Exome sequencing of prostate cancer supports the hypothesis of independent tumour origins

BACKGROUND: Prostate cancer (PCa) is a clinically and pathologically heterogeneous disease. The rapid development of sequencing technology has the potential to deliver new biomarkers with emphasis on aggressive disease and to revolutionise personalised cancer treatment. However, a prostate harbouring cancer commonly contains multiple separate tumour foci, with the potential to aggravate tumour sampling. The level of intraprostatic tumour heterogeneity remains to be determined.

OBJECTIVE: To determine the level of intraprostatic tumour heterogeneity through genome-wide, high-resolution profiling of multiple tumour samples from the same individual.

DESIGN, SETTINGS, AND PARTICIPANTS: Multiple tumour samples were obtained from four individuals following radical prostatectomy. One individual (SWE-1) contained >70% cancer cells in all tumour samples, whereas the other three (SWE-2 to SWE-4) required the use of laser capture microdissection for tumour cell enrichment. Subsequently, DNA was extracted from all tissue samples, and exome sequencing was performed. All tumour foci of SWE-1 were also profiled using a high-resolution array for the identification of copy number alterations (CNA).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Shared somatic high-frequency single nucleotide variants (SNV) and CNAs were used to infer the level of intraprostatic tumour heterogeneity.

RESULTS AND LIMITATIONS: No high-frequency mutations, common for the three tumour samples of SWE-1, were identified. Ten randomly chosen positions were validated with Sanger sequencing in all foci, which verified the exome data. The high level of intraprostatic heterogeneity was consistent in all individuals. In total, three out of four individuals harboured tumours without an apparent common somatic denominator. Although we cannot exclude the presence of common structural rearrangements, a high-density array was used for the detection of deletions and amplifications in SWE-1, which agreed with the exome data.

CONCLUSIONS: We present evidence for the presence of somatically independent tumours within the same prostate. This finding will have implications for personalised cancer treatment and biomarker discovery.

Observation of an intact noncovalent homotrimer of detergent-solubilized rat microsomal glutathione transferase-1 by electrospray mass spectrometry

Microsomal glutathione transferase-1 (MGST1) is a membrane-bound enzyme involved in the detoxification of xenobiotics and the protection of cells against oxidative stress. The proposed active form of the enzyme is a noncovalently associated homotrimer that binds one substrate glutathione molecule/trimer. In this study, this complex has been directly observed by electrospray mass spectrometry analysis of active rat liver MGST1 reconstituted in a minimum amount of detergent. The measured mass of the homotrimer is 53 kDa, allowing for the mass of three MGST molecules in complex with one glutathione molecule. Collision-induced dissociation of the trimer complex resulted in the formation of monomer and homodimer ion species. Two distinct species of homodimer were observed, one unliganded and one identified as a homodimer.glutathione complex. Activation of the enzyme by N-ethylmaleimide through modification of Cys(49) (Svensson, R., Rinaldi, R., Swedmark, S., and Morgenstern, R. (2000) Biochemistry 39, 15144-15149) was monitored by the observation of an appropriate increase in mass in both the denatured monomeric and native trimeric forms of MGST1. Together, the data correspond well with the proposed functional organization of MGST1. These results also represent the first example of direct electrospray mass spectrometry analysis of a detergent-solubilized multimeric membrane protein complex in its native state.

The addition of CO2 to four superbase ionic liquids: a DFT study

The addition of carbon dioxide to four superbase ionic liquids, [P3333][Benzim], [P3333][124Triz], [P3333][123Triz] and [P3333][Bentriz] was studied using a molecular DFT approach involving anions alone and individual ion pairs. Intermolecular bonding within the individual ion pairs is characterised by a number of weak hydrogen bonds, with the superbase anion geometrically arranged so as to maximize interactions between the heterocyclic N atoms and the cation. The pairing energies show no correlation to the observed CO2 adsorption capacity. Addition of CO2 to the anion alone clearly resulted in the formation of a covalently-bound carbamate function with the strength of binding correlated to experimental capacity. In the ion pair however the cation significantly alters the nature of the bonding such that the overall cohesive energy is reduced. Formation of a strong carbamate function occurs at the expense of weakening the interaction between anion and cation. In the more weakly absorbing ion pairs which contain [123Triz]- and [Bentriz]-, the carbamate-functionalised systems are very close in energy to adducts in which CO2 is more weakly bound, suggesting an equilibrium between the chemi- and physisorbed CO2.

On the Security of Balanced Encoding Countermeasures

Most cryptographic devices should inevitably have a resistance against the threat of side channel attacks. For this, masking and hiding schemes have been proposed since 1999. The security validation of these countermeasures is an ongoing research topic, as a wider range of new and existing attack techniques are tested against these countermeasures. This paper examines the side channel security of the balanced encoding countermeasure, whose aim is to process the secret key-related data under a constant Hamming weight and/or Hamming distance leakage. Unlike previous works, we assume that the leakage model coefficients conform to a normal distribution, producing a model with closer fidelity to real-world implementations. We perform analysis on the balanced encoded PRINCE block cipher with simulated leakage model and also an implementation on an AVR board. We consider both standard correlation power analysis (CPA) and bit-wise CPA. We confirm the resistance of the countermeasure against standard CPA, however, we find with a bit-wise CPA that we can reveal the key with only a few thousands traces.

SOPS: A System for Efficient Processing of Spatial-Keyword Publish/Subscribe

Massive amount of data that are geo-tagged and associated with text information are being generated at an unprecedented scale. These geo-textual data cover a wide range of topics. Users are interested in receiving up-to-date geo-textual objects (e.g., geo-tagged Tweets) such that their locations meet users’ need and their texts are interesting to users. For example, a user may want to be updated with tweets near her home on the topic “dengue fever headache.” In this demonstration, we present SOPS, the Spatial-Keyword Publish/Subscribe System, that is capable of efficiently processing spatial keyword continuous queries. SOPS supports two types of queries: (1) Boolean Range Continuous (BRC) query that can be used to subscribe the geo-textual objects satisfying a boolean keyword expression and falling in a specified spatial region; (2) Temporal Spatial-Keyword Top-k Continuous (TaSK) query that continuously maintains up-to-date top-k most relevant results over a stream of geo-textual objects. SOPS enables users to formulate their queries and view the real-time results over a stream of geotextual objects by browser-based user interfaces. On the server side, we propose solutions to efficiently processing a large number of BRC queries (tens of millions) and TaSK queries over a stream of geo-textual objects.

Effect of the Presence of MEA on the CO2 Capture Ability of Superbase Ionic Liquids

The miscibility of monoethanolamine (MEA) in five superbase ionic liquids (ILs), namely the trihexyl-tetradecylphosphonium benzotriazolide ([P66614][Bentriz]), trihexyl-tetradecylphosphonium benzimidazolide ([P66614][Benzim]), trihexyl-tetradecylphosphonium 1,2,3-triazolide ([P66614][123Triz]), trihexyl-tetradecylphosphonium 1,2,4-triazolide ([P66614][124Triz]), and trihexyl-tetradecylphosphonium imidazolide ([P66614][Im]) was determined at 295.15 K using 1H NMR spectroscopy. The solubility of carbon dioxide (CO2) in equimolar (IL + MEA) mixtures was then studied experimentally using a gravimetric technique at 295.15 K and 0.1 MPa. The effect of MEA on the CO2 capture ability of these ILs was investigated together with the viscosity of these systems in the presence or absence of CO2 to evaluate their practical application in CO2 capture processes. The effect of the presence of MEA on the rate of CO2 uptake was also studied. The study showed that the MEA can enhance CO2 absorption over the ideal values in the case of [P66614][123Triz] and [P66614][Bentriz] while in the other systems the mixtures behave ideally. A comparison of the effect of MEA addition with the addition of water to these superbase ILs showed that similar trends were observed in each case for the individual ILs studied.

Peer tutoring in a medical school: perceptions of tutors and tutees

Background: Peer tutoring has been described as “people from similar social groupings who are not professional teachers helping each other to learn and learning themselves by teaching”. Peer tutoring is well accepted as a source of support in many medical curricula, where participation and learning involve a process of socialisation.
Peer tutoring can ease the transition of the junior students from the university class environment to the hospital workplace. In this paper, we apply the Experienced Based Learning (ExBL) model to explore medical students’ perceptions of their experience of taking part in a newly established peer tutoring program at a hospital based
clinical school.
Methods: In 2014, all students at Sydney Medical School – Central, located at Royal Prince Alfred Hospital were invited to voluntarily participate in the peer tutoring program. Year 3 students (n = 46) were invited to act as tutors for Year 1 students (n = 50), and Year 4 students (n = 60) were invited to act as tutors for Year 2 students (n = 51). Similarly, the ‘tutees’ were invited to take part on a voluntary basis. Students were invited to attend focus groups, which were held at the end of the program. Framework analysis was used to code and categorise data into themes.
Results: In total, 108/207 (52 %) students participated in the program. A total of 42/106 (40 %) of Year 3 and 4 students took part as tutors; and of 66/101 (65 %) of Year 1 and 2 students took part as tutees. Five focus groups were held, with 50/108 (46 %) of students voluntarily participating. Senior students (tutors) valued the opportunity to practice and improve their medical knowledge and teaching skills. Junior students (tutees) valued the opportunity for additional practice and patient interaction, within a relaxed, small group learning environment.
Conclusion: Students perceived the peer tutoring program as affording opportunities not otherwise available within the curriculum. The peer teaching program provided a framework within the medical curriculum for senior students to practice and improve their medical knowledge and teaching skills. Concurrently, junior students were provided with a valuable learning experience that they reported as being qualitatively different to traditional teaching by faculty.

An Ultrasonic Relaxation Study of 1-Alkyl-3-Methylmidazolium-Based Room Temperature Ionic Liquids: Probing the Role of Alkyl Chain Length in the Cation

Ultrasound absorption spectra of four 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide were determined as a function of the alkyl chain length on the cation from 1-propyl- to 1-hexyl- from 293.15 to 323.15 K at ambient pressure. Herein, the ultrasound absorption measurements were carried out using a standard pulse technique within a frequency range from 10 to 300 MHz. Additionally the speed of sound, density and viscosity have been measured. The presence of strong dissipative processes during the ultrasound wave propagation was found experimentally, i.e. relaxation processes in the megahertz range were observed for all compounds over the whole temperature range. The relaxation spectra (both relaxation amplitude and relaxation frequency) were shown to be dependent on the alkyl side chain length of the 1-alkyl-3-methylimidazolium ring. In most cases, a single Debye model described the absorption spectra very well. However, a comparison of the determined spectra with the spectra of a few other imidazolium-based ionic liquids reported in the literature (in part recalculated in this work) shows that the complexity of the spectra increases rapidly with the elongation of the alkyl chain length on the cation. This complexity indicates that both the volume viscosity and the shear viscosity are involved in relaxation processes even in relatively low frequency ranges. As a consequence, the sound velocity dispersion is present at relatively low megahertz frequencies.

Effect of cation structure on the oxygen solubility and diffusivity in a range of bis{(trifluoromethyl)sulfonyl}imide anion based ionic liquids for lithium-air battery electrolytes

This paper reports on the solubility and diffusivity of dissolved oxygen in a series of ionic liquids (ILs) based on the bis{(trifluoromethyl)sulfonyl}imide anion with a range of related alkyl and ether functionalised cyclic alkylammonium cations. Cyclic voltammetry has been used to observe the reduction of oxygen in ILs at a microdisk electrode and chronoamperometric measurements have then been applied to simultaneously determine both the concentration and the diffusion coefficient of oxygen in the different ILs. The viscosity of the ILs and the calculated molar volume and free volume is also reported. It is found that, within this class of ILs, the oxygen diffusivity generally increases with decreasing viscosity of the neat IL. An inverse relationship between oxygen solubility and IL free volume is reported for the two IL families implying oxygen is not simply occupying the available empty space. In addition, it is reported that the introduction of ether-group into the IL cation structure promotes the diffusivity of dissolved oxygen but reduces the solubility of the gas.

The Influence of Cation Structure on the Chemical-Physical Properties of Protic Ionic Liquids

In this study we investigated the influence of five different cations on the physical-chemical properties of protic ionic liquids (PILs) based on bis(trifluoromethanesulfonyl)imide (TFSI-). We showed that the viscosities, ionic conductivities, densities and thermal properties of these PIL are strongly affected by the structure of the protic cation. Furthermore, the influence of the cation structure on the lithium coordination was investigated by Raman spectroscopy for all investigated PIL-based electrolytes for lithium-ion batteries (LIBs). This investigation clearly demonstrates, that the lithium average coordination number in PIL-based electrolytes is strongly affected by (ring) size and the number of protons on the cations structure and, more importantly, it might be significantly lower (more than 60 of that of electrolytes containing aprotic ionic liquids (AILs). Electrochemical performances of these PILs-based electrolytes were then also investigated to dress some conclusion on their applicability for LIB.

Temperature and Pressure Induced Structural Changes of Cobalt (II) in a Phosphonium Based Ionic Liquid

In this paper the temperature and pressure induced paramagnetic switching of cobalt (II) complex in binary mixture of phosphonium based ionic liquid [P6,6,6,14]SCN and [Co(NCS)2], is reported. This arises from a structural change in the coordination of the cobalt (II) center from tetrahedral [Co(NCS)4]2- to octahedral [Co(NCS)6]4- when mobile thiocyanate ions are added. These properties are reflected in the abrupt change of conductivity behavior of the magnetic ionic liquid. Therefore, as demonstrated herein the reversible switching in coordination of cobalt from tetrahedral to octahedral can be easily monitored at ambient as well as elevated pressure by tracking the dc-conductivity changes.

Techno-Economic Feasibility of Selective CO2 Capture Processes from Biogas Streams using Ionic Liquids as Physical Absorbents

Biogas from anaerobic digestion of sewage sludge is a renewable resource with high energy content, which is formed mainly of CH4 (40-75 vol.%) and CO2 (15-60 vol.%) Other components such as water (H2O, 5-10 vol.%) and trace amounts of hydrogen sulfide and siloxanes can also be present. A CH4-rich stream can be produced by removing the CO2 and other impurities so that the upgraded bio-methane can be injected into the natural gas grid or used as a vehicle fuel. The main objective of this paper is to develop a new modeling methodology to assess the technical and economic performance of biogas upgrading processes using ionic liquids which physically absorb CO2. Three different ionic liquids, namely the 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, 1-hexyl-3-methylimidazoliumbis[(trifluoromethyl)sulfonyl]imide and trihexyl(tetradecyl)phosphonium bis[(trifluoromethyl)sulfonyl]imide, are considered for CO2 capture in a pressure-swing regenerative absorption process. The simulation software Aspen Plus and Aspen Process Economic Analyzer is used to account for mass and energy balances as well as equipment cost. In all cases, the biogas upgrading plant consists of a multistage compressor for biogas compression, a packed absorption column for CO2 absorption, a flash evaporator for solvent regeneration, a centrifugal pump for solvent recirculation, a pre-absorber solvent cooler and a gas turbine for electricity recovery. The evaluated processes are compared in terms of energy efficiency, capital investment and bio-methane production costs. The overall plant efficiency ranges from 71-86 % whereas the bio-methane production cost ranges from £6.26-7.76 per GJ (LHV). A sensitivity analysis is also performed to determine how several technical and economic parameters affect the bio-methane production costs. The results of this study show that the simulation methodology developed can predict plant efficiencies and production costs of large scale CO2 capture processes using ionic liquids without having to rely on gas solubility experimental data.

Revival: The Aesthetics of Revival Subcultures and Re-enactment Groups Explored Through Fashion Image-making

This research aims, through performance, fashion photography, video making and the theatrical devices that accompany such practice, to explore the style of a contemporary, largely male, subcultural collective. The common term that joins these loosely bound groups is revival as they appear driven by an impulse to simulate and re-enact the dress, rites and rituals of British and American subcultures from a perceived golden era. The similarities with re-enactment societies are also explored and exploited to the end of developing new style- based aesthetics in male fashion image-making formed around an elaborate re- enactment of Spartacus and the Third Servile Wars. Examined through comparative visuals (revivalists / re-enactors) a common thread is found in the wearing of leather as a metaphor for resistance, style and a pupa-like second skin. Subsequent findings of this research suggest that the cuirass of popular culture emerges as the motorcycle jacket of both the sword and sandal epic and the historical re-enactor. Addressing extremes in narcissistic dress and behaviour amongst certain individuals within these older male communities, this study also questions parts of established theory on subcultural development within the field of cultural studies and postulates on a metaphorical dandy gene. Citing two leading practitioners in the field of fashion photography the work of both Richard Prince and Bruce Weber is viewed through the lens of the subcultural aesthete and conclusions drawn as to their role as agents provocateurs in the development of the fashion image with a revival based narrative. In addition the often used term retro is examined, categorised and granted its own genre within fashion image- making and defined as being separate from the practice element of this research. Reflecting a multi-disciplinary approach that engages the researcher as Bricoleur and participant observer this research operates in the reflexive realm and uses simulation as a key method of enquiry. The practice-led outcome of this investigation takes the form of a final research exhibition that takes the form of a substantial installation of photography, video, clothing and textile prints. Key terms: dandy gene, historical re-enactment groups, internal theatre, narcissism, narrative image-making, reflexive practice, revival as theatre, subcultures,

Exploring the Roles of Technology and Social Play in Art Museums

This co-written chapter was included in an edited book featuring invited authors from different countries and different areas of museum research and practice. The chapter uses a theory of play by Johan Huizinga (1938) to frame case studies of play-based interactive experiences in museums in various countries. The aim was to use theory to ground museum practice, in order to evaluate existing practical implementations as well as to inform the design of new ones. The book was nominated as one of the 10 best museum education books of 2011 by Museum Education Monitor, and the chapter led to a subsequent technology residency the author undertook in the Spike Island gallery, Bristol in 2012, funded by the National Endowment for Science, Technology and the Arts, Arts and Humanities Research Council and Arts Council England. It also informed his subsequent postgraduate teaching, an example of which is a recent MA project, which deconstructs play from a computational perspective. Collaborations have continued with the co-author, which have resulted in a number of invited lectures. In this chapter the authors explore play as a structure for supporting visitor learning, drawing from international research in museums and interaction design. Four aspects of play first proposed by Huizinga are explored – the free-choice aspect of play, play as distinct from real life, play as an ordering structure, and the role of play in bridging communities. The chapter argues that play provides museums with ready-made structures and concepts, which can help planning for visitor learning. The research was equally divided between the co-authors, who developed the conceptual and theoretical aspects of the article by drawing on their own research alongside key examples of museum design and digital media.

The Prince and the Pauper due date card

This is a due date card for the book titled the Prince and the Pauper.