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Home » Abstract Artistry by Marianne Glick at A to Z Cafe July 1
Abstract Artistry by Marianne Glick at A to Z Cafe July 1
Get ready to be energized and inspired. From 5:30pm until 6:30pm on Thursday, July 1, 2010 art lovers will gather at the A2Z Café on 96th Street to behold the beautifully abstract, mixed-media paintings of Indianapolis artist, philanthropist and business person, Marianne Glick. With an exhilarating blend of color and texture, Glick's work is a vivid and personal exploration of the abstract nature of life.
Glick began painting in 2004 in an attempt to fill the cold Winter months with productivity and positivity. Though her green thumb keeps her busy Spring, Summer and Fall, Marianne's inability to connect with nature during the icy Winter motivated her to create beauty in an entirely new realm. Since then, her paintings have blossomed into brilliant abstract works in water color and acrylic. Each piece exudes both vibrancy and confidence as colors intermingle and the concept of line is challenged. With compositional technique that draws your eye naturally across the canvas, its easy to peer into the cheery heart of this artist as she shares her self through her work.
A philanthropist at heart, Marianne Glick believes strongly in giving back to the community. She has donated paintings and profits from paintings to various Indianapolis nonprofit organizations like the Children's Bureau of Indiana, Dress For Success, Girls Inc., Habitat for Humanity, Haiti Earthquake Relief, Joy's House, Make a Wish Fund, Peyton Manning's Children's Hospital, Planned Parenthood and more. Her work even hangs in the halls of Ball State University.
In her six years of experience painting, Glick has been accepted into an impressive number of juried competitions sponsored by groups like the Hoosier Salon, California Art Day, Indianapolis Art Center, International Society of Acrylic Painters, Midwest Abstract National Exhibit, Watercolor Society of Indiana and Women's Works 2010. In addition, Glick has exhibited throughout Indianapolis art galleries like the Indianapolis Museum of Art, Indianapolis Monthly's Art House and the Indiana State Museum. Her work is even in high demand out of state, traveling to the Sarasota Art Center, PGA National Members Club, the Coral Springs Museum of Art in Florida, the Old Courthouse Gallery in Woodstock, Illinois and the Learning Art Expo in Pasadena.
A leader in the Indianapolis community, Marianne Glick's work as philanthropist plays an important role in her art. Her dedication to the Marilyn K. Glick School of Art, an Indianapolis art school and exhibition space located in the outdoor halls of the ARTSPARK of the Indianapolis Art Center in Broad Ripple Village, has been noted. In only a few short years, Marianne Glick has managed to become an integral part of the Indianapolis art community.
To peruse Marianne Glick's latest work, head to the A to Z Cafe on 96th Street in Indianapolis, Indiana. Take a piece home or join Marianne in her spirit of giving: purchase one to donate to a deserving Indianapolis organization. For more information about the artist, visit her official website here. After this Indianapolis art show, stick around for dinner at this Indianapolis restaurant. Or head to any of these refreshing Indianapolis bars to discuss your impression of Marianne Glick's work over cocktails.
Stay tuned to Indianapolis News, Events and Information on Fun City Finder.com for all the latest on fun things to do in Indianapolis. We cover Indianapolis arts to Indianapolis sports and everything in between. Get out in Indy and find some fun! Make the Circle City your playground!
Marianne Glick Art Show
Thursday, July 1 at 5:00 pm
A to Z Cafe
Filed Under: Arts, News, People

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Gates Cambridge Scholarships are competitive full scholarships awarded to applicants of outstanding intellectual ability, leadership abilities, and who are committed to improving the lives of others.
University nomination is not required, but you are encouraged to contact Dr. Ben Rayder for assistance in applying for this competitive award.
Intend to pursue one of the following full-time residential courses of study: PhD (three year research-only degree); MSc or MLitt (two year research-only degree); or a one year postgraduate course (e.g. MPhil, LLM, MASt, Diploma, MBA etc.).
Demonstrate academic excellence, leadership abilities, and concern for the greater good.
Review the information and instructions online.
Plan to provide the names of three (3) letter writers.
Bring in a résumé listing awards, honors, activities, research, jobs, service, leadership, hobbies, etc.
Contact Dr. Ben Rayder if you're interested in applying for this scholarship.


This course aims to introduce students to the application of psychometric analysis, from a research perspective. Psychometrics involves measurements of people's beliefs, moods, attitudes, aptitudes, and abilities; measuring these constructs in people requires a set of tools that allow us to make links between the thing we are actually assessing (i.e. the answers to questions given by individuals) and the thing we are actually interested in (the psychological state of the individuals who have completed the measures). It is this distinction that makes psychological measurement both challenging and interesting. We cannot make decisions about policy to improve outcomes if we cannot measure those outcomes.
We will focus on the application of psychometric theory, not on the mathematical proof of that theory. Students should have an understanding of basic statistics, probability, correlation, and linear and logistic regression. The course will cover the development and testing of a psychometric instrument, developed by the student.


Fresh off of a wonderful closing keynote at Compliance Week 2016, Compliance Strategists is proud to offer you a resource hub for all the knowledge you need to become a Subject Matter Expert in a Compliance 2.0 world. The Compliance 2.0 website will list all of our favorite resources, including articles, white papers, reports, surveys, and general thought leadership – all relevant to moving the industry to an independent and empowered model. We plan on further updates to bring you relevant compliance news, including highlighting what industry experts are saying about the latest scandals and how the elements of Compliance 2.0 become more and more necessary. Click here to access all the great features.
Tying all of this together is the introduction of the Compliance 2.0 infographic. Please download and share to help us continue the momentum towards freeing the compliance function.


Milwaukee » Miller Park » FAN TIPS » Stores to hit up at Miller Park ?
They have a number of different stores within the park on all four levels of the stadium. I personally go in merely to peruse from time-to-time as the merchandise, like the concessions in any other park is over-priced. But that's part of the ballpark experience. They have pretty much everything you could want, from player jerseys to racing sausage shirts, keychains, hats, etc. They also have Hank the Ballpark Pup merchandise which is a really big hit among fans.
Conveniently located on the Field Level in the left-field Hot Corner, the Brewers Team Store by Majestic is home to the largest selection of official Brewers merchandise, including Authentic Collection items from Majestic, Nike and New Era, customized jerseys, and special game-used items. The Brewers Team Store features two special sections: the newly remodeled Brewed for Her, a section dedicated to women's apparel and accessories, and The Meat Locker, a unique space for Klements Famous Racing Sausage Mascots and tailgate merchandise.
The Brewers are endorsed by Majestic and even though I love Nike and Reebox the Majestic people make some good stuff. There is everything you could ever want from the Brewers including little lego ballplayers, jerseys, baseball cards, and other Brewer memorabilia.
I mean, the only store you should only want to go to at the Park should be the team store. This store is really big for a memorbilia store if you ask me. Of course, the things there are a bit pricey – as all stadium things are, but I managed to walk out with a little sausage keychain that fit my budget!


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The Gym Bag: 6 Plainsmen earn football awards; New Year Singles Classic, soccer title and more
By Joe D'Amodio | damodio@siadvance.com
Cristian Pinto, left, and Reginald McClure show off their awards. (Photo courtesy of the Plainsmen)
Honoring the Plainsmen
The 2019 Richmond Boro Plainsmen eighth-grade tackle football team held its championship awards banquet two Sundays ago at the Hilton Garden Inn.
While the whole team was honored for winning the New Jersey Suburban Youth Football League, six players were recognized with distinguished player awards.
The players are Cristian Pinto, Reginald McClure, Salvatore Scalici, Alan Petrov, Nicholas Souffrin and Xavier Fully.
Pinto and McClure were presented with the Fred Claudio Memorial Award, which is bestowed annually to the player or players most pivotal to the eighth-grade team's success, all while performing with the utmost sportsmanship, inspiring those around them.
"Although Coach Claudio is no longer with us, his spirit and selfless devotion to the game of football and its players will live on," said a Plainsmen representative. "This year's recipients, Cristian Pinto and Reginald McClure, have been the backbone of the 2019 team. They have demonstrated, by way of their actions on and off the field, to have both the character and athleticism needed to succeed and flourish as Plainsmen and young men. Cristian and Reggie have proven to be a true force in the NJSYFL league, while their on-field play and actions helped rally and inspire all those around them."
Don't Edit
Salvatore Scalici, left, and Alan Petrov picked up some nice hardware. (Photo courtesy of the Plainsmen)
More Plainsmen awards
Scalici and Petrov were presented with the Vincent "Sonny" DiForte Jr. Memorial Award bestowed to the player or players who demonstrate superior leadership and commitment to the team.
"As founder of Staten Island Pee Wee League and coach, Sonny DiForte instilled the same values in his team as he did in his own large family of 11," said a Plainsmen representative. "To lead a football team, you need love, respect and commitment. This year's recipients demonstrated these qualities by leading by example. Always giving their all, and their fearless play on the field, exemplified the qualities of the Vincent "Sonny" Award. Sal and Alan possess what Sonny DiForte, Jr. regarded as the most important quality in a football player, but more importantly a young man -- heart.
Nicholas Souffrin holds his awards. (Photo courtesy of Plainsmen)
Souffrin and Fully were presented with the Gail and Richard Addeo Scholarship Award. The Addeos were major benefactors of the Plainsmen football program, who aided tremendously in helping this organization evolve into what it has become over the years.
"This award is presented annually to the player or players who embody the consistent characteristics of hard work, devotion, determination and a 'team-first' mentality," said a Plainsmen official. "Nick and Xavier have shown unparalleled mental and physical stamina, defining the persona of the Plainsmen organization. Nick and Xavier have provided our team with an identity that is relentless, hardworking, poised and a determined demeanor."
From left, Cristian Pinto, Alan Petrov, Salvatore Scalici and Nicholas Souffrin were selected to the 2019 New Jersey Suburban Youth All-Star football team. (Photo courtesy of the Plainsmen)
More Plainsmen honors
Photo courtesy of Cedar Stars
15U Cedar Stars win tournament
The Under-15 Cedar Stars soccer team captured the Massapequa College Showcase last weekend in Brentwood State Park on Long Island by going 4-0.
The squad beat SUSA, 2-0, in the title game.
Richie Kliesch led the way offensively on the weekend as he netted six goals. Riley Tait and Ari Klayman paced the defense.
Leo Perelman had the clean sheet in the final.
New Year Singles Classic taking entries
Entries are now being accepted for the opening squad (Jan. 4, 2020 at 1 p.m.) of the 45th annual New Year Singles Classic at Rab's Country Lanes.
All bowlers entering the first squad will receive a complimentary additional qualifying squad.
Qualifying squads will continue for the first three weekends in January with squads set for 1 and 2:30 p.m. on each Saturday and Sunday.
Entry fee is $50.
The fee for the first squad must be paid in full and has a limited number of spots.
Entries may be forwarded to tournament director Jim Elliott at Just For Kicks, 91 Lincoln Avenue, Staten Island, N.Y. 10306.
For more information call, 718-667-5120.
Interesting sports news? Send it our way
The Gym Bag will publish every Wednesday on the web and will appear in the Staten Island Advance shortly after. This is where we will feature short stories, tidbits and morsels about your players or teams going forward in place of the daily game results we used to take.
You can send us interesting information about your team after a strong start to the season, a championship season, a first win, a player who did something extraordinary in a particular game or event, etc.
If you have any news or tidbits like that, please email the sports desk at sports2@siadvance.com where we will evaluate the message and see if the content qualifies for our notebook.


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Hindus Still Don't Own the Narrative about themselves
This essay is more in the nature of an attempt. To examine the socio-political and cultural narrative about India that was set in motion roughly around the colonial period.
This narrative continues to remain profoundly Adharmic. More dangerously, the Hindus don't own this narrative about themselves. Even worse, influential sections have swallowed this toxic and self-destructive narrative wholesale. And so, for example, if we have virulently, openly anti-Hindu judges in the SC no less–not to mention most areas of public discourse and the bureaucracy–it is because this poisonous narrative has endured for over two centuries. And it is this narrative that informs them.
In turn, the roots of this narrative are to be found by asking just one question: how was it that a race of people who came to India as supplicants, who sought permission to trade with us ended up as our imperial overlords? This question is definitely not new but it needs to be asked again owing to two major factors, nay, consequences staring at our face:
The near-total absence of this question in our history textbooks used in schools and colleges.
The comprehensive Christianisation of our educational system which consequently became the dominant strain in India's "mainstream" public discourse.
The Narrative and its Consequence
One major and illustrative consequence of this narrative is what befalls Hindus who resist Christian conversions. Sample just two data points.
The Congress-led UPA Government awarded the Padmashri to Graham Staines' widow, Gladys Staines in 2005. Thanks to Graham Staines, large parts of the tribal belt of Odisha have now become hotbeds of intra and inter-tribal hostilities culminating in violence. Former neighbours after conversion become sworn enemies.
The Indian Express headline on 25 August 2008, just two days after Swami Lakshmanananda Saraswati's barbaric murder, reads thus: "Slain vhp man was conversion king." And it goes on to downplay the brutality of his murder by drawing spurious equivalences between fundamentalist Christian conversion sprees and the attempts of the Swami to preserve and safeguard the millennia-old continuum of Sanatana ethos in the state.
For the longest time, Hindu Swamis were considered out of reach of targeted, violent attacks much less daylight assassinations in this fashion. In this backdrop, here is yet another incident apart from Swami Lakshmanananda Saraswati's barbaric gunning down.
In July 2008, Swami Punyalokananda of the Ramakrishna Order was tied to a tree by a gang of Muslim and Communist goons and beaten to pulp in West Bengal's South 24 Paraganas District.
The media back then didn't emit as much as a whimper — let alone reporting it, it lapsed into a deafening radio silence.
Image Source: Hindu Jagruti
The fact that both incidents related to Hindu Swamis occurred during the rule of the Congress-led UPA Government is perhaps coincidental. Perhaps not. What is not coincidental is the truth of the frightening levels of power that the Jihadi-Communist-Missionary network so assiduously cultivated and acquired mostly since the 1960s that gave it the confidence to mount such daring assaults.
I leave the reader with this question: what is the assurance that some time in the future, a similar attack will not be launched against say, the Sringeri Swami?
A Sense of History
Which is why it is important to trace and understand these continuing and alarming consequences of the aforementioned narrative from a sense of history. While there is more than an ample supply of past and present literature dealing with this issue, some pointers are in order. Because, as we note, this detrimental narrative about India continues to strengthen its grip not just within India but globally.
This essay will focus on several key strands of this narrative including but not limited to Christianity, Colonialism, Marxism, Eurocentrism, and their offshoots in the form of secularism, caste-cow-curry bias, the Dalit discourse, feminism, and how these play out in the academia, media, intelligentsia, and shape public opinion.
The chief feature that becomes immediately evident in any study about India is the fact that it is the only surviving non-Abrahamic ancient culture and civilisation. Almost all non-Abrahamic cultures and civilisations were wiped out at their initial encounters with Christianity or Islam.
Only Sanatana Dharma has lived to tell the tale.
And the day India loses the memory of this tale — with all its horrific and monumental tragedies —is the day it will meet the fate of say Egypt or Persia.
Bharata's cultural continuity has been more or less maintained intact in almost all realms: in dress, family life, social interactions, basic ethical conceptions like dharma, rituals, institutions, places of worship, traditions, art, music and so on. The reason why this continuity has been preserved owes to India's fundamental philosophical conceptions rooted in the Vedas and the Dharmashastras. And these realms are the practical or outward manifestations of our Dharmashastras.
Here is P V Kane writing in his matchless volumes of the History of the Dharmashastra:
Our ancient sages laid the foundation [for philosophical and social harmony] by insisting that there is and must be harmony between man's spirit and the spirit of the world…social reforms and politics have to be preached through our age old…philosophy. If our leaders and people throw away or neglect the Hindu religion and spirituality altogether, the probability is that we shall lose both spiritual life and social betterment. [Volume 5: Part 2. Emphasis added]
P V Kane wrote these prophetic lines in the late 1950s/early 1960s. Compare what "betterment" Bharata has achieved by a single-minded demonisation of Sanatana Dharma ever since.
At any rate, to realise this harmony of spirit and the world, ancient India beautifully conceptualised a fundamental attitude. This attitude is how one regards life itself. Our ancients regarded life as a grand celebration in all its aspects; life was worth living to the fullest with all enjoyments — for example, as the celebrated Chamaka Prashna shows us — as long as our enjoyment didn't violate Dharma.
What this also shows is that one of the central features of India's philosophical underpinnings is the total absence of pessimism. This is equally the central message of all the Upanishads and the Bhagavad Gita. This is also Bharatavarsha's greatest and timeless gift to mankind. This is why concepts like absolute evil and nihilism never took root in this sacred Bhoomi.
However, both the Abrahamic cults stand out in sharp contrast in this fundamental conception of life. While Christianity conceives birth itself as sinful, the core doctrines of Islam take this to violent and extreme ends. Indeed, murderous and religion-sanctioned notions of Jihad, Crusades, White Man's Burden etc arise precisely due to this attitude towards birth and life itself. And from this conception arises the need to convert — violently if necessary — the entire world to their respective religions.
Which then brings us to an even more fundamental point: the definition of the term "religion" itself. To be clear, there can be no fundamental equivalence between our Dharmic system and the Abrahamic religions. And yet, in almost all of contemporary discourse on comparative religions etc, Sanatana Dharma is given the label of "religion" in the same sense of Abrahamic religions. And this incongruent discourse has become mainstream, like some received truth.
Needless, this state of affairs has a long history and in the specific case of India, it is history that continues to repeat itself in the facets of colonialism, conversion and the ensuing societal fissures, all driven by alien ideologies.
To repeat a well-known quote from the towering historian Dr R.C. Majumdar, "Real history…teaches us that the major part of India lost independence about five centuries before, and merely changed masters in the eighteenth century," [Italicised] referring to the first external Muslim invasions and subsequent imperialism over large parts of India.
Guru and "Father"
Yet, a key difference between the protracted Muslim rule in India and the British rule is the fact that while Muslim Sultans settled in India, the British never made India their home. Their sole purpose was to relentlessly exploit India using every foul method in the book.
Along with this, the British also spearheaded a fundamental change that almost overnight, profoundly altered the national and social character of India. This was the well-known introduction of English education which was simultaneously accompanied by the comprehensive destruction of our traditional modes of learning.
Think about it from a routine, real-life standpoint. Under this new educational system, who actually "taught" our children? It was the Christian missionaries with the full backing of the colonial British crown and its deeply-entrenched bureaucracy. It is thus not a mere coincidence that even today, it is the Church that monopolises the educational sphere.
Spot the difference between the cultural and mental change Indians underwent when the innate reverence towards a Guru was replaced by something called a "Father." It's the same difference that operated — and continues to operate — when Rta, Satya, Dharma, Shraddha, etc were replaced by "moral science," a cloak for spreading the Christian cult.
Indeed, one recalls Ananda Coomaraswamy's early warning[i] that an English-educated Indian would be cut off from his roots and become
an intellectual pariah who does not belong to the East or the West, the past or the future. The greatest danger for India is the loss of her spiritual integrity. Of all Indian problems the educational is the most difficult and most tragic.
And when we observe the ideological and political battles being fought in the education establishment today, we notice how this tragedy has escalated almost irreversibly. The truth is brutal: civilisational axes like the RTE were made possible by modern-day Hindus.
Yet another fundamental notion lies in the distorted conception of Hindus about their own history, culture, society, etc. However, when we look at this from a civilisational perspective, a different reality emerges. Both the dominant, proselytising cults do not make a distinction between the varna (incorrectly referred to as "caste") of Hindus because the core doctrines of their cults enjoin treating both a Brahmin and a Dalit as a heathen or kaffir. What explains the fact that various Christian denominations continue to invest massive resources in converting say, Dalits en masse, or use subtle intellectual tactics to convert the urban "upper castes?"
India as an Outpost of the West
For over 300 years, the Christian West never gave up studying India and Hinduism in all its aspects. Even today, scholars like Sheldon Pollock continue to undertake this study for achieving purely religio-political ends. And guess who helps them in their studies? Our own Pandits who feel flattered that a white-skinned man displays — or feigns — deep interest in our Shastras without critically analysing their true intent. There is of course valuable literature exploring this phenomenon so I'll stop at this.
How does one even reverse this mindset? And where does this lead to?
Observe the fairly recent history of say South Korea, Philippines and East Timor, and it becomes clear that India is the last non-Abrahamic bastion to be subverted and bloodlessly conquered by the Christian West or bloodily taken over by the forces of Jihad. These countries have now become mere Christian outposts of powerful nations of the West. From another perspective, India has about 1000 years of experience dealing with Islam and containing it fairly successfully. It is the Christian missionary machinery that Hindus have been unable to successfully combat although the Sangh Parivar and various Hindu groups have attained some impressive successes but that's too little too late.
More fundamentally, this is also a failure of our education, which looks down upon Sanskrit or classical studies, and has all but banished these disciplines from mainstream learning.
Here is an extreme example of where such spiritually-devoid intellectual perversities have led. The following is a poem by the Feminist-Christian-Communist activist, Meena Kandaswamy:
This poem denigrates Hindus.
This poem shows them in poor light.
This poem celebrates Krishna's freedom to perch on a naked woman.
This poem flames with the fires of a woman hungry for sex.
This poem makes the Shiva lingam the male sexual organ.
This poem prides itself in its perverse mindset.
This poem gossips about the sex between Sita and Laxman.
This situation has occurred in an India because its post-Independence elite was largely informed and conditioned in the Western-Christian mould. Once again, it pays to recall P.V. Kane's caution[ii]:
In these days of growing popular education, when [an ancient] myth becomes exposed, the men who once believed it not only give up that myth but also might give up everything contained in ancient works as unbelievable…the chief catalytic agencies are modern science and Western thought and literature. The old structure…is tottering and laxity in morals has made great headway…whatever happens, we must so regulate society that the family as a social unit is preserved. [Emphasis added]
The bedrock of Sanatana Dharma, the one thing that saved it from extinction at the hands of Abrahamic cults is the value it places on Grihastashrama Dharma: loosely speaking, the family unit. And we must revive its importance, stress on it repeatedly and inculcate its value among our children if we need to halt the tide of brazen evangelism and other assaults against Santana civilisation and culture.
Finally, a couple of points by way of what can be done.
We need to first invest massively in people who can critically study, generally speaking, these dangerous trends and machinations. We need to simultaneously develop an independent cultural and national narrative instead of aping and developing upon intellectual currents prevalent in the West.
Secondly, in the contemporary period, the West regards both ideas and ideology as a means to a political goal. But to the inherited cultural and civilisational consciousness of majority of Indians, politics is only one of the means to a loftier spiritual goal. This is perhaps why we have largely been unable to fathom how and why the Western mind can discern politics in say our Deities, festivals, temples, places of pilgrimage, and write thousands of "expert" academic theses.
About two decades ago, China initiated such a study of Western systems, and continues to reap its rewards today. Equally, over a period, it endowed numerous American universities with grants and chairs in the field of Chinese Cultural Studies, etc. The control of these institutions completely rests in Chinese hands. This among other reasons is why it receives negligible negative coverage by the Western press and other institutions. For instance, when the Western media in 2015-2016 published an expose of the cruel "dog festival," in China, it retaliated by publishing a similar report in a British paper covering the shocking state of Britain's slaughterhouses.
Thirdly, and this has been a refrain for several decades, a complete and thorough reform of Education needs to occur, starting at the primary level. In other words, we must take back control of the narrative about ourselves from alien hands.
I shall close this by quoting Ananda Coomaraswamy[iii] again:
An India free in name but subdued by Europe in her…soul would ill justify the price of freedom…we should not rest satisfied until the entire control of Indian education is in Indian hands. No European should have a voice [in it]. [Emphasis added]
[i] Ananda Coomaraswamy: "Education in India," Essays in National Idealism
[ii] P V Kane: History of the Dharmashastras Vol 5, Part 2: pp 1710
[iii] Ananda Coomaraswamy: "Preface," Essays in National Idealism
Ananda Coomaraswamy
Adharma
Colonised Indians
William Dalrymple


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You are here: Home › Sun Microsystems Announces Sun N1 System Manager; Updates Sun N1 Service Provisioning System
Sun Microsystems Announces Sun N1 System Manager; Updates Sun N1 Service Provisioning System
By SPARC Editor on May 3, 2005 in 2005
New Software Simplifies Management of Data Center Servers and Business Services
During its quarterly Network Computing '05 (NC05Q2) launch today, Sun Microsystems, Inc. (NASDAQ: SUNW) announced two new software releases within its Sun N1(TM) product family: Sun N1 System Manager, an easy to use tool for managing large and small installations of Sun systems, starting with Sun's x64 servers and broadening out to include more systems in the future and the latest version of Sun N1 Service Provisioning System, which introduces bare-metal operating system (OS) provisioning of: Java(TM) 2 Platform, Enterprise Edition (J2EE(TM) platform) application servers, Web servers and databases.
"MCI is adopting new technologies that deliver next generation services for our customers," said Tim Muilenburg, vice president of MCI IT Infrastructure. "The equipment and software behind these technologies must be best in quality so our services meet the expectations of our enterprise and government customers. We expect Sun's N1 tools to help us achieve our goals by automating application provisioning and increasing our data center efficiency. Also, as we utilize the N1 Service Provisioning System, we will be able to accelerate the delivery of business services from several days to a few hours."
Sun N1 System Manager offers customers an efficient way of managing large and small numbers of Sun systems. Core capabilities include:
Discovery – users are able to automatically discover their systems from bare-metal and logically organize systems into user defined groups.
Provisioning – enables users to remotely install their operating systems onto bare-metal systems or to re-provision existing systems.
Remote Monitoring – offers administrators detailed hardware monitoring for attributes such as temperature, fan and disk usage, as well as OS monitoring for attributes such as memory, CPU, and file systems.
Remote Management – provides users with secure lights out management capabilities, such as powering systems on and off with role-based access control that grants access privileges to specific users.
The Sun N1 System Manager also features a hybrid user interface that integrates both the Graphical User Interface (GUI) and Command Line Interface (CLI). With the hybrid interface, operations performed in the GUI are simultaneously reflected in the CLI and vice versa.
"Sun's N1 software tools are making it easier for organizations to manage the complex systems that deliver their business services," said Tom Goguen, vice president of product marketing, Operating Platforms at Sun. "With Sun N1 System Manager and Sun N1 Service Provision System, companies can now control the entire stack from bare-metal system through OS to applications and business services."
The Sun N1 Service Provisioning System simplifies application lifecycle management by rapidly provisioning business services that span multiple tiers – J2EE application servers, Web servers, and databases – across heterogeneous environments. It offers organizations a standard method for deploying business services and tracking changes throughout the deployment process and includes an audit trail to help customers meet regulatory compliance. New features include:
Application Library – delivers pre-built models for deploying industry leading J2EE application servers, web servers, or database servers from Sun, Oracle, BEA and IBM onto the Solaris OS, including Solaris Containers, and other operating systems, including: Windows Server, Red Hat Enterprise Linux and AIX.
Bare-Metal OS Provisioning – allows system administrators to remotely install, configure and rapidly provision operating systems such as the Solaris(TM) OS, Microsoft Windows Server and Red Hat Enterprise Linux. Through built-in procedures, customers can also rapidly deploy Solaris OS packages and patches, Red Hat Linux package manager files, and Microsoft Windows-based applications, eliminating the need to individually update systems.
Sun N1 System Manager pricing will start at $299 (USD) per managed server and will be available for download on at: www.sun.com/n1, in late summer 2005. The N1 Service Provisioning System pricing starts at $1400 (USD) per managed server and is available now for download at: www.sun.com/n1. Alternatively, customers can purchase N1 Service Provisioning System as part of the Sun Java(TM) Enterprise System.
Sun's NC05Q2 Web event is available at: http://www.sun.com/nc/05q2. More information on today's announcements, including full Press Releases and product details, can be viewed at Sun's online press kit: http://www.sun.com/aboutsun/media/presskits/networkcomputing05q2/.
About Sun Microsystems, Inc.
Since its inception in 1982, a singular vision — "The Network Is The Computer" — has propelled Sun Microsystems, Inc. (Nasdaq: SUNW) to its position as a leading provider of industrial-strength hardware, software and services that make the Net work. Sun can be found in more than 100 countries and on the World Wide Web at http://sun.com
Sun, Sun Microsystems, the Sun logo, Solaris, Java, J2EE, N1, Sun Fire, and The Network Is The Computer are trademarks or registered trademarks of Sun Microsystems, Inc. in the United States and other countries.
Continuous Computing® Acquires Key Assets in China from UP Technologies
CSO leads the way with new business reporting technology
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Created into the deep lands of the Bourbons in 2000, SÜHNOPFER is the black metal project of multi-instrumentalist and sole member Ardraos (also drummer for CHRISTICIDE, PESTE NOIRE, AORLHAC).
SÜHNOPFER has since built up a discography of three demos, an EP ("L'Aube des Trépassés", 2007) and 2 full-length albums: "Nos Sombres Chapelles" (2010), and the resounding last one "Offertoire", released at the end of 2014.
SÜHNOPFER delivers a violent medieval and melodic atmosphere, with themes dealing with a medieval, knightly, obscurantist and religious dimension, by adding typical aspects of his powerful and glorious homeland.


text:
Kombucha? You betcha!
By Lucy Marrett on February 6, 2018 in Beverages, Category insights, Insights, News 0
The idea of the kombucha health drink is not new.
Kombucha isn't new, in fact it's an ancient, fermented, tea-based drink that originated in China and is often called the "tea of immortality" for its reputed health benefits. It offers a rapidly growing health alternative to carbonated soft drinks as it has lower sugar content.
During its fermentation process, the yeast converts the sugar to alcohol and the bacteria in the drink, converts the alcohol to organic acids. What's left is the sour drink with a hint of vinegar; depending on the flavour, the vinegar can be a welcome and refreshing taste.
Due to its recent spike in popularity, there are many Australian brands that have begun to make and distribute their kombucha products.
Liquefy Health co-founder Trent Butler said he found Kombucha to be an interesting space.
"I spend a lot of time in America and it's definitely much bigger there already. It was started by the cafes and the hipsters but it is going mainstream," he said.
"There's a big trend in looking backwards in order to find the way forward."
Remedy Kombucha Co-Founder Emmet Condon said he, along with his co-founder Sarah, started making kombucha at their home.
"We started making kombucha at home many years ago as part of a wider obsession with crafting and nurturing a whole range of fermented food and drinks for ourselves and our kids," he said.
"We loved how they tasted and how they made us feel.
"Around this time, we found ourselves increasingly frustrated with the food industry and the number of misleading so-called 'healthy' products on shelves. Rather than focus on the negative, we decided to pour that energy into good, and make something that was truly natural and good for you."
A health phenomenon
In a poll run by Choice.com.au, 79% of voters said that they drank Kombucha for the health benefits.
A Choice community member commented that it is appealing for its "sherbet-y taste" and probiotics.
Kombucha's live culture of bacteria and yeast can act as a probiotic offering health benefits including improved digestion function, protection against some diseases and strengthening the immune system and its function.
SCOBY is the acronym for 'symbiotic culture of bacteria and yeast'. A scoby is the living conglomerate of bacteria and yeast that transforms the tea and sugar combination into the final kombucha product. It sits on the top of the liquid and seals it off from air while it ferments.
CSIRO senior research scientist Dr Michael Conlon specialises in diet and gut health. He told Choice.com.au: "The health potential of probiotics more generally can vary depending on the number and type of microbes, what you consume them with, and the composition of your own gut microflora. It's likely the number of microbes in kombucha would be much lower than what you might see in a commercial probiotic product."
"Fermentation generates certain types of acid and other bioactive compounds that can be beneficial, but whether they get through to the large bowel so that a benefit can be gained is unknown," he said.
Mr Condon said there is a broad target market of both existing and potential customers.
"Remedy drinkers include both men and women, aged from around 18 to 60, although there are also plenty of fans in age brackets either side of this, too," he said.
"They are generally middle to high income earners who are health conscious and care about what they put into their body, but they still like to enjoy a tasty beverage."
Mr Butler said: "I read a study that said 90% of all illness can be traced back to your gut. That's a pretty big statistic when you think that a lot of disease can be linked back to how heathy your gut flora is.
"The people who discovered it feel a difference when they have it, it's not just a gimmick these beverages really do make you healthier," he said.
"We're all about health drinks; it's about things that can promote health for you."
Market to the market
Due to its appeal across all age groups, kombucha is a drink that is ideal for retailers to stock in convenience stores.
Mr Condon said kombucha has no age restrictions.
"Like water, all age groups should and can drink Remedy," he said.
"We see a lot of parents buying Remedy Kombucha for children as a healthy alternative to sugary soft drinks."
For merchandising and marketing purposes, Mr Condon recommends the beverage be placed alongside other healthy food products.
"The consumer is the same customer who will select a wrap or salad or other healthy food option." he said.
"Trial is the key to recruiting new drinks, once people taste it they are convinced."
According to Mr Condon, another important factor is: "Driving awareness of the health benefits of kombucha."
Remedy Kombucha has an offering for the convenience sector which includes 250ml cans at a lower price point to encourage consumers to trial the product, as well as 330m glass bottles.
Mr Butler said: "The way I think it's going to go mainstream is through actually being a health alternative to soft drink by actually mimicking the flavour profiles to a large extent of the "traditional" soft drink. We have a cola flavour that tastes a lot like the red label stuff.
"Especially for convenience stores, it's about making it easier for people to transition to health," he said.
Kombucha future
According to a report published by Zion Market Research in June 2017, the global Kombucha market was valued at around $1062 billion USD in 2016 and is expected to reach a value of $2457 billion USD by 2022.
Mr Condon said: "You only need to look at the kombucha market in the US as a guide, where kombucha is the fastest growing market in the functional beverages category."
"There are whole large fridges dedicated to kombucha in some US supermarkets, like what you see for milk here [in Australia], and it's even available in Target."
Remedy Kombucha is currently ranged in a number of convenience stores and continues to roll out its product to other branded convenience stores.
"As consumers continue to vote with their dollars for products that support a healthy organism, and share their new found love on social media, it seems obvious that kombucha has not even hit its peak."
Mr Butler said it was his job to track and understand trends in health and nutrition, and that Liquefy are experts in shelf stable products.
"Traditionally Kombucha was sold out of the fridge, but that's changing," he said.
"What we're seeing with the big players in America, we're seeing the move from refrigerated komchua to kombucha that is sold ambient.
"The probiotics in kombucha are actually much healthier at a room temperature than they are when they're refrigerated.
"We're going to see more and more health stable kombucha but there's a bit of understanding and education to go with it. In Australia we're going to see a lot of shelf-stable Kombucha pop up.
"It makes it easier for convenience stores to have their deliveries arrive in cartons."
According to Kombuchabrewers.org the industry is thriving and is showing no signs of slowing down.
"With continued 30% growth in the natural channel and 50% growth (or more) in the conventional channel year after year, kombucha is the fastest growing functional beverage category," the site said.
beverage, health drink, Kombucha, Liquefy, Liquefy health, Remedy kombucha, scoby, slider, sugar alternative, sugar-free beverage
AACS store of the year
Kombucha gets tick of approval


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text:
'Our PR Is Awful' - Expert slaughters Spurs over news last Fri that'll 'Hit Fans In The Pocket'
By support
11th May, 2017 | 8:22am
McManaman: Tottenham must do this to compete in Champions League
By Aramide Oladipo
Steve McManaman believes Tottenham can compete in the Champions League next season if they keep their best players and the nucleus of their squad intact
With the north London side set to finish second in the Premier League, Spurs have qualified for the elite European competition for the second consecutive season.
However, despite enjoying relative success in the Premier League this season, Spurs struggled to make an impact in the Champions League and they failed to qualify for the knockout rounds.
Tottenham only managed to secure seven points and finished in third place in a group which included Bayer Leverkusen, CSKA Moscow and eventual semi-finalists Monaco.
Speaking on BT Sport (Wednesday, 7.00pm) after the Champions League semi-final second leg between Atlético Madrid and Real Madrid, Steve McManaman claimed the key for English clubs is to keep their sides intact.
"It's no surprise that Madrid, Bayern, Barcelona and Juventus are getting to the latter stages ever single year," McManaman said.
"They change a few nuances here and there but in England, it seems to be, we've had a bad season here, let's just rip everything up and start again.
"You want people like Tottenham to have the patience and have the manager or the chairman to say you're not leaving, we're keeping you here," he said.
Tottenham enjoyed their best Champions League campaign under Harry Redknapp during the 2010/11 season when they reached the quarter-final stage before losing to Jose Mourinho's Real Madrid side.
For the second season in a row, Tottenham are going to play their home matches in the competition at Wembley Stadium as their new stadium is being built.
In other Tottenham news, fans have considered the potential signing of this 26-year-old right-back.
We've launched a << BREAKING NEWS FEED>> exclusively for your club. 'Like Us' on Facebook by clicking here if you want 24/7 updates on all Tottenham breaking news.
Euro giants ready to blow rivals out the water for PL wizard linked with Tottenham – reports
Confirmed: Tottenham open negotiations over player of the year, ace million per cent interested in transfer


Nduru and the Leopard is part of Fumo's Hadithis – a series of African folktales that take us into the oral tradition of the continent. This is a tale from the slopes of Mt. Kenya. Nduru the Squirrel finds himself cornered by a hungry Chui the Leopard who also happens to be king. Nduru has to devise a way to survive while Chui has to ensure he feeds.
Fumo's Hadithis is a series of African folktales that take us into the oral tradition of the continent. In this story, Nduru the Squirrel finds himself cornered by a hungry Chui the Leopard who also happens to be king. Nduru has to devise a way to survive while Chui has to ensure he feeds. This is a tale from the slopes of Mt Kenya.
Githanda Githae is a Kenyan oral storyteller. He is committed to preserving and propagating the culture of African Orature for present and future generations. A pioneer of interweaving performance elements with orature 'language' to the written story.


text:
Een verkeersweg:
 N733 (België)
 N733 (Frankrijk)
 N733 (Nederland), zie Provinciale weg 733

Wikipedia:Met bot gemaakte doorverwijzing

redpajama_set_name: RedPajamaWikipedia


Air pollution finds a mention in the manifestos of the Bharatiya Janata Party, the Congress and the CPI(M), but none promises to ensure the country meets the national safe air quality standard in the next five years.
A new report titled "Political Leaders Position and Action on Air Quality in India" released by Climate Trends, a Delhi-based communications strategy initiative, on Tuesday also highlighted that members of parliament in 14 Indian cities, among the most polluted cities globally as per the WHO 2018 urban air quality database, have done little to get their cities to comply with safe air quality standards locally.
They haven't even raised the issue in public fora despite data showing dangerous levels of air pollution.
To be sure, in many cases, MPs have little to do with local interventions, which are managed by state governments or local bodies. They do, however, have funds from the MP Local Area Development Scheme to spend on local interventions.
The BJP manifesto released on Monday says that through concerted action, it will reduce pollution levels by at least 35% over the next five years in 102 cities. It also said the National Clean Air Plan (NCAP) would be made into a mission. But given the record of the National Mission for Clean Ganga, experts said declaring the programme a mission may not be enough to guarantee its implementation. The BJP also claimed that speed and effectiveness in issuing forest and environmental clearances led to adding of around 9,000 sqkm to the forest cover of the country.
"It's a gem. The diversion of forest land led to creation of forests! Maybe they meant compensatory plantations, but didn't Cromptroller and Auditor General (CAG) and Supreme Court not conclude that too was a failure?" tweeted Kanchi Kohli, legal researcher at Centre for Policy Research (CPR).
The Congress manifesto calls air pollution a "national public health emergency" and promises to strengthen the NCAP by stipulating sectoral emission standards. Congress also promises to assess district level forest cover, and increase forest cover from 21% nationally to 25% by 2025.
All three parties have promised to improve public transport, walking and cycling infrastructure. The Climate Trends report highlights that air pollution levels in the 14 cities have been on the rise, but that there has been little political motivation to reverse the trend.
For example, in Kanpur, PM10 concentrations increased from 200 micrograms per cubic metres to 224 micrograms per cubic metres between 2014 and 2018.
In PM Modi's constituency Varanasi, PM10 levels were 140 micrograms per cubic metres in 2014 and rose to 244 micrograms per cubic metres in 2017.
In Lucknow, BJP MP and home minister, Rajnath Singh's constituency, PM 10 levels rose from 174 micrograms per cubic metres to 246 micrograms per cubic metres.
"To decongest the city, a 100-km long ring road is to be constructed in Lucknow. The ministry of road transport and highways has given clearance for it and the project will cost more than ₹3,000 crore," Singh said in 2015 but there were no substantial local measures taken to bring down concentrations.
In Delhi, air pollution levels fell marginally from 278 micrograms per cubic metres in 2017 to 240 micrograms per cubic metres in 2018.
"Clearly in Delhi NCR, emergency action in the form of graded response action plan and longer term comprehensive action plan have been taken forward. Delhi has shut down power plants, stopped use of polluting fuels like pet coke and furnace oil in industries, brick kilns in the region have moved to clean technology, and there are local area pollution plans so we are now seeing early signs of stabilisation," Roychowdhury added.


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Q: How to specify which Ivy resolver to use My understanding is that <ivy:resolve/> copies dependencies from the configured repo into the local Ivy cache (rooted under ${USER_HOME}/.ivy2). But after looking at the task's docs, I was surprised to find that there is no resolver attribute, like:
<ivy:resolve file="ivy.xml" conf="compile" resolver="theResolverToUse"/>

So I ask: how do you specify which resolver to use, especially if (in ivysettings.xml), you can define 1+ resolvers? Thanks in advance.
Update:
For instance, here's a snippet of the resolver defined in my (emerging) ivysettings.xml:
<resolvers>
    <chain name="chainResolver" returnFirst="true">
        <url name="urlResolver">
            <ivy pattern="${ivyRepoRoot}/module_descriptors/${ivyModDescriptorPattern}"/>
            <artifact pattern="${ivyRepoRoot}/artifacts/${ivyArtifactPattern}"/>
        </url>

        <filesystem name="localFileResolver">
            <artifact pattern="${user.home}/.ivy2/local-cache/[artifact]-[revision].[ext]"/>
        </filesystem>
    </chain>
    <sftp name="publisherResolver" user="fizz" userPassword="buzz" host="example.com">
        <ivy pattern="sftp://example.com:22/usr/local/apache/htdocs/ivy/module_descriptors/${ivyModDescriptorPattern}"/>
        <artifact pattern="sftp://example.com:22/usr/local/apache/htdocs/ivy/artifacts/${ivyArtifactPattern}"/>
    </sftp>
</resolvers>

A: In Ivy, resolvers and their relationships, priorities and chains are defined separately from the resolve task.
Multiple resolvers can be chained together and in chained resolvers, pay special attention to the first resolver in the chain and the notion of 'find first'.
If resolvers and/or chains are configured properly, you should not have to choose which resolver to use.  This comes in very handy when resolvers have different behaviour in different environments.

A: Chain resolvers are handy, but if you want more control I'd suggest using a modules section as explained in the following answer:

*

*Use public maven repository with ivy

redpajama_set_name: RedPajamaStackExchange


Until today, the one and only time Apple released a Mac with more than one processor inside was 1996, when the company released a power-mad Power Mac 9500. It had two 180MHz PowerPC 604e processors, and to really take advantage of the second one, you'd need to use software specially written for the task.
With the announcement of Apple's two new dual-processor-bearing Power Mac G4 models (at the same prices as the company's original one-processor counterparts), Apple has gone back to the future. With G4 processors running at 450MHz or 500MHz, these new Power Macs are surely speedier than the multiprocessor Mac of 1996. Don't start adding two 500MHz G4s together and coming up with a gigahertz, though: the Mac OS of today still isn't multiprocessor-savvy enough to tax both processors to their limits.
But unlike that evolutionary dead end of four years ago, the placement of these new dual-G4 Macs firmly in the Power Mac product line shows that this latest permutation will stick around. Multiprocessor Macs are back, and this time it looks as though they're here to stay.
With these new Power Macs, Apple is pushing the Power Mac G4 minitower up into the high end. The base configuration remains the same -- you can still get a stripped-down Power Mac G4 at 400MHz, with a 20GB drive (running at 5,400 rpm, not the faster 7,200 rpm drives found in the multiprocessor models) and 64MB of RAM. But beyond that, the Power Mac minitowers are all about dual processors.
In the middle of the line sits a G4 with two 450MHz G4s. Apple's standard configuration for this model includes 128MB of RAM and 30GB hard drive. And high atop the mountain stands the new Mac speed king, a dual 500MHz box loaded with 256MB of RAM and a 40GB drive.
Mach Speed Ethernet Just as Apple broke new ground by rolling out 100BaseT Ethernet as a standard feature with the original iMacs, the company is again pushing networking to a higher standard with these new Power Macs. Gigabit Ethernet -- that's 1,000BaseT, or speeds 100 times faster than conventional 10BaseT Ethernet -- is standard on all these models, making them primed for any network environment requiring the high-speed transfer of large graphics or multimedia files.
The real change with these new Macs is the addition of a second G4 processor. Because of the way Mac OS is designed, adding a second processor doesn't actually double your processing power. That's because the current version of Mac OS was never really designed to be run on more than one processor.
In 1995 and with Apple's blessing and cooperation, clone maker DayStar Digital developed a system extension, nPower, that let the Mac OS work with multiple CPUs when you run programs designed for multiprocessing, and became the first company to ship a multiprocessor Mac. Users of Adobe Photoshop, for example, could benefit -- even today, owners of multiprocessor Macs can take advantage of a Photoshop's multiprocessing support to speed roughly 300 different commands, from filters to color corrections. Other early benificiaries of the technology included software from Elastic Reality, Insignia Solutions, Live Picture, Macromedia, and Strata. But the Finder, which was clueless about the extra processors, saw no benefit -- one processor had to do all the work.
Apple licensed DayStar's technology and made it the basis of the Power Mac 9500 MP, as well as integrating it into the Mac OS. But when the PowerPC G3 processor hit the scene, the Mac multiprocessor market stagnated.
The G3 Loner Unlike the PowerPC 604 chip, which could do multiprocessing, the PowerPC G3 is unable to play well with others. As a result, Macs had to go it alone -- and Mac users had to decide between sticking with a gaggle of slower chips or one single fast G3.
However, the G4 processor is able to act in tandem with others of its kind, and Apple set the stage for its announcements today by tuning up Mac OS 9 to work better with multiprocessing systems. (Prior to the OS update, multiprocessor users couldn't use Virtual Memory, among other quirks.) Although we originally reported that the Finder was also helped by additional processors, Apple Hardware Chief Jon Rubenstein confirmed to us that, in fact, Mac OS 9, Finder is completely unable to take advantage of the Power Mac G4's second processor.
The Big Break The fact is, while these new multiprocessing Macs will make killer machines for Photoshop users, they won't dramatically transform the entire Mac experience until the advent of Mac OS X. Unlike the current Mac OS, Apple's new operating system can innately use multiple processors, splitting out all the duties of the computer with ease. On a Mac running OS X, two 500MHz processors really could make you feel as if you're running at 1 gigahertz, because the system will be able to push both of those processors to their limits.
If you're a Photoshop user -- or the user of any other program that shines when using multiprocessing -- these new systems will blow you away. For the rest of the Mac users out there, the advantages are a bit more subtle right now. But when Mac OS X arrives, the performance boosts that these new Power Mac G4s will experience will be gigantic.


text:
Armando Marques (Algés, 1 de Maio de 1937) é um atleta português de tiro, do Sporting Clube de Portugal, que recebeu uma medalha de prata na prova de fosso olímpico nos Jogos Olímpicos de Verão de 1976. Foi vencedor da Medalha Olímpica Nobre Guedes em 1974.

Ligações externas

Naturais de Oeiras (Portugal)
Atiradores desportivos de Portugal
Desportistas do Sporting Clube de Portugal
Atiradores nos Jogos Olímpicos de Verão de 1964
Atiradores nos Jogos Olímpicos de Verão de 1972
Atiradores nos Jogos Olímpicos de Verão de 1976
Medalhistas olímpicos de prata de Portugal


Carrera Evolution Sets are intended for ages 8+ and offer unlimited extension possibilities with track, scenery and cars. All of the standard straight and curve pieces in the Evolution series are compatible with the Digital 1/24 and 1/32 series, and the 1/32 scale cars included in this Fast Classics analog system are digital upgrade ready. The set combines 1/32 cars with 1/24 Mega Tracks that can be expanded to 4, 6 or 8 lanes!.
Compare prices on Ho Slot Car Parts at ShoppinGent.com – use promo codes and coupons for best offers and deals. Start smart buying with ShoppinGent.com right now and choose your golden price on every purchase.


Well, I know its a little late but Jordan and I celebrated our 4th anniversary on Cinco de Mayo! Jordan suprised me and took me to Park City for the night. Mckenzie was able to stay with Grandma Farr so it was a night out. We drove up to Park City to find that our coupon didn't work :( but we did find a Sushi restaurant close by and stopped in... YUMM! Then we went swimming and alas I think we are getting old, we both fell asleep watching tv at 9:30. We woke up at 1:30 and decided to shut off the lights and say prayers. We then had a hard time trying to go back to sleep! We were able to go to the temple the next morning and spend the day together. It's been a wonderful 4 years! Many more to come!
I know this isn't a wedding picture but it was on our Honeymoon so it was close! Happy Anniversary Jordan! Love ya!


text:
Back to Journals » Drug Design, Development and Therapy » Volume 10
Selective CDK7 inhibition with BS-181 suppresses cell proliferation and induces cell cycle arrest and apoptosis in gastric cancer
Authors Wang B, Liu Q, Cao J, Chen J, Liu Z
Received 9 April 2015
Accepted for publication 15 August 2015
DOI https://doi.org/10.2147/DDDT.S86317
Editor who approved publication: Prof. Dr. Wei Duan
Bo-Yong Wang, Quan-Yan Liu, Jun Cao, Ji-Wei Chen, Zhi-Su Liu
Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China
Abstract: Cyclin-dependent kinase (CDK) family members have been considered as attractive therapeutic targets for cancer. In this study, we aim to investigate the anticancer effects of a selective CDK7 inhibitor, BS-181, in gastric cancer (GC) cell line. Human GC cells (BGC823) were cultured with or without BS-181 at different concentrations for 24–72 hours. BS-181 significantly reduced the activity of CDK7 with downregulation of cyclin D1 and XIAP in GC cells. Treatment with BS-181 induced cell cycle arrest and apoptosis. The expression of Bax and caspase-3 was significantly increased, while Bcl-2 expression was decreased in cells treated with BS-181. In addition, the inhibition of CDK7 with BS-181 resulted in reduced rates of proliferation, migration, and invasion of gastric cells. Those results demonstrated the anticancer activities of selective CDK7 inhibitor BS-181 in BGC823 cells, suggesting that CDK7 may serve as a novel therapeutic target or the treatment of GC.
Keywords: selective CDK7 inhibitor, gastric cancer, BS-181, anticancer activities
Gastric cancer (GC) is one of the most common types of malignant cancer in the world.1 Despite a decrease in the past several decades, it still remains the second leading cause of cancer death.2 Current choices of treatment for GC include chemotherapy, surgery, and radiation therapy. However, unfortunately, the overall prognosis of the disease is disappointing, especially for those with advanced GC. Chemotherapy resistance and metastasis largely contribute to the failure of curative treatment. Thus, it is of great necessity and importance to develop new drugs.
Cyclin-dependent kinases (CDKs) are a large group of serine/threonine protein kinases that have central roles in controlling the cell cycle and transcription. Activation of specific CDKs is required for the appropriate progression through the cell cycle and into the next stage of the cell cycle. CDK–cyclin complexes were also identified as conserved components of the RNA polymerase II (Pol II) transcriptional machinery.3 Two nonoverlapping sets of CDKs have been defined in metazoans: CDK1, CDK2, CDK4, and CDK6, which regulate the cell division, and CDK8 and CDK9, which are dedicated to transcription control. CDK7 is the only one that cannot be easily classified. Phosphorylation of the first group of CDKs is mediated by CDK-activating kinase that has three subunits including CDK7, cyclin H, and MAT1.4
Additionally, as an essential component of the transcription factor TFIIH, CDK7 is also involved in transcription initiation by phosphorylating the COOH-terminal domain of the largest subunit of RNA pol II.5 Thus, CDK7 is becoming an attractive target for anticancer treatment. Inhibition of CDK7 activity is expected to inhibit both transcription and cell progression, therefore, leading to an antitumor effect. The first generation of CDK inhibitors has entered late-stage clinical trials but so far has only shown modest activity because of unfavorable pharmacology.6 Most of the CDK inhibitors target the highly conserved kinase domain and could inhibit multiple CDK family members, which in part explain the undesirability of those trials. Hence, the identification of more selective and potent CDK inhibitors is imperative. BS-181, a pyrazolo [1,5-α] pyrimidine-derived compound, is a novel selective inhibitor of CDK7 by computer-aided drug design. In the previous study, it was demonstrated that BS-181 inhibited the phosphorylation of the PolII C-terminal domain (CTD) at Ser,5 which is known as a CDK7 substrate, thus promoting cell cycle arrest and apoptosis to inhibit the growth of cancer cells in a breast cancer cell line.7 Furthermore, compared to roscovitine, a broad-spectrum CDK inhibitor, BS-181 exhibits a substantially higher preference for CDK7. The results mentioned earlier strongly indicated the potential of BS-181 in anticancer treatment. However, no literature has shown the antitumor effect of BS-181 in GC.
In the present study, we investigated whether BS-181 inhibited the tumor growth and metastatic behavior of GC in vitro as well as in vivo and the underlying mechanisms.
The Ethics Committee of Zhongnan Hospital of Wuhan University approved this study (2014-02-ZN012).
The biological effects of BS-181 on GC have been investigated using BGC823. BGC823 cells were purchased from The Medical Experiment Center of Zhongnan Hospital of Wuhan University (Wuhan, Hubei, People's Republic of China). BGC823 cells were cultured in F-12 Ham medium (Thermo Fisher Scientific, Waltham, MA, USA) supplemented with 10% fetal bovine serum (MP Bio-medicals, Solon, OH, USA). Cultures were maintained at 37°C in a humidified atmosphere of 95% air and 5% CO2.
BS-181 was purchased from Biofavor Biotech Service Co., Ltd. (Wuhan, Hubei, People's Republic of China). Cyclin D1 (sc-753) antibody was purchased from Santa Cruz Biotechnology Inc. (Dallas, TX, USA); PolII (N-20) and PolII phosphoserine-5 (ab5131) antibodies were purchased from Santa Cruz Biotechnology Inc.; Bcl-2 (#2870p) antibody was purchased from Cell Signaling Technology, Inc. (Beverly, MA, USA); Bax (BS-2538) antibody was purchased from Bioworld Technology, Inc. (MN, USA). Caspase-3 antibody was purchased from Sanying (Wuhan, People's Republic of China); XIAP (ab86227) antibody was purchased from Abcam (Shanghai, People's Republic of China). Anti-β-actin and horseradish peroxidase-labeled secondary antibodies were purchased from Boster (Wuhan, Hubei, People's Republic of China); the concentrations of all antibodies were used according to the manufacturers' instruction.
Kinase assays in vitro
As previously described,7 kinase assays were performed to evaluate the inhibitory effects of BS-181 on CDK activities in vitro. Kinase assays were carried out using substrate peptides purchased from ProQinase GmbH (Freiburg, Germany). A luciferase assay (PKLight assay; Cambrex, UK) was used to determine ATP remaining at the end of the kinase reaction according to the manufacturer's protocols.
Whole-cell lysates were prepared from BGC823 cells, and standard Western blot analysis was performed. Protein concentrations were detected using Bradford dye (Bio-Rad Laboratories Inc., Hercules, CA, USA). Equal amounts of protein extracts (10 μg) were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The membrane was probed with specific primary antibodies including XIAP (1:300), cyclin D1 (1:300), BCl-2 (1:800), Bax (1:600), and caspase-3 (1:600). The protein bands were normalized with β-actin, and all the blots were quantified with Software Quantity One (Bio-Rad Laboratories Inc.).
Cell cycle and apoptosis analysis
Cells were seeded on plates in Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum. After incubation with BS-181 for 12 hours, 24 hours, 48 hours, and 72 hours at 0 μM, 1 μM, 10 μM, and 20 μM, cells were harvested, rinsed with cold PBS, and fixed with 70% ice-cold ethanol for 30 minutes and then incubated with propidium iodide (PI) for 30 minutes prior to flow cytometry (BD Biosciences, San Jose, CA, USA). Cell apoptosis was determined by flow cytometry using Annexin V-FITC/PI (BD Biosciences) double staining assay. Annexin V-positive and PI-negative cells were identified as apoptotic cells. The apoptotic rate was determined using CellQuest software (FCM, BD Biosciences).
Cell viability was detected using Cell Counting Kit (CCK-8 kit, Dojindo Laboratory, Japan) according to supplier's introductions. Briefly, BGC823 cells were seeded at 104 cells per well for 48 hours with or without BS-181. Then, the absorbance was detected at 450 nm (reference at 650 nm) in each well.
Cell migration and invasion assay
To evaluate cell migration, BGC823 cells (1×105/mL, in minimum essential medium supplemented with 1% fetel bovine serum) were placed into top chamber of transwell migration chambers (8 μm pores Transwell inserts, BD BioCoat™). The lower chamber was filled with 0.1% bovine serum albumin–DMEM without serum. After 24 hours, unmigrated cells were removed from the upper surface of transwell membrane, and migrated cells in the lower chamber were fixed, stained, photographed, and counted. To assess invasion in vitro, invasion assays were done under the same conditions as the transwell migration assays, but in matrigel-coated transwells.
Animal preparation and human tumor xenografts
Sixty-seven-week-old male BALB/c-nu mice were purchased from the Hubei Center for Disease Control and Prevention (Wuhan, Hubei, People's Republic of China). All animal experiments were performed in the Animal Research Center of Wuhan University (Wuhan, Hubei, People's Republic of China) and were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals of Wuhan University. The Ethics Committee of Zhongnan Hospital of Wuhan University approved the animal study (20140120ZN01). Animals were raised under controlled conditions with a temperature of 24°C±2°C and a relative humidity of 50%±15%.
Human tumor xenografts were established as previously described.7 In total, 5×106 BGC823 cells (0.1 mL) were injected subcutaneously into the flank of the mice. Tumor measurements were performed two times per week, and volumes were calculated using the formula: tumor size = (length [mm] × width2 [mm])/2. Finally, 30 mice (tumor volume 100–200 mm3) were selected and randomly assigned into three groups. As previously described,7 BS-181 was prepared in 10% dimethyl sulfoxide/50 mM HCl/5% Tween 20/85% saline. Mice received BS-181 injection (ip) twice daily at indicated doses (BS-181 [10 mg/kg/d or 20 mg/kg/d] or roscovitine [20 mg/kg/d]) for a total of 14 days. Control mice were injected with vehicles. Animal weights and tumor volume were measured each day throughout the 14-day treatment. In addition, all rats were kept for another 30 days for survival observation. Mice were injected intraperitoneally twice daily with BS-181 at 5 mg/kg or 10 mg/kg.
Comparisons among all groups were performed with the one-way analysis of variance test or unpaired Student's t-test. The survival analysis was estimated with the Kaplan–Meier method. The significance of comparison was calculated with the log-rank test. A two-tailed P<0.5 was considered significant. All data were analyzed using SPSS software version 21.0 (StataCorp LP, College Station, TX, USA).
BS-181-inhibited gastric cancer cell proliferation, migration, and invasion
To evaluate the antiproliferative ability of BS-181 in GC, several different cell lines including MKN28, SGC-7901, AGS, and BGC823 were treated with increasing concentrations of BS-181 for 48 hours. CCK-8 assay showed that GC cell growth was inhibited by BS-181, with inhibitory concentration (IC50) ranging from 17 to 22 μM. For normal gastric epithelial RGM-1 cell line, IC50 was 6.5 μM (Table 1). In addition, we investigated the effects of BS-181 on cell migration and invasion ability. As expected, BS-181 significantly inhibited cell migration and invasion ability in a dose-dependent manner (P<0.05, respectively; Figure 1).
Table 1 In vitro growth inhibitory activity of BS-181 on gastric cancer and normal cell lines
Notes: Different gastric cancer cell lines including MKN28, SGC-7901, AGS, and BGC823 were treated with increasing concentrations of BS-181 for 48 hours. CCK-8 assay showed that gastric cancer cell growth was inhibited by BS-181, with IC50 ranging from 17 μM to 22 μM; atested by CCK-8 assay.
Abbreviations: IC50, inhibitory concentration; SD, standard deviation.
Figure 1 BS-181 decreased the migration and invasion ability of BGC823 cells.
Notes: BGC823 cells were treated with BS-181 for 24 hours at indicated concentrations. Migration and invasion assay of BGC823 cells (A). BS-181 significantly decreased the number of migrated (B) and invaded (C) cells. Compared with control group *P<0.05 and **P<0.01; compared to other groups ##P<0.01.
BS-181-induced cell apoptosis and cell cycle arrest in gastric cancer cells
Cell apoptosis was determined using flow cytometry. Significant increases in apoptotic cells were observed in BS-181-treated BGC823 cells compared to control (P<0.05, respectively; Figure 2A). Our results also showed that BS-181-induced cell apoptosis in a dose- and time-dependent manner. Additionally, caspase-3 and Bax expressions have been significantly increased, while Bcl-2 level has been reduced in cells treated with BS-181 compared to control (P<0.05, respectively) (Figure 2B). These results indicated that BS-181 could induce apoptosis in GC cells. Furthermore, the inhibition of CDK7 activity led to a significant reduction of key antiapoptotic protein XIAP and cell cycle regulator cyclin D1 (P<0.05) (Figure 2C). Thus, BS-181 may regulate cell apoptosis and cell cycle progression via downregulating XIAP and cyclin expression in BGC823 cells. In the present study, cell cycle distribution was analyzed by flow cytometry (Figure 3). Treatment of BS-181 showed an increase in cells in G0/G1, accompanied by a reduction of cell population in S and G2/M phases. These results indicated that BS-181-induced cell cycle arrest in the G0/G1 phase and delayed the progression of the cell cycle.
Figure 2 BS-181 induced cell apoptosis (A) and regulated apoptosis-related protein expressions (B and C).
Notes: BS-181-induced BGC823 cell apoptosis in a dose- and time-dependent manner. Additionally, BS-181 increased expression of proapoptotic proteins and decreased expression of antiapoptotic proteins. Compared with control group *P<0.05 and **P<0.01; compared to other groups #P<0.05 and ##P<0.01.
Figure 3 BS-181-impaired cell cycle progression in BGC823 cells.
Notes: Cell cycle distribution was analyzed by flow cytometry (A). Data are presented as the mean of triplicate experiments (B). Administration of BS-181 significantly increased the percentage of cells in the G0/G1 phase, and significantly decreased the S and G2/M phase fractions.
BS-181-inhibited CDK7 activity in gastric cancer cells
BS-181 was synthesized as a specific CDK7 inhibitor. In this study, we also confirmed that BS-181 is a specific inhibitor of CDK7. As shown in Table 2, BS-181-inhibited CDK7 activity with an IC50 =0.019 μM, while the IC50 achieved with roscovitine was 0.48 μM. In addition, the IC50 values for inhibition of other CDKs by BS-181 were >1 μM, which is much more higher than that of CDK7. In addition, immunoblotting showed that BS-181 inhibited the phosphorylation of the RNA polymerase II CTD at the well-established CDK7 phosphorylation site serine 5 (P-Ser5) (Figure 4).
Table 2 Inhibition of cyclin-dependent protein kinase activity by BS-181
Notes: The mean IC50 values (μM) for roscovitine and BS-181 were obtained from three independent experiments. Roscovitine is a potent and selective CDK inhibitor. Data are expressed as mean ± SD.
Abbreviations: IC50, inhibitory concentration; SD, standard deviation; CDK, cyclin-dependent kinase.
Figure 4 BS-181-inhibited phosphorylation of CDK7 substrates.
Notes: Whole cell lysates were prepared from BGC823 cells treated with BS-181 for 4 hours at indicated concentrations. Immunoblotting was carried out using antibodies for RNA polymerase II or Pol II phosphorylated at Ser5 in the C-terminal domain (A). Data are presented as mean ± SD of three independent experiments (B). Compared to other groups #P<0.05 and ##P<0.01.
BS-181-inhibited tumor growth in vivo and increased survival rate
As previously described,7 the maximum tolerated single dose for BS-181 given intraperitoneally was 30 mg/kg/d, and a dose of 10 mg/kg/d or 20 mg/kg/d was well-tolerated in BALB/c-nu mice. In this study, mice received intraperitoneal injection of BS-181 twice daily with 5 mg/kg/d or 10 mg/kg/d to give daily doses of 10 mg/kg or 20 mg/kg, over a period of 2 weeks. In addition, another group of 15 rats received roscovitine (20 mg/kg/d) injection for a total of 14 days. We observed that tumor growth was significantly inhibited by BS-181 in a dose-dependent manner compared to the control group (P<0.05, respectively) (Figure 5A). However, there was no significant difference in mice body weights between groups during a 14-day observation (Figure 5B). This indicated that there was no apparent toxicity at a daily dose of 10 mg/kg or 20 mg/kg. In addition, all animals were kept for another 30 days for survival observation. As seen in Figure 5C, eight of ten mice (80%) died in the control group, five of ten (50%) died in the roscovitine group, while six of ten (60%, 10 mg/kg/d) and three of ten (30%, 20 mg/kg/d) mice died in BS-181-treated groups. The overall difference in survival rate between rats treated with or without BS-181 was significant (P<0.05, respectively).
Figure 5 BS-181-inhibited gastric cancer growth in vivo and increased survival rate.
Notes: The change in tumor volume (A) was determined for each animal, as tumor volume relative to the tumor volume of each animal at day 1; mice body weights (B) were similar between groups for a 14-day observation; treatment with BS-181 significantly increased survival rate in an additional 30-day observation (C); roscovitine was used as a positive control. Compared to control group *P<0.05, **P<0.01, and ***P<0.001. Compared to other groups #P<0.05.
GC represents an important burden on human health, with hundreds of thousands of newly diagnosed cases and related deaths in the world per year. Thus, the needs for improved understanding of the disease at the basic molecular level and the search for new effective drugs are imperative. CDK7, which plays critical roles in the regulation of transcription and cell cycle, is now an attractive target for the development of anticancer drugs.8 As a member of the transcriptional CDKs, CDK7 facilitates efficient transcriptional initiation, pause release, and elongation by phosphorylating the CTD of RNA Pol II. Moreover, CDK7 is also known to regulate the cell cycle of metazoans by controlling the activation of CDKs through T-loop phosphorylation.9 Inhibition of CDK7 perturbs transcriptional elongation, resulting in the downregulation of short-lived antiapoptotic proteins, such as Mcl-1 and XIAP, and cell cycle regulators such as cyclin D1.10 Previous study has shown that BS-181 selectively inhibited CDK7 by blockage of phosphorylation of the CDK7 substrate, Ser5, in the Pol II COOH-terminal domain, thus leading to anticancer effects in breast cancer cells.7 In the present study, we examined the antitumor effect of BS-181 in GC both in vitro and in vivo. We demonstrated that BS-181 strongly inhibited tumor cell growth in different GC cell lines of which the differentiation levels range from well-differentiated to undifferentiated. Considering that the undifferentiated GC has generally a worse prognosis, BGC823 cells were selected for the rest of our studies at cellular and molecular levels. Moreover, the results of in vivo studies demonstrate that BS-181 reduced the tumor volume in a time- and dose-dependent manner. To further explore the underlying mechanisms of cell growth inhibition, we conducted a cell cycle analysis by flow cytometry, which reveals that GC cells treated with BS-181 accumulated in the G0/G1 phase of the cell cycle, whereas the number of cells in S and G2/M phases significantly decreased. This coincided with the downregulation of cyclin D1 demonstrated by Western blotting. Cyclin D1 is a key regulator of G1 to S phase progression of the cell cycle. Accumulation of cyclin D1 in early to mid-G1 phase leads to activation of the kinases that phosphorylate and inactivate the tumor suppressor Rb, which is necessary for cell cycle progression through the G1 to S phases.11 Previous studies show that blockage of cyclin D1 prevented from cell cycle from proceeding into S phase,12 which is in concordance with the result of our studies. Cyclin D1 overexpression was found in a series of tumor types, including GC,13 breast cancer14 and colon cancer,15 and is a prognostic indicator associated with poor survival of cancer.16 Our results suggest that the downregulation of cyclin D1 can be part of the mechanisms in which BS-181 suppressed cell proliferation and tumor growth of GC.
Apart from the interference in the cell cycle, inhibition of CDK7 by BS-181 also induced cell apoptosis in GC cell lines, as shown by cytometry in our present study. Additionally, immunoblotting shows downregulation of XIAP, and expression of Bcl-2 was also reduced by BS-181. Bcl-2 is the prototype of a class of genes that contribute to tumor progression by inhibiting cell apoptosis. The family of Bcl-2-related proteins constitutes one of the apoptosis-regulatory gene products acting at the effector stage of apoptosis.17 X chromosome-linked inhibitor of apoptosis (XIAP) is a key member of the newly discovered family of intrinsic inhibitors of apoptosis (IAP) proteins. Unlike Bcl-2 that elicits the antiapoptotic effects by regulating the intrinsic pathway, IAP proteins act mainly by blocking cell death directly binding and inhibiting initiator as well as caspases. XIAP is known as a potent inhibitor of caspases-3, -7, and -9.18 As our results show, both Bax, a member of Bcl-2 family, and caspase-3 were reduced by BS-181. Thus, induction of apoptosis via Bcl-2 and XIAP pathways might contribute to the antitumor effects of BS-181 in GC.
Metastasis is responsible for most of the cancer mortalities. The capability of cell migration and invasion is considered to be one of the important determinants in the process of metastasis. In the current study, we found that BS-181 could decrease the GC cell migration and invasion in vitro. It was demonstrated that in breast cancer cells, cyclin D1 was required for TGF β-mediated migration,19 and higher Bcl-2 levels were also shown to be correlated with better outcomes in metastatic breast cancer.20 Based on observations of our present study, we postulated that the antiinvasion and antimigration effect of BS-181 might be partly due to the modulation of cell cycle and antiapoptotic mechanism. However, further evidences are required.
In conclusion, our study demonstrates that BS-181, the selective inhibitor of CDK7, prevents cell growth both in vitro and in vivo, induces the G1 arrest and apoptosis, and inhibits cell migration and invasion of GC. Therefore, BS-181 provides potent and selective CDK7 inhibitor with the potential as an antigastric cancer agent.
The authors would like to thank the Center for Medical Experiment (Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China) for technical assistance.
All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Bertuccio P, Chatenoud L, Levi F, et al. Recent patterns in gastric cancer: a global overview. Int J Cancer. 2009;125(3):666–673.
Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19(8):1893–1907.
Bregman DB, Pestell RG, Kidd VJ. Cell cycle regulation and RNA polymerase II. Front Biosci. 2000;5:D244–D257.
Harper JW, Elledge SJ. The role of Cdk7 in CAK function, a retro-retrospective. Genes Dev. 1998;12(3):285–289.
Fisher RP. Secrets of a double agent: CDK7 in cell-cycle control and transcription. J Cell Sci. 2005;118(pt 22):5171–5180.
Kaliszczak M, Patel H, Kroll SH, et al. Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance. Br J Cancer. 2013;109(9):2356–2367.
Ali S, Heathcote DA, Kroll SH, et al. The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res. 2009;69(15):6208–6215.
Larochelle S, Merrick KA, Terret ME, et al. Requirements for Cdk7 in the assembly of Cdk1/cyclin B and activation of Cdk2 revealed by chemical genetics in human cells. Mol Cell. 2007;25(6):839–850.
Chipumuro E, Marco E, Christensen CL, et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell. 2014;159(5):1126–1139.
Wesierska-Gadek J, Borza A, Komina O, Maurer M. Impact of roscovitine, a selective CDK inhibitor, on cancer cells: bi-functionality increases its therapeutic potential. Acta Biochim Pol. 2009;56(3):495–501.
Zhao J, Pestell R, Guan JL. Transcriptional activation of cyclin D1 promoter by FAK contributes to cell cycle progression. Mol Biol Cell. 2001;12(12):4066–4077.
Baldin V, Lukas J, Marcote MJ, Pagano M, Draetta G. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 1993;7(5):812–821.
Feakins RM, Nickols CD, Bidd H, Walton SJ. Abnormal expression of pRb, p16, and cyclin D1 in gastric adenocarcinoma and its lymph node metastases: relationship with pathological features and survival. Hum Pathol. 2003;34(12):1276–1282.
Sutherland RL, Musgrove EA. Cyclins and breast cancer. J Mammary Gland Biol Neoplasia. 2004;9(1):95–104.
Bondi J, Bukholm G, Nesland JM, Bukholm IR. Expression of non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 in relation to patient outcome in human colon adenocarcinomas. APMIS. 2004;112(1):49–56.
Kim JK, Diehl JA. Nuclear cyclin D1: an oncogenic driver in human cancer. J Cell Physiol. 2009;220(2):292–296.
Kroemer G. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat Med. 1997;3(6):614–620.
Holcik M, Gibson H, Korneluk RG. XIAP: apoptotic brake and promising therapeutic target. Apoptosis. 2001;6(4):253–261.
Dai M, Al-Odaini AA, Fils-Aime N, et al. Cyclin D1 cooperates with p21 to regulate TGFbeta-mediated breast cancer cell migration and tumor local invasion. Breast Cancer Res. 2013;15(3):R49.
Smerage JB, Budd GT, Doyle GV, et al. Monitoring apoptosis and Bcl-2 on circulating tumor cells in patients with metastatic breast cancer. Mol Oncol. 2013;7(3):680–692.


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24M Selected for $3.2 Million Federal Funding from ARPA-E to Develop More Efficient EV Batteries
by Casper Benedict
in Battery
24M announced today that it has been awarded $3.2 million in funding from the U.S. Department of Energy's Advanced Research Projects Agency-Energy (ARPA-E) as part of the EVs4ALL program. The program aims to develop more affordable, convenient, efficient, and resilient electric vehicle (EV) batteries.
"We are pleased to be chosen for this initiative and help strengthen the domestic supply chain for advanced batteries that power electric vehicles," said Naoki Ota, president and CEO of 24M. "The demand for lower-cost, higher-capacity batteries is greater than ever before. The current processes to manufacture lithium-ion batteries are approaching performance and cost limits and require an innovative manufacturing platform that improves performance while reducing costs."
In partnership with the Massachusetts Institute of Technology (MIT) and Carnegie Mellon University (CMU), 24M will use its versatile SemiSolid manufacturing platform to develop low-cost, fast-charging sodium metal batteries with good low-temperature performance for EVs.
"As the U.S. Department of Energy looks to expand domestic adoption of electric vehicles, sodium metal batteries can play an important role in ensuring low costs for all consumers," said Dr. JunZheng Chen, director of advanced R&D at 24M. "This funding will help us develop, manufacture and deliver these batteries at scale."
The 24M cell design will incorporate an ultra-thick SemiSolid cathode made of advanced cobalt-free, nickel-free sodium cathode active material, an advanced wide-temperature, fast-charging electrolyte developed using machine learning and automated high-throughput screening technology, and a sodium super ionic conductor.
#24M has received $3.2 million in funding from @ENERGY for @ARPAE's EVs4ALL program. As part of the new initiative, we will use the versatile SemiSolid manufacturing platform to develop low-cost, fast-charging sodium metal batteries. https://t.co/MvtmPJHvDU pic.twitter.com/IHYoTc1A5W
— 24M Technologies (@24M_Tech) January 23, 2023
Tags: 24Mbatterieselectric vehicleelectric vehiclesfundingLithium-ionsodiumsupply chaintechnology
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