Rogowski and D-Dot Sensors for Nanosecond High-Voltage and High-Current Pulse Measurements in Impedance-Matched Pulse Generators

To measure the output voltage and current in our impedance-matched solid-state Marx generator we developed a voltage and current sensor integrated with the IMG structure. One of the advantages of our IMG structure is the coaxial inner transmission line (TL). The end of this TL is the output connection, which consists of a grounded ring and a smaller high-voltage (HV) inner conductor (coaxial). This structure is ideal for fitting D-dot and Rogowski-coil sensors, as these sensors can benefit from the strictly defined electric and magnetic fields in this waveguide. We developed D-dot and Rogowski-coil sensors on printed circuit boards (PCB) and show their usability in our application for measuring HV pulses. The sensors have a bandwidth of about 200 MHz, measure voltages up to 20 kV, and currents up to hundreds of amperes. Their simple PCB design makes them easily reproducible and cheap compared to commercial sensors. Although designed for our IMG, they can be fit on any coaxial line. Next, we made passive integrators to partly integrate the differentiated sensor signal, which improves the signal quality when measured with an oscilloscope. Finally, after software signal postprocessing, we achieve far better voltage measurements and similar current measurements compared to commercial probes.</p

Химиотерапия взрослых больных с саркомами мягких тканей

В обзоре рассмотрены общие принципы цитостатического лечения взрослых больных с саркомами мягких тканей. Роль химиотерапии при этом заболевании на протяжении последних лет повышается. Hаиболее эффективными цитостатиками являются доксорубицин и ифосфамид, причем у обоих препаратов установлена зависимость эффективности от дозы. Химиотерапию применяют как элемент радикального комбинированного лечения, а также как паллиативный метод при метастатическом процессе. При рабдомиосаркоме химиотерапия эффективна практически при любой стадии заболевания.Chemotherapy has an increasing role in the therapy of soft tissue sarcomas. Meanwhile, chemotherapy of these tumors is frequently considered in general without taking into account the peculiar clinical features of various subtypes. Doxorubicin and ifosfamide are the most active drugs in the treatment of soft tissue sarcomas. Chemotherapy could be used both for radical and for palliative treatment. For rhabdomyosarcoma, chemotherapy is effective in all the stages of such disease

MRI-based screening for metabolic insufficiency of leg muscle during aerobic exercise in Cystic Fibrosis

There is evidence for mitochondrial dysfunction in various tissues in Cystic Fibrosis (CF) including muscle. Among others, a slow rate of high-energy phosphate resynthesis following exercise involving single limb muscle activity was found in human CF using in vivo 31P magnetic resonance spectroscopy (MRS). This raises the question whether this outcome would be ameliorated versus exacerbated if instead an exercise regime is used that puts a significant cardiopulmonary load on the body as in running or bicycling. This is of interest because exercise therapy is commonly prescribed in CF. To investigate this matter, ten pediatric CF patients (age 12–16 years) and healthy peers performed two ramp exercise tests to volitional exhaustion using a bicycle ergometer fit for use inside a MR scanner. Endurance, VO2max and heart rate were determined in the exercise laboratory. Quadriceps muscle energy-and acid/base balance during exercise and recovery were measured on a separate day using MR imaging-based 31P MRS. This study brings together for the first time this powerful biomedical imaging platform and whole body exercise testing in the clinical setting of human CF

The influence of a six degrees of freedom couch and an individual head support in patient positioning in radiotherapy of head and neck cancer

Reproducible patient positioning is important in radiotherapy (RT) of head-and-neck cancer. We therefore compared set-up errors in head-and-neck RT resulting from three different patient positioning systems. Patients were either treated with a standard head support (SHS) and conventional treatment couch (SHS-3, n = 10), a SHS and rotational couch (SHS-6, n = 10), or an individual head support (IHS) and rotational couch (IHS-6, n = 10). Interfraction mean translation vector lenghts were significantly lower for IHS-6 compared to SHS-3 (0.8 ± 0.3 mm vs. 1.4 ± 0.7 mm, P = 0.001). Intrafraction displacement was comparable among cohorts. This study showed that the use of a six degrees of freedom couch combined with an IHS in head-and-neck RT resulted in better interfraction reproducibilit

Assessing urban ecosystem services in support of spatial planning in the Hague, the Netherlands

Green infrastructure (GI) is increasingly addressed in urban planning and research to enhance urban sustainability and resilience through the provisioning of ecosystem services (ES). Yet, few applications exist of planning models for multifunctional GI in high spatial and thematic detail that simultaneously align with stakeholder interests. We address these gaps by developing and presenting a spatially explicit model to inform urban planners on priority areas for multifunctional GI development. This model was made possible by spatial analyses on multiple scales, enabling us to assess ES in sufficient detail, while simultaneously matching the preferences for scale and ES-indicators of decision makers and urban planners. The model involves a novel weighting scheme based upon the local capacity of GI to mitigate problems. We applied our model to the city of The Hague using a set of three policy-relevant problems: air pollution, the urban heat island effect and storm water flooding. Our results show that the capacity of GI to mitigate these problems varies spatially, both within and between ES, and depends on local characteristics of GI and the environmental context. We illustrate the relevance of using a multiscale approach in spatial ES analysis, and underline that GI planning measures should be assessed in high spatial detail due to their often locally distinct ES capacity. Our approach makes important strides towards the deployment of nature-based solutions for urban challenges in the light of demands for increasing resilience and sustainability.Environmental BiologyIndustrial Ecolog

Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy

Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P. We found that GM-CSF and pRNA had similar effects on their target cells, whereas pRNA and CpG-P induced stronger type I interferon (IFN) expression than FSME. In general, the pathways most affected by all stimuli were related to immune activity and cell migration. GM-CSF stimulation, however, also induced a significant increase of genes related to nonsense-mediated decay, indicating a possible deleterious effect of this stimulus. Taken together, the two novel stimuli appear to be promising alternatives. Our study demonstrates how RNA-seq based investigation of changes in a large number of genes and gene groups can be exploited for fast and unbiased, global evaluation of clinical-grade stimuli, as opposed to the general limited evaluation of a pre-specified set of genes, by which one might miss important biological effects that are detrimental for vaccine efficacy

Metabolomic and lipidomic signatures associated with activation of human cDC1 (BDCA3(+)/CD141(+)) dendritic cells

Dendritic cells (DCs) bridge the connection between innate and adaptive immunity. DCs present antigens to T cells and stimulate potent cytotoxic T-cell responses. Metabolic reprogramming is critical for DC development and activation; however, metabolic adaptations and regulation in DC subsets remains largely uncharacterized. Here, we mapped metabolomic and lipidomic signatures associated with the activation phenotype of human conventional DC type 1, a DC subset specialized in cross-presentation and therefore of major importance for the stimulation of CD8(+) T cells. Our metabolomics and lipidomic analyses showed that Toll-like receptor (TLR) stimulation altered glycerolipids and amino acids in cDC1. Poly I:C or pRNA stimulation reduced triglycerides and cholesterol esters, as well as various amino acids. Moreover, TLR stimulation reduced expression of glycolysis-regulating genes and did not induce glycolysis. Conversely, cDC1 exhibited increased mitochondrial content and oxidative phosphorylation (OXPHOS) upon TLR3 or TLR7/8 stimulation. Our findings highlight the metabolic adaptations required for cDC1 maturation.Proteomic

Prevalence of sensitization to the predatory mite Amblyseius cucumeris as a new occupational allergen in horticulture

Background: Protection against thrips, a common pest in bell pepper horticulture is effectively possible without pesticides by using the commercially available predatory mite Amblyseius cucumeris (Ac). The prevalence of sensitization to Ac among exposed greenhouse employees and its clinical relevance was studied. Methods: Four hundred and seventytwo employees were asked to fill in a questionnaire and were tested on location. Next to RAST, skin prick tests (SPTs) were performed with common inhalant allergens, the storage mite Tyrophagus putrescentiae (Tp) which serves as a temporary food source during the cultivation process and Ac. Furthermore, nasal challenge tests with Ac were carried out in 23 sensitized employees. Results: SPTs positive to Ac were found in 109 employees (23%). Work-related symptoms were reported by 76.1%. Sensitization to Tp was found in 62 employees of whom 48 were also sensitized to Ac. Immunoglobulin (Ig)E-mediated allergy to inhalant allergens appeared to be an important risk factor for sensitization to Ac. Employees with rhinitis symptoms showed a significantly higher response to all Ac doses during the nasal challenge test compared with employees without rhinitis symptoms. Conclusions: The predatory mite Ac is a new occupational allergen in horticulture which can cause an IgE-mediated allergy in exposed employees. It is biologically active on the mucous membranes of the nose and therefore clinically relevant for the development of work-related symptoms

Quantum resource estimates for computing elliptic curve discrete logarithms

We give precise quantum resource estimates for Shor's algorithm to compute discrete logarithms on elliptic curves over prime fields. The estimates are derived from a simulation of a Toffoli gate network for controlled elliptic curve point addition, implemented within the framework of the quantum computing software tool suite LIQ$Ui|\rangle$. We determine circuit implementations for reversible modular arithmetic, including modular addition, multiplication and inversion, as well as reversible elliptic curve point addition. We conclude that elliptic curve discrete logarithms on an elliptic curve defined over an $n$-bit prime field can be computed on a quantum computer with at most $9n + 2\lceil\log_2(n)\rceil+10$ qubits using a quantum circuit of at most $448 n^3 \log_2(n) + 4090 n^3$ Toffoli gates. We are able to classically simulate the Toffoli networks corresponding to the controlled elliptic curve point addition as the core piece of Shor's algorithm for the NIST standard curves P-192, P-224, P-256, P-384 and P-521. Our approach allows gate-level comparisons to recent resource estimates for Shor's factoring algorithm. The results also support estimates given earlier by Proos and Zalka and indicate that, for current parameters at comparable classical security levels, the number of qubits required to tackle elliptic curves is less than for attacking RSA, suggesting that indeed ECC is an easier target than RSA.Comment: 24 pages, 2 tables, 11 figures. v2: typos fixed and reference added. ASIACRYPT 201