Test of Lepton-Flavor Universality in B→K

We present a measurement of R_{K^{*}}, the branching fraction ratio B(B→K^{*}µ^{+}µ^{-})/B(B→K^{*}e^{+}e^{-}), for both charged and neutral B mesons. The ratio for the charged case R_{K^{*+}} is the first measurement ever performed. In addition, we report absolute branching fractions for the individual modes in bins of the squared dilepton invariant mass q^{2}. The analysis is based on a data sample of 711 fb^{-1}, containing 772×10^{6} BB[over ¯] events, recorded at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The obtained results are consistent with standard model expectations.

First Observation of the Hadronic Transition ϒ(4S)→ηh(b)(1P) and New Measurement of the h(b)(1P) and η(b)(1S) Parameters.

Using a sample of 771.6×10(6) ϒϒ(4S) decays collected by the Belle experiment at the KEKB e(+)e(-) collider, we observe, for the first time, the transition ϒ(4S)→ηh(b)(1P) with the branching fraction B[ϒ(4S)→ηh(b)(1P)]=(2.18±0.11±0.18)×10(-3) and we measure the h(b)(1P) mass M(h(b)(1P))=(9899.3±0.4±1.0) MeV/c(2), corresponding to the hyperfine (HF) splitting ΔM(HF)(1P)=(0.6±0.4±1.0) MeV/c(2). Using the transition h(b)(1P)→γη(b)(1S), we measure the η(b)(1S) mass M(η(b)(1S))=(9400.7±1.7±1.6) MeV/c(2), corresponding to ΔM(HF)(1S)=(59.6±1.7±1.6) MeV/c(2), the η(b)(1S) width Γ(η(b)(1S))=(8(-5)(+6)±5) MeV/c(2) and the branching fraction B[h(b)(1P)→γη(b)(1S)]=(56±8±4)%.

Search for the dark photon and the dark Higgs boson at belle.

The dark photon A^{'} and the dark Higgs boson h^{'} are hypothetical constituents featured in a number of recently proposed dark sector models. Assuming prompt decays of both dark particles, we search for their production in the so-called Higgstrahlung channel e^{+}e^{-}→A^{'}h^{'}, with h^{'}→A^{'}A^{'}. We investigate ten exclusive final states with A^{'}→e^{+}e^{-}, µ^{+}µ^{-}, or π^{+}π^{-} in the mass ranges 0.1 GeV/c^{2}

Developing Demonstration Test Catchments as a platform for transdisciplinary land management research in England and Wales.

Whilst a large body of plot and field-scale research exists on the sources, behaviour and mitigation of diffuse water pollution from agriculture, putting this evidence into a practical, context at large spatial scales to inform policy remains challenging. Understanding the behaviour of pollutants (nutrients, sediment, microbes and pesticides) and the effectiveness of mitigation strategies over whole catchments and long timeframes requires new, interdisciplinary approaches to organise and undertake research. This paper provides an introduction to the demonstration test catchments (DTC) programme, which was established in 2009 to gather empirical evidence on the cost-effectiveness of combinations of diffuse pollution mitigation measures at catchment scales. DTC firstly provides a physical platform of instrumented study catchments in which approaches for the mitigation of diffuse agricultural water pollution can be experimentally tested and iteratively improved. Secondly, it has established national and local knowledge exchange networks between researchers and stakeholders through which research has been co-designed. These have provided a vehicle to disseminate emerging findings to inform policy and land management practice. The role of DTC is that of an outdoor laboratory to develop knowledge and approaches that can be applied in less well studied locations. The research platform approach developed through DTC has brought together disparate research groups from different disciplines and institutions through nationally coordinated activities. It offers a model that can be adopted to organise research on other complex, interdisciplinary problems to inform policy and operational decision-making.

Poorly differentiated synovial sarcoma: an analysis of clinical, pathologic, and molecular genetic features.

Poorly differentiated synovial sarcoma is a variant of synovial sarcoma in which the tumor cells lack the bland spindle cell appearance of the usual type monophasic synovial sarcoma. Although poorly differentiated synovial sarcoma has been recognized as an entity for many years, no series addressing the clinicopathologic features of this variant have appeared. We describe the histologic, immunohistologic, and molecular findings of a series of 20 poorly differentiated synovial sarcomas. Three types of poorly differentiated synovial sarcoma can be recognized: a large cell epithelioid variant, a small cell variant, and a high-grade spindle cell variant. Epithelial membrane antigen reactivity was seen in 95% of cases, and reactivity for cytokeratin was seen in 42%. The S100 antigen was expressed in 63% of cases. Electron microscopic findings in poorly differentiated synovial sarcoma parallel those found in usual type synovial sarcoma. In 10 cases, material was available for molecular studies; 9 of 10 cases showed the presence of t(X;18) or the associated fusion gene product. These data indicate that poorly differentiated synovial sarcoma is a lesion that shares immunologic, ultrastructural, and molecular characteristics with the usual synovial sarcoma. Follow-up data were available in 16 patients with a mean follow-up of 39 months. Eight patients died with a mean survival time of 33 months. Poorly differentiated synovial sarcoma is a variant of synovial sarcoma that may be associated with a poor prognosis.

Sezary cell leukaemia: a distinct T cell disorder or a variant form of T prolymphocytic leukaemia?

We report the clinical, ultrastructural, immunophenotypic and virological features of nine cases of a rare type of mature T cell disorder formerly designated Sezary cell leukaemia. All patients presented with lymphocytosis ranging from 12.7 to 133 x 10(9)/l, bone marrow infiltration, splenomegaly and lymphadenopathy. Skin involvement was absent at presentation but developed as a terminal event in two patients, one of whom showed a pattern of dermal infiltration different from that characteristic of Sezary syndrome. Cells from eight cases bore a mature T cell phenotype and electronmicroscopy revealed lymphocytes with cerebriform nuclei resembling Sezary cells. All cases except one were HTLV-I negative. Patients were treated with various chemotherapy regimens but with poor outcome, the median survival being 13 months. Laboratory and clinical data suggest great similarity between Sezary cell leukaemia and T prolymphocytic leukaemia (T-PLL), namely coexpression of CD4 and CD8 (3/9 cases), identical chromosomal abnormalities in the three cases studied (isochromosome 8q plus inversion 14 or t(X;14)(q28;q11)) and a remarkable sensitivity to CAMPATH-1H (complete remission of 21 months' duration in one patient), suggesting that this entity could be considered a variant form of T-PLL. The alternative diagnosis of adult T cell leukaemia/lymphoma could not be excluded in one patient in whom positive HTLV-I serology was documented.

Relationship of T leukaemias with cerebriform nuclei to T-prolymphocytic leukaemia: a cytogenetic analysis with in situ hybridization.

Sezary cell leukaemia (SCL) is a mature T-cell leukaemia with characteristic cerebriform nuclei, whereas Sezary syndrome (SS) involves a mature T-cell lymphoma with a similar nuclear morphology. We have examined these diseases by cytogenetics chromosome painting and fluorescence in situ hybridization (FISH). Both diseases had complex cytogenetic abnormalities. All three cases of SCL investigated had inv(14)(q11:q32) and two had iso(8q). No case of SS had these abnormalities but, instead, iso(17q) or 17p+ was present in the three cases of SS investigated and FISH indicated loss of heterozygosity due to deletion of a region at 17p 13 that included the tumour suppressor gene P53, implicating it in this malignancy. One case of SCL had iso(17q). The abnormalities of chromosomes 8 and 14 in SCL are commonly observed in T-prolymphocytic leukaemia (T-PLL) and suggest that SCL may be a variant of T-PLL rather than of SS.

The ultrastructure of mantle cell lymphoma and other B-cell disorders with translocation t(11;14)(q13;q32).

We conducted an ultrastructural study in 22 cases of B-lymphoproliferative disorders in leukaemic phase bearing the t(11;14) translocation. The features of peripheral blood leukaemic cells in nine cases of mantle cell lymphoma (MCL) were compared to those diagnosed as B-prolymphocytic leukaemia (B-PLL) (five cases), splenic lymphoma with villous lymphocytes (SLVL) (four cases), lymphoplasmocytic lymphoma (LPL) (one case), chronic lymphocytic leukaemia with > 10% prolymphocytes (CLL/ PL) (one case) and unclassified B-non Hodgkin's lymphoma (B-NHL) (two cases). The ultrastructural characteristics were also compared to those present in B-NHL without t(11;14), including cases of follicular centre lymphoma (FCL). This study shows that MCL has distinct ultrastructural features including a cleaved or indented nucleus with an even heterochromatin distribution, an absent or inconspicuous nucleolus, low N/C ratio, abundant mitochondria, a well developed Golgi zone, profiles of endoplasmic reticulum and centrioles. This pattern clearly differs from that found in FCL cells. The nuclear pattern of MCL cells also differed from the cells in the other disorders with t(11;14), but shared an organelle-rich cytoplasm, and features which were not apparent in cases without t(11;14). The cytoplasmic changes observed in cells bearing t(11;14) suggest increased cellular activity which may relate to the chromosome translocation and the resulting over-expression of bcl-1.

Immunoblastic transformation of a Sezary syndrome in a black Caribbean patient without evidence of HTLV-I.

We describe an unusual case of Sezary syndrome which transformed into a large T-cell non Hodgkin's lymphoma (immunoblastic) in a black man of Caribbean descent with negative HTLV-I serology and no evidence of HTLV-I infection by DNA analysis using sensitive techniques. The disease presented as a small-cell Sezary syndrome and transformed in an inguinal lymph node one year from diagnosis. Immunological markers in the small and large cells showed a mature T-cell phenotype CD4+, CD8- with expression of T-cell activation markers and a high proliferative rate. Ultrastructural analysis confirmed small Sezary cells with serpentine nucleus in the peripheral blood and immunoblasts in the lymph node. Cytogenetics demonstrated complex clonal chromosome abnormalities with involvement of 7q35, the locus for the beta chain of the T-cell receptor (TCR). Southern-blot analysis showed the same rearrangement of the TCR beta, gamma, delta chain genes in lymph node and peripheral blood cells. Antibodies to HTLV-I were not detected in the serum by ELISA and particle agglutination (PA) nor HTLV-I specific sequences were demonstrated by nested polymerase chain reaction with primers to the envelope proteins, LTR and tax/rex of HTLV-I in both tissues, blood and lymph node. The disease had an aggressive course and was refractory to therapy; the patient died of progressive disease 28 months from presentation. Two unusual features characterised this patient's illness: immunoblastic transformation of a Sezary syndrome in a patient of Afro-Caribbean origin without evidence of HTLV-I DNA sequences and negative HTLV-I serology and the atypical lymph node histology resembling ATLL.

Ossifying fibromyxoid tumor of soft parts with stromal cyst formation and ribosome-lamella complexes.

Ossifying fibromyxoid tumor of soft parts (OFMT) is a recently named soft tissue tumor of uncertain nature. A case is described that presented in a 13-year-old boy as a discrete mass in the muscles of the lower abdominal wall. Light microscopy showed, in addition to the typical features of this entity, microcysts formed by accumulations of the myxoid stroma. Bone formation was lacking. Tumor cells were strongly immunoreactive for vimentin and glial fibrillary acidic protein and weakly so for S-100 protein. A few cells stained for desmin and alpha-smooth muscle actin. Ultrastructurally, there were abundant, patternless cytoplasmic intermediate filaments; short, poorly interdigitating processes; and discontinuous segments of thick external lamina. In addition, several cells contained typical ribosome-lamella complexes in small groups. Ribosome-lamella complexes occur in neoplastic hematopoietic cells but are uncommon in solid tumors, particularly those affecting the soft tissues. These findings extend the range of appearances described for OFMT, which is added to the list of tumors in which ribosome-lamella complexes have been demonstrated. The balance of evidence suggests that OFMT may represent a peripheral nerve sheath tumor of low-grade malignancy, although the picture is incomplete.

Hepatitis A and evidence against the community dissemination of Helicobacter pylori via feces.

Seroprevalence data from 1501 subjects was used to test the hypothesis that Helicobacter pylori may be transmitted by the fecal-oral route. Antibody to hepatitis A virus was used as a marker of fecal-oral exposure. Of the 1501 subjects, 35.5% were seropositive for both H. pylori and hepatitis A, 19.1% were seronegative for both, 36.5% were seropositive for hepatitis A only, and 8.8% were seropositive for H. pylori only. Cross-sectional data from rural areas supported an association between hepatitis A and H. pylori. However, in the urban area there was no evidence of hepatitis A infection in persons < 10 years old, yet the seroprevalence of H. pylori was high in this group (approximately 32%). From our data, we suggest that communitywide fecal-oral spread of H. pylori may be of limited importance.

A transgenic mouse model of sickle cell disorder.

A single base-pair mutation (beta s) in codon 6 of the human beta-globin gene, causing a single amino-acid substitution, is the cause of sickle cell anaemia. The mutant haemoglobin molecule, HbS, polymerizes when deoxygenated and causes deformation of the erythrocytes to a characteristic 'sickled' shape. Sickling of cells in small vessels causes painful crises and other life-threatening complications. Although the molecular basis for sickle cell anaemia has been known for 30 years, no definitive treatment is available. An animal model of sickle cell anaemia would not only allow a detailed analysis of the factors that initiate erythrocyte sickling in vivo and of the pathophysiology of the disease, but would also permit the development of novel approaches to the treatment of the disease. By using the dominant control region sequences from the human beta-globin locus, together with human alpha- and beta s-globin genes, we have obtained three transgenic mice with HbS levels ranging from 10 to 80% of total haemoglobin in their red cells. As observed in homozygous and heterozygous Hbs patients, the erythrocytes of this mouse sickle readily on deoxygenation. Irreversibly sickled cells, which are characteristic of sickle-cell patients homozygous for beta s, are also observed in the peripheral blood of the mouse with high levels of HbS.

The distribution of GAWK-like immunoreactivity in neuroendocrine cells of the human gut, pancreas, adrenal and pituitary glands and its co-localisation with chromogranin B.

GAWK is a recently discovered peptide isolated from extracts of human pituitary gland and subsequently shown to be identical to sequence 420-493 of human chromogranin B. The distribution of this peptide was studied in human gut, pancreas, adrenal and pituitary glands using antisera to two portions of the 74 amino acid peptide (sequences 1-17 and 20-38). In addition, the co-existence of GAWK immunoreactivity with other peptides and chromogranin B was investigated using comparative immunocytochemistry. In the gut, GAWK was localised mainly to serotonin-containing cells of the mucosal epithelium, where electron microscopy showed it to be stored in typical electron-dense (250 nm diameter) granules, and to a moderate population of nerve fibres in the gut wall. Considerable quantities of GAWK-like immunoreactivity were measured in the gut, up to 36.3 +/- 18 pmol GAWK 1-17/g wet weight of tissue (mean +/- SEM) and 12.4 +/- 2.9 pmol GAWK 20-38/g. Chromatography of gut extracts revealed several GAWK-like immunoreactive peaks. GAWK-like immunoreactivity was also detected in endocrine cells of pancreas, pituitary gland and adrenal medulla, where the highest concentrations of GAWK-like immunoreactivity were measured (GAWK 1-17 2071.8 +/- 873.2 and GAWK 20-38 1292.7 +/- 542.7 pmol/g). Endocrine cells containing GAWK-like immunoreactivity were found also to be immunoreactive for chromogranin B. Our results define a discrete distribution of GAWK immunoreactivity in human endocrine cells and nerves and provide morphological support for the postulated precursor-product relationship between chromogranin B and GAWK. Details of the functions of this peptide are awaited.

Pancreastatin distribution and plasma levels in the pig.

Pancreastatin is a peptide isolated from porcine pancreas which has insulin-suppressive actions in vitro and sequence homology with chromogranin A. Using radioimmunoassay and immunocytochemistry we investigated whether pancreastatin has a more widespread distribution and a possible endocrine role in the pig. Pancreastatin immunoreactivity was found in plasma, adrenal gland, pancreas, anterior pituitary and throughout the gastrointestinal tract. The immunoreactivity was colocalized with chromogranin immunoreactivity in endocrine cells and ultrastructurally (in the pancreas) to storage granules. Characterization of pancreastatin-like immunoreactivity, using gel permeation and high performance liquid chromatography, separated 3 different pancreastatin-like immunoreactive forms: one molecular form, indistinguishable from synthetic pancreastatin 1-49, was predominant in pancreas and thyroid and released into the circulation postprandially. However, a high dose (greater than 1 nmol/l) infusion of pancreastatin 33-49 (the biologically active moiety in vitro) into conscious pigs had no effect on either basal or glucose-stimulated insulin secretion.

Expression of the atrial natriuretic peptide gene in the cardiac muscle of rat extrapulmonary and intrapulmonary veins.

Atrial natriuretic peptide is a peptide regulating salt and water balance, originally isolated from the cardiac atrium, where it is synthesised as part of a precursor molecule in specialised myocardial cells. The myocardium extends into the extrapulmonary part of the pulmonary veins in many species, including man. In some small mammals, however, such as the rat, mouse, and bat, it extends further to veins in the peripheral parts of the lung. Since this myocardial layer is continuous with that in the atrium, we have looked for the possible expression of the atrial natriuretic peptide gene in this tissue in rats. Strong immunoreactivity was seen for both the peptide and the N terminal sequence (cardiodilatin) of its precursor in extrapulmonary veins and in intrapulmonary veins extending into the lung as far as the second branching point, where it was localised in the dense cored granules by electron microscopy; in situ hybridisation showed atrial natriuretic peptide messenger RNA at identical sites. Chromatography and radioimmunoassay of extracts of extrapulmonary and intrapulmonary veins showed most of the atrial natriuretic peptide immunoreactivity to be in the uncleaved (precursor molecule) form. Thus the peptide is synthesised in veins both outside and inside the lung, and these extra-atrial sites may be an important additional source of circulating atrial natriuretic peptide.

Sensitivity to X-irradiation of peripheral blood lymphocytes from ageing donors.

The proliferation of human blood lymphocytes from ageing donors, responding to concanavalin A, showed greater sensitivity to inhibition by X-rays than similar cells from younger donors. This increased sensitivity was associated with deficiency in repair of X-ray-induced damage to nuclear material, as measured by density in sucrose gradients, and with increased incidence of chromosomal damage following exposure of freshly isolated lymphocytes. There was also an increased frequency of spontaneous chromosomal aberrations in ageing subjects whose lymphocytes were deficient in repair of DNA damage.

Radiation injury in mouse lung: dependence on oxygen levels in the inspired gas.

The relationship between radiosensitivity and the partial pressure of oxygen (PO2) in the inspired gas has been established for radiation pneumonitis as a measure of lung damage following irradiation of the mouse thorax. The radiosensitivity at low PO2 (0-1 per cent) fitted the linear transformation of the Alper, Howard-Flanders relationship giving a K value for lung tissue of 1.35 per cent oxygen with an oxygen enhancement ratio, m, of 2.13. The radiosensitivity at higher PO2 (5-21 per cent) did not fit the Alper, Howard-Flanders relationship probably because the PO2 of the inspired gas was greater than the PO2 in the alveolus. At the low PO2 levels in the inspired gas, back diffusion of oxygen from blood into the alveolus may lead to errors in the estimated value of K. If the low value of m is due to this 'contaminating' oxygen from blood then by taking a higher value for m, the amount of contaminating oxygen can be calculated (0.23 per cent) and a 'true' value for K(1.1 per cent) determined. Other uncertainties in this estimate of K due to the radiolytic consumption of oxygen and possible inadequacies in equilibration are discussed. Allowing for the uncertainties, it is concluded that the K value for lung damage lies towards the upper end of the range of K values measured for cells in vitro.