Copy Number Alterations and Methylation in Ewing's Sarcoma

Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs) and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease

Land Use and Land Cover Change Dynamics across the Brazilian Amazon: Insights from Extensive Time-Series Analysis of Remote Sensing Data

Throughout the Amazon region, the age of forests regenerating on previously deforested land is determined, in part, by the periods of active land use prior to abandonment and the frequency of reclearance of regrowth, both of which can be quantified by comparing time-series of Landsat sensor data. Using these time-series of near annual data from 1973–2011 for an area north of Manaus (in Amazonas state), from 1984–2010 for south of Santarém (Pará state) and 1984–2011 near Machadinho d’Oeste (Rondônia state), the changes in the area of primary forest, non-forest and secondary forest were documented from which the age of regenerating forests, periods of active land use and the frequency of forest reclearance were derived. At Manaus, and at the end of the time-series, over 50% of regenerating forests were older than 16 years, whilst at Santarém and Machadinho d’Oeste, 57% and 41% of forests respectively were aged 6–15 years, with the remainder being mostly younger forests. These differences were attributed to the time since deforestation commenced but also the greater frequencies of reclearance of forests at the latter two sites with short periods of use in the intervening periods. The majority of clearance for agriculture was also found outside of protected areas. The study suggested that a) the history of clearance and land use should be taken into account when protecting deforested land for the purpose of restoring both tree species diversity and biomass through natural regeneration and b) a greater proportion of the forested landscape should be placed under protection, including areas of regrowth

Associations of Near-Surface Soil Moisture and Annual Plant Community Dynamics

Invasive species have become an increasingly large concern, particularly in already degraded ecosystems, such as sagebrush (Artemisia tridentata)-steppe of the Intermountain West. Much of this ecosystem is already infested with large cheatgrass (Bromus tectorum) stands and is potentially at risk for future invasions depending on biotic and abiotic conditions. In these ecosystems, the existing vegetation, whether native or non-native, may not effectively utilize the soil moisture resources in the upper portion of the soil, termed the growth pool. If the existing vegetation does not effectively utilize moisture in the growth pool, an open resource is left for the establishment of other plants, including invasives. Through a combination of soil moisture modeling and observational studies, we identified three potential invasion pathways, particularly by annual plants, into a cheatgrass-dominated system, all consistent with the fluctuating resource hypothesis, and all resulting from an available water resource in the growth pool. Results suggest these arid and semi-arid systems are likely to be protected from novel invasive species by complete utilization of growth pool soil water resources by any existing vegetation, whether native or non-native. Our results also suggest the same features which make the site more prone to novel annual invaders may also be useful in guiding establishment of desired vegetation during restoration efforts

Mapping major land cover types and retrieving the age of secondary forests in the Brazilian Amazon by combining single-date optical and radar remote sensing data

Secondary forests play an important role in restoring carbon and biodiversity lost previously through deforestation and degradation and yet there is little information available on the extent of different successional stages. Such knowledge is particularly needed in tropical regions where past and current disturbance rates have been high but regeneration is rapid. Focusing on three areas in the Brazilian Amazon (Manaus, Santarém, Machadinho d'Oeste), this study aimed to evaluate the use of single-date Landsat Thematic Mapper (TM) and Advanced Land Observing Satellite (ALOS) Phased Arrayed L-band Synthetic Aperture Radar (PALSAR) data in the 2007–2010 period for i) discriminating mature forest, non-forest and secondary forest, and ii) retrieving the age of secondary forests (ASF), with 100 m × 100 m training areas obtained by the analysis of an extensive time-series of Landsat sensor data over the three sites. A machine learning algorithm (random forests) was used in combination with ALOS PALSAR backscatter intensity at HH and HV polarizations and Landsat 5 TM surface reflectance in the visible, near-infrared and shortwave infrared spectral regions. Overall accuracy when discriminating mature forest, non-forest and secondary forest is high (95–96%), with the highest errors in the secondary forest class (omission and commission errors in the range 4–6% and 12–20% respectively) because of misclassification as mature forest. Root mean square error (RMSE) and bias when retrieving ASF ranged between 4.3–4.7 years (relative RMSE = 25.5–32.0%) and 0.04–0.08 years respectively. On average, unbiased ASF estimates can be obtained using the method proposed here (Wilcoxon test, p-value > 0.05). However, the bias decomposition by 5-year interval ASF classes showed that most age estimates are biased, with consistent overestimation in secondary forests up to 10–15 years of age and underestimation in secondary forests of at least 20 years of age. Comparison with the classification results obtained from the analysis of extensive time-series of Landsat sensor data showed a good agreement, with Pearson's coefficient of correlation (R) of the proportion of mature forest, non-forest and secondary forest at 1-km grid cells ranging between 0.97–0.98, 0.96–0.98 and 0.84–0.90 in the 2007–2010 period, respectively. The agreement was lower (R = 0.82–0.85) when using the same dataset to compare the ability of ALOS PALSAR and Landsat 5 TM data to retrieve ASF. This was also dependent on the study area, especially when considering mapping secondary forest and retrieving ASF, with Manaus displaying better agreement when compared to the results at Santarém and Machadinho d'Oeste

Sorting Guilty Minds

Because punishable guilt requires that bad thoughts accompany bad acts, the Model Penal Code (MPC) typically requires that jurors infer the past mental state of a criminal defendant. More specifically, jurors must sort that mental state into one of four specific categories - purposeful, knowing, reckless, or negligent - which in turn defines the nature of the crime and the extent of the punishment. The MPC therefore assumes that ordinary people naturally sort mental states into these four categories with a high degree of accuracy, or at least can reliably do so when properly instructed. It also assumes that ordinary people will order these categories of mental state, by increasing amount of punishment, in the same severity hierarchy that the MPC prescribes. The MPC, now turning 50 years old, has previously escaped the scrutiny of comprehensive empirical research on these assumptions underlying its culpability architecture. Our new empirical studies, reported here, find that most of the mens rea assumptions embedded in the MPC are reasonably accurate as a behavioral matter. Even without the aid of the MPC definitions, subjects were able to regularly and accurately distinguish among purposeful, negligent, and blameless conduct. Nevertheless, our subjects failed to distinguish reliably between knowing and reckless conduct. This failure can have significant sentencing consequences in some types of crimes, especially homicide

Potential for Modulation of the Fas Apoptotic Pathway by Epidermal Growth Factor in Sarcomas

One important mechanism by which cancer cells parasitize their host is by escaping apoptosis. Thus, selectively facilitating apoptosis is a therapeutic mechanism by which oncotherapy may prove highly advantageous. One major apoptotic pathway is mediated by Fas ligand (FasL). The death-inducing signaling Ccmplex (DISC) and subsequent death-domain aggregations are created when FasL is bound by its receptor thereby enabling programmed cell death. Conceptually, if a better understanding of the Fas pathway can be garnered, an oncoselective prodeath therapeutic approach can be tailored. Herein, we propose that EGF and CTGF play essential roles in the regulation of the Fas apoptotic pathway in sarcomas. Tumor and in vitro data suggest viable cells counter the prodeath signal induced by FasL by activating EGF, which in turn induces prosurvival CTGF. The prosurvival attributes of CTGF ultimately predominate over the death-inducing FasL. Cells destined for elimination inhibit this prosurvival response via a presently undefined pathway. This scenario represents a novel role for EGF and CTGF as regulators of the Fas pathway in sarcomas

A two-way photonic interface for linking Sr+ transition at 422 nm to the telecommunications C-band

We report a single-stage bi-directional interface capable of linking Sr+ trapped ion qubits in a long-distance quantum network. Our interface converts photons between the Sr+ emission wavelength at 422 nm and the telecoms C-band to enable low-loss transmission over optical fiber. We have achieved both up- and down-conversion at the single photon level with efficiencies of 9.4% and 1.1% respectively. Furthermore we demonstrate noise levels that are low enough to allow for genuine quantum operation in the future.Comment: 5 pages, 4 figure

At-Risk Populations for Osteosarcoma: The Syndromes and Beyond

Osteosarcoma is the most common primary malignancy of bone. Most cases are sporadic without a known genetic or environmental cause. Heritable genetic predisposition syndromes are associated with a small percentage of osteosarcomas. Study of these rare disorders has provided insight into the molecular pathogenesis of osteosarcoma. Screening of at-risk families and surveillance of affected individuals for these syndromes may permit earlier diagnosis and more effective treatment of osteosarcoma in these populations. This paper reviews the genetic and clinical features of the known osteosarcoma predisposition syndromes