QSAR model to predict Kp,uu,brain with a small dataset, incorporating predicted values of related parameter.

The unbound brain-to-plasma concentration ratio (Kp,uu,brain) is a parameter that indicates the extent of central nervous system penetration. Pharmaceutical companies build prediction models because many experiments are required to obtain Kp,uu,brain. However, the lack of data hinders the design of an accurate prediction model. To construct a quantitative structure-activity relationship (QSAR) model with a small dataset of Kp,uu,brain, we investigated whether the prediction accuracy could be improved by incorporating software-predicted brain penetration-related parameters (BPrPs) as explanatory variables for pharmacokinetic parameter prediction. We collected 88 compounds with experimental Kp,uu,brain from various official publications. Random forest was used as the machine learning model. First, we developed prediction models using only structural descriptors. Second, we verified the predictive accuracy of each model with the predicted values of BPrPs incorporated in various combinations. Third, the Kp,uu,brain of the in-house compounds was predicted and compared with the experimental values. The prediction accuracy was improved using five-fold cross-validation (RMSE = 0.455, r2 = 0.726) by incorporating BPrPs. Additionally, this model was verified using an external in-house dataset. The result suggested that using BPrPs as explanatory variables improve the prediction accuracy of the Kp,uu,brain QSAR model when the available number of datasets is small.

First Measurements of Absolute Branching Fractions of the Ξ_{c}

We present the first measurements of absolute branching fractions of Ξ_{c}^{0} decays into Ξ^{-}π^{+}, ΛK^{-}π^{+}, and pK^{-}K^{-}π^{+} final states. The measurements are made using a dataset comprising (772±11)×10^{6} BB[over ¯] pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. We first measure the absolute branching fraction for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} using a missing-mass technique; the result is B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})=(9.51±2.10±0.88)×10^{-4}. We subsequently measure the product branching fractions B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→Ξ^{-}π^{+}), B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→ΛK^{-}π^{+}), and B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+}) with improved precision. Dividing these product branching fractions by the result for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} yields the following branching fractions: B(Ξ_{c}^{0}→Ξ^{-}π^{+})=(1.80±0.50±0.14)%, B(Ξ_{c}^{0}→ΛK^{-}π^{+})=(1.17±0.37±0.09)%, and B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+})=(0.58±0.23±0.05)%. For the above branching fractions, the first uncertainties are statistical and the second are systematic. Our result for B(Ξ_{c}^{0}→Ξ^{-}π^{+}) can be combined with Ξ_{c}^{0} branching fractions measured relative to Ξ_{c}^{0}→Ξ^{-}π^{+} to yield other absolute Ξ_{c}^{0} branching fractions.

Influence of radiologic expertise in detecting lung tumors on chest radiographs.

PURPOSE: To analyze the influence of radiologic expertise in detecting lung tumors on chest radiographs. MATERIALS AND METHODS: We retrieved posteroanterior chest radiographs and CT examination obtained from 283 patients with solitary primary malignant lung tumors who underwent surgical resection. There were 176 men and 107 women with a mean age of 67.0±9.1 (SD) years (range: 33-88 years). Thirteen first-year post-graduate (PGY-1) trainees and nine pulmonary specialists (three radiologists, three thoracic surgeons, and three pulmonologists) interpreted the chest radiographs. Detection rates among trainees and specialists were compared using Student t test. RESULTS: The total numbers of detected tumors ranged from 103 (36.4%) to 136 (48.1%) with a mean of 127.9±9.1 (45.2±3.2%) in the trainee group, and 137 (48.4%) to 182 (64.3%) with a mean of 161.6±13.1 (57.1±4.6%) in the specialist group; the intergroup difference was statistically significant (P<0.001). Significant intergroup detectability differences of >10% were noted for tumors in the peripheral zone with (i) ground glass opacity (GGO) ratio ≥10% and <70% and any size, or (ii) GGO ratio <10% and size ≤2cm; and for tumors hidden by the mediastinum, heart, or diaphragm with (i) GGO ratio ≥10% and <30% and size >3cm, or (ii) GGO ratio <10% and size >2cm. CONCLUSION: Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.

Preceding haemorrhagic shock as a detrimental risk factor for respiratory distress after excessive allogeneic blood transfusion.

BACKGROUND AND OBJECTIVES: Whether transfusion-associated circulatory overload arises as a simple result of over-transfusion or requires another trigger remains unclear. Here, we examined whether respiratory distress could be reproduced by massive transfusion alone in an animal model. MATERIALS AND METHODS: A total of 20 anaesthetized swine were equipped with monitors. Allogeneic blood was obtained from 10 donor swine. A 4-stage loading protocol with each stage equivalent to 25% of the blood volume (BV) in the recipient swine was then used to infuse crystalloid (CR), hydroxyethyl starch (HES) or allogeneic blood (TR) (n = 5 each). The five remaining animals were subjected to a haemorrhagic shock (HS) prior to an allogeneic blood transfusion (TRS). RESULTS: The PaO2 /FiO2 (P/F) ratio did not decrease to the level of respiratory distress in either the CR group or the HES group after loading with a volume corresponding to 100% of the recipient BV. However, the TRS and TR groups exhibited significant reductions in the P/F ratio after fluid overloading (227 ± 29 and 267 ± 133, respectively). Blood transfusion after HS expanded the blood volume, but over-transfusion alone did not. HS was accompanied by an increase in the white blood cell count. CONCLUSION: The lung and the heart can tolerate volume overloads with HES, CR and even transfused blood. However, a preceding HS may induce an inflammatory response, making the lung vulnerable to subsequent blood overloads. In this study, a preceding haemorrhagic shock mediated respiratory distress following massive transfusion in a swine model. (247 words).

Measurement of the τ Lepton Polarization and R(D

We report the first measurement of the τ lepton polarization P_{τ}(D^{*}) in the decay B[over ¯]→D^{*}τ^{-}ν[over ¯]_{τ} as well as a new measurement of the ratio of the branching fractions R(D^{*})=B(B[over ¯]→D^{*}τ^{-}ν[over ¯]_{τ})/B(B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ}), where ℓ^{-} denotes an electron or a muon, and the τ is reconstructed in the modes τ^{-}→π^{-}ν_{τ} and τ^{-}→ρ^{-}ν_{τ}. We use the full data sample of 772×10^{6} BB[over ¯] pairs recorded with the Belle detector at the KEKB electron-positron collider. Our results, P_{τ}(D^{*})=-0.38±0.51(stat)_{-0.16}^{+0.21}(syst) and R(D^{*})=0.270±0.035(stat)_{-0.025}^{+0.028}(syst), are consistent with the theoretical predictions of the standard model.

Observation of D

We report the first observation of the radiative charm decay D^{0}→ρ^{0}γ and the first search for CP violation in decays D^{0}→ρ^{0}γ, ϕγ, and K[over ¯]^{*0}(892)γ, using a data sample of 943 fb^{-1} collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The branching fraction is measured to be B(D^{0}→ρ^{0}γ)=(1.77±0.30±0.07)×10^{-5}, where the first uncertainty is statistical and the second is systematic. The obtained CP asymmetries A_{CP}(D^{0}→ρ^{0}γ)=+0.056±0.152±0.006, A_{CP}(D^{0}→ϕγ)=-0.094±0.066±0.001, and A_{CP}(D^{0}→K[over ¯]^{*0}γ)=-0.003±0.020±0.000 are consistent with no CP violation. We also present an improved measurement of the branching fractions B(D^{0}→ϕγ)=(2.76±0.19±0.10)×10^{-5} and B(D^{0}→K[over ¯]^{*0}γ)=(4.66±0.21±0.21)×10^{-4}.

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, increases the number of circulating CD34⁺CXCR4⁺ cells in patients with type 2 diabetes.

We investigated the effects of sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on the number of circulating CD34(+)CXCR4(+)cells, a candidate for endothelial progenitor cells (EPCs), plasma levels of stromal cell-derived factor (SDF)-1α, a ligand for CXCR4 receptor and a substrate for DPP-4, and plasma levels of interferon-inducible protein (IP)-10, for a substrate for DPP-4, in patients with type 2 diabetes. We studied 30 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with metformin and/or sulfonylurea. Thirty diabetic patients were randomized in a 2:1 ratio into a sitagliptin (50 mg/day) treatment group or an active placebo group (glimepiride 1 mg/day) for 12 weeks. Both groups showed similar improvements in glycemic control. The number of circulating CD34(+)CXCR4(+) cells was increased from 30.5 (20.0, 47.0)/10(6) cells at baseline to 55.5 (31.5, 80.5)/10(6) cells at 12 weeks of treatment with 50 mg/day sitagliptin (P = 0.0014), while showing no significant changes in patients treated with glimepiride. Plasma levels of SDF-1α and IP-10, both physiological substrates of endogenous DPP-4 and chemokines, were significantly decreased at 12 weeks of sitagliptin treatment. In conclusion, treatment with sitagliptin increased the number of circulating CD34(+)CXCR4(+) cells by approximately 2-fold in patients with type 2 diabetes.

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}

Measurement of the τ-lepton lifetime at Belle.

The lifetime of the τ lepton is measured using the process e+ e- → τ+ τ- , where both τ leptons decay to 3πν(τ). The result for the mean lifetime, based on 711 fb(-1) of data collected with the Belle detector at the ϒ(4S) resonance and 60 MeV below, is τ=(290.17±0.53(stat)±0.33(syst))×10(-15) s. The first measurement of the lifetime difference between τ+ and τ- is performed. The upper limit on the relative lifetime difference between positive and negative τ leptons is |Δτ|/τ<7.0×10(-3) at 90% C.L.

Precision measurement of charged pion and kaon differential cross sections in e+ e- annihilation at sqrt[s]=10.52 GeV.

Measurements of inclusive differential cross sections for charged pion and kaon production in e+ e- annihilation have been carried out at a center-of-mass energy of sqrt[s]=10.52 GeV. The measurements were performed with the Belle detector at the KEKB e+ e- collider using a data sample containing 113×10(6) e+ e- → qq events, where q={u,d,s,c}. We present charge-integrated differential cross sections dσ(h±)/dz for h±={π±,K±} as a function of the relative hadron energy z=2E(h)/sqrt[s] from 0.2 to 0.98. The combined statistical and systematic uncertainties for π± (K±) are 4% (4%) at z∼0.6 and 15% (24%) at z∼0.9. The cross sections are the first measurements of the z dependence of pion and kaon production for z>0.7 as well as the first precision cross section measurements at a center-of-mass energy far below the Z0 resonance used by the experiments at LEP and SLC.

Impact of immunoreactive substances contained in apheresis platelet concentrate on postoperative respiratory function in surgical patients receiving platelet transfusion: a prospective cohort study.

OBJECTIVES: To construct an alternative policy for the donor selection of platelet concentrate (PC), a clinical study exploring the features of lung injury following PC administration is needed. BACKGROUND: Although a male-donor-only policy for plasma products appears to have efficiently reduced transfusion-related acute lung injury (TRALI), this policy may not be applied to PC because of supply shortages. METHODS AND MATERIALS: We prospectively examined pulmonary function after the transfusion of PC in informed surgical patients treated at a tertiary university hospital in Japan. The contributions of immunoreactive substances contained in the PC to respiratory function after PC transfusion was then statistically examined. RESULTS: Eighty-six patients (56 men, 30 women) were enrolled in the analysis. Fifty-four cases experienced respiratory failure (PaO2 /FiO2 <300 mmHg) after transfusion. Five cases were diagnosed as possible TRALI based on permeability pulmonary oedema, while 23 cases were diagnosed as transfusion-associated circulatory overload (TACO) based on chest radiograph findings. A multivariate logistic regression analysis identified the presence of anti-granulocyte antibody as a significant predictor of possible TRALI [P = 0.023; odds ratio (OR), 13.0; 95% confidence interval (CI), 1.4-118.3]. Meanwhile, anti-leukocyte antibody class II was identified as a significant independent predictor of TACO (P = 0.010; OR, 18.4; 95% CI, 2.0-170.1). CONCLUSIONS: Our data suggest that antibodies contained in PC may contribute to the deterioration of respiratory function after PC transfusion, although the diagnoses of TACO and TRALI may have overlapped among the patients with pulmonary distress in this cohort.

High-precision alignment of electron tomography tilt series using markers formed in helium-ion microscope.

Tungsten nanodots formed in a helium-ion microscope (HIM) provide a practical means of aligning markers of electron tomography tilt series with a high degree of precision. The nanodots were formed using a HIM equipped with a W(CO)6 gas injection system, enabling the precise placement of the nanodots at desired locations of a sample. Template matching was applied to the markers formed in the HIM to detect the positions automatically. The relation between the positions of the markers and the accuracy of the alignment was also determined in order to achieve precise alignment. The method was applied to the markers in order to reconstruct three-dimensional (3D) images of a rod-shaped specimen that contained a 65-nm-diameter via structure in a Cu/Low-k interconnect.

Evidence for B- → τ- ν(τ) with a hadronic tagging method using the full data sample of Belle.

We measure the branching fraction of B- → τ- ν(τ) using the full Υ(4S) data sample containing 772×10(6) BB pairs collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider. Events with BB pairs are tagged by reconstructing one of the B mesons decaying into hadronic final states, and B- → τ- ν(τ) candidates are detected in the recoil. We find evidence for B- → τ- ν(τ) with a significance of 3.0 standard deviations including systematic errors and measure a branching fraction B(B- → τ- ν(τ))=[0.72(-0.25)(+0.27)(stat)±0.11(syst)]×10(-4).

Evidence for CP violation in the decay D+ → K(S)(0)π+.

We observe evidence for CP violation in the decay D+ → K(S)(0)π+ using a data sample with an integrated luminosity of 977 fb(-1) collected by the Belle detector at the KEKB e+ e- asymmetric-energy collider. The CP asymmetry in the decay is measured to be (-0.363±0.094±0.067)%, which is 3.2 standard deviations away from zero, and is consistent with the expected CP violation due to the neutral kaon in the final state.

Observation of new resonant structures in γγ → ωϕ, ϕϕ, and ωω.

The processes γγ → ωϕ, ϕϕ, and ωω are measured using an 870 fb(-1) data sample collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider. Production of vector meson pairs is clearly observed and their cross sections are measured for masses that range from threshold to 4.0 GeV. In addition to signals from well established spin-zero and spin-two charmonium states, there are resonant structures below charmonium threshold, which have not been previously observed. We report a spin-parity analysis for the new structures and determine the products of the η(c), χ(c0), and χ(c2) two-photon decay widths and branching fractions to ωϕ, ϕϕ, and ωω.

Convergent pre-motoneuronal inputs to single trigeminal motoneurons.

Because pre-motor neurons targeting trigeminal motoneurons are located in various regions, including the supratrigeminal (SupV) and intertrigeminal (IntV) regions, the principal sensory trigeminal nucleus (PrV), and the region dorsal to the PrV (dRt), a single trigeminal motoneuron may receive differential convergent inputs from these regions. We thus examined the properties of synaptic inputs from these regions to masseter motoneurons (MMNs) and digastric motoneurons (DMNs) in brainstem slice preparations obtained from P1-5 neonatal rats, using whole-cell recordings and laser photolysis of caged glutamate. Photostimulation of multiple regions within the SupV, IntV, PrV, and dRt induced post-synaptic currents (PSCs) in 14 of 19 MMNs and 18 of 26 DMNs. Furthermore, the stimulation of the lateral SupV significantly induced burst PSCs in MMNs more often than low-frequency PSCs in MMNs or burst PSCs in DMNs. Similar results were obtained in the presence of the GABA(A) receptor antagonist SR95531 and the glycine receptor antagonist strychnine. These results suggest that both neonatal MMNs and DMNs receive convergent glutamatergic inputs from the SupV, IntV, PrV, and dRt, and that the lateral SupV sends burst inputs predominantly to the MMNs. Such convergent pre-motoneuronal inputs to trigeminal motoneurons may contribute to the proper execution of neonatal oro-motor functions.

Precise measurement of the CP violation parameter sin2φ1 in B0→(cc¯)K0 decays.

We present a precise measurement of the CP violation parameter sin2φ1 and the direct CP violation parameter A(f) using the final data sample of 772×10(6) BB[over ¯] pairs collected at the Υ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B meson is reconstructed in a J/ψK(S)(0), ψ(2S)K(S)(0), χ(c1)K(S)(0), or J/ψK(L)(0) CP eigenstate and its flavor is identified from the decay products of the accompanying B meson. From the distribution of proper-time intervals between the two B decays, we obtain the following CP violation parameters: sin2φ1=0.667±0.023(stat)±0.012(syst) and A(f)=0.006±0.016(stat)±0.012(syst).

First observation of B(s)(0) → J/ψη and B(s)(0) → J/ψη'.

We report first observations of B(s)(0) → J/ψη and B(s)(0) → J/ψη'. The results are obtained from 121.4 fb(-1) of data collected at the Υ(5S) resonance with the Belle detector at the KEKB e+ e- collider. We obtain the branching fractions B(B(s)(0) → J/ψη)=[5.10±0.50(stat)±0.25(syst)(-0.79)(+1.14)(N(B(s)(*) B(s)(*))]×10(-4), and B(B(s)(0) → J/ψη')=[3.71±0.61(stat)±0.18(syst)(-0.57)(+0.83)(N(B(s)(*) B(s)(*))]×10(-4). The ratio of the two branching fractions is measured to be (B(B(s) → J/ψη'))/(B(B(s) → J/ψη))=0.73±0.14(stat)±0.02(syst).

Observation of two charged bottomoniumlike resonances in Υ(5S) decays.

We report the observation of two narrow structures in the mass spectra of the π(±)Υ(nS) (n=1, 2, 3) and π(±)h(b)(mP) (m=1, 2) pairs that are produced in association with a single charged pion in Υ(5S) decays. The measured masses and widths of the two structures averaged over the five final states are M(1)=(10,607.2±2.0) MeV/c2, Γ(1)=(18.4±2.4) MeV, and M(2)=(10,652.2±1.5) MeV/c2, Γ(2)=(11.5±2.2) MeV. The results are obtained with a 121.4 fb(-1) data sample collected with the Belle detector in the vicinity of the Υ(5S) resonance at the KEKB asymmetric-energy e+ e- collider.

First observation of the P-wave spin-singlet bottomonium states hb(1P) and hb(2P).

We report the first observations of the spin-singlet bottomonium states h(b)(1P) and h(b)(2P). The states are produced in the reaction e(+)e(-)→h(b)(nP)π(+)π(-) using a 121.4 fb(-1) data sample collected at energies near the Υ(5S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. We determine M[h(b)(1P)]=(9898.2(-1.0-1.1)(+1.1+1.0)) MeV/c(2) and M[h(b)(2P)]=(10,259.8±0.6(-1.0)(+1.4)) MeV/c(2), which correspond to P-wave hyperfine splittings ΔM(HF)=(+1.7±1.5) and (+0.5(-1.2)(+1.6)) MeV/c(2), respectively. The significances of the h(b)(1P) and h(b)(2P) are 5.5σ and 11.2σ, respectively. We find that the production of the h(b)(1P) and h(b)(2P) is not suppressed relative to the production of the Υ(1S), Υ(2S), and Υ(3S).