Energy of the

The low-lying isomeric state of ^{229}Th provides unique opportunities for high-resolution laser spectroscopy of the atomic nucleus. We determine the energy of this isomeric state by taking the absolute energy difference between the excitation energy required to populate the 29.2-keV state from the ground state and the energy emitted in its decay to the isomeric excited state. A transition-edge sensor microcalorimeter was used to measure the absolute energy of the 29.2-keV γ ray. Together with the cross-band transition energy (29.2 keV→ground) and the branching ratio of the 29.2-keV state measured in a recent study, the isomer energy was determined to be 8.30±0.92 eV. Our result is in agreement with the latest measurements based on different experimental techniques, which further confirms that the isomeric state of ^{229}Th is in the laser-accessible vacuum ultraviolet range.

First measurement of the form factors in the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e).

The beauty to up quark coupling constant |V(ub)| can be extracted from B → ρ e+ ν(e) combined with the form factors for D → K* e+ ν(e) and B → V ℓ+ ℓ- and D → ρ e+ ν(e). Using the entire CLEO-c ψ(3770) → DD event sample, corresponding to an integrated luminosity of 818 pb(-1) and approximately 5.4×10(6) DD events, we measure the form factors for the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e) for the first time and the branching fractions with improved precision. A four-dimensional unbinned maximum likelihood fit determines the form factor ratios to be V(0)/A1(0)=1.48±0.15±0.05 and A2(0)/A1(0)=0.83±0.11±0.04. Assuming Cabibbo-Kobayashi-Maskawa unitarity, the known D meson lifetimes, and our measured branching fractions we obtain the form factor normalizations A1(0), A2(0), and V(0). We also present a measurement of the branching fraction for D+ → ω e+ ν(e) with improved precision.

Nosocomial infection with rotavirus vaccine strain in paediatric patients with immunodeficiency.

In infants with immunodeficiency, rotavirus (RV) vaccines can be continuously excreted in stool. We analysed nosocomial infection with RV vaccine strain in immunodeficient paediatric patients. RV1 RNAs were detected in stool and serum samples from case A, who was vaccinated with RV1, and case B, who was not. PAGE analysis of serial stool samples of case A revealed several rearrangements of the RV genome. In case B, the only band pattern detected was the same as a rearrangement detected in case A at the same time. In summary, RV vaccination of infants with immunodeficiency poses a risk of nosocomial infections.

Observation of the h(c)(1P) Using e+ e- collisions above the DD threshold.

Using 586 pb(-1) of e+ e- collision data at E(c.m.) = 4170 MeV, produced at the Cornell Electron Storage Ring collider and collected with the CLEO-c detector, we observe the process e+ e- → π+ π- h(c)(1P). We measure its cross section to be 15.6±2.3±1.9±3.0 pb, where the third error is due to the external uncertainty on the branching fraction of ψ(2S) → π0 h(c)(1P), which we use for normalization. We also find evidence for e+ e- → ηh(c)(1P) at 4170 MeV at the 3σ level and see hints of a rise in the e+ e- → π+ π- h(c)(1P) cross section at 4260 MeV.

Nanotechnology: 'buckypaper' from coaxial nanotubes.

Double-walled carbon nanotubes are needed in a pure, highly crystalline form before features such as their electronic properties, thermal transport and mechanical behaviour can be investigated. Here we fabricate a paper-like material that consists of hexagonally packed bundles of clean, coaxial carbon nanotubes whose double walls vary little in diameter; it is prepared in high yields using chemical-vapour deposition with a conditioning catalyst and two-step purification. Our results will enable investigation of the physical properties of double-walled carbon nanotubes, which are predicted to be superior to those of both their single- and multiwalled relatives.

Novel microcantilever design for versatile mass sensor application.

This study presents a new microcantilever design for versatile mass sensor application. The novel comb-type cantilever provides a sensitive microcantilever structure for normal sensor application, and its sensing responses are compared with those of a commercial cantilever. While the comb-type cantilever has a similar total surface area to the commercial cantilever, there is a distinct difference in the design of the regional surface area. The results for a static charge interaction, used to compare the sensitivity of normal sensor applications, show a significant resonant frequency change for the comb-type cantilever when compared with that for the commercial cantilever, indicating the importance of the large surface area in the highly sensitive cantilever region. Thus, a schematic structure of a microcantilever for fabricating a highly sensitive mass sensor is proposed.

Midkine (MK), a heparin-binding growth/differentiation factor, is regulated by retinoic acid and epithelial-mesenchymal interactions in the developing mouse tooth, and affects cell proliferation and morphogenesis.

Midkine (MK) is the first cloned gene in a new family of heparin-binding growth/differentiation factors involved in the regulation of growth and differentiation. We have analyzed the expression of MK mRNA and protein during tooth development in mouse embryos and studied the regulation of MK expression and the biological effects of MK protein in organ cultures. MK expression was restricted and preferential in the tooth area as compared to the rest of the developing maxillary and mandibular processes suggesting specific functions for MK during tooth morphogenesis. MK mRNA and protein were expressed during all stages of tooth formation (initiation, morphogenesis, and cell differentiation), and shifts of expression were observed between the epithelial and mesenchymal tissue components. However, the expression of mRNA and protein showed marked differences at some stages suggesting paracrine functions for MK. Tissue recombination experiments showed that MK gene and protein expression are regulated by epithelial-mesenchymal interactions, and, moreover, that dental tissue induces the ectopic expression of MK protein in non-dental tissue. The expression of MK gene and protein in the mandibular arch mesenchyme from the tooth region were stimulated by local application of retinoic acid in beads. Cell proliferation was inhibited in dental mesenchyme around the beads releasing MK, but this effect was modulated by simultaneous application of FGF-2. Morphogenesis and cell differentiation were inhibited in tooth germs cultured in the presence of neutralizing antibodies for MK, whereas the development of other organs (e.g., salivary gland, kidney) was unaffected. These results suggest important roles for MK in the molecular cascade that regulates tooth development.

Neointima formation in a restenosis model is suppressed in midkine-deficient mice.

Neointima formation is a common feature of atherosclerosis and restenosis after balloon angioplasty. To find a new target to suppress neointima formation, we investigated the possible role of midkine (MK), a heparin-binding growth factor with neurotrophic and chemotactic activities, in neointima formation. MK expression increased during neointima formation caused by intraluminal balloon injury of the rat carotid artery. Neointima formation in a restenosis model was strongly suppressed in MK-deficient mice. Continuous administration of MK protein to MK-deficient mice restored neointima formation. Leukocyte recruitment to the vascular walls after injury was markedly decreased in MK-deficient mice. Soluble MK as well as that bound to the substratum induced migration of macrophages in vitro. These results indicate that MK plays a critical role in neointima formation at least in part owing to its ability to mediate leukocyte recruitment.

Mitemcinal (GM-611), an orally active motilin agonist, facilitates defecation in rabbits and dogs without causing loose stools.

The effects of mitemcinal (GM-611), an orally active motilin agonist, on defecation were investigated in rabbits and dogs. In normal rabbits, within 0-3 h of dosing, orally administered mitemcinal (2.5-10 mg kg(-1)) increased stool weight in a dose-dependent manner without causing loose stools. Sennoside (12-48 mg kg(-1)) also facilitated defecation within 2-9 h of oral administration, but the stools were significantly loosened. In the morphine-induced constipation model, the stool weight of morphine-treated rabbits (1 mg kg(-1)) was only 37.5% of that of untreated animals. Mitemcinal (0.5-20 mg kg(-1)) dose-dependently increased stool weight without increasing stool water content. At the highest dose of mitemcinal, stool weight recovered to 83.9% of that of untreated animals. In normal dogs, mitemcinal (0.3-3 mg kg(-1)) reduced the time to first bowel movement after oral administration without inducing diarrhoea at any dose. These results indicate that mitemcinal facilitates defecation without inducing severe diarrhoea. It is suggested that mitemcinal may be a novel therapeutic agent for constipation that enables easier control of the timing of defecation because of the early onset and short duration of its action, compared with sennoside.

Nutritional assessment using stable isotope ratios of carbon and nitrogen in the scalp hair of geriatric patients who received enteral and parenteral nutrition formulas.

BACKGROUND & AIMS: The δ13C and δ15N values in the scalp hair of geriatric patients in Japan who received the enteral or parenteral nutrition formula were measured to assess nutritional status. METHODS: The relations among δ13C, δ15N, calorie intake, BMI, albumin concentration, total cholesterol (T-CHO) and geriatric nutritional risk index (GNRI) in the patients were investigated. Furthermore, the enrichment of δ13C and δ15N from the nutrients to the hair was investigated. RESULTS: The δ13C values in the hair of patients who received enteral nutrition decreased with decreases in the calories received, while the δ15N values increased, suggesting malnutrition in some patients with a low calorie intake due to a negative nitrogen balance. The distribution of patients with a low calorie intake (below 20 kcal/kg/day) when δ13C was plotted against δ15N differed from that of control subjects, but the distribution of patients with a high calorie intake (above 20 kcal/kg/day) was similar to that of control subjects. No significant differences were observed in BMI, albumin concentration, T-CHO or GNRI between the low and high calorie groups. The enrichment of δ13C and δ15N from the enteral nutrients to the hair were inversely correlated with the δ13C and δ15N in the enteral nutrients. The enrichment levels of δ13C and δ15N tended to be higher and lower, respectively, in the high calorie group. On the other hand, the δ13C and δ15N values in the hair of patients who received parenteral nutrition were higher and lower than those in the control subjects and in the patients who received enteral nutrition, respectively, reflecting the higher δ13C and lower δ15N contents of the parenteral nutrients. CONCLUSIONS: The δ13C and δ15N values in the hair of patients who received enteral nutrition may be effective indicators for evaluating the long-term nutritional status of geriatric patients. A calorie intake of 20 kcal/kg/day may be a cut-off value for malnutrition in Japanese geriatric patients receiving enteral nutrition. However, caution is necessary when dealing with patients switching from parental nutrition as parenteral nutrition resulted in different changes in δ13C and δ15N. The enrichment levels of δ13C and δ15N from the enteral nutrients to the hair may be inversely correlated with the δ13C and δ15N values of enteral nutrients and vary according to the calorie intake.

Biochemical properties of the high-molecular-weight glycopeptides released from the cell surface of human teratocarcinoma cells.

The present study deals with the biochemical properties of high-molecular-weight glycopeptides isolated from the surface of human teratocarcinoma cells. This cell surface material released by mild trypsin digestion from galactose-labeled human teratocarcinoma cells, Tera I and PA1, was digested extensively with pronase. Most of the resulting glycopeptides were large and were excluded from a Sephadex G-50 column. The properties of these large cell surface glycopeptides isolated from Tera I cells have been examined in detail. It is clear from these experiments that they are neither acidic mucopolysaccharides nor mucin-type glycopeptides with short oligosaccharide chains. Although the glycopeptides are hardly hydrolyzed by beta-galactosidase even after prior digestion with neuraminidase, around 30% of the glycopeptides are depolymerized by treatment with endo-beta-galactosidase from Escherichia freundii. The large cell surface glycopeptides from Tera I cells therefore appear to be very similar to the large glycopeptides seen on mouse embryonal carcinoma cells, which have core structures composed of galactose and N-acetylglucosamine. Like the mouse cell glycopeptides, a fraction of the large glycopeptides from these human cells bind to agarose-conjugated fucose-binding proteins and peanut agglutinin.

Superoxide dismutase in SAS human tongue carcinoma cell line is a factor defining invasiveness and cell motility.

This article describes an apparent inverse relationship between cell motility and intracellular Cu-Zn superoxide dismutase (SOD) activity of two human squamous carcinoma-derived clones, SAS-H1 with high invasiveness and SAS-L1 with low invasiveness. Clone SAS-H1 exhibited significantly greater motility than SAS-L1 but had significantly lower levels of intracellular Cu-ZnSOD than SAS-L1 cells. We then transfected Cu-ZnSOD antisense cDNA into SAS-L1 to reduce the intracellular Cu-ZnSOD activity. Antisense cDNA transfected SAS-L-AS clones had lower Cu-ZnSOD activity than control vector-transfected SAS-L-Neo clones, and this was associated with increased motility. Invasiveness of SAS-H1 and SAS-L-AS1 was enhanced by superoxide treatment, while the invasiveness of SAS-L1 was unaffected. These findings indicate that intracellular SOD is involved in cell motility by virtue of its action in scavenging superoxide in the cells.

Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas.

Cyclooxygenase (COX)-2 expression was immunohistochemically examined in 59 human lung cancers as well as in normal and premalignant lung specimens. In contrast to scattered weak reactivity seen in normal peripheral airway epithelial cells, markedly up-regulated COX-2 expression was detected in about one-third of atypical adenomatous hyperplasias and carcinoma in situ specimens, and a significant increase in COX-2 expression was observed in 70% of invasive adenocarcinoma cases. Interestingly, the proportion of adenocarcinoma cells with marked COX-2 expression was much greater in lymph node metastases than in the corresponding primary tumors. In contrast, small cell carcinomas showed virtually negligible expression, and squamous cell carcinomas showed infrequent and low expression. These findings suggest that an increase in COX-2 expression may be associated with the development of adenocarcinomas and possibly with acquisition of an invasive and metastatic phenotype.

Incidence of gastroesophageal reflux associated with percutaneous endoscopic gastrostomy contrast agent viscosity: a randomized controlled crossover trial.

BACKGROUND/OBJECTIVES: Semisolid formulae are increasingly used in Japan to reduce the risks of gastroesophageal reflux (GER) and aspiration pneumonia in patients undergoing percutaneous endoscopic gastrostomy (PEG). We compared the incidences of GER after the use of liquid or semisolid contrast agents during PEG. SUBJECTS/METHODS: Patients who planned to undergo PEG were randomly assigned to the liquid-first (LF) group (liquid contrast agent on day 1 after PEG and a semisolid contrast agent on day 2) or the semisolid-first (SF) group (reversed order). A 200-ml agent bolus was administered via a PEG tube to the patient in the supine position. The upper gastrointestinal tract was radiologically examined from onset to 1 min after the end of administration. The incidences of GER were compared. We also evaluated the daily changes in GER incidence, effect of hiatal hernia severity and adverse events. RESULTS: We analyzed the results of 66 patients (32, LF group; 34, SF group). The incidence of GER observed using only liquid contrast was 27% (18/66) and that using only semisolid was 11% (7/66) (P=0.028). There was no difference in the GER incidences between day 1 and day 2. In patients with severe, mild and no hiatal hernia, GER incidences in the liquid contrast agent were 80% (4/5), 61% (11/18) and 33% (13/43), respectively (P=0.031). GER incidence after using the semisolid contrast agent was lower in patients with no and mild hiatal hernia. The predominant adverse event was diarrhea; aspiration was not observed. CONCLUSIONS: Semisolid contrast agents reduced the incidence of GER after PEG.

Functional characterization of a novel GFI1B mutation causing congenital macrothrombocytopenia.

UNLABELLED: Essentials Two groups recently reported GFI1B as a novel causative gene for congenital macrothrombocytopenia. We performed functional analysis of a novel GFI1B mutation and previous mutations. An immunofluorescence analysis of the platelet CD34 expression can be useful as a screening test. Mutant-transduced megakaryocytes produced enlarged proplatelet tips which were reduced in number. SUMMARY: Background GFI1B is an essential transcription factor for megakaryocyte and erythrocyte development. Two groups have recently identified GFI1B as a novel causative gene for congenital macrothrombocytopenia associated with α-granule deficiency. Methods We performed whole exome sequencing and identified a novel GFI1B p.G272fsX274 mutation in a family with macrothrombocytopenia, and a decreased number of platelet α-granules and abnormally shaped red blood cells. p.G272fsX274 and the previous two mutations all predicted disruption of an essential DNA-binding domain in GFI1B. We therefore performed functional studies to characterize the biochemical and biological effects of these three patient-derived mutations. Results An immunofluorescence analysis revealed decreased thrombospondin-1 and increased CD34 expression in platelets from our patient. Consistent with the previous studies, the three patient-derived mutants were unable to repress the expression of the reporter gene and had a dominant-negative effect over wild-type GFI1B. In addition, the three mutations abolished recognition of a consensus-binding site in gel shift assays. Furthermore, transduction of mouse fetal liver-derived megakaryocytes with the three GFI1B mutants resulted in the production of abnormally large proplatelet tips, which were reduced in number. Conclusions Our study provides further proof of concept that GFI1B is an essential protein for the normal development of the megakaryocyte lineage.

Fluorination of double-walled carbon nanotubes.

Fluorine atoms are selectively attached to the sidewall of the outer shell of DWNTs without disrupting the double-layered morphology; the stoichiometry of the fluorinated DWNTs is CF(0.30).

Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines.

In recent years, a combination of two demographic phenomena, an increase in the number of older people in the population and an increase in the incidence of lung cancer with age, has made it mandatory to develop therapeutic modalities with less toxicity for the treatment of inoperable elderly patients with lung cancer. Our study shows that a cyclooxygenase (COX)-2 inhibitor, nimesulide, can inhibit proliferation of non-small cell lung cancer cell lines in vitro in a dose-dependent manner, in part by inducing apoptosis even at clinically achievable low concentrations. Our observations also suggest that the responsiveness of non-small cell lung cancer to COX-2 inhibitors does not require the presence of wild-type p53, but may be influenced by the degree of COX-2 expression. In addition, we found that nimesulide, when used in combination at clinically achievable concentrations, reduced the IC50 values of various anticancer agents by up to 77%, although the level of reduction varied considerably. Because our previous studies have indicated a significantly increased COX-2 expression in up to 70% of adenocarcinoma cases, the present findings are of great clinical interest. In conjunction with the recent development of next generation, highly selective COX-2 inhibitors, they can be expected to lead to even greater efficacy of their use as adjuncts to various anticancer agents for the treatment of high-risk patients without compromising their quality of life.

Growth of double-walled carbon nanotubes using a conditioning catalyst.

Here we describe the effect of different synthetic conditions on the quality and purity of double-walled carbon nanotubes (DWNTs) with the aid of a conditioning catalyst. By lowering the reaction temperature down to 875 degrees C and utilizing a conditioning catalyst, increased purity and a decreased inner diameter of the DWNTs was achieved, while adverse results were observed with increasing reaction temperature. Based on detailed high-resolution transmission electron microscopy studies on the diameter distribution of the tubes, preferential growth conditions for DWNTs over single-wall carbon nanotubes are identified solely from increased carbon solubility considerations (caused by an increased portion of active carbon species by use of Mo) for the same distribution of metal particles.

Second allogeneic hematopoietic stem cell transplantation in children with severe aplastic anemia.

The outcome of 55 children with severe aplastic anemia (SAA) who received a second hematopoietic stem cell transplantation (HSCT) was retrospectively analyzed using the registration data of the Japanese Society for Hematopoietic Cell Transplantation. The 5-year overall survival (OS) and failure-free survival (FFS) after the second transplantation were 82.9% (95% confidence interval (CI), 69.7-90.8)) and 81.2% (95% CI, 67.8-89.4), respectively. FFS was significantly better when the interval between the first and second transplantation was >60 days (88.9%; 95% CI, 73.0-95.7) than when it was ⩽60 days (61.4%; 95% CI, 33.3-80.5; P=0.026). All 12 patients who were conditioned with regimens containing fludarabine and melphalan were alive with hematopoietic recovery. These findings justify the recommendation of a second HSCT for children with SAA who have experienced graft failure after first HSCT.

Midkine is expressed during repair of bone fracture and promotes chondrogenesis.

Midkine (MK) is a heparin-binding growth/differentiation factor implicated in the control of development and repair of various tissues. Upon fracture of the murine tibia, MK was found to be transiently expressed during bone repair. MK was immunohistochemically detected in spindle-shaped mesenchymal cells at the fracture site on day 4 after fracture and in chondrocytes in the area of endochondral ossification on day 7. MK expression was decreased on day 14 and scarcely seen on day 28 when bone repair was completed. This mode of MK expression is reminiscent of MK expression during development. MK was expressed in hypertrophic chondrocytes of the prebone cartilage rudiments on embryonic day 14 in mouse embryos. MK was also strongly expressed in the epiphyseal growth plate. MK was localized intracellularly during both bone repair and development, and this localization was confirmed by immunoelectron microscopy for embryonic chondrocytes. When MK cDNA was transfected into ATDC5 chondrogenic cells and overexpressed, the majority of transfected cells with strong MK expression showed enhanced chondrogenesis as revealed by increased synthesis of sulfated glycosaminoglycans, aggrecan, and type II collagen. These results suggest that MK plays important roles in chondrogenesis and contributes to bone formation and repair.