The difluoromethylene (CF2) group in aliphatic chains : synthesis and conformational preference of palmitic acids and nonadecane containing CF2 groups

Funding: ERC Advanced Investigator Grant (D.O'H).The syntheses of palmitic acids and a nonadecane are reported with CF2 groups located 1,3 or 1,4 to each other along the aliphatic chain. Specifically 8,8,10,10- and 8,8,11,11-tetrafluorohexadecanoic acids (6b and 6c) are prepared as well as the singly modified analogue 8,8-difluorohexadecanoic acid (6a). Also 8,8,11,11-tetrafluorononadecane (27) is prepared as a pure hydrocarbon containing a 1,4-di-CF2 motif. The modified palmitic acids are characterized by differential scanning calorimetry (DSC) to determine melting points and phase behaviour relative to palmitic acid (62.5 degrees C). It emerges that 6c, with the CF2 groups placed 1,4- to each other, has a significantly higher melting point (89.9 degrees C) when compared to the other analogues and palmitic acid itself. It is a crystalline compound and the structure reveals an extended anti-zig-zag chain. Similarly 8,8,11,11-tetrafluorononadecane (27) adopts an extended anti-zig-zag structure. This is rationalized by dipolar relaxation between the two CF2 groups placed 1,4 to each other in the extended anti-zig-zag chain and suggests a design modification for long chain aliphatics which can introduce conformational stability.Publisher PDFPublisher PDFPeer reviewe

The vicinal difluoro motif : the synthesis and conformation of erythro- and threo-diastereoisomers of 1,2-difluorodiphenylethanes, 2,3-difluorosuccinic acids and their derivatives

Background: It is well established that vicinal fluorines (RCHF-CHFR) prefer to adopt a gauche rather than an anti conformation when placed along aliphatic chains. This has been particularly recognised for 1,2-difluoroethane and extends to 2,3-difluorobutane and longer alkyl chains. It follows in these latter cases that if erythro and threo vicinal difluorinated stereoisomers are compared, they will adopt different overall conformations if the fluorines prefer to be gauche in each case. This concept is explored in this paper with erythro- and threo- diastereoisomers of 2,3-difluorosuccinates. Results: A synthetic route to 2,3-difluorosuccinates has been developed through erythro- and threo- 1,2-difluoro-1,2-diphenylethane which involved the oxidation of the aryl rings to generate the corresponding 2,3- difluorosuccinic acids. Ester and amide derivatives of the erythro- and threo- 2,3-difluorosuccinic acids were then prepared. The solid and solution state conformation of these compounds was assessed by X-ray crystallography and NMR. Ab initio calculations were also carried out to model the conformation of erythro- and threo- 1,2-difluoro-1,2-diphenylethane as these differed from the 2,3-difluorosuccinates. Conclusion: In general the overall chain conformations of the 2,3-difluorosuccinates diastereoisomers were found to be influenced by the fluorine gauche effect. The study highlights the prospects of utilising the vicinal difluorine motif (RCHF-CHFR) as a tool for influencing the conformation of performance organic molecules and particularly tuning conformation by selecting specific diastereoisomers (erythro or threo).Publisher PDFPeer reviewe

Women and substance abuse: gender-specific social, biological and psychological differences and treatment considerations

Until recently, substance abuse research focused almost entirely on men – leaving women underrepresented or overlooked entirely. Traditional methods of treatment were developed on the findings of purely male-centric research which was applied to the entire population. Research has since identified a number of gender-specific variables which limit the application of these approaches and present a case for the universal implementation of treatment-types developed specifically for women. This article represents an exploration of the cultural expectations, trauma and adverse life experiences together with comorbidity of psychiatric disorders and the role of ovarian hormones in the onset and treatment of substance abuse in women

Does the use of illicit drugs specifically class a drugs influence the crime rate?

Class A drugs are very potent substances with lethal side effects; they are considered the most dangerous of illicit drugs. The crime rate over the past decade has shown a rise and fall in the quantity of crimes committed due to drugs. Illegal drug traffickers, smuggling heroin, cocaine and other substances into the UK, Europe and U.S; are enticing more younger adolescents to join the craze. These traffickers conceal and manipulate their way into countries such as the UK where demand is always expanding. This paper will explore whether or not drugs, specifically Class A have an effect on the crime rate. In this paper, results are shown to indicate a minor positive correlation between the relationship of drugs and the crime rate; there is still a large proportion of uncertainty on the title at present. This review provides an outline of the typical users of drugs, how cocaine and heroin is trafficked into Europe and data concerning the link between drugs and the ever-rising crime rate. Keywords: crime rate, cocaine, heroin, legislation, class a, economic compulsive, psychopharmacological, systemic, drug la

Evaluation of elicitation methods to quantify Bayes linear models

The Bayes linear methodology allows decision makers to express their subjective beliefs and adjust these beliefs as observations are made. It is similar in spirit to probabilistic Bayesian approaches, but differs as it uses expectation as its primitive. While substantial work has been carried out in Bayes linear analysis, both in terms of theory development and application, there is little published material on the elicitation of structured expert judgement to quantify models. This paper investigates different methods that could be used by analysts when creating an elicitation process. The theoretical underpinnings of the elicitation methods developed are explored and an evaluation of their use is presented. This work was motivated by, and is a precursor to, an industrial application of Bayes linear modelling of the reliability of defence systems. An illustrative example demonstrates how the methods can be used in practice

The Emerging Role of Epigenetic Modifiers in Repair of DNA Damage Associated with Chronic Inflammatory Diseases

At sites of chronic inflammation epithelial cells are exposed to high levels of reactive oxygen species (ROS), which can contribute to the initiation and development of many different human cancers. Aberrant epigenetic alterations that cause transcriptional silencing of tumor suppressor genes are also implicated in many diseases associated with inflammation, including cancer. However, it is not clear how altered epigenetic gene silencing is initiated during chronic inflammation. The high level of ROS at sites of inflammation is known to induce oxidative DNA damage in surrounding epithelial cells. Furthermore, DNA damage is known to trigger several responses, including recruitment of DNA repair proteins, transcriptional repression, chromatin modifications and other cell signaling events. Recruitment of epigenetic modifiers to chromatin in response to DNA damage results in transient covalent modifications to chromatin such as histone ubiquitination, acetylation and methylation and DNA methylation. DNA damage also alters non-coding RNA expression. All of these alterations have the potential to alter gene expression at sites of damage. Typically, these modifications and gene transcription are restored back to normal once the repair of the DNA damage is completed. However, chronic inflammation may induce sustained DNA damage and DNA damage responses that result in these transient covalent chromatin modifications becoming mitotically stable epigenetic alterations. Understanding how epigenetic alterations are initiated during chronic inflammation will allow us to develop pharmaceutical strategies to prevent or treat chronic inflammation-induced cancer. This review will focus on types of DNA damage and epigenetic alterations associated with chronic inflammatory diseases, the types of DNA damage and transient covalent chromatin modifications induced by inflammation and oxidative DNA damage and how these modifications may result in epigenetic alterations

The Role of Inflammation and Inflammatory Mediators in the Development, Progression, Metastasis, and Chemoresistance of Epithelial Ovarian Cancer

Inflammation plays a role in the initiation and development of many types of cancers, including epithelial ovarian cancer (EOC) and high grade serous ovarian cancer (HGSC), a type of EOC. There are connections between EOC and both peritoneal and ovulation-induced inflammation. Additionally, EOCs have an inflammatory component that contributes to their progression. At sites of inflammation, epithelial cells are exposed to increased levels of inflammatory mediators such as reactive oxygen species, cytokines, prostaglandins, and growth factors that contribute to increased cell division, and genetic and epigenetic changes. These exposure-induced changes promote excessive cell proliferation, increased survival, malignant transformation, and cancer development. Furthermore, the pro-inflammatory tumor microenvironment environment (TME) contributes to EOC metastasis and chemoresistance. In this review we will discuss the roles inflammation and inflammatory mediators play in the development, progression, metastasis, and chemoresistance of EOC

Joint modelling of the body and tail of bivariate data

In situations where both extreme and non-extreme data are of interest, modelling the whole data set accurately is important. In a univariate framework, modelling the bulk and tail of a distribution has been extensively studied before. However, when more than one variable is of concern, models that aim specifically at capturing both regions correctly are scarce in the literature. A dependence model that blends two copulas with different characteristics over the whole range of the data support is proposed. One copula is tailored to the bulk and the other to the tail, with a dynamic weighting function employed to transition smoothly between them. Tail dependence properties are investigated numerically and simulation is used to confirm that the blended model is sufficiently flexible to capture a wide variety of structures. The model is applied to study the dependence between temperature and ozone concentration at two sites in the UK and compared with a single copula fit. The proposed model provides a better, more flexible, fit to the data, and is also capable of capturing complex dependence structures.Comment: 36 pages, 12 figure

Crisis Translation Training Challenges Arising from New Contexts of Translation

Focused on material design and self-reflective practices, this article discusses a Crisis Translation Training pitched at master-level translation and interpreting students, developed within the research activities carried out for the INTERACT International Crisis Translation Network. The course was designed to enable them to develop a broader skillset in support of multilingual crisis settings. The learning objectives underpinning the materials address training lacunae in enabling linguists to be involved in relief operations (Federici, 2016; O’Brien, 2016). The authors perceive the complementary skills as crucial in the development of language mediation services assisting linguists operating in such zones of liminality as are crisis settings. Multilingual communication in crisis includes professional forms of translation, signing, and interpreting, as well as forms of intercultural mediation, and social work (Drugan, 2017). Emergencies and prolonged crises have an impact on the communicative dynamics among international relief operators, local institutions, and crisis-affected populations. The authors developed training materials to prepare students to work in crisis settings by harnessing their language competences in crisis translation as a form of community translation (Taibi and Ozolins, 2016). Culturally and linguistically diverse (CALD) communities often need support in language combinations that rarely match commercially viable combinations (Federici and Cadwell, 2018; Shackleton, 2018). This article critically reviews non-language specific Crisis Translation Training, delivered in three iterations across two sites. Reporting on the first phases of the process of material design and enhancement, the article reflects on how issues in delivery, emerging findings regarding the authentic needs of mostly untrained translators, and different pathways of delivery shaped the re-definition of the initial learning objectives and pushed towards a translator trainer approach that would suit a range of new contexts of language mediation