Development of the high energy engineering X-ray (HEX) superconducting wiggler, magnetic measurement, installation, and commissioning.

The High energy Engineering X-ray (HEX) diffraction beamline at the National Synchrotron Light Source II (NSLS-II) at Brookhaven National Lab (BNL) is the first high-energy beamline capable of reaching 200 keV for a monochromatic beam. With the 3 GeV electron beam energy for the NSLS-II ring, only the superconducting wiggler (SCW) producing greater than 4 T peak field can cover these ranges with a sufficient number of photons. The 1.2 m-long HEX-SCW has a period length of 70 mm and a field strength on-axis of 4.3 T. It utilizes no liquid helium, and the vertical aperture size of the electron beam vacuum chamber is 8 mm. Unlike regular undulators/wigglers, there is no standard configuration for the magnetic measurement system for superconducting insertion devices. The NSLS-II Insertion Devices group has developed, in collaboration with the vacuum group, a novel in-vacuum Hall mapper with a 1.75 m in-vacuum linear motor and an in-vacuum flip coil system utilizing many commercial-off-the-shelf products. The measurements were conducted at the BNL, and the device was installed in the ring and commissioned. This paper provides a description of the SCW and its magnetic measurement systems, as well as a brief account of the installation and commissioning efforts.

Middle meningeal artery embolization for chronic subdural hematoma with cerebrospinal fluid hypovolemia: A report of 2 cases.

BACKGROUND: Chronic subdural hematoma (CSDH) with cerebrospinal fluid hypovolemia syndrome (CHS) remains refractory to standard treatment with hematoma drainage by burr hole and irrigation and/or epidural blood patch. Previously, we reported the utility of middle meningeal artery (MMA) embolization for intractable CSDH. In this study, we present the usefulness of MMA embolization as a treatment for CSDHs with CHSs. CASES: We present two cases of CSDHs with CHSs occurring in patients, 1 treated with burr hole craniotomy and irrigation, and the other treated with the epidural blood patch. Both patients exhibited similar-appearing bilateral relatively-thin hematomas, hyperplasia, and enhanced contrast effects in the dura mater, and extradural hygroma in the cervical portion on enhanced magnetic resonance imaging scans. Also, to reviewing prior literature and imaging findings, they had already undergone conventional treatment. We added MMA embolization treatment and they followed a good course. RESULTS: Despite the known intractable outcomes of patients with CSDHs with CHSs, MMA embolization worked well in the current case series. CONCLUSION: MMA embolization might be considered as a preferred therapeutic option for CSDHs with CHSs in order to buy time before the epidural blood patch starts working.

Factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus: decision-curve analysis.

AIMS: To identify factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus, using decision-curve analysis. METHODS: A retrospective cohort study was performed. The participants were 123 Japanese women with gestational diabetes who underwent 75-g oral glucose tolerance tests at 8-12 weeks after delivery. They were divided into a glucose intolerance and a normal glucose tolerance group based on postpartum oral glucose tolerance test results. Analysis of the pregnancy oral glucose tolerance test results showed predictive factors for postpartum glucose intolerance. We also evaluated the clinical usefulness of the prediction model based on decision-curve analysis. RESULTS: Of 123 women, 78 (63.4%) had normoglycaemia and 45 (36.6%) had glucose intolerance. Multivariable logistic regression analysis showed insulinogenic index/fasting immunoreactive insulin and summation of glucose levels, assessed during pregnancy oral glucose tolerance tests (total glucose), to be independent risk factors for postpartum glucose intolerance. Evaluating the regression models, the best discrimination (area under the curve 0.725) was obtained using the basic model (i.e. age, family history of diabetes, BMI ≥25 kg/m2 and use of insulin during pregnancy) plus insulinogenic index/fasting immunoreactive insulin <1.1. Decision-curve analysis showed that combining insulinogenic index/fasting immunoreactive insulin <1.1 with basic clinical information resulted in superior net benefits for prediction of postpartum glucose intolerance. CONCLUSIONS: Insulinogenic index/fasting immunoreactive insulin calculated using oral glucose tolerance test results during pregnancy is potentially useful for predicting early postpartum glucose intolerance in Japanese women with gestational diabetes.

Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation.

In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm3 /kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.

Rat Articular Cartilages Change Their Tissue and Protein Compositions During Perinatal Period.

Articular cartilage (AC) covers the surface of bones in joints and functions as a cushion against mechanical loading. The tissue contains abundant extracellular matrix (ECM), which mainly consists of proteoglycans (PG) and collagen (COL) fibres. The property of AC is gradually changing by ageing with gravity loading. To know the property change of AC by initial gravity loading during short period after birth, we performed histological assays and proteomics assay on the AC of the femoral condyle in knee joints of perinatal rats. The water content (%) was significantly decreased in neonate AC compared with fetal AC. During the perinatal stages (E19 and P0), the localizations of glycosaminoglycan (GAG) and type I and II COLs were homogeneous. The density of chondrocytes was significantly decreased in the deeper layers comparing with the surface layer in neonate AC. In addition, we found a drastic change in the protein expression pattern on proteomic analysis. The expressions of ECM components were relatively increased in neonate AC compared with fetal AC.

Pegylated feline granulocyte colony-stimulating factor increases neutrophil levels in cats.

Neutropenia can often be corrected by treatment with granulocyte-colony stimulating factor (G-CSF) and off-label use of commercial human G-CSF (HuG-CSF) is a commonly used treatment for neutropenic animals. However, long-term HuG-CSF treatment can be associated with adverse effects, including neutropenia. Here, feline (Fe) G-CSF was produced in Pichia pastoris, pegylated (Peg) FeG-CSF and tested in cats. A randomized controlled clinical trial was conducted to evaluate the efficacy of PegFeG-CSF compared to FeG-CSF or HuG-CSF in FIV-infected (n=14), FIV-uninfected healthy cats (n=19), and in HuG-CSF-induced neutropenic cats (n=4). Daily FeG-CSF doses induced higher neutrophil production than HuG-CSF after the second week of treatment (P ⩽ 0.002). Weekly doses of PegFeG-CSF induced higher neutrophil counts and showed greater sustained activity than weekly doses of FeG-CSF. PegFeG-CSF provided the most therapeutic and sustainable neutrophil production (P<0.001) in both FIV-uninfected and FIV-infected cats, without the development of neutralizing antibodies. Conversely, all HuG-CSF-treated cats developed neutralizing antibodies, suggesting cross-reactive antibodies to endogenous G-CSF in a majority of the cases with severe neutropenia. Strikingly, when PegFeG-CSF was used to rescue cats with HuG-CSF-induced neutropenia, clinically normal neutrophil numbers returned. Thus, PegFeG-CSF appears to be a superior treatment for neutropenia in feline patients.

IL-33 stimulates CXCL8/IL-8 secretion in goblet cells but not normally differentiated airway cells.

BACKGROUND: IL-13, a helper T cell type 2 (Th2) cytokine, transforms cultured airway epithelial cells to goblet cells, and this is not inhibited by corticosteroids. IL-33 stimulates Th2 cytokines and is highly expressed in airways of persons with asthma. The effect of IL-33 on goblet cell differentiation and cytokine secretion has not been described. OBJECTIVE: We examined the effect of IL-33 on CXCL8/IL-8 secretion from goblet or normally differentiated human bronchial epithelial (NHBE) cells and signalling pathways associated with IL-33 activation in these cells. METHODS: Normal human bronchial epithelial cells were grown to goblet or normally differentiated ciliated cell phenotype at air-liquid interface in the presence or absence of IL-13. After 14 days, differentiated cells were exposed to IL-33 for 24 h. RESULTS: CXCL8/IL-8 secretion into the apical (air) side of the goblet cells was greater than from normally differentiated cells (P < 0.01), and IL-33 stimulated apical CXCL8/IL-8 release from goblet cells, but not from normally differentiated cells (P < 0.01). IL-33 increased ERK 1/2 phosphorylation in goblet cells (P < 0.05), and PD98059, a MAPK/ERK kinase inhibitor, attenuated IL-33-stimulated CXCL8/IL-8 secretion from goblet cells (P < 0.001). IL-13 induced ST2 mRNA (P < 0.02) and membrane-bound ST2 protein expression on the apical side surface of goblet cells compared with normally differentiated cells, and neutralization with anti-ST2R antibody attenuated IL-33-induced apical CXCL8/IL-8 secretion from goblet cells (P < 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Goblet cells secrete CXCL8/IL-8, and this is increased by IL-33 through ST2R-ERK pathway, suggesting a mechanism for enhanced airway inflammation in the asthmatic airway with goblet cell metaplasia.

Ontogenetic diet shift of age-0 year Pacific bluefin tuna Thunnus orientalis.

Stomach contents of 437 age-0 year Pacific bluefin tuna Thunnus orientalis (20·3-59·4 cm fork length, L(F)) caught in the Tsushima Current and the Kuroshio regions around Japan were examined to investigate their ontogenetic diet shift. Prey compositions were diverse and different between regions. Although the seasonal growth patterns were different between regions, ontogenetic diet shifts shared a common pattern. In the Tsushima Current region (Sea of Japan), small T. orientalis (20-25 cm L(F)) preyed upon small squid (juvenile Enoploteuthis chunii), and larger ones (25-35 cm L(F)) gradually shifted their diet to mesopelagic fish (Maurolicus japonicus). In the Kuroshio region (Pacific Ocean), small T. orientalis (20-25 cm L(F)) preyed upon small zooplankton (mostly crustacean larvae), and larger ones (25-40 cm L(F)) shifted to epipelagic fishes (Etrumeus teres, Sardinops melanostictus and Engraulis japonicus). The observed data suggest that T. orientalis switch to a diet more based on fish prey items, which have more body mass and greater swimming ability than small squid and zooplankton, after they reach a L(F) of 25 cm.

Age and growth of albacore Thunnus alalunga in the North Pacific Ocean.

The age and growth of North Pacific albacore Thunnus alalunga were investigated using obliquely sectioned sagittal otoliths from samples of 126 females and 148 males. Otolith edge analysis indicated that the identified annulus in a sagittal otolith is primarily formed during the period from September to February. The assessments of the fish age at first annulus formation indicated that the first annulus represents an age of <1 year. This study presents an age estimate (0·75 years) for the formation of the first annulus. The oldest fish ages observed in this study were 10 years for females and 14 years for males. The von Bertalanffy growth parameters of females estimated were L(∞) = 103·5 cm in fork length (L(F) ), K = 0·340 year(-1) and t(0) = -0·53 years, and the parameters of males were L(∞) = 114·0 cm, K = 0·253 year(-1) and t(0) = -1·01 years. Sexual size dimorphism between males and females seemed to occur after reaching sexual maturity. The coefficients of the power function for expressing the L(F) -mass relationship obtained from sex-pooled data were a = 2·964 × 10(-5) and b = 2·928.

Clinicopathologic analysis of acute vascular rejection cases after renal transplantation.

INTRODUCTION: Histopathologic change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathologic analysis of AVR cases after renal transplantation. PATIENTS: AVR was diagnosed in 28 renal transplant recipients followed up in our institute between January 2003 and November 2010. RESULTS: Among 28 cases of AVR, 18 were mild (v1 in Banff 07 classification), 8 were moderate (v2), and 2 were severe (v3). Interstitial inflammation was present in 25 biopsy specimens. Moderate to severe tubulitis (t2-t3) was present in 10 biopsy specimens and transplant glomerulitis in 17; peritubular capillaritis was in 25 of the 28 biopsy specimens. C4d deposition in peritubular capillaries was observed in 11/28 cases. By using assays with plastic beads coated with human leukocyte antigen (HLA) in the 28 cases, we detected circulating anti-HLA alloantibody in 18 patients, among which 11/28 were donor-specific. Acute antibody-mediated rejection was diagnosed in 6 cases. Among AVR cases, 19/28 displayed steroid-resistant rejection (SRR) requiring greater anti-rejection therapy (ART), including muromonab CD3 injection, gusperimus injections, plasmapheresis, intravenous immune globulin, and/or rituximab injections. Twenty of 28 patients recovered renal allograft function after ART, and 26/28 grafts are functioning. Among the 2 cases of graft loss, only 1 patient lost his graft due to AVR. CONCLUSIONS: In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good using available immunosuppression.

IL-13-induced MUC5AC production and goblet cell differentiation is steroid resistant in human airway cells.

BACKGROUND: Glucocorticosteroids (GCS) are used to treat bronchial asthma, but are not uniformly effective, especially in severe asthma. IL-13 is a T helper type 2 cytokine implicated in the pathogenesis of asthma, and IL-13 induces mucus production and goblet cell hyperplasia in airway epithelial cells. The effect of GCS on IL-13-induced mucin production is not well characterized. OBJECTIVE: The aim of this study was to evaluate the effect of dexamethasone (Dex), a potent synthetic GCS, on IL-13-induced MUC5AC mucin expression and goblet cell proliferation in differentiated normal human bronchial epithelial cells (NHBECs). METHODS: NHBECs were cultured for 14 days at an air-liquid interface with IL-13, with or without Dex. MUC5AC protein secretion and mRNA expression was determined using ELISA and quantitative real-time PCR. IL-8 production was assayed using ELISA. Histochemical analysis was performed using H&E and periodic acid-Schiff stain, and MUC5AC immunostaining. RESULTS: Although Dex dose dependently inhibited IL-8 release induced by 5 ng/mL IL-13, Dex 0.001-1 µg/mL had no effect on IL-13 induced MUC5AC protein secretion or mRNA expression. Dex paradoxically increased MUC5AC induced by IL-13 at 0.5 and 1 ng/mL, but had no effect alone or with IL-13 at 0.1 ng/mL. Dex 0.001-1 µg/mL did not inhibit the differentiation of cells into goblet cells and MUC5AC-positive cells induced by IL-13. CONCLUSION AND CLINICAL RELEVANCE: Dex at therapeutic concentrations did not inhibit the effects of IL-13 on goblet cell differentiation, characteristic of severe asthma. Paradoxically, MUC5AC production was increased with lower dose IL-13 exposure. This may lead to airway mucus obstruction commonly seen in life-threatening asthma.

SCN1B is not related to benign partial epilepsy in infancy or convulsions with gastroenteritis.

We hypothesized that benign partial epilepsy in infancy (BPEI) and convulsions with gastroenteritis (CwG) may have a similar genetic background, because previous studies indicate that clinical features overlap between BPEI and CwG. As carbamazepine is effective for cessation of clustering seizures in children with BPEI and CwG, some genetic mutations regarding sodium channels may be related to the development of BPEI and/or CwG. We focused on SCN1B encoding the voltage-dependent sodium channel ß subunit. We explored SCN1B mutation in 6 children with BPEI and 6 children with CwG. Genomic DNAs were extracted from peripheral blood samples accumulated from the patients and all 5 exons of SCN1B were amplified by standard PCR amplification. There were no SCN1B mutations or pathological single nucleotide polymorphisms in any of the patients, although the phenotypes of our patients were typical for BPEI or CwG. Our study demonstrated that SCN1B may not be related to the occurrence of BPEI or CwG.

Observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ).

We report the observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) based on 342 fb(-1) of data collected at the Υ(4S) resonance with the BABAR detector at the PEP-II e+ e- storage rings at SLAC. A simultaneous fit to three D(s)(+) decay chains is performed to extract the signal yield from measurements of the squared missing mass in the B meson decay. We observe the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) with a significance greater than 5 standard deviations (including systematic uncertainties) and measure its branching fraction to be B(B- → D(s)((*)+) K- ℓ- ν(ℓ)) = [6.13(-1.03)(+1.04)(stat)±0.43(syst)±0.51(B(D(s)))]×10(-4), where the last error reflects the limited knowledge of the D(s) branching fractions.

Test of lepton universality in Υ(1S) decays at BABAR.

The ratio R(τµ)(Υ(1S))=Γ(Υ(1S)→τ+ τ-)/Γ(Υ(1S)→µ+ µ-) is measured using a sample of (121.8±1.2)×10(6)Υ(3S) events recorded by the BABAR detector. This measurement is intended as a test of lepton universality and as a search for a possible light pseudoscalar Higgs boson. In the standard model (SM) this ratio is expected to be close to 1. Any significant deviations would violate lepton universality and could be introduced by the coupling to a light pseudoscalar Higgs boson. The analysis studies the decays Υ(3S)→Υ(1S)π+ π-, Υ(1S)→l+ l-, where l=µ, τ. The result, R(τµ)(Υ(1S))=1.005±0.013(stat)±0.022(syst), shows no deviation from the expected SM value, while improving the precision with respect to previous measurements.

Evidence for direct CP violation in the measurement of the Cabbibo-Kobayashi-Maskawa angle γ with B∓ → D(*)K(*)∓ decays.

We report the measurement of the Cabibbo-Kobayashi-Maskawa CP-violating angle γ through a Dalitz plot analysis of neutral D-meson decays to K(S)(0) π+ π- and K(S)(0) K+ K- produced in the processes B∓ → DK∓, B∓ D* K∓ with D* → Dπ(0), Dγ, and B∓ → DK*∓ with K*∓ → K(S)(0) π∓, using 468 million BB pairs collected by the BABAR detector at the PEP-II asymmetric-energy e+ e- collider at SLAC. We measure γ = (68 ± 14 ± 4 ± 3)° (modulo 180°), where the first error is statistical, the second is the experimental systematic uncertainty, and the third reflects the uncertainty in the description of the neutral D decay amplitudes. This result is inconsistent with γ = 0 (no direct CP violation) with a significance of 3.5 standard deviations.

Measurements of charged current lepton universality and |Vus| using tau lepton decays to e- ν(e) ν(τ), µ- ν(µ) ν(τ), π- ν(τ), and K- ν(τ).

Using 467 fb(-1) of e+e- annihilation data collected with the BABAR detector, we measure (B(τ- → µ- ν(µ) ν(τ)))/(B(τ- → e- ν(e) ν(τ))) =(0.9796±0.0016±0.0036), (B(τ- → π- ν(τ)))/(B(τ- → e- ν(e) ν(τ))) = (0.5945±0.0014±0.0061), and (B(τ- → K- ν(τ)))/(B(τ- → e- ν(e) ν(τ))) = (0.03882±0.00032±0.00057), where the uncertainties are statistical and systematic, respectively. From these precision τ measurements, we test the standard model assumption of µ-e and τ-µ charge current lepton universality and provide determinations of |Vus| experimentally independent of the decay of a kaon.

Measurement of D0-D0 mixing parameters using D0 → K(S)(0)π+ π- and D0 → K(S)(0)K+ K- decays.

We report a direct measurement of D0-D0 mixing parameters through a time-dependent amplitude analysis of the Dalitz plots of D(0) → K(S)(0) π+ π- and, for the first time, D0 → K(S)(0)K+ K- decays. The low-momentum pion π(s)(+) in the decay D*+ → D0 π(s)(+) identifies the flavor of the neutral D meson at its production. Using 468.5 fb(-1) of e+ e- colliding-beam data recorded near square root(s)=10.6 GeV by the BABAR detector at the PEP-II asymmetric-energy collider at SLAC, we measure the mixing parameters x = [1.6 ± 2.3(stat) ± 1.2(syst) ± 0.8(model)] × 10(-3), and y = [5.7 ± 2.0(stat) ± 1.3(syst) ± 0.7(model)] × 10(-3). These results provide the best measurement to date of x and y. The knowledge of the value of x, in particular, is crucial for understanding the origin of mixing.

Search for charged lepton flavor violation in narrow upsilon decays.

Charged-lepton flavor-violating processes are unobservable in the standard model, but they are predicted to be enhanced in several extensions to the standard model, including supersymmetry and models with leptoquarks or compositeness. We present a search for such processes in a sample of 99x10(6)Upsilon(2S) decays and 117x10(6)Upsilon(3S) decays collected with the BABAR detector. We place upper limits on the branching fractions B(Upsilon(nS)-->e(+/-)tau(-/+)) and B(Upsilon(nS)-->mu(+/-)tau(-/+)) (n=2,3) at the 10(-6) level and use these results to place lower limits of order 1 TeV on the mass scale of charged-lepton flavor-violating effective operators.

Measurement of |V(cb)| and the form-factor slope in B --> Dl- nu(l) decays in events tagged by a fully reconstructed B meson.

We present a measurement of the Cabibbo-Kobayashi-Maskawa matrix element |V(cb)| and the form-factor slope rho2 in B --> Dl- nu(l) decays based on 460x10(6) BB events recorded at the Upsilon(4S) resonance with the BABAR detector. B --> Dl- nu(l) decays are selected in events in which a hadronic decay of the second B meson is fully reconstructed. We measure B(B- --> D0 l- nu(l))/B(B- --> Xl- nu(l)) = (0.255+/-0.009+/-0.009) and B(B0 --> D+ l- nu(l))/B(B0 --> Xl- nu(l)) = (0.230+/-0.011+/-0.011), along with the differential decay distribution in B --> Dl- nu(l) decays. We then determine G(1)|V(cb)| = (42.3+/-1.9+/-1.4)x10(-3) and rho2 = 1.20+/-0.09+/-0.04, where G(1) is the hadronic form factor at the point of zero recoil.