Investigations into the molecular pathogenesis of essential thrombocythaemia

In order to explore the phenotypic heterogeneity of the myeloproliferative neoplasm essential thrombocythaemia (ET), the role of the JAK2 mutation V617F in the pathogenesis of the disease was investigated, in particular its relationship to myeloid clonality. The clinical, haematological and molecular characteristics of 133 ET patients were studied. JAK2 V617F was detected in 55 (41%) patients; a clonal X-chromosome inactivation pattern (XCIP) was found in 24 (39%) of the 62 evaluable female patients. There was no association between JAK2 mutational status and XCIP status or thrombotic risk, but higher JAK2 V617F mutant levels were noted in patients who had a thrombosis. A trend towards a higher thrombotic rate was observed in patients whose XCIP was clonal. In 10 untreated JAK2 V617F-positive ET patients, JAK2 WT thrombopoiesis was not suppressed despite the presence of a thrombocytosis, suggesting that the regulation of JAK2 WT thrombopoiesis was abnormal. Eleven patients were screened for the presence of more than one JAK2 V617F-positive population using an exonic SNP located near the mutation. In ten (91%) of these the mutation appeared to have been independently acquired on at least two occasions. Furthermore, XCIP analysis of JAK2 V617Fpositive erythroid colonies from six ET patients revealed that in one patient the V617F-positive populations were not derived from a single clonal population. An association between the reported JAK2 haplotype (known as ‘46/1’) and JAK2 V617F-positive ET patients was observed in the cohort studied. Methylation studies indicated that this haplotype introduced additional methylated sites near to the mutation locus, which may potentially affect conformation of the DNA and mutability of the JAK2 locus. Together, the studies reported in this thesis suggest that JAK2 V617F is not the initiating event at least in some cases of ET, and that its presence does not invariably indicate the presence of a monoclonal disorder

Evidence of two-electron tunneling interference in Nb/InAs junctions

The impact of junction transparency in driving phase-coherent charge transfer across diffusive semiconductor-superconductor junctions is demonstrated. We present conductivity data for a set of Nb-InAs junctions differing only in interface transparency. Our experimental findings are analyzed within the quasi-classical Green-function approach and unambiguously show the physical processes giving rise to the observed excess zero-bias conductivity.Comment: 10 pages (RevTex), 4 figures (PostScript), accepted for pubblication in Physical Review

The perseverance of Pacioli's goods inventory accounting system

This paper details sources of the 'undoubtedly strange' (Yamey, 1994a, p.119) system of goods inventory records described in Pacioli’s 1494 bookkeeping treatise and traces the longevity and widespread use of this early perpetual inventory recording (EPIR) system in English language texts. By doing so and contrasting this system with the bookkeeping treatment of modern texts, it is shown that the EPIR system persisted as the dominant form of goods inventory accounting for between 400 and 500 years and that the reasons for its demise are worthy of further consideration and research

Detection of antibacterial activity of essential oil components by TLC-bioautography using luminescent bacteria

The aim of the present study was the chemical characterization of some medically relevant essential oils (tea tree, clove, cinnamon bark, thyme and eucalyptus) and the investigation of antibacterial effect of the components of these oils by use of a direct bioautographic method. Thin layer chromatography (TLC) was combined with biological detection in this process. The chemical composition of the oils was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Eucalyptol (84.2%) was the main component of the essential oil of eucalyptus, eugenol (83.7%) of clove oil, and trans-cinnamic aldehyde (73.2%), thymol (49.9%) and terpinen-4-ol (45.8%) of cinnamon bark, thyme and tea tree oils, respectively. Antibacterial activity of the separated components of these oils, as well as their pure main components (eucalyptol, eugenol, trans-cinnamic aldehyde and thymol) was observed against the Gram-negative luminescence tagged plant pathogenic bacterium Pseudomonas syringae pv. maculicola (Psmlux) and the Gram-negative, naturally luminescent marine bacterium Vibrio fischeri. On the whole, the antibacterial activity of the essential oils could be related to their main components, but the minor constituents may be involved in this process. Trans-cinnamic aldehyde and eugenol were the most active compounds in TLC-bioautography. The sensitivity of TLC-bioautographic method can be improved with using luminescent test bacteria. This method is more cost-effective and provides more reliable results in comparison with conventional microbiological methods, e.g. disc-diffusion technique

Andreev reflections in the pseudogap state of cuprate supercondcutors

We propose that, if the pseudogap state in the cuprate superconductors can be described in terms of the phase-incoherent preformed pairs, there should exist Andreev reflection from these pairs even above the superconducting transition temperature, $T_c$. After giving qualitative arguments for this effect, we present more quantitative calculations based on the Bogoliubov--de Gennes equation. Experimental observations of the effects of Andreev reflections above $T_c$---such as an enhanced tunneling conductance below the gap along the copper oxide plane---could provide unambiguous evidence for the preformed pairs in the pseudogap state.Comment: 5 pages, 1 figur

Comprehensive functional profiling of long non-coding RNAs through a novel pan-cancer integration approach and modular analysis of their protein-coding gene association networks

Background Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes in diseases such as cancer, although the functions of most remain poorly understood. To address this, here we apply a novel strategy to integrate gene expression profiles across 32 cancer types, and cluster human lncRNAs based on their pan-cancer protein-coding gene associations. By doing so, we derive 16 lncRNA modules whose unique properties allow simultaneous inference of function, disease specificity and regulation for over 800 lncRNAs. Results Remarkably, modules could be grouped into just four functional themes: transcription regulation, immunological, extracellular, and neurological, with module generation frequently driven by lncRNA tissue specificity. Notably, three modules associated with the extracellular matrix represented potential networks of lncRNAs regulating key events in tumour progression. These included a tumour-specific signature of 33 lncRNAs that may play a role in inducing epithelial-mesenchymal transition through modulation of TGFβ signalling, and two stromal-specific modules comprising 26 lncRNAs linked to a tumour suppressive microenvironment and 12 lncRNAs related to cancer-associated fibroblasts. One member of the 12-lncRNA signature was experimentally supported by siRNA knockdown, which resulted in attenuated differentiation of quiescent fibroblasts to a cancer-associated phenotype. Conclusions Overall, the study provides a unique pan-cancer perspective on the lncRNA functional landscape, acting as a global source of novel hypotheses on lncRNA contribution to tumour progression

Dressed Sliver solutions in Vacuum String Field Theory

We consider a new class of solutions (dressed slivers) in Vacuum String Field Theory, which represent D25-branes. For each dressed sliver we introduce a deformation parameter and define a family of states which are characterized by new abelian star-subalgebras. We show that this deformation parameter can be used as a regulator: it allows us to define for each such solution a finite norm and energy density. Finally we show how to generalize these results to parallel coincident and to lower dimensional branes.Comment: 39 pages, JHEP style. v2:minor corrections, references adde

Atmospheric aerosols at the Pierre Auger Observatory and environmental implications

The Pierre Auger Observatory detects the highest energy cosmic rays. Calorimetric measurements of extensive air showers induced by cosmic rays are performed with a fluorescence detector. Thus, one of the main challenges is the atmospheric monitoring, especially for aerosols in suspension in the atmosphere. Several methods are described which have been developed to measure the aerosol optical depth profile and aerosol phase function, using lasers and other light sources as recorded by the fluorescence detector. The origin of atmospheric aerosols traveling through the Auger site is also presented, highlighting the effect of surrounding areas to atmospheric properties. In the aim to extend the Pierre Auger Observatory to an atmospheric research platform, a discussion about a collaborative project is presented.Comment: Regular Article, 16 pages, 12 figure

A possible rheological model of gum candies

An appropriate rheological model can be used in production of good quality gum candy required by consumers. For this purpose Creep-Recovery Test (CRT) curves were recorded with a Stable Micro System TA.XT-2 precision texture analyser with 75 mm diameter cylinder probe on gum candies purchased from the local market. The deformation speed was 0.2 mm s−1, the creeping- and recovering time was 60 s, while the loading force was set to 1 N, 2 N, 5 N, 7 N, and 10 N. The two-element Kelvin-Voigt-model, a three-element model, and the four-element Burgers-model were fitted on the recorded creep data, and then the parameters of the models were evaluated. The best fitting from the used models was given by the Burgers model

Abelian and nonabelian vector field effective actions from string field theory

The leading terms in the tree-level effective action for the massless fields of the bosonic open string are calculated by integrating out all massive fields in Witten's cubic string field theory. In both the abelian and nonabelian theories, field redefinitions make it possible to express the effective action in terms of the conventional field strength. The resulting actions reproduce the leading terms in the abelian and nonabelian Born-Infeld theories, and include (covariant) derivative corrections.Comment: 49 pages, 1 eps figur