The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches

The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.

Observation of the inhomogeneous spatial distribution of MeV ions accelerated by the hydrodynamic ambipolar expansion of clusters

An inhomogeneous spatial distribution of laser accelerated carbon/oxygen ions produced via the hydrodynamic ambipolar expansion of CO₂ clusters has been measured by using CR-39 detectors. An inhomogeneous etch pits spatial distribution has appeared on the etched CR-39 detector installed on the laser propagation direction, while homogeneous ones are appeared on those installed at 45°and 90°from the laser propagation direction. From the range of ions in CR-39 obtained by using the multi-step etching technique, the averaged energies of carbon/oxygen ions for all directions are determined as 0.78 ± 0.09 MeV/n. The number of ions in the laser propagation direction is about 1.5 times larger than those in other directions. The inhomogeneous etch pits spatial distribution in the laser propagation direction could originate from an ion beam collimation and modulation by the effect of electromagnetic structures created in the laser plasma.

Ion acceleration and plasma jet formation in ultra-thin foils undergoing expansion and relativistic transparency

At sufficiently high laser intensities, the rapid heating to relativistic velocities and resulting decompression of plasma electrons in an ultra-thin target foil can result in the target becoming relativistically transparent to the laser light during the interaction. Ion acceleration in this regime is strongly affected by the transition from an opaque to a relativistically transparent plasma. By spatially resolving the laser-accelerated proton beam at near-normal laser incidence and at an incidence angle of 30°, we identify characteristic features both experimentally and in particle-in-cell simulations which are consistent with the onset of three distinct ion acceleration mechanisms: sheath acceleration; radiation pressure acceleration; and transparency-enhanced acceleration. The latter mechanism occurs late in the interaction and is mediated by the formation of a plasma jet extending into the expanding ion population. The effect of laser incident angle on the plasma jet is explored.

A high-value, low-cost bubble continuous positive airway pressure system for low-resource settings:technical assessment and initial case reports

Acute respiratory infections are the leading cause of global child mortality. In the developing world, nasal oxygen therapy is often the only treatment option for babies who are suffering from respiratory distress. Without the added pressure of bubble Continuous Positive Airway Pressure (bCPAP) which helps maintain alveoli open, babies struggle to breathe and can suffer serious complications, and frequently death. A stand-alone bCPAP device can cost $6,000, too expensive for most developing world hospitals. Here, we describe the design and technical evaluation of a new, rugged bCPAP system that can be made in small volume for a cost-of-goods of approximately $350. Moreover, because of its simple design--consumer-grade pumps, medical tubing, and regulators--it requires only the simple replacement of a <$1 diaphragm approximately every 2 years for maintenance. The low-cost bCPAP device delivers pressure and flow equivalent to those of a reference bCPAP system used in the developed world. We describe the initial clinical cases of a child with bronchiolitis and a neonate with respiratory distress who were treated successfully with the new bCPAP device.

Laser-fabricated PET-Ti Hybrid Joints for Medical Device Applications

Currently, micro-joining of plastic parts to metal parts in medical devices is achieved by using medical adhesives, For example, pacemakers, defibrillators and neurological stimulators are designed using silicone adhesive to seal the joint between the polyurethane connector module and the titanium can [1]. Nevertheless, the use of adhesive is problematic because it requires a long time to cure and has high tendency to produce leachable products which might be harmful to the human body. An alternative for directly joining plastics to metal without adhesive is therefore required. Laser transmission joining (LTJ) is growing in importance, and has the potential to gain the niche in micro-fabrication of plastics-metal hybrid joints for medical device applications. The possibility of directly joining plastics to metal by LTJ technique have been demonstrated by a number of studies in recent literature [2]. The widely-accepted understanding of LTJ between plastics and metal is that generation and rapid expansion of micro-bubbles at the plastics-metal interface exert high local pressure to press the melted plastics towards the metal surface features during the laser processing [2]. This subsequently creates the plastics-metal hybrid joint by the mechanisms of mechanical interlocking as well as chemical and physical bonds between the plastics and metal surfaces. Although the micro-bubbles can help promote the mechanical interlocking effect to increase the joint strength, the creation of bubble is a random and complex process depending on the complicated interactions between the laser intensity, thermal degradation properties of plastics, surface temperature and topographical features of metal. In an ideal situation, it is desirable to create the hybrid plastics-metal joint without bubbles. However, the mechanical performance of the hybrid plastics-metal joint without bubbles is still unknown, and systematic comparison between the hybrid joints with and without bubbles is lacking in literature. This becomes the objective of this study. In this work, the laser process parameters were carefully chosen from a preliminary study, such that different hybrid joints: with and without bubbles can be produced and compared. Biocompatible PET and commercially pure Ti were selected as materials for laser joining.

The History of Expansion of the Genus Bursaphelenchus (Nematoda: Aphelenchida: Parasitaphelenchidae)

Because of globalization and removal of geographical barriers, frequent biological invasions of introduced species become an urgent environmental problem. According to the Convention on Biological Diversity (CBD), precise identification of dangerous aggressive species at the early stages of their invasion to new regions is the most important component of the environmental control and monitoring. To resist the potential environmental hazard, the precise data are required on the current distribution and history of expansion of pests that are of global economic importance.

Increasing inter-generational social mobility: is educational expansion the answer?

Reforms which increase the stock of education in a society have long been held by policy-makers as key to improving rates of intergenerational social mobility. Yet, despite the intuitive plausibility of this idea, the empirical evidence in support of an effect of educational expansion on social fluidity is both indirect and weak. In this paper we use the raising of the minimum school leaving age from 15 to 16 years in England and Wales in 1972 to estimate the effect of educational participation and qualification attainment on rates of intergenerational social class mobility. Because, in expectation, children born immediately before and after the policy was implemented are statistically exchangeable, the difference in the amount of education they received may be treated as exogenously determined. The exogenous nature of the additional education gain means that differences in rates of social mobility between cohorts affected by the reform can be treated as having been caused by the additional education. The data for the analysis come from the ONS Longitudinal Study, which links individual records from successive decennial censuses between 1971 and 2001. Our findings show that, although the reform resulted in an increase in educational attainment in the population as a whole and a weakening of the association between attainment and class origin, there was no reliably discernible increase in the rate of intergenerational social mobility.

From dispersed to monopolized violence: expansion and consolidation of the Primeiro Comando da Capital's hegemony in São Paulo's prisons

The present work aims to understand the process of expansion and consolidation of the organized criminal group the Primeiro Comando da Capital (PCC) in São Paulo’s prison system over the past 20 years, and the social configuration that has formed as a result of the PCCs monopolization of opportunities of power. To this end, the work of Norbert Elias is utilized to analyze empirical data collected from various sources. The article consists of two lines of analysis. First, the PCC phenomenon is approached from a macro-sociological point of view, focusing on the social, political and administrative problems that are directly or indirectly linked to the PCCs social development. Second, a figurational analysis is used to explore the social dynamics produced from this process. In comparison to the “pre-PCC” situation, it is shown that the new social configuration produced from the hegemony of the PCC consists of a complexity of interdependencies, including greater functional division and social integration. Given this intensification of mutual dependencies, the social controls on individual behavior have been expanded and centralized. Here, the structure and organization of the PCC, its political dynamics, and individual self-control are central issues. The article concludes by calling into question the view that the most significant effect of the PCCs consolidation has been social pacification of São Paulo’s prison system. Fragilities in the power of the PCC are explored, principally the precarious nature of the relationship between the PCC and state authorities, and the extent to which the PCC’s authority is imposed.

Multivariate Moments Expansion Density: Application of the Dynamic Equicorrelation Model

In this study, we propose a new semi-nonparametric (SNP) density model for describing the density of portfolio returns. This distribution, which we refer to as the multivariate moments expansion (MME), admits any non-Gaussian (multivariate) distribution as its basis because it is specified directly in terms of the basis density’s moments. To obtain the expansion of the Gaussian density, the MME is a reformulation of the multivariate Gram-Charlier (MGC), but the MME is much simpler and tractable than the MGC when positive transformations are used to produce well-defined densities. As an empirical application, we extend the dynamic conditional equicorrelation (DECO) model to an SNP framework using the MME. The resulting model is parameterized in a feasible manner to admit two-stage consistent estimation and it represents the DECO as well as the salient non-Gaussian features of portfolio return distributions. The in- and out-of-sample performance of a MME-DECO model of a portfolio of 10 assets demonstrate that it can be a useful tool for risk management purposes.

A data-mining-based methodology for transmission expansion planning

In recent decades, all over the world, competition in the electric power sector has deeply changed the way this sector’s agents play their roles. In most countries, electric process deregulation was conducted in stages, beginning with the clients of higher voltage levels and with larger electricity consumption, and later extended to all electrical consumers. The sector liberalization and the operation of competitive electricity markets were expected to lower prices and improve quality of service, leading to greater consumer satisfaction. Transmission and distribution remain noncompetitive business areas, due to the large infrastructure investments required. However, the industry has yet to clearly establish the best business model for transmission in a competitive environment. After generation, the electricity needs to be delivered to the electrical system nodes where demand requires it, taking into consideration transmission constraints and electrical losses. If the amount of power flowing through a certain line is close to or surpasses the safety limits, then cheap but distant generation might have to be replaced by more expensive closer generation to reduce the exceeded power flows. In a congested area, the optimal price of electricity rises to the marginal cost of the local generation or to the level needed to ration demand to the amount of available electricity. Even without congestion, some power will be lost in the transmission system through heat dissipation, so prices reflect that it is more expensive to supply electricity at the far end of a heavily loaded line than close to an electric power generation. Locational marginal pricing (LMP), resulting from bidding competition, represents electrical and economical values at nodes or in areas that may provide economical indicator signals to the market agents. This article proposes a data-mining-based methodology that helps characterize zonal prices in real power transmission networks. To test our methodology, we used an LMP database from the California Independent System Operator for 2009 to identify economical zones. (CAISO is a nonprofit public benefit corporation charged with operating the majority of California’s high-voltage wholesale power grid.) To group the buses into typical classes that represent a set of buses with the approximate LMP value, we used two-step and k-means clustering algorithms. By analyzing the various LMP components, our goal was to extract knowledge to support the ISO in investment and network-expansion planning.

Market expansion and the co-opetition of criminal organizations in Italy

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

COMTEMP: Financing expansion through private equity?

COMTEMP – Companhia de Temperos, Lda. is a Portuguese company that produces vinegars (e.g. CRISTAL vinegars), sauces and condiments. This case study aims to analyze its attractiveness to receive a venture capital investment. The main covered topics are arranged into the following sections: foundation, company, industry, competition, industrial kitchen opportunity, financial strategy and decision.