Quenched phosphorescence as alternative detection mode in the chiral separation of methotrexate by electrokinetic chromatography

Quenched phosphorescence was used, for the first time, as detection mode in the chiral separation of methotrexate (MTX) enantiomers by electrokinetic chromatography. The detection is based on dynamic quenching of the strong emission of the phosphorophore 1-bromo-4-naphthalene sulfonic acid (BrNS) by MTX under deoxygenated conditions. The use of a background electrolyte with 3 mg/mL 2-hydroxypropyl-β-cyclodextrin and 20% MeOH in 25 mM phosphate buffer (pH 7.0) and an applied voltage of 30 kV allowed the separation of l-MTX and its enantiomeric impurity d-MTX with sufficient resolution. In the presence of 1 mM BrNS, a detection limit of 3.2 × 10−7 M was achieved, about an order of magnitude better than published techniques based on UV absorption. The potential of the method was demonstrated with a degradation study and an enantiomeric purity assessment of l-MTX. Furthermore, l-MTX was determined in a cell culture extract as a proof-of-principle experiment to show the applicability of the method to biological samples

Carbon stable isotope analysis of cereal remains as a way to reconstruct water availability: preliminary results

Reconstructing past water availability, both as rainfall and irrigation, is important to answer questions about the way society reacts to climate and its changes and the role of irrigation in the development of social complexity. Carbon stable isotope analysis of archaeobotanical remains is a potentially valuable method for reconstructing water availability. To further define the relationship between water availability and plant carbon isotope composition and to set up baseline values for the Southern Levant, grains of experimentally grown barley and sorghum were studied. The cereal crops were grown at three stations under five different irrigation regimes in Jordan. Results indicate that a positive but weak relationship exists between irrigation regime and total water input of barley grains, but no relationship was found for sorghum. The relationship for barley is site-specific and inter-annual variation was present at Deir ‘Alla, but not at Ramtha and Khirbet as-Samra

A Unique Human-Fox Burial from a Pre-Natufian Cemetery in the Levant (Jordan)

New human burials from northern Jordan provide important insights into the appearance of cemeteries and the nature of human-animal relationships within mortuary contexts during the Epipalaeolithic period (c. 23,000–11,600 cal BP) in the Levant, reinforcing a socio-ideological relationship that goes beyond predator-prey. Previous work suggests that archaeological features indicative of social complexity occur suddenly during the latest Epipalaeolithic phase, the Natufian (c. 14,500–11,600 cal BP). These features include sedentism, cemeteries, architecture, food production, including animal domestication, and burials with elaborate mortuary treatments. Our findings from the pre-Natufian (Middle Epipalaeolithic) cemetery of ‘Uyun al-Hammam demonstrate that joint human-animal mortuary practices appear earlier in the Epipalaeolithic. We describe the earliest human-fox burial in the Near East, where the remains of dogs have been found associated with human burials at a number of Natufian sites. This is the first time that a fox has been documented in association with human interments pre-dating the Natufian and with a particular suite of grave goods. Analysis of the human and animal bones and their associated artefacts provides critical data on the nature and timing of these newly-developing relationships between people and animals prior to the appearance of domesticated dogs in the Natufian

Pre-agricultural plant management in the uplands of the central Zagros: the archaeobotanical evidence from Sheikh-e Abad

Prior to the emergence of agriculture in southwest Asia, sedentarising human communities were experimenting with a diverse range of wild plant species over a prolonged period. In some cases, this involved the cultivation of species that would go on to be domesticated and form the foundation of future agricultural economies. However, many forms of plant use did not follow this trajectory, and in multiple places farming was only taken up later as an established ‘package’. In this paper, we present new archaeobotanical evidence from the Early Neolithic site of Sheikh-e Abad in the central Zagros of western Iran. Sheikh-e Abad is unique in being the only settlement known to date within southwest Asia that lies at an altitude above 1000m and which has occupation spanning the agricultural transition. Thus, it provides a rare opportunity to examine pre-agricultural plant management strategies in an upland zone. Our analyses of the plant remains from Sheikh-e Abad suggest that from its earliest occupation inhabitants were unconsciously ‘auditioning’ a suite of locally available wild grasses which ultimately were never domesticated. We discuss the possible reasons for this from a socio-ecological perspective, considering both the biology and ecology of the plant species in question, as well as the ways in which they were potentially managed

Malthusian assumptions, Boserupian response in models of the transitions to agriculture

In the many transitions from foraging to agropastoralism it is debated whether the primary drivers are innovations in technology or increases of population. The driver discussion traditionally separates Malthusian (technology driven) from Boserupian (population driven) theories. I present a numerical model of the transitions to agriculture and discuss this model in the light of the population versus technology debate and in Boserup's analytical framework in development theory. Although my model is based on ecological -Neomalthusian- principles, the coevolutionary positive feedback relationship between technology and population results in a seemingly Boserupian response: innovation is greatest when population pressure is highest. This outcome is not only visible in the theory-driven reduced model, but is also present in a corresponding "real world" simulator which was tested against archaeological data, demonstrating the relevance and validity of the coevolutionary model. The lesson to be learned is that not all that acts Boserupian needs Boserup at its core.Comment: Chapter in: "Society, Nature and History: The Legacy of Ester Boserup", Springer, Vienna (in press

The Spread of Inequality

The causes of socioeconomic inequality have been debated since the time of Plato. Many reasons for the development of stratification have been proposed, from the need for hierarchical control over large-scale irrigation systems to the accumulation of small differences in wealth over time via inheritance processes. However, none of these explains how unequal societies came to completely displace egalitarian cultural norms over time. Our study models demographic consequences associated with the unequal distribution of resources in stratified societies. Agent-based simulation results show that in constant environments, unequal access to resources can be demographically destabilizing, resulting in the outward migration and spread of such societies even when population size is relatively small. In variable environments, stratified societies spread more and are also better able to survive resource shortages by sequestering mortality in the lower classes. The predictions of our simulation are provided modest support by a range of existing empirical studies. In short, the fact that stratified societies today vastly outnumber egalitarian societies may not be due to the transformation of egalitarian norms and structures, but may instead reflect the more rapid migration of stratified societies and consequent conquest or displacement of egalitarian societies over time

Mutation of the PIK3CA oncogene in human cancers

It is now well established that cancer is a genetic disease and that somatic mutations of oncogenes and tumour suppressor genes are the initiators of the carcinogenic process. The phosphatidylinositol 3-kinase signalling pathway has previously been implicated in tumorigenesis, and evidence over the past year suggests a pivotal role for the phosphatidylinositol 3-kinase catalytic subunit, PIK3CA, in human cancers. In this review, we analyse recent reports describing PIK3CA mutations in a variety of human malignancies, and discuss their possible implications for diagnosis and therapy

Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study

International audienceSentinel node biopsy (SNB) for axillary staging in breast cancer allows the application of more extensive pathologic examination techniques. Micrometastases are being detected more often, however, coinciding with stage migration. Besides assessing the prognostic relevance of micrometastases and the need for administering adjuvant systemic and regional therapies, there still seems to be room for improvement. In a population-based analysis, we compared survival of patients with sentinel node micrometastases with those with node-negative and node-positive disease in the era after introduction of SNB. Data from the population-based Eindhoven Cancer Registry were used on all ( = 6803) women who underwent SNB for invasive breast cancer in the Southeast Region of The Netherlands in the period 1996-2006. In 451 patients (6.6%) a sentinel node micrometastasis (pN1mi) was detected and in 126 patients (1.9%) isolated tumor cells (pN0(i+)). Micrometastases or isolated tumor cells in the SNB did not convey any significant survival difference compared with node-negative disease. After adjustment for age, pT, and grade, still no survival difference emerged pN1mi: [HR 0.9 (95% CI, 0.6-1.3)] and pN0(i+): [HR 0.4 (95% CI, 0.14-1.3)] and neither was the case after additional adjustment for adjuvant systemic therapy. Our practice-based study showed that the presence of sentinel node micrometastases in breast cancer patients has hardly any impact on breast cancer overall survival during the first years after diagnosis

Craniometric Data Supports Demic Diffusion Model for the Spread of Agriculture into Europe

BACKGROUND:The spread of agriculture into Europe and the ancestry of the first European farmers have been subjects of debate and controversy among geneticists, archaeologists, linguists and anthropologists. Debates have centred on the extent to which the transition was associated with the active migration of people as opposed to the diffusion of cultural practices. Recent studies have shown that patterns of human cranial shape variation can be employed as a reliable proxy for the neutral genetic relationships of human populations. METHODOLOGY/PRINCIPAL FINDINGS:Here, we employ measurements of Mesolithic (hunter-gatherers) and Neolithic (farmers) crania from Southwest Asia and Europe to test several alternative population dispersal and hunter-farmer gene-flow models. We base our alternative hypothetical models on a null evolutionary model of isolation-by-geographic and temporal distance. Partial Mantel tests were used to assess the congruence between craniometric distance and each of the geographic model matrices, while controlling for temporal distance. Our results demonstrate that the craniometric data fit a model of continuous dispersal of people (and their genes) from Southwest Asia to Europe significantly better than a null model of cultural diffusion. CONCLUSIONS/SIGNIFICANCE:Therefore, this study does not support the assertion that farming in Europe solely involved the adoption of technologies and ideas from Southwest Asia by indigenous Mesolithic hunter-gatherers. Moreover, the results highlight the utility of craniometric data for assessing patterns of past population dispersal and gene flow

Skin tribology: Science friction?

The application of tribological knowledge is not just restricted to optimizing mechanical and chemical engineering problems. In fact, effective solutions to friction and wear related questions can be found in our everyday life. An important part is related to skin tribology, as the human skin is frequently one of the interacting surfaces in relative motion. People seem to solve these problems related to skin friction based upon a trial-and-error strategy and based upon on our sense for touch. The question of course rises whether or not a trained tribologist would make different choices based upon a science based strategy? In other words: Is skin friction part of the larger knowledge base that has been generated during the last decades by tribology research groups and which could be referred to as Science Friction? This paper discusses the specific nature of tribological systems that include the human skin and argues that the living nature of skin limits the use of conventional methods. Skin tribology requires in vivo, subject and anatomical location specific test methods. Current predictive friction models can only partially be applied to predict in vivo skin friction. The reason for this is found in limited understanding of the contact mechanics at the asperity level of product-skin interactions. A recently developed model gives the building blocks for enhanced understanding of friction at the micro scale. Only largely simplified power law based equations are currently available as general engineering tools. Finally, the need for friction control is illustrated by elaborating on the role of skin friction on discomfort and comfort. Surface texturing and polymer brush coatings are promising directions as they provide way and means to tailor friction in sliding contacts without the need of major changes to the produc