthesis using non-linear incremental learning.

Stable myoelectric control of hand prostheses remains an open problem. The only successful human-machine interface is surface electromyography, typically allowing control of a few degrees of freedom. Machine learning techniques may have the potential to remove these limitations, but their performance is thus far inadequate: myoelectric signals change over time under the influence of various factors, deteriorating control performance. It is therefore necessary, in the standard approach, to regularly retrain a new model from scratch. We hereby propose a non-linear incremental learning method in which occasional updates with a modest amount of novel training data allow continual adaptation to the changes in the signals. In particular, Incremental Ridge Regression and an approximation of the Gaussian Kernel known as Random Fourier Features are combined to predict finger forces from myoelectric signals, both finger-by-finger and grouped in grasping patterns. We show that the approach is effective and practically applicable to this problem by first analyzing its performance while predicting single-finger forces. Surface electromyography and finger forces were collected from 10 intact subjects during four sessions spread over two different days; the results of the analysis show that small incremental updates are indeed effective to maintain a stable level of performance. Subsequently, we employed the same method on-line to teleoperate a humanoid robotic arm equipped with a state-of-the-art commercial prosthetic hand. The subject could reliably grasp, carry and release everyday-life objects, enforcing stable grasping irrespective of the signal changes, hand/arm movements and wrist pronation and supination.

Vascular targeting by EndoTAG-1 enhances therapeutic efficacy of conventional chemotherapy in lung and pancreatic cancer.

Cationic lipid complexed paclitaxel (EndoTAG-1) is a novel vascular targeting agent for the treatment of cancer. Here, the aim was to investigate intratumoral drug distribution after EndoTAG-1 therapy and analyze the impact of EndoTAG-1 scheduling on antitumoral efficacy. The therapeutic effect of EndoTAG-1 in combination with conventional gemcitabine or cisplatin therapy was evaluated in L3.6pl orthotopic pancreatic cancer and a subcutaneous Lewis lung (LLC-1) carcinoma model. Oregon Green paclitaxel encapsulated in cationic liposomes in combination with intravital fluorescence microscopy clearly exhibited delivery of the drug by EndoTAG-1 to the tumor endothelium, whereas Oregon Green paclitaxel dissolved in cremophor displayed an interstitial distribution pattern. The therapeutic efficacy of EndoTAG-1 was critically dependent on the application schedule with best therapeutic results using a metronomic rather than a maximum tolerated dose application sequence. The combination of EndoTAG-1 therapy and cytotoxic chemotherapy significantly enhanced antitumoral efficacy in both tumor models. Interestingly, only EndoTAG-1 in combination with gemcitabine was able to inhibit the incidence of metastasis in pancreatic cancer. In conclusion, vascular targeting tumor therapy by EndoTAG-1 combined with standard small molecular chemotherapy results in markedly enhanced antitumoral efficacy. Therefore, this combination represents a promising novel strategy for clinical cancer therapy.

Peripheral facial nerve axotomy in mice causes sprouting of motor axons into perineuronal central white matter: time course and molecular characterization.

Generation of new axonal sprouts plays an important role in neural repair. In the current study, we examined the appearance, composition and effects of gene deletions on intrabrainstem sprouts following peripheral facial nerve axotomy. Axotomy was followed by the appearance of galanin(+) and calcitonin gene-related peptide (CGRP)(+) sprouts peaking at day 14, matching both large, neuropeptide(+) subpopulations of axotomized facial motoneurons, but with CGRP(+) sprouts considerably rarer. Strong immunoreactivity for vesicular acetylcholine transporter (VAChT) and retrogradely transported MiniRuby following its application on freshly cut proximal facial nerve stump confirmed their axotomized motoneuron origin; the sprouts expressed CD44 and alpha7beta1 integrin adhesion molecules and grew apparently unhindered along neighboring central white matter tracts. Quantification of the galanin(+) sprouts revealed a stronger response following cut compared with crush (day 7-14) as well as enhanced sprouting after recut (day 8 + 6 vs. 14; 14 + 8 vs. 22), arguing against delayed appearance of sprouting being the result of the initial phase of reinnervation. Sprouting was strongly diminished in brain Jun-deficient mice but enhanced in alpha7 null animals that showed apparently compensatory up-regulation in beta1, suggesting important regulatory roles for transcription factors and the sprout-associated adhesion molecules. Analysis of inflammatory stimuli revealed a 50% reduction 12-48 hours following systemic endotoxin associated with neural inflammation and a tendency toward more sprouts in TNFR1/2 null mutants (P = 10%) with a reduced inflammatory response, indicating detrimental effects of excessive inflammation. Moreover, the study points to the usefulness of the facial axotomy model in exploring physiological and molecular stimuli regulating central sprouting.

Paclitaxel encapsulated in cationic liposomes increases tumor microvessel leakiness and improves therapeutic efficacy in combination with Cisplatin.

PURPOSE: Paclitaxel encapsulated in cationic liposomes (EndoTAG-1) is a vascular targeting formulation for the treatment of solid tumors. It triggers intratumoral microthrombosis, causing significant inhibition of tumor perfusion and tumor growth associated with endothelial cell apoptosis. Here, we quantified the effects of repeated EndoTAG-1 therapy on tumor microvascular leakiness with respect to leukocyte-endothelial cell interactions, the targeting property of cationic liposomes, and the therapeutic combination with conventional cisplatin chemotherapy. EXPERIMENTAL DESIGN: Using dorsal skinfold chamber preparations in Syrian Golden hamsters, in vivo fluorescence microscopy experiments were done after repeated EndoTAG-1 treatment of A-Mel-3 tumors. Controls received glucose, paclitaxel alone, or cationic liposomes devoid of paclitaxel. Extravasation of rhodamine-labeled albumin was measured to calculate microvessel permeability, and intratumoral leukocyte-endothelial cell interactions were quantified. Subcutaneous tumor growth was evaluated after combination therapy followed by histologic analysis. RESULTS: Microvascular permeability was significantly increased only after treatment with EndoTAG-1, whereas intratumoral leukocyte-endothelial cell interactions were not affected by any treatment. In separate skinfold chamber experiments, fluorescently labeled cationic liposomes kept their targeting property for tumor endothelial cells after repeated EndoTAG-1 treatment and no signs of extravasation were observed. Subcutaneous A-Mel-3 tumor growth was significantly inhibited by the combination of cisplatin and EndoTAG-1. CONCLUSIONS: These data show that vascular targeting with EndoTAG-1 increases tumor microvessel leakiness probably due to vascular damage. This mechanism is not mediated by inflammatory leukocyte-endothelial cell interactions. Manipulating the blood-tumor barrier by repeated tumor microvessel targeting using EndoTAG-1 can effectively be combined with tumor cell-directed conventional cisplatin chemotherapy.

A prospective study comparing different iodine concentrations for triphasic multidetector row CT of the upper abdomen.

OBJECTIVES: To investigate the effect of different iodine concentrations at either constant injection or iodine administration rates but constant total iodine load on contrast enhancement of liver, pancreas and spleen by multidetector row CT. MATERIALS AND METHODS: One hundred and twenty consecutive patients (70+/-6 years) underwent triphasic liver CT at a four-channel multidetector-row CT using the non-ionic contrast medium iopromide. Patients were divided into six equal groups-I: 150 ml, 240 mg/ml at 4 ml/s; II: 120 ml, 300 mg/ml at 4 ml/s; III: 97.3 ml, 370 mg/ml at 4 ml/s; IV: 150 ml, 240 mg/ml at 5 ml/s; V: 120 ml, 300 mg/ml, 60 ml at 6 ml/s, 60 ml at 3 ml/s; VI: 97.3 ml, 370 mg/ml at 3.3 ml/s. ROIs were measured in the liver, the pancreas, and the spleen in unenhanced, arterial, portal venous, and equilibrium phase. RESULTS: At a constant injection rate of 4 ml/s, pancreatic enhancement over baseline only in the arterial phase was significantly higher at 370 mg/ml (58+/-15 HU versus 59+/-18 HU versus 74+/-20 HU for groups I-III, respectively (p<0.02)). Comparison of different iodine concentrations at constant iodine administration rate (groups II, IV and VI) and of all six protocols revealed no significant differences at either phase. CONCLUSIONS: At a constant iodine load and constant injection rates, the high-iodinated contrast agent iopromide at 370 mg/ml improves pancreatic enhancement in the arterial phase. At constant iodine load and constant iodine administration rates, there is no significant effect of different iodine concentrations.

Absence of alpha 7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy.

Both the dystrophin-glycoprotein complex and alpha7beta1 integrin have critical roles in the maintenance of muscle integrity via the provision of mechanical links between muscle fibres and the basement membrane. Absence of either dystrophin or alpha7 integrin results in a muscular dystrophy. To clarify the role of alpha7 integrin and dystrophin in muscle development and function, we generated integrin alpha7/dystrophin double-mutant knockout (DKO) mice. Surprisingly, DKO mice survived post-natally and were indistinguishable from wild-type, integrin alpha7-deficient and mdx mice at birth, but died within 24-28 days. Histological analysis revealed a severe muscular dystrophy in DKO mice with endomysial fibrosis and ectopic calcification. Weight loss was correlated with the loss of muscle fibres, indicating that progressive muscle wasting in the double mutant was most likely due to inadequate muscle regeneration. The data further support that premature death of DKO mice is due to cardiac and/or respiratory failure. The integrin alpha7/dystrophin-deficient mouse model, therefore, resembles the pathological changes seen in Duchenne muscular dystrophy and suggests that the different clinical severity of dystrophin deficiency in human and mouse may be due to a fine-tuned difference in expression of dystrophin and integrin alpha7 in both species. Together, these findings indicate an essential role for integrin alpha7 in the maintenance of dystrophin-deficient muscles.

Evaluation of papillomaviruses associated with cyclosporine-induced hyperplastic verrucous lesions in dogs.

OBJECTIVE: To determine whether cyclosporine A-induced hyperplastic skin lesions of dogs were associated with papillomavirus infections. ANIMALS: 9 dogs that were treated with cyclosporine A and developed hyperplastic skin lesions. PROCEDURE: History and clinical and histopathologic data were collected. Paraffin-embedded skin biopsy specimens from hyperplastic skin lesions were immunostained for common papillomavirus genus-specific structural antigens by use of a polyclonal rabbit anti-bovine papillomavirus type 1 antiserum. Sections from each tissue block underwent DNA extraction, and polymerase chain reaction (PCR) assays were performed with several sets of primers to amplify a wide range of papillomavirus DNA from humans and other animals. RESULTS: In 7 of 9 dogs, there were more than 10 hyperplastic skin lesions that microscopically resembled those of psoriasiform lichenoid dermatosis. In those dogs, results of testing for papillomavirus via immunohistochemical analyses and PCR assays were negative. In the other 2 dogs, there were only 1 and 3 verrucous lesions, and in those dogs, histologic evaluation revealed koilocytes and nuclear viral inclusions that were immunoreactive for papillomavirus antigens. Papillomavirus DNA was amplified from both dogs. One of the sequences was characteristic for the canine oral papillomavirus, whereas the other had similarities with the recently described canine papillomavirus 2. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, hyperplastic skin lesions occasionally develop during treatment with cyclosporine A. Most of the lesions resemble those of psoriasiform lichenoid dermatosis, although papillomavirus can be detected in some instances.

Psoriasiform-lichenoid-like dermatosis in three dogs treated with microemulsified cyclosporine A.

Cyclosporine has been reported to be effective for the treatment of various cutaneous autoimmune disorders in dogs. Adverse reactions have generally been limited to gastrointestinal tract disturbances and cutaneous eruptions. The article describes antimicrobial-responsive cutaneous reactions in 3 dogs being treated with microemulsified cyclosporine A because of various dermatologic conditions. Cutaneous reactions in these dogs were similar to psoriasiform-lichenoid dermatitis and may represent an atypical staphylococcal infection.

Lymphocyte infiltration in the injured brain: role of proinflammatory cytokines.

Studies using mouse axotomised facial motoneuron model show a strong and highly selective entry of CD3+ lymphocytes into the affected nucleus, with a maximum at Day 14, which coincides with the peak of neuronal cell death, microglial phagocytosis, and increased synthesis of interleukin-1 beta (IL1beta), tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). We explored the possible involvement of these cytokines during the main phase of lymphocyte recruitment into the axotomised facial motor nucleus 7-21 days after nerve cut using mice homozygously deficient for IL1 receptor type 1 (IL1R1-/-), TNF receptor type 1 (TNFR1-/-), type 2 (TNFR2-/-) and type 1 and 2 (TNFR1&2-/-), IFNgamma receptor type 1 (IFNgammaR1-/-), and the appropriate controls for the genetic background. Transgenic deletion of IL1R1 led to a 54% decrease and that of TNFR2 to a 44% reduction in the number of CD3+ T-cells in the axotomised facial motor nucleus, with a similar relative decrease at Day 7, 14, and 21. Deletion of TNFR1 or IFNgammaR1 had no significant effect. Deletion of both TNFR1 and 2 (TNFR1&2-/-) caused a somewhat stronger, 63% decrease than did TNFR2 deletion alone, but this could be due to an almost complete inhibition of neuronal cell death. No mutations seemed to inhibit aggregation of CD3+ T-cells around glial nodules consisting of Ca-ion binding adaptor protein-1 (IBA1)+ phagocytotic microglia and neuronal debris. Altogether, the current data show the importance of IL1R1 and TNFR2 as the key players during the main phase of lymphocyte recruitment to the damaged part of the central nervous system.

Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels.

Recently, cationic liposomes have been shown to preferentially target the angiogenic endothelium of tumors. It was the aim of our study to investigate the influence of liposomal surface charge on the uptake and kinetics of liposomes into solid tumors and tumor vasculature. Experiments were performed in the amelanotic hamster melanoma A-Mel-3 growing in the dorsal skinfold chamber preparation of male Syrian golden hamsters. Fluorescently labeled liposomes with different surface charge were prepared. Accumulation of i.v. injected liposomes was assessed by quantitative intravital fluorescence microscopy of tumor and surrounding host tissue. The histological distribution of liposomes was analyzed by double-fluorescence microscopy 20 min after application of fluorescently labeled lectin as a vascular marker. After i.v. application of anionic and neutral liposomes, we observed an almost homogeneous distribution of liposome-induced fluorescence throughout the chamber preparation without specific targeting to tumor tissue. In contrast, cationic liposomes exhibited a significantly enhanced accumulation in tumor tissue and tumor vasculature up to 3-fold compared to surrounding tissue (p<0.05). The histological distribution of neutral and anionic liposomes revealed extravasation 20 min after i.v. injection, while cationic liposomes displayed a highly selective accumulation on the vascular endothelium. In conclusion, cationic liposomes exhibited a preferential uptake in angiogenic tumor vessels and therefore may provide an efficient tool for the selective delivery of diagnostic or therapeutic agents to angiogenic blood vessels of solid tumors. On the other hand, anionic and neutral liposomes may be used as carriers of drugs to the extravascular compartment of tumors due to their extravasation.