730 research outputs found

    Geology of Cat Island, Bahamas: A Field Trip Guide

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    See other Smith authored Field Trip Guides of Gerace Research Centre

    Pleistocene and Holocene Carbonate Environments on San Salvador Island, Bahamas: A Field Trip Guide

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    Although isolated and small in size, San Salvador Island is in many ways a unique place - an all carbonates setting on a small, tectonically stable platform, surrounded by deep oceanic waters, and an historical footnote as the widely accepted first landing site of Christopher Columbus in the New World in 1492. Columbus\u27 stay here was brief, and the major events of subsequent history largely have passed San Salvador by. This is not a tourist island; the natural beauty, floras, and faunas of the Bahamas are well preserved here. The overview theme of this series of field excursions on San Salvador will be interpretation of paleodepositional environments for the well-exposed Pleistocene and Holocene carbonate rocks that cap the island and recognition of modem analogues from the varied carbonate environments found on the island and its surrounding shelf. Questions of sea level history, diagenetic change, and the surficial processes operating on carbonate island terranes also will be considered. Our trip will begin with a low-attitude overflight to view features of the main Bahama platform enroute to San Salvador, which lies just beyond the eastern edge of the platform. The field trip leaders all have been working on San Salvador and elsewhere in the Bahamas for the past decade. We have experienced the good and the bad - a pleasant tropical climate, warm and alive marine waters, a generally unspoiled setting, and the friendly Bahamian people, along with sometimes fierce no-see-um attacks, sun-burnt skin, and unexpected soakings from tropical storms. Throughout, the experiences have been rewarding and the challenges of geologic interpretation great. We look forward to sharing some of our findings and experiences with you. Welcome to the Bahamas and San Salvador Island! See other Smith authored Field Trip Guides of Gerace Research Centre

    Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

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    Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

    A survey of case studies on the use of forensic three-dimensional printing in England and Wales

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    3D printing has rapidly developed and been applied in forensic science due to its use in creating demonstrations for courts of law. Much of the literature on this specific topic has focused on the use of 3D printed models in academia, the potential influence on a jury, and its use as a long-term documentation process, but with few actual forensic case examples. This paper offers an insight into the development of 3D printing in forensic practice and how 3D printing is currently being used in the criminal justice system in England and Wales. A series of case reports were gathered from multiple police forces and forensic practitioners in the UK to identify how 3D printing was being used. These discussions established who was requesting 3D printed exhibits, what type of technologies were being utilised, what type of exhibits were being printed, and resulting feedback for the use of 3D printed material within a criminal case. As a result, this research demonstrates the current use of 3D printing in England and Wales, discussing the associated cases that have been known to incorporate 3D prints. Likewise, this work explores the limitations that have been encountered by forensic practitioners and identifies a series of research questions that should be considered in future investigations

    Being tolerated and being discriminated against:Links to psychological well-being through threatened social identity needs

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    We investigated whether and how the experience of being tolerated and of being discriminated against are associated with psychological well‐being in three correlational studies among three stigmatized groups in Turkey (LGBTI group members, people with disabilities, and ethnic Kurds, total N = 862). Perceived threat to social identity needs (esteem, meaning, belonging, efficacy, and continuity) was examined as a mediator in these associations. Structural equation models showed evidence for the detrimental role of both toleration and discrimination experiences on positive and negative psychological well‐being through higher levels of threatened social identity needs. A mini‐meta analysis showed small to moderate effect sizes and toleration was associated with lower positive well‐being through threatened needs among all three stigmatized groups

    ‘This restless enemy of all fertility’: exploring paradigms of coastal dune management in Western Europe over the last 700 years

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    Drifting sand has inundated settlements and damaged agricultural land along the coasts of Western Europe for the last 700 years. The need to control sand migration has been an important driver of the management of coastal sand dunes and here we analyse original archival materials to provide new insights into historically changing coastal dune management practices. Records of coastal sand movement in Denmark, The Netherlands, Britain, Ireland and France were reviewed and three distinct management approaches were identified. The ways in which these approaches have played out in space and time were examined with particular reference to records from landed estates in Britain and Ireland. We demonstrate how historical evidence can be used to inform contemporary debates on dune management strategy and practice. We propose a new place-based approach to the future management of coastal dunes that can incorporate both expert and locally produced ‘knowledges’ and that is underpinned by an understanding of how both natural forces and human interventions have shaped these dune landscapes over time

    High Mitochondrial DNA Stability in B-Cell Chronic Lymphocytic Leukemia

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    BACKGROUND: Chronic Lymphocytic Leukemia (CLL) leads to progressive accumulation of lymphocytes in the blood, bone marrow, and lymphatic tissues. Previous findings have suggested that the mtDNA could play an important role in CLL. METHODOLOGY/PRINCIPAL FINDINGS: The mitochondrial DNA (mtDNA) control-region was analyzed in lymphocyte cell DNA extracts and compared with their granulocyte counterpart extract of 146 patients suffering from B-Cell CLL; B-CLL (all recruited from the Basque country). Major efforts were undertaken to rule out methodological artefacts that would render a high false positive rate for mtDNA instabilities and thus lead to erroneous interpretation of sequence instabilities. Only twenty instabilities were finally confirmed, most of them affecting the homopolymeric stretch located in the second hypervariable segment (HVS-II) around position 310, which is well known to constitute an extreme mutational hotspot of length polymorphism, as these mutations are frequently observed in the general human population. A critical revision of the findings in previous studies indicates a lack of proper methodological standards, which eventually led to an overinterpretation of the role of the mtDNA in CLL tumorigenesis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that mtDNA instability is not the primary causal factor in B-CLL. A secondary role of mtDNA mutations cannot be fully ruled out under the hypothesis that the progressive accumulation of mtDNA instabilities could finally contribute to the tumoral process. Recommendations are given that would help to minimize erroneous interpretation of sequencing results in mtDNA studies in tumorigenesis

    Formal modeling and analysis of cognitive agent behavior

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    From an external perspective, cognitive agent behavior can be described by specifying (temporal) correlations of a certain complexity between stimuli (input states) and (re)actions (output states) of the agent. From an internal perspective the agent’s dynamics can be characterized by direct (causal) temporal relations between internal and mental states of the agent. The latter type of specifications can be represented in a relatively simple, executable format, which enables different types of analysis of the agent’s behavior. In particular, simulations of the agent’s behavior under different (environmental) circumstances can be explored. Furthermore, by applying verification techniques, automated analysis of the consequences of the agent’s behavior can be carried out. To enable such types of analysis when only given an external behavioral specification, this has to be transformed first into some type of executable format. An automated procedure for such a transformation is proposed in this paper. The application of the transformation procedure is demonstrated for a number of cases, showing examples of the types of analysis as mentioned for different forms of behavior

    Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death

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    Sudden cardiac death (SCD) in patients with heart failure (HF) is allied with an imbalance in reduction and oxidation (redox) signaling in cardiomyocytes; however, the basic pathways and mechanisms governing redox homeostasis in cardiomyocytes are not fully understood. Here, we show that cytochrome b5 reductase 3 (CYB5R3), an enzyme known to regulate redox signaling in erythrocytes and vascular cells, is essential for cardiomyocyte function. Using a conditional cardiomyocyte-specific CYB5R3-knockout mouse, we discovered that deletion of CYB5R3 in male, but not female, adult cardiomyocytes causes cardiac hypertrophy, bradycardia, and SCD. The increase in SCD in CYB5R3-KO mice is associated with calcium mishandling, ventricular fibrillation, and cardiomyocyte hypertrophy. Molecular studies reveal that CYB5R3-KO hearts display decreased adenosine triphosphate (ATP), increased oxidative stress, suppressed coenzyme Q levels, and hemoprotein dysregulation. Finally, from a translational perspective, we reveal that the high-frequency missense genetic variant rs1800457, which translates into a CYB5R3 T117S partial loss-of-function protein, associates with decreased event-free survival (~20%) in Black persons with HF with reduced ejection fraction (HFrEF). Together, these studies reveal a crucial role for CYB5R3 in cardiomyocyte redox biology and identify a genetic biomarker for persons of African ancestry that may potentially increase the risk of death from HFrEF.These studies were supported by NIH grants R35 HL 161177 (to ACS), R01 HL 133864 (to ACS), R01 HL 128304 (to ACS), R41 HL15098 (to GS), R01 GM 122091 (to PHT), GM125944 (to FJS), R01 DK112854 (to FJS), R21 NS112787 (to MF), NS121706 (to YLW), EB023507 (to YLW), F31 HL149241 (to HMS), and F31 HL151173 (to JCG). Support was also provided by American Heart Association grants 19EIA34770095 (to ACS), AHA 18CDA34140024 (to YLW), and 19PRE34380152 (to NTC); the Spanish Ministry of Health (grant FIS PI17-01286); Junta de Andalucía BIO-177 and the FEDER Funding Program from the European Union and CIBERER (U729)-ISCIII (to PN); Department of Defense W81XWH1810070 (to YLW); and Vitalant. This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. Specifically, this work used the HTC cluster, which is supported by NIH award number S10OD028483.Peer reviewe
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