Rethinking Immunotherapy for Brain Tumors

As highlighted in our prior articles, growing evidence indicates that the field of cancer immunotherapy, broadly defined as including passive immunization, active immunization, and immunostimulation, is coming of age.? More than 40 unique active cancer immunotherapies are currently being tested in over 60 clinical trials, with nearly a dozen readouts from randomized Phase 2 or Phase 3 trials expected during the next 12-months.

Immunotherapy for cancers of the central nervous system [CNS], however, continues to be met with skepticism. ?Amongst the reasons for such incredulity are concerns that the nervous system may be immunologically privileged[i] and the presence of the blood-brain barrier, which only allows entry of select immune cells from the peripheral blood into the brain. ?However, all of these premises have now been substantially discounted and tumors in the CNS should not be considered ?off-limits? to immunotherapy[ii].

In addition, recent observations of how the CNS system behaves and interacts with the immune system have shed some light into the potential role of immunotherapy in the treatment of brain cancer. ?Consider the following facts:

• People with impaired immune systems have an increased risk of developing CNS lymphomas[iii], suggesting that the immune system has a role in the manifestation of tumors in these patients. ?People with compromised immune systems include organ transplantation patients taking immunosuppressive drugs, HIV patients, and cancer patients being treated with chemotherapy, which can weaken immune functionality.
• Bridget McCarthy, Ph.D. of the University of Illinois at Chicago found that patients with gliomas were significantly less likely to report having any type of allergy. ?In fact, patients who had more types of allergies, such as seasonal, medication, pet, or food allergies, had up to a 64% reduction in risk of developing glioma[iv]. This suggests a relationship between immunological activity and potential protection from the development of CNS tumors.
• Neurologists and neurosurgeons provide anecdotal reports that glioma patients who experience postoperative infections near the tumor bed seem to do better than the average patient similar to the observations made over a century ago by Coley[v]. ?This suggests that exogenous factors, such as infections, may result in the activation of the immune system and improve the odds of combating CNS tumors.

Collectively, these observations suggest that proper activation of the immune system in patients with CNS tumors could be beneficial.? Accordingly, we sought to review select companies advancing immunotherapy approaches for brain tumors [see Table 1].

Table 1. Eight Companies with Immunotherapy Approaches for Brain Tumors

Company	Market Cap	Clinical Pipeline	Corporate Partner(s)	Stage(s) [# of programs]
Agenus, Inc. (AGEN)	$62M	Prophage Series*, QS-21 Stimulon? adjuvant, HerpV	GlaxoSmithKline (GSK), Johnson & Johnson (JNJ), ChemRar, and Integrated Biotherapeutics	Phase III [4], Phase II [10], Phase 1 [1]
Celldex Therapeutics (CLDX)	$202M	Rindopepimut [CDX-110]; CDX-011, CDX-1401, CDX-1127, CDX-301	n/a	Phase III [1], Phase II [3], Phase I [2]
Immatics Biotechnologies (private)	n/a	IMA-901, IMA-910, IMA-950	n/a	Phase III [1], Phase II [1], Phase I [1]
ImmunoCellular Therapeutics (IMUC)	$72M	ICT-107	n/a	Phase II [1]
Innocell Corp (031390.KQ)	n/a	Immuncell-LC**	n/a	Phase III [1]
Northwest Biotherapeutics (NWBO)	$31M	DCVax?	n/a	Phase II [1]
Oncovir, Inc. (private)	n/a	Hiltonol (Poly-ICLC)	n/a	Phase II [2], Phase I [2]
TVAX Biomedical (private, IPO planned)	~$80M at IPO	TV1-Brain-1, TV1-Kidney-1	n/a	Phase II [1]

* Marketed in Russia as Oncophage? for intermediate-risk renal cell carcinoma,?** Marketed in Korea for hepatocellular carcinoma

About Glioma

Glioma is the most common form of primary brain tumors. ?They are solid tumors that arise from glial cells, which help support the function of the neurons.? Glial cells include astrocytes, oligodendrocytes and ependymal cells.? The overgrowth of abnormal glial cells may begin in the brain or spinal cord tissues.

Gliomas can be divided into two categories: low-grade, which are not benign but have a better prognosis, or high-grade, which are malignant and often cause death within months, despite surgery or treatment with chemotherapy or radiation, according to the National Cancer Institute.

Glioblastoma multiforme [GBM], a high-grade glioma, is the most common and aggressive primary brain tumor.? In contrast, tumors originating from astrocytes [astrocytoma] range from Grade 1, which are very benign, to Grade 4, which is the same as a glioblastoma.

Amenable to Immunotherapy

Beyond recent observations suggesting a role for immunotherapy in treating brain tumors, several other factors make glioma an ideal indication for immunotherapy.? First, glioma rarely metastasizes beyond the brain, resulting in a low overall tumor burden within the body.? Second, while the blood-brain barrier is thought to restrict entry of immune cells from the peripheral blood into the brain of healthy individuals, glioma disrupts the blood brain barrier, allowing for the freer trafficking of T-cells.? Finally, glioma tumor tissue, especially in patients who are newly diagnosed, is amenable to surgical resection therefore lowering tumor burden at time of vaccination [minimal residual disease].? Studying cancer immunotherapy in settings with bulky or metastatic disease might help explain some of the past failures, as the immune system may not be able to thwart such extensive disease.? Accordingly, minimal disease settings are ideal for cancer immunotherapy.

Strategies for Immunotherapy in Glioma

In general, two categories of immunotherapeutic approaches for the treatment of glioma are currently being pursued: cell-free vaccines and cell-based vaccines.

Cell-free vaccines

Cell-free vaccines may contain heat-shock protein-peptide (HSP) complexes derived from the patient?s tumor following surgery [autologous] or incorporate one or more defined tumor peptides plus an adjuvant [non-autologous].? The following companies are advancing cell-free vaccines:

• Agenus, Inc.: autologous HSPs that elicit both CD4+ and CD8+ T-cell response and also innate response
• Celldex Therapeutics: a single EGFRvIII peptide
• Immatics Biotechnologies: 11 tumor associated, synthetic peptides

Cell-based vaccines

Cell-based vaccines often incorporate dendritic cells [DC] pulsed with defined tumor peptides, tumor cell lysate, brain tumor stem cell mRNA.? Alternatively, some cell-based vaccines consist of adoptive lymphocyte infusion and/or irradiated tumor cells.? The following companies are advancing cell-based vaccines:

• ImmunoCellular Therapeutics: DCs pulsed with shared HLA-A1/A2 tumor peptides
• Innocell Corp: adaptive transfer of cytokine-induced T-cells/NK cells
• Northwest Biotherapeutics: DCs pulsed with tumor lysate
• Oncovir, Inc.: a-type 1 polarized DCs pulsed with defined HLA-A2 peptides plus poly-ICLC adjuvant
• TVAX Biomedical: whole cell vaccination plus adoptive transfer of lymphocytes

To date, commercializing cell-based vaccines has been challenging.? For example, Dendreon?s (DNDN) Provenge? [sipuleucel-T] for prostate cancer is a cell-based vaccine that fell short of Wall Street analyst expectations during the first full year of commercial launch.? Provenge and other DC-based cancer vaccines require leukopherisis to acquire a patient?s dendritic cells. ?This process adds to the overall cost of producing the vaccine and makes the logistics somewhat complicated. ?In contrast, cell-free vaccines can be derived from synthetic peptides or from the patient?s tumor following standard surgical resection, making the treatment process more user friendly from both a physician and patient perspective.

Clinical Development of Immunotherapy for GBM

The current standard of care for GBM, based on a prospective, randomized controlled trial published in 2005, involves maximal surgical resection with adjuvant radiation therapy and temozolomide[vi].? Despite this therapeutic regimen, median overall survival is between 14.6 and 19.6 months for newly diagnosed patients and between 6 and 9 months for recurrent GBM[vii]^,[viii].

While immunotherapy approaches for GBM would be expected to perform better in the newly diagnosed setting, some companies first established proof-of-concept for their product candidates in the relapsed setting.? Due to the shorter expected survival, these Phase I/II studies may be faster and less expensive.? If hints of efficacy are observed in the relapsed disease setting, the product candidates can then be explored in the newly diagnosed setting.

In view of differences among histologies, ages, trial designs, and the small number of patients with immunotherapy studies published to date in the recurrent GBM setting, comparing and contrasting the findings is difficult [see Table 2].? For example, in the largest single study [56 patients] from the Catholic University of Leuven, the median age was the lowest [45 years] due to the inclusion of children above the age of seven.? In addition, some of the studies included patients that were not diagnosed with GBM, such as astrocytomas that can vary in grade.

In contrast to the results obtained with current standard of care, several of the studies with cancer vaccines for recurrent GBM have demonstrated a median overall survival greater than nine months. ?Some of these trials where immune responses have been measured, such as the Prophage G-200 [HSPPC-96] trial, have shown impressive immunological activity post vaccination. ?More impressive and certainly more relevant, these responses have also been measurable locally at the tumor site, which suggests such a response may be more meaningful from the perspective of effectively combating the disease.

Table 2. Recurrent GBM Vaccine Data

Company/ Institution	Product/ Reference	Clinical Stage	# Patients w/ GBM	Median Age	Overall Survival
Agenus, Inc.	Prophage G-200 [HSPPC-96][ix]	Phase II	33/33	53 [n=33]	11 [n=33]
Catholic University of Leuven, Belgium	DC pulsed w/ tumor lysate [+/- booster of lysate without DC][x]	Phase I/II	56/56	45 [n=56]	9.6 [n=56]
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, California	DC pulsed w/ tumor lysate[xi]	Phase II	21/32	54 [n=32]	13.4 [n=12] to 20 [n=9]
TVAX Biomedical	TV1-Brain-1[xii]	Phase I	16/19	50 [n=19]	12 [n=19]
Niigata University School of Medicine, Niigata, Japan	DC pulsed w/ tumor lysate[xiii]	Phase I/II	18/24	53 [n=18]	16 [n=18]
Oncovir/University of Pittsburgh	a-type 1 polarized DCs pulsed w/ defined HLA-A2 peptides plus poly-ICLC adjuvant[xiv]	Phase I/II	13/22	54 [n=13]	12 [n=13]

?

Several companies are also currently conducting immunotherapy trials in newly diagnosed GBM, with encouraging results presented to date, including Agenus [ClinicalTrials.gov: NCT00905060], Celldex Therapeutics [ClinicalTrials.gov: NCT01480479], Immatics [ClinicalTrials.gov: NCT01222221], ImmunoCellular [ClinicalTrials.gov: NCT01280552], Innocell Corporation [ClinicalTrials.gov: NCT00807027], and Northwest Biotherapeutics [ClinicalTrials.gov: NCT00045968].

An important future direction for the successful treatment of these very difficult tumors may involve the combination of immunotherapeutic agents with other synergistic treatments. ?Such approaches could simultaneously address the immunosuppressive, angiogenic, invasive, and hypoxic nature of GBM.? In this regard, combination approaches with Avastin? [bevacizumab] and other potentially synergistic agents would make imminent sense to pursue.

Note: For further information on this topic, click here to view a replay of the plenary session ?Advances in immunotherapy for glioma? by Andrew T. Parsa, M.D., Ph.D., University of California, San Francisco, from MD Becker Partners? 2nd Annual ?Cancer Immunotherapy: A Long-Awaited Reality? Conference held October 6, 2011.

References

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[i] Medawar PB.? Immunity to homologous grafted skin: the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol. 1948 Feb;29(1):58-69.

[ii] Heimberger AB, Sampson JH.? Immunotherapy coming of age: What will it take to make it standard of care for glioblastoma?? Neuro Oncol. 2011 Jan;13(1):3-13. Epub 2010 Dec 10.

[iii] Guinto G, F?lix I, Ar?chiga N, Arteaga V, Kovacs K. Primary central nervous system lymphomas in immunocompetent patients.? Histol Histopathol. 2004 Jul;19(3):963-72.

[iv] McCarthy BJ, Rankin K, Il?yasova D, Erdal S, Vick N, Ali-Osman F, Bigner DD, Davis F. Assessment of type of allergy and antihistamine use in the development of glioma.? Cancer Epidemiol Biomarkers Prev. 2011 Feb;20(2):370-8.

[v] Nauts HC, McLaren JR. Coley toxins ? the first century.? Adv Exp Med Biol. 1990;267:483-500.

[vi] Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.? N Engl J Med. 2005 Mar 10;352(10):987-96.

[vii] Grossman SA, Ye X, Piantadosi S, Desideri S, Nabors LB, Rosenfeld M, Fisher J; NABTT CNS Consortium.? Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States.? Clin Cancer Res. 2010 Apr 15;16(8):2443-9. Epub 2010 Apr 6.

[viii] Caroli M, Locatelli M, Campanella R, Motta F, Mora A, Prada F, Borsa S, Martinelli-Boneschi F, Saladino A, Gaini SM.? Temozolomide in glioblastoma: results of administration at first relapse and in newly diagnosed cases. Is still proposable an alternative schedule to concomitant protocol?? J Neurooncol. 2007 Aug;84(1):71-7. Epub 2007 Mar 15.

[ix] A. Parsa, C. Crane, S. Han, V. Kivett, A. Fedoroff, N. A. Butowski, S. M. Chang, J. L. Clarke, M. S. Berger, M. McDermott, M. Aghi, C. Yanes, M. Prados, A. E. Sloan, J. N. Bruce.? Autologous heat shock protein vaccine (HSPPC-96) for patients with recurrent glioblastoma (GBM): Results of a phase II multicenter clinical trial with immunological assessments.? J Clin Oncol 29: 2011 (suppl; abstr 2565)

[x] De Vleeschouwer S, Fieuws S, Rutkowski S, Van Calenbergh F, Van Loon J, Goffin J, Sciot R, Wilms G, Demaerel P, Warmuth-Metz M, Soerensen N, Wolff JE, Wagner S, Kaempgen E, Van Gool SW.? Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme.? Clin Cancer Res. 2008 May 15;14(10):3098-104.

[xi] Wheeler CJ, Black KL, Liu G, Mazer M, Zhang XX, Pepkowitz S, Goldfinger D, Ng H, Irvin D, Yu JS.? Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients.? Cancer Res. 2008 Jul 15;68(14):5955-64.

[xii] Sloan AE, Dansey R, Zamorano L, Barger G, Hamm C, Diaz F, Baynes R, Wood G.? Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes.? Neurosurg Focus. 2000 Dec 15;9(6):e9.

[xiii] Yamanaka R, Homma J, Yajima N, Tsuchiya N, Sano M, Kobayashi T, Yoshida S, Abe T, Narita M, Takahashi M, Tanaka R.? Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial.? Clin Cancer Res. 2005 Jun 1;11(11):4160-7.

[xiv] Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, Zeh H, Holtzman MP, Reinhart TA, Whiteside TL, Butterfield LH, Hamilton RL, Potter DM, Pollack IF, Salazar AM, Lieberman FS.? Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma.? J Clin Oncol. 2011 Jan 20;29(3):330-6. Epub 2010 Dec 13.

Source: http://lifesciencedigest.com/2012/02/22/rethinking-immunotherapy-for-brain-tumors/

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Morgan Rotondi: "You Speak German Well... for an American"

Contrary to popular belief, the above-mentioned phrase is decidedly not a compliment, regardless of the intentions of the speaker. These words can be said in English, in German, or with any variety of well-meaning tones of voice. The phrase remains the worst sort of backhanded compliment: an unintentional one.

The unsaid statement behind the phrase is, "I'm surprised you can speak a foreign language well, because most Americans can't." My immediate reaction is to refute such a claim: What the hell does my Passport have to do with my knowledge of German? Since when does citizenship determine foreign language proficiency? Unfortunately, when my righteous anger died down, I came to a terrible realization. They might be right.

My Massachusetts public education first exposed me to foreign languages in the 7th Grade, when I was 13 years old. We had a trimester of French, Spanish, and German, giving each of us a taste of the language so we could better decide which introductory language course to take in the 8th Grade. In most European countries, students start learning a foreign language when they are eight years old. For most U.S. eight-year-olds, learning a foreign language is not even an option. Only 24% of public elementary schools in the United States offer foreign language courses, according to the Center for Applied Linguistics. Among those schools that do offer foreign language instruction, 79% focus on introductory exposure rather than overall proficiency.

As someone who values foreign language education, I have a huge problem with these figures. But am I just biased on the issue? Europeans come into contact with foreign languages much more often than U.S. citizens, simply by living in a part of the world where so many countries with different cultures, languages, and dialects of language coexist. Of course someone from Luxembourg is going to need to speak multiple languages; Luxembourg has three official languages and borders Belgium, France, and Germany. And isn't English a so-called "world language" anyway? To achieve international success in either business or science, a strong grasp of the English language is crucial. At least, that's what my U.S. upbringing has led me to believe.

I cannot disprove the usefulness of English as a first language; on the contrary, I can only confirm from various traveling experiences that my knowledge of the English language allowed me to communicate when I otherwise could not. And yes, from my hometown in Massachusetts the nearest non-English speaking country is Canada, in the Quebec province, and that's quite a trip. So why should U.S. citizens bother to learn a foreign language when "everybody speaks English anyway," when opportunities to use foreign language skills are few and far between?
Studies have shown that learning a second language benefits students in other academic subjects. Students in the U.S. who study a foreign language statistically perform better on standardized tests than those who do not in core areas such as math, reading, and English language literacy. Even problem solving skills are positively affected. If enhanced academic performance is not reason enough, let's look at the "global dominance" of the English language. In terms of global population, the percentage of native English speakers is on the decline. With a worldwide decrease in native English speakers, it is only natural that other languages, like Mandarin Chinese, will grow in proportion to their native-speaking populations. While I'm not suggesting we all begin learning Mandarin, I am suggesting that the U.S. needs to re-assess its values in education. We cannot simply assume English is the "world language," or that English will indefinitely remain vital in global discourse.

Personally, learning the German language has shaped and enriched the person I am today. Since moving to Dresden, Germany I have met so many wonderful, patient people not only willing, but excited to help me learn German. Even after all the embarrassing mistakes, misunderstandings, and unintentional backhanded compliments, at the end of each day I've learned something, and it's not always language-related. Learning a foreign language has been one of the most rewarding experiences of my life, a learning experience from which all people, regardless of citizenship, can benefit.

?

Source: http://www.huffingtonpost.com/morgan-rotondi/post_3019_b_1287879.html

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2012 Trends in General Aviation | Golden Wisdom Nuggets

General aviation has sure been a tough row to hoe in the last good many years. Nevertheless things are not looking so bad moving forward. It looks as if China will open their general aviation market meaning wealthy Chinese will own private business jets, and light aircraft. That?s good news for US aircraft manufacturers, but it also means that China will be breaking into the general aviation manufacturing sector, which has typically been owned by US companies. That will change the global dynamics of this sector.

Business jets are finally making a comeback, after being maligned by the Obama Administration, and the class warfare issues which currently are pervasive throughout our society. The costs to operate aircraft today are an incredible challenge for general aviation, thus, things like lighter materials, better aerodynamic designs, and more efficient electronics will be in demand to help in overcoming those challenges. Many of the new carbon composite advances in the airline sector and the military sector are now making their way into general aviation.

This also means lighter and more efficient aircraft with better performance, safety, and fuel economy. One trend which has some folks on edge is the prospect of more autonomous aircraft flying around in the same airspace posing a safety risk for general aviation aircraft. In fact these dangers may cause the Federal Aviation Administration to require all small light aircraft of any size to have special electronics for positioning data at all times. In some regards this takes away the freedom in general aviation, but it also introduces safety features which may come forth allowing for the future flying cars.

Another challenge is that with GPS systems, especially those devices on the lower end. The interference of devices made by light squared for mobile communication are a real issue now in debate. This ?could? or ?might? also cause safety risks, and it has the general aviation sector up in arms, as well they should. Some say these challenges are blown out of proportion, but we have to wait and see.

There have been some concepts floated in Congress about establishing taxes for each flight, if those are imposed as stated it would have a dire effect on general aviation overall. We don?t know if that legislation will move forward, but perhaps not.

The very light jet market seems to have had a bubble burst in its early lifecycle just as it was getting off the ground, but you can expect in the future that this sector will be moving along at a more practical growth rate. Well, that?s all for now, however you might wish to subscribe to my articles so that you don?t miss future trends as they occur. Indeed I hope you will please consider all this and think on it.

Cake Pops Recipe

This entry was posted on Monday, February 20th, 2012 at 2:10 am and is filed under Outdoors. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.

Source: http://www.goldenwisdomnuggets.mobi/2012-trends-in-general-aviation/

target

On West Coast, Obama courts campaign donors

President Barack Obama greets supporters as he arrives on Air Force One at Los Angeles International airport Wednesday, Feb. 15, 2012, in Los Angeles. (AP Photo/Damian Dovarganes)

President Barack Obama greets supporters as he arrives on Air Force One at Los Angeles International airport Wednesday, Feb. 15, 2012, in Los Angeles. (AP Photo/Damian Dovarganes)

President Barack Obama arrives at Los Angeles International Airport in Los Angeles, Wednesday, Feb. 15, 2012.(AP Photo/Damian Dovarganes)

LOS ANGELES (AP) ? Courting donors in Democrat-rich California, President Barack Obama is raising millions of dollars for his re-election bid while warning supporters that a long campaign awaits.

Obama was holding four fundraisers Thursday in the Los Angeles area and in San Francisco, reeling in campaign cash from reliable Democratic donors at a time when the Republican presidential contest remains unsettled. The president was expected to raise more than $8 million from events that will take him from Los Angeles and San Francisco on Thursday to the Seattle area on Friday.

At the posh home of a Hollywood soap opera producer, the president urged Democrats to mobilize, telling supporters that the 2012 election "is not going to be easier this time. It's going to be harder this time."

"People out there are hurting and they need us to do more," Obama said on a star-studded night that included a performance by the Foo Fighters and appearances by actors Jack Black and Rashida Jones.

Obama later told donors at an intimate dinner ? including actors George Clooney and Jim Belushi ? that he understood that some of his supporters remain frustrated that the war in Afghanistan has yet to end and the U.S. naval prison at Guantanamo Bay, Cuba, remains open. He reminded the guests that former New York Gov. Mario Cuomo often referred to campaigning in poetry and governing in prose.

"We've been slogging through prose for the last three years," Obama said. "People, they like the poetry."

California has been a mainstay of Democratic party fundraising ? and a reliably blue state ? and Obama's campaign expected to collect millions from six events in Los Angeles and San Francisco over two days.

On Thursday, Obama was attending a fundraising luncheon in Corona del Mar, Calif., outside Los Angeles, with 125 supporters paying tickets starting at $2,500.

The president was then traveling to San Francisco, where he was meeting with 20 supporters paying $35,800 per person, and then attending a dinner for 70 people paying the same amount.

A larger fundraiser was planned at the Nob Hill Masonic Center for 2,500 people, featuring a performance by singer Chris Cornell. Tickets started at $100 for the reception. The events support the Obama Victory Fund, a joint fundraising committee of the Obama campaign and the Democratic National Committee.

The president raised more than $220 million for his campaign and the DNC in 2011 and is trying to use a protracted Republican presidential primary to build a financial buffer zone to help his cause in the November general election. Democrats have warned that outside groups supporting Republicans will pour hundreds of millions of dollars into the campaign against Obama.

Obama was making his first fundraising trip outside Washington since his campaign announced it would encourage supporters to donate to a Democratic super PAC backing Obama's re-election. Obama, Vice President Joe Biden and their wives do not plan to appear at events for the super PAC, Priorities USA.

It was also Obama's first trip to Hollywood since Congress delayed action on legislation cracking down on online piracy. The legislation was pushed by the film industry and garnered major opposition from Internet companies, pitting two Democratic constituencies against each other, before it stalled.

Obama has said any legislation must protect intellectual property that creates jobs in the U.S., while still respecting the integrity of the Internet as an open system. The president made no mention of the issue during remarks Wednesday.

The president was traveling along the West Coast as Congress reached a tentative agreement to extend a payroll tax cut that would mean an extra $40 per paycheck for a typical family, along with an extension of unemployment benefits. The payroll tax break was as the heart of Obama's jobs plan.

___

Follow Ken Thomas on Twitter: http://twitter.com/AP_Ken_Thomas

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/89ae8247abe8493fae24405546e9a1aa/Article_2012-02-16-Obama/id-515d7f5e29e04175a88c33e3007de086

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Your Backyard Is Likely To Improve By Using Window Boxes And ...

Posted on February 15th, 2012 | by Joshinator |

Homes come with many tiny jobs that you don?t exactly anticipate. Some of these jobs tend to be on the inside of the house, but many are for making the outside of your home look nicer. When you take the time to improve your yard, it will make your home a much nice placer to look at. Nothing will make your home look nicer than a lush, green, magnificently landscaped yard.

Landscaping is one thing that just about every house needs. It could be nice to always have a landscaping expert come in and tidy up everything. Even though you do, there are times that you would like to touch up some spots, such as where water drifts, or maybe you want to adds some minor layers. Though simple in nature, these kinds of improvements often require the right tools and equipment needed to do the job properly. There are some equipment that are absolutely essential, where others would just be nice to have, but you can get by without. Specific tools are very expensive, and are generally only in the possession of those who are in the landscaping business.

Renting can be the most efficient choice as it is not viable to spend a lot of money on something that you?ll use less than three times a year. A lot of people possess tools such as certain kinds of applicators or fertilizer spreaders but do not know how they are used for landscaping. Landscape design tools are not always classified properly. If you have these tools, and they may be just laying there unused, then it is time for you to start taking advantage of them. These kinds of tools can give your yard the style you want, and transform into something more beautiful than you expected. can have lush looking turf that is flourishing, instead of having outbreaks of those ugly weeds.

Even though we are offering a solid overview with some pertinent details about Hpotter.com, there is much more than you may realize. We really had to pare down a lot of content to squeeze so much into this, but we are not done by any means. As you go through this, some things will standout more than others, but do not throw the baby out with the bathwater, either. Once you have more time to think about things, we think you will arrive at the conclusion that it actually is helpful. We urge you to be open to information even if at first glance it does not seem like it will help you. In the rest of our discussion, we will offer more information that will reinforce what you have already learned, and then you will be better equipped to understand.

So, if you think that you will not be able to remember it all, you can and we have confidence that it will gel with some helpful tips to follow. Irrigation tools really are a must to be used very often if you intend to keep up with your yard work yourself. Irrigating is needed for new foliage or cultivating any plants or trees. If you have any flowers or shrubs that happen to be dying, they will definitely need to be watered consistently. Timed sprinklers will be the best possible solution in terms of watering your plants. When you elect to get timers, you can be on holiday and your plants, shrubs, and grass will still get watered. Additionally it is able to take advantage of limited water supplies, to enable you to water at the proper times.

Landscaping tools can make having lush greenery in your yard much easier and complement the way your home looks. While using the internet, it is less difficult to locate the best deals for landscaping equipment and tools.

Source: http://www.strappedupwaistwear.com/strapped-up-waist-wear/of-improvements-often

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Source: http://uliybcmut.posterous.com/your-backyard-is-likely-to-improve-by-using-w

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Batman Mr. Potato Head Is the Tuber Gotham Deserves [Toys]

Many years ago SNL created a commercial for the fictional toy line available for the Tom Hanks' film Philadelphia. It was of course completely inappropriate for the tone of the film, just like this Dark Knight-themed Potato Head. More »

Source: http://feeds.gawker.com/~r/gizmodo/full/~3/HK86WdLSKj8/batman-mr-potato-head-is-the-tuber-gotham-deserves

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Nokia accidentally reveals white Lumia 900

It looks like it. It seems plenty of you were enraptured by that hypnotic white Lumia 800 we paid a visit to yesterday, but in all the glossy fun, Nokia accidentally revealed the above press shot -- a white Lumia 900. The picture was soon lifted from Nokia's Conversations blog, but it remains on its Facebook page, flashing an exposed micro-USB port and front-facing camera that identifies this snow-white slab as the Lumia 900 kind. The press shot also flashes a view of that non-curved glass front; it certainly looks like our wishes are coming true. Now we just have to wait and see if this color option is ready for that plausible March release date.

Update: Dave Zatz was apparently offered a choice of white or black models when discussing his Lumia 900 pre-order options at a Microsoft store. Maybe we'll see this one from launch.

[Thanks to everyone who sent this in.]

Nokia accidentally reveals white Lumia 900 originally appeared on Engadget on Tue, 07 Feb 2012 04:26:00 EDT. Please see our terms for use of feeds.

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