Mathematical Model of Ship Collision Probability

A mathematical model for estimating the probability of collision of ships passing through a uniform channel is proposed. The model takes into account the give-way motions of the encountered ships and the wake position characteristics under the given channel conditions such as width, length and centerline like buoys. The probability of collision is defined as the probability of an event where a ship fails to give way. Using this probability of collision, the “Collision Risk of Channel” is defined. The proposed model is examined by the collision statistics of some channels and straits in Japan. According to these statistics, the present model gives a good estimation of the collision risk of a channel. Since the proposed model takes account of traffic characteristics such as traffic volume, ship size distribution, and sailing velocity distribution, as well as channel conditions such as width, length and centerline mark like buoys, the effects of their change or control on the probability of collision can be easily predicted. Therefore, the proposed model is quite useful for the engineering planning and design of any channel

Distorted antibody repertoire developed in the absence of pre-B cell receptor formation

The pre-B cell receptor (pre-BCR), consisting of the μ heavy chain (μHC) and the surrogate light chain (SLC, Vpre-B and λ5), plays important roles during B cell development. The formation of the pre-BCR, which enables the nascent immunoglobulin HC to associate with the SLC, is considered a prerequisite for B cell development. However, a significant number of peripheral mature (leaky) B cells exist in SLC-deficient mice. These leaky B cells develop in the absence of pre-BCR and do not undergo the pre-BCR checkpoint. The antibody repertoires of leaky B cells thus reflect the absence of pre-BCR function. To investigate how the absence of the pre-BCR is circumvented by these leaky-B cells and examine the effect of the pre-BCR checkpoint on the antibody system, we analyzed the antibody repertoires of λ5-deficient (λ5−/−) mice using next-generation sequencing. In λ5−/− mice, spleen B cells displayed different patterns of VDJ-usage, relative to those in wild-type (WT) mice. Moreover, leaky B cells were neither derived from unusual B2 cells, characterized by particular LC gene rearrangements in the absence of pre-BCR signaling, nor from B1 cells, originating from different B cell progenitors. Analysis of the CDR-H3 amino acid sequences of μ-chain repertoires revealed that certain bone marrow B cells with particular CDR-H3 profiles undergo clonal expansion in λ5−/− mice. Part of these CDR-H3s contain arginine(s) in the middle of the CDR-H3 loop in λ5−/− mice, whereas few arginine(s) exist in this middle loop in WT CDR-H3s in the absence of clonal expansion. This CDR-H3 feature in λ5−/− mice presumably reflects the role of the pre-BCR in autoantibody regulation, since arginine(s) are often found in the antigen-binding site of autoantibodies. Here, we present a unique viewpoint on the role of pre-BCR, by assessing the whole antibody repertoire formed in SLC-deficient mice

Novel Oral Derivative UD-017, a Highly Selective CDK7 Inhibitor, Exhibits Anticancer Activity by Inducing Cell-Cycle Arrest and Apoptosis in Human Colorectal Cancer

Objective: This study aimed to investigate the anticancer profile of a new cyclin-dependent kinase 7 (CDK7) inhibitor, UD-017, by examining its mechanism of action using HCT-116 colorectal cancer cells. Methods: The anticancer properties of UD-017 were assessed using several assays, including in vitro kinase, proliferation, and apoptosis assays, western blot analysis, and an in vivo xenograft mouse model. Results: UD-017 significantly inhibited CDK7 activity (IC50 = 16 nM) with high selectivity in an in vitro kinase assay testing a panel of over 300 proteins and lipid kinases. UD-017 also inhibited the growth of HCT-116 cells (GI50 = 19 nM) and inhibited the phosphorylation of various downstream mediators of CDK7 signaling. In cell cycle and apoptosis assays using HCT-116 cells, UD-017 increased the number of cells in both G1 and G2/M phases and induced apoptosis. In vivo, UD-017 inhibited tumor growth in an HCT-116 xenograft mouse model by 33%, 64%, and 88% at doses of 25, 50, and 100 mg/kg, respectively, with clear dose-dependency. Co-administration of 5-FU and 50 mg/kg UD-017 had a strong synergistic effect, as reflected in the complete inhibition of tumor growth. Conclusion: CDK7 may play a major role in colorectal cancer growth by regulating the cell cycle and apoptosis. UD-017 is a promising candidate therapeutic agent for the treatment of cancer involving CDK7 signaling

Effect of Co-Substitution on Hydrogen Absorption and Desorption Reactions of YMgNi4-Based Alloys

YMgNi4-based alloys exhibit reversible hydrogen absorption and desorption reactions at near room temperature. Here, we report that Co-substituted YMgNi4-based alloys exhibited higher hydrogen contents and lower hydrogen absorption and desorption reaction pressures than unsubstituted alloys. The effects of Co-substitution viewed from atomic arrangements were particularly clarified by synchrotron radiation powder X-ray diffraction, neutron diffraction, and inelastic neutron scattering. Powder neutron diffraction of the Co-substituted alloy at 5 MPa of D-2 pressure suggested the formation of gamma-phase deuteride (higher deuterium content) from beta-phase deuteride (lower deuterium content). However, no gamma-phase deuteride was observed in the unsubstituted alloys at 5 MPa. Therefore, the gamma-phase deuteride formation of the Co-substituted alloy at lower pressure led to higher hydrogen contents than the unsubstituted alloys. The combined results of powder neutron diffraction and inelastic neutron scattering suggested that the gamma-phase hydride of the Co-substituted alloy was continuously generated due to additional H atoms at the H atom sites in the beta-phase hydride because of the disordered H atomic arrangement involving H-H interactions. As a result, hydrogen absorption and desorption reaction pressures for the gamma-phase deuteride formation with higher hydrogen storage capacity were lowered

Y: Newly established monoclonal antibodies for immunological detection of H5N1 influenza virus

SUMMARY: The H5N1 subtype of the highly pathogenic (HP) avian influenza virus has been recognized for its ability to cause serious pandemics among humans. In the present study, new monoclonal antibodies (mAbs) against viral proteins were established for the immunological detection of H5N1 influenza virus for research and diagnostic purposes. B-cell hybridomas were generated from mice that had been hyperimmunized with purified A/Vietnam/1194/2004 (NIBRG-14) virion that had been inactivated by UV-irradiation or formaldehyde. After screening over 4,000 hybridomas, eight H5N1-specific clones were selected. Six were specific for hemagglutinin (HA) and had in vitro neutralization activity. Of these, four were able to broadly detect all tested clades of the H5N1 strains. Five HA-specific mAbs detected denatured HA epitope(s) in Western blot analysis, and two detected HP influenza virus by immunofluorescence and immunohistochemistry. A highly sensitive antigen-capture sandwich ELISA system was established by combining mAbs with different specificities. In conclusion, these mAbs may be useful for rapid and specific diagnosis of H5N1 influenza. Therapeutically, they may have a role in antibody-based treatment of the disease

Effect of Co-Substitution on Hydrogen Absorption and Desorption Reactions of YMgNi₄‑Based Alloys

YMgNi4-based alloys exhibit reversible hydrogen absorption and desorption reactions at near room temperature. Here, we report that Co-substituted YMgNi4-based alloys exhibited higher hydrogen contents and lower hydrogen absorption and desorption reaction pressures than unsubstituted alloys. The effects of Co-substitution viewed from atomic arrangements were particularly clarified by synchrotron radiation powder X-ray diffraction, neutron diffraction, and inelastic neutron scattering. Powder neutron diffraction of the Co-substituted alloy at 5 MPa of D2 pressure suggested the formation of γ-phase deuteride (higher deuterium content) from β-phase deuteride (lower deuterium content). However, no γ-phase deuteride was observed in the unsubstituted alloys at 5 MPa. Therefore, the γ-phase deuteride formation of the Co-substituted alloy at lower pressure led to higher hydrogen contents than the unsubstituted alloys. The combined results of powder neutron diffraction and inelastic neutron scattering suggested that the γ-phase hydride of the Co-substituted alloy was continuously generated due to additional H atoms at the H atom sites in the β-phase hydride because of the disordered H atomic arrangement involving H–H interactions. As a result, hydrogen absorption and desorption reaction pressures for the γ-phase deuteride formation with higher hydrogen storage capacity were lowered