Detection of DNA mutations using novel SERS (Surface-Enhanced Raman Spectroscopy) diagnostic platform

This article describes the detection of DNA mutations using novel Au-Ag coated GaN substrate as SERS (surface-enhanced Raman spectroscopy) diagnostic platform. Oligonucleotide sequences corresponding to the BCR-ABL (breakpoint cluster region-Abelson) gene responsible for development of chronic myelogenous leukemia were used as a model system to demonstrate the discrimination between the wild type and Met244Val mutations. The thiolated ssDNA (single-strand DNA) was immobilized on the SERS-active surface and then hybridized to a labeled target sequence from solution. An intense SERS signal of the reporter molecule MGITC was detected from the complementary target due to formation of double helix. The SERS signal was either not observed, or decreased dramatically for a negative control sample consisting of labeled DNA that was not complementary to the DNA probe. The results indicate that our SERS substrate offers an opportunity for the development of novel diagnostic assays.

Novel solutions for a model of wound healing angiogenesis

We prove the existence of novel, shock-fronted travelling wave solutions to a model of wound healing angiogenesis studied in Pettet et al (2000 IMA J. Math. App. Med. 17 395–413) assuming two conjectures hold. In the previous work, the authors showed that for certain parameter values, a heteroclinic orbit in the phase plane representing a smooth travelling wave solution exists. However, upon varying one of the parameters, the heteroclinic orbit was destroyed, or rather cut-off, by a wall of singularities in the phase plane. As a result, they concluded that under this parameter regime no travelling wave solutions existed. Using techniques from geometric singular perturbation theory and canard theory, we show that a travelling wave solution actually still exists for this parameter regime. We construct a heteroclinic orbit passing through the wall of singularities via a folded saddle canard point onto a repelling slow manifold. The orbit leaves this manifold via the fast dynamics and lands on the attracting slow manifold, finally connecting to its end state. This new travelling wave is no longer smooth but exhibits a sharp front or shock. Finally, we identify regions in parameter space where we expect that similar solutions exist. Moreover, we discuss the possibility of more exotic solutions.

Hyperlinking history and illegitimate imagination : the historiographic metafictional E-novel

‘Historiographic Metafiction’ (HM) is a literary term first coined by creative writing academic Linda Hutcheon in 1988, and which refers to the postmodern practice of a fiction author inserting imagined--or illegitimate--characters into narratives that are intended to be received as authentic and historically accurate, that is, ostensibly legitimate. Such adventurous and bold authorial strategies frequently result in “novels which are both intensely self-reflexive and yet paradoxically also lay claim to historical events and personages” (Hutcheon, A Poetics 5). They can be so entertaining and engaging that the overtly intertextual, explicitly inventive work of biographical HM can even change the “hegemonic discourse of history” (Nunning 353) for, as Philippa Gregory, the author of HM novel The Other Boleyn Girl (2001), has said regarding this genre of creative writing: “Fiction is about imagined feelings and thoughts. History depends on the outer life. The novel is always about the inner life. Fiction can sometimes do more than history. It can fill the gaps” (University of Sussex). In a way, this article will be filling one of the gaps regarding HM...

H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

BACKGROUND: About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients' normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as gammaH2AX) occurs rapidly in response to DNA DSBs, and, among its other roles, contributes to repair protein recruitment to these damaged sites. Mammalian cell lines have also been crucial in facilitating the successful cloning of many DNA DSB repair genes; yet, very few mutant cell lines exist for non-syndromic clinical radiosensitivity (RS). METHODS: Here, we survey DNA DSB induction and repair in whole cells from RS patients, as revealed by gammaH2AX foci assays, as potential predictive markers of clinical radiation response. RESULTS: With one exception, both DNA focus induction and repair in cell lines from RS patients were comparable with controls. Using gammaH2AX foci assays, we identified a RS cancer patient cell line with a novel ionising radiation-induced DNA DSB repair defect; these data were confirmed by an independent DNA DSB repair assay. CONCLUSION: gammaH2AX focus measurement has limited scope as a pre-RT predictive assay in lymphoblast cell lines from RT patients; however, the assay can successfully identify novel DNA DSB repair-defective patient cell lines, thus potentially facilitating the discovery of novel constitutional contributions to clinical RS.

Rupturing otherness : becoming Estonian in the context of contemporary Britain

While identity construction continues to be a widely discussed and researched area in contemporary social sciences, the existing theories have overlooked the importance of understanding why and how identities as semiotic constructions emerge in individuals' consciousness in the flow of their everyday functioning. This article seeks to address this limitation in the theorizing by proposing an alternative conceptualization of identity, according to which identity construction is triggered by rupturing life-experience, which surfaces another perspective and makes the person aware of a possibility to be otherwise or of the reality of being different. Theoretical claims put forward in the paper are drawn from data gathered in a recent study, which explored lived-through experiences of young Estonians, who made study-visits to the United Kingdom. The discussed data will also highlight some interesting aspects in Estonians' self-definition as it is constructed in relation to Eastern-European identity in the context of contemporary Britain.

Flammability and thermal properties of novel semi aromatic polyamide/organoclay nanocomposite

The development of semi aromatic polyamide/organoclays nanocomposites (PANC) is reported in this communication. New polyamide (PA) was successfully synthesized through direct polycondensation reaction between bio-based diacid and aromatic diamine. PA exhibited strong UV vis absorption band at 412 nm. Its photoluminescence spectrum showed maximum band at 511 nm in the green region. The surface modification of montmorillonite was carried out through ion-exchange reaction using 1,4-bis[4-aminophenoxy]butane (APB) as a modifier. Then PANCs containing 3 and 6 wt.% of the modified montmorillonite (MMT-APB) were prepared. Flammability and thermal properties of PA and the nanocomposites were studied by microscale combustion calorimeter (MCC), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). TGA results in both air and nitrogen atmospheres indicated improving in thermal properties of PANCs compared to the neat PA. According to MCC analysis, a 31.6% reduction in pHRR value has been achieved by introducing 6 wt.% of the organoclay in PA matrix.

Solar Assisted Fast Pyrolysis: A Novel Approach of Renewable Energy Production

Biofuel produced by fast pyrolysis from biomass is a promising candidate. The heart of the system is a reactor which is directly or indirectly heated to approximately 500°C by exhaust gases from a combustor that burns pyrolysis gas and some of the by-product char. In most of the cases, external biomass heater is used as heating source of the system while internal electrical heating is recently implemented as source of reactor heating. However, this heating system causes biomass or other conventional forms of fuel consumption to produce renewable energy and contributes to environmental pollution. In order to overcome these, the feasibility of incorporating solar energy with fast pyrolysis has been investigated. The main advantages of solar reactor heating include renewable source of energy, comparatively simpler devices, and no environmental pollution. A lab scale pyrolysis setup has been examined along with 1.2 m diameter parabolic reflector concentrator that provides hot exhaust gas up to 162°C. The study shows that about 32.4% carbon dioxide (CO2) emissions and almost one-third portion of fuel cost are reduced by incorporating solar heating system. Successful implementation of this proposed solar assisted pyrolysis would open a prospective window of renewable energy.

Reason of state and a new notion of fortune : Historicising the risk society

Since the 1980s the concept of risk has produced a large and diverse volume of sociological research. Ulrich Beck’s groundbreaking risk society thesis provides a particularly engaging contribution, since it seems that nearly every sociological account of risk engages with this work. For Beck, we are living in second modernity – a new epoch that breaks with pre-modernity and industrial society due to the centrality, incalculability and reflexivity of globalised risk. While Beck’s theory is compelling, a reading of other theorists such as Foucault (2007[1978]) and Hacking (1975,1990) suggests that a difficulty with Beck’s work is that in attempting to explain what is novel about risk in contemporary times, he too quickly passes over the complexities and ruptures of historical change that impact on the history and contingency of risk. This paper begins by presenting a brief analysis of the present state of risk by introducing Beck’s historical narrative of risk from pre-modernity to the risk society; it then outlines the challenges with the “risk as epoch” argument by considering a range of literature, which suggests risk has a more complex history than proposed by Beck; and finally it highlights the value in examining strategies of statecraft in early modern Europe, specifically Machiavelli’s The Prince (2008[1513]) and Giovanni Botero’s political treatise, Della Ragion di Stato (1956[1589]) – as a means of more thoroughly understanding how our current concept of risk emerges. In doing so, this paper seeks to open up new trajectories in the historicisation of risk for other interested scholars.

A novel ambiguity acceptance test threshold determination method with controllable failure rate

Ambiguity validation as an important procedure of integer ambiguity resolution is to test the correctness of the fixed integer ambiguity of phase measurements before being used for positioning computation. Most existing investigations on ambiguity validation focus on test statistic. How to determine the threshold more reasonably is less understood, although it is one of the most important topics in ambiguity validation. Currently, there are two threshold determination methods in the ambiguity validation procedure: the empirical approach and the fixed failure rate (FF-) approach. The empirical approach is simple but lacks of theoretical basis. The fixed failure rate approach has a rigorous probability theory basis, but it employs a more complicated procedure. This paper focuses on how to determine the threshold easily and reasonably. Both FF-ratio test and FF-difference test are investigated in this research and the extensive simulation results show that the FF-difference test can achieve comparable or even better performance than the well-known FF-ratio test. Another benefit of adopting the FF-difference test is that its threshold can be expressed as a function of integer least-squares (ILS) success rate with specified failure rate tolerance. Thus, a new threshold determination method named threshold function for the FF-difference test is proposed. The threshold function method preserves the fixed failure rate characteristic and is also easy-to-apply. The performance of the threshold function is validated with simulated data. The validation results show that with the threshold function method, the impact of the modelling error on the failure rate is less than 0.08%. Overall, the threshold function for the FF-difference test is a very promising threshold validation method and it makes the FF-approach applicable for the real-time GNSS positioning applications.

A novel tuning method for advanced line drop compensator and its application to response coordination of distributed generation with voltage regulating devices

Nowadays, integration of small-scale electricity generators, known as Distributed Generation (DG), into distribution networks has become increasingly popular. This tendency together with the falling price of DG units has a great potential in giving the DG a better chance to participate in voltage regulation process, in parallel with other regulating devices already available in the distribution systems. The voltage control issue turns out to be a very challenging problem for distribution engineers, since existing control coordination schemes need to be reconsidered to take into account the DG operation. In this paper, a control coordination approach is proposed, which is able to utilize the ability of the DG as a voltage regulator, and at the same time minimize the interaction of DG with another DG or other active devices, such as On-load Tap Changing Transformer (OLTC). The proposed technique has been developed based on the concepts of protection principles (magnitude grading and time grading) for response coordination of DG and other regulating devices and uses Advanced Line Drop Compensators (ALDCs) for implementation. A distribution feeder with tap changing transformer and DG units has been extracted from a practical system to test the proposed control technique. The results show that the proposed method provides an effective solution for coordination of DG with another DG or voltage regulating devices and the integration of protection principles has considerably reduced the control interaction to achieve the desired voltage correction.

Novel polymer synthesis methodologies using combination of thermally and photochemically-induced nitroxide mediated polymerisation

The combination of thermally- and photochemically-induced polymerization using light sensitive alkoxyamines was investigated. The thermally driven polymerizations were performed via the cleavage of the alkoxyamine functionality, whereas the photochemically-induced polymerizations were carried out either by nitroxide mediated photo-polymerization (NMP2) or by a classical type II mechanism, depending on the structure of the light-sensitive alkoxyamine employed. Once the potential of the various structures as initiators of thermally- and photo-induced polymerizations was established, their use in combination for block copolymer syntheses was investigated. With each alkoxyamine investigated, block copolymers were successfully obtained and the system was applied to the post-modification of polymer coatings for application in patterning and photografting.

Identification and characterization of novel proteolytic interactions of prostate cancer-expressed kallikrein-related peptidases, type II transmembrane serine proteases and matrix metalloproteinases

This study investigated interactions of protein-cleaving enzymes (or proteases) that promote prostate cancer progression. It provides the first evidence of a novel regulatory network of protease activity at the surface of cells. The proteases kallikrein-related peptidases 4 and 14, and matrix metalloproteinases 3 and 9 are cleaved at the cell surface by the cell surface proteases hepsin and TMPRSS2. These cleavage events potentially regulate activation of downstream targets of kallikrein 4 and 14 such as cell surface signalling via the protease-activated receptors (PARs) and cell growth-promoting factors such as hepatocyte-growth factor.