Shipper collaboration matching: fast enumeration of triangular transports with high cooperation effects

The logistics industry in Japan is facing a severe shortage of labor. Therefore, there is an increasing need for joint transportation allowing large amounts of cargo to be transported using fewer trucks. In recent years, the use of artificial intelligence and other new technologies has gained wide attention for improving matching efficiency. However, it is difficult to develop a system that can instantly respond to requests because browsing through enormous combinations of two transport lanes is time consuming. In this study, we focus on a form of joint transportation called triangular transportation and enumerate the combinations with high cooperation effects. The proposed algorithm makes good use of hidden inequalities, such as the distance axiom, to narrow down the search range without sacrificing accuracy. Numerical experiments show that the proposed algorithm is thousands of times faster than simple brute force. With this technology as the core engine, we developed a joint transportation matching system. The system has already been in use by over 150 companies as of October 2022, and was featured in a collection of logistics digital transformation cases published by Japan's Ministry of Land, Infrastructure, Transport and Tourism.Comment: 16 pages, 7 figure

Paradoxical activation of c-Src as a drug-resistant mechanism

抗がん剤抵抗性の新規メカニズムの解明 --薬剤抵抗性がん細胞は抗がん剤により増殖する--. 京都大学プレスリリース. 2021-03-25.ATP-competitive inhibitors have been developed as promising anti-cancer agents. However, drug-resistance frequently occurs, and the underlying mechanisms are not fully understood. Here, we show that the activation of c-Src and its downstream phosphorylation cascade can be paradoxically induced by Src-targeted and RTK-targeted kinase inhibitors. We reveal that inhibitor binding induces a conformational change in c-Src, leading to the association of the active form c-Src with focal adhesion kinase (FAK). Reduction of the inhibitor concentration results in the dissociation of inhibitors from the c-Src-FAK complex, which allows c-Src to phosphorylate FAK and initiate FAK-Grb2-mediated Erk signaling. Furthermore, a drug-resistant mutation in c-Src, which reduces the affinity of inhibitors for c-Src, converts Src inhibitors into facilitators of cell proliferation by enhancing the phosphorylation of FAK and Erk in c-Src-mutated cells. Our data thus reveal paradoxical enhancement of cell growth evoked by target-based kinase inhibitors, providing potentially important clues for the future development of effective and safe cancer treatment

Lymphopenia at diagnosis predicts survival of patients with immunodeficiency-associated lymphoproliferative disorders

The number of patients who are administered immunosuppressive agents has been increasing. Accordingly, more patients face higher risks for developing immunodeficiency-associated lymphoproliferative disorders (LPD). Although immunodeficiency-associated LPD are distinct from other lymphoid neoplasms in terms of their immunocompromised backgrounds, little is known about the impact of lymphopenia at diagnosis on survival in patients with these LPD. Seventy-one immunodeficiency-associated LPD in Kyoto University Hospital (post-transplant LPD (PTLD), n = 26; other iatrogenic immunodeficiency-associated LPD, n = 45) were reviewed and analyzed. The median age at diagnosis was 63 years (range, 3–83). Diffuse large B cell lymphoma was the most common subtype (n = 33), followed by Hodgkin lymphoma (n = 12), B cell monomorphic LPD not specified (n = 11), and polymorphic LPD or early-phase diseases (n = 15). The median follow-up period for survivors was 2.5 years and overall survival (OS) and progression-free survival (PFS) at 2.5 years were 75% and 67%, respectively. Multivariate analysis showed that lymphopenia (≤ 800/μL) at diagnosis predicted inferior OS (HR, 3.72; P = 0.043) and PFS (HR, 3.82; P = 0.012). Serum albumin values also strongly affected OS (> 3.18 g/dL vs. ≤ 3.18 g/dL; HR, 0.21; P = 0.010) and PFS (HR, 0.26; P = 0.013). Lymphopenia at diagnosis is suggested to predict inferior OS and PFS in patients with immunodeficiency-associated LPDs. Immunocompromised status might affect disease progression in these distinct lymphoid neoplasms growing under immunocompromised backgrounds

Triethylated chromones with substituted naphthalenes as tubulin inhibitors

Previously synthesized 2-(benzo[]thiophene-3′-yl)-6,8,8-triethyldesmosdumotin B (, TEDB-TB) and 2-(naphth-1′-yl)-6,8,8-triethyldesmosdumotin B () showed potent activity against multiple human tumor cell lines, including a multidrug-resistant (MDR) subline, by targeting spindle formation and/or the microtubule network. Consequently, ester analogues of hydroxylated naphthyl substituted TEBDs (–) were prepared and evaluated for their effects on tumor cell proliferation and on tubulin assembly. Among all new compounds, compound , a 4′-acetoxynaphthalen-1′-yl derivative, displayed the most potent antiproliferative activity (IC 0.2–5.7 μM). Selected analogues were confirmed to be tubulin assembly inhibitors in cell-free and cell-based assays using MDR tumor cells. The new analogues partially inhibited colchicine binding to tubulin, suggesting their binding mode would be different from that of colchicine. This observation was supported by computational docking model analyses. Thus, the newly synthesized triethylated chromones with esterified naphthalene groups have good potential for development as a new class of mitotic inhibitors that target tubulin

Symptomatic foramen of Magendie arachnoid cyst in an elderly patient

Background: Arachnoid cysts (ACs) are congenital anomalies of the central nervous system and arise in virtually all locations where the arachnoid membrane exists. Posterior fossa ACs are considered to develop in the posterior aspect of the rhombencephalic roof plate and do not communicate freely with the fourth ventricle or perimedullary subarachnoid space. Although posterior fossa ACs have been reported a number of times, ACs arising from the foramen of Magendie are very rare. Case Description: We report here on a 76-year-old female who presented with progressive gait disturbance. Magnetic resonance imaging of the head showed a large AC in the foramen of Magendie that was compressing the inferior vermis and medial aspects of the cerebellar hemisphere without causing hydrocephalus. Neurological examination revealed cerebellar ataxia without Romberg\u27s sign. A nearly total excision of the cyst was safely performed via a median suboccipital approach. The patient\u27s postoperative course was excellent and her neurological recovery was remarkable. Conclusion: Most cases of ACs located in the foramen of Magendie are reported in children, and it is extremely rare to observe such ACs in the elderly. In fact, to our knowledge, a symptomatic foramen Magendie AC has never been reported previously in an elderly person. Our results indicate that proper surgical intervention can yield highly positive outcomes in such cases

Next‐generation sequencing in two cases of de novo acute basophilic leukaemia

Acute basophilic leukaemia (ABL) is a rare subtype of acute myeloid leukaemia (AML); therefore, few data are available about its biology. Herein, we analysed two ABL patients using flow cytometry and next-generation sequencing (NGS). Two cell populations were detected by flow cytometry in both patients. In Case no. 1, blasts (CD34⁺, CD203c⁻, CD117⁺, CD123dim⁺) and basophils (CD34⁻, CD203c⁺, CD117±, CD123⁺) were identified, both of which were found by NGS to harbour the 17p deletion and have loss of heterozygosity of TP53. In Case no. 2, blasts (CD33⁺, CD34⁺, CD123⁻) and basophils (CD33⁺, CD34⁺, CD123⁺) were identified. NGS detected NPM1 mutations in either blasts or basophils, and TET2 in both. These data suggest an overlap of the mutational landscape of ABL and AML, including TP53 and TET2 mutations. Moreover, additional mutations or epigenetic factors may contribute for the differentiation into basophilic blasts

Detection of adenovirus hepatitis and acute liver failure in allogeneic hematopoietic stem cell transplant patients

Human adenovirus (HAdV) is an important cause of the common cold and epidemic keratoconjunctivitis in immunocompetent individuals. In immunocompromised patients, HAdV can sometimes cause severe infection such as cystitis, gastroenteritis, pneumonia, encephalitis, hepatitis, or disseminated disease, resulting in significant morbidity and also mortality. In particular, severe cases have been reported in patients after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Indeed HAdV has been recognized as a pathogen that requires careful monitoring in allo‐HSCT patients. While HAdV hepatitis leading to severe acute liver failure is rare, such liver failure progresses rapidly and is often fatal. Unfortunately, HAdV hepatitis has few characteristic symptoms and physical findings, which makes it difficult to promptly confirm and start treatment. We report here four cases of HAdV hepatitis after allo‐HSCT and their autopsy findings

A Case of Cervical Epidural Abscess -Diagnosis using MRI and non -surgical treatment -

A 65-year-old man with cervical epidural abscess presented with high fever and severe neck pain. On admission, he had difficulty in walking, and the next day paralysis and hyposthesia below the level of C6 developed. Magnetic resonance imaging (MRI) revealed an anterior epidural abscess at C5-7, verteveral bodies levels. All of three blood cultures were positive for Staphylococcus aureus. He was treated with ceftazidame and ampicillin, supplemented with rifampicin and isoniazid for four weeks. The follow-up MRI demonstrated resolution of the abscess and cord compression. After three months, the patient was able to walk with a stick

First Cool-Down Performance of the LHD

The first cool-down test of the Large Helical Device (LHD) and the performance of the LHD cryogenic system during the first cycle operation are described. The first cool-down started on Feb. 23, 1998 and finished on Mar. 22. After the cool-down, the excitation tests of the SC coils up to 1.5 T and the first cycle operations for plasma physics experiments were conducted until May 18. The first cycle operation was successfully completed after the warm-up process to room temperature from May 19 to Jun. 15. The cooling characteristics of the LHD, such as temperature distribution during cool-down, heat loads under steady state condition, reliability during long-term operation, are reporte