Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease

IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed

Synthesis, structure-activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues.

Lamellarin α and six different types of lamellarin α 20-sulfate analogues were synthesized and their structure-activity relationships were investigated using a single round HIV-1 vector infection assay. All lamellarin sulfates having pentacyclic lamellarin core exhibited anti-HIV-1 activity at a 10μM concentration range regardless of the number and position of the sulfate group. On the other hand, non-sulfated lamellarin α and ring-opened lamellarin sulfate analogues did not affect HIV-1 vector infection in similar concentrations. The lamellarin sulfates utilized in this study did not exhibit unfavorable cytotoxic effect under the concentrations tested (IC(50)>100μM). Confocal laser scanning microscopic analysis indicated that hydrophilic lamellarin sulfates were hardly incorporated in the cell. HIV-1 Env-mediated cell-cell fusion was suppressed by lamellarin sulfates. These results suggested that lamellarin sulfates have a novel anti-HIV-1 activity besides the previously reported integrase activity inhibition, possibly at a viral entry step of HIV-1 replication

Infection of XC Cells by MLVs and Ebola Virus Is Endosome-Dependent but Acidification-Independent

Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells

How We Broke the World Record for Computing Digits of Pi

We have calculated 31.4 trillion digits of Pi in 2019 and broke the world record in the Pi computation. The process took about four months and 200 TiB of storage. Record-breaking Pi calculations have traditionally been done on supercomputers and special-made hardware, but we did it on Cloud for the first time. This talk will discuss the nature of the calculation, the architecture, challenges and techniques, and of course the brief history of Pi computation. Calculating Pi has been the speaker's childhood dream and this talk will also explain how the small dream grew to the new world record. About the speaker Emma is a developer advocate for Google Cloud Platform, focusing on application developers experience and high performance computing. She has been a C++ developer for more than 15 years and worked on embedded systems and the Chromium Project. Emma is passionate about learning and explaining the most fundamental technologies such as operating systems, distributed systems, and internet protocols. Besides software engineering, she likes games, traveling, and eating delicious food.</p

Sensitivity to Morphological Spelling Regularities in Chinese-English Bilinguals and English Monolinguals

Evidence of sensitivity to graphotactic and morphological patterns in English spelling has been extensively examined in monolinguals. Comparatively few studies have examined bilinguals’ sensitivity to spelling regularities. The present study compared late Chinese-English bilinguals and English monolinguals on their sensitivity to systematic inflectional and derivational spelling regularities. One hundred and twenty-nine undergraduate students completed a forced-choice spelling task, in which nonword pairs were presented in a sentence context requiring a choice of the relevant grammatical form. English ability measures were administered to examine possible inter-individual differences in morphological sensitivity. The results showed that both monolinguals and bilinguals demonstrated knowledge of spelling patterns, but the groups differed in their sensitivity to inflectional and derivational spelling regularities. Specifically, bilinguals showed more consistent use of morphological spelling regularities in guiding their decision on spelling choice compared to monolinguals. The results are argued to be consistent with the predictions of statistical learning accounts of spelling acquisition

Sensitivity to Morphological Spelling Regularities in Chinese-English Bilinguals and English Monolinguals

Evidence of sensitivity to graphotactic and morphological patterns in English spelling has been extensively examined in monolinguals. Comparatively few studies have examined bilinguals’ sensitivity to spelling regularities. The present study compared late Chinese-English bilinguals and English monolinguals on their sensitivity to systematic inflectional and derivational spelling regularities. One hundred and twenty-nine undergraduate students completed a forced-choice spelling task, in which nonword pairs were presented in a sentence context requiring a choice of the relevant grammatical form. English ability measures were administered to examine possible inter-individual differences in morphological sensitivity. The results showed that both monolinguals and bilinguals demonstrated knowledge of spelling patterns, but the groups differed in their sensitivity to inflectional and derivational spelling regularities. Specifically, bilinguals showed more consistent use of morphological spelling regularities in guiding their decision on spelling choice compared to monolinguals. The results are argued to be consistent with the predictions of statistical learning accounts of spelling acquisition

Reproducibility and Variance of a Stimulation-Induced Hemodynamic Response in Barrel Cortex of Awake Behaving Mice

The present work evaluated the reproducibility and variance of the cerebral blood flow (CBF) response to natural whisker stimulation in the barrel cortex of awake-behaving mice. The animal was placed on an air float ball that allowed the animal to walk, while the head of the animal was fixed in a custom-made stereotactic apparatus. Dynamic CBF changes in the barrel cortex and animal locomotion were simultaneously monitored with laser-Doppler flowmetry (LDF) and an optical motion sensor that detected the rotation distance of the ball, respectively. Whisker stimulation-induced CBF measured under daytime and nighttime conditions showed consistent responses (24% and 23% of the pre-stimulus baseline, respectively), whereas the amount of locomotion was 1.4 times higher during nighttime relative to daytime. Repeated longitudinal experiments over seven days showed a reproducible, evoked CBF (13% to 26% relative to the baseline among 7 animals). The mean of the variance coefficient (i.e., standard deviation divided by mean) across multiple days was 0.11 and 0.75 for evoked CBF and locomotion, respectively. These results showed reproducible and reliable measurements of longitudinal CBF response in behaving mice regardless of day-to-day variations in locomotion. Furthermore, we confirmed that the CBF response to whisker stimulation was well localized and reproducible, measured with laser speckle imaging under awake condition. The results further show the capability of long-term hemodynamic imaging in normal and disease-model mice, which is of particular importance for understanding the longitudinal changes and plasticity of neurovascular coupling and behavioral performances such as during growth, development and aging