Finance Minister Dr. Ashni Singh yesterday afternoon announced that Monday,? March 25? is Budget Day for 2013. On that day, Minister Singh will present his seventh consecutive national budget, having first presented the budget in 2007 after his appointment as the PPP/C?s Finance Minister in September 2006.
Finance Minister Dr. Ashni Singh
The Minister stated that the Government?s focus will remain on accelerating economic growth and social development, with continued emphasis on macroeconomic stability and preserving the conditions that are conducive to attracting investment, expanding and upgrading physical infrastructure, expanding access and improving the quality of social services, and strengthening the institutional and regulatory environment. The Minister further stated that Budget 2013 will reflect the PPP/C?s overriding concern with making steady improvements in the standard of living enjoyed by every citizen of Guyana and with creating and expanding opportunities for personal upliftment and betterment. ?The steady growth that has been achieved in our economy, and the marked improvement in key social indicators across our country, must not be taken for granted. They were achieved as a result of deliberate policy positions taken by this Government and sustained effort at implementing responsible policies over the years, including by making hard choices where these were needed. Our Government will not divert from our policy focus on further improving the circumstances of the people of our country and further strengthening the performance of our economy,? stated Minister Singh. (GINA)
Loren Brichter got his start working on the original iPhone at Apple, then created and ultimately sold Tweetie to Twitter, and is now responsible for the phenomenal word game, Letterpress. Jessica E. Lessin has profiled Brichter, and elaborated on his influence on mobile interface design in the Wall Street Journal:
When Dominique Leca wanted feedback on his Sparrow mail mobile app in 2010, he sought out Mr. Brichter. Mr. Brichter responded to Mr. Leca with copious notes about the Sparrow app, including suggesting an adjustment to Sparrow's text placement and advising Mr. Leca to "delay the fade-out animation by a second or so." Mr. Leca says he followed much of the advice and asked Mr. Brichter to be an adviser; Sparrow later received much acclaim and was acquired by Google Inc. last year.
Pull-to-refresh, sliding panel layers, and swipe-to-reveal are just a few of the things the WSJ reports have been picked up by everyone from Apple to BlackBerry to Facebook to Google. I think they even try to stick him with hamburger buttons and basements, the now ubiquitous 3-line icons that reveal a sidebar filled with menu items. Busted, Brichter!
The full article is a great read, but might be blocked by a paywall. This Google search link might get you in.
We've been honored to have Brichter talk about his background and work on both Iterate and Debug:
Toyota recall due to possibility that front seat belts could come off. Two-thirds of Toyota recalled FJ Cruisers are in the US.?
By Reuters / March 15, 2013
Visitors look around Toyota's FJ cruiser at its showroom in Tokyo in 2011. Toyota Motor Corp. announced it was recalling 310,000 FJ Cruisers worldwide because of weak seat-belt anchoring. The Toyota recall involves models from 2007 to 2013
Kim Kyung-Hoon/Reuters/File
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Toyota Motor Corp is recalling 310,000 of its FJ Cruiser sports utility vehicles worldwide because the seatbelt anchor could become detached through wear, the company said on Friday.
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Two-thirds of the vehicles to be recalled are in the United States. The affected FJ Cruisers are from model years 2007 to 2013, Toyota said.
No accidents or injuries have been reported due to the problem, Toyota said.
"The seatbelt retractors for the driver and front passenger seat belts are mounted on the rear doors of the vehicles," Toyota said in a press statement. "Due to insufficient strength of the rear door panel, cracks may develop over an extended period of time if the rear door is repeatedly and forcefully closed."
After recent launch problems, Ford Motor Co. is tightening the build quality of prototype vehicles, says Barb Samardzich, vice president for product development at Ford of Europe.
"We make sure that when we build our first set of prototypes that the quality of parts accurately represents what our production intent is so that we can ferret out any design issues very early," she said.
Ford issued several recalls of the redesigned Fusion mid-sized car and Escape SUV last year. Samardzich said recent European launches had been glitch-free, but she acknowledged that new technology such as the MyFord Touch connectivity system can cause problems.
Said Samardzich: "You do run a risk that you may be taking a step backward in some of the quality delivery because of the newness of the technology even though you've put it through all the robust processes."
By Mark Lamport-Stokes INDIAN WELLS, California (Reuters) - Rafa Nadal produced vintage form against an out-of-sorts Roger Federer, crushing the Swiss 6-4 6-2 in their heavily anticipated quarter-final at the BNP Paribas on Thursday. The Spanish left-hander, competing in his first hardcourt event since his return from seven months on the sidelines with a knee injury, outplayed his long-time rival with a sharp display at the Indian Wells Tennis Garden. ...
Study shows additional role for abiraterone in blocking tumor growth in CRPCPublic release date: 15-Mar-2013 [ | E-mail | Share ]
Contact: Ivanka Moerkerken i.moerkerken@uroweb.org 31-026-389-0680 European Association of Urology
Arnhem, 14 March 2013 - As part of an EU-supported IMI-PREDECT consortium (http://www.predect.eu), a Dutch study showed that anti-androgenic properties of the drug abiraterone may provide an additional mechanism of action in blocking tumour growth of castration resistant prostate cancer (CRPC).
The study, which won the first prize for best abstract in oncology at the 28th European Association of Urology (EAU) Congress to be held in Milan from March 15 to 19, demonstrated that although the use of abiraterone can potentially lead to an accumulation of precursor hormones, its anti-androgenic properties may stop precursor hormone-induced androgen receptor (AR) activation.
"Our results show that high concentrations of androgen precursors can drive CRPC growth through direct activation of (overexpressed) AR and not necessarily via the result of (intratumoural) CYP17-metabolism. This suggests that CRPC may not rely solely on de novo androgen synthesis," said lead author Dr. Jan Matthijs Moll of the Erasmus Medical Center, Dept. of Urology in Rotterdam, Netherlands.
Men with castration resistant prostate cancer are a difficult group to treat. Although metastatic prostate cancer may respond well to androgen ablation therapy initially, castration resistance usually develops within three years. Even though circulating testosterone levels are low in these patients, the androgen receptor reactivates, which indicates the AR remains an important target in CRPC.
The Rotterdam-based group has previously demonstrated that conversion of adrenal androgens into testosterone, rather than intratumoural de novo steroidogenesis, is the major source of testosterone in CRPC tumours. [1]
Clinical trials have demonstrated that abiraterone acetate plus prednisone/prednisolone can increase survival in CRPC patients even after chemotherapy [2]. "Blocking androgen synthesis (pregnenolone and progesterone are converted to androgens via CYP17A1 enzymatic activity) in CRPC patients has demonstrated a prolonged survival, but may eventually fail because androgen precursors can activate the AR directly," explained Moll.
In their study, the researchers generated castration resistant clones by long-term culture of VCaP and DuCaP cell lines in steroid-stripped medium (DCC), with or without addition of anti-androgens used in the clinic. Experiments were conducted with a subset of AR-overexpressing CRPC clones to test cell growth and AR-activation in the presence of adrenal androgen precursors, pregnenolone and progesterone or dihydrotestosterone in combinations with increasing levels of abiraterone.
The results showed that high (100 nM) levels of progesterone, but not of pregnenolone, induced cell growth in VCaP and DuCaP CRPC clones, which could not be blocked by low levels of abiraterone (0,1 M) that are known to fully inhibit CYP17A1 activity (and thus potential subsequent testosterone production).
In a second experiment, the researchers showed that high levels of precursor androgens can directly activate the AR using a model with a fluorescent AR and that ligand-induced AR-translocation from the cytoplasm to the nucleus was slowed down by abiraterone.
"However, high levels of abiraterone (>5 mM) inhibited steroid-induced, but not basal growth of these (CRPC) cells. This finding, together with the observation that DHT-induced growth was inhibited by high levels of abiraterone, indicates that abiraterone can act as an anti-androgen," the researchers wrote.
"We show that abiraterone, a CYP17A1-blocking drug that has recently been approved in the treatment of CRPC, possesses an additional antiandrogenic property and can block androgen precursor-induced AR-activation at higher concentrations than what is needed for CYP17A1 specific inhibition. This may be a good argument to increase abiraterone exposure in the treatment of CRPC," added Moll.
Moll also said that "it is clear that the AR remains the most important target in the treatment of CRPC."
"Blockade of androgen synthesis seems not sufficient to prevent AR activation. New drugs that block AR activation irrespective of the activating ligand may provide new ammunition to last another 'round' for clinicians to treat CRPC," he said. "We believe it is vital to identify which metabolites have the potential to activate the mutated or overexpressed AR present in CRPC, which under normal conditions may not activate the AR. In that perspective, we are currently working together with our partner, Janssen, and other partners within the IMI-PREDECT consortium on developing new model systems for CRPC to further understand its biology and test new potential pathway perturbations that may benefit CRPC patients in the future."
###
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Study shows additional role for abiraterone in blocking tumor growth in CRPCPublic release date: 15-Mar-2013 [ | E-mail | Share ]
Contact: Ivanka Moerkerken i.moerkerken@uroweb.org 31-026-389-0680 European Association of Urology
Arnhem, 14 March 2013 - As part of an EU-supported IMI-PREDECT consortium (http://www.predect.eu), a Dutch study showed that anti-androgenic properties of the drug abiraterone may provide an additional mechanism of action in blocking tumour growth of castration resistant prostate cancer (CRPC).
The study, which won the first prize for best abstract in oncology at the 28th European Association of Urology (EAU) Congress to be held in Milan from March 15 to 19, demonstrated that although the use of abiraterone can potentially lead to an accumulation of precursor hormones, its anti-androgenic properties may stop precursor hormone-induced androgen receptor (AR) activation.
"Our results show that high concentrations of androgen precursors can drive CRPC growth through direct activation of (overexpressed) AR and not necessarily via the result of (intratumoural) CYP17-metabolism. This suggests that CRPC may not rely solely on de novo androgen synthesis," said lead author Dr. Jan Matthijs Moll of the Erasmus Medical Center, Dept. of Urology in Rotterdam, Netherlands.
Men with castration resistant prostate cancer are a difficult group to treat. Although metastatic prostate cancer may respond well to androgen ablation therapy initially, castration resistance usually develops within three years. Even though circulating testosterone levels are low in these patients, the androgen receptor reactivates, which indicates the AR remains an important target in CRPC.
The Rotterdam-based group has previously demonstrated that conversion of adrenal androgens into testosterone, rather than intratumoural de novo steroidogenesis, is the major source of testosterone in CRPC tumours. [1]
Clinical trials have demonstrated that abiraterone acetate plus prednisone/prednisolone can increase survival in CRPC patients even after chemotherapy [2]. "Blocking androgen synthesis (pregnenolone and progesterone are converted to androgens via CYP17A1 enzymatic activity) in CRPC patients has demonstrated a prolonged survival, but may eventually fail because androgen precursors can activate the AR directly," explained Moll.
In their study, the researchers generated castration resistant clones by long-term culture of VCaP and DuCaP cell lines in steroid-stripped medium (DCC), with or without addition of anti-androgens used in the clinic. Experiments were conducted with a subset of AR-overexpressing CRPC clones to test cell growth and AR-activation in the presence of adrenal androgen precursors, pregnenolone and progesterone or dihydrotestosterone in combinations with increasing levels of abiraterone.
The results showed that high (100 nM) levels of progesterone, but not of pregnenolone, induced cell growth in VCaP and DuCaP CRPC clones, which could not be blocked by low levels of abiraterone (0,1 M) that are known to fully inhibit CYP17A1 activity (and thus potential subsequent testosterone production).
In a second experiment, the researchers showed that high levels of precursor androgens can directly activate the AR using a model with a fluorescent AR and that ligand-induced AR-translocation from the cytoplasm to the nucleus was slowed down by abiraterone.
"However, high levels of abiraterone (>5 mM) inhibited steroid-induced, but not basal growth of these (CRPC) cells. This finding, together with the observation that DHT-induced growth was inhibited by high levels of abiraterone, indicates that abiraterone can act as an anti-androgen," the researchers wrote.
"We show that abiraterone, a CYP17A1-blocking drug that has recently been approved in the treatment of CRPC, possesses an additional antiandrogenic property and can block androgen precursor-induced AR-activation at higher concentrations than what is needed for CYP17A1 specific inhibition. This may be a good argument to increase abiraterone exposure in the treatment of CRPC," added Moll.
Moll also said that "it is clear that the AR remains the most important target in the treatment of CRPC."
"Blockade of androgen synthesis seems not sufficient to prevent AR activation. New drugs that block AR activation irrespective of the activating ligand may provide new ammunition to last another 'round' for clinicians to treat CRPC," he said. "We believe it is vital to identify which metabolites have the potential to activate the mutated or overexpressed AR present in CRPC, which under normal conditions may not activate the AR. In that perspective, we are currently working together with our partner, Janssen, and other partners within the IMI-PREDECT consortium on developing new model systems for CRPC to further understand its biology and test new potential pathway perturbations that may benefit CRPC patients in the future."
###
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Mar. 15, 2013 ? The cyanobacterium Synechocystis produces toxins that often lead to its own demise. The biologists Stefan Kopfmann and Prof. Dr. Wolfgang Hess from the University of Freiburg have determined the logic governing this mechanism.
Their findings have been published in the Journal of Biological Chemistry (JBC) and PLoS ONE.
The cyanobacterium Synechocystis produces several toxins. However, most of the time they cannot become active because the unicellular organism usually only produces them together with an antitoxin that neutralizes their poisonous effect. This is a trick of nature: The genes for the toxin and the antitoxin are located together on a plasmid, i.e. a fragment of DNA that exists independently of the actual bacterial chromosome. In contrast to the toxin, the antitoxin is not very stable. When a cell loses the plasmid during cell division, both of the genes are lost. Since the toxin is more stable than the antitoxin and is thus effective for a longer period of time, these cells eventually die off. Hence, the toxin-antitoxin pairs constitute a natural selection mechanism that sees to it that only cells which retain the plasmid survive.
The plasmid pSYSA of the cyanobacterium Synechocystis has not one but seven different systems of this kind and is thus well protected. The reason for this is because in addition to the genes for the seven toxin-antitoxin pairs, the plasmid pSYSA possesses the genetic information for a bacterial immune system. If the plasmid with this system gets lost in cell division, several toxins thus see to it that the bacterium is killed. The fact that the genes responsible for it are combined with a high amount of toxin-antitoxin pairs indicates that this system has special significance for the cyanobacterial cell.
The project is supported by funding from the German Research Foundation.
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The above story is reprinted from materials provided by Albert-Ludwigs-Universit?t Freiburg.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal References:
S. Kopfmann, W. R. Hess. Toxin-Antitoxin Systems on the Large Defense Plasmid pSYSA of Synechocystis sp. PCC 6803. Journal of Biological Chemistry, 2013; 288 (10): 7399 DOI: 10.1074/jbc.M112.434100
Ingeborg Scholz, Sita J. Lange, Stephanie Hein, Wolfgang R. Hess, Rolf Backofen. CRISPR-Cas Systems in the Cyanobacterium Synechocystis sp. PCC6803 Exhibit Distinct Processing Pathways Involving at Least Two Cas6 and a Cmr2 Protein. PLoS ONE, 2013; 8 (2): e56470 DOI: 10.1371/journal.pone.0056470
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Public release date: 15-Mar-2013
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