Intellectual property strategy : analysis of the flash memory industry

Thesis (S.M.M.O.T.)--Massachusetts Institute of Technology, Sloan School of Management, Management of Technology Program, 2006.Page 150 blank.Includes bibliographical references (o, 120-121).This thesis studies the intellectual property strategy of companies in the flash memory industry, with special emphasis on technology and the development of nitride-based flash, a new and emerging type of memory technology. First, general perspectives and frameworks for licensing of patents and know-how are explored. Then, the participants in the flash memory industry are mapped to a product value chain, which is in turn mapped to an intellectual property value chain. We use a patent database analysis software IPVision in order to examine the patent portfolios of some of the memory chip companies. Analysis of the patent positions allows us to draw conclusions about the direction of technology development.by Tomoko H. Ogura.S.M.M.O.T

Activities of bone morphogenetic proteins in prolactin regulation by somatostatin analogs in rat pituitary GH3 cells

Involvement of the pituitary BMP system in the modulation of prolactin (PRL) secretion regulated by somatostatin analogs, including octreotide (OCT) and pasireotide (SOM230), and a dopamine agonist, bromocriptine (BRC), was examined in GH3 cells. GH3 cells are rat pituitary somato-lactotrope tumor cells that express somatostatin receptors (SSTRs) and BMP system molecules including BMP-4 and -6. Treatment with BMP-4 and -6 increased PRL and cAMP secretion by GH3 cells. The BMP-4 effects were neutralized by adding a BMP-binding protein Noggin. These findings suggest the activity of endogenous BMPs in augmenting PRL secretion by GH3 cells. BRC and SOM230 reduced PRL secretion, but OCT failed to reduce the PRL level. In GH3 cells activated by forskolin, BRC suppressed forskolin-induced PRL secretion with reduction in cAMP levels. OCT did not affect forskolin-induced PRL level, while SOM230 reduced PRL secretion and PRL mRNA expression induced by forskolin. BMP-4 treatment enhanced the reducing effect of SOM230 on forskolin-induced PRL level while BMP-4 did not affect the effects of OCT or BRC. Noggin treatment had no significant effect on the BRC actions reducing PRL levels by GH3 cells. However, in the presence of Noggin, OCT elicited an inhibitory effect on forskolin-induced PRL secretion and PRL mRNA expression, whereas the SOM230 effect on PRL reduction was in turn impaired. It was further found that BMP-4 and -6 suppressed SSTR-2 but increased SSTR-5 mRNA expression of GH3 cells. These findings indicate that Noggin rescues SSTR-2 but downregulates SSTR-5 by neutralizing endogenous BMP actions, leading to an increase in OCT sensitivity and a decrease in SOM230 sensitivity of GH3 cells. In addition, BMP signaling was facilitated in GH3 cells treated with forskolin. Collectively, these findings suggest that BMPs elicit differential actions in the regulation of PRL release dependent on cellular cAMP-PKA activity. BMPs may play a key role in the modulation of SSTR sensitivity of somato-lactotrope cells in an autocrine/paracrine manner

Isolation and gene analysis of interferon α-resistant cell clones of the hepatitis C virus subgenome

AbstractHepatitis C virus (HCV) proteins appear to play an important role in IFN-resistance, but the molecular mechanism remains unclear. To clarify the mechanism in HCV replicon RNA harboring Huh-7 cells (Huh-9-13), we isolated cellular clones with impaired IFNα-sensitivity. Huh-9-13 was cultured for approximately 2 months in the presence of IFNα, and 4 IFNα-resistant cell clones showing significant resistances were obtained. When total RNA from clones was introduced into Huh-7 cells, the transfected cells also exhibited IFNα-resistance. Although no common mutations were present, mutations in NS3 and NS5A regions were accumulated. Transactivation of IFNα and IFNα-stimulated Stat-1 phosphorylation were reduced, and the elimination of HCV replicon RNA from the clones restored the IFNα signaling. These results suggest that the mutations in the HCV replicon RNA, at least in part, cause an inhibition of IFN signaling and are important for acquisition of IFNα resistance in Huh-9-13

Multiple functions of precursor BDNF to CNS neurons: negative regulation of neurite growth, spine formation and cell survival

<p>Abstract</p> <p>Background</p> <p>Proneurotrophins and mature neurotrophins elicit opposite effects via the p75 neurotrophin receptor (p75^NTR) and Trk tyrosine kinase receptors, respectively; however the molecular roles of proneurotrophins in the CNS are not fully understood.</p> <p>Results</p> <p>Based on two rare single nucleotide polymorphisms (SNPs) of the <it>human brain-derived neurotrophic factor (BDNF) </it>gene, we generated R125M-, R127L- and R125M/R127L-BDNF, which have amino acid substitution(s) near the cleavage site between the pro- and mature-domain of BDNF. Western blot analyses demonstrated that these BDNF variants are poorly cleaved and result in the predominant secretion of proBDNF. Using these cleavage-resistant proBDNF (CR-proBDNF) variants, the molecular and cellular roles of proBDNF on the CNS neurons were examined. First, CR-proBDNF showed normal intracellular distribution and secretion in cultured hippocampal neurons, suggesting that inhibition of proBDNF cleavage does not affect intracellular transportation and secretion of BDNF. Second, we purified recombinant CR-proBDNF and tested its biological effects using cultured CNS neurons. Treatment with CR-proBDNF elicited apoptosis of cultured cerebellar granule neurons (CGNs), while treatment with mature BDNF (matBDNF) promoted cell survival. Third, we examined the effects of CR-proBDNF on neuronal morphology using more than 2-week cultures of basal forebrain cholinergic neurons (BFCNs) and hippocampal neurons. Interestingly, in marked contrast to the action of matBDNF, which increased the number of cholinergic fibers and hippocampal dendritic spines, CR-proBDNF dramatically reduced the number of cholinergic fibers and hippocampal dendritic spines, without affecting the survival of these neurons.</p> <p>Conclusion</p> <p>These results suggest that proBDNF has distinct functions in different populations of CNS neurons and might be responsible for specific physiological cellular processes in the brain.</p

An analysis of intestinal morphology and incretin-producing cells using tissue optical clearing and 3-D imaging

Tissue optical clearing permits detailed evaluation of organ three-dimensional (3-D) structure as well as that of individual cells by tissue staining and autofluorescence. In this study, we evaluated intestinal morphology, intestinal epithelial cells (IECs), and enteroendocrine cells, such as incretin-producing cells, in reporter mice by intestinal 3-D imaging. 3-D intestinal imaging of reporter mice using optical tissue clearing enabled us to evaluate both detailed intestinal morphologies and cell numbers, villus length and crypt depth in the same samples. In disease mouse model of lipopolysaccharide (LPS)-injected mice, the results of 3-D imaging using tissue optical clearing in this study was consistent with those of 2-D imaging in previous reports and could added the new data of intestinal morphology. In analysis of incretin-producing cells of reporter mice, we could elucidate the number, the percentage, and the localization of incretin-producing cells in intestine and the difference of those between L cells and K cells. Thus, we established a novel method of intestinal analysis using tissue optical clearing and 3-D imaging. 3-D evaluation of intestine enabled us to clarify not only detailed intestinal morphology but also the precise number and localization of IECs and incretin-producing cells in the same samples

ジンソクナ バイスタンダー シンパイ ソセイホウ ニヨリ トツゼンシ オ マヌガレ シャカイ フッキ デキタ コウコウセイ ノ 2 ショウレイ

Bystander CPR means that people who find cardiopulmonary arrest perform cardiopulmonary resuscitation on the spot. Quick CPR contributes to increase in the rate of returning to the society as well as one-month survival rate and neurological prognosis. We report our experience with two high school students who underwent quick Bystander CPR, avoided sudden death, and returned to the society. ［Case 1］ Eighteen-year-old man : He collapsed suddenly in his home. Bystander CPR was performed by his family until emergency crews arrived there. Automated external defibrillator （AED） worked twice and his heartbeat started again. In electrocardiogram, coved type ST elevation in lead V1 was observed, and he was diagnosed as Brugada syndrome. We implanted an implantable cardioverter-defibrillator. Since his condition was stable, he was discharged on the 19th day. ［Case 2］ Seventeen-year-old woman : She collapsed suddenly walking with her family. Her father confirmed that she had no response, and started Bystander CPR. Her father got AED quickly and AED worked once, and she started to breathe again. She was admitted to our hospital for a work-up. Torsades de pointes （TdP） was observed in monitor electrocardiogram, and her QTc time was 513 msec in 12‐lead electrocardiogram. She was diagnosed as congenital long QT syndrome because genetic test showed that she had LQT2. Her QTc time was improved （approximately 350 msec） by medication, and she was discharged on the 25th day. Utstein-style statistics in Japan shows that the rate of returning to the society can be doubled by performing Bystander CPR on patients with cardiopulmonary arrest. However, performing rate of Bystander CPR is less than 50％ in Japan. In order to increase survival rate of patients with cardiopulmonary arrest for the future, it is important to inform people about CPR and to promote CPR, and in fact, we have been promoting CPR

Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton

AbstractOver the course of evolution, the acquisition of novel structures has ultimately led to wide variation in morphology among extant multicellular organisms. Thus, the origins of genetic systems for new morphological structures are a subject of great interest in evolutionary biology. The larval skeleton is a novel structure acquired in some echinoderm lineages via the activation of the adult skeletogenic machinery. Previously, VEGF signaling was suggested to have played an important role in the acquisition of the larval skeleton. In the present study, we compared expression patterns of Alx genes among echinoderm classes to further explore the factors involved in the acquisition of a larval skeleton. We found that the alx1 gene, originally described as crucial for sea urchin skeletogenesis, may have also played an essential role in the evolution of the larval skeleton. Unlike those echinoderms that have a larval skeleton, we found that alx1 of starfish was barely expressed in early larvae that have no skeleton. When alx1 overexpression was induced via injection of alx1 mRNA into starfish eggs, the expression patterns of certain genes, including those possibly involved in skeletogenesis, were altered. This suggested that a portion of the skeletogenic program was induced solely by alx1. However, we observed no obvious external phenotype or skeleton. We concluded that alx1 was necessary but not sufficient for the acquisition of the larval skeleton, which, in fact, requires several genetic events. Based on these results, we discuss how the larval expression of alx1 contributed to the acquisition of the larval skeleton in the putative ancestral lineage of echinoderms