The Beach in Anglophone Literatures and Cultures: Reading Littoral Space

From early colonial encounters to the ecological disasters of the twenty-first century, the performativity of contact has been a crucial element in the political significance of the beach. Conceptualising the beach as a creative trope and as a socio-cultural site, as well as an aesthetically productive topography, this collection examines its multiplicity of meanings and functions as a natural environment engendering both desire and fear in the human imagination from the Victorian period to the present. The contributors examine literature, film, and art, in addition to moments of encounter and environmental crisis, to highlight the beach as a social space inspiring particular codes of behaviour and specific discourses, as a geographical frontier between land and water, as an historical site of contact and conflict, and as a vacationscape promising regeneration and withdrawal from everyday life. The diversity of the beach is reflected in the geographical range, with essays on locales and texts from Britain, Ireland, the Caribbean, South Africa, the United States, Polynesia, and New Zealand. Focusing on the changed function of the beach as a result of processes of industrialisation and the rise of a modern leisure and health culture, this interdisciplinary volume theorises the beach as a demarcater of the precarious boundary between land and the sea, as well as between nature and culture.

Vertical mobility in the Swiss Alps. The alpine pass Schnidejoch and indications of early pastoralism.

Since 2003 a melting ice field on the Schnidejoch pass (2756 a.s.l) delivered several hundred objects from the Neolithic, the Bronze and Iron Age as well as from Roman and Early Medieval times. The oldest finds date to the beginning 5th millennium BC, the youngest ones date around 1000 AD. Most of the objects stem from the Neolithic and the Bronze Age and are of organic origin. A series of more than 70 radiocarbon dates confirms that the Schnidejoch pass, linking the Bernese Highlands with the River Rhone valley, was in use at least from 4800–4500 BC on. The accessibility of the pass was easy when the glaciers descending from the nearby Wildhorn mountain range (peak on 3248 a.s.l) were in a retreating phase. In contrary glacier advances closed the way to the pass. In 2010 a palaeoecological study of sediment cores researched nearby Lake Iffig (2065 m a.s.l.). The results show clear indications of early human impact in this alpine area. Linking archaeological finds from Schnidejoch pass and River Rhone valley with the palaeoecological data can be interpreted as early indications of alpine pastoralism and transhumance. The combined archaeological and paleoecolical research allows to explain vertical mobility in the Swiss Alps.

Material culture entanglements of early wetland sites in central Switzerland (4300-3850 BC)

In central Switzerland, the earliest wetland settlements with definitely attested finds and features date into the second half of the 5th millennium BC. Combining the information they have yielded with that from dryland sites, we can construct a detailed picture of material culture at the turn of the 5th to the 4th millennium. On this basis, the definition of clearly delimited archaeological cultures seems questionable, not only from a theoretical point of view. Similiarities and differences in the pottery show small-scale regional units defined via vessel forms as well as stylistic and technological aspects. Yet there are also inter-regional connections: roundbased vessels with opposing handles are typical for Lake Zurich, central and western Switzerland, the Valais and the central Rhône valley. In turn, ‘foreign‘ types such as shoulder-band beakers indicate regular connections between groups living in central Switzerland and those in Alsace and southern Germany. Are these beakers ‘imports‘ or locally produced items (‘imitations‘) indicating the adoption of ‘foreign‘ vessel types and concepts? This and similar material culture phenomena result in a picture of many material entanglements and problematise the kinds of relationships and mobility which might have existed. Our paper addresses these questions and discusses how and whether these interwoven connections changed in the early 4th millennium.

The Five Senses in Medieval and Early Modern England

Edited by Annette Kern-Stähler, Beatrix Busse, and Wietse de Boer The essays collected in The Five Senses in Medieval and Early Modern England examine the interrelationships between sense perception and secular and Christian cultures in England from the medieval into the early modern periods. They address canonical texts and writers in the fields of poetry, drama, homiletics, martyrology and early scientific writing, and they espouse methods associated with the fields of corpus linguistics, disability studies, translation studies, art history and archaeology, as well as approaches derived from traditional literary studies. Together, these papers constitute a major contribution to the growing field of sensorial research that will be of interest to historians of perception and cognition as well as to historians with more generalist interests in medieval and early modern England.

14-3-3 zeta overexpression in early stage breast disease and tumor progression

Recent progress in diagnostic tools allows many breast cancers to be detected at an early pre-invasive stage. Thus, a better understanding of the molecular basis of early breast cancer progression is essential. 14-3-3 is a family of highly conserved and ubiquitously expressed proteins that are expressed in all eukaryotic organisms. In mammals there are seven isoforms, which bind to phosphor-serine/threonine residues regulating essential cellular processes such as signal transduction, cell cycle progression, and apoptosis. Our laboratory has discovered that a particular 14-3-3 family member, Zeta, is overexpressed in over 40% of breast tumor tissues. Furthermore, I examined the stage of breast disease in which 14-3-3ζ overexpression occurs and found that increased expression of 14-3-3ζ begins at the stage of atypical ductal hyperplasia, a very early stage of breast disease that confers increased risk for progress toward breast cancer. To determine whether 14-3-3ζ overexpression is a decisive early event in breast cancer, I overexpressed 14-3-3ζ in MCF10A cells, a non-transformed mammary epithelial cell (MEC) line and examined its impact on acini formation in a three dimensional (3D) culture model which simulates a basic unit of structure in the mammary gland. I discovered that 14-3-3ζ overexpression severely disrupted the acini architecture resulting in the disruption of polarity and luminal filling. Both are critical morphological events in the pre-neoplastic breast disease. This thesis focuses on the molecular mechanism of luminal filling. Proper lumen formation is a result of anoikis, a specific type apoptosis of cells not attached to the basement membrane. I found that 14-3-3ζ overexpression conferred a resistance to anoikis. Additionally, 14-3-3ζ overexpression in MCF10A cells and in MECs from 14-3-3ζ transgenic mice reduced expression of p53, which is known to mediate anoikis. Mechanistically, 14-3-3ζ induced hyperactivation of the PI3K/Akt pathway which led to phosphorylation and translocation of the MDM2 to the nucleus resulting in increased p53 degradation. Ectopic expression of p53 restored luminal apoptosis in 14-3-3ζ overexpressing MCF10A acini in 3D cultures. These data suggest that 14-3-3ζ overexpression is a critical event in early breast disease and down-regulation of p53 is one of the mechanisms by which 14-3-3ζ alters MEC acini structure and may increase the risk of progression to breast cancer. ^

Identification of an early T cell progenitor for a pathway of T cell maturation in the bone marrow

We have identified a rare (≈0.05–0.1%) population of cells (Thy-1hiCD16+CD44hiCD2−TCRαβ−B220−Mac-1−NK1.1−) in the adult mouse bone marrow that generates CD4+ and CD8+ TCRαβ+ T cells after tissue culture for 48 hr in the presence of Ly5 congenic marrow cells. The essential stages in the maturation of the progenitors were determined; the stages included an early transition from CD2−CD16+CD44hiTCRαβ− to CD2+CD16int/−CD44int/−TCRαβ− cells, and a later transition to CD4+CD8+TCRαβ+ double-positive T cells that rapidly generate the CD4+ and CD8+ single-positive T cells. The maturation of the progenitors is almost completely arrested at the CD2+TCRαβ− stage by the presence of mature T cells at the initiation of cultures. This alternate pathway is supported by the marrow microenvironment; it recapitulates critical intermediary steps in intrathymic T cell maturation.

Endogenous expression of Müllerian inhibiting substance in early postnatal rat Sertoli cells requires multiple steroidogenic factor-1 and GATA-4-binding sites

Müllerian inhibiting substance (MIS) is a key element required to complete mammalian male sex differentiation. The expression pattern of MIS is tightly regulated in fetal, neonatal, and prepubertal testes and adult ovaries and is well conserved among mammalian species. Although several factors have been shown to be essential to MIS expression, its regulatory mechanisms are not fully understood. We have examined MIS promoter activity in 2-day postnatal primary cultures of rat Sertoli cells that continue to express endogenous MIS mRNA. Using this system, we found that the region between human MIS−269 and −192 is necessary for full MIS promoter activity. We identified by DNase I footprint and electrophoretic mobility-shift analyses a distal steroidogenic factor-1 (SF-1)-binding site that is essential for full promoter activity. Mutational analysis of this new distal SF-1 site and the previously identified proximal SF-1 site showed that both are necessary for transcriptional activation. Moreover, the proximal promoter also contains multiple GATA-4-binding sites that are essential for functional promoter activity. Thus multiple SF-1- and GATA-4-binding sites in the MIS promoter are required for normal tissue-specific and developmental expression of MIS.

Coculturing diverse clonal populations prevents the early-stage neoplastic progression that occurs in the separate clones

Most human cancers are of monoclonal origin and display many genetic alterations. In an effort to determine whether clonal expansion itself could account for the large number of genetic alterations, we compared spontaneous transformation in cloned and uncloned populations of NIH 3T3 cells. We have reported that progressive transformation of these cells, which is driven by the stress of prolonged contact inhibition at confluence, occurs far more frequently in cultures of recent monoclonal origin than in their uncloned progenitors. In the present work we asked how coculturing six clones at early and late stages of progression would affect the dynamics of transformation in repeated rounds of confluence. When coculture started with clones in early stages of transformation, marked by light focus formation, there was a strong inhibition of the progression to the dense focus formation that occurred in separate cultures of the individual clones. In contrast, when coculture started after the individual clones had progressed to dense focus formation, there was selection of transformants from the clone producing the largest and densest foci. Mixing the cells of a single clone with a large excess of uncloned cells from a subline that was refractory to transformation markedly decreased the size of dense foci from clones in transit from light to dense focus formation, but had much less effect on foci from clones with an established capacity for dense focus formation. The major finding of protection against progression by coculturing clones in early stages of transformation suggests that the expansion of a rogue clone in vivo increasingly isolates many of its cells from genetically stabilizing interactions with surrounding clones. Such clonal isolation might account for the increase in mutation rates associated with the dysplasia in colorectal adenomas that signifies the transition between benign and malignant growth.

The Minoans and their interpretations of nature in comparison with succeeding cultures

"Some of the finest interpretations ot nature ever to be expressed by an were painted by the Minoan fresco artists of Crete. Discovered only since the turn of the 20th century, the Kinoan Bronze Age civilization was amazingly progressive and notably modern. Apparently, the Minoans gained their high standard of living mainly through economic prosperity and secarity provided by a great navy. Arts, architecture and craft relice uncovered have been numerous, well-preserved and invaluable sources of historical knowledge"

Trade relations between the Mycenaean Greeks and the civilizations of the Eastern Mediterranean in the Late Bronze Age

The Mycenaean Greeks are often assumed to have been in contact with the civilizations of the Mediterranean throughout the Late Bronze Age. The extent of this contact however is not as clearly understood, and the archaeological evidence that has survived provides a sample of what must have exchanged hands. This thesis will examine the archaeological, textual and iconographic evidence from a number of sites and sources, from the Anatolian plains to the Kingdom of Egypt and major settlements in-between during the Late Bronze Age to examine what trade may have looked like for the Mycenaeans. Due to the extensive finds in some regions and a lack of evidence in others, this paper will also try to understand the relationship between the Mycenaeans and other cultures to determine whether a trade embargo was enacted on the Mycenaeans by the Central Anatolian Hittites during this period, or whether other factors contributed to the paucity of objects in Central Anatolia.

Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

The metacestode (larval) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV), comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

Archaeological sites in China during the Neolithic and Bronze Age

A total of 51,074 archaeological sites from the early Neolithic to the early Iron Age (c. 8000-500 BC), with a spatial extent covering most regions of China (c. 73-131°E and c. 20-53°N), were analysed over space and time in this study. Site maps of 25 Chinese provinces, autonomous regions and municipalities, published in the series 'Atlas of Chinese Cultural Relics', were used to extract, digitalise and correlate its archaeological data. The data were, in turn, entered into a database using a self-developed mapping software that makes the data, in a dynamic way, analysable as a contribution to various scientific questions, such as population growth and migrations, spread of agriculture and changes in subsistence strategies. The results clearly show asynchronous patterns of changes between the northern and southern parts of China (i.e. north and south of the Yangtze River, respectively) but also within these macro-regions. In the northern part of China (i.e. along the Yellow River and its tributaries and in the Xiliao River basin), the first noticeable increase in the concentration of Neolithic sites occurred between c. 5000 and 4000 BC; however, highest site concentrations were reached between c. 2000 and 500 BC. Our analysis shows a radical north-eastern shift of high site-density clusters (over 50 sites per 100 * 100 km grid cell) from the Wei and middle/lower Yellow Rivers to the Liao River system sometime between 2350 BC and 1750 BC. This shift is hypothetically discussed in the context of the incorporation of West Asian domesticated animals and plants into the existing northern Chinese agricultural system. In the southern part of China, archaeological sites do not show a noticeable increase in the absolute number of sites until after c. 1500 BC, reaching a maximum around 1000 BC.

Early patterns of sexual activity: age cohort differences in Australia

Patterns of first sexual activity among Australians born between the 1940s and 1980s were analysed using data from a national telephone survey of 1784 adults (876 males; 908 females). Sixty-one percent of those randomly selected from the Australian electoral roll and contactable by telephone responded. Many trends, including earlier first intercourse - from 20 to 18 years (females) and 18.8 to 17.8 years (males) - were established with the 40-49 year cohort, whose sexual debut was in the late 1960s-70s. Significant age-cohort effects saw women in the contemporary (18-29 year) cohort draw level with males for age at first intercourse and first sex before age 16 and before leaving school. First intercourse contraceptive use climbed from 30% to 80'%. Condom use quadrupled to 70%. Australian age-cohort effects are remarkably consistent with those in similar western cultures: gender convergence in sexual experience and increasing avoidance of sexually transmitted disease and pregnancy. If such trends continue, positive long-term outcomes for health and social wellbeing should result.