Writing projective representations over subfields

Let G=〈X〉be an absolutely irreducible subgroup of GL(d, K), and let F be a proper subfield of the finite field K. We present a practical algorithm to decide constructively whether or not G is conjugate to a subgroup of GL(d, F).K×, where K× denotes the centre of GL(d, K). If the derived group of G also acts absolutely irreducibly, then the algorithm is Las Vegas and costs O(|X|d3+d2log|F|) arithmetic operations in K. This work forms part of a recognition project based on Aschbacher’s classification of maximal subgroups of GL(d, K)

Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus

OBJECTIVES: Current models of clonal expansion in human Barrett's oesophagus are based upon heterogenous, flow-purified biopsy analysis taken at multiple segment levels. Detection of identical mutation fingerprints from these biopsy samples led to the proposal that a mutated clone with a selective advantage can clonally expand to fill an entire Barrett's segment at the expense of competing clones (selective sweep to fixation model). We aimed to assess clonality at a much higher resolution by microdissecting and genetically analysing individual crypts. The histogenesis of Barrett's metaplasia and neo-squamous islands has never been demonstrated. We investigated the oesophageal gland squamous ducts as the source of both epithelial sub-types. METHODS: Individual crypts across Barrett's biopsy and oesophagectomy blocks were dissected. Determination of tumour suppressor gene loss of heterozygosity patterns, p16 and p53 point mutations were carried out on a crypt-by-crypt basis. Cases of contiguous neo-squamous islands and columnar metaplasia with oesophageal squamous ducts were identified. Tissues were isolated by laser capture microdissection and genetically analysed. RESULTS: Individual crypt dissection revealed mutation patterns that were masked in whole biopsy analysis. Dissection across oesophagectomy specimens demonstrated marked clonal heterogeneity, with multiple independent clones present. We identified a p16 point mutation arising in the squamous epithelium of the oesophageal gland duct, which was also present in a contiguous metaplastic crypt, whereas neo-squamous islands arising from squamous ducts were wild-type with respect to surrounding Barrett's dysplasia. CONCLUSIONS: By studying clonality at the crypt level we demonstrate that Barrett's heterogeneity arises from multiple independent clones, in contrast to the selective sweep to fixation model of clonal expansion previously described. We suggest that the squamous gland ducts situated throughout the oesophagus are the source of a progenitor cell that may be susceptible to gene mutation resulting in conversion to Barrett's metaplastic epithelium. Additionally, these data suggest that wild-type ducts may be the source of neo-squamous islands

A growing threat to the ozone layer from short-lived anthropogenic chlorocarbons

Large and effective reductions in emissions of long-lived ozone-depleting substance (ODS) are being achieved through the Montreal Protocol, the effectiveness of which can be seen in the declining atmospheric abundances of many ODSs. An important remaining uncertainty concerns the role of very short-lived substances (VSLSs) which, owing to their relatively short atmospheric lifetimes (less than 6 months), are not regulated under the Montreal Protocol. Recent studies have found an unexplained increase in the global tropospheric abundance of one VSLS, dichloromethane (CH2Cl2), which has increased by around 60 % over the past decade. Here we report dramatic enhancements of several chlorine-containing VSLSs (Cl-VSLSs), including CH2Cl2 and CH2ClCH2Cl (1,2-dichloroethane), observed in surface and upper-tropospheric air in East and South East Asia. Surface observations were, on occasion, an order of magnitude higher than previously reported in the marine boundary layer, whilst upper-tropospheric data were up to 3 times higher than expected. In addition, we provide further evidence of an atmospheric transport mechanism whereby substantial amounts of industrial pollution from East Asia, including these chlorinated VSLSs, can rapidly, and regularly, be transported to tropical regions of the western Pacific and subsequently uplifted to the tropical upper troposphere. This latter region is a major provider of air entering the stratosphere, and so this mechanism, in conjunction with increasing emissions of Cl-VSLSs from East Asia, could potentially slow the expected recovery of stratospheric ozone

Die Rangfolge psychischer und sozialer Prädiktoren und Kriterien für die Prognose Herztransplantierter

Bei 44 Herztransplantierten wurden präoperativ und bis zu einem und drei Jahre postoperativ psychiatrisch/psychologische Untersuchungen durchgeführt und psychosoziale Daten erhoben. Die Prädiktoren und Kriterien für eine gute Prognose wurden ihrer Rangfolge nach hierarchisiert. Es ergab sich folgende Prädiktorrangfolge: 1. die eindeutige Motivation und der unauffällige psychopathologische Befund, 2. der gute soziale Rückhalt und die vor der Transplantation zum Ausdruck gebrachte positive Berufsperspektive, 3. das Bewußtsein der Geborgenheit durch die Familie und die reife psychologische Verarbeitung der Herzerkrankung und der bevorstehenden Herztransplantation, 4. der fortgeschrittene Schweregrad der Herzerkrankung (Schweregrad IV NYHA), 5. der relativ geringe Fernsehkonsum (weniger als an 4 Abenden), und 6. u. a. noch lebende Eltern und das Vorhandensein von Kindern. Für die 7 prognostischen Kriterien ließ sich folgendeKriterienrangfolge ermitteln: 1. die soziale Reintegration, 2. die Lebenszufriedenheit, 3. die Compliance und der psychopathologische Befund, 4. die berufliche Rehabilitation, und 5. die körperliche Belastbarkeit und der körperliche Zustand. Die Studie zeigt, daß es eine unterschiedliche Gewichtung psychosozialer Faktoren vor und nach der Herztransplantation gibt, und daß die soziale Reintegration der beste Indikator für eine erfolgreiche Herztransplantation ist.44 patients underwent psychiatric/psychological and psychosocial examinations before and for one to three years after heart transplantation. Predictors and prognostic criteria for a good result were established according to the rank of their significance. The rank sequence for the predictors were 1. strong motivation and absence of psychiatric symptomatology, 2. good social support and determination to return to work after transplantation, 3. the feeling of being cared for by the family and a mature psychological coping with the heart disease and the expected transplantation, 4. advanced heart failure (stage IV NYHA), 5. watching TV less than 4 evenings a week, 6. parents still living and having one’s own children. The rank sequence for the 7 prognostic criteria for a good result after heart transplantation were 1. social reintegration, 2. being content with life. 3. good compliance and absence of psychopathology, 4. returning to work, and 5. physical exercise tolerance and general physical condition. The study shows that there is a different magnitude of significance for psychosocial factors before and after heart transplantation and that social reintegration is the best indicator for a good result after heart transplantation

Bromocarbons in the tropical coastal and open ocean atmosphere during the Prime Expedition Scientific Cruise 2009 (PESC 09)

Atmospheric concentrations of very short-lived species (VSLS) bromocarbons, including CHBr3, CH2Br2, CHCl2Br, CHClBr2, and CH2BrCl, were measured in the Strait of Malacca and the South China and Sulu–Sulawesi seas during a two-month research cruise in June–July 2009. The highest bromocarbon concentrations were found in the Strait of Malacca, with smaller enhancements in coastal regions of northern Borneo. CHBr3 was the most abundant bromocarbon, ranging from 5.2 pmol mol−1 in the Strait of Malacca to 0.94 pmol mol−1 over the open ocean. Other bromocarbons showed lower concentrations, in the range of 0.8–1.3 pmol mol−1 for CH2Br2, 0.1–0.5 pmol mol−1 for CHCl2Br, and 0.1–0.4 pmol mol−1 for CHClBr2. There was no significant correlation between bromocarbons and in situ chlorophyll a, but positive correlations with both MODIS and SeaWiFS satellite chlorophyll a. Together, the shortlived bromocarbons contribute an average of 8.9 pmol mol−1 (range 5.2–21.4 pmol mol−1) to tropospheric bromine loading, which is similar to that found in previous studies from global sampling networks (Montzka et al., 2011). Statistical tests showed strong Spearman correlations between brominated compounds, suggesting a common source. Log–log plots of CHBr3/CH2Br2 versus CHBr2Cl/CH2Br2 show that both chemical reactions and dilution into the background atmosphere contribute to the composition of these halocarbons at each sampling point. We have used the correlation to make a crude estimate of the regional emissions of CHBr3 and to derive a value of 32 Gg yr−1 for the Southeast (SE) Asian region (10◦ N–20◦ S, 90–150◦ E). Finally, we note that satellite-derived chlorophyll a (chl a) products do not always agree well with in situ measurements, particularly in coastal regions of high turbidity, meaning that satellite chl a may not always be a good proxy for marine productivity

Immunosuppressive niche engineering at the onset of human colorectal cancer

The evolutionary dynamics of tumor initiation remain undetermined, and the interplay between neoplastic cells and the immune system is hypothesized to be critical in transformation. Colorectal cancer (CRC) presents a unique opportunity to study the transition to malignancy as pre-cancers (adenomas) and early-stage cancers are frequently resected. Here, we examine tumor-immune eco-evolutionary dynamics from pre-cancer to carcinoma using a computational model, ecological analysis of digital pathology data, and neoantigen prediction in 62 patient samples. Modeling predicted recruitment of immunosuppressive cells would be the most common driver of transformation. As predicted, ecological analysis reveals that progressed adenomas co-localized with immunosuppressive cells and cytokines, while benign adenomas co-localized with a mixed immune response. Carcinomas converge to a common immune “cold” ecology, relaxing selection against immunogenicity and high neoantigen burdens, with little evidence for PD-L1 overexpression driving tumor initiation. These findings suggest re-engineering the immunosuppressive niche may prove an effective immunotherapy in CRC

Modelling the chemistry and transport of bromoform within a sea breeze driven convective system during the SHIVA Campaign

We carry out a case study of the transport and chemistry of bromoform and its product gases (PGs) in a sea breeze driven convective episode on 19 November 2011 along the North West coast of Borneo during the "Stratospheric ozone: Halogen Impacts in a Varying Atmosphere" (SHIVA) campaign. We use ground based, ship, aircraft and balloon sonde observations made during the campaign, and a 3-D regional online transport and chemistry model capable of resolving clouds and convection explicitly that includes detailed bromine chemistry. The model simulates the temperature, wind speed, wind direction fairly well for the most part, and adequately captures the convection location, timing, and intensity. The simulated transport of bromoform from the boundary layer up to 12 km compares well to aircraft observations to support our conclusions. The model makes several predictions regarding bromine transport from the boundary layer to the level of convective detrainment (11 to 12 km). First, the majority of bromine undergoes this transport as bromoform. Second, insoluble organic bromine carbonyl species are transported to between 11 and 12 km, but only form a small proportion of the transported bromine. Third, soluble bromine species, which include bromine organic peroxides, hydrobromic acid (HBr), and hypobromous acid (HOBr), are washed out efficiently within the core of the convective column. Fourth, insoluble inorganic bromine species (principally Br2) are not washed out of the convective column, but are also not transported to the altitude of detrainment in large quantities. We expect that Br2 will make a larger relative contribution to the total vertical transport of bromine atoms in scenarios with higher CHBr3 mixing ratios in the boundary layer, which have been observed in other regions. Finally, given the highly detailed description of the chemistry, transport and washout of bromine compounds within our simulations, we make a series of recommendations about the physical and chemical processes that should be represented in 3-D chemical transport models (CTMs) and chemistry climate models (CCMs), which are the primary theoretical means of estimating the contribution made by CHBr3 and other very short-lived substances (VSLS) to the stratospheric bromine budget

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

Time, the Written Record, and Professional Practice: The Case of Contemporary Social Work

Drawing on a three year ethnographically-oriented study exploring contemporary professional social work writing, this paper focuses on a key concern: the amount of time taken up with writing, or ‘paperwork’. We explore the relationship between time and professional social work writing in three key ways. Firstly, as a discrete, measurable phenomenon - how much time is spent on writing? Secondly, as a textual dimension to social work writing – how do institutional documents drive particular entextualisations of time and how do social worker texts entextualise time? Thirdly, as a particular timespace configuration of lived experience - how is time experienced by professional social workers? Findings indicate that a dominant institutional chronotope is governing social work textual practice underpinned by an ideology of writing which is at odds with social workers’ desired practice and professional goals. Methodologically, the paper illustrates the value of combining a range of data and analytic tools, using textual and contextual data, as well as qualitative and quantitative frames of analysis

NOTUM from Apc-mutant cells biases clonal competition to initiate cancer

The tumour suppressor APC is the most commonly mutated gene in colorectal cancer. Loss of Apc in intestinal stem cells drives the formation of adenomas in mice via increased WNT signalling1, but reduced secretion of WNT ligands increases the ability of Apc-mutant intestinal stem cells to colonize a crypt (known as fixation)2. Here we investigated how Apc-mutant cells gain a clonal advantage over wild-type counterparts to achieve fixation. We found that Apc-mutant cells are enriched for transcripts that encode several secreted WNT antagonists, with Notum being the most highly expressed. Conditioned medium from Apc-mutant cells suppressed the growth of wild-type organoids in a NOTUM-dependent manner. Furthermore, NOTUM-secreting Apc-mutant clones actively inhibited the proliferation of surrounding wild-type crypt cells and drove their differentiation, thereby outcompeting crypt cells from the niche. Genetic or pharmacological inhibition of NOTUM abrogated the ability of Apc-mutant cells to expand and form intestinal adenomas. We identify NOTUM as a key mediator during the early stages of mutation fixation that can be targeted to restore wild-type cell competitiveness and provide preventative strategies for people at a high risk of developing colorectal cancer