The three-site spin correlation, S_{i}·(S_{j}×S_{k}) on the neighboring triangular sites i, j and k, termed scalar spin chirality, can endow the conduction electron with a quantum Berry phase and resultant transverse (Hall) transport. The paramagnetic barely metallic state was prepared in hole-doped Y_{2}Mo_{2}O_{7} with pyrochlore lattice using a high-pressure synthesis method, which is further endowed with the spin chirality by partially replacing Y site with Tb (content x). The local spin chirality formed by the adjacent three Tb Ising moments on the pyrochlore lattice can couple to the conduction electrons to give rise to the topological Hall effect whose magnitude increases in proportion to x^{3} or the density of the Tb-moment triangular clusters.

What is known and Objective:  Although new thrombopoietin (TPO) receptor agonist drugs, such as romiplostim and eltrombopag, are highly effective and well tolerated for patients with immune thrombocytopenia (ITP) refractory to first-line treatments such as prednisolone, the cross-resistance of these two TPO receptor agonists is still unknown. Case summary:  An 84-year-old Japanese female patient with steroid-refractory ITP received eltrombopag with a gradually increasing dose schedule from 12·5 to 25 mg/day, 37·5 mg/day and finally 50 mg/day. As no increase in platelet count was observed even at the maximum dose of 50 mg/day, and eltrombopag-related grade 3 elevation of aspartate aminotransferase was observed, another TPO receptor agonist, romiplostim, was administered at 1 μg/kg/week subcutaneously. A rapid increase in platelet count was observed 1 week after the first injection. The dose of romiplostim was escalated to 4 μg/kg according to the platelet count and a complete response was achieved 7 weeks after the first injection without any adverse events. What is new and Conclusion:  The successful treatment of ITP refractory to eltrombopag with romiplostim strongly suggests that the absence of cross-resistance between these two approved TPO receptor agonists and possible differences in mechanism of action. Further study of the mechanisms of action of TPO receptor agonists is called for along with further exploration of the potential of romiplostim in refractory ITP.

PUB domains are identified in several proteins functioning in the ubiquitin (Ub)-proteasome system and considered as p97-binding modules. To address the further functional roles of these domains, we herein characterized the interactions of the PUB domain of peptide:N-glycanase (PNGase) with Ub and Ub-like domain (UBL) of the proteasome shuttle factor HR23. NMR data indicated that PNGase-PUB exerts an acceptor preferentially for HR23-UBL, electrostatically interacting with the UBL surface employed for binding to other Ub/UBL motifs. Our findings imply that PNGase-PUB serves not only as p97-binding module but also as a possible activator of HR23 in endoplasmic reticulum-associated degradation mechanisms. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: PNGasebinds to HR23A by affinity chromatography technology (View interaction) PNGase and HR23Abind by nuclear magnetic resonance (View interaction) PNGase and HR23Bbind by nuclear magnetic resonance (View interaction).

Bone metabolism markers associated with 4 menstrual cycle phases were evaluated in 14 healthy young females without menstrual disorder. Menstrual cycle phases were confirmed with basal body temperature for 3 months, luteinizing hormone kits, and sexual hormone concentrations of serum. The bone metabolism markers used were osteocalcin (OC), which was measured by immunoradiometric assay (IRMA), and tartrate resistant acid phosphatase 5b (TRACP-5b), which was measured by enzyme immunometric assay (EIA). The highest values of OC and TRACP-5b were observed in the ovulation phase, and TRACP-5b increased significantly when compared with levels in the menstrual phase (p<0.05). Furthermore, the changes in sex-hormone secretion involved in OC and TRACP-5b showed specific patterns during the menstrual cycle. In other words, TRACP-5b levels are influenced by sex hormones produced during the menstrual period and are based on the bone-formation status. Therefore, it is presumed that the TRACP-5b levels during ovulation play a central role in bone formation and bone metabolism.

Generalized block-lifting factorization of M- channel (M > 2) biorthogonal filter banks (BOFBs) for lossyto- lossless image coding is presented in this paper. Since the proposed block-lifting structure is more general than the conventional lifting factorizations and does NOT require many restrictions such as paraunitary, number of channels and McMillan degree in each building block unlike the conventional lifting factorizations, its coding gain is higher than the previous methods. Several proposed BOFBs are designed and applied to image coding. Comparing the results with conventional lossy-tolossless image coding structures, including the 5/3 and 9/7-tap discrete wavelet transforms (DWTs) in JPEG 2000 and a 4 8 hierarchical lapped biorthogonal transform (HLBT) in JPEG XR, the proposed BOFBs achieve better result in both objective measure and perceptual visual quality for the images with a lot of high frequency components.

The aim of this study was to demonstrate the effects of sex and age on serum levels of 1,5-AG in nondiabetic subjects.A total of 1 134 nondiabetic subjects aged 16-96 years with HbA1c less than 6.8% were recruited and divided into 4 HbA1c groups (Q1: HbA1c≤5.3; Q2: 5.4-5.8; Q3: 5.9-6.3; and Q4: 6.4-6.8 [%]). 38 elderly subjects (65 years or older) in the Q3 and Q4 groups (13 men and 25 women) underwent a 75-g oral glucose tolerance test (OGTT).The Q4 group had significantly lower 1,5-AG levels than did the Q1 group among nonelderly males, nonelderly females, and elderly men. In elderly women, 1,5-AG levels did not differ among the 4 HbA1c groups. In both nonelderly and elderly subjects, the 1,5-AG level of the Q1 group was significantly higher in males than in females. Stepwise multivariate regression analysis showed that age was significantly associated with 1,5-AG level in both sexes. HbA1c was significantly associated with the 1,5-AG level in males, while there was no significant association between HbA1c and the 1,5-AG level in females. In the elderly OGTT group, although the glucose levels of both sexes during OGTT were identical, the mean urinary glucose levels and the percentages of subjects with glucosuria were significantly higher in elderly men than in elderly women.Serum 1,5-AG levels were significantly associated with age and sex. The sensitivity of the 1,5-AG level for identifying postprandial hyperglycemia in elderly women with near-normoglycemia is less reliable because they have a higher renal threshold for glucose.

Blockade of the CD40-CD154 costimulatory signal is an attractive strategy for immunosuppression and tolerance induction in organ transplantation. Treatment with anti-CD154 monoclonal antibodies (mAbs) results in potent immunosuppression in nonhuman primates (NHPs). Despite plans for future clinical use, further development of these treatments was halted by complications. As an alternative approach, we have been focusing on the inhibition of the counter receptor, CD40 and have shown that a novel human anti-CD40 mAb, ASKP1240, markedly prolongs renal allograft survival in NHPs, although allografts eventually underwent chronic allograft nephropathy. On the basis of our previous findings that a CD40-CD154 costimulation blockade induces tolerance to hepatic, but not cardiac, allografts in rodents, we tested here our hypothesis that a blockade of CD40 by ASKP1240 allows acceptance of hepatic allografts in NHPs. A 2-week ASKP1240 induction treatment prolonged liver allograft survival in NHPs; however, the graft function deteriorated due to chronic rejection. In contrast, a 6-month ASKP1240 maintenance monotherapy efficiently suppressed both cellular and humoral alloimmune responses and prevented rejection on the hepatic allograft. No serious side effects, including thromboembolic complications, were noted in the ASKP1240-treated monkeys. We conclude that CD40 blockade by ASKP1240 would be a desirable immunosuppressant for clinical liver transplantation.

During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global inportance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: Classification and Nomenclature; definition of stable disease; definition of Koebner's phenomenon; and "autoimmune vitiligo". These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo (SV) be classified separately from all other forms of vitiligo and that the term "vitiligo" be used as an umbrella term for all non-segmental forms of vitiligo, including "mixed vitiligo" in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of Koebner's phenomenon for vitiligo as proposed by the VETF (history-based, clinical observation-based, or experimentally induced). Lastly, the conference agreed that "autoimmune vitiligo" should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms. Significance:  There is a need for more homogenous reporting in vitiligo research. A broad international consensus was implemented on nomenclature and related issues (definition of stability, Koebner's phenomenon, and discussion of "autoimmune vitiligo" as an automomous entity). © 2012 John Wiley & Sons A/S.

Tumor vascular invasion is one of the worst factors of metastasis and/or recurrence in hepatocellular carcinoma (HCC) patients after living donor liver transplantation (LDLT), leading to poor outcomes. We investigated the relevance between preoperative parameters and histological vascular invasion among HCC patients who underwent LDLT. We enrolled 27 HCC patients who underwent LDLT from September 2003 to February 2011 in our hospital. Their primary diseases were hepatitis C (n = 16) hepatitis B (n = 9), primary biliary cirrhosis (n = 1), and cryptogenic liver cirrhosis (n = 1). The 2 groups were positive (N = 7) versus negative (N = 20) histological vascular invasion. We compared the greatest size and numbers of tumors from preoperative enhanced computerized axial tomography (CAT) scans, preoperative serum levels of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), as well as preoperative anticancer therapy. The preoperative greatest average diameter and numbers of tumor were 2.99 cm and 2.43, respectively, among positive patients, and 1.93 cm and 1.3, respectively, among patients with negative vascular invasion. The mean values of AFP and PIVKA-II were 3568.7 ng/mL and 2511.7 mAU/mL, respectively, among positive patients, and 812.8 ng/mL and 134.8 mAU/mL, respectively, among patients with negative vascular invasion. Five positive and 11 negative patients received preoperative anticancer therapy. Even if the tumor was within Milan criteria, namely, maximum size 3 cm and number of tumors 3, preoperative treatment may be a preoperative predictive factor for positive histological vascular invasion.