The Archaeological Survey of Sudanese Nubia, 1963-69

Of the Nubian Archaeological Campaigns responding to the construction of the Aswan High Dam, the survey and excavations carried out within Sudanese Nubia represent the most substantial achievement of the larger enterprise. Many components of the larger project of the UNESCO – Sudan Antiquities Service Survey have been published, in addition to the reports of a number of other major projects assigned separate concessions within the region. However, the results of one major element, the Archaeological Survey of Sudanese Nubia (ASSN) between the Second Cataract and the Dal Cataract remain largely unpublished. This volume, focusing on the pharaonic sites, is the first of a series which aims to bring to publication the records of the ASSN. These records represent a major body of data relating to a region largely now lost to flooding. This is also a region of very considerable importance for understanding the archaeology and history of Nubia more generally, not least in relation to the still often poorly understood relationships between Lower Nubia to the north and the surviving areas of Middle and Upper Nubia, to the south. The ASSN project fieldwork was undertaken over six years between 1963 and 1969, investigating c.130km of the river valley between Gemai, at the south end of the Second Cataract, and Dal

The Archaeological Survey of Sudanese Nubia, 1963-69

Of the Nubian Archaeological Campaigns responding to the construction of the Aswan High Dam, the survey and excavations carried out within Sudanese Nubia represent the most substantial achievement of the larger enterprise. Many components of the larger project of the UNESCO – Sudan Antiquities Service Survey have been published, in addition to the reports of a number of other major projects assigned separate concessions within the region. However, the results of one major element, the Archaeological Survey of Sudanese Nubia (ASSN) between the Second Cataract and the Dal Cataract remain largely unpublished. This volume, focusing on the pharaonic sites, is the first of a series which aims to bring to publication the records of the ASSN. These records represent a major body of data relating to a region largely now lost to flooding. This is also a region of very considerable importance for understanding the archaeology and history of Nubia more generally, not least in relation to the still often poorly understood relationships between Lower Nubia to the north and the surviving areas of Middle and Upper Nubia, to the south. The ASSN project fieldwork was undertaken over six years between 1963 and 1969, investigating c.130km of the river valley between Gemai, at the south end of the Second Cataract, and Dal

Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma

Background Patients with malignant melanoma often relapse after treatment with BRAF and/or mitogen‐activated protein kinase kinase (MEK) inhibitors (MEKi) owing to development of drug resistance. Objectives To establish the temporal pattern of CD271 regulation during development of resistance by melanoma to trametinib, and determine the association between development of resistance to trametinib and induction of prosurvival autophagy. Methods Immunohistochemistry for CD271 and p62 was performed on human naevi and primary malignant melanoma tumours. Western blotting was used to analyse expression of CD271, p62 and LC3 in melanoma subpopulations. Flow cytometry and immunofluorescence microscopy was used to evaluate trametinib‐induced cell death and CD271 expression. MTS viability assays and zebrafish xenografts were used to evaluate the effect of CD271 and autophagy modulation on trametinib‐resistant melanoma cell survival and invasion, respectively. Results CD271 and autophagic signalling are increased in stage III primary melanomas vs. benign naevi. In vitro studies demonstrate MEKi of BRAF‐mutant melanoma induced cytotoxic autophagy, followed by the emergence of CD271‐expressing subpopulations. Trametinib‐induced CD271 reduced autophagic flux, leading to activation of prosurvival autophagy and development of MEKi resistance. Treatment of CD271‐expressing melanoma subpopulations with RNA interference and small‐molecule inhibitors to CD271 reduced the development of MEKi resistance, while clinically applicable autophagy modulatory agents – including Δ9‐tetrahydrocannabinol and Vps34 – reduced survival of MEKi‐resistant melanoma cells. Combined MEK/autophagy inhibition also reduced the invasive and metastatic potential of MEKi‐resistant cells in an in vivo zebrafish xenograft. Conclusions These results highlight a novel mechanism of MEKi‐induced drug resistance and suggest that targeting autophagy may be a translatable approach to resensitize drug‐resistant melanoma cells to the cytotoxic effects of MEKi

Analysis of United Kingdom Off-Highway Construction Machinery Market and Its Consumers Using New-Sales Data

The off-highway construction machinery market and its consumers have attracted minimal previous research. This study addresses that void by analyzing annual United Kingdom (UK) (volume/portfolio) new-sales data for the 10 most popular products within that market, 1990–2010 inclusive. Graphical, descriptive statistical, Pearson-correlational, autocorrelational, and elementary modeling are employed to identify contrasts in sales regarding (1) high- and low-volume items; (2) growth trends and significant recessionary effects on volumes; (3) a demand change point circa 1997, since when annual product portfolio has changed little; and (4) product associations in consumer demand. Significant association is demonstrated between demand and construction output, especially with the value of new housing. Subsequently, consumption of wheeled loaders is modeled using construction volume, and demand for mini and crawler excavators is modeled using new-housing data. Time series trends for these machinery types are presented and forecast through 2015. The primary contribution of this study is a deeper understanding of the UK new-machinery market and the predilections of its consumers over the last two decades (to present)

Mechanisms of Bacterial Extracellular Electron Exchange.

The biochemical mechanisms by which microbes interact with extracellular soluble metal ions and insoluble redox-active minerals have been the focus of intense research over the last three decades. The process presents two challenges to the microorganism; firstly electrons have to be transported at the cell surface, which in Gram negative bacteria presents an additional problem of electron transfer across the ~ 6 nm of the outer membrane. Secondly the electrons must be transferred to or from the terminal electron acceptors or donors. This review covers the known mechanisms that bacteria use to transport electrons across the cell envelope to external electron donors/acceptors. In Gram negative bacteria electron transfer across the outer membrane involves the use of an outer membrane β-barrel and cytochrome. These can be in the form of a porin-cytochrome protein, such as Cyc2 of Acidothiobacillus ferrioxydans, or a multiprotein porin-cytochrome complex like MtrCAB of Shewanella oneidensis MR-1. For mineral respiring organisms there is the additional challenge of transferring the electrons from the cell to mineral surface. For the strict anaerobe Geobacter sulfurreducens this requires electron transfer through conductive pili to associated cytochrome OmcS that directly reduces Fe(III)oxides, while the facultative anaerobe S. oneidensis MR-1 accomplishes mineral reduction through direct membrane contact, contact through filamentous extentions and soluble flavin shuttles, all of which require the outer membrane cytochromes MtrC and OmcA in addition to secreted flavin

Intramolecular Telomeric G-Quadruplexes Dramatically Inhibit DNA Synthesis by Replicative and Translesion Polymerases, Revealing their Potential to Lead to Genetic Change

Recent research indicates that hundreds of thousands of G-rich sequences within the human genome have the potential to form secondary structures known as G-quadruplexes. Telomeric regions, consisting of long arrays of TTAGGG/AATCCC repeats, are among the most likely areas in which these structures might form. Since G-quadruplexes assemble from certain G-rich single-stranded sequences, they might arise when duplex DNA is unwound such as during replication. Coincidentally, these bulky structures when present in the DNA template might also hinder the action of DNA polymerases. In this study, single-stranded telomeric templates with the potential to form G-quadruplexes were examined for their effects on a variety of replicative and translesion DNA polymerases from humans and lower organisms. Our results demonstrate that single-stranded templates containing four telomeric GGG runs fold into intramolecular G-quadruplex structures. These intramolecular G quadruplexes are somewhat dynamic in nature and stabilized by increasing KCl concentrations and decreasing temperatures. Furthermore, the presence of these intramolecular G-quadruplexes in the template dramatically inhibits DNA synthesis by various DNA polymerases, including the human polymerase δ employed during lagging strand replication of G-rich telomeric strands and several human translesion DNA polymerases potentially recruited to sites of replication blockage. Notably, misincorporation of nucleotides is observed when certain translesion polymerases are employed on substrates containing intramolecular G-quadruplexes, as is extension of the resulting mismatched base pairs upon dynamic unfolding of this secondary structure. These findings reveal the potential for blockage of DNA replication and genetic changes related to sequences capable of forming intramolecular G-quadruplexes

The Crystal Structure of the Extracellular 11-heme Cytochrome UndA Reveals a Conserved 10-heme Motif and Defined Binding Site for Soluble Iron Chelates

Members of the genus Shewanella translocate deca- or undeca-heme cytochromes to the external cell surface thus enabling respiration using extracellular minerals and polynuclear Fe(III) chelates. The high resolution structure of the first undeca-heme outer membrane cytochrome, UndA, reveals a crossed heme chain with four potential electron ingress/egress sites arranged within four domains. Sequence and structural alignment of UndA and the deca-heme MtrF reveals the extra heme of UndA is inserted between MtrF hemes 6 and 7. The remaining UndA hemes can be superposed over the heme chain of the decaheme MtrF, suggesting that a ten heme core is conserved between outer membrane cytochromes. The UndA structure has also been crystallographically resolved in complex with substrates, an Fe(III)-nitrilotriacetate dimer or an Fe(III)-citrate trimer. The structural resolution of these UndA-Fe(III)-chelate complexes provides a rationale for previous kinetic measurements on UndA and other outer membrane cytochromes

An assessment of the benefits of yellow Sigatoka (Mycosphaerella musicola) control in the Queensland Northern Banana Pest Quarantine Area

The banana leaf spotting disease yellow Sigatoka is established and actively controlled in Australia through intensive chemical treatments and diseased leaf removal. In the State of Queensland, the State government imposes standards for de-leafing to minimise the risk of the disease spreading in 6 banana pest quarantine areas. Of these, the Northern Banana Pest Quarantine Area is the most significant in terms of banana production. Previous regulations imposed obligations on owners of banana plants within this area to remove leaves from plants with visible spotting on more than 15 per cent of any leaf during the wet season. Recently, this leaf disease threshold has been lowered to 5 per cent. In this paper we examine the likely impact this more-costly regulation will have on the spread of the disease. We estimate that the average net benefit of reducing the diseased leaf threshold is only likely to be $1.4 million per year over the next 30 years, expressed as the annualised present value of tightened regulation. This result varies substantially when the timeframe of the analysis is changed, with shorter time frames indicating poorer net returns from the change in protocols. Overall, the benefit of the regulation change is likely to be minor

A statistical evaluation of the effects of gender differences in assessment of acute inhalation toxicity

Acute inhalation toxicity of chemicals has conventionally been assessed by the median lethal concentration (LC50) test (organisation for economic co-operation and development (OECD) TG 403). Two new methods, the recently adopted acute toxic class method (ATC; OECD TG 436) and a proposed fixed concentration procedure (FCP), have recently been considered, but statistical evaluations of these methods did not investigate the influence of differential sensitivity between male and female rats on the outcomes. This paper presents an analysis of data from the assessment of acute inhalation toxicity for 56 substances. Statistically significant differences between the LC50 for males and females were found for 16 substances, with greater than 10-fold differences in the LC50 for two substances. The paper also reports a statistical evaluation of the three test methods in the presence of unanticipated gender differences. With TG 403, a gender difference leads to a slightly greater chance of under-classification. This is also the case for the ATC method, but more pronounced than for TG 403, with misclassification of nearly all substances from Globally Harmonised System (GHS) class 3 into class 4. As the FCP uses females only, if females are more sensitive, the classification is unchanged. If males are more sensitive, the procedure may lead to under-classification. Additional research on modification of the FCP is thus proposed