Traceless component of the conformal curvature tensor in Kähler manifold

summary:We investigate the traceless component of the conformal curvature tensor defined by (2.1) in Kähler manifolds of dimension $\ge 4$, and show that the traceless component is invariant under concircular change. In particular, we determine Kähler manifolds with vanishing traceless component and improve some theorems (for example, [4, pp. 313–317]) concerning the conformal curvature tensor and the spectrum of the Laplacian acting on $p$ $(0\le p\le 2)$-forms on the manifold by using the traceless component

Development of a high yield purification process for the production of influenza virus vaccines

Production of influenza virus in animal cells has emerged as an alternative to conventional platforms such as egg-based production system. Animal cells, especially MDCK and VERO cell lines, are widely used as the primary production cell for influenza virus vaccine because of their high susceptibility to infection with various influenza viruses. Recently, a robust and reliable purification process was successfully developed for the production of quadri-valent HA proteins (from two strains of the type A virus and two strains of the type B virus) by using animal cell-based production system in Green Cross Corp., Korea. The UF/DF process, Benzonase treatment at high temperature as well as column chromatography strategy was optimized to maximize the final HA production yields. Benzonase treatment was conducted to reduce in hcDNA (host cell DNA) because hcDNA was main impurity for cell-based influenza virus vaccine. A simple and stable UF/DF process has been tested with membrane molecular weight cutoffs of 100 and 300 kDa as well as 0.2 and 0.45 um microfiltration membrane. Anion exchange chromatography (AEC) and size exclusion chromatography (SEC) were selected for acceptable reduction in hcDNA and HCP. AEC was used to separate hcDNA from virus at a salt concentration of 0.5 M sodium chloride. The HA yield through AEC & SEC combination process was sufficiently achieved under specific purification process condition. Overall, the amount of residual hcDNA was reduced to an acceptable level (10ng/dose) and the increased HA yield was maintained throughout the whole process. The performance, productivity and scalability of the purification process were successfully demonstrated in over 30 GMP batches using 4 different influenza virus strains

Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis

Background/Aims Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. Methods We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve. Results Plasma GPC3 levels in HCC patients were very low (0–3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729. Conclusion The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted

Effects of cyclic adenosine monophosphate modulators on maturation and quality of vitrified-warmed germinal vesicle stage mouse oocytes

Background It is still one of the unresolved issues if germinal vesicle stage (GV) oocytes can be successfully cryopreserved for fertility preservation and matured in vitro without damage after warming. Several studies have reported that the addition of cyclic adenosine monophosphate (cAMP) modulators to in vitro maturation (IVM) media improved the developmental potency of mature oocytes though vitrification itself provokes cAMP depletion. We evaluated whether the addition of cAMP modulators after GV oocytes retrieval before vitrification enhances maturation and developmental capability after warming of GV oocytes. Methods Retrieved GV oocytes of mice were divided into cumulus-oocyte complexes (COCs) and denuded oocytes (DOs). Then, GV oocytes were cultured with or without dibutyryl-cAMP (dbcAMP, cAMP analog) and 3-isobutyl-l-methylxanthine (phosphodiesterase inhibitor) during the pre-vitrification period for 30 min. Results One hour after warming, the ratio of oocytes that stayed in the intact GV stage was significantly higher in groups treated with cAMP modulators. After 18 h of IVM, the percentage of maturation was significantly higher in the COC group treated with dbcAMP. The expression of F-actin, which is involved in meiotic spindle migration and chromosomal translocation, is likewise increased in this group. However, there was no difference in chromosome and spindle organization integrity or developmental competence between the MII oocytes of all groups. Conclusions Increasing the intracellular cAMP level before vitrification of the GV oocytes maintained the cell cycle arrest, and this process may facilitate oocyte maturation after IVM by preventing cryodamage and synchronizing maturation between nuclear and cytoplasmic components. The role of cumulus cells seems to be essential for this mechanism.This work was supported by the grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C1999 and HI18C0081), supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (grant number: NRF-2017R1C1B2003897), and supported by the grant from the Seoul National University Bundang Hospital (SNUBH) Research Fund (grant number: 02–2014-022)

Ultrasound-guided Lateral Femoral Cutaneous Nerve Block in Meralgia Paresthetica

Meralgia paresthetica is a rarely encountered sensory mononeuropathy characterized by paresthesia, pain or sensory impairment along the distribution of the lateral femoral cutaneous nerve (LFCN) caused by entrapment or compression of the nerve as it crossed the anterior superior iliac spine and runs beneath the inguinal ligament. There is great variability regarding the area where the nerve pierces the inguinal ligament, which makes it difficult to perform blind anesthetic blocks. Ultrasound has developed into a powerful tool for the visualization of peripheral nerves including very small nerves such as accessory and sural nerves. The LFCN can be located successfully, and local anesthetic solution distribution around the nerve can be observed with ultrasound guidance. Our successfully performed ultrasound-guided blockade of the LFCN in meralgia paresthetica suggests that this technique is a safe way to increase the success rate

Structural and Biochemical Bases for the Inhibition of Autophagy and Apoptosis by Viral BCL-2 of Murine γ-Herpesvirus 68

All gammaherpesviruses express homologues of antiapoptotic B-cell lymphoma-2 (BCL-2) to counter the clearance of infected cells by host antiviral defense machineries. To gain insights into the action mechanisms of these viral BCL-2 proteins, we carried out structural and biochemical analyses on the interactions of M11, a viral BCL-2 of murine γ-herpesvirus 68, with a fragment of proautophagic Beclin1 and BCL-2 homology 3 (BH3) domain-containing peptides derived from an array of proapoptotic BCL-2 family proteins. Mainly through hydrophobic interactions, M11 bound the BH3-like domain of Beclin1 with a dissociation constant of 40 nanomole, a markedly tighter affinity compared to the 1.7 micromolar binding affinity between cellular BCL-2 and Beclin1. Consistently, M11 inhibited autophagy more efficiently than BCL-2 in NIH3T3 cells. M11 also interacted tightly with a BH3 domain peptide of BAK and those of the upstream BH3-only proteins BIM, BID, BMF, PUMA, and Noxa, but weakly with that of BAX. These results collectively suggest that M11 potently inhibits Beclin1 in addition to broadly neutralizing the proapoptotic BCL-2 family in a similar but distinctive way from cellular BCL-2, and that the Beclin1-mediated autophagy may be a main target of the virus