text:
EYEWITNESS LOCAL NEWSMan Shot In Rand, Deputies Looking For Suspect
from Eyewitness News Online
Reported by: Leslie Rubin
Web Producer: Mamie Buoy
Reported: Dec. 10, 2013 8:26 PM EST
Updated: Dec. 11, 2013 9:39 AM EST
Rand , Kanawha County , West Virginia
We have new information about a shooting Tuesday evening in Rand.
Deputies say a man was beaten before he was shot in the leg at an apartment building on Raven Drive.
The shooting happened around 7:30 p.m..
Deputies believe the victim knew three to four of the attackers. They say they were black males wearing hooded sweatshirts.
Deputies believe the suspects fled in a white SUV.
The victim's name and a motive are not being released at this time.
A man is in the hospital after a shooting in Rand.
It happened in the 5100 block of Raven Drive around 7:30 p.m. Tuesday.
We are told the man was hit in the leg and deputies are searching for a suspect.
Witnesses say they heard a gunshot and saw a white SUV leaving the scene. At this time, it is unclear if the person driving that vehicle was involved.
The victim's name has not been released.
Anybody with information should call the Kanawha County Sheriff's Office.
Send email to firstname.lastname@example.com for information or comments concerning WCHS-TV Eyewitness News.
Copyright ©2014, WCHS-TV8. Portions are Copyright 2014 Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or distributed.
WCHS ABC 8 provides local news, weather forecasts, traffic updates, notices of events and items of interest in the community, sports and entertainment programming for Charleston and nearby towns and communities in the Tri-State area, including Huntington, Dunbar, Marmet, Montgomery, Nitro, South Charleston, St. Albans, Cedar Grove, Chesapeake, Clendenin, East Bank, Glasgow, Pratt, Cross Lanes, Elkview, Pinch, Sissonville, Big Chimney, Cabin Creek, Chelyan, Davis Creek, Institute, Jefferson, Loudendale, Mink Shoals, Pocatalico, Quick, Quincy, Rand, Buffalo, Eleanor, Hurricane, Nitro, Poca, Winfield, Culloden, Fraziers Bottom, Hometown, Red House, Scott Depot, Teays Valley, Danville, Madison, Hamlin, Logan, Chapmanville, Man, Delbarton, Kermit, Gilbert, Matewan, Williamson, Summersville, Richwood, Flatwoods, Gassaway, Sutton, Spencer, Ravenswood, Ripley, Mason, Point Pleasant, Ashland, Pikeville, Ironton, Portsmouth, Gallipolis, and Athens.


text:
Gender: Male
Years in Practice: 14 Years
Languages Spoken: English, Spanish
Medical School: SUNY Downstate Medical Center College of Medicine
Graduation Date: 2000
Hospital Affiliations: Mercy Medical Center, South Nassau Communities Hospital, Eastern Long Island Hospital, Winthrop University Hospital, Long Island Jewish Medical Center, Franklin Hospital, North Shore University Hospital
Specialties: Neurological Surgery
*This physician has multiple office locations. See Appointments for details.
©2005-2014 WebMD, LLC. All rights reserved.
WebMD does not provide medical advice, diagnosis or treatment. See additional information.

subset: commoncrawl


text:
AMSTERDAM _ The air was biting cold outside, but it was warm in the old pickup, tooling along the Thruway.
``This is our exit,'' said Hon, who had printed out a Google map.
``Amsterdam.'' Uncle Chet looked toward the old brick city. ``Haven't been here in a while.''
``I haven't been here in 40 years,'' I said.
``We're still a ways from Cambridge,'' he said. ``That's just north of where I was born.''
``Never thought I'd go to just north of where you were born to get a claw-foot bathtub.'' I glanced at Hon.
``They're pretty rare,'' she said, ``especially when they're small and deep like this one.''
``Are you buying this thing, sight unseen?'' Uncle Chet asked as we slowed down on the curving exit ramp.
``We're not driving six hours to go window shopping,'' I said.
``It looked good in the photos,'' Hon said. ``And the ad said the porcelain is perfect.''
``Wonder how old it is?'' I slowed for a tollbooth in a line of traffic.
But when I clutched to down-shift, the clutch froze to the floor. I hit the pedal again; it stayed down. I swore, braked harder, reached down with my left hand to my left heel, stretching until my nose was just above the dashboard and I got a finger under the pedal.
I pulled the pedal up, then pushed it halfway down again with my foot and wiggled the shift into neutral.
``Is that an Olympic sport?'' Uncle Chet said.
``That's Toyota quality,'' I said. ``But it's happened before, so I know what to do.''
``You mean, you're going to do that every time we shift?'' he said. ``I'm getting out right here.''
``No, I just can't put the pedal all the way down,'' I assured him. ``Something freezes when it hits the floor.''
``Why don't you get it fixed?'' he asked as we idled up to the toll attendant.
``It only happened once; I thought it went away.''
``We should have taken my truck,'' he said ruefully.
``We'll be fine.'' I took the change and closed the window. ``When we get home, I'll call Toyota and ask them to recall all their '93 pickups.''
``There are no other '93s,'' he said. ``They've done their 350,000 miles and been recycled.''
``Take Route 30 north,'' Hon pointed to the sign.
``Then I'll ask Congress to investigate,'' I said. ``It's an outrage, clutches wearing out after only 17 years.''
``I think Toyota should be investigating Congress, not the other way around,'' Uncle Chet said. ``How many people has Toyota killed with its faulty brakes?''
``I heard 19,'' Hon said.
``Nineteen?'' Uncle Chet said. ``Toyota sells 2 million vehicles a year here. There must be at least 20 million on the road, so your odds of being killed by Toyota's faulty brakes would seem to be less than one in a million.''
``Sounds right,'' I said as we wound through downtown.
``And what are the odds of finding a senator lining his pocket, representing Big Business?'' he asked.
``Oh, probably even money,'' I said.
``Or having a mistress on the side?''
``Three in 10?'' I posited.
``I say even money on that, too,'' Hon said as we glided past Walgreens in a line of traffic.
``And what are the odds of a senator soliciting carnal favors in the men's room?''
``That, we know is at least one in a hundred,'' I said.
``And how many people has Congress killed with the endless wars it funds and the endless stalling on universal health care?''
``Thousands, tens of thousands,'' I said.
``So there you have it. Congress is rife with ethics problems, in the pocket of the high and mighty, and people are dying.'' Uncle Chet said. ``Toyota should have a field day looking into this.''
Cooperstown Bureau Reporter Tom Grace is traveling with his Uncle Chet, who he says is imaginary. Grace's column appears every other week. For more of his columns, visit www.thedailystar.com/tomgrace.


text:
vendor info...
Koalita Craft
Koalita Craft gives the special touch to make your party memorable.
product info: ...
Wedding/party Hearts Decorations - christmas, autumn shades, brown, yellow, white - Set of 6 - Ornaments/favors/decor/gifts
These Hearts are perfect for a fall wedding, birthday party decoration or even to cherish your home this Autumn. In white, shades of yellow and shades of brown. These ornaments are made with felt and filled with polyester toy filling.
This listing is for a set of 6 Hearts in 6 different colours.
Each heart measures: approx. 5 cm plus approx. 7 cm thread
Handmade by me in the UK with love and care and sent with the same attention.
Allow 5-7 days to make the order before shipping.
We do custom orders. If you would like to have other quantities or colours just convo me.
Thank you for your visit. To see more: http://www.etsy.com/shop/KoalitaCraft
etsy products... View all Etsy products →
The term 'Etsy' is a trademark of Etsy, Inc. This application uses the Etsy API but is not endorsed or certified by Etsy, Inc.


text:
The new pope chose Francis in honor of St. Francis of Assisi, one of the Catholic Churchs holiest figures. The news services are reporting that hundreds if not thousands of newly born boys are being given that name. Its a good name for someone dedicated to a life of healing and understanding.
The original Francis hometown lived up to the love that he proclaimed, to be an instrument of peace and where there was despair to bring hope.
During World War II, the town of Assisi witnessed a beautiful occurrence. All 26 convents and monasteries helped or hid Jewish refugees from Hitlers Gestapo.
Christians and non-Christians regard St. Francis of Assisi as a saint.
Francis was born in 1181, the time when poetry in the Italian language was just beginning. His ways of love and dedication to God quickly became the stuff that the poets sang about. This folklore was eventually written down in Latin and translated into medieval Italian as the Fioretti (The Little Flowers) of St. Francis.
St. Francis was named Giovanni or John at birth, the son of Pietro di Bernadone, a wealthy cloth merchant in the rugged Umbrian Mountain range of central Italy about 80 miles north of Rome.
His mother was born in Provence, the bountiful region of southeastern France. The boy was quickly called Francis by most of the family friends and townspeople.
Assisi fought a series of wars with her neighbor, the larger and more prosperous town of Perugia. Francis was captured in a battle and imprisoned for a year in Perugia.
His family ransomed him and he returned to Assisi a changed person. Rather than return to fight another war, Francis began to minister to the poor.
One day Francis saw a leper in the forest outside Assisi. At first, Francis drew back in fear. Victims of leprosy were objects of great dread in medieval and early modern society. They were required to carry a wooden bell or clacker, singing out Beware Leprosy Beware.
Then Francis decided that he must embrace the thing he feared most. Only then could he be free. He grasped the mangled limbs and embraced the withered body of the leper, and in doing so realized he was embracing Christ Jesus.
Afterward, he passed by the church of San Damiano outside Assisi. The ancient crucifix within the derelict church seemed to call out to Francis: Go, repair my house, which you see is falling down.
Francis thought he was called to repair the ruined structure. Later he realized he was called to heal the church mankind.
He sold some of his fathers cloth to pay for the repairs, and his furious father locked him in a storeroom from which he escaped.
Francis left his family and renounced his inheritance. He chose a life of poverty, begging for his food. He used the language of courtly love to express suffering, thanking Brother Flea for biting him and reminding him of the suffering of Christ. He thanked Brother Sun for burning his skin and Sister Moon for providing light with which to light his path through the night. Francis embraced Lady Poverty with the good manners of a gentle knight.
Francis was joined by seven disciples. They lived communally in the Portiuncula (The Little Portion) near Assisis leper colony.
They called themselves the little brothers. Francis sought approval for the group from church authorities. He was required to establish a formal set of rules, which included poverty, chastity and obedience to the pope. They became the order of Friars Minor. Usually theres an O.F.M. after the name of members of the order.
The Little Brothers became one of the largest religious movements within the Christian church. Francis followers came to California in 1769, but thats another story.
Dan Kriegers column is special to The Tribune. He is a professor emeritus of history at Cal Poly and past president of the California Mission Studies Association.


text:
TICONDEROGA — Stephen Pell Dechame died suddenly at his family home, Le Petite Pavillion, Ticonderoga, N.Y., on Wednesday, Oct. 23, 2013.
He was born Dec. 18, 1947, at Moses-Ludington Hospital, Ticonderoga, N.Y. The beloved son of Stephanie Pell and Roger Dechame, Stephen shared his parents lifelong love, and devotion to Fort Ticonderoga. Through his parents, Stephen was a direct descendent of the Lords of the Manor of Pelhham, N.Y., and Stephen H.P. and Sarah G. T. Pell, who began the reconstruction of Fort Ticonderoga in 1908.
He attended Ticonderoga Public Schools, The North Country School, Lake Placid N.Y., The Pomfret School in Pomfret, Conn., Case Western Reserve University, Cleveland, Ohio and the New England School of Law, Boston, Mass.
Stephen's life was dedicated to the fulfillment of Social Justice. In addition to his service to Fort Ticonderoga, Stephen gave his life completely to his clients in the Massachusettes Juvenile Justice System where he served as a Juvenile Defender, Guardian Ad Liten, and advocate for reform. His efforts touched and benefited uncounted lives.
While Stephen would never accept praise or allow himself to be distinguished for his work as a Public Defender and Advocate, he was particularly proud to be a Trustee of Fort Ticonderoga, a position he maintained throughout his life through July, 2013. With a passion of all aspects of Fort Ticonderogas vast and diverse history, Stephen took particular interest in the arrival of Samuel de Champlain in July 1609. Stephen's devotion to his Mother, Stephanie Pell Dechame, especially in her later years, was an inspiration to all who knew them.
Stephen is survived by his devoted brother, Robert Pell Dechame of Charleston, S.C.; his beloved cousins, William Hudson, and Sarah Hudson Krueger; his God-children, Mimi Krueger Rozek, and Christopher Krueger. He is also survived by his aunts, the Countess Mary Elizabeth de Lyrot, Alexandra Pell Kuhel; and his uncles, Frederick H. Allen and Anthony Pell; nieces, nephews and cousins. He is remembered by special friends, James O'Neil, Pope Simmons, and Frederick, Thomas and Audrey Provoncha.
Private Services will take place at the convenience of the family.
Contributions to his memory may be made to the Fort Ticonderoga Association, P.O. Box 390, Ticonderoga, NY, 12883.
Arrangements are under the direction of the Wilcox & Regan Funeral Home of Ticonderoga, N.Y.


text:
Dubai to get another high-rise building by 2017
Builder of the Burj Khalifa awarded AED1.8 billion construction contract.November 6, 2013 4:11
Register for our free newsletter
Drake & Scull said on Monday that its shareholders had approved issuing a convertible bond worth 55 million dirhams.
Etihad Airways confirms that it is not in talks with Malaysia Airlines about the possibility of an equity investment in the carrier.
Oil prices are at a suitable level for OPEC members and the group sees no shortage in supply, says UAE Energy Minister.
Israel's parliament has given initial approval to a law to enable the force-feeding of Palestinian prisoners on a hunger strike.
Turkey is investigating 28 truck drivers ferrying diesel to the Iraqi city of Mosul have been abducted by militants.
At least 27 people including 10 militants were killed at an attack on Karachi Jinnah Airport on June 8.
Israel announced on Thursday it would build 1,500 more settler homes in response to the formation of a Palestinian unity government.
Saudi MERS deaths rise to 282 from 190, cases from 688 from 575.
Kuwait's oil minister said his country was looking to sign an agreement with Iran to secure natural gas supplies.
The CID of the UAE has launched an aggressive campaign to track down illegal satellite service providers.
Builder of the Burj Khalifa awarded AED1.8 billion construction contract.November 6, 2013 4:11
Dubai-based developer issues statement to dismiss media reports.November 4, 2013 11:31
By Steven Bond, published first on sister website AMEinfo.com Cyber tourists can now reach dizzying new heights, but keep their…June 26, 2013 1:00
Cayan Tower opens with a bang and breaks world recordJune 11, 2013 5:44
Builder of Burj Khalifa hints at building something taller...May 2, 2013 10:13
At 828 meters, the Burj Khalifa stands tall and proud as Dubai's prized landmark and the world's tallest, possibly glitziest building; but behind the glittering façade is the sordid story of struggle and disappointment. And Dubai's extravagant, ostentatious outlook might have something to do with it.July 22, 2012 2:19
China, Saudi Arabia and Azerbaijan are all vying to out-build each other in the race to erect the tallest building in the world. What's pushing these countries to the brink of the stratosphere?June 13, 2012 5:46
Three of the UAE's cities have made it onto a list of tallest cities in the world, compiled by a German building data company. Kipp takes a look at the Arab cities that have skylines worth watching.May 1, 2012 3:45
The Earth in TimeLapse; How Do You Get a Million People to Buy a Gadget That Nobody's Even Used Yet?November 17, 2011 3:58
What makes a singles pad different from a families? Not that much apparently, except the bachelors would much rather stick together. Precious de Leon cuts through the cheese.August 29, 2011 3:06


text:
|Interferon alpha/beta domain
The molecular structure of human interferon-alpha
Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens such as viruses, bacteria, parasites or tumor cells. They allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.
IFNs belong to the large class of glycoproteins known as cytokines. Interferons are named after their ability to "interfere" with viral replication within host cells. IFNs have other functions: they activate immune cells, such as natural killer cells and macrophages; they increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes; and they increase the ability of uninfected host cells to resist new infection by virus. Certain symptoms, such as aching muscles and fever, are related to the production of IFNs during infection.
About ten distinct IFNs have been identified in mammals; seven of these have been described for humans. They are typically divided among three IFN classes: Type I IFN, Type II IFN, and Type III IFN. IFNs belonging to all IFN classes are very important for fighting viral infections.
Types of interferon[edit]
Based on the type of receptor through which they signal, human interferons have been classified into three major types.
- Interferon type I: All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains.[1] The type I interferons present in humans are IFN-α, IFN-β, IFN-ε, IFN-κ and IFN-ω.[2]
- Interferon type II: Binds to IFNGR that consists of IFNGR1 and IFNGR2 chains. In humans this is IFN-γ.
- Interferon type III: Signal through a receptor complex consisting of IL10R2 (also called CRF2-4) and IFNLR1 (also called CRF2-12). Acceptance of this classification is less universal than that of type I and type II, and unlike the other two, it is not currently included in Medical Subject Headings.[3]
All interferons share several common effects; they are antiviral agents and can fight tumors.
As an infected cell dies from a cytolytic virus, viral particles are released that can infect nearby cells. However, the infected cell can warn neighboring cells of a viral presence by releasing interferon. The neighboring cells, in response to interferon, produce large amounts of an enzyme known as protein kinase R (PKR). This enzyme phosphorylates a protein known as eIF-2 in response to new viral infections; the phosphorylated eIF-2 forms an inactive complex with another protein, called eIF2B, to reduce protein synthesis within the cell. Another cellular enzyme, RNAse L—also induced following PKR activation—destroys RNA within the cells to further reduce protein synthesis of both viral and host genes. Inhibited protein synthesis destroys both the virus and infected host cells. In addition, interferons induce production of hundreds of other proteins—known collectively as interferon-stimulated genes (ISGs)—that have roles in combating viruses.[4][5] They also limit viral spread by increasing p53 activity, which kills virus-infected cells by promoting apoptosis.[6][7] The effect of IFN on p53 is also linked to its protective role against certain cancers.[6]
Another function of interferons is to upregulate major histocompatibility complex molecules, MHC I and MHC II, and increase immunoproteasome activity. Higher MHC I expression increases presentation of viral peptides to cytotoxic T cells, while the immunoproteasome processes viral peptides for loading onto the MHC I molecule, thereby increasing the recognition and killing of infected cells. Higher MHC II expression increases presentation of viral peptides to helper T cells; these cells release cytokines (such as more interferons and interleukins, among others) that signal to and co-ordinate the activity of other immune cells.
Interferons, such as interferon gamma, directly activate other immune cells, such as macrophages and natural killer cells.
Interferons can inflame the tongue and cause dysfunction in taste bud cells, restructuring or killing taste buds entirely.[8]
Induction of interferons[edit]
Production of interferons predominantly occurs in response to microbes, such as viruses and bacteria, and their products. Binding of molecules uniquely found in microbes—viral glycoproteins, viral RNA, bacterial endotoxin (lipopolysaccharide), bacterial flagella, CpG motifs—by pattern recognition receptors, such as membrane bound Toll like receptors or the cytoplasmic receptors RIG-I or MDA5, can trigger release of IFNs. Toll Like Receptor 3 (TLR3) is important for inducing interferon in response to the presence of double-stranded RNA viruses; the ligand for this receptor is double-stranded RNA (dsRNA). After binding dsRNA, this receptor activates the transcription factors IRF3 and NF-κB, which are important for initiating synthesis of many inflammatory proteins. RNA interference technology tools such as siRNA or vector-based reagents can either silence or stimulate interferon pathways.[9] Release of IFN from cells is also induced by mitogens. Other cytokines, such as interleukin 1, interleukin 2, interleukin-12, tumor necrosis factor and colony-stimulating factor, can also enhance interferon production.[10]
Downstream signaling[edit]
By interacting with their specific receptors, IFNs activate signal transducer and activator of transcription (STAT) complexes; STATs are a family of transcription factors that regulate the expression of certain immune system genes. Some STATs are activated by both type I and type II IFNs. However each IFN type can also activate unique STATs.[11]
STAT activation initiates the most well-defined cell signaling pathway for all IFNs, the classical Janus kinase-STAT (JAK-STAT) signaling pathway.[11] In this pathway, JAKs associate with IFN receptors and, following receptor engagement with IFN, phosphorylate both STAT1 and STAT2. As a result, an IFN-stimulated gene factor 3 (ISGF3) complex forms—this contains STAT1, STAT2 and a third transcription factor called IRF9—and moves into the cell nucleus. Inside the nucleus, the ISGF3 complex binds to specific nucleotide sequences called IFN-stimulated response elements (ISREs) in the promoters of certain genes, known as IFN stimulated genes ISGs. Binding of ISGF3 and other transcriptional complexes activated by IFN signaling to these specific regulatory elements induces transcription of those genes.[11] A collection of known ISGs is available on Interferome, a curated online database of ISGs (www.interferome.org);[12] Additionally, STAT homodimers or heterodimers form from different combinations of STAT-1, -3, -4, -5, or -6 during IFN signaling; these dimers initiate gene transcription by binding to IFN-activated site (GAS) elements in gene promoters.[11] Type I IFNs can induce expression of genes with either ISRE or GAS elements, but gene induction by type II IFN can occur only in the presence of a GAS element.[11]
In addition to the JAK-STAT pathway, IFNs can activate several other signaling cascades. Both type I and type II IFNs activate a member of the CRK family of adaptor proteins called CRKL, a nuclear adaptor for STAT5 that also regulates signaling through the C3G/Rap1 pathway.[11] Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription.[11] Antiviral and antiproliferative effects specific to type I IFNs result from p38 MAP kinase signaling. The phosphatidylinositol 3-kinase (PI3K) signaling pathway is also regulated by both type I and type II IFNs. PI3K activates P70-S6 Kinase 1, an enzyme that increases protein synthesis and cell proliferation; phosphorylates of ribosomal protein s6, which is involved in protein synthesis; and phosphorylates a translational repressor protein called eukaryotic translation-initiation factor 4E-binding protein 1 (EIF4EBP1) in order to deactivate it.[11]
Virus resistance to interferons[edit]
Many viruses have evolved mechanisms to resist interferon activity.[13] They circumvent the IFN response by blocking downstream signaling events that occur after the cytokine binds to its receptor, by preventing further IFN production, and by inhibiting the functions of proteins that are induced by IFN.[14] Viruses that inhibit IFN signaling include Japanese Encephalitis Virus (JEV), dengue type 2 virus (DEN-2) and viruses of the herpesvirus family, such as human cytomegalovirus (HCMV) and Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8).[14][15] Viral proteins proven to affect IFN signaling include EBV nuclear antigen 1 (EBNA1) and EBV nuclear antigen 2 (EBNA-2) from Epstein-Barr virus, the large T antigen of Polyomavirus, the E7 protein of Human papillomavirus (HPV), and the B18R protein of vaccinia virus.[15][16] Reducing IFN-α activity may prevent signaling via STAT1, STAT2, or IRF9 (as with JEV infection) or through the JAK-STAT pathway (as with DEN-2 infection).[14] Several poxviruses encode soluble IFN receptor homologs—like the B18R protein of the vaccinia virus—that bind to and prevent IFN interacting with its cellular receptor, impeding communication between this cytokine and its target cells.[16] Some viruses can encode proteins that bind to double-stranded RNA (dsRNA) to prevent the activity of RNA-dependent protein kinases; this is the mechanism reovirus adopts using its sigma 3 (σ3) protein, and vaccinia virus employs using the gene product of its E3L gene, p25.[17][18][19] The ability of interferon to induce protein production from interferon stimulated genes (ISGs) can also be affected. Production of protein kinase R, for example, can be disrupted in cells infected with JEV [14] Some viruses escape the anti-viral activities of interferons by gene (and thus protein) mutation. The H5N1 influenza virus, also known as bird flu, has resistance to interferon and other anti-viral cytokines that is attributed to a single amino acid change in its Non-Structural Protein 1 (NS1), although the precise mechanism of how this confers immunity is unclear.[20]
Interferon therapy[edit]
The immune effects of interferons have been exploited to treat several diseases. Agents that activate the immune system, such as small imidazoquinoline molecules that activate TLR7, can induce IFN-α. Imidazoquinoline is the main ingredient of Aldara (Imiquimod) cream, a treatment approved in the United States by the Food and Drug Administration (FDA) for actinic keratosis, superficial basal cell carcinoma, papilloma and external genital warts.[21] Synthetic IFNs are also made, and administered as antiviral, antiseptic and anticarcinogenic drugs, and to treat some autoimmune diseases.
New research has shown that imiquimod's anti-proliferative effect is totally independent of immune system activation or function. Imiquimod exerts its effect by increasing levels of the opioid growth factor receptor (OGFr). Blocking OGFr function with siRNA technology resulted in loss of any antiproliferative effect of imiquimod.[22]
Interferon beta-1a and interferon beta-1b are used to treat and control multiple sclerosis, an autoimmune disorder. This treatment is effective for reducing attacks in relapsing-remitting multiple sclerosis and slowing disease progression and activity in secondary progressive multiple sclerosis.[23]
Interferon therapy is used (in combination with chemotherapy and radiation) as a treatment for many cancers.[21] This treatment is most effective for treating hematological malignancy; leukemia and lymphomas including hairy cell leukemia, chronic myeloid leukemia, nodular lymphoma, cutaneous T-cell lymphoma.[21] Patients with recurrent melanomas receive recombinant IFN-α2b.[24] Type I IFNs have a therapeutic potential for the treatment of a wide variety of leukemias and solid tumors due to their antiproliferative and apoptotic effects, their anti-angiogenic effects and their ability to modulate an immune response specifically activating dendritic cells, cytolytic T cells and NK cells. Research in this area is receiving intensive investigation.[25]
Both hepatitis B and hepatitis C are treated with IFN-α, often in combination with other antiviral drugs.[26][27] Some of those treated with interferon have a sustained virological response and can eliminate hepatitis virus. The most harmful strain—hepatitis C genotype I virus—can be treated with a 60-80% success rate with the current standard-of-care treatment of interferon-α, ribavirin and recently approved protease inhibitors such as Telaprevir (Incivek) May 2011, Boceprevir (Victrelis) May 2011 or the nucleotide analog polymerase inhibitor Sofosbuvir (Sovaldi) December 2013.[28] Biopsies of patients given the treatment show reductions in liver damage and cirrhosis. Some evidence shows giving interferon immediately following infection can prevent chronic hepatitis C, although diagnosis early in infection is difficult since physical symptoms are sparse in early hepatitis C infection. Control of chronic hepatitis C by IFN is associated with reduced hepatocellular carcinoma.[29]
Administered intranasally in very low doses, interferon is extensively used in Eastern Europe and Russia as a method to prevent and treat viral respiratory diseases such as cold and flu. However, mechanisms of such action of interferon are not well understood; it is thought that doses must be larger by several orders of magnitude to have any effect on the virus. Although most scientists are skeptical of any claims of good efficacy,[30] recent findings suggest that interferon applied to mucosa may act as an adjuvant against influenza virus, boosting the specific immune system response against the virus.[29] A flu vaccine that uses interferon as adjuvant is currently under clinical trials in the US.[31]Alpha interferon exhibited a significant adjuvant effect in mice, but in a preliminary study it did not exhibit an adjuvant effect for induction of antibody in respiratory secretions of humans to inactivated influenza virus vaccine given intranasally.[32]
A systematic review studied the effect of interferon as a treatment for individuals suffering from herpes simplex virus epithelial keratitis. Topical interferon therapy was shown to be an effective treatment, especially with higher concentrations.[33] Interferon, either used alone or in combination with debridement, appears to be effective as a nucleoside antiviral agent.[33] The combination of interferon and another nucleoside antiviral agent may speed the healing process.[33]
When used in the systemic therapy, IFNs are mostly administered by an intramuscular injection. The injection of IFNs in the muscle, in the vein, or under skin is generally well tolerated. The most frequent adverse effects are flu-like symptoms: increased body temperature, feeling ill, fatigue, headache, muscle pain, convulsion, dizziness, hair thinning, and depression. Erythema, pain and hardness on the spot of injection are also frequently observed. IFN therapy causes immunosuppression, in particular through neutropenia and can result in some infections manifesting in unusual ways.[34]
Drug formulations[edit]
|Generic name
|Trade name
|Interferon alpha 2a
|Roferon A
|Interferon alpha 2b
|Intron A/Reliferon/Uniferon
|Human leukocyte Interferon-alpha (HuIFN-alpha-Le)
|Interferon beta 1a, liquid form
|Interferon beta 1a, lyophilized
|Interferon beta 1a, biogeneric (Iran)
|Interferon beta 1b
|Betaseron / Betaferon
|Interferon gamma 1b
|PEGylated interferon alpha 2a
|PEGylated interferon alpha 2a (Egypt)
|Reiferon Retard
|PEGylated interferon alpha 2b
|PEGylated interferon alpha 2b plus ribavirin (Canada)
Several different types of interferon are now approved for use in humans. By March 10, 2009, Multiferon — a brand name known generically as human leukocyte interferon-alpha (HuIFN-alpha-Le) — was being used in 14 European countries. This drug was approved for treatment of patients with high risk (stage IIb–III) cutaneous melanoma, after two treatment cycles with dacarbazine, following a clinical trial performed in Germany.[35][36][37]
In January 2001, the Food and Drug Administration (FDA) approved the use of PEGylated interferon-alpha in the USA; in this formulation, polyethylene glycol is added to make the interferon last longer in the body. Initially used for production of PEGylated interferon-alpha-2b (Pegintron), approval for PEGylated interferon-alpha-2a (Pegasys) followed in October 2002. These PEGylated drugs are injected once weekly, rather than administering three times per week, as is necessary for conventional interferon-alpha. When used with the antiviral drug ribavirin, PEGylated interferon is effective in treatment of hepatitis C; at least 75% people with hepatitis C genotypes 2 or 3 benefit from interferon treatment, although this is effective in less than 50% of people infected with genotype 1 (the more common form of hepatitis C virus in both the U.S. and Western Europe).[38][39][40] Interferon-containing regimens may also include protease inhibitors such as boceprevir and telaprevir.
During research to produce a more efficient vaccine for smallpox, Yasu-ichi Nagano and Yasuhiko Kojima—two Japanese virologists working at the Institute for Infectious Diseases at the University of Tokyo—noticed inhibition of viral growth in an area of rabbit-skin or testis previously inoculated with UV-inactivated virus. They hypothesised that some "viral inhibitory factor" was present in the tissues infected with virus and attempted to isolate and characterize this factor from tissue homogenates. In 1954, these findings were published in a French journal now known as the Journal de la Société de Biologie.[41] After Nagano and Kojima separated the viral inhibitory factor from the viral particles using ultracentrifugation, they confirmed its antiviral activity lasted 1–4 days and did not result from antibody production; their findings were published in 1958.[42][43][44] Nagano's work was never fully appreciated in the scientific community; possibly because it was printed in French, but also because his in vivo system was perhaps too complex to provide clear results in the characterisation and purification of interferon.[45]
Meanwhile, the British virologist Alick Isaacs and the Swiss researcher Jean Lindenmann, at the National Institute for Medical Research in London, noticed an interference effect caused by heat-inactivated influenza virus on the growth of live influenza virus in chicken egg chorioallantoic membrane. They published their results, attaining wide recognition, in 1957;[46] in this paper they coined the term "interferon", and today that specific interfering agent is known as a "Type I interferon".[47] Independently, Monto Ho, in John Ender's lab, made a seminal discovery in 1957 that the RMC virus conferred a species specific anti-viral effect in human amniotic cell cultures. They named this effect the viral inhibitory factor (VIF). Subsequently, Enders and Isaacs agreed that the VIF and Interferon belonged to the same class of viral inhibitory factors.[48] The majority of the credit for discovering interferon goes to Isaacs and Lindenmann, with whom there is no record of Nagano ever having made personal contact.[45] It took another fifteen to twenty years, using somatic cell genetics, to show that the interferon action gene and interferon gene reside in different human chromosomes.[49][50][51] The purification of human beta interferon did not occur until 1977. Chris Y.H. Tan and his co-workers purified and produced biologically active, radio-labeled human beta interferon by superinducing the interferon gene in fibroblast cells, and they showed its active site contains tyrosine residues.[52][53] Tan's laboratory isolated sufficient enough amounts of human beta interferon to perform its first amino acid, sugar composition and N-terminal analyses.[54] They showed that human beta interferon was an unusually hydrophobic glycoprotein. This explained a large loss of interferon activity when interferon preparations were transferred from test tube to test tube or from vessel to vessel during purification. The analyses ascertained once and for all, the reality of interferon activity by chemical verification.[54][55][56][57] The purification of human alpha interferon was not reported until 1978. A series of publications from the laboratories of Sidney Pestka and Alan Waldman between 1978 and 1981, describe the purification of the type I interferons IFN-α and IFN-β.[58] By the early 1980s, the genes for these interferons were cloned, allowing for further definitive proof that interferons really were responsible for interfering with viral replication.[59][60] Gene cloning also confirmed that IFN-α was encoded by, not one gene, but a family of related genes.[61] The type II IFN (IFN-γ) gene was also isolated around this time.[62]
Interferon was scarce and expensive until 1980, when the interferon gene was inserted into bacteria using recombinant DNA technology, allowing mass cultivation and purification from bacterial cultures[63] or derived from yeast (e.g. Reiferon Retard is the first yeast derived interferon-alpha 2a) Interferon can also be derived from recombinant mammalian cells.[64] Before this, in the early 1970s the large scale reproduction of human interferon was pioneered by Kari Cantell. He produced large amounts of human alpha interferon from massive quantities of human white blood cells collected from and by the Finnish Blood Bank.[65] Large amounts of human beta interferon were made by superinducing the beta interferon gene in human fibroblast cells, a procedure Chris Y.H.Tan discovered with Monto Ho.[66][67]
Cantell's and Tan's methods of making large amounts of natural interferons were critical to make purified interferons for their chemical characterisation,for their clinical trials and for the preparations of the scarce amount of interferon messenger RNAs to the clone the human alpha and beta interferon genes. The superinduced human beta interferon messenger RNA was prepared by Tan's lab for Cetus corp. to clone the human beta interferon gene into bacteria and the recombinant interferon was developed as 'betaseron' and approved for the treatment of MS. Superinduction of the human beta interferon gene was also used by Israeli scientists to manufacture human beta interferon, used as a topical anti-herpes agent.
Human interferons[edit]
See also[edit]
- ATC code L03#L03AB Interferons
- Immunosuppression
- Immunosuppressive drug
- Immunotherapy
- Interferon Consensus Sequence-binding protein
- ^ de Weerd NA, Samarajiwa SA, Hertzog PJ (2007). "Type I interferon receptors: biochemistry and biological functions". J Biol Chem 282 (28): 20053–20057. doi:10.1074/jbc.R700006200. PMID 17502368.
- ^ Liu YJ (2005). "IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors". Annu Rev Immunol 23: 275–306. doi:10.1146/annurev.immunol.23.021704.115633. PMID 15771572.
- ^ Vilcek, Novel interferons
- ^ Fensterl V, Sen GC (2009). "Interferons and viral infections". BioFactors 35 (1): 14–20. doi:10.1002/biof.6. PMID 19319841.
- ^ de Veer MJ, Holko M, Frevel M, Walker E, Der S, Paranjape JM, Silverman RH, Williams BR (2001). "Functional classification of interferon-stimulated genes identified using microarrays". Journal of leukocyte biology 69 (6): 912–20. PMID 11404376.
- ^ a b Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K, Shibue T, Honda K, Taniguchi T (2003). "Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence". Nature 424 (6948): 516–23. Bibcode:2003Natur.424..516T. doi:10.1038/nature01850. PMID 12872134.
- ^ Moiseeva O, Mallette FA, Mukhopadhyay UK, Moores A, Ferbeyre G (2006). "DNA Damage Signaling and p53-dependent Senescence after Prolonged β-Interferon Stimulation". Mol. Biol. Cell 17 (4): 1583–92. doi:10.1091/mbc.E05-09-0858. PMC 1415317. PMID 16436515.
- ^ Wang H, Zhou M, Brand J, Huang L (2007). "Inflammation Activates the Interferon Signaling Pathways in Taste Bud Cells". Neurosci 27 (40): 10703–10713. doi:10.1523/JNEUROSCI.3102-07.2007. PMC 2096741. PMID 17913904.
- ^ Whitehead KA, Dahlman JE, Langer RS, Anderson DG (2011). Silencing or stimulation? siRNA delivery and the immune system 2. pp. 77–96. doi:10.1146/annurev-chembioeng-061010-114133. PMID 22432611.
- ^ Haller O, Kochs G, Weber F (October–Dec 2007). "Interferon, Mx, and viral countermeasures". Cytokine Growth Factor Rev. 18 (5–6): 425–33. doi:10.1016/j.cytogfr.2007.06.001. PMID 17683972.
- ^ a b c d e f g h Platanias LC (May 2005). "Mechanisms of type-I- and type-II-interferon-mediated signalling". Nature reviews. Immunology 5 (5): 375–386. doi:10.1038/nri1604. ISSN 1474-1733. PMID 15864272.
- ^ Samarajiwa SA, Forster S, Auchettl K, Hertzog PJ (January 2009). "INTERFEROME: the database of interferon regulated genes.". Nucleic Acids Res. 37: D852–7. doi:10.1093/nar/gkn732. PMC 2686605. PMID 18996892.
- ^ Navratil V, de Chassey B, Meyniel L, Pradezynski F, André P, Rabourdin-Combe C, Lotteau V (2010-11-05). "Systems-level comparison of protein-protein interactions between viruses and the human type I interferon system network". Journal of Proteome Research 9 (7): 3527–36. doi:10.1021/pr100326j. PMID 20459142.
- ^ a b c d Lin RJ, Liao CL, Lin E, Lin YL (2004 aaa). "Blocking of the Alpha Interferon-Induced Jak-Stat Signaling Pathway by Japanese Encephalitis Virus Infection". J. Virol. 78 (17): 9285–94. doi:10.1128/JVI.78.17.9285-9294.2004. PMC 506928. PMID 15308723.
- ^ a b Sen GC (2001). "Viruses and interferons". Annu. Rev. Microbiol. 55: 255–81. doi:10.1146/annurev.micro.55.1.255. PMID 11544356.
- ^ a b Alcamí A, Symons JA, Smith GL (December 2000). "The Vaccinia Virus Soluble Alpha/Beta Interferon (IFN) Receptor Binds to the Cell Surface and Protects Cells from the Antiviral Effects of IFN". J. Virol. 74 (23): 11230–9. doi:10.1128/JVI.74.23.11230-11239.2000. PMC 113220. PMID 11070021.
- ^ Minks MA, West DK, Benvin S, Baglioni C (October 1979). "Structural requirements of double-stranded RNA for the activation of 2',5'-oligo(A) polymerase and protein kinase of interferon-treated HeLa cells". J. Biol. Chem. 254 (20): 10180–3. PMID 489592.
- ^ Miller JE, Samuel CE (September 1992). "Proteolytic cleavage of the reovirus sigma 3 protein results in enhanced double-stranded RNA-binding activity: identification of a repeated basic amino acid motif within the C-terminal binding region". J. Virol. 66 (9): 5347–56. PMC 289090. PMID 1501278.
- ^ Chang HW, Watson JC, Jacobs BL (June 1992). "The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase". Proc. Natl. Acad. Sci. U.S.A. 89 (11): 4825–9. Bibcode:1992PNAS...89.4825C. doi:10.1073/pnas.89.11.4825. PMC 49180. PMID 1350676.
- ^ Seo SH, Hoffmann E, Webster RG (August 2002). "Lethal H5N1 influenza viruses escape host anti-viral cytokine responses". Nature Medicine 8 (9): 950–954. doi:10.1038/nm757. PMID 12195436.
- ^ a b c Goldstein D, Laszlo J (Sep 1988). "The role of interferon in cancer therapy: a current perspective" (Free full text). CA: a cancer journal for clinicians 38 (5): 258–277. doi:10.3322/canjclin.38.5.258. ISSN 0007-9235. PMID 2458171.
- ^ Zagon IS, Donahue RN, Rogosnitzky M, McLaughlin PJ (August 2008). "Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function". Exp. Biol. Med. (Maywood) 233 (8): 968–79. doi:10.3181/0802-RM-58. PMID 18480416.
- ^ Paolicelli D, Direnzo V, Trojano M (14 September 2009). "Review of interferon beta-1b in the treatment of early and relapsing multiple sclerosis". Biologics: Targets & Therapy 3: 369–376. ISSN 1177-5475. PMC 2726074. PMID 19707422.
- ^ Hauschild A, Gogas H, Tarhini A, Middleton MR, Testori A, Dréno B, Kirkwood JM (Mar 2008). "Practical guidelines for the management of interferon-alpha-2b side effects in patients receiving adjuvant treatment for melanoma: expert opinion". Cancer 112 (5): 982–994. doi:10.1002/cncr.23251. ISSN 0008-543X. PMID 18236459.
- ^ Mossman, K (editor) (2011). Viruses and Interferon: Current Research. Caister Academic Press. ISBN 978-1-904455-81-3.
- ^ Cooksley WG (Mar 2004). "The Role of Interferon Therapy in Hepatitis B". MedGenMed : Medscape general medicine 6 (1): 16. PMC 1140699. PMID 15208528.
- ^ Shepherd J, Waugh N, Hewitson P (2000). "Combination therapy (interferon alfa and ribavirin) in the treatment of chronic hepatitis C: a rapid and systematic review" (Free full text). Health technology assessment (Winchester, England) 4 (33): 1–67. ISSN 1366-5278. PMID 11134916.
- ^ Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (2009). "Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance". Nature 461 (7262): 399–401. Bibcode:2009Natur.461..399G. doi:10.1038/nature08309. PMID 19684573.
- ^ a b Ishikawa T (Oct 2008). "Secondary prevention of recurrence by interferon therapy after ablation therapy for hepatocellular carcinoma in chronic hepatitis C patients" (Free full text). World Journal of Gastroenterology 14 (40): 6140–6144. doi:10.3748/wjg.14.6140. ISSN 1007-9327. PMC 2761574. PMID 18985803.
- ^ Joseph M. Cummins, DVM, PhD and Chad G. Thompson, BA. Low Dose Interferon, Immune Modulation and Emergency Influenza Prophylaxis. Amarillo Biosciences. Retrieved 2010-07-14.
- ^ "Interferon as a Mucosal Adjuvant for Influenza Vaccine Given Intranasally". ClinicalTrials.gov. Retrieved 2010-07-14.
- ^ Couch RB, Atmar RL, Cate TR, Quarles JM, Keitel WA, Arden NH, Wells J, Niño D, Wyde PR (2009). "Contrasting effects of type I interferon as a mucosal adjuvant for influenza vaccine in mice and humans". Vaccine 27 (39): 5344–8. doi:10.1016/j.vaccine.2009.06.084. PMC 2778204. PMID 19607949.
- ^ a b c Wilhelmus KR (2010). "Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis". Cochrane Database Syst Rev 12: CD002898. doi:10.1002/14651858.CD002898.pub4. PMID 21154352.
- ^ Bhatti Z, Berenson CS (2007). "Adult systemic cat scratch disease associated with therapy for hepatitis C". BMC Infect Dis 7: 8. doi:10.1186/1471-2334-7-8. PMC 1810538. PMID 17319959.
- ^ stage http://en.wikipedia.org/wiki/Melanoma#Staging
- ^ Läkemedelsverkerhttp 3 milj IE solu f inj pre-filled syringe ENG
- ^ Stadler, R., et al. "Long-term survival benefit after adjuvant treatment of cutaneous melanoma with dacarbazine and low dose natural interferon alpha: A controlled, randomised multicentre trial". Acta Oncologica, Volume 45, Issue 4 June 2006, pages 389–399.
- ^ Jamall IS, Yusuf S, Azhar M, Jamall S (November 2008). "Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3?". World J. Gastroenterol. 14 (43): 6627–31. doi:10.3748/wjg.14.6627. PMC 2773302. PMID 19034963.
- ^ "NIH Consensus Statement on Management of Hepatitis C: 2002". NIH Consens State Sci Statements 19 (3): 1–46. 2002. PMID 14768714.
- ^ Sharieff KA, Duncan D, Younossi Z (February 2002). "Advances in treatment of chronic hepatitis C: 'pegylated' interferons". Cleve Clin J Med 69 (2): 155–9. doi:10.3949/ccjm.69.2.155. PMID 11990646.
- ^ Nagano Y, Kojima Y (October 1954). "Pouvoir immunisant du virus vaccinal inactivé par des rayons ultraviolets". C. R. Seances Soc. Biol. Fil. (in French) 148 (19–20): 1700–2. PMID 14364998.
- ^ Ozato K, Uno K, Iwakura Y (May 2007). "Another road to interferon: Yasuichi Nagano's journey". J. Interferon Cytokine Res. 27 (5): 349–52. doi:10.1089/jir.2007.9988. PMID 17523866.
- ^ Nagano Y, Kojima Y (1958). "Inhibition de l'infection vaccinale par un facteur liquide dans le tissu infecté par le virus homologue". C. R. Seances Soc. Biol. Fil. (in French) 152 (11): 1627–9. PMID 13639454.
- ^ Watanabe Y (December 2004). "Fifty years of interference". Nat. Immunol. 5 (12): 1193. doi:10.1038/ni1204-1193. PMID 15549114.
- ^ a b Uno K, Iwakura Y, Ozato K (October 2005). "Another Road to Interferon: Yasuichi Nagano's Journey". International Society For Interferon And Cytokine Research 12 (3): 9–13.
- ^ Isaacs A, Lindenmann J (September 1957). "Virus interference. I. The interferon". Proc. R. Soc. Lond., B, Biol. Sci. 147 (927): 258–67. Bibcode:1957RSPSB.147..258I. doi:10.1098/rspb.1957.0048. PMID 13465720.
- ^ Mergiran, TC. Worldbook Science Year, 1980
- ^ Ho M (2005). Several worlds: reminiscences and reflections of a Chinese-American physicia. Hackensack, NJ: World Scientific. ISBN 978-981-256-409-2.
- ^ Tan YH, Tischfield J, Ruddle FH (1973). "The linkage of genes for the human interferon-induced antiviral protein and indophenol oxidase-B traits to chromosome G-21". J. Exp. Med. 137 (2): 317–30. PMC 2139494. PMID 4346649.
- ^ Tan YH (1976). "Chromosome 21 and the cell growth inhibitory effect of human interferon preparations". Nature 260 (5547): 141–3. PMID 176593.
- ^ Meager A, Graves H, Burke DC, Swallow DM (1979). "Involvement of a gene on chromosome 9 in human fibroblast interferon production". Nature 280 (5722): 493–5. PMID 460428.
- ^ Berthold W, Tan C, Tan YH (1978). "Chemical modifications of tyrosyl residue(s) and action of human-fibroblast interferon". Eur. J. Biochem. 87 (2): 367–70. doi:10.1111/j.1432-1033.1978.tb12385.x. PMID 678325.
- ^ Berthold W, Tan C, Tan YH (1978). "Purification and in vitro labeling of interferon from a human fibroblastoid cell line". J. Biol. Chem. 253 (14): 5206–12. PMID 670186.
- ^ a b Tan YH, Barakat F, Berthold W, Smith-Johannsen H, Tan C (1979). "The isolation and amino acid/sugar composition of human fibroblastoid interferon". J. Biol. Chem. 254 (16): 8067–73. PMID 468807.
- ^ Zoon KC, Smith ME, Bridgen PJ, Anfinsen CB, Hunkapiller MW, Hood LE (1980). "Amino terminal sequence of the major component of human lymphoblastoid interferon". Science 207 (4430): 527–8. PMID 7352260.
- ^ Okamura H, Berthold W, Hood L, Hunkapiller M, Inoue M, Smith-Johannsen H, Tan YH (1980). "Human fibroblastoid interferon: immunosorbent column chromatography and N-terminal amino acid sequence". Biochemistry 19 (16): 3831–5. PMID 6157401.
- ^ Knight E, Hunkapiller MW, Korant BD, Hardy RW, Hood LE (1980). "Human fibroblast interferon: amino acid analysis and amino terminal amino acid sequence". Science 207 (4430): 525–6. PMID 7352259.
- ^ Pestka S (July 2007). "The interferons: 50 years after their discovery, there is much more to learn". J. Biol. Chem. 282 (28): 20047–51. doi:10.1074/jbc.R700004200. PMID 17502369.
- ^ Weissenbach J, Chernajovsky Y, Zeevi M, Shulman L, Soreq H, Nir U, Wallach D, Perricaudet M, Tiollais P, Revel M (December 1980). "Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia coli cloning studies". Proc. Natl. Acad. Sci. U.S.A. 77 (12): 7152–6. Bibcode:1980PNAS...77.7152W. doi:10.1073/pnas.77.12.7152. PMC 350459. PMID 6164058.
- ^ Taniguchi T, Fujii-Kuriyama Y, Muramatsu M (July 1980). "Molecular cloning of human interferon cDNA". Proc. Natl. Acad. Sci. U.S.A. 77 (7): 4003–6. Bibcode:1980PNAS...77.4003T. doi:10.1073/pnas.77.7.4003. PMC 349756. PMID 6159625.
- ^ Nagata S, Mantei N, Weissmann C (October 1980). "The structure of one of the eight or more distinct chromosomal genes for human interferon-alpha". Nature 287 (5781): 401–8. Bibcode:1980Natur.287..401N. doi:10.1038/287401a0. PMID 6159536.
- ^ Gray PW, Goeddel DV (August 1982). "Structure of the human immune interferon gene". Nature 298 (5877): 859–63. Bibcode:1982Natur.298..859G. doi:10.1038/298859a0. PMID 6180322.
- ^ Nagata S, Taira H, Hall A, Johnsrud L, Streuli M, Ecsödi J, Boll W, Cantell K, Weissmann C (March 1980). "Synthesis in E. coli of a polypeptide with human leukocyte interferon activity". Nature 284 (5754): 316–20. Bibcode:1980Natur.284..316N. doi:10.1038/284316a0. PMID 6987533.
- ^ US patent 6207146, Tan YH, Hong WJ, "Gene expression in mammalian cells.", issued 2001
- ^ Cantell K (1998). The story of interferon: the ups and downs in the life of a scientis. Singapore ; New York: World Scientific. ISBN 978-981-02-3148-4.
- ^ Tan YH, Armstrong JA, Ke YH, Ho M (1970). "Regulation of cellular interferon production: enhancement by antimetabolites". Proc. Natl. Acad. Sci. U.S.A. 67 (1): 464–71. PMC 283227. PMID 5272327.
- ^ US patent 3773924, Ho M, Armstrong JA, Ke YH, Tan YH, "Interferon Production", issued 1973


text:
Howard County Police are looking for a man who set up secret video cameras in an Ellicott City condominium shared by two women in their 20s.
Police say the first camera was set up in late June in the bedroom of one of the women; over the next few months, the suspect returned to the condo several times to move the camera to the other woman's bedroom and bathroom.
There was no sign of forced entry into the condo, on the 8300 block of Montgomery Run Road, according to police.
One of the women discovered a camera hidden in a closet last month, police said. Images of the suspect were recorded as he set up the cameras. All of the footage of the suspect seems to be during the day, police said, and on several occasions he appears to be wearing the same clothes – possibly a uniform.
In several videos he wears a dark tan or light brown button up shirt and khaki shorts. He is also seen in a light-colored Polo shirt and khaki shorts; in some images he is wearing a Ravens cap.
Detectives say they have investigated contractors and workers in the area, but that an initial investigation has eliminated any leads or potential suspects.
Police describe the suspect as a white man in his 30s with a heavy build. He is bald on top with very short or shaved brown hair around the sides and back of his head.
The suspect will face multiple charges of breaking and entering and videotaping a person in a private place without consent. Police ask anyone with information to call them at 410-313-3200.
In 2001, Howard County Police arrested an Elkridge man for secretly videotaping two tenants who were each renting a room and a bathroom from him.
The tenants, 18 and 22, found a VCR and television in a storage room in the basement according to a police statement released at the time. The video tape contained footage from the tenants' bathrooms.
When detectives searched the house, they said they found four pinhole-style cameras hidden in the bathrooms rented by the women as well as a third one in the house, and a bedroom that had a tanning bed, which the women also used.
Police said the man had been recording for as long as eight weeks.
Edward George Campion was sentenced to six months in jail, the Baltimore Sun reported at the time.
For more local news, sign up for the Ellicott City Patch newsletter. Keep the conversation going on Facebook and Twitter.
This article has been updated to include information about a similar incident in 2001.


text:
LAKE WYLIE — The welcome mat is out at one of Lake Wylies newest neighborhoods.
David Weekley Homes held a grand opening and ribbon cutting Thursday at its Cottages at The Landing model home with the Lake Wylie Chamber of Commerce.
Chamber president Susan Bromfield said she heard many positive comments about the home and development.
The homes are beautiful, well-built and a terrific addition to Lake Wylie, offering more new patio home options in the hub of Lake Wylie, she said.
Rinehart Realty Realtor and chamber member Mary Sieck also said everything she heard was positive.
I was very impressed by the construction and by how well appointed the house is in items like the crown molding, she said.
She believes the homeowner association fees, which will include irrigation installation, shrubbery and watering the yards, will be a big attraction for home buyers.
You really dont have to do anything outside, she said. This is really going to appeal to people and Charlotte commuters who dont want to spend a day doing their lawn. Its a lifestyles choice.
Preston Nowaski, company sales consultant, said there will be 25 single-family homes with 55-foot-wide homesites with rear-alley entrance to garages. Homes are priced from the low $200s to low $300s.
We have sold one home, two contingent sales, three homes under construction and a fourth starting in July, he said.
There are six plans available in one-story ranch or two-story designs with master bedrooms on the first floor ranging from 1,654 to 2,424 square feet, according to the company website.
Buyers can choose from one of three showcase homes or customize a floor plan to be constructed on an available homesite. Nowaski said interest is high and hasnt waned since construction began in mid-May when he said we cant get it started fast enough.
Weve had a steady stream of traffic, he said. Were excited about entering back into the community.
The Cottages is a return to Lake Wylie for the company. David Weekley built homes in The Landing a decade ago.
The model home, called The Gilchrist, is open 10 a.m.-6 p.m. Monday-Saturday and 1-6 p.m. Sunday, or by appointment.
For more information, call 704-972-4222 or visit davidweekleyhomes.com.


text:
The tricorne or tricorn is a style of hat that was popular during the 18th century, falling out of style by 1800. At the peak of its popularity, the tricorne was worn as civilian dress and as part of military and naval uniforms.[1] Its distinguishing characteristic was a practical one: the turned-up portions of the brim formed gutters that directed rainwater away from the wearer's face, depositing most of it over his shoulders. Before the invention of specialized rain gear, this was a distinct advantage.[2]
The tricornes had a rather broad brim, pinned up on either side of the head and at the back, producing a triangular shape. The hat was typically worn with the point facing forward, though it was not at all unusual for soldiers, who would often rest a rifle or musket on their left shoulder, to wear the tricorne pointed above their left eyebrow to allow better clearance. The crown is low, unlike the steeple hats worn by the Puritans or the top hat of the 19th century.[3]
Tricornes ranged from the very simple and cheap to the extravagant, occasionally incorporating gold or silver lace trimming and feathers. In addition, military and naval versions usually bore a cockade or other national emblem at the front.
The tricorn appeared as a result of the evolution of the broad brim round hat used by Spanish soldiers in Flanders during the 17th century.[4] By pledging (binding) the brims, a triangular shape was obtained, and since the corners offered protection from the rainy Flemish weather, this shape was favored by Spanish soldiers. In 1667, war broke out between France and Spain in the Spanish Netherlands. During the subsequent military struggle, its use spread to the French armies. The style was brought back to France, where its usage spread to the French population and the royal court of King Louis XIV, who made it fashionable throughout Europe, both as a civilian and military wear. By the end of the 17th century, the tricorne was popular in both civilian fashion and in military uniforms. They remained one of the predominant European styles of hat throughout the 18th century. In the United States, only the first five Presidents, from George Washington to James Monroe, wore this style of hat according to the fashion of the 18th century.[5][6] James Monroe gained the nickname "The Last Cocked Hat" because of this.[7]
The tricorne quickly declined in use at the end of the 18th century. It evolved into the bicorne,[8] which was widely used by military officers in Europe from the 1790s until World War I, not completely fading out of style until World War II. For enlisted soldiers, the tricorne was replaced by the shako at the turn of the 19th century, which had become the new dominant style of military headgear from 1800 on. As the fashionable hat for civilian men, the tricorne was overtaken by the top hat.
Modern usage and legacy[edit]
Tricornes survive today as part of the traditional dress of the Chelsea Pensioners (UK)[9] and the Old Guard Fife and Drum Corps of the United States Army.,[10] and the distinctive hat of the Guardia Civil (Spain), called a tricornio in Spanish, originates from the tricorne. A black feathered tricorne is worn by the Lord Mayor of the City of London for all ceremonials and is in evidence at the annual Lord Mayor's Show in November, when the newly elected Lord Mayor enthusiastically waves it at the crowds.[11] The Lord Chancellor and the Speaker of the House of Commons are also traditionally entitled to wear or carry it when wearing state robes with full bottomed wigs at state occasions (and, in theory, the Lord Speaker is also entitled to do so as well).
In the United States, the tricorne is associated with the American Revolution and American Patriots of that era, especially Minutemen (militia members of the American Colonies).[12] Participants in reenactment events often don tricornes, and they also can be seen in sports culture as worn by fans of teams with Revolutionary names, such as the New England Patriots (an American football team),[13] the New England Revolution (a Major League Soccer team),[14] the United States men's national soccer team, the University of Massachusetts Amherst,[15] and the George Washington University. Voters associating themselves with the Tea Party movement use the tricorne as an icon to associate themselves with the patriots of the American Revolution, and their distaste for big government and excessive taxation.
In France, synagogue officiants (usually not rabbis), wear the tricorne on formal occasions. In the French navy and air force, tricorn are still worn by women as a piece of uniform.
The tricorne is a key feature in the University of Minho's academic dress, in Portugal. Its origins are as far as 18th century, as being the academic dress of Colégio de Estudos Superiores de S. Paulo, as depicted by tile panels in the Archbishop's Palace of Braga (now Rectorate of the University of Minho). Designated by "Tricórnio" (Portuguese for "tricorne"), this academic dress was redesigned and officially set 1989.
A folk song, to the tune of Carnival of Venice (song), goes, 'My hat it has three corners, three corners has my hat; and had it not three corners, it would not be my hat.' The song is usually sung several times in a row, each time omitting a specific word and replacing it with a gesture representing it (for instance, pointing at one's elbow whenever the word 'corners' is sung) and mouthing the omitted word.
Peter the Great reenactor wearing a tricorne hat, St. Petersburg, Russia
Figure of Louis XIV c. 1685
Charles Alexander, c. 1733–1737
Thomas Gage in 1743
Frederick the Great wearing a tricorne, c. 1750
Catherine the Great, c. 1760
Trumbull's depiction of the 1781 surrender of Lord Cornwallis at Yorktown
Charles III of Spain, c. 1786–88
Chelsea pensioners in tricornes
See also[edit]
- ^ Gentlemen of Fortune
- ^ See UMass Digital Collection: Tricorn hat.
- ^ Hats from the past till the present and their production (in Czech)
- ^ Castells, Albert. "Los tercios viejos y la presencia española en Flandes", Espasa, Madrid, 1997
- ^ Digital History, Steven Mintz. "Digital History". Digitalhistory.uh.edu. Retrieved April 20, 2010.
- ^ Real Life at the White House: 200 ... – Google Knihy. Books.google.cz. Retrieved April 20, 2010.
- ^ http://listoy.com/Presidents/James-Monroe.htm
- ^ Cocked Hat – Infoplease.com
- ^ The Royal Hospital Chelsea
- ^ Old Guard Fife and Drum Corps
- ^ Lord Mayor's Show
- ^ American Headgear of the Revolutionary War
- ^ New England Patriots
- ^ New England Revolution
- ^ University of Massachusetts Amherst – Official Athletic Site


text:
One last entry before I wrap up for the night.
Georgetown's lacrosse team – the same Georgetown team that narrowly missed the NCAA tournament last year – is again the favorite in the ECAC.
It's also the last time that will happen, since Big East lacrosse thankfully starts play in 2010, lending a heavyweight name to a sport that could use one or two.
But for now, the Hoyas will look to begin another streak of NCAA appearances, and winning the ECAC would ensure that would happen.
The coaches' vote indicated Loyola is probably the Hoyas' best competition, and that makes sense. The Greyhounds won the ECAC last year and have at least re-emerged as a competitive program under Charley Toomey.
Anyway, the Hoyas – who are simply littered with talent, especially in a deep junior class including Andrew Brancaccio, Craig Dowd and Barney Ehrmann – will probably be a preseason top-10 team. I can already hear some of my lacrosse press box colleagues anointing Georgetown as a final four sleeper. It certainly could happen, though it sure would help if they could make it through the conference unscathed.
Here, by the way, is the rundown of the coaches' voting in the league (which, if my math is correct, appears to have been done on a 7-6-5-4-3-2-1-0 scale), with first place votes in parentheses:
1. Georgetown (5), 47
2. Loyola (3), 43
3t. Penn State, 33
3t. Rutgers, 33
5. Massachusetts, 29
6. Fairfield, 14
7. Hobart, 13
8. St. John's, 12


text:
We can clean out black and stain currencies , our organization operate world wide and if you got any such problem . just a click then your problem will be solve .
Inter Finance Consortium is the pioneer of organised financial services in United Kingdom and has established itself as the one of best recognized Finance Firm nationally. Inter Finance Consortium was incepted in the year of 2000. We provide professional services for inbound and outbound business set up. We offer a complete range of financial solutions to our clients. We take care of investment banking & financial planning requirements by providing authentic advice. We possess a team of experts including qualified consultants who ensure to provide most feasible solution to our client financial hitches.Over the last 5 years, Inter Finance Consortuim has grown to be a premier executive provider of bank instruments for professionals both in United Kingdom and overseas.We are in affiliation with so many banks which enable us to provide our clients\' need globally.
We offer loans,business finance,project finance,bank instruments like MTN, BG, LC, SBLC, PPP, POF, CMO.These services we provide at reasonable rates and conditions from reputable lenders and providers.No chains of consultants as we are in direct contact with the lender and provider.
Matrix Cosine - Digital ISDN KTSThe Value Creator
EonSoft-Additional Features:Automatic Sensing of PC StatusAutomatic Sensing of Software StatusExecutive Mode with 20 DSS KeysHelp MenuIntegration with Microsoft Address BookKeyboard and Mouse OperationsOperator Mode with 148 DSS KeysProgrammable Tool TipsShortcut KeysStandard Windows User InterfaceTool Tips on Mouse Over


text:
These photos are too cute not to share. They were sent to me by one of the PNP pilots who has done several flights for rescue groups. A BIG THANK YOU is headed your way, you know who you are
"Three St Bernard pups and two doxie mix pups are now in Ft. Wayne" Thank you to Judy, Tammy and Carlean.
Captions for the collage photos below:
Making friends with the gal from the FBO.
Bonding with the fueler in Fort Wayne.
Carlean saying goodbye.
Those legs you see are the fuelers at CHA.
Five more saved!


text:
- Northern New York Newspapers
- Watertown Daily Times
- The Journal
- Daily Courier-Observer
- NNY Ads
- NNY Business
- NNY Living
- Malone Telegram
CANTON The St. Lawrence County Office of Emergency Services will contact all businesses soon to collect information for its 911/emergency contact file.
All information, which will be used by first responders in case of emergency, will be kept confidential. Participation is optional.
Anyone uncomfortable answering questions by phone may complete a form supplied by the Office of Emergency Services.
For more information, call the Office of Emergency Services, 379-2240, or the Sheriffs Office, 379-2365.
Thousands of readers like you have made Northern New York Newspapers the number one ranked website* for local news and sports coverage in the north country.
You can continue on to this article in a few seconds, or you can visit one of our websites:


text:
Simply confirm your registered email address below and click "Reset Password." We will immediately email you a link back to the site where you can enter a new password for this account.
We've found your existing At-Work Network account. Please login below to complete the Facebook login process.
- @Work Network Members, register below to win a pair of tickets to The 30th Anniversary DeBella DeBall.The 30th Anniversary DeBella DeBall, a dress to impress EVENT, will be held on December 14 at Vie (on Broad St. just North of Spring Garden). WHO's PLAYING:Music by Johnny O & The Classic Dogs of Love PLUS Special guests David Uosikkinen's In The Pocket featuring Members of THE HOOTERS, TOMMY CONWELL, RICHARD BUSH (of the A's)WHO IS INVITED?This is an Invite only event. You must receive an email confirmation from MGK in order to attend this event. Please do not attend unless you have been notified via email that you are on the guest list.Just registering for tickets does not mean that you will receive them. This is a 21+ event. Please DRESS TO IMPRESS.HOW ELSE CAN YOU WIN TICKETS: Listen to The John DeBella Show OR register below. When to listen.....Week of 11/26 - Listen at 8:40a & be the 1st to correctly answer Classic Rock Riddle Week of 12/3 - Listen at 6:10a & be the 1st to correctly answer Question From HellWeek of 12/10 - Listen at 8:40a & be the 1st to correctly answer Classic Rock Riddle DRINKS ANYONE?There will be a CASH bar. There is no ATM on the premises & Vie does not accept credit cards. LET'S EATThere will be butlered hors d'oeuvres, a pasta station and a slider station. PARKING$10 Valet parking will be available. There may be free parking available in the surrounding neighborhood. The 30th Anniversary DeBella DeBall is proudly sponsored by:
MGK wants to send you to L.A. in VIP style, to meet Paul Stanley & Gene Simmons of KISS.
HOW TO QUALIFYAnswer John DeBella's Classic Rock Riddle at 8:35a OR text in when we tell you to throughout the day. Each time we tell you to text in, our computer will select one random texter as the qualifier. Find out how to qualify without texting below.
ALL QUALIFIERS SCORE KISS/DEF LEPPARD TICKETSAll qualifiers score free tickets to see KISS & Def Leppard on August 3 at Sus...
Go Register ->
- @Work Network Members, make a Noontime Nuggets requestbelow and Debbi might pick your request, call you up, put you on-air and reward you with the following: a $50 Giant Gift Card
For truly local produce at truly great prices, your local Giant is the obvious choice. Nobody works harder to serve up a huge variety of the freshest fruits and vegetables at tremendous savings to you, every day!
Go Register ->
If you've ever dreamed of becoming the next Jim Gaffigan or Amy Schumer, you should enter John DeBella's Comedy Competition. The winner will receive $1,000, open up for John Heffron at Helium Comedy Club (9/18) & more. Find out how to enter.
Go Register ->
- @Work Network Members register below for your chance to win tickets to the GoBowling.com 400 at Pocono Raceway on August 3rd. One winner will get the Grand Prize: 2 Terrace Club tickets.
For race info and tickets go to www.poconoraceway.com .
Go Register ->
- @Work Network Members register below for your chance to win a pair of run of engagement passes for Universal Pictures' GET ON UP, the James Brown biopic, in theaters on August 1st.
In his follow-up to the four-time Academy Award®-nominated blockbuster The Help, Tate Taylor directs 42's Chadwick Boseman as James Brown in Get on Up. Based on the incredible life story of the Godfather of Soul, the film will give a fearless look inside the music, moves and moods of Brown, taking aud...
Go Register ->
@Work Network Members register below for your chance to win a pair of tickets to Long Long Time: A Historic Tribute to Billy Joel, by his Original 1971-1972 Band on August 26 at World Cafe Live Philadelphia.Tickets on sale now at philly.worldcafelive.com. Tickets are $25 and there will be a 'Meet & Greet' upgrade at 6:30PM for an additional $10.
After over one million bootleg copies of Billy Joel's 1972 Sigma Sound Studios radio concert were in circulation, SONY/Legacy Records released...
Go Register ->
Fill out the checkboxes below to tell us who your favorite MGK artists are. You can click as many as you like - and you've got two "write-in" spaces in case you don't see your choices listed. Giving us this information makes you eligible for special inside information and prizes related to the artists you care about most.
You can change your mind as often as you like by clicking on the link from the @Work Network member's page.
Go Register ->
- Do you have a favorite local watering hole in your town that's staffed by friendly, welcoming people & full of good natured, enthusiastic patrons. Is this a place that makes you feel great whenever you stop in for a drink or a bite to eat? We want to know about it and we want to do a FREE live broadcast there. Nominate a bar/tavern/pub for a MGK Hometown of the Week live broadcast.
If we pick your establishment, we'll let the bar owner know that we're there because of you. ...
Go Register ->
- @Work Network Members register below for your chance to win a four pack of tickets to Conklin's Comedy Night on Wednesday, 7/30.
Conklin's Comedy Night happens Wednesdays, 8pm - 10pm at Parx Casino's 360. Get lucky and get laughing! Parx is proud to present Joe Conklin's Comedy Night! A weekly show featuring "the man of a thousand voices" Joe Conklin and three hilarious comedians each week.
Get your tickets here.
Go Register ->
PECO is giving you the opportunity to win up to $5,000 in energy efficient upgrades. You could also win a free personalized home energy assessment where a PECO Energy Advisor will visit your home to show you how it can run more efficiently. To enter the sweepstakes, visit peco.com/SmartIdeas. No purchase necessary. Open to PECO customers 18+ owning residential property (restrictions apply). Ends 11:59pm on 8/17/14. Subject to Official Rules at peco.com/SmartIdeas.
Go Register ->


text:
ERIE, Pa. — Sarah R. Schenck, of Conneaut, Ohio, died Wednesday morning, July 24, 2013, at St. Mary's East, Erie, Pa. Calling hours are Friday from 2 to 4 p.m. and 6 to 8 p.m. and from 9 to 10:30 a.m.., Saturday morning, at Marcy Funeral Home, 208 Liberty St., Conneaut.
Funeral services will be 11 a.m., Saturday, at New Leaf United Methodist Church, 283 Buffalo St., Conneaut.
Complete arrangements will be announced by Marcy Funeral Home, Conneaut.


text:
This is not a vent board or any other kind of therapy. Before you hit the POST button, ask yourself if your contribution will add to the level of discussion going on.
Important notes on articles:
Message:The food was very good, though obviously not Alinea. We had passed appetizers that we chose, salad/soup (don't remember which), entrees (choice of fish, steak, and maybe something else like chicken?), and dessert. The bar can be whatever you want it to be, so we chose a good quality assortment without being crazy, and I think said that if someone wanted something specific that we didn't have that they should go ahead and pour it. Don't remember what particular wine we served with dinner but I do recall that it was pretty good and reasonably priced. Honestly, neither my wife and I nor my folks had any complaints so far as I know...other than that my wife had to marry me the next day. Now this was three years ago, so I can't say what might be different now, but we were very pleased all around and I'd recommend it.
HTTP Link (optional):
Poster's E-Mail (optional):


text:
Y-12 expects to meet this year's production goals, despite security crisis
Photo/B&W Y-12
The Beta-2E facility, foreground, is where Y-12 workers dismantle components of old nuclear weapon systems.
A federal spokesman said the Y-12 nuclear weapons plant expects to meet this year's production goals -- for warhead rehab projects, as well as dismantlement activities -- despite the security crisis.
"At this point, Y-12 has already met many of its production commitments for this year," said Steven Wyatt of the National Nuclear Security Administration. He was referring to the mission goals for Fiscal Year 2012, which concludes Sept. 30.
"For those remaining commitments still in production, plans are in place that would accomplish all by the end of the year. We will continue to assess impacts of the stand down, but we cannot provide any further details at this time."
The production missions at the nuclear weapons facility resumed last week (Aug. 15) following a 2 1/2-week security stand-down that followed by the July 28 incident in protesters broke into the plant in early morning darkness, reached the high-security Protected Area and pierced the Oak Ridge plant's aura of invincibility.
As Wyatt confirmed the day before the security breach, there is only one warhead "life-extension project" currently under way, and that involves remanufacturing of parts for the W76 (Trident) warhead.
The federal spokesman also reaffirmed that three old weapon systems are currently being dismantled at Y-12 -- the B61, B53 and B83.
All told, four variations of the B61 bomb (long a mainstay of the U.S. nuclear arsenal) have been or will be undergoing dismantlemet at Y-12 this year.
"We are also doing the B61 - 3 systems so far this year and are heading for the 4th. We have been doing the B61 all year, along with B53 and B83," Wyatt said.


text:
As I sat at the kitchen table contemplating what I wanted for breakfast, my wife entered the room.
Normally, she places the newspaper on the kitchen table, but on this particular morning, she tossed a black shingle on my placemat.
"What are we going to do about this?" she said.
I didn't know what to say.
"Is it a new advertising gimmick?" I asked.
She didn't think it was funny.
I tried my best to deflect her inquiry.
"It looks like some roofing business came up with a great advertisement, but they didn't put the company name on it," I said.
In short, I was informed that it was time to get serious about getting my house in order.
It's odd. When something goes wrong or needs fixing, it's always my house.
I tried to explain that the shingle most likely blew off a neighbor's house and ended up in our front yard.
But she informed me that because we had a mild winter, doesn't mean the cold didn't take its toll.
"That spring Nor'easter must have caused a storm of shingles to be ripped from the roof," she said.
One shingle does not constitute a storm.
I said it to myself knowing that saying it out loud would cause a bigger squall.
I didn't like where this conversation was leading.
I didn't have to wait long to get my marching orders.
"You'd better get the ladder out and check for damage," she said.
Ah, the ladder.
Ladders and I don't get along anymore. I own a 40-foot wooden ladder that has been stored in the garage for decades.
I used the monstrosity when I did my own siding, soffit and facia work on "my" home.
That seems like a lifetime ago.
Judging from the stiffness in my knees, I'm not buying into the 60 is the new 40 notion.
I also have a 24-foot extension ladder that I use to clean gutters.
But I opted to use my newest favorite tool: The telephone.
I looked in the yellow pages under Cheap Roofing Companies and picked a firm called Cheap Roofing, Done Cheap.
A guy by the name of Ronnie showed up to inspect my roof and offer an estimate.
I suspected that something may not be kosher when he asked if I had a ladder he could borrow.
I took him to my garage and pointed to the 40-footer.
"Man, that's too heavy; do you have something lighter?" he complained.
I was about to run him off my property when he spotted the smaller ladder.
"Grab the other end, man, and we'll carry it to the house," he said.
He climbed the ladder and disappeared from view as he surveyed the roof.
About two minutes later, he reappeared and came down the ladder.
"It looks bad, man," he said.
"Any idea what this may cost me?" I inquired.
He said it all depends on what I want.
"Your roof would look good with a weather vane," he said.
He said he could work it into the deal if I decided to sign a contract that afternoon.
He gave me a quote for the roof and said the weather vane would be an extra $1,400.
The estimator got a puzzled look on his face when I asked him how many square of shingles it would take to cover my roof.
After a brief pause, he said, "Whatever it takes, man."
Needless to say, he didn't get the job.
If I were younger, I would do it myself.
But I don't need a weather vane to show me which way the wind is blowing.
With age comes wisdom and telltale signs that things change.
I've discovered that I no longer try to hold my stomach in, no matter who walks into the room, and my knees buckle easier than my belt.
But I'm confident things will work out.
The one thing I haven't lost is hope.
Click here to subscribe to The Tribune-Democrat print edition.
Click here to subscribe to The Tribune-Democrat e-edition.


text:
A former Nebraska football team captain has been given 300 days in jail on a marijuana charge.
Thirty-eight-year-old Vershan Jackson was sentenced Thursday in Lincoln. He'd pleaded no contest to attempted possession for sale of a controlled substance. Prosecutors had lowered the charge in return for Jackson's plea.
Lincoln police say an officer watched a marijuana sale occur July 18, 2012 between Jackson and another man in a grocery store parking lot. The other man, 33-year-old Presha Allen, was given the same sentence after pleading guilty to a marijuana charge.
Jackson, a tight end, was a captain during the Huskers' 1997 season.


text:
Commonwealth Journal
October 25, 2012
A load to bear
Creature caught on camera may be Pulaski's biggest
by Bill Mardis
Commonwealth Journal
Ano —
A black bear photographed by a game camera in the Ano community may be one of the largest to roam the hills of eastern Pulaski County.
The bear, caught on camera at 3:34 p.m. October 5 on Boat House Ridge, was estimated to weigh 500 pounds and appeared to be more than 7 feet long. It was eating out of a deer feeder near Rooney Turner's hunting cabin.
Turner said the bear's length was estimated by the height of a 5-foot-tall cylinder-shaped deer feeder. The bear was standing on its hind legs getting corn out of the feeder.
"The bear was not standing up straight," said Turner, a backhoe operator for the Pulaski County Road Depart-ment. "If it stood up straight, it would be 7 to 7 1/2 feet tall."
Alan Sidwell, owner of Sidwell Wildlife and Rehabilitation at Dahl, didn't see the picture of the bear at Ano, but he was a bit skeptical of the estimated weight of 500 pounds.
"That would be a giant," said Sidwell. He said a male black bear weighing 350 pounds is an awfully big bear. " ... their bone structure is such it would be difficult to weigh 500 pounds unless there was rolls of fat all over it." However, Sidwell noted at this time of year bears are fat as they get ready for the coming winter.
Sidwell said the resident population of black bears in Pulaski County is not great, " ... maybe 20." However, male black bears are always on the move and they come in and out of the county.
"A lot of deer hunters with game cameras are getting photographs of black bears," Sidwell said. "They put corn in deer feeders and if there is a black bear anywhere in the area, it comes to the feeder."
The good folks in the Ano community of eastern Pulaski County probably don't like their area being called "Wild Country," but some of the biggest rattlesnakes that ever slithered across the ground have been killed near where the bear was photog-raphed.
Most of the big rattlers are seen at a place known locally as "Rattlesnake Crossing," a section of Boat House Ridge Road about a quarter of a mile from Turner's hunting cabin.
Tony Fletcher killed a rattler crossing Boat House Ridge Road that measured 59 1/2 inches. "(State Representative) Tommy (Turner) and I measured it," Rooney recalled.
Turner was not surprised about the big bear messing around his deer feeder.
"I see bear tracks around here all the time, especially in Baker Hollow," Turner said. "Baker Hollow is just below my hunting cabin."


text:
Put your list here...
What's the Scariest experience you had in childhood?
What's the Scariest experience you had in childhood?
when i moved to oregoncountvladwolfenstein on Sunday, August 29, 2010 - 9:40am
we got to our new house and i was in the fourth grade. my room was in the basement where i found a dead bird on arrival. and every night i spent in that room i saw shadows in the dark, weird things started happening. people talking down the hall, things would come up missing then show up somewhere where they shouldnt be. we werent in that house for verry long,because of this.
Scary Childhoodaprilc1 on Saturday, September 18, 2010 - 1:47pm
Off hand my scariest childhood experience happened at age 6. It was winter and I was wearing a hand knitted hat made by my gramma that had a big tassel on the top. We had a dog chained out back Iwalked past and the grabbed the tassel (did I mention it buttoned under my chin?) and dragged me through the run, nearly choking me to death, reminiscent of Final Destination 3, I don't remember how I got loose but I remember it today. Consequently, when my daughter was young, none of her hats fastenend like that.
What's the Scariest experience you had in childhood?baileythomas9 on Friday, July 8, 2011 - 8:42am
I was hiding from my grandfather one day and I got into one of those old iceboxes the kind that locks when you shut them, it was fun till I tried to get out I could hear my grandpa hollering for me but he couldn't hear me,I kicked that door from the inside and it rocked a couple of times but that door came open and I got the hell out of there. I never told him about that
What's the Scariest experience you had in childhood?ladygaga1977 on Monday, October 17, 2011 - 12:26am
i was swimming in the ocean and went out a little too far and was trying to come back into shore when a huge wave came and pulled me under and the undertow kept pulling me further and further out. i just remember praying for God to give me enough strength to get me back to the shore and he did, but that was so scary because i almost drowned and i could swim very good.
what's the scaries experiance you had i childhooddoomrider1 on Monday, October 17, 2011 - 12:35am
Playing with a wigi board and leaving to use the bathroom and returning to find the board on the floor and not on my bed and no one was in the house but me
- Oldest
- ‹ previous
- 1
- 2
- 3


text:
I feel really weird opening up my personal life this way," says John Belushi. "But what is there to see? Just a lot of old boxes." Hoisting one on my shoulder, I walk downstairs from his Greenwich Village apartment and dump it in the trunk of the Bluesmobile, a 1967 Dodge Monaco with a fresh coat of jet-black paint. Belushi has discovered a unique way of making reporters useful: if they must ask nosy questions, the least they can do is save you some bucks in moving expenses. Actually, there is more to see in the apartment than old boxes – enormous piles of dirty clothes, two Persian cats, an autographed picture of Ray Charles – but the day is hot, my wind short and my eye for the revealing detail concomitantly dull. As if to reward my efforts, he selects a revealing detail for me.
"They'd just shot me up with morphine," he says, indicating a photograph of himself as a dazed cowboy on the set of Go South, one of three movies Belushi acted in during the past year, in addition to twenty Saturday Night Live shows. "A squib exploded in my hand. We were in Mexico, so they just picked out the splinters and shot me up and we went on with the scene."
Did the morphine affect his acting ability?
"I don't know. It was just a gunfight . . . I think it'll be a great movie. It has Indians, Mexicans, Orientals, gold, railroads, barroom brawls, bank robberies, horse stealing, everything a Western should havebut no heavy violence."
Dressed in army fatigues and a white T-shirt, Belushi looks capable of handling any sort of violence. Or starting it. His face gives the permanent impression of demented anger lurking barely beneath the surface – an impression reinforced just now by an incipient beard (now that he is off Saturday Night for the summer) and a potbelly of the sort usually associated with redneck sheriffs. When he plays the samurai or the crazy weatherman on TV, the effect is hilarious, but up close it's disconcerting. I've known the guy for over a year and have never been quite sure he wasn't about to crush my knees with a brick.
The same violent urge that makes John great will also ultimately destroy him," says Michael O'Donoghue, a National Lampoon alumnus and writer for three seasons on Saturday Night Live. (This coming season, he is doing his own show, Television). O'Donoghue's humor is best exemplified by his infamous imitation of Tony Orlando and Dawn with needles poked in their eyes. He expects SNL to fall into "the enema bank" without him to keep the show in the mainstream of American humor.
"I appeared with John once on Midday Live [a local New York talk program hosted by Bill Boggs]." O'Donoghue continues. "Boggs kept asking him to do an Elvis Presley imitation, and I knew John had no ending for it. Finally he agreed, and to get out of the bit, he picked up a glass of water, threw it at Boggs, hit him in the chest and knocked over a table full of plants. You should have seen Steve Allen's face. It turned into the Hollywood Wax Museum. I don't see John ever becoming that stable. He's one-hundred percent Albanian, you know, the only one you're ever likely to meet. I tell him Albanians are gypsies whose wagons broke down. I have this vision of him with a goose under his arm, trying to sneak out of the room. Yes, that is John: an Albanian goose thief.
"He's one of those hysterical personalities that will never be complete. I look for him to end up floating dead after the party. Comedy is a baby seal hunt."
Sitting in the backyard of Belushi's new apartment after we have moved a Bluesmobile full of boxes into storage in the basement, Belushi counts the steps on the stairway to his second-floor balcony. He is pleased to discover they number thirteen, the same as on the gallows where he tries to hang Jack Nicholson in Goin' South. The huge new apartment has two floors and a chandeliered living room – highly suitable for a television star on the verge of almost certain movie stardom in the coming year. Maybe even the coming month, with Animal House, a comedy premiering in New York City July 28th and scheduled for release in 400 theaters by the middle of August. Universal is counting on a hit, having budgeted about $3.5 million for promotion (the movie itself cost $2.8 million). Their faith is well placed. Animal House is hilarious. Written by Douglas Kenney and Chris Miller of the National Lampoon and Harold Ramis, formerly of Playboy, the movie has much the same sensibility that made the Lampoon's high-school yearbook such a hit. The characters are all stereotypes, but such accurate ones that you recognize everyone you went to college with. Belushi plays Bluto, the most animallike member of the animal fraternity that is expelled from Faber College for crimes that amount to having a good time at the expense of good grades. They seek vengeance by destroying a villainous dean (a tad too villainous, probably. The guy uses four-letter words and is overly frank about his evil intentions. I've never known an educational administrator who didn't sleaze through life on an oil slick of euphemism), a villainous mayor and a villainous rival fraternity. The product of people in their midtwenties to early thirties, the film relays a message from a generation that marched against the war and held gross-out contests to a generation that gets congratulated in U.S. News and World Report for shutting up and wanting to go to medical school: go out and trash something, people, or you won't have anything to remember at your five-year reunion.
"I've seen Animal House two and a half times now at sneak previews with a real audience, and the reaction was great." says Belushi. "Your face ends up forty feet high and if you blow a line during the filming, you can just do it again. If you blow it on TV, it's gone forever. But I want to continue doing both next season. After that, I don't know."
Belushi's schedule this past season was overwhelming. On Sundays after the TV show, he flew to location (Durango, Mexico, for Goin' South; Eugene, Oregon, for Animal House; and Los Angeles for Old Boyfriends) and flew back on Thursdays for Saturday Night Live rehearsals. Because three days of stubble was required for two of the movies and outlawed on the show, just keeping his shaving schedule straight was complicated enough, let alone learning his lines. To keep his life together under such circumstances, I suggest he must be on a more even keel than he was during the first two years of the show.
"Those were very hard times . . . uh . . . very tough, dealing with fame and success, while trying to fulfill your responsibility to the audience," he says. "The trick is knowing what you want to do and then resolving to do everything you have to do to get there."
Does that mean his self-destructive tendencies are under control?
"I think it . . . uh . . . I don't know. It comes along with a certain kind of lifestyle, which you don't change after becoming well known. Everything becomes more heightened, takes on more urgency, and the tendency to self-destruct heightens too. I'm learning to cope and not deny my own success, but I still think it's not happening a lot. I get nervous, and I am capable of doing something to blow it on purpose. A lot of actors have that problem."
To read the new issue of Rolling Stone online, plus the entire RS archive: Click Here
|Music Main
MUSIC 9 Classic Devo Videos
OLYMPICS 18 Epic Opening Ceremonies
Picks From Around the Web
blog comments powered by Disqus
Featured News From thedailybeast
We may use your e-mail address to send you the newsletter and offers that may interest you, on behalf of Rolling Stone and its partners. For more information please read our Privacy Policy.
Most Popular
Photos & Videos
Random Notes: Hottest Rock Pictures


text:
The installation of the sculpture has been delayed a couple of times in the past two weeks but we hope to be on track for the installation to occur this week.
If you have been by the sculpture site (the largest traffic island in front of Sullivan's Pharmacy) recently you'll notice there is a traffic cone wrapped in caution tape. Dig Safe did their final inspection last week and detected a large NStar conduit box two to four feet below the surface right in line with where the sculpture is to be installed. This is a major problem since the foundation for the sculpture will be eight feet below the surface.
Fortunately, we did an excavation two years ago that clearly showed no utilities running under the site. However, based on what Dig Safe found, our contractor wouldn't take the risk of using power equipment and required a substantial amount of additional money to hand dig the hole. So, because Roslindale Village Main Street doesn't have a few thousand dollars hanging around, yours truly got out his shovel and post hole digger from the basement and proceeded to dig a beautiful hole in the traffic island.
On Wednesday I went down four feet and when I finished in the dark around 5:30 I proudly sent off proof in a couple of pictures to the engineer overseeing the project. His reply was, "Can you make it five feet?" So yesterday I went back and got down to 5-feet 6-inches just to be sure. We are waiting to hear back from the contractor about when the installation will occur. Come by the site anytime and check out my hole -- it's a beaut!
We will host a dedication ceremony for "Traffic" at the Greek Church featuring George Greenamyer, the sculptor of "Traffic" and the Mayor sometime after the New Year. We've commissioned a musical composition based on "Traffic" from two Berklee students, Andrew Ikenberry and Jason Lim. Jason and Andrew will perform their composition at the ceremony. They recently went to George's workshop and to several Roslindale Village shops to record sounds that will be used in the piece.
I'll let you know more when we hear from the contractor.
Steve Gag
Roslindale Village Main Street