The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

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Cancer nanomedicine: progress, challenges and opportunities.

Overview of membrane science and technology membrane transport theory membrane and modules concentration polarization reverse osmosis ultrafiltration microfiltration gas separation pervaporation ion exchange membrane processes - electrodialysis carrier facilitated transport medical applications of membranes other membranes processed.

Membrane Technology and Applications

Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases; for example, by allowing the targeted delivery of a drug to particular subsets of cells. However, so far, such nanoparticles have not proved capable of surmounting all of the biological barriers required to achieve this goal. Nevertheless, advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are creating new opportunities for the development of nanoparticles for therapeutic applications. This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.

Strategies in the design of nanoparticles for therapeutic applications

The genomes of various tumour cells contain mutant oncogenes that act dominantly, in that their effects can be observed when they are introduced into non-malignant cells. There is evidence for another class of oncogenes, in which tumour-predisposing mutations are recessive to wild-type alleles. Retinoblastoma is a prototype biological model for the study of such recessive oncogenes. This malignant tumour, which arises in the eyes of children, can be explained as the result of two distinct genetic changes, each causing loss of function of one of the two homologous copies at a single genetic locus, Rb, assigned to the q14 band of human chromosome 13. Mutations affecting this locus may be inherited from a parent, may arise during gametogenesis or may occur somatically. Those who inherit a mutant allele at this locus have a high incidence of non-ocular, second tumours, almost half of which are osteosarcomas believed to be caused by the same mutation. Here we describe the isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus. The gene is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas. The cDNA fragment detects a locus spanning at least 70 kilobases (kb) in human chromosome band 13q14, all or part of which is frequently deleted in retinoblastomas and osteosarcomas.

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A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma

Conventional forms of drug administration generally rely on pills, eye drops, ointments, and intravenous solutions. Recently, a number of novel drug delivery approaches have been developed. These approaches include drug modification by chemical means, drug entrapment in small vesicles that are injected into the bloodstream, and drug entrapment within pumps or polymeric materials that are placed in desired bodily compartments (for example, the eye or beneath the skin). These techniques have already led to delivery systems that improve human health, and continued research may revolutionize the way many drugs are delivered.

http://science.sciencemag.org/content/sci/249/4976/1527.full.pdf

New methods of drug delivery.

We describe and analyze observations by the Solar Dynamics Observatory of the emergence of a small, bipolar active region within an area of unipolar magnetic flux that was surrounded by a circular, quiescent filament. Within only 8 hours from the start of the emergence, a partial splitting of the filament and two consecutive coronal mass ejections took place. We argue that all three dynamic events occurred as a result of particular magnetic-reconnection episodes between the emerging bipole and the pre-existing coronal magnetic field. To substantiate our interpretation, we consider 3D magnetohydrodynamic simulations that model the emergence of magnetic flux in the vicinity of a large-scale coronal flux rope. The simulations qualitatively reproduce most of the reconnection episodes suggested by the observations, as well as the filament splitting, the first eruption, and the formation of sheared/twisted fields that may have played a role in the second eruption. Our results suggest that the position of emerging flux with respect to the background magnetic configuration is a crucial factor for the resulting evolution, while previous results suggest that parameters such as the orientation or the amount of emerging flux are important as well. This poses a challenge for predicting the onset of eruptions that are triggered by flux emergence, and calls for a detailed survey of the relevant parameter space by means of numerical simulations.

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Sequential Eruptions Triggered by Flux Emergence: Observations and Modeling

• The gene for hereditary retinoblastoma (Rb), an autosomal dominant trait localized to the long arm of chromosome 13, is linked to the locus for the enzyme esterase D (EsD). We analyzed a three-generation family that demonstrates cosegregation of alleles at the EsD locus and the Rb locus. This kindred yields a logarithm of the odds ratio (LOD) score of 2.46 at a recombination fraction (θ) of 0.0. When combined with five other recently reported families, the resulting maximum score was 11.08 at θ = 0.0. This combined LOD score and the lack of demonstrable crossovers in more than 65 individuals indicate that predictions of the Rb gene carrier state based on EsD genotyping are at least 90% accurate.

Accuracy of Detection of the Retinoblastoma Gene by Esterase D Linkage

Acute and Subacute Toxicity of 100% PFOB Emulsion

On the 29 March 2014 NOAA active region (AR) 12017 produced an X1 flare which was simultaneously observed by an unprecedented number of observatories. We have investigated the pre-flare period of this flare from 14:00 UT until 19:00 UT using joint observations made by the Interface Region Imaging Spectrometer (IRIS) and the Hinode Extreme Ultraviolet Imaging Spectrometer (EIS). Spectral lines providing coverage of the solar atmosphere from chromosphere to the corona were analysed to investigate pre-flare activity within the AR. The results of the investigation have revealed evidence of strongly blue-shifted plasma flows, with velocities up to 200 km/s, being observed 40 minutes prior to flaring. These flows are located along the filament present in the active region and are both spatially discrete and transient. In order to constrain the possible explanations for this activity, we undertake non-potential magnetic field modelling of the active region. This modelling indicates the existence of a weakly twisted flux rope along the polarity inversion line in the region where a filament and the strong pre-flare flows are observed. We then discuss how these observations relate to the current models of flare triggering. We conclude that the most likely drivers of the observed activity are internal reconnection in the flux rope, early onset of the flare reconnection, or tether cutting reconnection along the filament.

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Observations and Modelling of the Pre-Flare Period of the 29 March 2014 X1 Flare

The most consistent and reliable physical sign of impending parturition in pregnant laboratory beagle bitches was palpable relaxation of pelvic and abdominal musculature A drop in rectal temperature was of some value but was found to be too variable between individuals to use as the sole criterion Abrupt changes in attitude or appetite were the chief behavioral changes observed Since the institution of a standardized record form for all pregnant dogs, 15 consecutive term litters have been successfully derived from pregnant dogs into gnotobiotic life isolation units

David Long

Papers

Sequential Eruptions Triggered by Flux Emergence: Observations and Modeling

Accuracy of Detection of the Retinoblastoma Gene by Esterase D Linkage

Acute and Subacute Toxicity of 100% PFOB Emulsion

Observations and Modelling of the Pre-Flare Period of the 29 March 2014 X1 Flare

Signs of impending parturition in the laboratory bitch.