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This paper is concerned with asymptotic theory for penalized spline estimator in bivariate additive model. The focus of this paper is put upon the penalized spline estimator obtained by the backfitting algorithm. The convergence of the algorithm as well as the uniqueness of its solution are shown. The asymptotic bias and variance of penalized spline estimator are derived by an efficient use of the asymptotic results for the penalized spline estimator in marginal univariate model. Asymptotic normality of estimator is also developed, by which an approximate confidence interval can be obtained. Some numerical experiments confirming theoretical results are provided., Comment: 24 pages, 6 figures

U_A(1) symmetry breaking is studied by introducing the flavor mixing interaction proposed by Kobayashi, Maskawa and 't Hooft. Combining the one gluon exchange interaction, the rainbow like Schwinger-Dyson equation and the ladder like Bethe-Salpeter equation are derived. The anomalous PCAC relation in the framework of this approximation is considered. The masses of the pseudoscalar mesons pi,eta and eta' are calculated. It is found that the pion mass is not sensitive to the strength of the flavor mixing interaction. On the other hand, the masses of eta and eta' are reproduced by a relatively weak flavor mixing interaction, for which the chiral symmetry breaking is dominantly induced by the soft-gluon exchange interaction. The decay constants are calculated and the anomalous PCAC relation is numerically checked. It is found that the flavor structures of the eta and eta' mesons significantly depend on their masses and therefore it is quetionable to define a flavor mixing angle for eta and eta'., Comment: 31 pages, LaTex, 8 figures

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Groups of three or four male and female beagle dogs were maintained for 6 months on diets containing BHA at concentrations of 0 (control group), 0.25, 0.5 and 1.0% (w/w). The average daily intake of BHA was about 60 mg/kg body weight in the 0.25% group, 110 mg/kg in the 0.5% group and 220 mg/kg in the 1.0% group. All animals survived the entire experimental period without showing signs of toxicity other than a dose-related retardation of growth. Serum biochemical examinations conducted at 1, 3 and 6 months revealed a slight decrease in albumin concentration and an elevation of alkaline phosphatase and leucine aminopeptidase activity in the higher dose groups. Histopathological and histometrical examination showed no evidence of mucosal alteration in the stomach, oesophagus or duodenum attributable to the administration of BHA. The mitotic index in the squamous epithelium of the distal oesophagus was comparable in the control and BHA-treated groups. Liver weights were increased in BHA-treated groups, but there were no related histopathological changes. From these data it is concluded that feeding of BHA-supplemented diets at palatable concentrations for 6 months has no pathological effects on the stomach, oesophagus, duodenum or liver of beagle dogs.

Two monoclonal antibodies (anti-3–3 and anti-3–40) were produced, which identify two new leukemia-associated antigens. Both antibodies reacted with most cell lines derived from patients with T lymphoblastic leukemia (T-ALL), but were not detected on suspensions of normal hematopoietic cells (including thymocytes) by cytotoxicity, absorption, or indirect immunofluorescence assays. Analysis of fresh leukemic cells indicated that anti-3–3 only reacted with T-ALL cells, while anti-3–40 also reacted with some non-T, non-B ALL cells and a few acute myelocytic leukemia (AML) cells. The 3–40 antigen was also found histopathologically in frozen sections of several normal tissues, including the epithelial cells and a few lymphoid cells of the thymus, and some malignant tissues. The 3–3 antigen was not found in any tissue studied. A “double absorption” assay provided additional serologic evidence that the two antibodies identify different antigenic determinants. Biochemical analysis indicated that the molecules immunoprecipitated by anti-3–3 and anti-3–40 have molecular weights of 35,000–40,000 daltons. This study demonstrated that the 3–3 and 3–40 antigens are markers for human T-ALL and can be used along with the normal T-lymphocyte antigen, 3A1, to discriminate T-ALL from cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia (ATL), and T-cell chronic lymphocytic leukemia (T-CLL).

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.