Intermolecular-medium and intramolecular-weak hydrogen bonding chains in the crystals of chiral trifluoromethylated amino alcohols

A structural feature of hydrogen bonding chains found in the crystals of trifluoromethylated amino alcohols is reported. Hydrogen bondings of 3-(N,N-dialkylamino)-1,1,1-trifluoro-2-propanols construct chiral spiral hydrogen bonding chains. Lone pairs on the nitrogen atoms of the amino alcohols participate in two hydrogen bondings. Detailed structural analysis of the hydrogen bonds of the 3-(N,N-dimethylamino)-1,1,1-trifluoro-2-propanol suggested that the chain built up with alternating intermolecular medium and intramolecular weak hydrogen bonds. The medium intermolecular hydrogen bond, which transfers a proton from the hydroxy group to the amino nitrogen, would make a tentative zwitterionic form of the molecule. Then, electrostatic attraction between the charges in the zwitterion centers induced a weak intramolecular hydrogen bond.</p

Phosphatidic acid-dependent localization and basal de-phosphorylation of RA-GEFs regulate lymphocyte trafficking

Background: Lymphocytes circulate between peripheral lymphoid tissues via blood and lymphatic systems, and chemokine-induced migration is important in trafficking lymphocytes to distant sites. The small GTPase Rap1 is important in mediating lymphocyte motility, and Rap1-GEFs are involved in chemokine-mediated Rap1 activation. Here, we describe the roles and mechanisms of Rap1-GEFs in lymphocyte trafficking. Results: In this study, we show that RA-GEF-1 and 2 (also known as Rapgef2 and 6) are key guanine nucleotide exchange factors (GEF) for Rap1 in lymphocyte trafficking. Mice harboring T cell-specific knockouts of Rapgef2/6 demonstrate defective homing and egress of T cells. Sphingosine-1-phosphate (S1P) as well as chemokines activates Rap1 in a RA-GEF-1/2-dependent manner, and their deficiency in T cells impairs Mst1 phosphorylation, cell polarization, and chemotaxis toward S1P gradient. On the other hand, B cell-specific knockouts of Rapgef2/6 impair chemokine-dependent retention of B cells in the bone marrow and passively facilitate egress. Phospholipase D2-dependent production of phosphatidic acid by these chemotactic factors determines spatial distribution of Rap1-GTP subsequent to membrane localization of RA-GEFs and induces the development of front membrane. On the other hand, basal de-phosphorylation of RA-GEFs is necessary for chemotactic factor-dependent increase in GEF activity for Rap1. Conclusions: We demonstrate here that subcellular distribution and activation of RA-GEFs are key factors for a directional movement of lymphocytes and that phosphatidic acid is critical for membrane translocation of RA-GEFs with chemokine stimulation

Bayesian phase difference estimation algorithm for direct calculation of fine structure splitting: accelerated simulation of relativistic and quantum many-body effects

Despite rapid progress in the development of quantum algorithms in quantum computing as well as numerical simulation methods in classical computing for atomic and molecular applications, no systematic and comprehensive electronic structure study of atomic systems that covers almost all of the elements in the periodic table using a single quantum algorithm has been reported. In this work, we address this gap by implementing the recently-proposed quantum algorithm, the Bayesian Phase Difference Estimation (BPDE) approach, to compute accurately fine-structure splittings, which are relativistic in origin and it also depends on quantum many-body (electron correlation) effects, of appropriately chosen states of atomic systems, including highly-charged superheavy ions. Our numerical simulations reveal that the BPDE algorithm, in the Dirac--Coulomb--Breit framework, can predict the fine-structure splitting of Boron-like ions to within 605.3 cm$^{-1}$ of root mean square deviations from the experimental ones, in the (1s, 2s, 2p, 3s, 3p) active space. We performed our simulations of relativistic and electron correlation effects on Graphics Processing Unit (GPU) by utilizing NVIDIA's cuQuantum, and observe a $\times 42.7$ speedup as compared to the CPU-only simulations in an 18-qubit active space.Comment: 7+4 pages, 2 figure

Laparoscopic Hepatectomy: Current State in Japan Based on the 4th Nationwide Questionnaire

Purpose. Since laparoscopic hepatectomy (LH) became covered by national health insurance in April 2010 in Japan, the numbers of applied cases and institutions performing it have increased and the indication has expanded. We surveyed the current state and safety of LH in Japan. Methods. A questionnaire survey was performed in 41 institutions related to the Japanese Endoscopic Liver Surgery Study Group and 747 institutions certified by the Japanese Society of Gastroenterological Surgery, and responses concerning all 2962 cases of LH performed by August 2011 were obtained. Results. The surgical procedure employed was hemihepatectomy in 234 (8%), segmentectomy in 88 (3%), left lateral segmentectomy in 434 (15%), segmentectomy in 156 (5%), and partial resection in 1504 (51%) cases. The approach was pure laparoscopy in 1835 (63%), hand-assisted laparoscopic surgery in 201 (7%), and laparoscopy-assisted surgery in 926 (31%). Regarding perioperative complications, surgery was switched to laparotomy in 59 (2.0%), reoperation was performed in 4 (0.1%), and surgery-related death occurred in 2 (0.07%). Intraoperative accidents occurred in 68 (2.3%), and postoperative complications developed in 94 (3.2%). Conclusions. When the selection of cases is appropriate, LH for liver diseases can be safely performed

FZD10-targeted α-radioimmunotherapy with 225Ac-labeled OTSA101 achieves complete remission in a synovial sarcoma model

Synovial sarcomas are rare tumors arising in adolescents and young adults. The prognosis for advanced disease is poor, with an overall survival of 12-18 months. Frizzled homolog 10 (FZD10) is overexpressed in most synovial sarcomas, making it a promising therapeutic target. The results of a phase 1 trial of β-radioimmunotherapy (RIT) with the 90Y-labeled anti-FZD10 antibody OTSA101 revealed a need for improved efficacy. The present study evaluated the potential of α-RIT with OTSA101 labeled with the α-emitter 225Ac. Competitive inhibition and cell binding assays showed that specific binding of 225Ac-labeled OTSA101 to SYO-1 synovial sarcoma cells was comparable to that of the imaging agent 111In-labeled OTSA101. Biodistribution studies showed high uptake in SYO-1 tumors and low uptake in normal organs, except for blood. Dosimetric studies showed that the biologically effective dose (BED) of 225Ac-labeled OTSA101 for tumors was 7.8 Bd higher than that of 90Y-labeled OTSA101. 90Y- and 225Ac-labeled OTSA101 decreased tumor volume and prolonged survival. 225Ac-labeled OTSA101 achieved a complete response in 60% of mice, and no recurrence was observed. 225Ac-labeled OTSA101 induced a larger amount of necrosis and apoptosis than 90Y-labeled OTSA101, although the cell proliferation decrease was comparable. The BED for normal organs and tissues was tolerable; no treatment-related mortality or obvious toxicity, except for temporary body weight loss, was observed. 225Ac-labeled OTSA101 provided a high BED for tumors and achieved a 60% complete response in the synovial sarcoma mouse model SYO-1. RIT with 225Ac-labeled OTSA101 is a promising therapeutic option for synovial sarcoma

Conformation and absolute configuration of (1S,2S)-2-(phenyl­selan­yl)cyclo­hexyl (R)-2-meth­oxy-2-(1-naphth­yl)propionate

The relative and absolute configurations of the title compound, C26H28O3Se, were assigned from the known configuration of (R)-(−)-2-meth­oxy-2-(1-naphth­yl)propionic acid used as starting material, and by examination of the Bijvoet (Friedel) pairs, using the anomalous dispersion data collected with Mo Kα radiation at low temperature. The geometry around the carbonyl group exists in the syn conformation, as reflected in torsion angles involving this group, and the stability of the structure is affected by weak bifurcated intra­molecular C—H⋯O hydrogen bonds

ABCC6

Purpose. To report the spectrum of ABCC6 variants in Japanese patients with angioid streaks (AS). Patients and Methods. This was a single-center cohort study. The medical records of 20 patients with AS from 18 unrelated Japanese families were retrospectively reviewed. Screening of the ABCC6 gene (exons 1 to 31) was performed using PCR-based Sanger sequencing. Results. Eight ABCC6 variants were identified as candidate disease-causing variants. These eight variants included five known variants (p.Q378X, p.R419Q, p.V848CfsX83, p.R1114C, and p.R1357W), one previously reported variant (p.N428S) of unknown significance, and two novel variants (c.1939C>T [p.H647Y] and c.3374C>T [p.S1125F]); the three latter variants were determined to be variants of significance. The following four variants were frequently identified: p.V848CfsX83 (14/40 alleles, 35.0%), p.Q378X (7/40 alleles, 17.5%), p.R1357W (6/40 alleles, 15.0%), and p.R419Q (4/40 alleles, 10.0%). The ABCC6 variants were identified in compound heterozygous or homozygous states in 13 of 18 probands. Two families showed a pseudodominant inheritance pattern. Pseudoxanthoma elasticum was seen in 15 of 17 patients (88.2%) who underwent dermatological examination. Conclusions. We identified disease-causing ABCC6 variants that were in homozygous or compound heterozygous states in 13 of 18 families (72.2%). Our results indicated that ABCC6 variants play a significant role in patients with AS in the Japanese population

Onycholysis Associated with Graves\u27 Disease

This paper presents a case of onycholysis associated with Graves\u27 disease. Onycholysis in association with Graves\u27 disease is rarely seen in Japan. The patient is a twenty-two-year-old female with a half year history of receiving antithyroid treatment for Graves\u27 disease. An initial physical examination revealed onycholysis in the right ring finger, although she achieved euthyroid state