Ultrasound mapping of lymph node and subcutaneous metastases in patients with cutaneous melanoma: Results of a prospective multicenter study

Background: Ultrasound (sonography, B-mode sonography, ultrasonography) examination improves the sensitivity in more than 25% compared to the clinical palpation, especially after surgery on the regional lymph node area. Objective: To evaluate the distribution of metastases during follow-up in the draining lymph node areas from the scar of primary to regional lymph nodes ( head and neck, supraclavicular, axilla, infraclavicular, groin) in patients with cutaneous melanoma with or without sentinel lymph node biopsy (SLNB) or former elective or consecutive complete lymph node dissection in case of positive sentinel lymph node (CLND). Methods: Prospective multicenter study of the Departments of Dermatology of the Universities of Homburg/Saar, Tubingen and Munich (Germany) in which the distribution of lymph node and subcutaneous metastases were mapped from the scar of primary to the lymphatic drainage region in 53 melanoma patients ( 23 women, 30 men; median age: 64 years; median tumor thickness: 1.99 mm) with known primary, visible lymph nodes or subcutaneous metastases proven by ultrasound and histopathology during the follow-up. Results: Especially in the axilla, infraclavicular region and groin the metastases were not limited to the anatomic lymph node regions. In 5 patients (9.4%) ( 4 of them were in stage IV) lymph node metastases were not located in the corresponding lymph node area. 32 patients without former SLNB had a time range between melanoma excision and lymph node metastases of 31 months ( median), 21 patients with SLNB had 18 months ( p < 0.005). In 11 patients with positive SLNB the time range was 17 months, in 10 patients with negative SLNB 21 months ( p < 0.005); in 32 patients with CLND the time range was 31 m< 0.005). In thinner melanomas lymph node metastases occurred later ( p < 0.05). Conclusions: After surgery of cutaneous melanoma, SLNB and CLND the lymphatic drainage can show significant changes which should be considered in clinical and ultrasound follow-up examinations. Especially for high-risk melanoma patients follow-up examinations should be performed at intervals of 3 months in the first years. Patients at stage IV should be examined in all regional lymph node areas clinically and by ultrasound. Copyright (c) 2006 S. Karger AG, Basel

A possible mechanism for cold denaturation of proteins at high pressure

We study cold denaturation of proteins at high pressures. Using multicanonical Monte Carlo simulations of a model protein in a water bath, we investigate the effect of water density fluctuations on protein stability. We find that above the pressure where water freezes to the dense ice phase ($\approx2$ kbar), the mechanism for cold denaturation with decreasing temperature is the loss of local low-density water structure. We find our results in agreement with data of bovine pancreatic ribonuclease A.Comment: 4 pages for double column and single space. 3 figures Added references Changed conten

University rankings:What do they really show?

University rankings as developed by the media are used by many stakeholders in higher education: students looking for university places; academics looking for university jobs; university managers who need to maintain standing in the competitive arena of student recruitment; and governments who want to know that public funds spent on universities are delivering a world class higher education system. Media rankings deliberately draw attention to the performance of each university relative to all others, and as such they are undeniably simple to use and interpret. But one danger is that they are potentially open to manipulation and gaming because many of the measures underlying the rankings are under the control of the institutions themselves. This paper examines media rankings (constructed from an amalgamation of variables representing performance across numerous dimensions) to reveal the problems with using a composite index to reflect overall performance. It ends with a proposal for an alternative methodology which leads to groupings rather than point estimates

A probability-conserving cross-section biasing mechanism for variance reduction in Monte Carlo particle transport calculations

In Monte Carlo particle transport codes, it is often important to adjust reaction cross sections to reduce the variance of calculations of relatively rare events, in a technique known as non-analogous Monte Carlo. We present the theory and sample code for a Geant4 process which allows the cross section of a G4VDiscreteProcess to be scaled, while adjusting track weights so as to mitigate the effects of altered primary beam depletion induced by the cross section change. This makes it possible to increase the cross section of nuclear reactions by factors exceeding 10^4 (in appropriate cases), without distorting the results of energy deposition calculations or coincidence rates. The procedure is also valid for bias factors less than unity, which is useful, for example, in problems that involve computation of particle penetration deep into a target, such as occurs in atmospheric showers or in shielding

AFM-Detected Apoptotic Changes in Morphology and Biophysical Property Caused by Paclitaxel in Ishikawa and HeLa Cells

The apoptosis of cancer cells is associated with changes in the important cell properties including morphology, surface roughness and stiffness. Therefore, the changes in morphology and biophysical properties can be a good way of evaluating the anticancer activity of a drug. This study examined the effect of paclitaxel on the properties of Ishikawa and HeLa cells using atomic force microscopy (AFM), and the relationship between the changes in morphology and the biophysical properties and apoptosis was discussed. The viability and proliferation of the cells were analyzed using the methylthiazol tetrazolium (MTT) method and a TUNEL assay to confirm cellular apoptosis due to a paclitaxel treatment. AFM observations clearly showed the apoptotic morphological and biophysical changes in Ishikawa and HeLa cells. After the paclitaxel treatment, the cell membrane was torn and holed, the surface roughness was increased, and the stiffness was decreased. These changes were observed more apparently after a 24 h treatment and in Ishikawa cells compared to HeLa cells. The MTT and TUNEL assays results revealed the Ishikawa cells to be more sensitive to paclitaxel than HeLa cells and definite apoptosis occurred after a 24 h treatment. These results showed good agreement with the AFM results. Therefore, research on the morphological and biophysical changes by AFM in cancer cells will help to evaluate the anticancer activities of the drugs

Use of Spatial Information and Search Strategies in a Water Maze Analog in Drosophila melanogaster

Learning the spatial organization of the environment is crucial to fitness in most animal species. Understanding proximate and ultimate factors underpinning spatial memory is thus a major goal in the study of animal behavior. Despite considerable interest in various aspects of its behavior and biology, the model species Drosophila melanogaster lacks a standardized apparatus to investigate spatial learning and memory. We propose here a novel apparatus, the heat maze, conceptually based on the Morris water maze used in rodents. Using the heat maze, we demonstrate that D. melanogaster flies are able to use either proximal or distal visual cues to increase their performance in navigating to a safe zone. We also show that flies are actively using the orientation of distal visual cues when relevant in targeting the safe zone, i.e., Drosophila display spatial learning. Parameter-based classification of search strategies demonstrated the progressive use of spatially precise search strategies during learning. We discuss the opportunity to unravel the mechanistic and evolutionary bases of spatial learning in Drosophila using the heat maze

Molecular mechanism for the interaction between gibberellin and brassinosteroid signaling pathways in Arabidopsis

[EN] Plant development is modulated by the convergence of multiple environmental and endogenous signals, and the mechanisms that allow the integration of different signaling pathways is currently being unveiled. A paradigmatic case is the concurrence of brassinosteroid (BR) and gibberellin (GA) signaling in the control of cell expansion during photomorphogenesis, which is supported by physiological observations in several plants but for which no molecular mechanism has been proposed. In this work, we show that the integration of these two signaling pathways occurs through the physical interaction between the DELLA protein GAI, which is a major negative regulator of the GA pathway, and BRASSINAZOLE RESISTANT1 (BZR1), a transcription factor that broadly regulates gene expression in response to BRs. We provide biochemical evidence, both in vitro and in vivo, indicating that GAI inactivates the transcriptional regulatory activity of BZR1 upon their interaction by inhibiting the ability of BZR1 to bind to target promoters. The physiological relevance of this interaction was confirmed by the observation that the dominant gai-1 allele interferes with BR-regulated gene expression, whereas the bzr1-1D allele displays enhanced resistance to DELLA accumulation during hypocotyl elongation. Because DELLA proteins mediate the response to multiple environmental signals, our results provide an initial molecular framework for the integration with BRs of additional pathways that control plant development.We thank the Nottingham Arabidopsis Stock Centre, Tai-ping Sun, Zhi-Yong Wang, Yanhai Yin, Ana Cano-Delgado, Luis Lopez-Molina, and Francois Parcy for providing seeds or reagents; Laura Garcia-Carcel and Gaston Pizzio for help in the early stages of this work; and Salome Prat for fruitful discussions, sharing unpublished results, and careful reading of the manuscript. J.G.-B. holds a Consejo Superior de Investigaciones Cientificas Fellowship of the Joint Admissions Exercise Predoctoral Program. E. G. M. is recipient of a postdoctoral "Juan de la Cierva" contract from the Spanish Ministry of Science and Innovation. A. 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Cell tracking in cardiac repair: what to image and how to image

Stem cell therapies hold the great promise and interest for cardiac regeneration among scientists, clinicians and patients. However, advancement and distillation of a standard treatment regimen are not yet finalised. Into this breach step recent developments in the imaging biosciences. Thus far, these technical and protocol refinements have played a critical role not only in the evaluation of the recovery of cardiac function but also in providing important insights into the mechanism of action of stem cells. Molecular imaging, in its many forms, has rapidly become a necessary tool for the validation and optimisation of stem cell engrafting strategies in preclinical studies. These include a suite of radionuclide, magnetic resonance and optical imaging strategies to evaluate non-invasively the fate of transplanted cells. In this review, we highlight the state-of-the-art of the various imaging techniques for cardiac stem cell presenting the strengths and limitations of each approach, with a particular focus on clinical applicability

Blood and Cerebrospinal Fluid α‐Tocopherol and Selenium Concentrations in Neonatal Foals with Neuroaxonal Dystrophy

BACKGROUND: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting genetically predisposed foals maintained on α‐tocopherol (α‐TP)‐deficient diet. OBJECTIVE: Intramuscular α‐TP and selenium (Se) administration at 4 days of age would have no significant effect on serum or cerebrospinal fluid (CSF) α‐TP in healthy foals. Serum and CSF α‐TP, but not Se, would be significantly decreased in NAD/EDM‐affected foals during first year of life. ANIMALS: Fourteen Quarter horse foals; 10 healthy foals supplemented with 0.02 mL/kg injectable α‐TP and Se (n = 5) or saline (n = 5) at 4 days of age and 4 unsupplemented NAD/EDM‐affected foals. METHODS: Complete neurologic examinations were performed, blood and CSF were collected before (4 days of age) and after supplementation at 10, 30, 60, 120, 180, 240, and 360 days of age. Additional blood collections occurred at 90, 150, 210, and 300 days. At 540 days, NAD/EDM‐affected foals and 1 unsupplemented healthy foal were euthanized and necropsies performed. RESULTS: Significant decreases in blood, CSF α‐TP and Se found in the first year of life in all foals, with most significant changes in serum α‐TP from 4–150 days. Dam α‐TP and Se significantly influenced blood concentrations in foals. Injection of α‐TP and Se did not significantly increase CSF Se, blood or CSF α‐TP in healthy foals. NAD/EDM‐affected foals had significantly lower CSF α‐TP through 120 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Injection of α‐TP and Se at 4 days of age does not significantly increase blood or CSF α‐TP. Despite all 14 foals remaining deficient in α‐TP, only the 4 genetically predisposed foals developed NAD/EDM