Boron delivery for boron neutron capture therapy targeting a cancer-upregulated oligopeptide transporter.

Boron neutron capture therapy (BNCT) is a radiotherapy utilizing the neutron capture and nuclear fission reaction of 10B taken up into tumor cells. The most commonly used boron agent in BNCT, p-borono-l-phenylalanine (BPA), is accumulated in tumors by amino acid transporters upregulated in tumor cells. Here, by using dipeptides of BPA and tyrosine (BPA-Tyr and Tyr-BPA), we propose a novel strategy of selective boron delivery into tumor cells via oligopeptide transporter PEPT1 upregulated in various cancers. Kinetic analyses indicated that BPA-Tyr and Tyr-BPA are transported by oligopeptide transporters, PEPT1 and PEPT2. The intrinsic oligopeptide transport activity in tumor cells clearly correlated with PEPT1 protein expression level but not with PEPT2, suggesting that PEPT1 is the predominant oligopeptide transporter at least in tumor cell lines. Furthermore, using BPA-Tyr and Tyr-BPA, boron was successfully delivered into PEPT1-expressing pancreatic cancer AsPC-1 cells via a PEPT1-mediated mechanism. Intravenous administration of BPA-Tyr into the mice bearing AsPC-1 xenograft tumors resulted in significant boron accumulation in the tumors. It is proposed that the oligopeptide transporters, especially PEPT1, are promising candidates for molecular targets of boron delivery in BNCT. The BPA-containing dipeptides would have a potential for the development of novel boron carriers targeting PEPT1.

Novel |V_{us}| Determination Using Inclusive Strange τ Decay and Lattice Hadronic Vacuum Polarization Functions.

We propose and apply a new approach to determining |V_{us}| using dispersion relations with weight functions having poles at Euclidean (spacelike) momentum which relate strange hadronic τ decay distributions to hadronic vacuum polarization (HVP) functions obtained from lattice quantum chromodynamics. We show examples where spectral integral contributions from the region where experimental data have large errors or do not exist are strongly suppressed but accurate determinations of the relevant lattice HVP combinations remain possible. The resulting |V_{us}| agrees well with determinations from K physics and three-family Cabibbo-Kobayashi-Maskawa unitarity. Advantages of this new approach over the conventional hadronic τ decay determination employing flavor-breaking sum rules are also discussed.

Micropore Formation of [Zn2(Oxac) (Taz)2]·(H2O)2.5 via CO2 Adsorption.

As-synthesized [Zn2(Oxac) (Taz)2]·(H2O)2.5, referred to as ZOTW2.5, was prepared from aqueous methanol solutions of Zn5(CO3)2(OH)6 and two kinds of ligands of 1,2,4-triazole (Taz) and oxalic acid (Oxac) at 453 K for 12 h. The crystal structure was determined by the Rietveld method. As-synthesized ZOTW2.5 was pretreated at 383 K and 1 mPa for tpt h, ZOTWx(tpth). ZOTWx(≥3h) showed a type I adsorption isotherm for N2 at 77 K having a saturation amount (Vs) of 180 mg/g, but that pretreated shortly showed only 1/10 in Vs. CO2 was adsorbed at 303 K in sigmoid on nonporous ZOTWx(≤2h) and in Langmuir-type on ZOTWx(≥3h) to reach the adsorption amount of 120 mg/g at 700 Torr. N2 adsorption on ZOTWx(≤2h)deCO2, degassed after CO2 adsorption on ZOTWx(≤2h), was promoted 5-fold from 180 mg/g on ZOTWx(tpth) and ZOTWx(≥3h)deCO2 up to ca. 1000 mg/g. The interaction of CO2 and H2O molecules in micropores may lead to a new route for micropore formation.

Light composite scalar in twelve-flavor QCD on the lattice.

On the basis of lattice simulations using highly improved staggered quarks for twelve-flavor QCD with several bare fermion masses, we observe a flavor-singlet scalar state lighter than the pion in the correlators of fermionic interpolating operators. The same state is also investigated using correlators of gluonic interpolating operators. Combined with our previous study that showed twelve-flavor QCD to be consistent with being in the conformal window, we infer that the lightness of the scalar state is due to infrared conformality. This result shed some light on the possibility of a light composite Higgs boson ("technidilaton") in walking technicolor theories.

Structural analysis of high-silica ferrierite with different structure-directing agents by solid-state NMR and ab initio calculations.

The host-guest interaction in high-silica ferrierite (FER) with different structure-directing agents (SDA), pyridine and piperidine, was analyzed by solid-state (29)Si NMR relaxation experiments and molecular-orbital calculations. Qualitative and quantitative knowledge of the SDA structure obtained by these methods provides significant insight for understanding the functions in a template, and the stabilizing role of the SDA. Relaxation experiments show a larger magnetic dipolar interaction between the silicon and hydrogen atoms in piperidine as compared to that in pyridine, and the results correlate with the bonding property in terms of the distance between the zeolite framework and the SDA. The (1)H MAS NMR spectrum shows that the pyridine molecules mainly act as pore fillers in the pyridine-FER. In contrast, it was presumed that piperidine, adjacent to the aluminosilicate framework and framework defects, acted as a counter cation to balance the charge in the piperidine-FER. H(+)-FER synthesized with piperidine shows a lower hydrothermal stability as compared to that synthesized with pyridine. The hydrothermal stability of H(+)-FER is discussed by considering the contributions of framework defects and the different properties pertaining to the bonding between the zeolite framework and the SDA.

[Anesthetic management of a patient with HOCM even after PTSMA].

A 74-year-old woman previously treated with percutaneous transluminnal septal myocardial ablation (PTSMA) for severe hypertrophic obstructive cardiomyopathy (HOCM) underwent laparoscopic cholecystectomy under general anesthesia. The PTSMA was performed for HOCM 5 month before surgery and the left ventricular outflow pressure gradient (LVOTG) was reduced from 100 mmHg to 30 mmHg. After anesthetic induction, severe hypotension occurred concomitantly with asymmetrical septal hypertrophy (ASH) and systolic anterior movement of the mitral valve leaflet (SAM). Hypotension was treated with fluid therapy and the vasopressors (methoxamine and noradrenaline). Care should be taken for the anesthetic management of a patient with HOCM even after PTSMA.

[Laparoscopic ovarian cystectomy with abdominal wall lift during pregnancy under combined spinal-epidural anesthesia].

Abdominal wall lift laparoscopic surgery is often used for patients during pregnancy because it is physiologically superior to CO2 pneumoperitoneum laparoscopic surgery. Operation for adnexal cysts is performed in the 1st trimester. We report seven cases of ovarian cysts during pregnancy, resected using gassless laparoscopic method with a whole abdominal wall lift under combined spinal-epidural anesthesia (CSEA). Combined spinal-epidural anesthesia had several advantages in these cases; 1. In the 1 st trimester, general anesthesia should be avoided. We could manage these cases without general anesthesia nor sedative medications. 2. During pregnancy, it is difficult to estimate the level of sensory blockade by spinal anesthesia. Epidural top-up helped us to easily control the level of sensory blockade. 3. Differential diagnosis of pain related to uterine contraction and postoperative pain is difficult. Post-operative analgesia was established by epidural PCA, thus anti uterine contraction medicines were prophylactically administered in only one of seven cases. There was no particular trouble during the anesthesia and all the operative procedures were performed uneventfully. Based on our limited experiences, CSEA may be a safe and appropriate anesthetic technique for laparoscopic ovarian cystectomy with abdominal wall lift during pregnancy.