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Reporting to the Associate Vice President, the GM is responsible for providing leadership, direction, and coaching to the managed client sales and service teams and support functions in order to ensure maximum sales and service delivery effectiveness across multiple client offers and to drive growth in business results through the deepening of client relationships.
Provide effective leadership, at the Cluster level, to the advisory sales and support team to achieve high performance levels. Build a culture emphasizing collaboration in the delivery of highest-quality service and trusted financial advice across multiple client offers.
Lead the sales process to maximize profitability (revenue, funds managed growth), productivity, and client satisfaction. Provide support and training to ensure the sustainment and effective use of contact and sales planning tools.
Monitor the progress of sales volumes to business/sales plan. Typically the cluster is expected to produce gross revenue of approximately $9.7 million, average Direct Operating Expense budget of $1.7 million and a Funds Managed Growth target of $1 million.
Establish on-going recruitment efforts to identify and select high potential sales and support candidates for the Cluster while managing FTE count at Plan.
Ensure effective deployment of resources, making appropriate decision to ensure delivery of efficient and effective client experience while maximizing business opportunities.
Establish effective Cluster strategies for deepening the relationship with clients in all offers, while increasing share of wallet, decreasing attrition rates and improving service use count.
Responsible for the relationship management and effective partnerships in the Cluster to ensure clients are aligned to the appropriate offer.
Provide leadership to enhance the client experience through embedding the sales and service management methodology to all the employees within the Cluster, ensuring the client is introduced to the right offer and/or partner (e.g. Wood Gundy, CIBC Private Investment Counsel) for their needs.
Monitor compliance on the financial advice component and ensure all aspects of risk are effectively managed within the Cluster.
Ensure that CIBC s policies and programs are properly administered and effectively managed within in the Cluster.
Develop and manage an effective Cluster business plan, standards, initiatives and establish activities for Relationship managed Clients ensuring effective implementation and alignment with Market, Regional, and Retail Distribution initiatives.
Establish effective Cluster strategies for increasing the number of high value clients and share of wallet while maximizing the leads generated by branch banking colleagues.
Provide on-going advice, guidance & mentoring to direct reports, including coaching on sales and service management disciplines, tools and techniques, processes and standards, and involvement in complex client negotiations.
Work in partnership with the Client Service Manager to ensure consistent coaching and alignment of messaging in the overall leadership and guidance of the cluster team.
Responsible for the relationship management and effective partnerships with key colleagues (e.g. District Leadership team, General Manager Segment Delivery, Manager Segment Delivery, GM Credit Management etc).
Establish and maintain contact with key CIBC clients and community groups.
Lead business development initiatives within the Cluster through active involvement in the business community.
Ensure the implementation of Retail Distribution programs, process changes, and initiatives at the Cluster level.
Provide leadership to enhance the employee experience and creates a performance-driven culture within the Cluster while ensuring continual improvement of the capabilities of the sales team within the Cluster.
Ensure appropriate reward and recognition activities are implemented within the Cluster that are aligned with District, Market, Regional, and Retail Distribution programs.
Implement and sustain the sales planning methodology through on-going coaching and validating continued usage by sales force to ensure consistent efficient and effective client experience while maximizing business opportunities.
NOTE : For GMs who work in an IDA management capacity :
The IDA Branch Manager is responsible for managing the general operation of a Branch office and all associated sub-Branch offices. As part of these duties, this individual is the person who is registered with the IDA as being responsible for the primary level of supervision of all activities within the branch including, but not limited to:
- ensuring the proper registration is held by advisers,
- the oversight of account activity,
- the assessment of advice given to clients; and
- the review of incoming/outgoing correspondence.
The IDA Branch Manager is responsible for helping ensure that the management of client business is within the bounds of both regulatory and ethical conduct, consistent with just and equitable principles of trade and it is not detrimental to the interests of the securities industry or CIBC. This registered person must advise senior sales management and CIBC Wealth Management Compliance of any significant issues.
Successful completion of the Canadian Securities Course (CSC) upon start date.
- Successful completion of the Conduct and Practices Handbook (CPH) within 3 months of start date.
- BMC (CSI) - completion within 6 months of start date
- EMS - within 12 months of BMC completion
- PFPC/WME - completion within 18 months of start date
- IIROC (formerly IDA) license required
(PLEASE NOTE: Employees in Quebec will need to have CSC Accreditation as of start date and complete the IQPF instead of the CFP. It is a requirement that the IQPF be completed within 5 years of hire, with a minimum of 2 courses per year)
o Successful completion of the Branch Managers Course (BMC) within 3 months of the CPH is a requirement.
- Successful completion of the Effective Management Seminar (EMS) within 12 months of obtaining the BMC is a requirement.
Effective leadership capabilities.
Strong business development expertise.
Well-developed sales management and advisory coaching experience and skills.
Superior people management and development capabilities.
Proven ability to provide financial advice and solutions to meet client needs through a high performing sales and service team.
Excellent relationship building skills to establish key relationships with District and Market sales leadership and a diverse sales force.
Ability to provide the appropriate ongoing learning and coaching to ensure the continuous improvement of the capabilities of the sales team within the Cluster.
Strong influencing skills sufficient to lead and shape thinking and decisions while responding to underlying concerns of the Cluster s sales, service and support team, particularly through change.
District and cluster leadership team, management and peers.
External clients and community groups to promote the interest of CIBC.
Key local partners in Wood Gundy, CIBC Private Investment Counsel.
Other groups within CIBC World Markets.
Managing direct reports in multiple locations and in some instances across remote geographies.
Balancing the achievement of the cluster sales plan against ensuring all. aspects of risk are effectively managed in the cluster.
Sales and service leadership for breakthrough results in a highly competititve marketplace.
Results oriented
Forward and strategic thinking
Team builder
Developer of people
Apply on company website


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About افلام اوربيه جنسيه
افلام اوربيه جنسيه We will continue to assist scholars and teachers, students and critics - all citizens - to know more about this medium and therefore, to understand and use it well as part of their personal and social experience. With a stronger knowledge of televisions past our aim is for those projects to continue our role as an important participant in media education. Ichigo and others Chad, Renji, Rukia, Ishida face previous some obstacles on the way to Las Noches such as the Fraccion of the Espada, or the filler episode guy who was not pretty damn cool for filler, I have not to say - they introduced him nicely and they meet Nel, who follows Ichigo on his way - and through battling the many low ranking previous Espada, he Ichigo learns to start control his power more effectively, as the case goes. Additionally, video cameras give the opportunity to see a sneak preview of the scenes and how they will also look when finished, enabling the animators to correct and improve them without having to complete them first.
افلام سكس الفنانين This allows the animators and directors to work out any script and timing issues that may exist with the current storyboard. افلام سكس جنسي عربي مجاني This arc is not mainly considered a mini arc before the Hueco Mundo arc, but they kinda flow together, so I consider them one in a whole. افلام اوربيه جنسيه The large amount of images to choose from may also make the process of creating a test commercial a bit easier, as opposed to creating an animatic, because changes to drawn art take time and money. افلام اوربيه جنسيه Many serialistic shows begin with a Previously on. The storyboard and soundtrack are amended if necessary, and a new animatic may be created and reviewed with the director until the storyboard is perfected. Adult manga, or hentai manga, is not manga designed for purely pornographic purposes.
افلام اوربيه جنسيه Other genres to feature story arcs include comedies and animated programming, especially mecha anime. افلام اوربيه جنسيه ..

subset: commoncrawl


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Latest Worm Stories
It sounds like a classic horror story—eyeless, mouthless worms lurk in the dark, settling onto dead animals and sending out green "roots" to devour their bones. In fact, such worms do exist in the deep sea.
The females of the recently discovered Osedax marine worms feast on submerged bones via a complex relationship with symbiotic bacteria, and they are turning out to be far more diverse and widespread than scientists expected.
In the most computationally intensive phylogenetic analysis to date, an international research team led by Brown University has found the first evolutionary branching for bilateral animals.
The large group of segmented worms known as annelids, which includes earthworms, leeches and bristle worms, evolved millions of years ago and can be found in every corner of the world.
Luminescent sea worms that eject glowing green blobs have been found off the Oregon coast at depths up to 11,000 feet, scientists said. Oregon is the hotbed for these guys, said co-discoverer Karen J.
Researchers have discovered a new species of worm, dubbed the "green bomber.â€
Working with researchers in China, biologists at UC San Diego have discovered how a Chinese drug effective in killing parasitic roundworms works.
The fossilized tracks of a giant marine worm that lived some 475 million years ago have been discovered byt the Spanish National Research Council (CSIC).
The coevolutionary struggle between a New Zealand snail and its worm parasite makes sex advantageous for the snail, whose females favor asexual reproduction in the absence of parasites
Scientists and researchers are scouring the Palouse region from eastern Washington into the Idaho panhandle in hopes of finding more of the dwindling giant Palouse earthworms.
Latest Worm Reference Libraries
Mexican Golden Red Rump Tarantula (Brachypelma albiceps) is a species of the genus Brachypelma. The carapace is a light golden color with legs and a black abdomen covered with longer red hairs. Females typically live for about fifteen years. The males normally live about five years or up to twelve months after the last molt. This spider is native to the central highlands of Mexico, especially in Guerrero and south of Morelos. In the wild, they construct underground burrows, typically under...
The Sagalla caecilian (Boulengerula niedini) is a long, earthworm-like amphibian from the family Caeciliidae. The species is native to the tiny area of south-eastern Kenya called Sagalla Hill. The Sagalla caecilian has a slender body, perfect for burrowing. Its skin is extremely pigmented, lending it a brownish color with a pinkish-red hint, and white cross segments that give the appearance of grooves. They can grow up to 12 inches in length. Along with tough skin and a bony head, the...
The trumpet worm (Lagis koreni) is a species of polychaete worm that is classified within the Annelida phylum. It can be found in the waters around Europe including the North Sea, the Arctic Ocean, the Mediterranean Sea, the Atlantic Ocean, and the Adriatic Sea. This species is typically found submersed in sand in the neritic zone. The trumpet worm can reach an average length of about one inch and is typically light pink in color, with visible red veins and two pairs of red gills. This...
The nightcrawler (Lumbricus terrestris), also known as the lob worm or the common earthworm in Britain and the dew worm in Canada, is a species of earthworm that is classified within the Annelida phylum. It is native to Europe, but has been introduced into other areas around the world. Although the species is not as abundant as other worms in its range, it is a widely known species in gardens of temperate habitats, where it moves about on the surface of the soil. The nightcrawler can reach...
The Pompeii worm (Alvinella pompejana) is a species of polychaete worm, or bristle worm that is only found in the Pacific Ocean. It resides at hydrothermal vents, making it an extremophile, and was first discovered French marine biologists of the coat of the Galapagos Islands in the 1980s. It was described by Lucien Laubier and Daniel Desbruyeres as a deep-sea polychaete that could withstand extreme amounts of heat. The Pompeii worm can reach an average length of up to five inches and is...
- Sleep; the state or condition of being asleep.
- The state or condition of numbness of a part due to pressure on a nerve: as, the obdormition of a limb.


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Added Sep 21, 2010
by junespoon
Belfast, United ...
steffi jacket made with ikea upholstery fabric that i thought was cool.
I like using decorator weight fabric because it holds its shape well without the need for interfacing (which i don't really like working with when sewing…it always seems to crease and crumple…actually i've just remembered..i HATE using interfacing!)
sorry about the dodgy photos…i'd just come in from work and was feeling grumpy!
Apr 12, 2014, 02.37 PMby Jodi Wade
love the fabric choice
Sep 21, 2010, 08.17 PMby seasidelaundry
Terrific fit including sleeves with weight of fabric. Design placement & number of buttons (& holes) great, too. I agree on firmer fabric use. That is a really cute skirt! Did you make it?
Sep 21, 2010, 06.50 PMby BeYou TiFul
Your jacket is really nice. I like the fabric, Ikea has always nice fabrics!
Add to Favorites 9 people added it
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This amazing Inspira Studio by Closetmaid thread cabinet could be yours!
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|By PR Newswire
Article Rating:
|November 8, 2012 06:12 AM EST
BASKING RIDGE, N.J., Nov. 8, 2012 /PRNewswire/ -- As businesses seek to increase productivity through unified communications and collaboration capabilities, they are often challenged by how to select and implement the appropriate strategy and solution. To meet this challenge, Verizon is introducing Managed UC&C for Microsoft Lync Server 2010, which enables businesses to more easily adopt advanced communications and collaboration throughout their organizations while leaving the service and infrastructure management to Verizon.
Verizon's new offering is immediately available in the U.S. and 19 European countries: Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Italy, Luxembourg, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland and the U.K.
Now, large multinational enterprises can maximize business agility, increase employee productivity and equip a mobile workforce with advanced UC&C capabilities. The new offering also provides the added reliability and performance enabled by Verizon's world-class IMPACT management platform, which now incorporates Microsoft System Center 2012.
"Demand for truly integrated, enterprise-ready communications platforms for information sharing and collaboration is exploding on a global basis," said Martin Burvill, senior vice president of global operations for Verizon Enterprise Solutions. "The introduction of Managed UC&C for Microsoft Lync is an important component of our overall strategy to advance the way businesses operate through more effective engagement with employees, customers and partners. Enabling a modern workforce to more quickly connect by using video, voice and the Web is essential to speeding decision-making for greater productivity."
Large companies can employ the advanced instant messaging and presence, audio, video and Web conferencing of Microsoft Lync along with enterprise voice across Verizon's expansive global IP network, an advanced VoIP platform, featuring Session Initiation Protocol (SIP) with public switched telephone network (PSTN) integration. Managed UC&C for Microsoft Lync can facilitate adoption of desktop video conferencing as well as promote enterprise mobility across mobile operating systems, so mobile workers can experience enhanced IM/presence, single-number reach, and audio and video conferencing support.
The new offering can be combined with Verizon SIP Trunking with managed session border controllers to create a comprehensive, end-to-end UC&C infrastructure that facilitates more effective collaboration and decision-making.
In a related announcement, Acme Packet announced on Thursday (Nov. 8) that its session border controllers, which help set up and complete VoIP communications, have achieved certification with Verizon SIP Trunking and Microsoft Lync Server 2010.
Cindy Whelan, principal analyst at Current Analysis, said, "Implementation and integration of new services into enterprise communications environments have been the greatest challenges to UC&C adoption. Verizon's proven record delivering managed services and the company's Microsoft Gold expertise in delivering professional services specifically for Microsoft Lync Server 2010 can create a catalyst for effective UC&C adoption across a global enterprise."
Verizon professional consultants, working with Microsoft Corp. technology partners, can help design, deploy and integrate Microsoft Lync and supporting applications including Microsoft Active Directory, Exchange and SharePoint into a global enterprise environment.
Verizon was one of the first global service providers to offer professional services specifically designed to help organizations employ Microsoft Lync. The consulting services include workshop and strategic planning services, assessment services, architecture and design services, deployment and integration services, and unified communications applications enablement planning services.
Giovanni Mezgec, general manager, Microsoft Lync, said, "Microsoft and Verizon have a long-standing strategic relationship, developing and delivering advanced UC&C capabilities for a global business market. Integrating the latest Microsoft technologies with Verizon's managed services platform gives Verizon a unique end-to-end view across its customers' networks and applications to effectively keep Lync services running smoothly across multiple customer locations."
Verizon Enterprise Solutions creates global connections that generate growth, drive business innovation and move society forward. With industry-specific solutions and a full range of global wholesale offerings provided over the company's secure mobility, cloud, strategic networking and advanced communications platforms, Verizon Enterprise Solutions helps open new opportunities around the world for innovation, investment and business transformation. Visit verizon.com/enterprise to learn more.
About Verizon
Verizon Communications Inc. (NYSE, Nasdaq: VZ), headquartered in New York, is a global leader in delivering broadband and other wireless and wireline communications services to consumer, business, government and wholesale customers. Verizon Wireless operates America's most reliable wireless network, with nearly 96 million retail customers nationwide. Verizon also provides converged communications, information and entertainment services over America's most advanced fiber-optic network, and delivers integrated business solutions to customers in more than 150 countries, including all of the Fortune 500. A Dow 30 company with $111 billion in 2011 revenues, Verizon employs a diverse workforce of 184,500. For more information, visit www.verizon.com.
VERIZON'S ONLINE NEWS CENTER: Verizon news releases, executive speeches and biographies, media contacts, high-quality video and images, and other information are available at Verizon's News Center on the World Wide Web at www.verizon.com/news. To receive news releases by e-mail, visit the News Center and register for customized automatic delivery of Verizon news releases.
SOURCE Verizon
Scott Jenson leads a project called The Physical Web within the Chrome team at Google. Project members are working to take the scalability and openness of the web and use it to talk to the exponentially exploding range of smart devices. Nearly every company today working on the IoT comes up with the same basic solution: use my server and you'll be fine. But if we really believe there will be trillions of these devices, that just can't scale. We need a system that is open a scalable and by using the URL as a basic building block, we open this up and get the same resilience that the web enjoys.
Nov. 25, 2014 09:30 PM EST Reads: 1,415
The Internet of Things is tied together with a thin strand that is known as time. Coincidentally, at the core of nearly all data analytics is a timestamp. When working with time series data there are a few core principles that everyone should consider, especially across datasets where time is the common boundary. In his session at Internet of @ThingsExpo, Jim Scott, Director of Enterprise Strategy & Architecture at MapR Technologies, discussed single-value, geo-spatial, and log time series data. By focusing on enterprise applications and the data center, he will use OpenTSDB as an example t...
Nov. 25, 2014 09:30 PM EST Reads: 1,452
P2P RTC will impact the landscape of communications, shifting from traditional telephony style communications models to OTT (Over-The-Top) cloud assisted & PaaS (Platform as a Service) communication services. The P2P shift will impact many areas of our lives, from mobile communication, human interactive web services, RTC and telephony infrastructure, user federation, security and privacy implications, business costs, and scalability. In his session at @ThingsExpo, Robin Raymond, Chief Architect at Hookflash, will walk through the shifting landscape of traditional telephone and voice services ...
Nov. 25, 2014 08:00 PM EST Reads: 1,633
The Domain Name Service (DNS) is one of the most important components in networking infrastructure, enabling users and services to access applications by translating URLs (names) into IP addresses (numbers). Because every icon and URL and all embedded content on a website requires a DNS lookup loading complex sites necessitates hundreds of DNS queries. In addition, as more internet-enabled 'Things' get connected, people will rely on DNS to name and find their fridges, toasters and toilets. According to a recent IDG Research Services Survey this rate of traffic will only grow. What's driving t...
Nov. 25, 2014 07:00 PM EST Reads: 1,496
Enthusiasm for the Internet of Things has reached an all-time high. In 2013 alone, venture capitalists spent more than $1 billion dollars investing in the IoT space. With "smart" appliances and devices, IoT covers wearable smart devices, cloud services to hardware companies. Nest, a Google company, detects temperatures inside homes and automatically adjusts it by tracking its user's habit. These technologies are quickly developing and with it come challenges such as bridging infrastructure gaps, abiding by privacy concerns and making the concept a reality. These challenges can't be addressed w...
Nov. 25, 2014 04:30 PM EST Reads: 1,508
Explosive growth in connected devices. Enormous amounts of data for collection and analysis. Critical use of data for split-second decision making and actionable information. All three are factors in making the Internet of Things a reality. Yet, any one factor would have an IT organization pondering its infrastructure strategy. How should your organization enhance its IT framework to enable an Internet of Things implementation? In his session at Internet of @ThingsExpo, James Kirkland, Chief Architect for the Internet of Things and Intelligent Systems at Red Hat, described how to revolutioniz...
Nov. 24, 2014 07:00 PM EST Reads: 1,997
Bit6 today issued a challenge to the technology community implementing Web Real Time Communication (WebRTC). To leap beyond WebRTC's significant limitations and fully leverage its underlying value to accelerate innovation, application developers need to consider the entire communications ecosystem.
Nov. 24, 2014 12:00 PM EST Reads: 1,721
The definition of IoT is not new, in fact it's been around for over a decade. What has changed is the public's awareness that the technology we use on a daily basis has caught up on the vision of an always on, always connected world. If you look into the details of what comprises the IoT, you'll see that it includes everything from cloud computing, Big Data analytics, "Things," Web communication, applications, network, storage, etc. It is essentially including everything connected online from hardware to software, or as we like to say, it's an Internet of many different things. The difference ...
Nov. 24, 2014 11:00 AM EST Reads: 2,086
Cloud Expo 2014 TV commercials will feature @ThingsExpo, which was launched in June, 2014 at New York City's Javits Center as the largest 'Internet of Things' event in the world.
Nov. 24, 2014 09:00 AM EST Reads: 1,939
SYS-CON Events announced today that Windstream, a leading provider of advanced network and cloud communications, has been named "Silver Sponsor" of SYS-CON's 16th International Cloud Expo®, which will take place on June 9–11, 2015, at the Javits Center in New York, NY. Windstream (Nasdaq: WIN), a FORTUNE 500 and S&P 500 company, is a leading provider of advanced network communications, including cloud computing and managed services, to businesses nationwide. The company also offers broadband, phone and digital TV services to consumers primarily in rural areas.
Nov. 23, 2014 07:30 PM EST Reads: 2,125
"There is a natural synchronization between the business models, the IoT is there to support ," explained Brendan O'Brien, Co-founder and Chief Architect of Aria Systems, in this SYS-CON.tv interview at the 15th International Cloud Expo®, held Nov 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Nov. 23, 2014 12:00 PM EST Reads: 2,065
The major cloud platforms defy a simple, side-by-side analysis. Each of the major IaaS public-cloud platforms offers their own unique strengths and functionality. Options for on-site private cloud are diverse as well, and must be designed and deployed while taking existing legacy architecture and infrastructure into account. Then the reality is that most enterprises are embarking on a hybrid cloud strategy and programs. In this Power Panel at 15th Cloud Expo (http://www.CloudComputingExpo.com), moderated by Ashar Baig, Research Director, Cloud, at Gigaom Research, Nate Gordon, Director of T...
Nov. 23, 2014 07:45 AM EST Reads: 2,120
An entirely new security model is needed for the Internet of Things, or is it? Can we save some old and tested controls for this new and different environment? In his session at @ThingsExpo, New York's at the Javits Center, Davi Ottenheimer, EMC Senior Director of Trust, reviewed hands-on lessons with IoT devices and reveal a new risk balance you might not expect. Davi Ottenheimer, EMC Senior Director of Trust, has more than nineteen years' experience managing global security operations and assessments, including a decade of leading incident response and digital forensics. He is co-author of t...
Nov. 22, 2014 05:30 PM EST Reads: 1,820
ARMONK, N.Y., Nov. 20, 2014 /PRNewswire/ -- IBM (NYSE: IBM) today announced that it is bringing a greater level of control, security and flexibility to cloud-based application development and delivery with a single-tenant version of Bluemix, IBM's platform-as-a-service. The new platform enables developers to build ap...
Nov. 22, 2014 05:30 PM EST Reads: 2,083
Technology is enabling a new approach to collecting and using data. This approach, commonly referred to as the "Internet of Things" (IoT), enables businesses to use real-time data from all sorts of things including machines, devices and sensors to make better decisions, improve customer service, and lower the risk in the creation of new revenue opportunities. In his General Session at Internet of @ThingsExpo, Dave Wagstaff, Vice President and Chief Architect at BSQUARE Corporation, discuss the real benefits to focus on, how to understand the requirements of a successful solution, the flow of ...
Nov. 21, 2014 08:00 PM EST Reads: 1,841
The security devil is always in the details of the attack: the ones you've endured, the ones you prepare yourself to fend off, and the ones that, you fear, will catch you completely unaware and defenseless. The Internet of Things (IoT) is nothing if not an endless proliferation of details. It's the vision of a world in which continuous Internet connectivity and addressability is embedded into a growing range of human artifacts, into the natural world, and even into our smartphones, appliances, and physical persons. In the IoT vision, every new "thing" - sensor, actuator, data source, data con...
Nov. 21, 2014 08:00 PM EST Reads: 1,778
"BSQUARE is in the business of selling software solutions for smart connected devices. It's obvious that IoT has moved from being a technology to being a fundamental part of business, and in the last 18 months people have said let's figure out how to do it and let's put some focus on it, " explained Dave Wagstaff, VP & Chief Architect, at BSQUARE Corporation, in this SYS-CON.tv interview at @ThingsExpo, held Nov 4-6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Nov. 21, 2014 07:00 PM EST Reads: 1,708
Focused on this fast-growing market's needs, Vitesse Semiconductor Corporation (Nasdaq: VTSS), a leading provider of IC solutions to advance "Ethernet Everywhere" in Carrier, Enterprise and Internet of Things (IoT) networks, introduced its IStaX™ software (VSC6815SDK), a robust protocol stack to simplify deployment and management of Industrial-IoT network applications such as Industrial Ethernet switching, surveillance, video distribution, LCD signage, intelligent sensors, and metering equipment. Leveraging technologies proven in the Carrier and Enterprise markets, IStaX is designed to work ac...
Nov. 20, 2014 09:15 PM EST Reads: 1,712
C-Labs LLC, a leading provider of remote and mobile access for the Internet of Things (IoT), announced the appointment of John Traynor to the position of chief operating officer. Previously a strategic advisor to the firm, Mr. Traynor will now oversee sales, marketing, finance, and operations. Mr. Traynor is based out of the C-Labs office in Redmond, Washington. He reports to Chris Muench, Chief Executive Officer. Mr. Traynor brings valuable business leadership and technology industry expertise to C-Labs. With over 30 years' experience in the high-tech sector, John Traynor has held numerous...
Nov. 20, 2014 06:00 PM EST Reads: 1,592
The 3rd International @ThingsExpo, co-located with the 16th International Cloud Expo - to be held June 9-11, 2015, at the Javits Center in New York City, NY - announces that it is now accepting Keynote Proposals. The Internet of Things (IoT) is the most profound change in personal and enterprise IT since the creation of the Worldwide Web more than 20 years ago. All major researchers estimate there will be tens of billions devices - computers, smartphones, tablets, and sensors - connected to the Internet by 2020. This number will continue to grow at a rapid pace for the next several decades.
Nov. 20, 2014 01:00 PM EST Reads: 2,145


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Winnipeg Free Press - PRINT EDITION
New law protects jobs of parents of sick kids
Parents of critically ill children would be able to take extended leaves from work without fear of losing their jobs under legislation introduced in the Manitoba legislature on Friday.
The bill would also protect the jobs of parents on leave because a child died or disappeared as a result of crime.
The legislation is designed to complement new federal income supports for families in these situations. The federal benefits will be available for parents of a murdered or missing child beginning in January. Benefits for parents of critically ill children are to begin in June.
"We want to make sure that if Manitoba families find themselves in that position, they can take advantage of those benefits, and they also don't have to fear losing their job if they take those leaves," Family Services and Labour Minister Jennifer Howard said after introducing Bill 3 in the legislature.
To qualify, employees must have worked for the same employer for at least 30 days and the child must be under age 18.
Employees entitled to these leaves from work include a person who has care, custody or control of the child.
In the case of missing children, the leave will be available where it is "probable, considering the circumstances, that the child disappeared as a result of a crime." A police investigation into the matter is required -- but it wouldn't necessarily require that Criminal Code charges be laid relating to the disappearance, a government spokesman said in an email.
An employee wishing to take one of these leaves would be required to give the employer advance notice of at least one pay period unless this is not possible. Notice of one pay period is also required when employees are returning to work early from the leave.
Provisions in the bill are based on unanimous recommendations by members of the province's Labour Management Review Committee, which is made up of business and labour representatives.
Protected leaves include:
Up to 37 weeks off to care for a critically ill child;
Up to 104 weeks off work if a child has died as a result of a crime; and
Up to 52 weeks off work if a child has disappeared as a result of a crime.
Republished from the Winnipeg Free Press print edition November 24, 2012 A5
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Prevention and therapeutics of bacterial infections based on the activation of the reticuloendothelial system with glucan having β-1, 3-linkage in the main chain, the derivatives and partially hydrolysed product thereof.
1. A method of preventing or treating bacterial infectious diseases which comprises administering to a man or animal in need of said treatment or in need of prevention of bacterial infectious diseases, an antibacterially effective amount of a compound which is a glucan having the following formula: ##SPC3## the methylether, the carboxymethylether, the diethylaminoethylether, the acetylester, sulfonylester or phosphorylester thereof wherein each of n1 . . . nm is the number of linearly β -- (1-3)-linked glucose residues, said n1 . . . nm is independently a number from 0 to about 10.
2. The method of claim 1, wherein the composition is administered intraperitoneally, in a dose of 0.001-100 mg/kg/day.
3. The method of claim 1 wherein the composition is administered intramuscularly and the dose is 0.001 - 100 mg/kg/day.
4. The method of claim 1 wherein the composition is administered subcutaneously and the dose is 0.001-100 mg/kg/day.
5. The method of claim 1 wherein the composition is administered intravenously and the dose is 0.001-100 mg/kg/day.
This application is a continuation-in-part of Ser. No. 255,682, filed May 22, 1972, which is the continuation of Ser. No. 37029, filed on May 13, 1970, which was a continuation-in-part application of Ser. No. 766,630 filed Oct. 10, 1968, the latter having now been abandoned Ser. No. 37,029 has now been abandoned.
The present invention relates to a method for the prevention and for the therapeutics of bacterial infections in man and animals based on the activation of the reticuloendothelial system by a glucan having β-1, 3-linkage in the main chain, the derivatives and partially hydrolysed product thereof.
An object of this invention is to prevent and treat various bacterial infectious diseases in man and animals by administration of the glucan of this invention, the derivatives and partially hydrolysed products of the glucan by stimulation of the phagocytic activity of the reticuloendothelial cells. Another object of this invention is to increase the therapeutic activity of antibiotics by combination with the same glucan, its derivatives and its hydrolyzed products.
The glucans, which are the subject matter of the present invention, are polymers of linearly β-(1→3)-linked D-glucopyranose residues having side chains at various intervals thereon, each of the said side chains comprising one mole of β-(1→6)-linked D-glucopyranose residue. The general structure of the glucans is as follows: ##EQU1## WHEREIN G represents a β-D-glucoopyranose residue, the indicia 1, 3 and 6 indicate the positions where adjacent glucose residues are linked, each [3G 1] unit representing linearly β-(1→3)linked D-glucopyranose residues, and each of n1 . . . nm is the number of said linearly linked glucose residues in each [3G 1] unit, said n1 . . . nm being independently a number from 0 to about 10.
Thus the general structure of the glucans is as follows, with the structure for each G being shown in conventional form and the numbering of one of the pyranose rings being indicated: ##SPC1##
Wherein n1, n2, - - - nm are as defined above. For a better understanding, by way of example, a glucan in which all n are 2 is shown as follows: ##SPC2##
Where x is more than 3.
As is known, glucans of the above formula can be obtained from various fungi. It has now been found that a large number of fungi belonging to the following strains also produce the glucans having the action described above.
A. Ascomycetes:
Chaetomium cochliodes
Cochliobolus sativus
Ophiobolus miyabeanus
Pyrenophora teres
Sclerotinia arachidis
Sclerotinia mali
Sclerotinia sclerotiorum
B. Basidiomycetes:
Corticium centrifugum
Flammulina velutipes
Lentinus edodes
Lindera bicolumnata
Melanoleuca verrucipes
Pholiota nameko
Russula emetica
Russula sororia
Scleroderma cepa
C. Fungi imperfecti:
Alternaria kikutiana
Cercospora cryptomeriae
Cladosporium fulvum
Myrothecium verrucaria
Sclerotium tuliparum
Sclerotium hydrophylum
The strains previously reported as producing such glucans are Sclerotinia libertiana (M. Kitahara et al.: J. Agr. Chem. Soc. Japan, 35, 468,474 (1961)), Sclerotium glucanicum, Sclerotium delphinii, Sclerotium rolfsii, Sclerotium coffeicolum, Corticium rolfsii, Sclerotinia gladoli, and Stromatinia narcissi (F. E. Halleck: U.S. Pat. No. 3,301,848), Schizophyllum commune (S. Kikumoto et al: Taito Kenkyusho Hokoku, 22, 77 (1964), 23, 77 (1965), Japanese Pat. No. 505,408), Claviceps purpurea, and Claviceps fusiformis (A. S. Perlin et al.: Can. J. Chem., 41, 2278 - 82 (1963), and K. Buck et al.: J. Gen. Microbiol., 51, 337 (1968)). Some of these glucans are useful as additives in the paper industry and as noncaloric stable gelling agents in the food industry. Some of the derivatives of the glucan which are active within the scope of the present invention are the methylether, the carboxymethylether, the diethylaminoethylether, the acetylester, the sulfonylester and the phosphoric acid ester. Jert-hydrolyzed products are obtained from the said glucan by treatment with β- 1, 3 - glucans, acids and alkalies.
According to the present invention, it has been found that pharmaceutical preparations of this glucan and the derivatives thereof significantly stimulate the function of the reticuloendothelial system, and cause acceleration of phagocytic activity of phagocytes. This type of activity is a very characteristic pharmacological function of the glucan against a living body. This activity can be proved by the test for reticuloendothelial function by intravenous injection of Pelikan ink into mice and measuring its clearance by blood level. It has been clearly indicated by this test that intraperitoneal injection of about 2.5 mg/kg of the glucan results in acceleration of the reticuloendothelial system function. In another test, about 2.5 mg/kg of this glucan was administered intraperitoneally to mice every other day for three times, the peritoneal macrophages were collected, and these macrophages were mixed in vitro with a definite number of cells of Saccharomyces cerevisiae and Candida albicans. After 30 and 8 minutes, respectively, the cells were stained with Giemsa and their phagocytic index (= number of phagocytising macrophage/100 phagocytes) was measured. This result indicated that the phagocytic activity of the reticuloendothelial cells had been accelerated about two fold.
Administration of the glucan of this invention in mice results not only in acceleration of phagocytic activity, but also in elevation of the activity of various enzymes in the peritoneal macrophage, and helps in efficient digestion of foreign matter. The form of the macrophage grew large and its acid phosphatase staining showed the presence of numerous acid phosphatase-positive vacuoles and lysosome granules, indicating the functional activation.
This acceleration of the phagocytic activity is manifestly effective against some bacterial infectious diseases.
Preventive tests on various infectious diseases in mice which had been infected not only with pathogenic bacteria like Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, and Mycobacterium tuberculosis, but also with pathogenic fungi like Candida albicans were carried out and survival of the infected and control mice was examined. Intraperitoneal injection of 1.25-5 mg/kg or intramuscular or subcutaneous injection of 20-100 mg/kg of the glucan of this invention resulted in a marked prolongation of the life of the infected mice.
Since the glucan of this invention does not show any antibacterial activity in vitro against these bacteria antibiotics. fungus, it is clear that its effect is due to a mechanism entirely different from that of antibiotics and, moreover, the effective dose is comparable to that of known anitbiotics.
The therapeutic activity of antibiotics is further increased by the combined treatment with the glucan of this invention. This fact is especially important in the case of diseases which progress chronically such as tuberculosis, in which appearance of side effect of antibiotics or chemopherapeutics on the nervous sytem and other functions of the body is observed rather often. This is due to the fact that the use of the glucan of this invention with antibiotics or synthetic antituberculous agents, such as streptomycin, ethambutal, and isonicotinic acid hydrazide, is able to reduce the dose of these antituberculous agents and consequently the side effects above described are reduced.
In diseases progressing chronically other than tuberculosis like the infection with Pseudomonas aeruginosa, so far no effective antibiotic of low toxicity is known and the antibiotic with strong side effects, Gentamycin, has to be used. In this case, combined dose of the glucan of this invention with a chemotherapeutics will enable the administration of smaller doses of Gentamycin resulting in reduction of its side effect.
It is well known that the present trend for a wide and frequent use of antibiotics has resulted in the marked appearance of resistant strains. Since the mechanism of action of the glucan of this invention resides in an increase of the phagocytic activity of the host, a specific feature of this glucan is that it is effective against either the resistant or sensitive strains of bacteria.
The toxicity of the glucan of the present invention is extremely low as in general with other polysaccharides. Various tests on rats given 1, 5, or 25 mg/kg of this glucan once daily intraperitoneally for one and three months showed no abnormality in increase of body weight, blood picture, weight of internal organs, and various biochemical tests on serum and urine, except for an increase of γ-globulin in serum which is not an ill effect, and splenomegaly observed in a group given 25 mg/kg. The characteristic point is the marked increase of reticuloendothelial cells in the spleen, lymph nodes, and the liver by histopathological examination. The fact indicates that the glucan of the present invention is effective in increasing phagocytic activity and accordingly advantageous against infectious diseases.
The glucan of the present invention did not show any antigenicity when examined by several immunological techniques.
The glucans of the present invention are dissolved in physiological saline and other physiologically tolerated vehicles such as the Ringer's or aqueous glucose solution. The preparations are usually administered intravenously, intramuscularly, subcutaneously, or intraperitoneally into hosts. The dosage of this glucan to a host differs according to the degree of the disease, and also according to the route of administration since the rate of diffusion from the site of administration differs accordingly. In general, the dose of the glucan of this invention is from 0.001 to 100 mg/kg/day.
The glucan of the present invention can be obtained by the following various methods.
This method comprises cultivation of mycelium of fungi in an appropriate liquid medium to produce glucans, and isolation and purification of said glucans through appropriate procedures. The culture medium may be either natural or synthetic.
The mycelium of fungi is inoculated in liquid medium, which is thereafter cultured as usual in a vessel such as a shaking flask, jar fermentor, or tank at 25� - 30�C, for 5 to 10 days. A supernatant freed from the mycelium by a suitable procedure such as filtration or centrifugation, is mixed with a suitable amount of an organic solvent miscible with water, such as methanol, ethanol, propanol, and acetone, to obtain glucans as a flocculent precipitate. If necessary, further purification by treatment with activated carbon, granular activated carbon or bone-char, and treatment with ion-exchange resins or dialysis and successive treatment with an increasing concentration of a solvent miscible with water yields white fibrous glucan. Glucan thus obtained is crushed and sieved to individual use. In some cases, of course, some of the above techniques may be omitted. The yield differs from fungus to fungus.
Many fungi, involving mostly Basidiomycetes, are covered with a mucous capsule on their surface. For example, capsule polysaccharides of Pholiota nameko, Pholiota adiposa, etc., can be easily extracted with cold or warm water. Precipitation and purification to recover glucan from the aqueous extract are carried out according to the method (a) mentioned above.
Using cold, warm, or hot water, or a few per cent of trichloroacetic acid solution, and a few per cent alkali solution, glucans can be easily extracted from mycelia. In such cases, it is desirable to homogenize fungi thoroughly.
Precipitation and purification to recover glucan from the extract are carried out according to the above mentioned (A).
The resulting glucans are usually grayish or white and fibrous, tasteless and odorless, and soluble in water, and highly viscous when they are in aqueous solution.
The facts that by the action of an exo-β-(1 - 3)-glucanase (E. T Reese et al.: Can. J. Microbiol., 5, 173 (1959); Y. Satomura et al.: Agr. Biol. Chem. (Tokyo), 25, 19 (1961) the glucan utilized in the present invention is easily hydrolysed to yield glucose and gentiobiose, and that after the Smith degradation (J. K. Hamilton, F. Smith: J. Am. Chem. Soc., 78, 5907 (1956), the same enzymic treatment produces glucose alone, indicate that the glucans have the structure mentioned hereinabove.
The methylether, carboxymethylether, diethylaminoethylether, acetylester, sulfonylester, and phosphorylester derivatives may be obtained by conventional methods, and partially hydrolyzed products may be obtained from the said glucan by treatment with enzymes, acids and alkalis.
The glucans of the present invention are difficult to prepare in an aqueous solution of higher concentration because of their high viscosity, and therefore, it is desirable to use them in a form of less than 0.5% aqueous solution. Furthermore, for the preparation of a composition suitable for medicinal use, it is necessary to add gradually glucan which is ground as fine as possible into a solvent with violent stirring for complete dispersion, and to continue the stirring until complete dissolution is obtained. In these cases, the use of a high-speed blender is preferable. The above procedures need to be carried out quite carefully, since when any lump is formed it is very difficult to dissolve completely.
The following examples are provided by way of illustration, and are not intended to limit this invention, the scope of which is indicated by the appended claims.
Humfeld's basal medium (T. Sugihara and H. Humfeld: Applied Microbiol., 2 (3), 170, 1954) was mixed with 3% of glucose, 0.3% of urea, and 1μg/ml of thiamine hydrochloride, the volume thereof was made to 1 liter and pH was adjusted to 4.50. Each 100 ml of the resulting medium was poured into a series of 500-ml Sakaguchi flasks. After sterilization at 120�C. for 15 minutes, each flask was inoculated with one loopful of Schizophyllum commune (T-189 strain) and cultivated on a reciprocal shaker at 28�C for seven days. After completion of fermentation, the culture broth was centrifuged at 8000 rpm for 5 minutes to remove the mycelium, the supernatant thus obtained was decolored with 0.05% of activated carbon, and filtered under suction with the help of diatomaceous earth. The filtrate was mixed with methanol up to the concentration of 35% to precipitate fibrous glucan, which was washed with portions of aqueous methanol. The concentration of methanol was increased successively and finally anhydrous methanol was used to dehydrate the material and thereafter the purified fibrous glucan was dried, crushed, and sieved, yielding 8 g of white glucan powder. One gram of the glucan thus obtained was dispersed in 2 liters of physiological saline and after treatment with a high-speed blender for 15 minutes, the fully dissolved glucan solution was filtered under suction with the help of diatomaceous earth. Each 20 ml of the filtrate was poured into ampules, the ampules were sealed, and sterilized at 120�C for 15 minutes.
Pelikan ink was injected into the tail vein of mice, 2 and 4 days after the intraperitoneal injection of the glucan and a control substance, zymosan, which is a known polysaccharide having activating effect on the reticuloendothelial system. The blood was drawn from the ophthalmic vein 3, 8, 13, and 18 minutes after injection of the pelikan ink, hemolysed by addition to 0.1% sodium carbonate solution, and concentration of the pelikan ink was measured from the optical density of this solution at 660 nm. The half-life, t1/2, was calculated from the optical density and the clearance index, K, was calculated from the following equation:
K= (log C1 - log C2)/T2 - T1
where C1 and C2 are the concentrations of the pelikan ink at time T1 and T2, respectively.
As shown in FIG., 1, the result of this experiment indicated that the glucan has the action of accelerating the reticuloendothelial function and the degree of this action of 2.5 mg/kg of the glucan was equal to that of 100 mg/kg of zymosan.
The glucan was adminstered intraperitoneally to mice every other day for three times and macrophages were collected from the peritoneum two days after the last administration. The collected macrophages were mixed with the cells of Saccharomyces cerevisiae (ATCC 9763) or of Candida albicans (YU 1200), the cells were stained with Giemsa solution 30 minutes later in the case of the former and 8 minutes later in the case of the latter, and the number of macrophages that had phagocytised was calculated.
As shown in FIG. 2, this result indicated that a higher phagocytic rate was found in animals given 0.63-5 mg/kg of the glucan than in control animals in proportion to the dose administered. The phagocytosis was especially marked against Candida albicans, the macrophages from the animals given 2.5 mg/kg of the glucan showing over twice the phagocytic rate of the control animals. In other words, acceleration in phagocytic action was observed by the administration of the glucan.
After intraperitoneal injection of the glucan of this invention, the cells were collected from the peritoneum of mice, 5 to a group, and from untreated control mice, and a cell suspension of 107 cells/ml was prepared. Activity of enzymes was measured with this cell suspension; that of alkaline phosphatase by the method of Fiske and Subbarow, that of β-glucuronidase by the p-nitrophenylglucuronide method, and that of cathepsin by the method of Cohn and Hirsch based on that of Adams and Smith. Histochemical staining for acid phosphatase and its determination followed the method of Tomonaga, using Naphthol AS-BI phosphate as a substrate. Results (FIGS. 1-4):
1. Activities of acid phosphatase, β-glucuronidase, and cathepsin in the intraperitoneal exudate cells markedly elevated from a day after the glucan administration, reached a peak after 3-5 days, and returned to the normal level after 15 days. There was no elevation in the activities of alkaline phosphatase and lysozyme.
2. Acid phosphatase staining of the peritoneal macrophages indicated that the cells from mice given the glucan were markedly larger than those from control mice, cytoplasm contained numerous acid phosphatase-positive vacuoles and lysosome granules, and generally showed evidence of functional activation.
These results indicate that administration of the glucan had stimulated the reticuloendothelial cells, and the macrophages showed active phagocytosis and digestive activity. Periodical changes in three enzyme activities of mouse peritoneal cells after intraperitoneal treatment with various amounts of the glucan.
______________________________________a) Acid phosphatase Days after treatmentDose 3 6 9 12 15(mg/kg, ip) Activity %)______________________________________Control 100 100 100 100 1001.25 182 171 139 124 1052.5 180 170 135 117 1095.0 234 219 140 118 112b) β-glucuronidaseControl 100 100 100 100 1001.25 223 215 200 160 1152.5 259 254 231 190 156c) Cathepsin:Control 100 100 100 100 1001.25 141 132 120 107 1022.5 140 132 129 111 93______________________________________
In bacterial infectious diseases, those of acute type could not be prevented unless the glucan was administered several days before infection with the bacteria.
The glucan was given intraperitoneally to 10 mice in a group every other day for 3 times and one of the following seven kinds of pathogenic bacteria and one kind of pathogenic fungus were infected 2 days after the last injection of the glucan to observe prolongation in survival.
The microorganisms used were as follows (the number of bacteria or fungus infected in a mouse and the route of administration are given in parentheses):
(1) Staphylococcus aureus 226 (10 � 108, ip)
(2) Diplococcus pneumoniae 1-100A (2 � 103, ip)
(3) Escherichia coli GN-2411 (8.8 � 106, ip)
(4) Salmonella enteritidis 116-54 (1.25 � 103, ip)
(5) Pseudomonas aeruginosa H7 (2 � 106, ip)
(6) Klebsiella pneumoniae (broth 0.2 ml, ip)
(7) Proteus vulgari (broth � 100, 0.2 ml, ip)
(8) Candida albicans YU-1200 (broth 0.3 ml, ip)
The results of the experiments are as follows:
No. of survival/ No. of mice testedDose(mg/kg) (1) (2) (3) (4) (5) (6) (7) (8)__________________________________________________________________________O (Control) 0/10 0/10 0/10 1/10 0/10 0/10 0/10 0/101.25 � 3 10/10 1/10 5/10 3/10 2/10 9/10 5/102.5 � 3 10/10 1/10 7/10 3/10 4/10 9/10 3/105.0 � 3 10/10 9/10 3/10 9/10 9/10 4/10 5/10__________________________________________________________________________
The result of intraperitoneal administration of 1.25-5 mg/kg of the glucan is summarized as follows:
a. Marked effect was observed against infection with Staphylococcus aureus Klebsiella pneumoniae and Escherichia coli.
b. Moderate effect was observed against infection with Pseudomonas aeruginosa, Proteus vulgaris, and Candida albicans.
c. Slight effect or almost ineffect was observed against infection with Salmonella enteritidis and Diplococcus pneumoniae.
Same as in Example 3, the mice were given intraperitoneal injection of the glucan every other day for three times and, two days after the last injection, a suspension of Pseudomonas aeruginosa H7, containing 32 times the number of bacterial cells required for a minimum lethal dose, was injected intraperitoneally. One hour after this infection, Gentamycin was given as a single subcutaneous injection and survival of the mice was examined. As shown in the following table, a marked effect of the combined use of Gentamycin and the glucan was observed.
______________________________________Gentamycin alone Gentamycin + the glucanDose No. of Gentamycin the glucan Number of(mg/kg) Survival (mg/kg) (mg/kg � 3) Survival______________________________________200 1/10 200 5 10/10100 0/10 100 5 10/1050 0/10 50 5 10/1025 0/10 25 5 5/1012.5 0/10 12.5 5 4/10Control 0/10 0 5 0/10______________________________________
Mice were infected with Escherichia coli GN-2411 and the same experiments as above were carried out. Results are given in the following table.
__________________________________________________________________________Amount of bacteriainfectedRoute of admini- Broth � 20, Broth � 10,stration of the 0.3 ml, ip 0.2 ml, ipglucanDose (mg/kg) ip* im sc ip im sc__________________________________________________________________________2.5 1/10 1/10 1/10 0/10 0/10 0/105.0 7/10 0/10 1/10 10/10 1/10 3/1020 10/10 3/10 1/10 10/10 5/10 2/1050 6/10 4/10 4/10 6/10 1/10 6/10__________________________________________________________________________ *ip = intraperitoneal, im = intramuscular, sc = subcutaneous
Intraperitoneal administration of the glucan showed a significant effect with the least dose, followed by intramuscular administration, and subcutaneous administration required the largest dose of over 50 mg/kg to be effective. This tendency was considered to be due to the difference in the rate of distribution of the glucan in body which is a high molecular substance.
In chronic infections like tuberculosis, administration of the glucan after infection was sufficiently effective. Mice were infected with 0.5 and 1 mg of sensitive strain of Mycobacterium tuberculosis Kurono or the human-type strain resistant to isonicotinic acid hydrazide and streptomycin, M. tuberculosis Schacht, intravenously. From the day after the infection, the glucan was given intraperitoneally, every other day for 10 times, and streptomycin and ethanbutol were given subcutaneously, every day for 20 days, and the survival of mice was compared in groups with the glucan alone and in those given combined treatment.
a. M. tuberculosis Kurono (sensitive human strain). (bacterial dose, 0.5 mg, intravenously)Dose 50% Survival 0% survival Survival over(mg/kg) (days) (days) 150 days__________________________________________________________________________None (Control) 43 94 0/10The glucan 5 � 10 (ip) 100 150 1/10Streptomycin 50 � 20 (sc) 66 106 0/10Streptomycin 50 (sc) +The glucan 5 (ip) 131 150 2/10__________________________________________________________________________
As shown above 5 mg/kg (ip) of the glucan and 50 mg/kg (sc) of streptomycin showed approximately the same survival while the combination of these two agents was more effective. The rate of survival in this experiment is shown in FIG. 4.
b. M, tuberculosis Schacht (human strain resistant to isonicotinic acid hydrazide and streptomycin)(1 mg, intravenously)
No. ofDose 50% survival 100 % survival survival(mg/kg) (days) (days) over 98 days__________________________________________________________________________None (Control 19 23 0/10The glucan 2.5 33 59 0/10The glucan 5.0 27 87 0/10Ethambutol 10 23 48 0/10Ethambutol 20 50 87 0/10Ethambutol 10 + the glucan 55 >98 2/102.5Ethambutol 10 + the glucan 57 >98 3/10Ethambutol 20 + the glucan 75 >98 3/105__________________________________________________________________________
The glucan showed survival effect even against the resistant strain at a intraperitoneal dose of 2.5 and 5 mg/kg, and the effect was approximately the same as 10 and 20 mg/kg subcutaneous dose of Ethambutol. Combined use of these two agents showed increased effect. Rate of survival of the animals in this experiment is shown in FIG. 4.
Patent Citations
Referenced by
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Can the Rock and Roll Hall of Fame Reunite Axl and Slash?Ke.Mazur/Getty Images
Most years, we'd gladly let you go about your day without a second thought as to who the Rock and Roll Hall of Fame selected for its short list of nominees. The Hall remains mostly irrelevant for all the reasons you may well be sick of hearing by now, like its allegedly shady voting practices (former Hall voter Joel Selvin, in 2007: "This thing has sunk to a shameful level of manipulation and behind-the-scenes chicanery") and the fact that, nearly three decades into the institution, the majority of music fans neither know nor care who's actually in the Hall of Fame. But this year is different. This year, Guns N' Roses have been nominated.
Yes! Twenty-five years after their formation (as per Hall rules, and alongside — deep breath — Heart, Joan Jett & the Blackhearts, the Cure, Small Faces/Faces, the Spinners, Rufus with Chaka Khan, Freddie King, Eric B. & Rakim, Donovan, Laura Nyro, War, Beastie Boys, the Red Hot Chili Peppers, and Donna Summer), GN'R are up for coronation. So what makes this so exciting?
Well, as you well may have noticed, Axl Rose has been dragging around a mercenary version of the band, staffed by hired guns with names like Buckethead and Bumblefoot, for the last decade and change. Rose has toured haphazardly with his new guys, abruptly canceling sets at giant European festivals while flaking out on other shows altogether. He's also put out Chinese Democracy, a project that had taken on near-mythical proportions until it was released in 2008 to lukewarm reception. But what Axl hasn't done is make amends with Slash. In fact, those two despise each other! Which means that, if GN'R does make the cut as one of the five inductees, we could have one gloriously awkward onstage reunion on our hands.
Of course, maybe none of them would even show up. But maybe they would! Things might not be so tense between Axl and former bassist Duff McKagan, who actually joined the band for an impromptu appearance during a London show last year. Guitarist Izzy Stradlin, who had played a few gigs with the band back in 2006, probably won't be too ornery either. Drummer Steven Adler, who's spent some time on Celebrity Rehab, might not be as polite: He made overtures toward joining GN'R 2.0 as part of a post-rehab career path, but was rebuffed. But the real potential fireworks would come from Slash's direction. In 2009, Axl hilariously explained that "There's zero possibility of me having anything to do with Slash other than by ambush, and that wouldn't be pretty … In a nutshell, personally I consider him a cancer." (His hatred of Slash has also led, indirectly, to multiple lawsuits.) They reportedly haven't spoken in years. How wonderful would it be if the — possibly violent?! — reunion took place on TV?
For the first time, we care enough to make a plea to the Rock and Roll Hall of Fame. Do the right thing, guys. Vote for GN'R.
Filed Under: Axl Rose, Guns N' Roses, Music, Rock and Roll Hall of Fame
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What's On
Games Masters – Celebrating Game Design
Posted by Kristian Hatton
21. Jun, 2012
|July 6, 2012
|10:00 am
|10:00 pm
Have you felt nostalgic lately for the good ol' days of arcade games, '80s style? Or am I just way too old to be writing about this particular event?
This exhibition at Federation Square celebrates those whose work has been enjoyed by millions over the years, but don't receive any recognition. Welcome to the artistry of the Video Game Designer.
Over 30 game designers' games are showcased, from Metal Gear Solid, to Nintendo's Super Mario Bros and The Legend of Zelda, and featuring full-body '80s classics like Hang On, Dance Central 2, and a four-player version of Real Racing.
Be a part of the Game Designers' art and world, which will feature special interviews, concept art and interactive displays. Of course, you'll be able to play over 125 different games, so it won't be your typical boring exhibition.
WHEN: Thursday 28 June – Sunday 28 October
WHERE: ACMI, Federation Square
WEB: acmi.net.au/game-masters.aspx
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Milk Bar Mag really recommends La Condesa's new summer frozen cocktail Boozy Snow Cones.


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Sr Project Engineer
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Project Manager - Engineer [Bilingual - up to $85K per year]
Project Manager - Engineer
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Transformer Design Engineer
Has 2 year experience minimum
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We have an immediate need for a Project Applications Engineer in Troy, MI for a premiere automation company that is rapidly growing and expanding their footprint providing automation solutions to some of the U.S.'s largest companies.
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Interior Designer for Office Furniture Dealer
Metro Office Environments is looking for a energetic person with excellent communication skills to join our team! We have an immediate opening for Interior Designer/Space Planner/Project Designer.
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Centrifuge Design Engineer
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Chief Mechanical Engineer Opening to $110K
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Electrical Engineer
Pontiac Michigan
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I want to know about the landline number of NADRA office of Islamabad. Please give me the number.
Tags: Islamabad, NADRA, Office, Telephone
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3.1 Phillip Lim Cropped Pencil Trousers
Stretch cotton blend cropped pencil trousers with center crease detail, quarter top pockets, and back welt pockets. 10" rise. 29" inseam 14" leg opening. Available in Key Lime. Imported. Cotton/elastane. Dry clean.
Sold Out
The most versatile wardrobe essential in a figure-loving cropped silhouette with a sleek flat front and slimming leg.;Banded waist with belt loops;Zip fly with hook-and-bar closure;Side-seam pockets;Back welt pockets;Rise, about 27";Inseam, about 13";Body: Cotton/polyamide/elastane;Trim: Viscose;Dry clean;Imported of Italian fabric;Model shown is 5'10" (175cm) wearing US size 4.
These cropped jersey riding pants put a modern spin on equestrian style. Angular pockets accent the hip, and a single welt pocket sits at the back. Hidden ankle zips allow for an easy fit. Hook-and-eye closure and zip fly. Fabric: Mid-weight jersey. 72% viscose/23% polyamide/5% elastane. Dry clean. Imported. Belt sold separately. MEASUREMENTS Rise: 8.5in / 22cm Inseam: 26in / 66cm Leg opening: 10in / 25cm
An impeccably tailored workwear staple is updated with a versatile cropped length and streamlined straight leg.;Belt loops and concealed hook-and-eye at self waist;Zip fly;Front slash pockets;Back welt pockets;Vented cuffs;Rise, about 91⁄2";Inseam, about 31";Cotton/nylon/elastane;Dry clean;Imported;Model shown is 5'10" (177cm) wearing US size 4.
These crisp, sharply tailored pants come to a subtle flare at their cuffs, creating a beautifully balanced silhouette for the classic style.;Belt loops and concealed hook-and-eye at self waist;Zip front;Creased legs;Side slash pockets;Back welt pocket;Rise, about 10";Inseam, about 26";Viscose/wool;Dry clean;Imported of Italian fabric;Model shown is 5'10" (175cm) wearing US size 4.
Chic, ankle-length 3.1 Phillip Lim trousers in sophisticated wool suiting. Slant hip pockets and welt back pockets. Hook-and-eye closure and zip fly. Fabric: Lightweight wool suiting. 98% wool/2% elastane. Dry clean. Imported, China. Measurements Rise: 10in / 25.5cm Inseam: 27in / 68.5cm Leg opening: 14in / 35.5cm Measurements from size 4
A streamlined pencil silhouette that enriches every wardrobe, rendered in plaid wool.;Self-waistband with belt loops;Concealed front closure;Zipper fly;Flat-front design;On-seam side pockets;Back welt pockets;Slim and cropped legs;Rise, about 11";Inseam, about 28";Wool/polyamide;Dry clean;Imported of Spanish fabric;Model shown is 5'10" (177cm) wearing US size 4.
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3.1 Phillip Lim is one of my favorite brands.


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Results: 1 - 1 of 1
The GQ Eye: GQ on Style
GQ Selects: Converse 1970s Chuck Taylor Canvas Sneakers
"I'd say these aren't your dad's Chucks, but they are! The higher midsole on these canvas sneakers is a throwback detail that looks fresh again by today's sneakerhead standards. Of course, any navy Chuck... read more
Friday, 5/23/2014 at 2:00PM
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- Canvas,
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Results: 1 - 1 of 1
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The 18ft long specimen, complete with tusks, was sold to a private collector at an auction house in Sussex today
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Scientists from the University of Sussex believe their smell receptors and bio-chemical sense of smell could inspire the next generation of contraband detection
Della Callagher, 46, died two days after eating the meal at the pub in east London, and dozens of others fell ill
Aimee Willett, 26, had her first routine smear test after turning 25 - the age at which NHS screening currently starts
Sunday People political editor Nigel Nelson watches David Cameron and Ed Miliband play the blame game over NHS failures
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Convicted paedophile John Allen, 73, preyed on boys and a girl aged seven to 15, grooming favourites with gifts
Supermarket took action after Karen Cole tweeted a picture of her superhero-loving daughter Maggie next to the offending sign
Dr Lam Hoe Yeoh's collected images of 1,000 victims as his stash of gadgets revealed including a watch-cam, a video-pen and hearing aid boxes rigged to make recordings
Stunned residents call emergency services after spotting the monster animal called Hulk walking the streets
The 23-year-old midfielder was in Birmingham playing in a 1-1 draw against Aston Villa when his South coast home was burgled on Monday night
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Photoshop Lady
Your Favourite Photoshop Tutorials in One Place
Making a Simple Art Portrait
Under Drawing Effect, Photoshop Tutorial
In this tutorial, you will see how to create this cool, grainy work with this art portrait. It will show you to create some vector portraits, then get texturing in Photoshop with self-made brushes.
Making an Aged Rocket Launcher
Drawing an aged rocket launcher is like drawing other normal objects, you need to start to sketch your object on the paper. Then you can work on your paintings step by step using appropriate brushes and colors. Normally, detail painting requires quite a few layers to stand out its details. Therefore, it would be time-consuming to process.
Idea of Digital Painting for Battle Scene in the Ocean
This tutorial will show you how to paint some Battle Scene in the Ocean. This will go through with you from the black and white picture and finalize with a nice colorful piece of artwork. You will see how every little details were added such as cannonball hit the water and smoke to form such a battle scene.
Techniques for Drawing a Nice Lady Portrait
Many of you may have worked on human portraits and find process to be very difficult. Different designers have their own set of skills to carry out. Here will present you a bit of tactics and stages for drawing a nice lady portrait.
Making a Fantastic Natural Scene in Photoshop
Here works through with you for making this fantastic natural scenery. It will demonstrate you how to draft your sky, flower land, grass etc. With this, you can form a nice natural scenery based on the same idea.
Drawing an Old Style Cartoon Scene
Old style cartoon gave you lots of good memories. To retain this, you can learn to draw your special scene for yourself. Here will give you some tips to work on it such as setting up brushes or color settings etc.
Natural Effect Creation – Realistic Lightning
Many natural effects can be created by Photoshop. You can create whatever scenery as your object background. Lightning effect is a popular scenery as a adversely inclement weather condition.
Transfer your Image into a Cartoon Art
To make your cartoon art image for yourself, different designers have different methods to implement. One of common way is to make a hand draft with reference your image, and then using brushes to paint. Here will highlight some ideas to workout your artwork nicely.
Making a Realistic Human Lip
This shows you a work through of making a realistic human lip. You can have an idea of how a lip to be made from the draft. You will see how the lip to be painted layer by layer as well as the shadow and reflection to be added on the lip.


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Best value deals in free agency
A look at the best bargains in the 2014 free-agent class
It's official: The NBA has lost its mind.
Every year, teams carefully tend to their books, slashing salary, attaching picks in deals to rid themselves of unfavorable contracts, pursuing deals where they shave their payroll sometimes by mere hundreds of thousands of dollars to drop under the tax threshold, and conduct cap machinations to line their ducks up in a row to be in a position of optimal cap flexibility. They evaluate talent year-round, identifying possible future fits expected to hit free agency, watch countless hours of film and meticulously come up with comparable contract negotiations from years past to craft the perfect proposal. They are aware of alternatives available via trade or free agency, they draft replacements, they have five-year plans of progression.
Then July 1 happens, and all hell breaks loose.
This year, the madness began with a three year, $19 million offer by the Detroit Pistons to Jodie Meeks, which was followed in short order by an offer by the Boston Celtics to Avery Bradley worth $32 million over four years, and then a five year, $60 million agreement between the Washington Wizards and Marcin Gortat. Did these teams really have these players valued this highly? Or were they compelled by new information, by agent pressures, or simply by the desire for certainty?
Fear not, frugal spenders: There are still some value deals left on the market. Here's a look at some of the talents who can be had for less-than-exorbitant prices:
Al-Farouq Aminu | SF | UFA
2013-14 Team: New Orleans Pelicans
2013-14 Salary: $3.7 million
Suggested AAV: $2.0 million/year, 3 years,
nonguarantee on third year
Aminu had an under-the-radar season playing in New Orleans, but he showed marked signs of improvement this year, playing on a one-year deal after he originally had the fourth-year option of his rookie scale contract declined. While he hasn't fulfilled the promise that so many had for him out of Wake Forest as a versatile wing, he has carved out something of a niche as an athletic, defensive combo forward. His length and quickness allow him to act as a disruption in pick and roll coverage, and his size helps him in defending some of the bigger face-up players in the league. Best of all, he's a high-level defensive rebounder, which can give a team some lineup flexibility. His perimeter shot is abysmal, but that's part of why he comes for cheap.
Gustavo Ayon | C | UFA2013-14 Team: Atlanta Hawks
2013-14 Salary: $1.5 million
Suggested AAV: $1.5 million/year, 3 years,
nonguarantee on second and third year
To read more about the best value deals in the 2014 free agent class, you must be an ESPN Insider.
Become an insider and get access to all our articles and tools.View Insider Benefits »
Magazine subscribers: activate your Insider account.
- Video coordinator, college scout, Phoenix Suns
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- Ford: Grades: Top 30 prospects | Champions


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Office Star® Designs® Metro 24" Parsons barstool features espresso Eco leather seat for comfort. Barstool has solid wood legs for durability and offers classy appearance to any decor.
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OSP Designs® Metro bonded leather parsons chair in kiwi green color measures 38" x 17 1/4" x 23 3/4" and features espresso finish ...
This Web site is intended for use by US residents only. See International Sites. See our delivery policy for full details. Copyright 1998-2014, Staples, Inc., All Rights Reserved.


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Thank you sa AMD Desktop Sir. Napakabait na seller.
Very professional kahit na nakakaintimidate :)
Highly Recommended Seller.
Thanks Sir! :)
Thank you TPC!
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text:
|NOTE: Due to the MediaWiki upgrade many lists on the site may appear incomplete such as new data on filterable lists. We do ask that you bear with us as the issues are addressed. For more information please see this blog post.
|Welcome to the Wiki!
Welcome to Narutopedia!
We are currently editing over 5,650 articles and 7,318 images and you can help!
|Be warned that this wiki is filled with SPOILERS about the Naruto series. This is your only warning, read at your own risk!
Twelve years before the start of the series, the Nine-Tailed Demon Fox attacked Konohagakure destroying much of the village and taking many lives. The leader of the village, the Fourth Hokage sacrificed his life to seal the Nine-Tails into a newborn, Naruto Uzumaki. Orphaned by the attack, Naruto was shunned by the villagers, who out of fear and anger, viewed him as the Nine-Tails itself. Though the Third Hokage outlawed speaking about anything related to the Nine-Tails, the children — taking their cues from their parents — inherited the same animosity towards Naruto. In his thirst to be acknowledged, Naruto vowed he would one day become the greatest Hokage the village had ever seen. Read more...
|Random Chapter
|Kakashi expresses surprise over the identities of the two men he had been following as Kisame and, more particularly, Itachi. When Kisame tries to take him on, Itachi tells him to stand down, citing that they are too equal in strength and that a fight would only become an inconvenience. As he would not have these same problems, he attacks Kakashi. Seeing Itachi's Mangekyō Sharingan, Kakashi instructs Asuma and Kurenai to shut their eyes since they are no match for him. Itachi uses Tsukuyomi on Kakashi, who just barely endures the attack because of his Sharingan. Struggling to remain standing, Kakashi asks why they have come to Konoha. Itachi replies that they are after the Fourth Hokage's legacy.
|Latest Episode
|Obito seemingly reaches his hand out, he instead strangles Naruto, claiming he has no regrets for the path he has chosen, much to Naruto's dismay. Frustrated, Naruto breaks free from Obito's grasp and punches him. As Naruto forcibly pulls Obito's hand to his side, the Uchiha is deprived of his powers after the Allied Shinobi Forces succeed in freeing the tailed beasts. Lying defeated, Obito looks up to the moon and grieves that he could not fill the hole in his heart. The tailed beasts then thank Naruto for freeing them. Read more...
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