News Article | May 26, 2017
Computex 2017 is next week, and the biggest brands and most die-hard fans in computing will descend upon Taipei, Taiwan. It’s arguably the most important show of the year for the desktop, laptop and components you’ll want to buy. This is the show for folks who are left disillusioned by the lack of overclocking competitions and talk of gigahertz and teraflops at more mainstream tech expos, like CES in Las Vegas. While we’ve already seen some of the wares that key computer makers will show off, namely that of Acer and MSI, there’s plenty more still behind all manner of curtains and veils. However, recent leaks and announcements from the firms yet to break their big news of the show can help us make some educated guesses as to what we might see. Here’s everything we are prepared to witness from the biggest computing companies planning to touch down in Taipei next week, from May 30 through June 3. This firm based out of the very same country Computex is held annually has already shown its cards regarding the big show. With that, we know with certainty that we can expect to get hands-on time with Acer’s Nitro 5 gaming laptop as well as its Acer Spin 1 2-in-1 laptop and new Android tablets with Quantum Dot displays. Having just come off of its massive annual media event in New York City this past April, chances are slim that we’ll see much more from Acer during Computex. If we had to wildly guess, perhaps Acer will have more in PC gaming hardware to show off, that being a major focus of the show these days – just don’t hold your breath. Having been teasing its new Vega graphics chip architecture for what seems like eons now, AMD will perhaps choose Computex as the place we’ll finally see new the first Vega graphics cards. After all, we’ve at least already seen the developer-grade Radeon Vega Frontier Edition. We have to be close to seeing the future of PC gaming on AMD hardware by this point. Speaking of which, we’ve been hearing plenty over the past few weeks of the next wave of AMD Ryzen processors, the Ryzen 9 Threadripper series. Designed to compete with Intel’s supposed Core i9 line of high-end chips, Threadripper will come rocking 16-core processors that may be slower than Ryzen 7 CPUs in frequency, but far more ready to handle multifaceted workloads. Computex would be the perfect venue to showcase the power of not only Vega GPUs, but these new Threadripper CPUs as well. This is one of the firms we know the least about in regards to what it might have to show during Computex 2017. That said, we do know that Asus will hold press conferences for both its core, eponymous brand and its gaming brand, Republic of Gamers (ROG). We’ve heard murmurs of the next Asus Zenbook Flip, the UX370, to succeed the current UX360, which we enjoyed quite a bit. On the gaming front, Asus ROG has outright teased a gaming laptop powered by Ryzen to be shown at Computex in the above looping video. Here’s to hoping that’s an all-AMD build with graphics that rhyme with “mega”. Frankly, we’ve seen very little in the way of leaks and rumors in the lead up to Computex, which doesn’t give us much, if anything, to go off of. However, one thing that we’re at least hoping to see in more detail is Dell’s head-mounted display for Microsoft’s Windows 10 Holographic program. With the headset expected to launch later this year alongside the rest of the lot, Computex would be a fine place to demonstrate its capabilities. We know for a fact that Dell will hold a press event during the show, so hopefully this will be the place to see Dell’s big dip into virtual reality – sorry, “mixed reality,” if you’re asking Microsoft. The one thing we expect to hear more about from Intel at Computex is its rumored Core i9 line of processors. According to leaks, this new echelon of Intel CPUs will include new Skylake-X and Kaby Lake-X models ranging from octa-core to dodeca-core dies. Of course, the logic here is that Intel is preparing its defenses for the oncoming assault of AMD’s Threadripper Ryzen 9 processors. However, unlike AMD, Intel has yet to make anything official. The firm should change that during its press event scheduled during Computex. This is another one of those component firms that won’t officially say much, if anything, about its plans (unlike a certain rosy rival) until it’s ready to discuss them in full. That said, Nvidia does tend to be leaky, and so we have talk of the firm’s Volta GPU architecture being prepared for a Q3 2017 launch, meaning any time after the end of June. And, whaddya know, that’s just in time AMD Vega’s expected debut. Specifically, sites like WCCFTech report to have heard that Volta will be brought to bear through GTX 20-series GPUs. If this is what Nvidia truly has in store for its Computex press event, then this ought to be a knock-down, drag-out summer for the red and green teams. Finally, we have the company that stands to shake up the show the most: Qualcomm. The firm has been largely silent on its plans to work with Microsoft to bring Windows 10 x86 app emulation to its next generation of Snapdragon processors since they were first announced last December. It’s potentially the lynch pin in Microsoft’s mobile ambitions moving forward. Again, Computex would be the time to demonstrate how Qualcomm’s technology works and what types of new mobile devices running Windows 10, much less any, that it can enable.
News Article | May 24, 2017
Board also reports quarterly dividend of $0.275 SPRINGFIELD, IL--(Marketwired - May 24, 2017) - Horace Mann Educators Corp. ( : HMN) today named Kimberly Johnson to the position of Vice President & Controller. Johnson will serve as the principal accounting officer for the company and report to Executive Vice President & Chief Financial Officer Bret Conklin. "Kim has proven her acumen and diligence as a finance leader at Horace Mann," Conklin said. "Her impressive technical skills combined with her strong leadership skills make her a natural fit for the Controller role." Johnson brings nearly 30 years of accounting experience to the role, including 15 years at Horace Mann, most recently as Vice President and Assistant Controller. Before coming to Horace Mann, she served in several roles at MSI Insurance and Ernst and Young, including controller, accountant and auditor. She has certifications as a public accountant and management accountant, and is an Associate in Reinsurance and a Fellow of the Life Management Institute. She holds a Bachelor of Science in Accounting and a Master of Business Administration, both from University of Minnesota's Carson School of Management. In addition, the Board of Directors today resolved that a quarterly dividend of $0.275 per share is hereby declared to be paid to all shareholders of record as of June 14, 2017 and made payable as of June 30, 2017. About Horace Mann Horace Mann -- the largest national multiline insurance company focusing on educators' financial needs -- provides auto, homeowners and life insurance, retirement products and other financial solutions. Founded by Educators for Educators® in 1945, the company is headquartered in Springfield, Ill. For more information, visit horacemann.com. Statements included in this news release that are not historical in nature are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995 and are subject to certain risks and uncertainties. Horace Mann is not under any obligation to (and expressly disclaims any such obligation to) update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Please refer to the company's Annual Report on Form 10-K for the period ended December 31, 2016 and the company's past and future filings and reports filed with the Securities and Exchange Commission for information concerning the important factors that could cause actual results to differ materially from those in forward-looking statements.
News Article | May 23, 2017
M S International, Inc. (MSI), North America’s leading supplier of natural stone slabs, hardscaping materials, porcelain tiles, and ceramic tiles, is pleased to announce that its entire line of Stile® Gauged Porcelain tile slabs is now Kosher certified with the Seal of the Kosher Trust (Seal-K). Seal-K certification makes Stile® Gauged Porcelain slabs suitable for Kosher food. MSI’s Q™ Premium Natural Quartz line is also Kosher certified. Seal-K is widely recognized by both US and European rabbinical authorities and approved by some of the most respected names in Kosher supervision. Guided by the highest standards, members of the Seal-K team are certified by the Chief Rabbinate of Israel. “Now that Stile® is Seal-K certified, we’re able to offer families and businesses over one dozen Kosher porcelain tile slabs in the most sought-after colors and patterns,” says Sam Kim, Vice President of MSI. He adds, “the feedback we received about Q™’s Seal-K certification was entirely positive—and we look forward to the same response with Stile®.” Stile® is a large-format, lightweight porcelain slab, suitable for virtually every interior and exterior design project including flooring, accent walls, showers, backsplashes, fireplace surrounds, and countertops for the 12mm thickness. Stile® is available in two sizes (126”x63” and 118"x59") and two thicknesses (12mm and 6mm). The line comes in polished and matte finishes—with the matte finish featuring a low-gloss shine with stone-like texture. Stile® Gauged Porcelain tile slabs are an especially smart design solution for remodels, as they easily install over existing surfaces—resulting in a luxurious, updated look at an affordable cost. In addition to being Seal-K certified, Kosher families will appreciate that Stile® is low-maintenance, impervious to germs and bacteria, and etch, stain, and heat resistant. These features make Stile® 12 mm slabs an outstanding choice for kitchen countertops. What’s more, Stile®’s large format minimizes distracting grout lines, resulting in a near seamless appearance that promotes an overall sense of elegance. Learn more about Stile® Gauged Porcelain care and maintenance, colors and patterns, and recommended applications. Founded in 1975, MSI is the leading supplier of Premium Surfaces including flooring, countertops, decorative mosaics and wall tile, and hardscaping products. MSI’s product offering includes an extensive selection of granite, marble, porcelain, ceramic, quartz, glass, quartzite, and other natural stone products. Headquartered in Orange, California, MSI also maintains distribution centers across the United States and Canada. MSI’s product line is imported from over 36 different countries on six continents bringing the very best products to the North American Market. The company maintains an inventory of over 125 million square feet of material. For more information on MSI, visit: http://www.msistone.com
News Article | May 24, 2017
To understand the contribution of α-amino acid metabolism to the cancer progression of CML, we analysed blood amino acid levels in mouse models that recapitulate the chronic and blast crisis phases of human CML3, 4. Using amine-specific fluorescent labelling coupled with high-performance liquid chromatography (HPLC), 16 amino acids were quantified in the blood plasma from leukaemic mice (Extended Data Fig. 1a–d). Mice bearing blast crisis (BC)-CML showed moderate but significant elevations of plasma glutamate, alanine and the BCAAs (namely valine, leucine and isoleucine) compared with chronic phase (CP)-CML mice, indicating hyperaminoacidaemia (Extended Data Fig. 1e). Intracellular levels of BCAAs and proline were higher in BC-CML, whereas intracellular glutamate and alanine were comparable in the two disease phases (Fig. 1a). These results suggest that increased BCAA uptake or metabolism may contribute to CML progression. We analysed the gene expression and found no significant upregulation of known BCAA transporters in BC-CML compared with CP-CML (data not shown). Leucine import into BC-CML cells was not greater than into CP-CML cells (Extended Data Fig. 1f), indicating that increased BCAA uptake does not explain the higher BCAA levels in BC-CML. To examine the possibility of altered intracellular BCAA metabolism, we next analysed the expression of genes encoding amino acid metabolic enzymes and found that the branched-chain amino acid aminotransferase 1 (Bcat1) was more highly expressed in BC-CML than in CP-CML at both the messenger RNA (mRNA) and protein levels (Fig. 1b–c and Extended Data Fig. 1g–h). In contrast, normal haematopoietic stem/progenitor cells (HSPCs) from healthy mice had very low levels of Bcat1 expression (Lin− Sca-1+ c-Kit+ (LSK) population; Fig. 1b), and normal tissues did not show detectable Bcat1 expression except for the brain and testis (Extended Data Fig. 1i). Bcat1 encodes an evolutionarily conserved cytoplasmic aminotransferase for glutamate and BCAAs, constituting a regulatory component of cytoplasmic amino acid and keto acid metabolism5 (Fig. 1d and Extended Data Fig. 1j). Bcat2, a paralogue encoding the mitochondrial BCAA aminotransferase, and alanine and aspartate aminotransferases did not show differential expression between CP- and BC-CML (Extended Data Fig. 1g, k–l). Although BCAT1 catalyses transamination in both directions, the breakdown of BCAAs is the predominant reaction in most cell types6. For BCAT1 to generate BCAAs via the reverse reaction, the corresponding branched-chain keto acids (BCKAs), as well as glutamate, must be present as substrates. We found that all three BCKAs, keto-isovalerate (KIV), keto-isocaproate (KIC) and keto-methylvalerate were present in both the blood plasma and leukaemia cells (Extended Data Fig. 2a–d). In BC-CML cells, BCKAs were present at concentrations equivalent to 22–55% of the corresponding BCAAs, suggesting that intracellular BCKAs can serve as substrates for BCAA production (Extended Data Fig. 2e). Next, we examined whether BCAAs are produced through BCAT1 transamination reactions in leukaemia cells by stable-isotope tracer experiments with [13C]valine or [13C]KIV. Intracellular 13C-labelled metabolites in K562 human BC-CML cells were analysed using one- and two-dimensional 1H–13C heteronuclear single-bond correlation (HSQC) analysis by high-field NMR spectroscopy (Fig. 1e–h and Extended Data Fig. 3). HSQC analysis detects only metabolites that have incorporated 13C isotope. To determine whether KIV is converted to valine, cells were cultured in media supplemented with uniformly labelled [(U)-13C]KIV and non-labelled valine at physiological concentrations (30 and 170 μM, respectively), and analysed for intracellular 13C-labelled metabolites. After 15 min of labelling, the generation of [13C]valine was clearly observed, indicating the efficient intracellular production of valine from KIV (Fig. 1f, h). In contrast, [13C]KIV formation was barely detectable in the cells cultured with non-labelled KIV and [(U)-13C]valine (Fig. 1e, g). Our observation of intracellular [13C]valine signals indicates its transport into BC-CML cells. We also detected robust signals for [13C]KIV when present (Extended Data Fig. 3d, f). The formation of valine from KIV, but not the breakdown of valine to KIV, was also observed when we used equal concentrations of KIV and valine in the labelling media (170 μM each; Fig. 1g, h). We did not detect KIC formation from [13C]leucine either (Extended Data Fig. 3g–i). These results indicate that little, if any, BCAAs are catabolized to BCKAs in leukaemia cells. To provide further evidence for the intracellular BCAA production through transamination, we performed alternative labelling experiments to track the fate of the amine group of glutamate. We cultured K562 cells with [15N]amine-labelled glutamine, which is metabolized to [15N]amine-glutamate by glutaminase upon cellular intake, and analysed the subsequent labelling of BCAAs via 1H NMR and 1H–15N heteronuclear multiple-bond correlation. This analysis detects only metabolites that have incorporated 15N, whereas 1H NMR detects any compounds containing protons (Extended Data Fig. 4a–f). At 29–72 h after labelling, we detected 15N-amine-labelled BCAAs, indicating transamination from glutamine to BCAAs (Fig. 1i). By 72 h, the 15N-amine-labelled BCAAs had accumulated to fractional abundances ranging from 24% to 39% (Extended Data Fig. 4g), indicating a significant contribution of transamination to the intracellular BCAA pool. Lentiviral BCAT1 knockdown resulted in greater than a 50% decrease in the amount of intracellular BCAAs produced (Fig. 1j). These data demonstrate that BCKA transamination by BCAT1 contributes to the BCAA pool in leukaemia cells. Given that Bcat1 is highly expressed and augments intracellular BCAAs in BC-CML, Bcat1 may functionally contribute to the acute properties of BC-CML. To test this possibility, we inhibited Bcat1 expression using a short hairpin RNA (shRNA)-mediated gene knockdown approach. We sorted the immature lineage-negative (Lin−) cells from primary BC-CML samples, a population that contains the leukaemia-initiating cells of this cancer, and introduced two independent retroviral shRNA constructs (Extended Data Fig. 1j; shBcat1-a and shBcat1-b). Both constructs inhibited Bcat1 expression in BC-CML compared with a non-targeting negative control shRNA (shCtrl) (Extended Data Fig. 5a–c). Bcat1 knockdown resulted in significantly smaller colonies and a 40–60% reduction in the colony-forming ability relative to a control (Fig. 2a). The co-introduction of a shRNA-resistant Bcat1 cDNA rescued the reduced clonogenic potential (Extended Data Fig. 5d). As an alternative approach to gene knockdown, we treated BC-CML cells with gabapentin (Gbp), a chemical inhibitor of BCAT1. Gbp is a structural analogue of leucine and specifically and competitively inhibits the transaminase activity of BCAT1 but not that of BCAT2 (ref. 7). BC-CML cells plated with Gbp formed smaller colonies and showed a dose-dependent impairment in clonogenic growth (Fig. 2b). In contrast, normal HSPCs were only minimally affected by gene knockdown or Gbp treatment (Extended Data Fig. 5e, f). These data suggest that BCAT1 inhibition may selectively impair the propagation of leukaemia without affecting normal haematopoiesis. To examine whether Bcat1 loss affects the propagation of BC-CML in vivo, Lin− cells expressing shBcat1 were transplanted into conditioned recipient mice. Whereas 75% of the recipients transplanted with control cells succumbed to the disease within 30 days, only 47% (shBcat1-a) and 31% (shBcat1-b) of the mice transplanted with Bcat1-knockdown cells developed the disease, and more than half of these mice survived even when followed out to 60 days (Fig. 2c). Among the mice that developed disease with Bcat1 knockdown, most had leukaemia that was characterized by differentiated granulocytes and lower levels of immature myeloblasts (Fig. 2d and Extended Data Fig. 5g). They also displayed a lower frequency of immature Lin− cells than control leukaemia (Extended Data Fig. 5h), indicating that the loss of Bcat1 induced differentiation and impaired the leukaemia-initiating cell activity. Consistent with these phenotypes, serial transplantation of the leukaemia cells revealed that while all the control leukaemia cells propagated the disease, none of the mice transplanted with Bcat1-knockdown leukaemia cells succumbed to the disease (line ‘1k’ in Fig. 2e). In addition, we established a doxycycline (Dox)-inducible Bcat1 knockdown system (i-shBcat1) and examined the impact of Bcat1 loss on the disease maintenance. Ten days after transplantation with BC-CML cells infected with i-shBcat1, leukaemic engraftment was assessed in each recipient, and Dox treatment was initiated (Extended Data Fig. 5i, j). While almost all the mice that were transplanted with control cells and the non-Dox-treated mice developed leukaemia, more than half of the Dox-treated i-shBcat1 mice remained disease-free (Extended Data Fig. 5k), indicating that Bcat1 is required for the continuous propagation of BC-CML. At the cellular level, we did not observe enhanced apoptosis or a decrease in actively cycling cells by Bcat1 knockdown (Extended Data Fig. 5l, m). These results demonstrate that Bcat1 is critical for the sustained growth and maintenance of leukaemia-initiating cells in BC-CML. We next examined whether the enforced expression of Bcat1 could drive blastic transformation in haematopoietic cells. Although we observed a significant increase in Bcat1 expression compared with the vector control, Bcat1 expression alone did not enhance the colony-forming ability of either LSK or Lin− c-Kit+ haematopoietic cells isolated from normal bone marrow (Extended Data Fig. 6a, b). To determine whether BCR–ABL1 cooperates with Bcat1 overexpression to confer an aggressive growth phenotype, we transduced normal HSPCs with Bcat1 and BCR–ABL1. Compared with the vector control, the combinatorial expression promoted clonogenic growth in vitro (Extended Data Fig. 6c), and the transplantation of the cells led to significantly elevated leukaemia burdens (Extended Data Fig. 6d, e), splenomegaly and increased mortality in the recipient mice (Fig. 2f), with a concomitant increase in plasma BCAA levels (Extended Data Fig. 6f). Accordingly, leukaemia that developed in response to Bcat1 overexpression exhibited a highly immature myeloblastic morphology compared with the control (Fig. 2g and Extended Data Fig. 6g). These data indicate that activated Bcat1 mediates the blastic transformation of CP-CML cells. Our results demonstrate that Bcat1 is essential for the development of BC-CML in mice, while normal bone marrow HSPCs show a very limited dependence on this metabolic enzyme. To investigate the contribution of BCAT1 to human leukaemia, we looked at a panel of 13 peripheral blood samples from healthy and leukaemic individuals and found human BCAT1 expression was higher in BC-CML than in either normal or CP-CML cells (Fig. 3a). To determine whether this expression pattern reflects a general trend in human CML, we analysed BCAT1 levels in a Gene Expression Omnibus (GEO) dataset of 113 cases of CML8. This focused analysis revealed a significant elevation in BCAT1 expression as the disease progresses from the chronic to the accelerated phase and then to the blast crisis phase (Fig. 3b). On average, BCAT1 expression was 15-fold higher in BC-CML than in CP-CML. We did not find significant changes in BCAT2 expression, which is consistent with the results from the mouse models (Fig. 3c and Extended Data Fig. 1g). These data indicate that activation of BCAT1 is a shared characteristic in the progression of human CML. Lentiviral BCAT1 knockdown or Gbp treatment markedly inhibited the colony-forming ability of K562 human BC-CML (Extended Data Fig. 7a–d) and patient-derived primary leukaemia cells (Fig. 3d, e and Extended Data Fig. 7e, f). Interestingly, we observed BCAT1 activation in primary human acute myeloid leukaemia as well (AML; Fig. 3f), and Gbp effectively inhibited the clonal growth of human AML cell lines and primary de novo AML cells (Fig. 3g and Extended Data Fig. 7g–i). Moreover, BCAT1 expression levels predict disease outcome in patient cohorts. Cases from The Cancer Genome Atlas (TCGA) AML dataset were divided into quartiles on the basis of BCAT1 expression levels (Extended Data Fig. 7j), and we found that the median survival time was 46% shorter in the BCAT1-high group (427 versus 792 days; Fig. 3h). These results demonstrate an essential role for BCAT1 in the pathogenesis of a wide array of human myeloid malignancies. To understand how the BCAT1-driven change in metabolism promotes leukaemia growth, we analysed intracellular amino acid concentrations upon BCAT1 inhibition and found that all three BCAAs were significantly reduced by shBCAT1 or Gbp treatment compared with the controls (Extended Data Fig. 8a, b). Interestingly, the addition of BCAAs, but not alanyl–glutamine (GlutaMax), functionally suppressed the reduction of colony-forming ability caused by BCAT1 knockdown (Fig. 3i), suggesting that BCAT1 enhances clonogenic growth through BCAA production via BCKA reamination. BCAAs, particularly leucine, activate the mTORC1 pathway via cytosolic leucine sensor proteins, which integrate multiple signals from nutrient sensing and growth factor stimuli to promote cell growth9, 10, 11, 12. Thus, we examined whether reduced BCAA production by BCAT1 inhibition results in the attenuation of the mTORC1 signal. Indeed, BCAT1 blockade by either shRNA or Gbp treatment significantly reduced the phosphorylation of S6 kinase (pS6K), a downstream target of mTORC1 kinase (Fig. 3j), suggesting BCAT1 activation of the mTORC1 pathway. We observed no apparent changes in the levels of phosphorylated AKT upon BCAT1 inhibition, suggesting a predominant contribution of BCAA nutrient signals to the activation of mTORC1 (Extended Data Fig. 8c). Consistently, the mTORC1 inhibitor rapamycin reversed the BCAA-induced suppression of colony formation (Fig. 3i) and the BCAA-induced increase in pS6K (Fig. 3k). To further investigate the BCAT1-mediated regulation of CML progression, we performed gene correlation analyses using tumour gene expression datasets available in the GEO and TCGA databases. We found that BCAT1 and MSI2 are often co-expressed in several types of cancer, including leukaemias, colorectal and breast cancers (Extended Data Fig. 9a, b). MSI2 is a member of the evolutionarily conserved Musashi RNA binding protein family, which regulates cell fates during development and in multiple adult stem-cell systems in metazoans13, 14, 15. At the molecular level, Musashi proteins bind to r(G/A)U AGU sequences (MSI binding elements, MBEs) and post-transcriptionally regulate gene expression via mRNA binding16, 17. Importantly, MSI genes are aberrantly activated in human malignancies, such as gliomas and breast and colorectal cancers18, 19. In human BC-CML, the MSI2 gene is upregulated and functionally required for the progression of this leukaemia20, 21. To determine whether BCAT1 is a direct target of the MSI2 RNA binding protein, we analysed the BCAT1 mRNA sequence and found 40 putative MBEs in the 3′ untranslated region (3′ UTR; Extended Data Fig. 9c). To test whether MSI2 binds to the BCAT1 transcripts, we expressed a Flag-tagged MSI2 protein in K562 cells and performed RNA immunoprecipitation (RIP). Flag–MSI2 co-precipitated the BCAT1 transcripts with a greater than 1,500-fold enrichment relative to the vector control (Fig. 4a). In contrast, when RIP was performed with a mutant MSI2 protein in which three phenylalanine residues essential for RNA binding were replaced with leucine16, the amount of the BCAT1 mRNA recovered was markedly diminished (Fig. 4a, RNA binding defective mutant (RBD)), indicating that the co-precipitation of BCAT1 transcript requires the RNA binding activity of MSI2. The transcripts for β-2-microglobulin (B2M) or c-Myc oncogene (MYC) contain only one copy of a putative MBE in their 3′ UTRs (data not shown), and MSI2 RIP did not enrich B2M or MYC mRNAs as efficiently as BCAT1 (Fig. 4a). Furthermore, RIP with an anti-MSI2 antibody showed that endogenous MSI2 proteins bound to BCAT1 transcripts, while B2M or MYC mRNAs exhibited minimal enrichment relative to that of an immunoglobulin-G (IgG) control (Fig. 4b), indicating that MSI2 is specifically associated with the BCAT1 transcripts. Because MSI2 knockdown reduced the levels of BCAT1 protein and p-S6K (Extended Data Fig. 9d), the binding of MSI2 to BCAT1 mRNA positively regulates BCAT1 translation and mTORC1 activation. Importantly, BCAT1 overexpression (Fig. 4c) and BCAA supplementation (Fig. 4d) effectively suppressed the attenuation of the colony-forming ability caused by MSI2 knockdown, with a concomitant increase in pS6K levels in a rapamycin-sensitive manner (Fig. 4e). The levels of AKT phosphorylation were unaffected by shMSI2 (Extended Data Fig. 8c). Collectively, our work presented here demonstrates an essential role for the MSI2–BCAT1 axis in myeloid leukaemia and provides a proof-of-principle for inhibiting the BCAA metabolic pathway to regulate CML progression (Fig. 4f). The upregulation and functional requirements of BCAT1 have been reported in glioblastoma and in colorectal and breast tumours22, 23. Interestingly, Musashi proteins also regulate the same spectrum of cancers including myeloid leukaemia18, 19, 20, 21, 24, 25, suggesting a highly conserved role for the MSI–BCAT1 pathway in multiple cancer types. Despite the conservation of this pathway, the metabolic role of BCAT1 seems distinct and dependent on the tissue of origin; in the brain, BCAT1 catalyses BCAA breakdown and glutamate production to enhance tumour growth in glioblastoma23, whereas it promotes BCAA production in leukaemia. Two different types of tumour, specifically pancreatic ductal adenocarcinoma and non-small-cell lung carcinoma, were recently shown to exhibit different usages of BCAAs26. Despite the same initiating events of KRAS activation and TP53 deletion, non-small-cell lung carcinoma cells actively utilize BCAAs by enhancing their uptake and oxidative breakdown to BCKAs, whereas pancreatic ductal adenocarcinoma cells display decreased uptake and thus little dependency on BCAAs. Consistently, BCAT1 and BCAT2 are required for tumour formation in non-small-cell lung carcinoma but not in pancreatic ductal adenocarcinoma. Although BCAT1 is functionally required for tumour growth in a broad range of malignancies, these reports and our studies highlight the context-dependent role of the BCAT1 metabolic pathway in cancer.
News Article | May 10, 2017
This award follows our 1st place finish in the HRO Today Magazine’s 2017 Baker’s Dozen Award – Relocation, announced in March, and our 1st place at the European 2016 EMMA Awards in London last November, and our 2016 win in the Re:locate Magazine Awards for Best Relocation Management Company. “Once again, out of a crowded field of contestants, MSI is delighted to be recognized by one of the relocation industry’s leading organizations,” commented Timm Runnion, MSI’s CEO. “To be regularly seen, acknowledged and recognized as a leading provider of Global Talent Solutions and an innovator in our industry, is validation of our mission, vision and purpose as a company” Runnion added. It is our people, our own talent, with their constant and diligent focus on quality service, client/transferee experience, and positive and successful outcomes, that makes this all possible. We want to thank and recognize them for their efforts and this accomplishment.” MSI is a professional services organization dedicated to helping companies grow, compete, and globalize through the development and implementation of highly effective human capital strategies and the alignment of resources and services necessary to carry them out. Global corporations depend on our trusted expertise and managed services capabilities in the specialized areas of:
News Article | May 12, 2017
Receive press releases from Aspose Pty Ltd: By Email Use Enhanced GS1 Barcode Generation & Recognition in SQL Server Reporting Services Using Aspose.BarCode for SSRS APIs 17.4 It Aspose.BarCode for SSRS APIs 17.4.0 enhanced functionality of GS1 coded barcode. It allows developers to generate GS1 coded barcode according to AI specifications. New validators have been incorporated that can validate text code having only digits & complex AIs. API will throw an exception in case it fails to validate. Functionality of ExportToXml method has been improved. ExportToXml method now export dimension properties along with other properties of newly define barcode into XML file. Lane Cove, Australia, May 12, 2017 --( We are happy to announce the new release of Aspose.BarCode for Reporting Services 17.4.0. The major development in this release is the enhanced functionality of GS1 coded barcode. More often it is seem that GS1 code text contains complex combination of digits and letters. With Aspose.BarCode for SSRS 17.4, parsing and validation of those complex combinations is possible. Aspose.BarCode for SSRS allows developers to generate GS1 coded barcode according to AI (Application Identifier) specifications. New validators have been incorporated that can validate text code having only digits and complex AIs (combination of digits & letters). API will throw an exception in case it fails to validate. According to AI specification (ref: 703 AI, with letters – 324a, with more than 4 symbols) code text “(703)123” is incorrect. Aspose.BarCode will throw following exception if user tries to generate the barcode with EncodeTypes as GS1Code128. The following exception message will be displayed for such an incorrect barcode. Functionality of ExportToXml method has been improved. ExportToXml method now export dimension properties along with other properties of the newly define barcode into XML file. Below is the list of new and improved features added in this new release. • Improve GS1 parsing and validation • BarCodeBuilder allows to generate incorrect GS1 barcodes • Barcode generator accepts incorrect GS1 codetext • BarCodeBuilder.ExportToXml method is not exporting dimensions of the barcode in the XML file • Reorganize properties in Properties Window Newly added documentation pages and articles Some new tips and articles have now been added into Aspose.BarCode for Reporting Services documentation that may guide users briefly how to use Aspose.BarCode for performing different tasks like the followings. - QR or Micro QR Barcode Encoding Selector: https://docs.aspose.com/display/barcodereportingservices/QR+or+Micro+QR+Barcode+Encoding+Selector - How to Display BarCodes in Report Header: http://www.aspose.com/docs/display/barcodereportingservices/How+to+Display+BarCodes+in+Report+Header Overview: Aspose.BarCode for Reporting Services Aspose.BarCode for Reporting Services is a .NET solution for the rendering of barcode images in SQL Server 2000, 2005 & 2008 Reporting Services. It supports 40+ linear (1D) and 2D barcode symbologies including MacroPdf417, Australia Post, OneCode, Code128, Code39, PDF417, UPCA, Codabar, MSI and QR etc. Also render barcode images on reports in BMP, JPG, PNG and GIF formats. Other features include EAN-128 application identifiers, DPI resolution settings, barcode size and location adjustments. More about Aspose.BarCode for Reporting Services - Homepage of Aspose.BarCode for Reporting Services: http://www.aspose.com/products/barcode/reporting-services - Download Aspose.BarCode for Reporting Services: http://www.aspose.com/downloads/barcode/reportingservices - Online documentation of Aspose.BarCode for Reporting Services : http://docs.aspose.com/display/barcodereportingservices/Home Contact Information Aspose Pty Ltd Suite 163, 79 Longueville Road Lane Cove, NSW, 2066 Australia http://www.aspose.com/ firstname.lastname@example.org Phone: 888.277.6734 Fax: 866.810.9465 Lane Cove, Australia, May 12, 2017 --( PR.com )-- What's New in this Release?We are happy to announce the new release of Aspose.BarCode for Reporting Services 17.4.0. The major development in this release is the enhanced functionality of GS1 coded barcode. More often it is seem that GS1 code text contains complex combination of digits and letters. With Aspose.BarCode for SSRS 17.4, parsing and validation of those complex combinations is possible. Aspose.BarCode for SSRS allows developers to generate GS1 coded barcode according to AI (Application Identifier) specifications. New validators have been incorporated that can validate text code having only digits and complex AIs (combination of digits & letters). API will throw an exception in case it fails to validate. According to AI specification (ref: 703 AI, with letters – 324a, with more than 4 symbols) code text “(703)123” is incorrect. Aspose.BarCode will throw following exception if user tries to generate the barcode with EncodeTypes as GS1Code128. The following exception message will be displayed for such an incorrect barcode. Functionality of ExportToXml method has been improved. ExportToXml method now export dimension properties along with other properties of the newly define barcode into XML file. Below is the list of new and improved features added in this new release.• Improve GS1 parsing and validation• BarCodeBuilder allows to generate incorrect GS1 barcodes• Barcode generator accepts incorrect GS1 codetext• BarCodeBuilder.ExportToXml method is not exporting dimensions of the barcode in the XML file• Reorganize properties in Properties WindowNewly added documentation pages and articlesSome new tips and articles have now been added into Aspose.BarCode for Reporting Services documentation that may guide users briefly how to use Aspose.BarCode for performing different tasks like the followings.- QR or Micro QR Barcode Encoding Selector: https://docs.aspose.com/display/barcodereportingservices/QR+or+Micro+QR+Barcode+Encoding+Selector- How to Display BarCodes in Report Header: http://www.aspose.com/docs/display/barcodereportingservices/How+to+Display+BarCodes+in+Report+HeaderOverview: Aspose.BarCode for Reporting ServicesAspose.BarCode for Reporting Services is a .NET solution for the rendering of barcode images in SQL Server 2000, 2005 & 2008 Reporting Services. It supports 40+ linear (1D) and 2D barcode symbologies including MacroPdf417, Australia Post, OneCode, Code128, Code39, PDF417, UPCA, Codabar, MSI and QR etc. Also render barcode images on reports in BMP, JPG, PNG and GIF formats. Other features include EAN-128 application identifiers, DPI resolution settings, barcode size and location adjustments.More about Aspose.BarCode for Reporting Services- Homepage of Aspose.BarCode for Reporting Services: http://www.aspose.com/products/barcode/reporting-services- Download Aspose.BarCode for Reporting Services: http://www.aspose.com/downloads/barcode/reportingservices- Online documentation of Aspose.BarCode for Reporting Services : http://docs.aspose.com/display/barcodereportingservices/HomeContact InformationAspose Pty LtdSuite 163, 79 Longueville RoadLane Cove, NSW, 2066Australiahttp://email@example.comPhone: 888.277.6734Fax: 866.810.9465 Click here to view the list of recent Press Releases from Aspose Pty Ltd
News Article | May 15, 2017
HONG KONG--(BUSINESS WIRE)--Motorola Solutions (NYI:MSI) will unveil highly advanced technology solutions to enhance the capabilities of nationwide public safety networks in the Asia Pacific at Critical Communications World 2017. The company’s mission-critical radio technologies, specialised software, mission critical broadband, command centre solutions and future innovation concepts will all be presented at Asia World Expo in Hong Kong. Motorola Solutions’ advanced technology showcase comes at a time when both mission-critical radio and public safety broadband solutions are in high demand throughout the Asia Pacific. This is reflected in forecasts that by 2020 there will be *almost 20 million active two-way radios in the region, while the ** North America and Asia Pacific regions combined will account for nearly 70 percent of all public safety broadband investment globally. Iain Clarke, corporate vice president and general manager, Asia Pacific, for Motorola Solutions, said the growth in both mission-critical communications and mobile broadband technologies is fuelled by demand for end-to-end, interoperable solutions combining the most needed elements of voice, data and multimedia communication. “ Public safety customers in Asia Pacific are among the most technically advanced in the world and are continuing their rapid adoption of mission-critical mobile intelligence services and smart technologies,” Clarke said. “ This is enabling them to filter and analyse the vast amounts of data available today so they can make better and faster decisions to protect our communities. “ Motorola Solutions’ deep domain expertise in delivering holistic public safety solutions will benefit those countries in Asia Pacific planning for large-scale, highly-available and secure deployments,” he said. Motorola Solutions continues to invest in new capabilities and skills to accelerate innovation within Asia Pacific - from its partnership with Singapore’s ST Electronics to develop advanced communications technologies to its acquisition of a large team of mobile application developers through the acquisition of Gridstone in Australia. Clarke said further evidence of his company’s much needed role in delivering secure and reliable critical communication services and global innovation was demonstrated through a series of major milestones. These include Motorola Solutions’: Motorola Solutions supports mission-critical systems in more than 20 countries globally including Hong Kong, Korea, Singapore, Australia, the U.S., the U.K. and countries in Europe. It also has a proven track record of delivering, managing and operating large-scale, complex and dependable public safety networks. “ At CCW we will demonstrate our broad capabilities to deliver end-to-end public safety software solutions as well as the powerful set of tools we have to enable organisations to work more safely and collaboratively with increased situational awareness,” Clarke said. Learn more about WAVE 5000 Learn more about the Si Series Learn more about CommandCentral Vault Learn more about Intelligent Middleware Motorola Solutions (NYSE: MSI) creates innovative, mission-critical communication solutions and services that help public safety and commercial customers build safer cities and thriving communities. For ongoing news, visit www.motorolasolutions.com/newsroom or subscribe to a news feed. * The number of active two-way radios in Asia Pacific is expected to increase to over 19.8 million by end 2020 (a CAGR growth of 3 percent from 2016-2020). Source: IHS Research ** The North America and Asia Pacific regions will account for nearly 70% of all public safety LTE investments over the next four years. Source: SNS Telecom report ‘Public Safety LTE & Mobile Broadband Market: 2016 – 2030 – Opportunities, Challenges, Strategies & Forecasts MOTOROLA, MOTOROLA SOLUTIONS and the Stylized M Logo are trademarks or registered trademarks of Motorola Trademark Holdings, LLC and are used under license. All other trademarks are the property of their respective owners. ©2017 Motorola Solutions, Inc. All rights reserved.
News Article | May 11, 2017
On Wednesday, shares in Hanover, Maryland headquartered Ciena Corp. recorded a trading volume of 2.47 million shares. The stock ended at $23.64, climbing 0.68% from the last trading session. The Company's shares have gained 7.80% in the last one month. The stock is trading above its 50-day and 200-day moving averages by 1.41% and 4.51%, respectively. Furthermore, shares of Ciena, which provides equipment, software, and services that support the transport, switching, aggregation, service delivery, and management of voice, video, and data traffic on communications networks worldwide, have a Relative Strength Index (RSI) of 64.96. On April 19th, 2017, Ciena announced that Globecomm has deployed the Company's converged packet-optical and packet networking solutions to meet growing content distribution requirements for a variety of critical applications, including video for breaking news stories, disaster recovery for armed forces, and essential connectivity to maritime ships crossing oceans around the world. With this network, Globecomm can cost-effectively increase the capacity, reliability, and availability of high-bandwidth services to more than 250 customers throughout its global footprint. Access our complete research report on CIEN for free at: Sunnyvale, California headquartered Infinera Corp.'s stock finished yesterday's session 0.94% lower at $9.49 with a total trading volume of 1.25 million shares. The Company's shares have gained 3.38% over the previous three months and 11.78% on an YTD basis. The stock is trading above its 200-day moving average by 2.03%. Furthermore, shares of Infinera, which provides optical transport networking equipment, software, and services worldwide, have an RSI of 43.10. On May 09th, 2017, Infinera announced a successful subsea field test with Canalink across its subsea cable. The test, conducted with the Infinera Infinite Capacity Engine, and featuring the Company's fourth-generation photonic integrated circuit, demonstrated the capability to upgrade the cable capacity 13-fold. The complimentary research report on INFN can be downloaded at: At the close of trading on Wednesday, shares in Suwanee, Georgia headquartered ARRIS International PLC rose 0.53%, ending the day at $28.19. The stock recorded a trading volume of 1.44 million shares. The Company's shares have advanced 5.86% in the last one month. The stock is trading 8.21% and 0.85% above its 50-day and 200-day moving averages, respectively. Moreover, shares of ARRIS International, which together with its subsidiaries, provides media entertainment and data communications solutions in the US and internationally, have an RSI of 73.31. On April 24th, 2017, ARRIS International announced two, new advanced Satellite Receiver solutions for satellite distribution networks: the DSR-7412 Integrated Receiver/Transcoder and DSR-4470 Integrated Receiver/Decoder. The new receivers feature next-generation HEVC UHD/4K decoding and DVB-S2X demodulation capabilities, adding to the Company's leading portfolio of satellite distribution solutions. Register for free on Stock-Callers.com and get access to the latest PDF format report on ARRS at: Chicago, Illinois headquartered Motorola Solutions Inc.'s shares ended the day 1.18% higher at $85.77. A total volume of 1.26 million shares was traded, which was above their three months average volume of 1.13 million shares. The stock has gained 2.46% in the last month, 10.24% over the previous three months, and 4.07% on an YTD basis. The Company's shares are trading 2.67% above their 50-day moving average and 8.92% above their 200-day moving average. Additionally, shares of Motorola Solutions, which provides mission-critical communication infrastructure, devices, accessories, software, and services in North America, Latin America, Asia/Pacific, Middle/East, Europe, and Africa, have an RSI of 57.79. On May 01st, 2017, Motorola Solutions announced that it has entered into an agreement to acquire Kodiak Networks, a privately held provider of broadband push-to-talk for commercial customers. The acquisition agreement is subject to customary closing conditions and is expected to close later this year. 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MSI Inc and Osaka University | Date: 2011-04-07
A distance measuring apparatus comprises: an edge specifying part 101 for specifying the edge of a probe 6 in a secondary portrait appearing on the surface of a work 9 and an image of the probe 6; a straight line inserting part 102 for inserting a straight line along the outer edge of the secondary portrait onto an image, and an overlap determining part 103 for determining an overlap of the edge and the straight line, wherein one or more LED lamps 7, and calculating part for calculating the distance wherein the imaging device and the probe 6 are movably held integrally for the surface of the work 9.
Osaka University and MSI Inc | Date: 2012-02-01
An ion source (10) is provided with a push-out electrode (1), a pull-out electrode (2), and a pull-in electrode (3) all for ionizing a sample and accelerating generated ions in a pulsed manner, wherein the push-out electrode (1) and/or the pull-in electrode (3) has a curved surface shape having a depression curved in the direction opposite to the direction of travel of the ions. As a result, a compact ion source capable of temporally and spatially focusing ions and outputting the ions, and a compact time-of-flight mass spectroscope with good detection resolution and detection sensitivity which is provided with the compact ion source can be provided.