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In the 1970s Joe Haldeman approached more than a dozen different publishers before he finally found one interested in The Forever War. The book went on to win both the Hugo and Nebula Awards, although a large chunk of the story had been cut out before it saw publication. Now Haldeman and Avon Books have released the definitive version of The Forever War, published for the first time as Haldeman originally intended. The book tells the timeless story of war, in this case a conflict between humanity and the alien Taurans. Humans first bumped heads with the Taurans when we began using collapsars to travel the stars. Although the collapsars provide nearly instantaneous travel across vast distances, the relativistic speeds associated with the process means that time passes slower for those aboard ship. For William Mandella, a physics student drafted as a soldier, that means more than 27 years will have passed between his first encounter with the Taurans and his homecoming, though he himself will have aged only a year. When Mandella finds that he can't adjust to Earth after being gone so long from home, he reenlists, only to find himself shuttled endlessly from battle to battle as the centuries pass. --Craig E. Engler --This text refers to an out of print or unavailable edition of this title.
"To say that The Forever War is the best science fiction war novel ever written is to damn it with faint praise. It is, for all its techno-extrapolative brilliance, as fine and woundingly genuine a war story as any I've read." ―William Gibson, author of Neuromancer, Spook Country
"There are a handful of moments when an American science fiction novel abruptly and seemingly effortlessly satisfied every possible expectation conveyed not only by the genre's ambitions, but of those of the whole literary landscape with which it was contemporary: Sturgeon's More Than Human, Dick's The Man In The High Castle, LeGuin's Dispossessed, Gibson's Neuromancer. The Forever War is one such book, and like those others still carries with it that air of recognition and possibility." ―Jonathan Lethem, author of Gun With Occcasional Music, Fortress of Solitude
"Perhaps the most important war novel written since Vietnam . . . Haldeman, a veteran, is a flat-out visionary . . . and protagonist William Mandella's attempt to survive and remain human in the face of an absurd almost endless war is harrowing hilarious heartbreaking and true . . . like all the best works of literature THE FOREVER WAR takes you apart and then, before you can turn that last page, puts you back together: better, wiser, more human. Simply extraordinary." ―Junot Diaz, Pulitzer Prize winning author of The Brief and Wondrous Life of Oscar Wao
"If there was a Fort Knox for Science Fiction writers, we'd have to lock Joe Haldeman up." ―Stephen King, author of The Shining, The Dead Zone, The Stand
"The Forever War is not just a great Science Fiction novel, it's a great Vietnam war novel - and a great war novel, without qualification- that is also Science Fiction. A classic to grace either genre." ―James Sallis, author of The Long Legged Fly, Drive, Cripple Creek
"FOREVER WAR is brilliant--one of the most influential war novels of our time. That it happens to be set in the future only broadens and enhances its message." ―Greg Bear, author of Moving Mars, Eon, The Forge of God
"A parable whose lessons are needful learning once more." ―John Scalzi, author of Old Man's War, The Ghost Brigades, Zoe's Tale
"I first read this twenty years ago and have never forgotten the wonder and fury it kindled at the time. Anyone who talks about the glory of war has obviously never read it. A beautifully detailed and intensely personal account of a conflict which lasts for over a thousand years, as told by one grunt who lives through it all. Only a writer as skillfull and knowledgeable as Haldeman could use war's dark glamour to lure the reader in and then deplou the sam fascination to show just what kind of effect this orchestrated barbarism can have on the human soul." ―Peter F. Hamilton, author of Pandora's Star, Judas Unchained, The Dreaming Void
"In a literature of ideas, The Forever War is a titan: a book filled with mind-bending ideas about relatavistic time-distortion and world-shaking ideas about the futility of war. In today's world, where we think declaring war on abstract nouns like TERROR is a winning strategy, we need THE FOREVER WAR." ―Cory Doctorow, author of Down and Out in the Magic Kingdom, Little Brother X
"It is to the Vietnam War what Catch-22 was to World War II, the definitive, bleakly comic satire." ―Thomas M. Disch, author of Camp Concentration, 334
"The Forever War does what the very best science fiction does. It deals with extremes both societal and teleological; it places a frame around humankind's place in the universe to show us what is outside the frame; and it functions simultaneously at the literal and metaphorical level. Inarguably one of the genre's great novels, it is also among the finest novels ever written about war." ―James Sallis, author of The Long Legged Fly, Drive, Cripple CreekSee all Editorial Reviews
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This book is fantastic. It's more fascinating than enthralling, although it has plenty of excitement as well. Read morePublished 3 days ago by Gabroll
Great minimalistic narrative, fast pace, and super-realistic feel in space adventure. Very impressive and a great read.Published 5 days ago by Daniel Farr
Excellent commentary on the futility of war. Would give 5 stars except for the unlikely and overly sappy ending.Published 5 days ago by Mike Colandro
Read the story soon after it was first published in 1974, and thought it was great. However, on a current re-reading, it doesn't have quite the impact. Read morePublished 6 days ago by samfromscottsdale
An interesting look into how war might occur across a galaxy taking into account Einstein's theory of relativity. Read morePublished 8 days ago by Mike Duffy


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Carlos Osorio, Associated Press
DETROIT — Vice President Joe Biden, an avowed "car junkie," said Thursday the U.S. auto industry's resurgence since the 2009 federal bailout provides a strong basis for a Motor City recovery.
Biden delivered a speech and toured the North American International Auto Show in Detroit, which showcases vehicles and hosts visitors from around the world. He promised an "American century in manufacturing" after the bankruptcies and near-industry meltdown about five years ago.
"We bet on American ingenuity, we bet on you and we won," Biden told the audience, flanked by a half-dozen General Motors, Ford and Chrysler vehicles.
All three Detroit automakers have made billions in the recovery following the Great Recession. Ford expects to post an $8.5 billion profit before taxes for 2013, while GM made $4.8 billion pretax through the first nine months. Chrysler, the smallest and least-profitable of the three, made $1.4 billion pretax through September.
All have rolled out strong new cars and trucks to catch the rise in auto sales from a low of 10.4 million in 2009 to 15.6 million last year.
Biden, the son of a car dealer and proud owner of a 1967 Chevrolet Corvette Stingray, said the industry revival also means good things for Detroit, which is undergoing the nation's largest municipal bankruptcy — four years after General Motors and Chrysler emerged from their own restructurings.
He said the automakers success comes in large part from significant hiring, adding that they aren't "just jobs, these are middle-class jobs — jobs upon which you can raise a family." There's also the psychological boost to a region whose primary industry is regaining market share, making award-winning vehicles and hosting an auto show that draws about 800,000 people.
"Just like the automobile industry came back, Detroit is going to come back," Biden said. "It's not only an important city but it's an iconic city. It symbolizes the manufacturing might of the United States of America."
Biden was introduced by new Detroit Mayor Mike Duggan, with whom the vice president dined at an Italian restaurant the evening before. The White House hasn't promised a Motor City bailout, but in September it pledged more than $100 million in grants to help Detroit tear down vacant buildings and spur job growth.
When the speech was over, Biden toured the auto show floor, hopping in cars and trucks and chatting with auto industry executives like new GM Chief Executive Mary Barra. He caressed the back of a shiny new Ford F-150 and told reporters, "I feel like a kid in a candy shop," and "I wanna take a couple of these home."
Follow Jeff Karoub on Twitter at https://twitter.com/jeffkaroub
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subset: commoncrawl


text:
Diversified Telecommunication Services
Company Overview of Liberty Global Europe, Inc.
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Member of Supervisory Board, Senior Vice President of Business of United, Senior Vice President of Legal Affairs of United and Secretary of United
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text:
Cimarosa Harmony Accommodation & Rooms
- Free WiFi
- Airport within 5 mi/8 km: Florence (FLR-Peretola)
Main amenities
- 5 guestrooms
- Breakfast available
- Self parking
- Train station pick-up service
- Air conditioning
- Multilingual staff
- Luggage storage
- Tour/ticket assistance
- Bike rental
What's around
- In Santa Maria Novella
- Cathedral of Santa Maria del Fiore (1.3 mi / 2.1 km)
- Ponte Vecchio (1.4 mi / 2.3 km)
- Santa Maria Novella Basilica and Museum (0.9 mi / 1.4 km)
- Battistero di San Giovanni (1.2 mi / 2 km)
I would never recommend this accommodation to anyone. We had a confirmation but…
A nice place to stay with reasonable price, I like the small "kitchen" with coffee vender…
Enter dates to check prices
Hotel Info: .from ZAR 953
- Double Room
- Triple Room
- Double Room (small)
- Quadruple Room
- Family Room, 1 Bedroom
- Single Room
Recommended hotels
At a glance
Key facts
Hotel size
- This hotel has 5 rooms
- This hotel is arranged over 1 floor
- Check-in time noon-7 PM
- Check-out time is 10:30 AM
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
Travelling with others
- No cribs (infant beds)
- No pets or service animals allowed
Extra people
- Rollaway beds available, charges may apply*
- Free WiFi in public areas
- Free WiFi in rooms
- Train station pickup *
- Self parking *
Nearby One Star Florence hotels
In the hotel
- Continental breakfast daily (surcharge)
- Bicycle rentals on site
- Hiking/biking trails nearby
- Tours/ticket assistance
- Luggage storage
- Number of buildings/towers - 1
- Year Built 2004
- Accessible bathroom
In the room
- Air conditioning
- Minibar
- Private bathroom
- Shower only
- Bidet
- Hair dryer
- Free WiFi
Top Florence hotels
Recently reviewed hotels in Florence
- Hotel Pitti Palace al Ponte VecchioFrom
"loved location and really pleasant stay, was not to happy with parking arrangement - car keys left in car for underground parking attendant to move around and they scratched our…"Aug 10, 2015
- Country Hotel Borgo Sant'IppolitoFrom
"Good value for money!"Jul 22, 2015
- Hotel CosmopolitanFrom
- San Gallo Palace HotelFrom
"Clean, very friendly staff. Only there one night. Yes I'd go back"Jul 9, 2015
Nearby hotels
Cimarosa Harmony Accommodation & Rooms's small print
Cash transactions at this property cannot exceed EUR 999.99, due to national regulations. For further details, please contact the property using information in the booking confirmation.
For transfers, guests must contact the property 72 hours prior to arrival at the number on the booking confirmation.
Mandatory fees
You'll be asked to pay the following charges at check in or check out:
- A tax is imposed by the city: EUR 2.50 per person, per night, up to 7 nights. This tax does not apply to children under 12 years of age.
Optional extras
Late check-in after 7 PM can be arranged for an extra charge
Self parking costs EUR 20 per day
Rollaway beds are available for EUR 25 per night
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


text:
Shilo Inn Suites - Newberg
No prices found through our partners. Please contact the business directly or check some of our recommended alternatives.
How has this hotel rated in the past?
- Continental Breakfast
- Room service
- Swimming pool
- Free High-Speed Internet
- Wheelchair accessibility
- Business Services
Travelers also recommend:
- More recommendations
TravelPod Member ReviewsShilo Inn Suites - Newberg
Gut ausgestattete Zimmer, aber ein sehr sehr hellhöriges Motel. Nur bedingt empfehlenswert.
This review is the subjective opinion of a TravelPod member and not of TravelPod.com.
TripAdvisor Reviews Shilo Inn Suites - Newberg
Travel Blogs from Newberg
Clackamas - Willamette Valley - Newberg
Als Kontrastprogramm zur tolle Natur gestern, gehen wir heute erstmal shoppen! In Oregon gibt es keine Sales Tax, das muss doch in den Woodburn Premium Outlets ausgenutzt werden, oder? Stunden sp�ter tragen wir immerhin eine (!) einzige (!) Einkaufst�te zum Auto, das sollte heute wohl nicht sein. Im Vergleich zu anderen USA Trips eine wirklich …
July Salem area and Stuart Island Washington
... for an 11 year old cat. I made several trips to the car getting things I needed but finally settled down and read some, later fixing potato soup for dinner. Around 11 the electric storm started and was a big and long lightening show. Very little thunder so was distant from our location. Later it rained, not a lot, but enough to wet everything thoroughly. Rudy slept near my head most of the night and then beside me in the morning hours. He just wants to be petted ALL the ...
Day 5: Explore Portland OR
... A few times during the movie freaked me out. After all, it was a 3D movie. They made sure to make it look like the dinosaur had seen you and might be coming after you. The last scene had a dinosaur scratching the screen. Scared me silly! It was quite an interesting movie. The restaurant was called Brasserie Monmarte. Yum! I had a perfectly done steak, and Greg had a perfectly done lamb. One of my best meals ever, along with food we had at the ...
Day 22 - Riding the Rails
... Amtrak train before, for meals they seat you at tables of 4 so you always eat with someone new. This always makes for good conversation. This might surprise you all but the steak I had for dinner was really good- kind of surprising but this is the second time I had steak on Amtrak and it was good.
The rocking of the rails lulls you to sleep like swaying in a breeze while lying on a ...
Day 21 - Centralia to Mount Rainier to Portland OR
... Dantes, for free, and watch a burlesque show, magic show, and some person in a straight jacket hanging upside down. The place was packed and had walking stages overhead where woman would dance. We came to find this place the next day and found their logo is "keeping Portland weird". The rest of the night was left with the whiskey.
Tomorrow we stay in Portland, OR and see the city we once wanted to live in.


text:
DENVER — Boosted by a strong performance in the first presidential debate in Denver, Republican Mitt Romney edged closer to President Barack Obama in a Colorado poll released Sunday.
Obama clung to the lead in a poll commissioned by the University of Denver, which hosted the debate. The poll showed Obama leading Romney among likely voters, 47 percent to 43 percent. The poll had a 4-point margin of error.
An earlier poll, released Sept. 20, showed a slightly wider lead for the president, 50 percent to 45 percent among likely voters. That poll had a margin of error of plus or minus 3 points and was conducted by NBC News/Wall Street Journal/Marist.
In the DU poll, more than 80 percent of the likely voters said they watched the first debate, and they overwhelmingly thought Romney did better. Sixty-eight percent said Romney did better than Obama. Two more debates are planned.
The poll showed a tossup for the marijuana legalization question. Fifty percent planned to vote for legalizing pot, 40 percent planned to vote against it, and 10 percent weren't sure.
Coloradans were more united on the question of same-sex couples. Seventy-three percent supported legal recognition of same-sex relationships, either marriage or civil unions. Earlier this year, Republicans in the state Legislature blocked a Democratic-sponsored civil unions measure.
The DU telephone survey included 604 likely voters. It was conducted Oct. 4-5 by Selzer & Co. of Des Moines, Iowa.
On immigration, Coloradans favored allowing illegal immigrants to stay, keep their jobs and eventually apply for legal status.
Sixty-three percent said they preferred that position on immigration, with 31 percent saying illegal immigrants should be deported to their home country. Asked about illegal immigrants who came here as children, the margin widened slightly, with 68 percent favoring allowing those illegal immigrants to stay and 24 percent opposing the new policy allowing illegal immigrants brought as children to obtain work permits and not face deportation.
Coloradans were more divided on the new health care law. Thirty-eight percent said the law should be repealed. Thirty-four percent said it contains good provisions but may need adjustments. And 16 percent said the law is good and should remain as is.
Asked to give their impressions about politicians from both parties, Coloradans gave higher marks to Democratic Gov. John Hickenlooper than to either presidential candidate. Sixty-eight percent said they had "very favorable" or "mostly favorable" feelings about the governor.
Find Kristen Wyatt at http://www.twitter.com/APkristenwyatt
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text:
Are you Dung-Tsa Chen?Claim your profile
Publications (63)265.33 Total impact
Article: Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous Neoplasms of the Pancreas[Show abstract] [Hide abstract]
ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide, partly because methods are lacking to detect disease at an early, operable stage. Noninvasive PDAC precursors called intraductal papillary mucinous neoplasms (IPMN) exist, and strategies are needed to aid in their proper diagnosis and management. Data support the importance of miRNAs in the progression of IPMNs to malignancy, and we hypothesized that miRNAs may be shed from IPMN tissues and detected in blood. Our primary goals were to measure the abundance of miRNAs in archived preoperative plasma from individuals with pathologically confirmed IPMNs and healthy controls and discover plasma miRNAs that distinguish between IPMN patients and controls and between "malignant" and "benign" IPMNs. Using novel nCounter technology to evaluate 800 miRNAs, we showed that a 30-miRNA signature distinguished 42 IPMN cases from 24 controls [area underneath the curve (AUC) = 74.4; 95% confidence interval (CI), 62.3-86.5, P = 0.002]. The signature contained novel miRNAs and miRNAs previously implicated in pancreatic carcinogenesis that had 2- to 4-fold higher expression in cases than controls. We also generated a 5-miRNA signature that discriminated between 21 malignant (high-grade dysplasia and invasive carcinoma) and 21 benign (low- and moderate-grade dysplasia) IPMNs (AUC = 73.2; 95% CI, 57.6-88.9, P = 0.005), and showed that paired plasma and tissue samples from patients with IPMNs can have distinct miRNA expression profiles. This study suggests feasibility of using new cost-effective technology to develop a miRNA-based blood test to aid in the preoperative identification of malignant IPMNs that warrant resection while sparing individuals with benign IPMNs the morbidity associated with overtreatment. Cancer Prev Res; 8(9); 1-9. ©2015 AACR. ©2015 American Association for Cancer Research.Cancer Prevention Research 08/2015; 8(9). DOI:10.1158/1940-6207.CAPR-15-0094 · 4.44 Impact Factor
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ABSTRACT: The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC) are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment decision-making process. To derive a prognostic gene signature for patients with early stage PDAC, a PDAC cohort from Moffitt Cancer Center (n = 63) was used with overall survival (OS) as the primary endpoint. This was further evaluated using an independent microarray cohort dataset (Stratford et al: n = 102). Technical validation was performed by NanoString platform. A prognostic 15-gene signature was developed and showed a statistically significant association with OS in the Moffitt cohort (hazard ratio [HR] = 3.26; p<0.001) and Stratford et al cohort (HR = 2.07; p = 0.02), and was independent of other prognostic variables. Moreover, integration of the signature with the TNM staging system improved risk prediction (p<0.01 in both cohorts). In addition, NanoString validation showed that the signature was robust with a high degree of reproducibility and the association with OS remained significant in the two cohorts. The gene signature could be a potential prognostic tool to allow risk-adapted stratification of PDAC patients into personalized treatment protocols; possibly improving the currently poor clinical outcomes of these patients.PLoS ONE 08/2015; 10(8). DOI:10.1371/journal.pone.0133562 · 3.23 Impact Factor
Article: EGR-1/Bax Pathway Plays a Role in Vitamin E δ-Tocotrienol-induced Apoptosis in Pancreatic Cancer Cells[Show abstract] [Hide abstract]
ABSTRACT: The anticancer activity of δ-tocotrienol, a bioactive vitamin E present in whole grain cereals, annatto beans and palm fruit, is strongly dependent on its effect on the induction of apoptosis. δ-Tocotrienol-induced apoptosis is associated with consistent induction in the expression of the proapoptotic protein Bcl-2-associated X protein (Bax). The molecular mechanism by which δ-tocotrienol regulates Bax expression is unknown. We carried out a DNA microarray study that identified δ-tocotrienol induction of the zinc finger transcription factor EGR-1 in pancreatic cancer cells. Here, we provide evidence linking δ-tocotrienol-induced apoptosis in pancreatic cancer cells to EGR-1 regulation of Bax expression. Forced expression of EGR-1 induces Bax expression and apoptosis in pancreatic cancer cells. In contrast, knockdown of δ-tocotrienol-induced EGR-1 by small interfering RNA attenuated δ-tocotrienol-induced Bax expression and reduced δ-tocotrienol-induced apoptosis. Further analyses showed that de novo protein synthesis was not required for δ-tocotrienol-induced EGR-1 expression, suggesting a direct effect of δ-tocotrienol on EGR-1 expression. Furthermore, a chromatin immunoprecipitation assay demonstrated that EGR-1 binds to the Bax gene promoter. Finally, δ-tocotrienol treatment induced Bax expression and activated EGR-1 in the pancreatic neoplastic cells of the PDX-Cre Kras genetically engineered model of pancreatic cancer. Our study provides the first evidence for EGR-1 as a direct target of vitamin E δ-tocotrienol, suggesting that EGR-1 may act as a proapoptotic factor in pancreatic cancer cells via induction of Bax. Copyright © 2015. Published by Elsevier Inc.The Journal of nutritional biochemistry 04/2015; 26(8). DOI:10.1016/j.jnutbio.2015.02.008 · 3.79 Impact Factor
Article: A Genome-Wide Investigation of MicroRNA Expression Identifies Biologically-Meaningful MicroRNAs That Distinguish between High-Risk and Low-Risk Intraductal Papillary Mucinous Neoplasms of the Pancreas[Show abstract] [Hide abstract]
ABSTRACT: Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursors. Differentiating between high-risk IPMNs that warrant surgical resection and low-risk IPMNs that can be monitored is a significant clinical problem, and we sought to discover a panel of mi(cro)RNAs that accurately classify IPMN risk status. In a discovery phase, genome-wide miRNA expression profiling was performed on 28 surgically-resected, pathologically-confirmed IPMNs (19 high-risk, 9 low-risk) using Taqman MicroRNA Arrays. A validation phase was performed in 21 independent IPMNs (13 high-risk, 8 low-risk). We also explored associations between miRNA expression level and various clinical and pathological factors and examined genes and pathways regulated by the identified miRNAs by integrating data from bioinformatic analyses and microarray analysis of miRNA gene targets. Six miRNAs (miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-130a) were down-regulated in high-risk versus low-risk IPMNs and distinguished between groups (P<10-3, area underneath the curve (AUC) = 87%). The same trend was observed in the validation phase (AUC = 74%). Low miR-99b expression was associated with main pancreatic duct involvement (P = 0.021), and serum albumin levels were positively correlated with miR-99a (r = 0.52, P = 0.004) and miR-100 expression (r = 0.49, P = 0.008). Literature, validated miRNA:target gene interactions, and pathway enrichment analysis supported the candidate miRNAs as tumor suppressors and regulators of PDAC development. Microarray analysis revealed that oncogenic targets of miR-130a (ATG2B, MEOX2), miR-342-3p (DNMT1), and miR-126 (IRS-1) were up-regulated in high- versus low-risk IPMNs (P<0.10). This pilot study highlights miRNAs that may aid in preoperative risk stratification of IPMNs and provides novel insights into miRNA-mediated progression to pancreatic malignancy. The miRNAs identified here and in other recent investigations warrant evaluation in biofluids in a well-powered prospective cohort of individuals newly-diagnosed with IPMNs and other pancreatic cysts and those at increased genetic risk for these lesions.PLoS ONE 01/2015; 10(1):e0116869. DOI:10.1371/journal.pone.0116869 · 3.23 Impact Factor
Article: Abstract 914: Development of a prognostic and predictive E2F signature in formalin-fixed, paraffin-embedded early-stage non-small cell lung cancer samplesCancer Research 10/2014; 74(19 Supplement):914-914. DOI:10.1158/1538-7445.AM2014-914 · 9.33 Impact Factor
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ABSTRACT: Objectives: We investigated whether annexin A8 (A-A8), a Ca-binding protein overexpressed in pancreatic cancer, plays a role in cell growth and migration and investigated its association with pancreatic cancer prognosis. Methods: Clinicopathological features and associations between increased A-A8 expression (determined by immunohistochemistry) and histologic grade were studied in a tissue microarray of 90 patients with resected stage I/II pancreatic cancer. We investigated A-A8's effect on cell migration, proliferation, and colony formation in 2 pancreatic cancer cells (BXPC-3 and Panc-1). Statistical analyses included Fisher exact test, t test, analysis of variance, and survival analysis. Results: Western blot showed increased A-A8 expression in human pancreatic cancer cells, with A-A8 knockdown in BXPC-3 and Panc-1 cells demonstrating decreased cell viability (P = 0.017 and P = 0.001), migration (2.5 vs 0.9 mm and 1.6 vs 1 mm at 96 hours; P = 0.048 and P = 0.004), and colony formation (approximately 75% and 40% from scramble; P ≤ 0.01), respectively. In our tissue microarray, A-A8 expression increased 5.9-fold (r = 0.31; P = 0.019) from low- to high-grade tumors, correlating with tumor grade (r = 0.23; P = 0.027). In addition, high A-A8 expression was associated with a decreased 5-year survival (P = 0.042). Conclusions: Our study is the first showing that increased A-A8 expression is associated with poor prognosis in early-stage pancreatic cancer, thus supporting its further investigation as a future therapeutic target and prognostic marker.Pancreas 09/2014; 44(1). DOI:10.1097/MPA.0000000000000218 · 2.96 Impact Factor
Article: Senescence-Associated-Gene signature identifies genes linked to age, prognosis, and progression of human gliomas.[Show abstract] [Hide abstract]
ABSTRACT: Background: Senescence-associated genes (SAGs) are responsible for the senescence-associated secretory phenotype, linked in turn to cellular aging, the aging brain, and the pathogenesis of cancer. Objective: We hypothesized that senescence-associated genes are overexpressed in older patients, in higher grades of glioma, and portend a poor prognosis. Methods: Forty-seven gliomas were arrayed on a custom version of the Affymetrix HG-U133 + 2.0 GeneChip, for expression of fo(u)rteen senescence-associated genes: CCL2, CCL7, CDKN1A, COPG, CSF2RB, CXCL1, ICAM-1, IGFBP-3, IL-6, IL-8, SAA4, TNFRSF-11B, TNFSF-11 and TP53. A combined "senescence score" was generated using principal component analysis to measure the combined effect of the senescence-associated gene signature. Results: An elevated senescence score correlated with older age (r = 0.37; P = .01) as well as a higher degree of malignancy, as determined by WHO, histological grade (r = 0.49; P < .001). There was a mild association with poor prognosis (P = .06). Gliosarcomas showed the highest scores. Six genes independently correlated with either age (IL-6, TNFRSF-11B, IGFBP-3, SAA4, and COPG), prognosis (IL-6, SAA4), or the grade of the glioma (IL-6, IL-8, ICAM-1, IGFBP-3, and COPG). Conclusion: We report: 1) a novel molecular signature in human gliomas, based on cellular senescence, translating the concept of SAG to human cancer, 2) the senescence signature is composed of genes central to the pathogenesis of gliomas, defining a novel, aggressive subtype of glioma; and 3) these genes provide prognostic biomarkers, as well as targets, for drug discovery and immunotherapy.Journal of Geriatric Oncology 09/2014; 5(4). DOI:10.1016/j.jgo.2014.08.003 · 1.86 Impact Factor
Article: Su2100 Increased Expression of the GLUT-1 Gene Is Associated With a Poorer Prognosis in Pancreatic CancerGastroenterology 05/2014; 146(5):S-1055-S-1056. DOI:10.1016/S0016-5085(14)63851-8 · 16.72 Impact Factor
Article: A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction[Show abstract] [Hide abstract]
ABSTRACT: Immune dysregulation is a mechanism contributing to ineffective hematopoiesis in a subset of myelodysplastic syndrome patients. We report the first US multicenter non-randomized, Phase 2 trial examining the efficacy of rabbit(r)-anti-thymocyte globulin using 2.5 mg/kg/day administered daily for 4 doses. The primary endpoint was hematological response; secondary endpoints included duration of response, time to response, time to progression, and tolerance. Nine (33%;95% confidence interval=17%-54%) of the 27 patients treated experienced durable hematologic improvement in an intent-to-treat analysis with a median time to response and median response duration of 75 and 245 days, respectively. While younger age is the most significant factor favoring equine(e)-anti-thymocyte globulin response, treatment outcome on this study was independent of age (p=0.499). A shorter duration between diagnosis and treatment showed a positive trend(p=0.18), but International Prognostic Scoring System score(p=0.150), karyotype(p=0.319), and age-adjusted bone marrow cellularity(p=0.369) were not associated with response classification. Since activated T-lymphocytes are the primary cellular target of anti-thymocyte globulin, a T-cell expression profiling was conducted in a cohort of 38 patients consisting of rabbit and equine-antithymocyte globulin-treated patients. A model containing disease duration, CD8 terminal memory T-cells and T-cell proliferation-associated-antigen expression predicted response with the greatest accuracy using a leave-one-out cross validation approach. This profile categorized patients independent of other covariates, including treatment type and age using a leave-one-out-cross-validation approach (75.7%). Therefore, rabbit-anti-thymocyte globulin has hematologic remitting activity in myelodysplastic syndrome and a T-cell activation profile has potential utility classifying those who are more likely to respond (NCT00466843 clinicaltrial.gov).Haematologica 01/2014; 99(7). DOI:10.3324/haematol.2012.083345 · 5.81 Impact Factor
Article: Vitamin E δ-tocotrienol prolongs survival in the LSL-Kras G12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) transgenic mouse model of pancreatic cancer[Show abstract] [Hide abstract]
ABSTRACT: Previous work has shown that vitamin E δ-tocotrienol (VEDT) prolongs survival and delays progression of pancreatic cancer in the LSL-KrasG12D/+;Pdx-1-Cre mouse model of pancreatic cancer. However, the effect of VEDT alone or in combination with gemcitabine in the more aggressive LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) mouse model is unknown. Here, we studied the effects of VEDT and the combination of VEDT and gemcitabine in the KPC mice. KPC mice were randomized into 4 groups: 1) vehicle (olive oil, 1.0 mL/kg PO twice/day and PBS 1.0 mL/kg IP twice/week), 2) gemcitabine (100 mg/kg IP twice/week), 3) VEDT (200 mg/kg PO twice/day), and 4) gemcitabine + VEDT. Mice received treatment until they displayed symptoms of impending death from pancreatic cancer, at which point animals were euthanized. At 16 weeks, survival was 10% in the vehicle group, 30% in the gemcitabine group, 70% in the VEDT group (P<0.01), and 90% in the VEDT combined with gemcitabine group (P<0.05). VEDT alone and combined with gemcitabine resulted in reversal of epithelial-to-mesenchymal transition in tumors. Biomarkers of apoptosis (plasma CK18), PARP1 cleavage, and Bax expression were more greatly induced in tumors subjected to combined treatment versus individual treatment. Combined treatment induced cell cycle inhibitors (p27Kip1 and p21Cip1) and inhibited VEGF, vascularity (CD31), and oncogenic signaling (pAKT, pMEK, and pERK) greater than individual drugs. No significant differences in body weight gain between drug treatment and control mice were observed. These results strongly support further investigation of VEDT alone and in combination with gemcitabine for pancreatic cancer prevention and treatment.Cancer Prevention Research 08/2013; 6(10). DOI:10.1158/1940-6207.CAPR-13-0157 · 4.44 Impact Factor
Article: Cytoplasmic Clusterin Expression Correlates With Pancreatic Neuroendocrine Tumor Size and Pathological Stage.[Show abstract] [Hide abstract]
ABSTRACT: Objectives: Cytoplasmic clusterin (Clusterin), a ubiquitous multifunctional secretory sulfated glycoprotein, plays a role in apoptosis and is reportedly overexpressed in a variety of tumors. The role of Clusterin in pancreatic neuroendocrine tumors (PNETs) has not been investigated. In this study, Clusterin expression was evaluated in a subset of PNETs, and the results were correlated with the clinical-pathological features of the tumors. Methods: Fifty-nine surgical cases were used to evaluate the immunohistochemical expression of Clusterin in PNETs. Using the avidin-biotin complex method, tissue sections from each case were stained with a rabbit anticlusterin antibody (Abcam, Cambridge, Mass). The immunohistochemical reactions were qualitatively and semiquantitatively evaluated by 2 pathologists. Results: Strong Clusterin reactivity was identified in 36 (61%) of 59 PNETs. In 23 (39%) of 59 cases, the Clusterin score was 3 or less. Clusterin expression scores significantly associated with tumor size (P = 0.03) and with tumor stage (P = 0.02). The immunohistochemical score index did not correlate with tumor grade (P = 0.15). Conclusions: We report the expression of Clusterin in PNETs. The correlation of Clusterin with tumor size and stage suggests involvement of this molecule in pancreatic neuroendocrine tumor progression. Clusterin may represent a new target of therapy for PNETs.Pancreas 06/2013; 42(6). DOI:10.1097/MPA.0b013e318293734b · 2.96 Impact Factor
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ABSTRACT: NF-κB is constitutively activated in many cancer types and is a potential key mediator of tumor-associated inflammation, tumor growth, and metastasis. We investigated the role of cancer cell NF-κB activity in T cell-mediated antitumor responses. In tumors rendered immunogenic by model antigen expression or following administration of antitumor vaccines, we found that high NF-κB activity leads to tumor rejection and/or growth suppression in mice. Using a global RNA expression microarray, we demonstrated that NF-κB enhanced expression of several T cell chemokines, including Ccl2, and decreased CCL2 expression was associated with enhanced tumor growth in a mouse lung cancer model. To investigate NF-κB function in human lung tumors, we identified a gene expression signature in human lung adenocarcinoma cell lines that was associated with NF-κB activity level. In patient tumor samples, overall lung tumor NF-κB activity was strongly associated with T cell infiltration but not with cancer cell proliferation. These results therefore indicate that NF-κB activity mediates immune surveillance and promotes antitumor T cell responses in both murine and human lung cancer.The Journal of clinical investigation 05/2013; 123(6). DOI:10.1172/JCI67250 · 13.22 Impact Factor
Article: Iclozan C, Antonia S, Chiappori A, Chen DT, Gabrilovich DTherapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer. Cancer Immunol Immunother 62: 909-918[Show abstract] [Hide abstract]
ABSTRACT: Myeloid-derived suppressor cells (MDSC) are one of the major factors limiting the efficacy of immune therapy. In a clinical trial of patients with extensive stage small cell lung cancer (SCLC), we tested the possibility that targeting MDSC can improve the induction of immune responses by a cancer vaccine. Forty-one patients with extensive stage SCLC were randomized into three arms: arm A-control, arm B-vaccination with dendritic cells transduced with wild-type p53, and arm C-vaccination in combination with MDSC targeted therapy with all-trans-retinoic acid (ATRA). Interim results of the ongoing clinical trial are presented. Pre-treatment levels of MDSC populations in patients from all three arms were similar. Vaccine alone did not affect the proportion of MDSC, whereas in patients treated with ATRA, the MDSC decreased more than twofold (p = 0.02). Before the start of treatment, no patients had detectable p53-specific responses in IFN-γ ELISPOT. Sequential measurements did not show positive p53 responses in any of the 14 patients from arm A. After immunization, only 3 out of 15 patients (20 %) from arm B developed a p53-specific response (p = 0.22). In contrast, in arm C, 5 out of 12 patients (41.7 %) had detectable p53 responses (p = 0.012). The proportion of granzyme B-positive CD8(+) T cells was increased only in patients from arm C but not in arm B. Depletion of MDSC substantially improved the immune response to vaccination, suggesting that this approach can be used to enhance the effect of immune interventions in cancer.Cancer Immunology and Immunotherapy 04/2013; 62(5). DOI:10.1007/s00262-013-1396-8 · 3.94 Impact Factor
Article: SNP-SNP Interaction Network in Angiogenesis Genes Associated with Prostate Cancer Aggressiveness[Show abstract] [Hide abstract]
ABSTRACT: Angiogenesis has been shown to be associated with prostate cancer development. The majority of prostate cancer studies focused on individual single nucleotide polymorphisms (SNPs) while SNP-SNP interactions are suggested having a great impact on unveiling the underlying mechanism of complex disease. Using 1,151 prostate cancer patients in the Cancer Genetic Markers of Susceptibility (CGEMS) dataset, 2,651 SNPs in the angiogenesis genes associated with prostate cancer aggressiveness were evaluated. SNP-SNP interactions were primarily assessed using the two-stage Random Forests plus Multivariate Adaptive Regression Splines (TRM) approach in the CGEMS group, and were then re-evaluated in the Moffitt group with 1,040 patients. For the identified gene pairs, cross-evaluation was applied to evaluate SNP interactions in both study groups. Five SNP-SNP interactions in three gene pairs (MMP16+ ROBO1, MMP16+ CSF1, and MMP16+ EGFR) were identified to be associated with aggressive prostate cancer in both groups. Three pairs of SNPs (rs1477908+ rs1387665, rs1467251+ rs7625555, and rs1824717+ rs7625555) were in MMP16 and ROBO1, one pair (rs2176771+ rs333970) in MMP16 and CSF1, and one pair (rs1401862+ rs6964705) in MMP16 and EGFR. The results suggest that MMP16 may play an important role in prostate cancer aggressiveness. By integrating our novel findings and available biomedical literature, a hypothetical gene interaction network was proposed. This network demonstrates that our identified SNP-SNP interactions are biologically relevant and shows that EGFR may be the hub for the interactions. The findings provide valuable information to identify genotype combinations at risk of developing aggressive prostate cancer and improve understanding on the genetic etiology of angiogenesis associated with prostate cancer aggressiveness.PLoS ONE 04/2013; 8(4):e59688. DOI:10.1371/journal.pone.0059688 · 3.23 Impact Factor
Article: Vitamin E δ-Tocotrienol Induces p27Kip1-Dependent Cell-Cycle Arrest in Pancreatic Cancer Cells via an E2F-1-Dependent Mechanism[Show abstract] [Hide abstract]
ABSTRACT: Vitamin E δ-tocotrienol has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we demonstrated that δ-tocotrienol exerted significant cell growth inhibition pancreatic ductal cancer (PDCA) cells without affecting normal human pancreatic ductal epithelial cell growth. We also showed that δ-tocotrienol-induced growth inhibition occurred concomitantly with G(1) cell-cycle arrest and increased p27(Kip1) nuclear accumulation. This finding is significant considering that loss of nuclear p27(Kip1) expression is a well-established adverse prognostic factor in PDCA. Furthermore, δ-tocotrienol inactivated RAF-MEK-ERK signaling, a pathway known to suppress p27(Kip1) expression. To determine whether p27(Kip1) induction is required for δ-tocotrienol inhibition of PDCA cell proliferation, we stably silenced the CDKN1B gene, encoding p27(Kip1), in MIAPaCa-2 PDCA cells and demonstrated that p27(Kip1) silencing suppressed cell-cycle arrest induced by δ-tocotrienol. Furthermore, δ-tocotrienol induced p27(Kip1) mRNA expression but not its protein degradation. p27(Kip1) gene promoter activity was induced by δ-tocotrienol through the promoter's E2F-1 binding site, and this activity was attenuated by E2F-1 depletion using E2F-1 small interfering RNA. Finally, decreased proliferation, mediated by Ki67 and p27(Kip1) expression by δ-tocotrienol, was confirmed in vivo in a nude mouse xenograft pancreatic cancer model. Our findings reveal a new mechanism, dependent on p27(Kip1) induction, by which δ-tocotrienol can inhibit proliferation in PDCA cells, providing a new rationale for p27(Kip1) as a biomarker for δ-tocotrienol efficacy in pancreatic cancer prevention and therapy.PLoS ONE 02/2013; 8(2):e52526. DOI:10.1371/journal.pone.0052526 · 3.23 Impact Factor
Article: Prolonged survival and delayed progression of pancreatic intraepithelial neoplasia in LSL-KrasG12D/+;Pdx-1-Cre mice by vitamin E -tocotrienol[Show abstract] [Hide abstract]
ABSTRACT: The highly lethal nature of pancreatic cancer and the increasing recognition of high-risk individuals have made research into chemoprevention a high priority. Here, we tested the chemopreventive activity of δ-tocotrienol, a bioactive vitamin E derivative extracted from palm fruit, in the LSL-KrasG12D/+;Pdx-1-Cre pancreatic cancer mouse model. At 10 weeks of age, mice (n = 92) were randomly allocated to three groups: 1) no treatment, 2) vehicle, and 3) δ-tocotrienol (200 mg/kg x 2/day, PO). Treatment was continued for 12 months. Mice treated with δ-tocotrienol showed increased median survival from the onset of treatment (11.1 months) compared to vehicle-treated mice (9.7 months) and non-treated mice (8.5 months) (P<0.025). Importantly, none of the mice treated with δ-tocotrienol harbored invasive cancer compared with 10% and 8% in vehicle-treated and non-treated mice, respectively. Furthermore, δ-tocotrienol treatment also resulted in significant suppression of mouse pancreatic intraepithelial neoplasm (mPanIN) progression compared to vehicle-treated and non-treated mice: mPanIN-1: 47-50% (P<0.09), mPanIN-2: 6-11% (P<0.001), mPanIN-3: 3-15% (P<0.001), and invasive cancer: 0-10% (P<0.001). δ-Tocotrienol treatment inhibited mutant Kras-driven pathways such as MEK/ERK, PI3K/AKT, and NF-kB/p65, as well as Bcl-xL and induced p27. δ-Tocotrienol also induced biomarkers of apoptosis such as Bax and activated caspase 3 along with an increase in plasma levels of CK18. In summary, δ-tocotrienol's ability to interfere with oncogenic Kras pathways coupled with the observed increase in median survival and significant delay in PanIN progression highlight the chemopreventative potential of δ-tocotrienol and warrant further investigation of this micronutrient in individuals at high risk for pancreatic cancer.Carcinogenesis 01/2013; 34(4). DOI:10.1093/carcin/bgt002 · 5.33 Impact Factor
Article: Tripartite Motif Containing 28 (Trim28) can Regulate Cell Proliferation by Bridging HDAC1/E2F Interactions.[Show abstract] [Hide abstract]
ABSTRACT: Background: Trim28 appears up-regulated in many cancers. Results: In early stage lung tumors high Trim28 correlates with increased overall survival and Trim28 reduces cell proliferation in model lung cancer cell lines through E2F interactions. Conclusion: Trim28 may have a tumor suppressing role in the early stages of lung cancer. Significance: These results suggest a complex role for Trim28 in lung cancer. Trim28 is a poorly understood transcriptional co-factor with pleiotropic biological activities. Although Trim28 mRNA is found in many studies to be up-regulated in both lung and breast cancer tissues relative to normal adjacent tissue, we found that within a panel of early-stage lung adenocarcinomas high levels of Trim28 protein correlate with better overall survival. This surprising observation suggests that Trim 28 may have anti-proliferative activity within tumors. To test this hypothesis, we used shRNAi to generate Trim28-knockdown breast and lung cancer cell lines and found that Trim28 depletion led to increased cell proliferation. Likewise, overexpression of Trim28 led to decreased cell proliferation. Confocal microscopy indicated co-localization of E2F3 and E2F4 with Trim28 within the cell nucleus, and co-immunoprecipitation assays demonstrated that Trim28 can bind both E2F3 and E2F4. Trim28 overexpression inhibited the transcriptional activity of E2F3 and E2F4, whereas Trim28 deficiency enhanced their activity. Co-immunoprecipitations further indicated that Trim28 bridges an interaction between E2Fs 3 and 4 and HDAC1. Promoter-reporter assays demonstrated that the ability of HDAC1 to repress E2F3 and E2F4-driven transcription is dependent on Trim28. Trim28 depletion increased E2F3 and E2F4 DNA binding activity, as measured by chromatin-immunoprecipitation (ChIP) assays while simultaneously reducing HDAC1 binding. Finally, ChIP-ReChIP experiments demonstrated that Trim/E2F complexes exist on several E2F-regulated promoters. Taken together, these results suggest that Trim28 has anti-proliferative activity in lung cancers via repression of members of the E2F family that are critical for cell proliferation.Journal of Biological Chemistry 10/2012; 287(48). DOI:10.1074/jbc.M112.380865 · 4.57 Impact Factor
Article: Targeting CSE1L in colorectal cancerJournal of the American College of Surgeons 09/2012; 215(3):S127. DOI:10.1016/j.jamcollsurg.2012.06.328 · 5.12 Impact Factor
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ABSTRACT: BACKGROUND: Of great interest in cancer prevention is how nutrient components affect gene pathways associated with the physiological events of puberty. Nutrient-gene interactions may cause changes in breast or prostate cells and, therefore, may result in cancer risk later in life. Analysis of gene pathways can lead to insights about nutrient-gene interactions and the development of more effective prevention approaches to reduce cancer risk. To date, researchers have relied heavily upon experimental assays (such as microarray analysis, etc.) to identify genes and their associated pathways that are affected by nutrient and diets. However, the vast number of genes and combinations of gene pathways, coupled with the expense of the experimental analyses, has delayed the progress of gene-pathway research. The development of an analytical approach based on available test data could greatly benefit the evaluation of gene pathways, and thus advance the study of nutrient-gene interactions in cancer prevention. In the present study, we have proposed a chain reaction model to simulate gene pathways, in which the gene expression changes through the pathway are represented by the species undergoing a set of chemical reactions. We have also developed a numerical tool to solve for the species changes due to the chain reactions over time. Through this approach we can examine the impact of nutrient-containing diets on the gene pathway; moreover, transformation of genes over time with a nutrient treatment can be observed numerically, which is very difficult to achieve experimentally. We apply this approach to microarray analysis data from an experiment which involved the effects of three polyphenols (nutrient treatments), epigallo-catechin-3-O-gallate (EGCG), genistein, and resveratrol, in a study of nutrient-gene interaction in the estrogen synthesis pathway during puberty. RESULTS: In this preliminary study, the estrogen synthesis pathway was simulated by a chain reaction model. By applying it to microarray data, the chain reaction model computed a set of reaction rates to examine the effects of three polyphenols (EGCG, genistein, and resveratrol) on gene expression in this pathway during puberty. We first performed statistical analysis to test the time factor on the estrogen synthesis pathway. Global tests were used to evaluate an overall gene expression change during puberty for each experimental group. Then, a chain reaction model was employed to simulate the estrogen synthesis pathway. Specifically, the model computed the reaction rates in a set of ordinary differential equations to describe interactions between genes in the pathway (A reaction rate K of A to B represents gene A will induce gene B per unit at a rate of K; we give details in the "method" section). Since disparate changes of gene expression may cause numerical error problems in solving these differential equations, we used an implicit scheme to address this issue. We first applied the chain reaction model to obtain the reaction rates for the control group. A sensitivity study was conducted to evaluate how well the model fits to the control group data at Day 50. Results showed a small bias and mean square error. These observations indicated the model is robust to low random noises and has a good fit for the control group. Then the chain reaction model derived from the control group data was used to predict gene expression at Day 50 for the three polyphenol groups. If these nutrients affect the estrogen synthesis pathways during puberty, we expect discrepancy between observed and expected expressions. Results indicated some genes had large differences in the EGCG (e.g., Hsd3b and Sts) and the resveratrol (e.g., Hsd3b and Hrmt12) groups. CONCLUSIONS: In the present study, we have presented (I) experimental studies of the effect of nutrient diets on the gene expression changes in a selected estrogen synthesis pathway. This experiment is valuable because it allows us to examine how the nutrient-containing diets regulate gene expression in the estrogen synthesis pathway during puberty; (II) global tests to assess an overall association of this particular pathway with time factor by utilizing generalized linear models to analyze microarray data; and (III) a chain reaction model to simulate the pathway. This is a novel application because we are able to translate the gene pathway into the chemical reactions in which each reaction channel describes gene-gene relationship in the pathway. In the chain reaction model, the implicit scheme is employed to efficiently solve the differential equations. Data analysis results show the proposed model is capable of predicting gene expression changes and demonstrating the effect of nutrient-containing diets on gene expression changes in the pathway. One of the objectives of this study is to explore and develop a numerical approach for simulating the gene expression change so that it can be applied and calibrated when the data of more time slices are available, and thus can be used to interpolate the expression change at a desired time point without conducting expensive experiments for a large amount of time points. Hence, we are not claiming this is either essential or the most efficient way for simulating this problem, rather a mathematical/numerical approach that can model the expression change of a large set of genes of a complex pathway. In addition, we understand the limitation of this experiment and realize that it is still far from being a complete model of predicting nutrient-gene interactions. The reason is that in the present model, the reaction rates were estimated based on available data at two time points; hence, the gene expression change is dependent upon the reaction rates and a linear function of the gene expressions. More data sets containing gene expression at various time slices are needed in order to improve the present model so that a non-linear variation of gene expression changes at different time can be predicted.Translational Cancer Research 08/2012; 1(2):61-73.
Article: Characterizing the Efficacy of Fermented Wheat Germ Extract Against Ovarian Cancer and Defining the Genomic Basis of Its Activity[Show abstract] [Hide abstract]
ABSTRACT: Most women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists. In this study, we investigated the activity of Avemar, a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level. We found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate < 0.2) representing 27 biologic pathways (P < 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity. Our findings confirm the value of FWGE as a natural product with anticancer properties that may also enhance the activity of existing therapeutic agents. Furthermore, our findings provide substantial insights into the molecular basis of FWGE's effect on human cancer cells. RESEARCH HIGHLIGHTS:International Journal of Gynecological Cancer 07/2012; 22(6):960-7. DOI:10.1097/IGC.0b013e318258509d · 1.95 Impact Factor
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Moffitt Cancer Center
Tampa, Florida, United States
- • Department of Biostatistics
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University of South Florida
Tampa, Florida, United States
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Academia Sinica
Taipei, Taipei, Taiwan
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University of Alabama at Birmingham
Birmingham, Alabama, United States
- • Comprehensive Cancer Center
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University of Houston
Houston, Texas, United States
- • Texas Institute for Measurement, Evaluation and Statistics
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|By Business Wire
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|August 8, 2012 10:01 AM EDT
Rapid7, the leading provider of security risk intelligence solutions, today announced that the new version of its vulnerability management solution, Rapid7® Nexpose, introduces features for discovering and scanning IPv6 assets that organizations may not even know they have. The new version also further reduces the signal-to-noise ratio of assessing security risk by filtering out unnecessary background noise that makes it hard for security professionals to identify and focus on the highest priority security issues. These features simplify vulnerability management for busy security professionals who must address hugely complex security challenges on a daily basis.
"Security professionals are overwhelmed by information. It's increasingly complex for them to even identify what assets the organization has, let alone associated threats and the steps needed to improve their security posture," said Richard Perkett, vice president of Engineering at Rapid7. "Rapid7 simplifies this process by pioneering dynamic discovery of assets that are otherwise hard to track, such as IPv6 and virtual assets. Combined with Nexpose's remediation prioritization and vulnerability filtering, the result is efficiency in identifying the threats and actions that will make a real difference to the organization's security posture, thereby increasing the credibility of security teams across the organization."
Discovery and Scanning for IPv6
Approximately 95% of IPv4 address space has already been allocated1 and with devices increasingly requiring one or many IPs, the transition to the next generation, IPv6, is not far off. In fact, while most organizations believe they are not yet deploying IPv6, many devices are enabled for it by default. This represents a significant risk due to a number of factors, starting with a lack of IPv6 readiness in security products. Meanwhile, attackers are starting to recognize the opportunities in IPv6 as an attack vector and can tunnel in through IPv4 devices to then exploit the IPv6 vulnerabilities currently not being identified and addressed.
This threat is amplified by the difficulty that security professionals encounter in finding IPv6 assets in existing IPv4 production environments. The new edition of Nexpose addresses this by dynamically discovering IPv6 and IPv4 assets and scanning both for vulnerabilities. With Nexpose you can:
- Perform an IPv6 discovery over an IPv4 network, thereby enabling organizations to disable IPv6 devices in IPv4 networks as they could present a potential security risk
- Create a dynamic asset group and find assets with known IPv4 addresses that also have previously undiscovered IPv6 addresses, creating significant efficiencies by automating traditionally manual processes
- Run a report to show IPv6 enabled devices
- Conduct a scan to discover vulnerabilities in these IPv6 devices
- Export data to Metasploit and then run a risk assessment to validate risk based on exploits
"Nexpose can easily discover and scan IPv6 assets even if users don't think IPv6 is relevant to them yet. The solution works directly from the user's IPv4 environment to help them assess whether they have any IPv6 devices, for example, routers that are enabled by default, and if they have any relevant vulnerabilities," explained Perkett.
Vulnerability Filtering to Reduce Signal-to-Noise Ratio
One of the hardest challenges security professionals face is discerning which "signals" they really need to listen to amongst all the "noise" they hear. In the case of vulnerability scanning, it is common for security professionals to receive reports of tens, if not hundreds, of thousands of vulnerabilities. Identifying which of these are the most critical and should be addressed first is a complex challenge. Nexpose already simplifies this by providing contextual risk information based on exploit exposure, malware exposure, malware kits and the age of vulnerabilities identified, all of which impact the risk factor. Rather than providing generic advice on what vulnerabilities should be patched, it specifically prescribes steps on what needs to be remediated or mitigated based on the specific environment.
With the new version of Nexpose, Rapid7 provides the industry's most comprehensive capabilities for reducing the signal-to-noise ratio for vulnerability management. Users can now also filter asset and vulnerability information into groups that make sense to the organization and its structure. This enables users to produce reports with a sharper focus on specific security issues, giving remediation teams the exact information they need to do their jobs and eliminate the "noise" of extraneous vulnerability data. For example, users can generate reports that only include Adobe vulnerabilities. Likewise, users can exclude certain categories, such as for a particular platform or service for which they have a patch program in place. Being able to tailor the information for their audience in this way increases the credibility and relevance of security teams, promoting greater collaboration with IT operations.
Nexpose now enables users to filter vulnerabilities into 145 key "signal" categories, including:
- Vendor vulnerabilities: Adobe, Apple, Microsoft
- Web: Apache, IIS, OWASP Top 10, PHP, XSS, SQL Injection, Browsers
- Operating Systems: Microsoft Windows, Linux, Mac OS X
- Databases: Oracle, Microsoft SQL Server, MySQL
- Desktop Attack Vectors: Adobe Reader, Acrobat, Quicktime, Browsers, Flash, Java
"Organizations are drinking from the firehose at the moment, and many may feel like they're drowning. The huge reports they have to wrestle with are a roadblock to productivity, and handing them off to IT operations for remediation hardly promotes a healthy collaborative relationship," said Perkett. "With Nexpose, users can quickly determine which vulnerabilities are more relevant than others, filtering out a lot of the noise. The reports they give IT operations can be tailored to reflect the organization's internal structure, so they are relevant and straight-to-the-point, increasing efficiency all round."
Pricing and Availability
Nexpose 5.4 is available immediately. For information on pricing please contact [email protected]. To learn more, or for a free trial, please visit http://www.rapid7.com/vulnerability-scanner.jsp.
About Rapid7
Rapid7 is the leading provider of security risk intelligence. Its integrated vulnerability management and penetration testing products, Nexpose and Metasploit, empower organizations to obtain accurate, actionable and contextual intelligence into their threat and risk posture. Rapid7's solutions are used by more than 2,000 enterprises and government agencies in more than 65 countries, while the Company's free products are downloaded more than one million times per year and enhanced by the more than 175,000 members of its open source security community. Rapid7 has been recognized as one of the fastest growing security companies by Inc. Magazine and as a "Top Place to Work" by the Boston Globe. Its products are top rated by Gartner®, Forrester® and SC Magazine. The Company is backed by Bain Capital Ventures and Technology Crossover Ventures. For more information about Rapid7, please visit http://www.rapid7.com.
About Rapid7 Nexpose
Nexpose proactively supports the entire vulnerability management lifecycle, including discovery, detection, verification, risk classification, impact analysis, reporting and mitigation. This gives organizations immediate insight into the security posture of their IT environment by conducting over 92,000 vulnerability checks for more than 31,800 vulnerabilities. The solution leverages one of the largest vulnerabilities databases to identify vulnerabilities across networks, operating systems, databases, Web applications and virtual assets. Risk is classified based on real exploit intelligence combined with industry standard metrics such as CVSS, as well as temporal and weighted risk scoring. Nexpose provides a detailed, sequenced remediation roadmap with time estimates for each task. Nexpose is used to help organizations improve their overall risk posture and security readiness as well as to comply with mandatory regulations, including security requirements for PCI, HIPAA, ARRA HITECH ACT, FISMA (including SCAP, USGCB, FDCC and CyberScope Compliance), Sarbanes-Oxley (SOX) and NERC CIP. Nexpose is a Common Criteria EAL3+ product and received the SC Magazine Vulnerability Assessment Tool of the Year Award in 2012.
1 Approximately 95% of IPv4 address space was already allocated as of Sept. 3, 2010, according to the American Registry for Internet Numbers, which delegates blocks of IPv4 and IPv6 addresses to carriers and enterprises in North America.
SYS-CON Events announced today that IBM Cloud Data Services has been named "Bronze Sponsor" of SYS-CON's 17th Cloud Expo, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. IBM Cloud Data Services offers a portfolio of integrated, best-of-breed cloud data services for developers focused on mobile computing and analytics use cases.
Oct. 6, 2015 10:00 PM EDT Reads: 652
In his session at @ThingsExpo, Tony Shan, Chief Architect at CTS, will explore the synergy of Big Data and IoT. First he will take a closer look at the Internet of Things and Big Data individually, in terms of what, which, why, where, when, who, how and how much. Then he will explore the relationship between IoT and Big Data. Specifically, he will drill down to how the 4Vs aspects intersect with IoT: Volume, Variety, Velocity and Value. In turn, Tony will analyze how the key components of IoT influence Big Data: Device, Connectivity, Context, and Intelligence. He will dive deep to the matrix...
Oct. 6, 2015 08:00 PM EDT Reads: 314
When it comes to IoT in the enterprise, namely the commercial building and hospitality markets, a benefit not getting the attention it deserves is energy efficiency, and IoT's direct impact on a cleaner, greener environment when installed in smart buildings. Until now clean technology was offered piecemeal and led with point solutions that require significant systems integration to orchestrate and deploy. There didn't exist a 'top down' approach that can manage and monitor the way a Smart Building actually breathes - immediately flagging overheating in a closet or over cooling in unoccupied ho...
Oct. 6, 2015 05:00 PM EDT Reads: 257
Scott Guthrie's keynote presentation "Journey to the intelligent cloud" is a must view video. This is from AzureCon 2015, September 29, 2015 I have reproduced some screen shots in case you are unable to view this long video for one reason or another. One of the highlights is 3 datacenters coming on line in India.
Oct. 6, 2015 02:00 PM EDT Reads: 231
SYS-CON Events announced today that ProfitBricks, the provider of painless cloud infrastructure, will exhibit at SYS-CON's 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. ProfitBricks is the IaaS provider that offers a painless cloud experience for all IT users, with no learning curve. ProfitBricks boasts flexible cloud servers and networking, an integrated Data Center Designer tool for visual control over the cloud and the best price/performance value available. ProfitBricks was named one of the coolest Clo...
Oct. 6, 2015 01:00 PM EDT Reads: 742
"The Internet of Things transforms the way organizations leverage machine data and gain insights from it," noted Splunk's CTO Snehal Antani, as Splunk announced accelerated momentum in Industrial Data and the IoT. The trend is driven by Splunk's continued investment in its products and partner ecosystem as well as the creativity of customers and the flexibility to deploy Splunk IoT solutions as software, cloud services or in a hybrid environment. Customers are using Splunk® solutions to collect and correlate data from control systems, sensors, mobile devices and IT systems for a variety of Ind...
Oct. 6, 2015 01:00 PM EDT Reads: 583
You have your devices and your data, but what about the rest of your Internet of Things story? Two popular classes of technologies that nicely handle the Big Data analytics for Internet of Things are Apache Hadoop and NoSQL. Hadoop is designed for parallelizing analytical work across many servers and is ideal for the massive data volumes you create with IoT devices. NoSQL databases such as Apache HBase are ideal for storing and retrieving IoT data as "time series data."
Oct. 6, 2015 12:45 PM EDT Reads: 461
Clearly the way forward is to move to cloud be it bare metal, VMs or containers. One aspect of the current public clouds that is slowing this cloud migration is cloud lock-in. Every cloud vendor is trying to make it very difficult to move out once a customer has chosen their cloud. In his session at 17th Cloud Expo, Naveen Nimmu, CEO of Clouber, Inc., will advocate that making the inter-cloud migration as simple as changing airlines would help the entire industry to quickly adopt the cloud without worrying about any lock-in fears. In fact by having standard APIs for IaaS would help PaaS expl...
Oct. 6, 2015 12:30 PM EDT Reads: 588
Organizations already struggle with the simple collection of data resulting from the proliferation of IoT, lacking the right infrastructure to manage it. They can't only rely on the cloud to collect and utilize this data because many applications still require dedicated infrastructure for security, redundancy, performance, etc. In his session at 17th Cloud Expo, Emil Sayegh, CEO of Codero Hosting, will discuss how in order to resolve the inherent issues, companies need to combine dedicated and cloud solutions through hybrid hosting – a sustainable solution for the data required to manage I...
Oct. 6, 2015 12:00 PM EDT Reads: 444
Mobile messaging has been a popular communication channel for more than 20 years. Finnish engineer Matti Makkonen invented the idea for SMS (Short Message Service) in 1984, making his vision a reality on December 3, 1992 by sending the first message ("Happy Christmas") from a PC to a cell phone. Since then, the technology has evolved immensely, from both a technology standpoint, and in our everyday uses for it. Originally used for person-to-person (P2P) communication, i.e., Sally sends a text message to Betty – mobile messaging now offers tremendous value to businesses for customer and empl...
Oct. 6, 2015 10:45 AM EDT Reads: 166
Apps and devices shouldn't stop working when there's limited or no network connectivity. Learn how to bring data stored in a cloud database to the edge of the network (and back again) whenever an Internet connection is available. In his session at 17th Cloud Expo, Bradley Holt, Developer Advocate at IBM Cloud Data Services, will demonstrate techniques for replicating cloud databases with devices in order to build offline-first mobile or Internet of Things (IoT) apps that can provide a better, faster user experience, both offline and online. The focus of this talk will be on IBM Cloudant, Apa...
Oct. 6, 2015 10:45 AM EDT Reads: 455
As more and more data is generated from a variety of connected devices, the need to get insights from this data and predict future behavior and trends is increasingly essential for businesses. Real-time stream processing is needed in a variety of different industries such as Manufacturing, Oil and Gas, Automobile, Finance, Online Retail, Smart Grids, and Healthcare. Azure Stream Analytics is a fully managed distributed stream computation service that provides low latency, scalable processing of streaming data in the cloud with an enterprise grade SLA. It features built-in integration with Azur...
Oct. 6, 2015 10:00 AM EDT Reads: 737
SYS-CON Events announced today that HPM Networks will exhibit at the 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. For 20 years, HPM Networks has been integrating technology solutions that solve complex business challenges. HPM Networks has designed solutions for both SMB and enterprise customers throughout the San Francisco Bay Area.
Oct. 6, 2015 09:00 AM EDT Reads: 573
The enterprise is being consumerized, and the consumer is being enterprised. Moore's Law does not matter anymore, the future belongs to business virtualization powered by invisible service architecture, powered by hyperscale and hyperconvergence, and facilitated by vertical streaming and horizontal scaling and consolidation. Both buyers and sellers want instant results, and from paperwork to paperless to mindless is the ultimate goal for any seamless transaction. The sweetest sweet spot in innovation is automation. The most painful pain point for any business is the mismatch between supplies a...
Oct. 6, 2015 09:00 AM EDT Reads: 144
The broad selection of hardware, the rapid evolution of operating systems and the time-to-market for mobile apps has been so rapid that new challenges for developers and engineers arise every day. Security, testing, hosting, and other metrics have to be considered through the process. In his session at Big Data Expo, Walter Maguire, Chief Field Technologist, HP Big Data Group, at Hewlett-Packard, will discuss the challenges faced by developers and a composite Big Data applications builder, focusing on how to help solve the problems that developers are continuously battling.
Oct. 6, 2015 04:00 AM EDT Reads: 412
As enterprises capture more and more data of all types – structured, semi-structured, and unstructured – data discovery requirements for business intelligence (BI), Big Data, and predictive analytics initiatives grow more complex. A company's ability to become data-driven and compete on analytics depends on the speed with which it can provision their analytics applications with all relevant information. The task of finding data has traditionally resided with IT, but now organizations increasingly turn towards data source discovery tools to find the right data, in context, for business users, d...
Oct. 5, 2015 08:00 AM EDT Reads: 381
SYS-CON Events announced today that MobiDev, a software development company, will exhibit at the 17th International Cloud Expo®, which will take place November 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. MobiDev is a software development company with representative offices in Atlanta (US), Sheffield (UK) and Würzburg (Germany); and development centers in Ukraine. Since 2009 it has grown from a small group of passionate engineers and business managers to a full-scale mobile software company with over 150 developers, designers, quality assurance engineers, project manage...
Oct. 5, 2015 05:00 AM EDT Reads: 742
Learn how IoT, cloud, social networks and last but not least, humans, can be integrated into a seamless integration of cooperative organisms both cybernetic and biological. This has been enabled by recent advances in IoT device capabilities, messaging frameworks, presence and collaboration services, where devices can share information and make independent and human assisted decisions based upon social status from other entities. In his session at @ThingsExpo, Michael Heydt, founder of Seamless Thingies, will discuss and demonstrate how devices and humans can be integrated from a simple clust...
Oct. 4, 2015 12:00 PM EDT Reads: 631
SYS-CON Events announced today that Cloud Raxak has been named "Media & Session Sponsor" of SYS-CON's 17th Cloud Expo, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. Raxak Protect automates security compliance across private and public clouds. Using the SaaS tool or managed service, developers can deploy cloud apps quickly, cost-effectively, and without error.
Oct. 3, 2015 01:15 PM EDT Reads: 628
Who are you? How do you introduce yourself? Do you use a name, or do you greet a friend by the last four digits of his social security number? Assuming you don't, why are we content to associate our identity with 10 random digits assigned by our phone company? Identity is an issue that affects everyone, but as individuals we don't spend a lot of time thinking about it. In his session at @ThingsExpo, Ben Klang, Founder & President of Mojo Lingo, will discuss the impact of technology on identity. Should we federate, or not? How should identity be secured? Who owns the identity? How is identity ...
Oct. 3, 2015 11:00 AM EDT Reads: 421


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VOV News English 1 month(s) ago
The Damen Group from the Netherlands and the local Song Thu Shipyard Corporation have begun building two Stan patrol ships, SPA 5009, for export to Venezuela.
Keywords: ShipssalvageoffshoreDredgingHa LongThe Netherlands
Báo Thanh Niên English 2 month(s) ago
Heavy rainfall in northern Vietnam has killed 17 people and inundated major coal mines, causing concern among environmentalists about contamination of local communities and the waters of a top tourist attraction, Ha Long Bay.
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Báo Đầu Tư English 2 month(s) ago
Rising Liverpool star Jordon Ibe mustered a superb solo effort to equalise against a spirited Malaysia XI side and salvage a draw as the Reds wrapped up an unbeaten Asia summer tour.
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Romain Bardet helped salvage some host pride with victory on the 18th stage of the Tour de France on Thursday.
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Báo Tuổi Trẻ English 3 month(s) ago
Two advanced ships, including a coast guard vessel with a helipad on board and a towing and rescuing boat, have been handed over to the Vietnam Coast Guard (VCG).
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VOV News English 3 month(s) ago
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Some large Greek banks may have to be shut and taken over by stronger rivals as part of a restructuring of the sector that would follow any bailout of the country, European officials have told Reuters.
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A massive landslide tore through a ravine in northwest Colombia on Monday before dawn, killing at least 61 people and injuring 37, authorities said.
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VOV News English 6 month(s) ago
The Republic of Korea said on April 22 it will raise the Sewol ferry that sank a year ago, killing more than 300 people, most of them children, yielding to pressure from mourning families who have called for a deeper investigation into the disaster.
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Báo Thanh Niên English 6 month(s) ago
Two US Navy ships will dock in the central city of Da Nang next week for annual exchange activities between the two countries' navies, according to the US consulate general in Ho Chi Minh City.
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Báo Tuổi Trẻ English 6 month(s) ago
Two U.S. naval ships will arrive at Tien Sa Port in the central Vietnamese city of Da Nang on April 6 for a five-day working visit as an annual activity, according to the U.S. Consulate General in Ho Chi Minh City.
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The South Korean government said on Wednesday it would pay about 420 million won ($380,000) compensation for each of the 250 students who died or remain missing from last year's ferry disaster, in the first settlement offer to victims' families.
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Search for two missing women is going on since a vessel carrying five to seven tonnes of farmed clams capsized last Saturday night in Thai Binh Province.
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- NT - All
Adelaide River Railway Station
The Adelaide River Railway Station is the only surviving example of its type in the N.T. and operated from 1888 until 1976 on a route between Darwin and Pine Creek.
The galvanised iron railway station building at Adelaide River was completed in 1889 and included a refreshment room for patrons. During World War Two, the railway station became part of a major military centre. For a few years after the war, until the end of 1950, it served as the Adelaide River Hotel. After the demise of NAR in 1976, the building became derelict. Major restoration was undertaken in 1985-86, and on 16 July 1988, the building was officially opened as a museum, one hundred years after the first train steamed into Adelaide River.
The Adelaide River Railway Station inlcudes:
- Car park
- Picnic Area & Shaded Area
- Public Toilet
- Visitor Information Centre
- Location:
- cnr Stuart Hwy & Dorat Rd, ADELAIDE RIVER, NT Map it
- Ages:
- All Ages / Family
- Cost:
- Free
- Event Info:
- call 08 8976 7101 for information Visit Website
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USU Student Association
Saturday Nature Walks -- Swaner EcoCenter
Join us for a nature walk on the Preserve! You will learn…
Transcendence: Abstraction and Symbolism in the American West
Sept. 1, 2015 – May 7, 2016 Highlighting works from…
Abstraction and the Dreaming: Australian Aboriginal Paintings
Sept. 12 – Dec. 11, 2015 Sept. 12 - Dec. 12 The…
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Join the American Festival Chorus and Orchestra for…
Robins Awards
Robins Awards 2014 - April 19 at 7pm in the TSC Ballroom
The Robins Awards are the most coveted of all Utah State honors. They reward students and faculty for hard work and dedication to their individual goals, as well as the goals of USU.
The awards memorialize William E. Robins, a campus hero who had a rare quality to turn his vision into Utah State's vision. Robins was a Sigma Nu at Utah State who served as USU's student body president in 1949. He was the primary and initial visionary of today's Taggart Student Center.
In 1954, Bill and wife Geraldine died in a plane crash, leaving behind a one-year old orphan boy. This prompted Bill's fraternity to set up a fund so the boy could go to USU when he was ready. Tragically, the boy died at the age of eight from leukemia. Since then, the fund has been used to continue the Robins Award tradition.
Each year, the gallant event is held in the evening, and several awards are presented. The ceremony is followed by the Spring Formal dance. Throughout the years, the name of Bill Robins has stood as a symbol of the best efforts students can offer. As a memorial to him, the night's feature award is called the Bill Robins Memorial Award. Other awards include: Achievement of the Year, Woman of the Year, Man of the Year, Organization of the Year, and the Val R. Christensen Service of the Year.


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Sitter in 1 portrait
Henry Charles Howard, 13th Duke of Norfolk(1791-1856), Lord Steward
Sitter in 1 portrait
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- Lady Adeliza Matilda Manners (née Howard) (daughter)
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l strong & light weight die-casting aluminum body
l Tool free quick-clear jam release
l Top 360° air deflector
l single sequential & dual action (by different triggers)
l A nice little viewing window to see how many brads are in the magazine
l Tool free depth depth control of drive
l No mar tip for work contact surface protection
l special hardened driver blade
l quick-clear jam release
l 360° air deflector
● strong & light weight die-casting aluminum body
● 360° air deflector
● special hardened driver blade
● nails fitting by manual
● full sequential
● Powerful and durable aluminium housing & cylinder cap.
● Direction adjustable air deflector.
● Hardened nylon nail housing.
● Contact trip actuation for industrial use