• The Schlumberger array - potential and pitfalls in archaeological prospection

      Gaffney, Christopher F.; Aspinall, A. (2001)
      The orientation-sensitive performance of the Schlumberger array, when used to survey narrow, linear features, has long been recognized in geophysical prospecting for geology. However, in spite of frequent use of the array for archaeological survey, particularly in eastern Europe and the Far East, this directional effect is not apparent in the survey of walls and ditches. In order to examine the array's performance some experiments were carried out in a shallow electrolytic tank using insulating and conducting cylinders. Broadside and longitudinal traverses with systematic expansion of the current electrode spacing facilitated the production of pseudosections. The results confirmed the high selectivity of the Schlumberger response to the orientation of the feature. Broadside traverse of the conductor and longitudinal traverse of the insulator produced very large changes: much smaller signals were recorded for the alternative orientations. A subsequent experiment, however, on a simulated ditch in bedrock revealed no signal. The directional effect for a linear insulator was confirmed in field studies of a simple stone-walled structure. Implications for survey of low-contrast linear archaeological features are discussed.
    • Scientific Analysis of Steatite: Recent results.

      Clelland, Sarah-Jane; Batt, Catherine M.; Stern, Ben; Jones, R.E. (2009)
    • Scleroderma fibroblasts suppress angiogenesis via TGF-β/caveolin-1 dependent secretion of pigment epithelium-derived factor

      Liakouli, V.; Elies, Jacobo; El-Sherbiny, Y.M.; Scarcia, M.; Grant, G.; Abignano, G.; Derrett-Smith, E.C.; Esteves, F.; Cipriani, P.; Emery, P.; et al. (2018-03)
      Objectives Systemic sclerosis (SSc) is characterised by tissue fibrosis and vasculopathy with defective angiogenesis. Transforming growth factor beta (TGF-β) plays a major role in tissue fibrosis, including downregulation of caveolin-1 (Cav-1); however, its role in defective angiogenesis is less clear. Pigment epithelium-derived factor (PEDF), a major antiangiogenic factor, is abundantly secreted by SSc fibroblasts. Here, we investigated the effect of TGF-β and Cav-1 on PEDF expression and the role of PEDF in the ability of SSc fibroblasts to modulate angiogenesis. Methods P EDF and Cav-1 expression in fibroblasts and endothelial cells were evaluated by means of immunohistochemistry on human and mouse skin biopsies. PEDF and Cav-1 were silenced in cultured SSc and control fibroblasts using lentiviral short-hairpin RNAs. Organotypic fibroblast–endothelial cell cocultures and matrigel assays were employed to assess angiogenesis. Results P EDF is highly expressed in myofibroblasts and reticular fibroblasts with low Cav-1 expression in SSc skin biopsies, and it is induced by TGF-β in vitro. SSc fibroblasts suppress angiogenesis in an organotypic model. This model is reproduced by silencing Cav-1 in normal dermal fibroblasts. Conversely, silencing PEDF in SSc fibroblasts rescues their antiangiogenic phenotype. Consistently, transgenic mice with TGF-β receptor hyperactivation show lower Cav-1 and higher PEDF expression levels in skin biopsies accompanied by reduced blood vessel density. Conclusions O ur data reveal a new pathway by which TGF-β suppresses angiogenesis in SSc, through decreased fibroblast Cav-1 expression and subsequent PEDF secretion. This pathway may present a promising target for new therapeutic interventions in SSc.
    • Scottish soldiers from the Battle of Dunbar 1650: a prosopographical approach to a skeletal assemblage

      Millard, A.R.; Annis, R.G.; Caffell, A.C.; Dodd, L.L.; Fischer, R.; Gerrard, C.M.; Graves, C.P.; Hendy, J.; Mackenzie, L.; Montgomery, J.; et al. (2020)
      After the Battle Dunbar between English and Scottish forces in 1650, captured Scottish soldiers were imprisoned in Durham and many hundreds died there within a few weeks. The partial skeletal remains of 28 of these men were discovered in 2013. Building on previous osteological work, here we report wide-ranging scientific studies of the remains to address the following questions: Did they have comparable diet, health and disease throughout their lives? Did they have common histories of movement (or lack of movement) during their childhoods? Can we create a collective biography of these men? Strontium and oxygen isotope analysis of tooth enamel investigated childhood movement. Carbon and nitrogen isotope analysis of incrementally sampled dentine addressed childhood diet and nutrition. Metaproteomic analysis of dental calculus investigated oral microbiomes and food residues; this was complemented by microscopic analysis of debris in calculus from ingested materials. Selected individuals were examined for dental microwear. The extent of hydroxylation of proline in collagen was examined as a potential biomarker for scurvy. An osteobiography for each man was created using the full range of data generated about him, and these were synthesised using an approach based on the historical method for a collective biography or prosopography. The childhood residences of the men were primarily within the Midland Valley of Scotland, though some spent parts of their childhood outside the British Isles. This is concordant with the known recruitment areas of the Scottish army in 1650. Their diets included oats, brassicas and milk but little seafood, as expected for lowland rather than highland diets of the period. Childhood periods of starvation or illness were almost ubiquitous, but not simultaneous, suggesting regionally variable food shortages in the 1620s and 1630s. It is likely there was widespread low-level scurvy, ameliorating in later years of life, which suggests historically unrecorded shortages of fruit and vegetables in the early 1640s. Almost all men were exposed to burnt plant matter, probably as inhaled soot, and this may relate to the high proportion of them with of sinusitis. Interpersonal violence causing skeletal trauma was rare. Based on commonalities in their osteobiographies, we argue that these men were drawn from the same stratum of society. This study is perhaps the most extensive to date of individuals from 17th century Scotland. Combined with a precise historical context it allows the lives of these men to be investigated and compared to the historical record with unprecedented precision. It illustrates the power of archaeological science methods to confirm, challenge and complement historical evidence.
    • Screening Indian plant species for antiplasmodial properties – ethnopharmacological compared to random selection.

      Kantamreddi, Venkata Siva Satya Narayana; Wright, Colin W. (2012-12)
      In the search for biologically active plant species, many studies have shown that an ethnopharmacological approach is more effective than a random collection. In order to determine whether this is true in the case of plant species used for the treatment of malaria in Orissa, India, the antiplasmodial activities of extracts prepared from 25 traditionally used species were compared with those of 25 species collected randomly. As expected, plant species used traditionally for the treatment of malaria were more likely to exhibit antiplasmodial activity (21 species (84%) active against Plasmodium falciparum strain 3D7) than plant species collected randomly (9 species (32%)). However, of the nine active randomly collected species, eight had not previously been reported to possess antiplasmodial activity while one inactive species had been reported to be active in another study. Of the 21 active species of traditional antimalarial treatments, only six had been reported previously. This study suggests that while the selection of traditional medicinal plants is more predictive of antiplasmodial study, random collections may still be of value for the identification of new antiplasmodial species.
    • Screening of Tanzanian medicinal plants against Plasmodium falciparum and human immunodeficiency virus.

      Maregesi, S.; Van Miert, S.; Pannecouque, C.; Feiz-Haddad, M.H.; Hermans, N.; Wright, Colin W.; Vlietinck, A. J.; Aspers, S.; Pieters, L. (Theime, 2010)
      Medicinal plants used to treat infectious diseases in Bunda district, Tanzania, were screened for activity against Plasmodium falciparum and human Immunodeficiency Virus Type 1 (HIV-1, IIIB strain) and Type 2 (HIV-2, ROD strain). Antiplasmodial activity was observed for the 80% MeOH extract of Ormocarpum kirkii (root; MIC = =31.25 ¿g/mL). Combretum adenogonium (leaves), Euphorbia tirucalli (root), Harrisonia abyssinica (root), Rhyncosia sublobata (root), Sesbania sesban (root), Tithonia diversifolia (leaves), and Vernonia cinerascens (leaves; MIC value of 62.5 ¿g/mL). With regard to HIV, 80% MeOH extracts of Barleria eranthemooides (root), Cambretum adenogonium (leaves and stem bark), Elaeodedron schlechteranum (stem bark and root bark), Lannea schweinfurthii (stem bark), Terminalia mollis (stem bark and root bark), Acacia tortilis (stem bark), Ficus cycamorus (stem bark) and Indigofera colutea (shoot), as well as H2O extracts from Barleria eranthemoides (root), Combretum adenogonium (leaves and stem bark)and Terminalia mollis (stem bark and root bark) exhibited IC50 values below 10 ¿g/mL against HIV-1 (IIIB strain). The highest anti-HIV-1 activity value was obtained for the B. eranthemoides 80% MeOH root extract (IC50 value 2.1 ¿g/mL). Only a few extracts were active against HIV-2, such as the 80% MeOH extract from Lannea schweinfurthii (stem bark) and Elaeodedron schlechteranum (root bark), showing IC50 values < 10 ¿g/mL.
    • Screening of textiles for contraband drugs using portable Raman spectroscopy and chemometrics

      Ali, Esam M.A.; Edwards, Howell G.M. (2014)
      The impregnation of items of clothing with drugs of abuse that are then smuggled through airports and ports of entry is a growing problem for law enforcement. This work describes the application of portable Raman spectroscopic techniques for the analysis of a range of natural and artificial fibre items of clothing impregnated with drugs of abuse. Textile pieces were soaked with the solutions of the drugs then left overnight to dry prior to spectroscopic examination. The feasibility of detection of the characteristic Raman spectral bands in the presence of background matrix signals is demonstrated, even for dyed clothing. Definitive evidence for contamination of the items of clothing concerned can be acquired within 20-25 s, without any form of sample pre-treatment or extraction being necessary. The feasibility of automatic spectral recognition of such illicit materials by Raman spectroscopy has been investigated by searching a database stored on the spectrometer computer and the use of principal component analysis. Copyright (c) 2014 John Wiley & Sons, Ltd.
    • Scytonin, a novel cyanobacterial photoprotective pigment: calculations of Raman spectroscopic biosignatures

      Varnali, T.; Edwards, Howell G.M. (2014-03)
      The Raman spectrum of scytonin, a novel derivative of the parent scytonemin, is predicted from DFT calculations of the most stable, lowest energy, conformational structure. The diagnostic importance of this study relates to the spectral ability to discriminate between scytonemin and its derivatives alone or in admixture with geological matrices from identified characteristic Raman spectral signatures. The successful interpretation of biosignatures from a wide range of cyanobacterial extremophilic colonization in terrestrial and extraterrestrial scenarios is a fundamental requirement of the evaluation of robotic spectroscopic instrumentation in search for life missions. Scytonemin is produced exclusively by cyanobacterial colonies in environmentally stressed habitats and is widely recognized as a key target biomarker molecule in this enterprise. Here, the detailed theoretical analysis of the structure of scytonin enables a protocol to be established for the recognition of characteristic bands in its Raman spectrum and to accomplish the successful differentiation between scytonin and scytonemin as well as other scytonemin derivatives such as the dimethoxy and tetramethoxy compounds that have been isolated from cyanobacterial colonies but which have not yet been characterized spectroscopically. The results of this study will facilitate an extension of the database capability for miniaturized Raman spectrometers which will be carried on board search for life robotic missions to Mars, Europa, and Titan.
    • Searching for new treatments of malaria

      Wright, Colin W. (2015-10)
      The aim of this chapter is to illustrate some current developments in natural product-derived antimalarial drugs. Traditional medicines have provided two of our most important antimalarial drugs (quinine and artemisinin) and have the potential to provide many novel antimalarial lead compounds of which several examples will be discussed. In addition, well- known natural antimalarials such as artemisinin continue to be an important focus of research and there is also increasing interest in investigating natural product sources that have not been traditionally used as antimalarials such as marine species of plants and animals. Assays based on specific malaria parasite targets such as thioredoxin reductase and heat shock protein have been employed to screen extracts and/or compounds and these have resulted in the identification of a number of potentially interesting antiplasmodial agents. However, since many victims of malaria are unable to afford antimalarial drugs, another approach adopted by some charities/NGO’s is to encourage people to grow their own medicinal plants such as Artemisia annua; some recent studies on this theme will be discussed.
    • A seasonal switch in histone deacetylase gene expression in the hypothalamus and their capacity to modulate nuclear signaling pathways

      Stoney, P.N.; Rodrigues, D.; Helfer, Gisela; Khatib, T.; Ashton, A.; Hay, E.A.; Starr, R.; Kociszewska, D.; Morgan, P.J.; McCaffery, P.J. (2016)
      Seasonal animals undergo changes in physiology and behavior between summer and winter conditions. These changes are in part driven by a switch in a series of hypothalamic genes under transcriptional control by hormones and, of recent interest, inflammatory factors. Crucial to the control of transcription are histone deacetylases (HDACs), generally acting to repress transcription by local histone modification. Seasonal changes in hypothalamic HDAC transcripts were investigated in photoperiod-sensitive F344 rats by altering the day-length (photoperiod). HDAC4, 6 and 9 were found to change in expression. The potential influence of HDACs on two hypothalamic signaling pathways that regulate transcription, inflammatory and nuclear receptor signaling, was investigated. For inflammatory signaling the focus was on NF-κB because of the novel finding made that its expression is seasonally regulated in the rat hypothalamus. For nuclear receptor signaling it was discovered that expression of retinoic acid receptor beta was regulated seasonally. HDAC modulation of NF-κB-induced pathways was examined in a hypothalamic neuronal cell line and primary hypothalamic tanycytes. HDAC4/5/6 inhibition altered the control of gene expression (Fos, Prkca, Prkcd and Ptp1b) by inducers of NF-κB that activate inflammation. These inhibitors also modified the action of nuclear receptor ligands thyroid hormone and retinoic acid. Thus seasonal changes in HDAC4 and 6 have the potential to epigenetically modify multiple gene regulatory pathways in the hypothalamus that could act to limit inflammatory pathways in the hypothalamus during long-day summer-like conditions.
    • Secretory phospholipase A2 as a tumor specific trigger for targeted delivery of a novel class of liposomal prodrug anticancer etherlipids

      Gill, Jason H.; Bibby, Michael C.; Jensen, S.S.; Shnyder, Steven D. (2004)
      The use of many common clinically relevant chemotherapeutics is often limited due to insufficient delivery to the tumor and dose-limiting systemic toxicities. Therefore, therapeutics that specifically target tumor cells and are nontoxic to normal cells are required. Here, we report the development of a novel class of liposomes composed of lipid prodrugs, which use the increased secretory phospholipase A2 type IIA (sPLA2) activity of the tumor microenvironment as a trigger for the release of anticancer etherlipids (AEL). Treatment of sPLA2-secreting tumor cells in vitro with liposomes consisting of proAELs resulted in growth inhibition comparable with addition of the AELs alone. Using a specific sPLA2 inhibitor, we showed the low cytotoxicity of the nonhydrolyzed proAEL liposomes and have proven the sPLA2 dependency of the activation of proAELs to cytotoxic AELs. In addition, we showed that our proAEL liposomes circumvent the inherent hemolytic toxicities associated with the use of etherlipids, thereby allowing i.v. administration of such therapeutics as nontoxic prodrug liposomes. Furthermore, using a sPLA2-secreting human colon cancer xenograft model, we showed that the proAEL liposomes are capable of inducing a tumor growth delay in vivo. Taken together, these data support the validity of this novel tumor-selective liposomal prodrug delivery strategy. This new approach also provides a promising system for tumor-selective delivery and release of conventional chemotherapeutics encapsulated in the sPLA2-degradable prodrug liposomes.
    • Sedimentary DNA from a submerged site reveals wheat in the British Isles 8000 years ago

      Smith, O.; Momber, G.; Bates, R.; Garwood, P.; Fitch, Simon; Pallen, M.; Gaffney, Vincent L.; Allaby, R.G. (2015-02-27)
      The Mesolithic-to-Neolithic transition marked the time when a hunter-gatherer economy gave way to agriculture, coinciding with rising sea levels. Bouldnor Cliff, is a submarine archaeological site off the Isle of Wight in the United Kingdom that has a well-preserved Mesolithic paleosol dated to 8000 years before the present. We analyzed a core obtained from sealed sediments, combining evidence from microgeomorphology and microfossils with sedimentary ancient DNA (sedaDNA) analyses to reconstruct floral and faunal changes during the occupation of this site, before it was submerged. In agreement with palynological analyses, the sedaDNA sequences suggest a mixed habitat of oak forest and herbaceous plants. However, they also provide evidence of wheat 2000 years earlier than mainland Britain and 400 years earlier than proximate European sites. These results suggest that sophisticated social networks linked the Neolithic front in southern Europe to the Mesolithic peoples of northern Europe.
    • Seeing beyond the site - an innovative approach to examining prehistoric Ireland

      Becker, Katharina; Gearey, B.; Eogan, J.; McClatchie, M.; Nagle, C.; Armit, Ian (2016)
    • Seeing or hearing? Perceptual independence, modality confusions, and crossmodal congruity effects with focused and divided attention

      McIlhagga, William H.; Baert, J.; Bundesen, C.; Larsen, A. (2003)
      Observers were given brief presentations of pairs of simultaneous stimuli consisting of a visual and a spoken letter. In the visual focused-attention condition, only the visual letter should be reported; in the auditory focused-attention condition, only the spoken letter should be reported; in the divided-attention condition, both letters, as well as their respective modalities, should be reported (forced choice). The proportions of correct reports were nearly the same in the three conditions (no significant divided-attention decrement), and in the divided-attention condition, the probability that the visual letter was correctly reported was independent of whether the auditory letter Was correctly reported. However, with a probability much higher than chance, the observers reportedihearing the visual stimulus letter or seeing the spoken stimulus letter (modality confusions). The strength of the effect was nearly the same with focused as with divided attention. We also discovered a crossmodal congruity effect: Performance was better when the two letters in a stimulus pair were the same than when they differed in type.
    • Segmental mobility studies of poly(N-isopropyl acrylamide) interactions with gold nanoparticles and its use as a thermally driven trapping system

      Swift, Thomas; Rehman, K.; Surtees, Alexander P.H.; Hoskins, Richard; Hickey, Stephen G. (2018-07)
      Thermal desolvation of poly(N‐isopropylacrylamide) (PNIPAM) in the presence of a low concentration of gold nanoparticles incorporates the nanoparticles resulting in suspended aggregates. By covalently incorporating <1% acenaphthylene into the polymerization feed this copolymer is enabled to be used as a model to study the segmental mobility of the PNIPAM backbone in response to gold nanoparticles both below and above the desolvation temperature, showing that there is a physical conformational rearrangement of the soluble polymer at ultralow nanoparticle loadings, indicating low affinity interactions with the nanoparticles. Thermal desolvation is capable of extracting >99.9% of the nanoparticles from their solutions and hence demonstrates that poly(N‐isopropylacrylamide) can act as an excellent scrubbing system to remove metallic nanomaterial pollutants from solution.
    • Selecting distending medium for out-patient hysteroscopy. Does it really matter?

      O'Donovan, Peter J.; Kaponis, A.; Makrydimas, G.; Paschopoulos, M.; Zikopoulos, K.; Alamanos, Y.; Paraskevaidis, E. (2004)
      The aim of this prospective randomized study was to evaluate the role of carbon dioxide (CO2) and normal saline for diagnostic accuracy in out-patient hysteroscopy. Women admitted to our Department in order to undergo total abdominal hysterectomy also underwent diagnostic hysteroscopy, 12¿24 h prior to surgery. The selection of distending medium was made after randomization. Two groups of patients were formed, group A (CO2; n=39) and group B (normal saline; n=35). More than half of the women in the study population were post-menopausal. Post-hysteroscopy, all women were asked to rank any symptom that they felt during the procedure on a 4-point scale (0 = none; 1 = mild; 2 = severe; 3 = inability to perform hysteroscopy). The hysteroscopic diagnosis was compared with the macroscopic findings and the histological examination of the surgical specimen after hysterectomy. The percentage who completed hysteroscopy was 89.74% within group A and 97.14% within group B. Most patients of both groups felt some pain of mild intensity. The diagnostic accuracy of hysteroscopy was similar for both media when major pathology [large polyps (group A 91.7%; group B 92.7%), myomas (group A 81.25%; group B 92.7%) and/or hyperplasia (group A 87.5%; group B 90.2%)] of the endometrial cavity was detected. In contrast, in cases of minor pathology (small polyps, mucosal elevations, crypts, hypervascularization), hysteroscopy with saline presented with significantly higher diagnostic accuracy (85.4%) compared with hysteroscopy with CO2 (64.6%). In out-patient hysteroscopy, CO2 and normal saline were comparable with regard to patient discomfort and for the detection of major pathology of the endometrial cavity. Normal saline seems to be the most appropriate medium for the detection of minor pathology of the endometrial cavity.
    • Selective and quantitative analysis of 4-hydroxybenzoate preservatives by microemulsion electrokinetic chromatography

      Clark, Brian J.; Altria, K.D.; Mahuzier, P.E. (Elsevier Science Direct, 27/07/2001)
      A microemulsion electrokinetic chromatography (MEEKC) method has been developed and validated for the determination of 4-hydroxybenzoates and their impurities. These materials are commonly known as parabens and are widely used as preservatives in foods, cosmetics and pharmaceuticals. The method was shown to be selective and quantitative for the methyl, ethyl, propyl and butyl esters of 4-hydroxybenzoic acid. An internal standard, 4-hydroxyacetophenone, was employed to improve injection precision and detector linearity. In addition, 4-hydroxybenzoic acid, the major degradent, could also be monitored at the 0.1% (m/m) level. The method was successfully validated for assay and detection of the impurities in 4-hydroxybenzoic acid methyl ester and 4-hydroxybenzoic acid propyl ester samples and for the determination of 4-hydroxybenzoic acid methyl ester in a liquid pharmaceutical formulation. The determination of paraben content by MEEKC in a liquid sample was consistent with HPLC analysis. This work is the first reported validated MEEKC method and shows that the methodology can be successfully implemented into routine quality control testing.
    • Selective Biodegradation in Hair Shafts Derived from Archaeological, Forensic and Experimental Contexts

      Wilson, Andrew S.; Dodson, Hilary I.; Pollard, A. Mark; Tobin, Desmond J.; Janaway, Robert C. (2007)
      Background Hair is degraded by the action of both dermatophytic and nondermatophytic microorganisms. The importance of understanding hair sample condition in archaeological and forensic investigation highlights the need for a detailed knowledge of the sequence of degradation in samples that have been either buried or left exposed at the ground surface. Objectives To investigate the sequence of biodegradative change to human terminal scalp hair from archaeological and forensic contexts. Methods Cut modern scalp hair from three individuals with caucasoid-type hair was inoculated with soil microorganisms through soil burial in the field and under laboratory conditions to produce experimentally degraded samples. The degraded hair fibres were subjected to detailed histological examination using a combination of high-resolution light microscopy, transmission electron microscopy and scanning electron microscopy to investigate the nature and sequence of degradative change to hair structural components. Results/discussion Degradation was found to occur first within the least structurally robust components that afford the least resistance to microbial/chemical attack. The sequence of degradation (most to least-reflecting degree of vulnerability) in the hair cuticle was as follows: (1) intercellular 6-layer (cell membrane complex); (2) endocuticle; (3) cell membrane ß-layers; (4) exocuticle; (5) epicuticle; and (6) A-layer. In the hair cortex this was as follows: (I) intercellular 6-layer (cell membrane complex); (II) cell membrane ß-layers; (III) intermacrofibrillar matrix/nuclear remnants; (IV) microfibrils; (V) intermicrofibrillar matrix; and (VI) pigment granules (the hair fibre component that was the least vulnerable to degradation). Conclusions The selective progress of degradation in the hair shaft has been charted and this provides a basis for further histological work in better understanding the condition of hair fibres derived from archaeological or forensic contexts as well as being relevant to investigation of diseased hair, in particular hair infected by dermatophytes and hair weakened by genetic hair shaft abnormalities.