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.

This report provides a record of a field excursion to the Shetland Islands in May 2014 to investigate sediments deposited from tsunamis generated from submarine landslides mainly located off the coast of Norway. The research was funded under a NERC Consortium Grant for a project entitled ‘Will climate change in the Arctic increase the landslide-tsunami risk to the UK?’ It was part of Work Block 2 (WB2): ‘What is the timing of tsunami deposits on the UK coastline, and how is it related to the age of major Arctic slides’?
The best known and most studied tsunami from the Norwegian submarine landslides is the Storegga event dated at 8,200BP. Sediments deposited from this tsunami are commonly found along the west coast of Norway, east coast of mainland Scotland, and also on the Shetland and Faeroe islands. However, there are other landslides off of Norway for which no associated tsunami has been identified, which poses the question as to whether these events did not generate a tsunami or whether the evidence for a tsunami has not yet been found.
Although evidence for seabed slumping off Norway was first discovered in the 1950’s (Holtedahl, 1955, 1971) and the scale and morphology of a massive submarine landslide, subsequently termed Storegga, mapped in the 1970’s (Bugge, 1983), it was not until 1985 that an associated tsunami was first proposed (Svendsen, 1985). The first supporting sedimentary evidence of the tsunami was first identified on mainland Scotland in 1988 (Dawson et al., 1988) then, subsequently, similar sediments were identified on the Shetland Islands (Smith, 1993a). The Storegga Slide has been dated to 8,150BP (Haflidason et al., 2005), however more recent research on the deposits on the Shetlands suggests that some may not all be from Storegga, because 14C age dating gives younger ages of ~5,000 and 1,500 cal yr BP (Bondevik et al., 2005). A major challenge posed by the ages of these younger dates is that they are confined to the Shetlands; there is no indication of these younger tsunamis on mainland Scotland. If the dating is correct and the sediments are indeed from tsunamis, then the submarine landslides off Norway would be an unlikely source, so a local source seems most likely, but none has yet been identified. Alternatively a non-tsunami source for the sediments may explain their presence.
The objectives of WB2 therefore are to investigate the tsunami deposits on Shetland that post-date the Storegga Slide, to validate their ages and, if possible, identify possible source locations of the submarine landslides that generated the tsunamis. On Shetland research on tsunami sediments was mainly based on evidence from coastal exposures around Sullom Voe where tsunami sands are dated as coeval with Storegga. The younger sands are mainly preserved in lake cores at locations on Shetland Mainland (Bondevik et al., 2005) where those of 5,000 BP overlie sands of Storegga age at 8,200 years BP age. At coastal sites along Basta Voe on Yell and at a mainland site at Dury Voe very young age dates of ~1,500 BP suggest an additional and very recent, late Holocene event (Bondevik et al., 2005; Dawson et al, 2006).
A preliminary field excursion to the Shetlands carried out in 2013 discovered possible new tsunami deposits preserved in peat on central Yell at Whale Firth, Mid Yell Voe and Kirkabister. Subsequent 14C age dating of these deposits resulted in a variety of ages, many much younger than that of Storegga. The 14C method is known to be subject to major uncertainties because of contamination, for example initial age dating in the 1990’s at sites around Sullom Voe returned ages of around 5,000 years BP, although these were subsequently rejected in favour of the earlier, 8,200 BP Storegga event.
Thus, validating the ages of the deposits on Yell, prospectively from a number of deposits laid down successively at one site (thereby reducing the sole reliance on 14C dating) was critical in validating the presence of more than one tsunami event on Shetland. The objective of the 2014 field visit to the Shetlands, therefore, was to return to Yell and validate the preliminary results from 2013; revisiting the sites at Whale Firth, Mid Yell and Kirkabister and searching the coastlines of Unst, Fetlar, Yell and north Mainland for additional sites where tsunami sediments might be preserved. Just before the visit new 14C dates from Mid Yell from samples collected in 2013 confirmed the previous results from other locations that had given a wide range of ages; at Whale Firth a single date gave a ‘young’ age of ~5,000 years BP, a range of ages with the oldest at 8,200 years BP were returned from Mid Yell Voe.
We first visited sites on north Mainland around Sullom Voe, as it was here that the first indications of the Storegga tsunami were identified on Shetland in 1992. The deposits are classic as they contain rip-up clasts characteristic of tsunami deposits elsewhere. We then visited the sites at Basta Voe, Whale Firth, Mid Yell and Kirkabister. We carried out reconnaissance surveys on Unst, Fetlar, Yell and north Mainland.
Preliminary results:
1. The new evidence supports the presence of tsunami sediments on Yell at Mid Yell Voe and Whale Firth, but the age of these sediments requires further research to confirm previous dating and their possible sources,
2. The youngest dated sediments (~1,500 BP) at Vasta Voe are most likely from a tsunami, but their limited areal extent suggests a local source, as yet undetermined,
3. The presence of three events at Mid Yell Voe based on surveys in 2013 was not confirmed,
4. The similarity of the deposits on Mid Yell with those around Sullom Voe on Mainland are suggestive of a similar source,
5. The wide range of the preliminary age dating at the Mid Yell sites (Whale Firth and Mid Yell Voe) is analogous to the early age dating of coastal deposits around Sullom Voe, suggesting the possibility of contamination of the peat material dated,
6. Whereas the 5,500BP event is identified in lake cores, no strongly supportive evidence for sands of this age were identified in the coastal sections,
7. Of the proposed three tsunami events proposed for Shetland only one, Storegga, has a confirmed source,
8. Further analysis of the peat stratigraphy at the coastal sites, reflects vegetation changes over the past ~8,000 years related to climate change, and these could be used to provide a broader context for the 14C age dating that may resolve the present dating issues,
9. Newly discovered sediments at Kirkabister require further research to determine their origin,
10. The origin(s) of the laminated deposits at Whale Firth, Mid Yell and Vatsetter is/are uncertain, but they are probably not from a tsunami,
11. No additional coastal exposures of peat with tsunami sands were located during the reconnaissance surveys on Mainland, Yell, Unst and Fetlar.
Postscript; Immediately after this report was finalised, age dating of peat sections at Whale Firth and Mid Yell Voe confirmed that the sands preserved in the woody peat here are of Storegga age, ~8,200 cal yr BP.

Shetlands Islands field trip May 2014 : summary of results

Studies of the structural and molecular features of the lymphatic vasculature, which clears fluid, macromolecules and leukocytes from the tissue microenvironment, have largely relied on animal models, with limited information in human organs beyond traditional immunohistochemical assessment. Here, we use three-dimensional imaging and single-cell RNA-sequencing to study lymphatics in the human kidney. We found a hierarchical arrangement of lymphatic vessels within human kidneys, initiating along specialised nephron epithelium in the renal cortex and displaying a distinct, kidney-specific transcriptional profile. In chronic transplant rejection we found kidney allograft lymphatic expansion alongside a loss of structural hierarchy, with human leukocyte antigen-expressing lymphatic vessels infiltrating the medulla, presenting a putative target for alloreactive antibodies. This occurred concurrently with lymphatic vessels invading and interconnecting tertiary lymphoid structures at early stages of lymphocyte colonisation. Analysis of intercellular signalling revealed upregulation of co-inhibitory molecule-mediated CD4+ T cell-lymphatic crosstalk in rejecting kidneys, potentially acting to limit local alloimmune responses. Overall, we delineate novel structural and molecular features of human kidney lymphatics and reveal perturbations to their phenotype and transcriptome in the context of alloimmunity. SUMMARY Lymphatics regulate fluid balance and immune cell accumulation but are under-studied in human organs such as the kidney. Jafree and colleagues profiled human kidney lymphatics using three-dimensional imaging and single-cell RNA-sequencing, revealing structural and transcriptional perturbations in rejecting kidney transplants.

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Three-dimensional imaging and single-cell transcriptomics of the human kidney implicate perturbation of lymphatics in alloimmunity

We present observations of an “EIT wave” associated with an X-class flare from 2012 July 6, the propagation of which was severely restricted by the magnetic structure of the solar corona surrounding the erupting active region. The “EIT wave” was observed by both SDO and STEREO-A, allowing a three-dimensional examination of how the propagation of the disturbance was affected both by a neighbouring coronal hole and a trans-equatorial loop system. In addition, the eruption was observed at the limb by the ground-based CoMP instrument, allowing the Doppler motion associated with the eruption and resulting coronal loop oscillation to be investigated in detail. This combination of data-sets provides a unique insight into the three-dimensional evolution of the “EIT wave” and its effects on the surrounding corona.

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Restricted propagation of an “EIT wave” in the low solar corona

NASA's Soil Moisture Active Passive (SMAP) mission originally included both passive and active <italic>L</italic>-band measurement capabilities. It was the first satellite instrument to provide global <italic>L</italic>-band radar observations of normalized radar cross section (<inline-formula><tex-math notation="LaTeX">$\sigma ^{0}$</tex-math></inline-formula>) at multiple resolutions. The SMAP radar collected high-resolution (<inline-formula><tex-math notation="LaTeX">$\sim$</tex-math></inline-formula>1–3 km) synthetic aperture radar (SAR) measurements over most of the earth's land mass. It simultaneously collected low-resolution 6 × 30 km “slice” and full-footprint 29 × 35 km measurements. The SMAP radar operated for 83 days, from day of the year 103 to 186 in 2015, before the transmitter failed. The SMAP radar was designed to make vegetation roughness measurements in support of the SMAP primary mission to measure soil moisture, but the radar data are useful for a variety of applications, particularly in the polar regions. Unfortunately, limitations in the data download volume precluded the downlink of high-resolution data over Antarctica, sea ice in the polar regions, and various islands. Nonetheless, low-resolution slice and footprint data were collected and downlinked over these areas. To better exploit these low-resolution data, this article employs image reconstruction techniques to create twice-daily enhanced resolution SMAP radar images from the slice and footprint measurements. To validate the resolution enhancement, the enhanced resolution data are compared to SAR results over Greenland and South America. The new dataset is provided to the science community to support cryosphere and climate studies.

Validation of the Effective Resolution of SMAP Enhanced Resolution Backscatter Products

(1) School of Environmental Sciences, University of Ulster, Coleraine BT52 1SA, UK, (2) Department of Geography, Durham University, Durham DH1 3LE, UK, (3) Department of Earth Sciences, University of Maine, Orono ME 04469-5711, USA, (4) School of Natural Sciences, Trinity College Dublin, Dublin 2, Republic of Ireland, (5) British Geological Survey, West Mains Road, Edinburgh, EH9 3LA, UK, (6) Department of Earth Sciences, University of Ottawa, Ottawa ON, K1N 6N5, Canada, (7) Geological Survey of Ireland, Dublin 4, Ireland

David Long

Papers

Shetlands Islands field trip May 2014 : summary of results

Three-dimensional imaging and single-cell transcriptomics of the human kidney implicate perturbation of lymphatics in alloimmunity

Restricted propagation of an “EIT wave” in the low solar corona

Validation of the Effective Resolution of SMAP Enhanced Resolution Backscatter Products

Deglacial and post-glacial sea-level history for Bantry Bay (SW Ireland) based on offshore evidence