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US5196191A - Temporal gamma-interferon administration for allergies - Google PatentsTemporal gamma-interferon administration for allergies Download PDF
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/217—IFN-gamma
This is a continuation of copending application Ser. No. 07/325,406 filed on Mar. 17, 1989, now U.S. Pat. No. 5,112,605.
This invention relates to methods for ameliorating allergic immune responses. Particularly, according to this invention, natural or recombinant gamma interferons are administered within a predetermined temporal period prior to suppress a patient's allergic immune response.
Allergy is a hypersensitivity or altered reactivity to an antigen (allergen) that can result in pathologic reactions upon the exposure of a sensitized host to that particular antigen. Although the mechanisms involved in the induction and control of allergic reactions are not completely understood, they have been classified into four types. These include immediate hypersensitivity reactions (Type I), toxic effects of anticell and antitissue antibodies (Type II), toxic effects of complexes between antibody and antigen (Type III), and delayed hypersensitivity (cellmediated) reactions (Type IV).
In Type I, or immediate-type reactions, a variety of immunologic mechanisms may operate, but it is generally believed that they have a mediation pathway that involves the release of pharmacologically active substances from mediator cells. The antibody which is responsible for immediate hypersensitivity belongs to the IgE class of immunoglobulin. IgE antibodies bind to receptors on mediator cells such as mast cells and basophils. Once the IgE antibody is bound to the receptor, an allergen may bind to the antibody, causing the mediator cell to release granules which contain the pharmacologically active substances which lead to an allergic response.
These immediate-type reactions are triggered primarily by ingestants (foods and drugs), injectants (drugs and vaccines) and inhalants (airborne organic and inorganic substances). Symptoms include hay fever, food allergies, asthma, anaphylaxis, and urticaria. Delayed-type hypersensitivity may be triggered by the same kinds of antigens, however the increased reactivity to these specific antigens is mediated not by antibodies but by T-cells. This type of reaction is seen in some autoimmune diseases, and allergic contact dermatitis.
Current therapy of allergic hypersensitivity centers on avoiding offending allergens when feasible, use of appropriate drugs to counteract the symptoms, and immunotherapy. The first approach is not always practicable, and the second is only useful on a short-term basis. Additionally, the effectiveness of drugs such as antihistamines can be limited by side effects such as drowsiness and impaired mental acuity. Similarly, the use of corticosteroids may be limited by the appearance of local and/or systemic toxicity. The use of parenteral immunotherapy has been limited by the potential for systemic allergic reactions including anaphylaxis, as well as the amount of time to reach maintenance doses and the overall duration of the therapy.
As an alternative therapeutic approach, it has been suggested to interfere in vivo with the stimuli that act on the B lymphocytes that are essential for the production of IgE. The literature demonstrating this approach are inconclusive, because the studies involve inducing polyclonal responses rather than clearly antigen-specific IgE responses. Finkelman et al., J. Immunol 141:2335 (1988); Finkelman et al., J. Immunol. 137:2878 (1986); Katona et al., J. Immunol. 140:3206 (1988); Finkelman et al., J. Immunol 142:403 (1989).
Several in vitro studies have suggested that gamma interferon inhibits the production of IgE and thus may suppress an allergic response. See, for example, Coffman et al., J. Immunol. 136:949 (1986); Snapper et al., Science 236:944 (1987); Coffman et al., Immune Regulation by Characterized Polypeptides, Alan R. Liss, Inc. 523-532 (1987); DeFrance et al., J. Exp. Med. 165:1459 (1987); and Hudak et al., PNAS 84:4606 (1987). These in vivo studies share the same basic defect as the in vivo studies discussed above, in that the involve polyclonal responses rather than clearly antigen-specific IgE responses. For example, in an in vivo study, Finkelman et al., J. Immunol. 140:1022 (1988) demonstrate that gamma interferon may suppress the polyclonal, anti-immunoglobulin, immune response in mice stimulated by the injection of a goat antibody to mouse IgD, which by itself induces large increases in levels of serum IgE and increases in other immunoglobulins.
A few studies have proposed to treat allergies by administering gamma interferon to a patient in the course of an allergic response, however these studies are anecdotal, and either inconclusive or contradictory. Australian Patent Application AUA-48412/85 describes the administration of a gamma interferon to a patient with a food allergy. The patient received subcutaneous injections of 0.1×million I.U. of a gamma interferon formulation once a week for four weeks. It is stated that the patient's allergy was resolved after the first injection and this improvement lasted for six months after the last injection. The protocol does not indicate whether or how the patient's reaction to the antigen was challenged, or how recently before the treatment the patient had been exposed to the antigen.
PCT Application WO 87/01288 also claims the use of gamma interferon for treatment of allergies. This application appears to present the same study as Parkin et al., Br. Med. J. [Clin. Res.] 294: 1185 (1987). They describe the administration of 10 and 3,000 micrograms/M2 of gamma interferon to AIDS patients. While some of the patients found their allergic symptoms were apparently ameliorated, these patients also developed increased immediate and delayed hypersensitivity to common allergens. It is also indicated that other individuals in the study developed different allergic sensitivities over the course of the treatment. The observations are anecdotal, and the study provides little specific information on the challenge with the target antigen.
Two recent clinical trials of gamma interferon administration for allergies reveal contradictory data. In an anecdotal report, Boguniewicz et al., J. Allergy and Clin. Immunol 83:307 (100) (1989) disclose the treatment of 14 atopic dermatitis patients with gamma interferon. No placebo controls were included. Symptoms appeared somewhat ameliorated in some of the patients, serum IgE did not decrease, and spontaneous IgE production of peripheral blood lymphocytes decreased.
A more extensive published trial of gamma interferon with allergic patients is described in Li et al., J. Allergy and Clin. Immunol. 83:307 (543) (1989), which documents the double-blind, placebo-controlled trial of recombinant gamma interferon with forty-five adults having documented ragweed hay fever. This study seems to indicate that gamma interferon had little or no effect. There were no significant differences between the control and treated groups in mean weekly symptom scores, supplemental medication scores or hay fever scores, and preliminary inspection of the weekly IgE antibody measurements to crude ragweed extract suggested no marked differences among the groups.
In all of these studies, the dosages of gamma interferon and method and timing of its administration vary widely, as do the results. There remains a need for a treatment for allergies which avoids the disadvantages of the conventional methods and the inconsistencies of published methods of using gamma interferon, and yet provides effective treatment for allergic hypersensitivity.
It is an object of this invention to provide an effective therapy for patients suffering from allergies.
It is a further object of this invention to provide a means of preventing the occurrence of allergic reactions.
It is another object of this invention to increase the therapeutic efficacy of gamma interferon in vivo.
The objects of this invention are accomplished by a method comprising treating a patient known to be susceptible to an allergic response by the administration of a pharmaceutically effective dose of gamma interferon to the patient within a predetermined temporal period prior to or following exposure to an allergen, which period is sufficient to suppress the allergic response in the patient upon subsequent exposure to the allergen. Surprisingly, this method of administration was found to result in consistent suppression of IgE response.
In one embodiment, gamma interferon was administered to an animal model for hyperimmunoglobulinemia E concurrent with or within approximately 3 days following exposure to the allergen, with a resulting suppression of IgE titer.
Gamma interferon may be administered along with additional anti-allergy therapeutic agents such as antihistamines or corticosteroids. It may also be administered along with a substance synergistic with gamma interferon in immunomodulatory assays, or which has synergistic anti-tumor or anti-viral effects, such as TNF-α or TNF-β.
FIG. 1 depicts the experimental schedule discussed in the Example. FIG. 1A shows the schedule for a primary (1°) immunization response. FIG. 1B shows the schedule for a secondary (2°) response. FIG. 1C shows the schedule for a tertiary (3°) response.
FIG. 2 shows the effect of gamma interferon on IgG response. FIG. 2A shows the effect of recombinant gamma interferon (IFN) given through intramuscular (IM), intraperitoneal (IP), and intravenous (IV) delivery on primary (1°) IgG response. FIG. 2B depicts the secondary (2°) IgG response.
FIG. 3 shows the enhancement by gamma interferon of primary (1°) IgE response to antigen. FIG. 3A shows that varying date of administration of the interferon, relative to the antigen gives varying degrees of enhancement. FIG. 3B shows that multiple injections of gamma interferon also enhances primary IgE response to antigen, whether given IP or IV. FIG. 3A shows that the enhancement by gamma interferon of primary IgE response is independent of the route of injection.
FIG. 4 shows the effect of varying temporal administration of gamma interferon on secondary IgE response to antigen.
FIGS. 5A and 5B show that the suppressive effect of gamma interferon on tertiary IgE response depends on the timing of administration. FIG. 5B depicts the tertiary response with selected points of administration, and also the tertiary IgG response at the same selected points of administration.
As used herein, "gamma interferon" refers variously to all forms of gamma interferon as are known to be biologically active in accepted gamma interferon assays, such as by inhibition of encephalomyocarditis virus replication in A549 cells (human lung carcinoma cell line), induction of class II antigens, heat lability, other antiviral and antitumor assays, or neutralization by antibodies having immunoreactivity for gamma interferon but not alpha- or beta-interferon, and is meant to include gamma interferon in a mature, pro, met or des (1-3) form, whether in the form of natural human gamma interferon, recombinant human gamma interferon, or related gamma interferon substances (e.g., non-human gamma interferons). A complete description of the preparation of recombinant human gamma interferon including its DNA and amino acid sequences is shown in U.S. Pat. No. 4,762,791. Amino acid, glycosylation and other variants or derivatives are included within this definition. It is expected that other variants and derivatives will become available in the future, and these are to be considered to fall within the scope of this invention.
It is currently believed that gamma interferon serves to down-regulate Interleukin-4, which is in turn involved in the up-regulation of IgE. Therefore, compositions which have the effect of down-regulating Interleukin-4, and compositions which are synergistic with gamma interferon in immunomodulatory assays, are encompassed within the scope of this invention.
TNF, as employed herein, refers, in general to the various forms of TNF which exhibit one or more biologic properties of tumor necrosis such as tumor cell lysis, inhibition of infectious agents, class II antigen induction and neutralization by antibody to TNF-α or TNF-β (lymphotoxin) but not by antibodies to other cytokines. It is believed that TNF is synergistic with gamma interferon in anti-tumor or antiviral assays for gamma interferon, and may therefore be desirably administered along with gamma interferon in the practice of this invention.
The formulations may contain agents such as antihistamines and corticosteroids previously suggested for use in allergy treatment. Gamma interferon also is suitably formulated together with known agents in order to modify or enhance the half-life or therapeutic activity of the interferon.
Gamma interferon is placed into sterile, isotonic formulations together with required cofactors. The formulation of gamma interferon is preferably liquid, and is ordinarily a physiologic salt solution or dextrose solution, together with conventional stabilizers and/or incipients. The composition may also be provided as lyophilized powder. Saline is a suitable carrier, although other conventional parenteral solutions or buffers are usable.
In a pharmacologic sense, in the context of the present invention, a therapeutically effective amount of gamma interferon refers to that amount effective to suppress the production of IgE by the B lymphocytes. The therapeutically effective dosage of gamma interferon to be administered to a human patient generally will range from about 5×105 to 5×106 units per dose, although the dose of the gamma interferon administered will be dependent upon the species of the patient, the properties of the gamma interferon employed, e.g. its activity and biological half-life, the concentration of the interferon in the formulation, the rate of dosage, the clinical tolerance of the patients involved, the pathological condition of the patients and the like, as is well within the skill of the physician. It will be appreciated that the practitioner will adjust the therapeutic dose in line with clinical experience for any given gamma interferon.
In the practice of the invention, compositions which include a therapeutically effective amount of gamma interferon are administered to patients known to be susceptible to an allergic immune response. Accordingly, in the practice of this invention, the gamma interferon, alone or with other agents as described above, is administered to a patient within a predetermined temporal period prior to or preferably, following the exposure to an allergen, which period is sufficient to suppress the allergic response in the patient upon subsequent exposure to the allergen.
It will be understood that the critical aspect of this invention resides in appreciating that the time of administration of gamma interferon in relation to intentional or adventitious exposure to allergen is determinative of whether the IgE response to the allergen will be up-regulated or down-regulated. For each animal species and man the critical period may vary from that shown herein for a murine model, i.e. it may be greater or longer than 3 days, or it may have a more narrow window of efficacy, e.g. 1-2 days.
The exact administration parameters suitable for any given patient or animal species will be determined by routine experimentation. Typically, the patient is first exposed to allergen, e.g. by subcutaneous, oral, or inhalation administration, and thereafter gamma interferon is administered in single or clustered doses at a predetermined time. The patient is observed for symptoms of hyperallergic response and for IgE induction. If the initial study is unsuccessful another point, usually single, of temporal administration is chosen and the process repeated with that variable. It is believed that the temporal effect will be largely constant within a given species, and may be constant among species.
It is envisioned that the gamma interferon is administered as substantially a single dose, although multiple dosages are within the scope of this invention. Injections may be intraperitoneal, intracutaneous, subcutaneous, intravenous, and intramuscular. It is presently preferred to administer the gamma interferon in an aerosol suitable for inhalation.
In one preferred embodiment, a patient who has been exposed to an allergen on at least two prior occasions is exposed again to that allergen, with that exposure being concurrent with or followed within up to about three days by administration of gamma interferon.
In other embodiments, a patient who has been exposed to an allergen on at least one prior occasion is exposed again to that allergen, with the patient receiving an administration of gamma interferon within a temporal period extending from about 4 days prior and 4 days subsequent to the allergen exposure.
This invention encompasses the predetermined exposure of the patient to an allergen, including by administration of that allergen to the patient. Thus it may be seen that the method of this invention may be utilized concurrently with standard desensitization therapy.
It is also envisioned that the method of this invention may be repeated a plurality of times from about four to six weeks apart.
The method of this invention may be used to treat patients, including cats, dogs, and humans. Patients having Acquired Immune Deficiency Syndrome ordinarily are excluded from the scope of this invention. According to this invention, patients from differing species are all treated by the pharmaceutically acceptable administration of gamma interferon in a pharmaceutically effective dosage and for a period of time sufficient to ameliorate and suppress the allergic response in the patient upon subsequent exposure to an antigen.
In order that the invention described herein may be more fully understood, the following example is set forth. It should be understood that this example is for illustrative purposes only, and is not to be construed as limiting this invention in any manner.
Immunizations: (C57BL/6×DBA/2) F1 (BDF1) mice were immunized by an intraperitoneal (ip) injection of 0.5 μg DNP2 OA absorbed to 1 mg aluminum hydroxide gel (alum). Groups of mice were treated with 105 units of recombinant murine gamma interferon by injecting 0.1 ml of the appropriate dilution ip, intramuscular (im), or intravenous (iv) as indicated in the individual experimental protocols. The experimental schedules for these experiments are shown in FIG. 1. Twenty-four animals were in each treatment group.
IgE: Anti-hapten IgE antibodies were titrated by passive cutaneous anaphylaxis (PCA) reactions in Sprague Dawley Rats. Twofold dilutions of the test mouse serum were injected intracutaneously and the reaction was elicited after a 4 hr sensitization period by an iv injection of 2.5 mg DNP6 -HSA (dinitrophenyl-human serum albumin) in 0.5 ml of 10% Evans Blue dye.
IgG: IgG anti-DNP antibodies in the test mouse sera were measured by an ELISA (Enzyme-linked immunoassay) using serum of anti DNP-OA primed mice as a reference standard. The ELISA was set up in 96 well plates. Each well was coated with 0.1 ml of 2.5 μg/ml DNP6 HSA for 24 hrs at 4° C. After blocking with 0.1% BSA, 0.1 ml of each test sera was added to the antigen coated plates in triplicate and the plates were incubated for 2 hrs at room temperature. The plates were washed 3× with PBS/0.02% Tween 20 and 0.1 ml of a 1:2000 dilution of rabbit anti-mouse IgG (Cappel Labs) was added to each well. Plates were again incubated 2 hrs and washed. Next 0.1 ml of a 1:1600 dilution of Goat anti-Rabbit Horseradish peroxidase-conjugated antiserum was then added to each well for 1 hr at room temperature. After washing, 0.1 ml of 0.2 mg/ml OPD (orthophenyl diamine), 0.01% H2 O2 in 0.05M citrate buffer was added to each well, the reaction was stopped with 2M H2 SO4 after 30 minutes, and the OD was read at 490 nm on a Microtect plate reader.
As can be seen in FIG. 3A, the results of these experiments suggest that gamma interferon can augment the priming of an in vivo IgE response. This augmentation appears to be independent of the route (ip vs. im vs. iv) of injection (FIG. 3A) or the number of doses (1, 2, or 3) of gamma interferon (FIG. 3B). Furthermore, if animals receive a second challenge with the antigen, the secondary (2°) IgE response is also enhanced compared to controls.
The results of these experiments suggest that gamma interferon can suppress antigen (allergen) driven IgE responses when administered in close proximity to antigen challenge. As shown in FIG. 4, in the case of the 2° response, when gamma is administered before antigen boost (0-4 days) or after boost (0-3 days), the IgE response to the antigen is significantly depressed compared to controls. In contrast, in the case of the 3° response shown in FIG. 5A, only administration of gamma interferon, after the boost (1-3 days) significantly depresses IgE responses. The clinical significance of these findings is that gamma interferon, if administered at the proper time following antigen challenge, reduces levels of IgE and therefore decreases the symptoms mediated by IgE triggering of mast cell/basophil degranulation. In addition, since the IgG response to the antigen, shown in FIG. 5B and FIGS. 2A and 2B, is unaffected by this treatment, and allergen desensitization shots operate under the principle that these shots decrease IgE levels while increasing IgG levels, gamma interferon may be useful as an adjunct to this form of therapy.
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Cited By (1)
|Publication number
|Priority date
|Publication date
|US20050220762A1 (en) *
|Ambrx, Inc.
|Modified human interferon polypeptides and their uses
Citations (3)
|Publication number
|Priority date
|Publication date
|WO1987001288A1 (en) *
|Biogen N.V.
|Process for treatment of allergies
|US4762791A (en) *
|Genentech, Inc.
|Human immune interferon
|US5112605A (en) *
|Genentech, Inc.
|Temporal gamma-interferon administration for allergies
Patent Citations (3)
|Publication number
|Priority date
|Publication date
|US4762791A (en) *
|Genentech, Inc.
|Human immune interferon
|WO1987001288A1 (en) *
|Biogen N.V.
|Process for treatment of allergies
|US5112605A (en) *
|Genentech, Inc.
|Temporal gamma-interferon administration for allergies
Non-Patent Citations (14)
|Boguniewicz et al., J. Allergy and Clin. Immunol. 83: 307 (100) (1989). *
|Coffman, et al., Immune Regulation by Characterized Polypeptides, 523 (1987). *
|Coffmen et al., J. Immunol. 136: 949 (1986). *
|F. D. Finkelman et al., J. Immunol. 137: 3878 (1986). *
|F. D. Finkelman et al., J. Immunol. 140: 1022 (1988). *
|F. D. Finkelman et al., J. Immunol. 141: 2335 (1988). *
|F. D. Finkelman et al., J. Immunol. 142: 403 (1989). *
|I. M. Katona et al., J. Immunol. 140: 3206 (1988). *
|J. M. Parkin et al., Br. Med. J. [Clin. Res.] 294: 1185 (1987).
|J. M. Parkin et al., Br. Med. J. Clin. Res. 294: 1185 (1987). *
|Li et al., J. Allergy and Clin. Immunol. 83: 307 (543) (1989). *
|S. A. Hudak et al., PNAS 84: 4606 (1987). *
|Snapper et al., Science 236: 944 (1987). *
|T. DeFrance et al., J. Exp. Med. 165: 1459 (1987). *
Cited By (4)
|Publication number
|Priority date
|Publication date
|US20050220762A1 (en) *
|Ambrx, Inc.
|Modified human interferon polypeptides and their uses
|US8097702B2 (en)
|Ambrx, Inc.
|Modified human interferon polypeptides with at least one non-naturally encoded amino acid and their uses
|US8119603B2 (en)
|Ambrx, Inc.
|Modified human interferon polypeptides and their uses
|US8232371B2 (en)
|Ambrx, Inc.
|Modified human interferon polypeptides and their uses
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Dave's Rating:
Daft junk
This stupidly funny ooga-booga-spirits-n-stuff thriller, formerly known as Shelter, was first released in Japan in March of 2010. It hit the U.K. the month after that. You read that correctly: three years ago. Since that time, people in Kazakhstan (April, 2011) and Spain (June, 2012) have also enjoyed the privilege of seeing this film before you. It's been available on Blu-ray in Finland as of 27 months ago, so those people didn't even have to leave their house to watch it. And you, lucky last Americans, are also allowed not to venture outside for its very limited theatrical release this weekend because it's been for rent here on the internet for a few weeks, too.
Or you can just keep reading while I spoil the whole thing for you.
And by "spoil" I mean encourage to see, ideally as a double feature with Tyler Perry's Temptation: Confessions of A Marriage Counselor. They make nice companion pieces, since both function within their own idiosyncratically supernatural economy. Perry's sucks the life out its characters with terminal illness as punishment for sexual misdeeds and this one sucks the souls out of everyone it can get its hands on via Satanic hillbilly grandmothers and evil spirits existing in the form of sound waves that resemble the album cover design for Joy Division's Unknown Pleasures. I'm not going off on a fantasy tangent here; both of these excellent inventions (and more) are really in this movie.
Julianne Moore plays a forensic psychiatrist goaded by her pushy, irritating psychiatrist father (Jeffrey DeMunn) into observing Jonathan Rhys Meyers, a man alleged to have multiple distinct personalities. She dismisses it all as the ginned up fantasies of "ill-conceived Hollywood movies," although, presumably, not the one she's starring in here. When JRM shifts between identities he has seizures and snaps his neck back like he's being spoon-bent by Satan, then affects a variety of regional dialects, including Tough New York Street Fellow and All People of The American South At Once. Meanwhile, everybody who comes into contact with JRM gets weird cross-like rashes on their backs. Then they begin coughing up dirt. Moore investigates the identities of the people inhabiting JRM by creeping around empty houses and uncovering unsettling facts about them, starting with how dead they all are.
Along the way to her ultimate showdown with evil she uncovers clues like sheet music hung on clotheslines, evidence of ritual slayings, old ladies succumbing to religious mania, rotary phones that pass the suggestion of evil spirits along (I guess because nobody uses them for anything else these days or else the spirits themselves are strictly analog entities), those black and ghostly sound wave monster-things that attack you in your sleep, backwoods surgery, Rob Halford-esque rock stars, Necronomican-style warnings tagged on every wall within a hundred miles, the reincarnation of an old-timey faith healer, albino children and people squirting mucus from their own eye sockets. Nothing scares Dr. Moore, though, she just drives around from place to place collecting evidence that makes no sense and being yelled at by her father for not asking enough "why"-based spiritual questions of herself. Dude, she's hunting down a phantom sound wave. Know how elusive those can be? She's BUSY.
"You're in great danger, Buckeroo!" yells JRM at one point near the end, when he realizes Moore has managed to piece together the wacky puzzle the film has decided to create, the one where he's the missing piece. And you get the feeling that he's not simply yelling into the void but, instead, trying to warn the real-life him that no good can come from acting in a film that requires impersonating a little girl whose soul you just inhaled, going all wide-eyed and calling Julianne Moore "Mommy" as she uses her last shred of dignity to impale you on an evil-vanquishing spike. Unless "Buckaroo" is one of the six souls, which is entirely possible. I lost count of them. You will too.
28 out of 100 Metascore®
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Story highlights
- Rebels say they liberated Aleppo neighborhoods
- Government says it killed dozens of "terrorists"
- Fighting across Syria kills at least 126 people, the opposition says
- The United States announces $15 million in non-lethal support for the unarmed opposition
Syrian government forces and rebels engaged Saturday in fierce clashes throughout the vital and culturally rich city of Aleppo, with portions of a storied marketplace going up in flames.
Abu Abdallah, an opposition activist in Aleppo, told CNN that rebel forces had liberated at least four neighborhoods by the third day of an offensive against President Bashar al-Assad's forces.
But the government trumpeted its actions against the opposition.
"The armed forces on Saturday continued to target hideouts and gatherings of terrorists in Aleppo city and its countryside, killing and injuring dozens of terrorists and destroying their vehicles," according to the state-run Syrian Arab News Agency (SANA).
The see-saw fight for Aleppo, once considered an al-Assad stronghold, has continued nearly unabated since July, though the number of casualties has steadily increased.
Syrian forces targeted "terrorists" at several sites, including part of the city's medieval souk, a historic market, and killed and wounded several of them, SANA reported.
Video posted on YouTube showed a fire that had been initially set off on Saturday night continued to spread through the souk Sunday amid the sound of gunfire. The description on the video said it was recorded Saturday after "Assad gangs" burned the market.
CNN is unable to independently verify the veracity of the video.
The marketplace, once popular with tourists, is a labyrinth of covered alleys.
The opposition Local Coordination Committees of Syria said, "the (rebel) Free Syrian Army and the families of the city were unable to extinguish the fire due to the spread of regime snipers."
Aleppo is a UNESCO World Heritage Site, dominated by an ancient citadel. The city also is a center for the art and was named Islamic capital of culture six years ago.
"No part of the ancient treasure of humanity shall be destroyed," Sok An, chair of the group's world heritage committee, said in August. "It is the collective responsibility of all humanity to urgently ensure the safeguarding and protection of Aleppo's cultural properties."
Opposition groups reported clashes near al-Nayrab Military Airport in the south of the city, where initial information indicate that the rebels damaged at least two helicopters and a main runway after firing mortars. Several districts of the city came under artillery shelling, the opposition said.
Government forces hammered rebels in several locations, inflicting substantial casualties, according to SANA. It said troops assumed control of the al-Amiriyeh area and much of Tal al-Zarazir in Aleppo.
Al-Assad has severely limited the access of international journalists to the country, so CNN is unable to verify opposition and government claims of violence.
At least 126 people were killed in fighting across the country Saturday, according to the LCC. Among those killed were 64 people in Damascus and its suburbs.
In the Damascus neighborhood of Barzeh, 43 people were killed over three days after government forces came through. The LCC linked to an online video, purportedly shot in Barzeh on Saturday, showing columns of armed, camouflaged soldiers walking down a busy street as two tanks rolled by.
SANA reported a military unit killed "many terrorists" in Barzeh.
Neighborhood residents in Homs held a friendship march Saturday, according to SANA. Homs Gov. Ahmad Munir Mohammad said, "no matter how hard the enemies try, the Syrian people will remain strong and steadfast in the face of the conspiracies."
U.S. to Iran: Stop shipping arms to Syria
The United States warned Iran to stop providing arms to al-Assad even as it announced millions of dollars in non-lethal support for the opposition attempting to oust the government.
Secretary of State Hillary Clinton called on Syria's neighbors to take steps to prevent Iran from using their land and airspace to transport weapons to al-Assad's forces.
Clinton's warning followed an admission, according to Iranian state-run media reports, by the commander of Iran's Revolutionary Guard that its elite Quds Force was operating inside Syria but not involved directly in military action.
Clinton announced the United States is donating $15 million to unarmed Syrian opposition groups, bringing the total U.S. aid for the opposition to nearly $45 million.
The latest donation "translates into more than 1,100 sets of communications equipment, including satellite-linked computers, telephones, and cameras, as well as training for more than 1,000 activists, students, and independent journalists," she said.
The United States also is donating an additional $30 million in humanitarian assistance, primarily in the form of food, water and medical supplies, Clinton said.
Syria's chemical weapons a target?
A former senior officer in the Syrian Army said Friday that Iranian technicians are helping with the Syrian government's research into chemical weapons.
Adnan Sillu, a former major general who says he was chief of staff of chemical warfare, also said Syria can easily transfer the weapons to Hezbollah, the Lebanese militia organization that fought a border conflict with Israel in 2006.
Syrian opposition posted a series of videos on YouTube suggesting rebels are beginning to focus on where al-Assad's government stores its chemical weapons.
The videos were first uploaded in July. Narrators using Google Earth satellite imagery describe in detail several sites where they allege that chemical weapons and missiles are stored or manufactured.
There is no way for CNN to independently verify what the videos purport to show.
Sillu said moving the weapons would be easy for the government should they be at risk of falling into the rebels' hands.
His comments follow word from U.S. Secretary of Defense Leon Panetta that the Syrian government has moved chemical weapons at various sites for security reasons.
U.S. officials have said they believe that the stashes remain secured by the Syrian military.
Background on the conflict
The Syrian conflict broke out in March 2011 after unarmed protesters, inspired by the success of popular uprisings in Egypt and Tunisia, took to the streets demanding political reform and an end to four decades of rule by the Assad family.
The movement quickly devolved into an armed conflict after a brutal and continuing crackdown by government forces.
Since the unrest began, more than 30,000 people have been killed, the opposition Syrian Observatory for Human Rights said.


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WASHINGTON (AP) – Three days into a government shutdown, President Barack Obama pointedly blamed House Speaker John Boehner on Thursday for keeping federal agencies closed while the bitter budget dispute moved closer to a more critical showdown over the nation's line of credit. The Treasury warned of calamitous results if Congress fails to raise the debt limit.
Answering Obama, Boehner complained that the president was "steamrolling ahead" with the implementation of the nation's new health care law. As the government operated sporadically, the stock market sank to its lowest level in nearly a month.
The shutdown was clearly leaving its mark. The National Transportation Safety Board wasn't sending investigators to Tennessee to probe a deadly church bus crash that killed eight people and sent 14 others to the hospital. The Labor Department said it wouldn't release the highly anticipated September jobs report on Friday because the government remains shuttered.
Despite the heated political rhetoric, some signs of a possible way out of the shutdown emerged. But the state of play remained in flux.
Two House Republicans said Boehner told them he would allow a House vote on re-starting the entire government – but only if conservative GOP lawmakers assured him they would not attack it for failing to contain curbs on the health care law. So far they have been unwilling to give that commitment. The two spoke on condition of anonymity to reveal details of private discussions.
The shutdown and the approaching debt ceiling were merging into one confrontation, raising the stakes for the president and Congress as well as for the economy.
Obama and his Treasury Department said that failure to raise the nation's borrowing limit, expected to hit its $16.7 trillion cap in mid-October, could precipitate an economic nosedive worse than the Great Recession. A default could cause the nation's credit markets to freeze, the value of the dollar to plummet and U.S. interest rates to skyrocket, according to the Treasury report.
The speaker's office reiterated Boehner's past assertion that he would not let the United States default on its debt.
Conservatives have insisted that either reopening the government or an increase of the debt ceiling must be accompanied by a measure that either delays or defunds the nation's new health care law.
Obama, for his part, firmly restated his opposition to a negotiation.
"You don't get to demand some ransom in exchange for keeping the government running," he said tartly. "You don't get to demand ransom in exchange for keeping the economy running."


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The Inefficiency of Feed ReadersFeed readers are a very inefficient way to keep up with the news. As most news sites and blogs have feeds, you might think you save time by adding your favorite sites to a feed reader. After all, you don't have to visit them ever again if they publish full feeds or only if you find some interesting if they publish partial feeds.
A feed reader shows you the latest information from each site you've subscribed to. Often, many blogs discuss a single news, but you don't have all these posts at a glance. A feed reader should cluster related posts.
Closed universe
You have a list of feeds, but you can't discover new feeds organically. Your list of feeds should automatically based on your preferences.
Lack of order
There's no hierarchy in your feed reader. You may have only 5 minutes to find out what's new, but you don't know where to start. A good feed reader should rank posts and prioritize breaking news.
Sense of guilt
If you don't open/visit a feed reader for a week, you may end up with hundreds of thousands of unread posts. You may want to mark all as read and move on, but what if you lose something important? A feed reader forces you to read (or scan) each and every post.
No related universes
Maybe there are other people with similar tastes that may help you improve your universe. A feed reader should automatically detect that and suggest posts that were considered interesting by your virtual group of anonymous friends.
In most of these affirmations, I've described a typical feed reader. If you know one that does all of these things (or only some of them), let us know.


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VP debates often more memorable
Vice presidential debates may not mean much in the long run — people vote for presidents, after all — but they tend to produce the most memorable moments.
"Democrat wars" …"Senator, you're no Jack Kennedy" …"Who am I? Why am I here?" -- all oft-echoed lines delivered during vice presidential debates.
Since their beginning in the 1976 election, vice presidential debates have featured future presidential nominees (Bob Dole, Walter Mondale and Al Gore), but only one future president (George H.W. Bush).
They have also spotlighted the first two women on national political tickets, Democrat Geraldine Ferraro in 1984 and Republican Sarah Palin in 2008.
As Vice President Biden and Republican Paul Ryan prepare to try and make their own history on Thursday night, let's take a look at the previous contests.
1976 -- The first veep contest took place Oct. 15 in Houston, as Democratic challenger Walter Mondale, Jimmy Carter's running mate, took on President Gerald Ford's political partner, Bob Dole.
The most memorable exchange came when Dole blamed the Democratic Party for global conflicts: "All Democrat wars, all in this century."
Mondale responded by saying, "Senator Dole has richly earned his reputation as a hatchet man."
Carter and Mondale won the election, barely.
1980 -- No vice presidential debate this year; aides to President Carter and Republican challenger Ronald Reagan had trouble agreeing to a format, and there was only one debate between the presidential candidates themselves.
Reagan was seen as winning that debate, and definitely won the election.
1984 -- This Oct. 11 contest in Philadelphia featured two historic participants: A future Republican president, incumbent Vice President George H.W. Bush, and Democratic challenger Geraldine Ferraro, the first woman on a national ticket.
Gender issues seemed to flare during the debate when Bush said, "let me help you with the difference, Ms. Ferraro, between Iran and the embassy in Lebanon."
Responded Ferraro: "I almost resent, Vice President Bush, your patronizing attitude that you have to teach me about foreign policy."
Perhaps the most memorable moment came after the debate, as Bush was caught on an open mike saying he "tried to kick a little ass."
Other observers awarded the debate to Ferraro, though Bush and President Reagan easily won second terms.
1988 -- Did this Oct. 5 vice presidential showdown at Creighton University in Omaha produce the most famous political put-down in history?
When George H.W. Bush's running mate Dan Quayle pointed out he had nearly as much congressional experience as John F. Kennedy, Democratic candidate Lloyd Bentsen pounced.
Said the Michael Dukakis running mate to Quayle: "Senator, I served with Jack Kennedy: I knew Jack Kennedy; Jack Kennedy was a friend of mine. … Senator, you're no Jack Kennedy."
Not that it mattered much: Bush and Quayle easily won the election.
1992 -- The only three-person vice presidential debate in history, and one best remembered for the third man: Ross Perot's running mate James Stockdale.
Flanked by GOP Vice President Quayle and Democratic challenger Al Gore, the retired admiral opened with a much-parodied line: "Who am I? Why am I here?"
Stockdale, who has also had trouble with his hearing aide that long night in Atlanta, took a pounding after the debate, including a merciless parody by comedian Phil Hartman on Saturday Night Live.
Nearly all of it was unfair.
An author and a scholar, a Vietnam prisoner of war, the late Admiral Stockdale was and is revered by many veterans — he just wasn't a politician, and he was put in an impossible situation.
Perot had tapped Stockdale as a place-holder to accommodate states that required a running mate for ballot qualification. When Perot was unable to attract a better known person to his ticket, Stockdale remained -- and basically got fed to political lions.
Note, however, that Stockdale fired off one of the best lines of the night, one that still resonates today. After of the many arguments between Gore and Quayle, Stockdale said: "I think America is seeing right now the reason this nation is in gridlock."
Gore and his running mate, Bill Clinton, won the election.
1996 –The match between incumbent Al Gore and Bob Dole's running mate Jack Kemp proved to be the least distinguished of the vice presidential debates.
Clinton and Gore glided to re-election.
2000 -- As George W. Bush run against Gore for the presidency, Dick Cheney and Joe Lieberman met in an Oct. 5 debate notable in part for its small town setting: Centre College in Danville, Ky., site of Thursday's showdown between Biden and Ryan.
The Cheney-Lieberman clash is more notable in retrospect.
Eight years later, Lieberman would again be considered for the vice presidential slot -- by a Republican, John McCain.
Cheney, meanwhile, went on to become maybe the most powerful vice president in history after George W. Bush's election.
2004 -- This Oct. 5 battle in Cleveland between Cheney and Democratic challenger John Edwards featured a notable Cheney line about the experience of Edwards, a first-term senator.
"The first time I ever met you was when you walked on the stage tonight,"' Cheney said.
The Cheney-Edwards set-to is also memorable in terms of future events.
Cheney's legacy will long be a source of debate.
Edwards sought the vice presidency four years before the sex scandal that gutted his career and reputation.
Cheney and Bush wound up winning a second term.
2008 -- Perhaps the most anticipated debate in political history, certainly among vice presidential contests.
The fascination with the suddenly famous Sarah Palin -- going up against veteran Biden -- drew some 70 million television viewers, the largest audience ever for a vice presidential debate.
"Can I call you Joe?" asked the first-term Alaska governor during the opening handshake.
Palin and Biden both did well in their Oct. 5 showdown in St. Louis, and their efforts had little effect on the presidential race.
Democrats Barack Obama and Biden handily defeated John McCain and Palin on Election Day.


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Big Rapids, Mich. - A veteran coach with more than 15 years of experience in directing an intercollegiate softball program has been tabbed as Ferris State University's next head softball coach as FSU Athletics Director Perk Weisenburger announced today (Nov. 19) the appointment of Sarah Rotta to lead the Bulldog program.
A Michigan native and former collegiate student-athlete at the University of Detroit, Rotta has served as a head coach at the collegiate level since 1998, including the last seven years at the University of Michigan-Dearborn. Previously, she was also the head coach from 1998 to 2006 at Macomb Community College. Her first official day at the Bulldog helm will be
Nov. 20.
Rotta will take over for former head coach Marie Foster, who departed in August to become the associate head coach at NCAA Division I Western Michigan after leading the Bulldogs to a 29-16 overall record and an NCAA Tournament appearance last spring.
"I am pleased to announce that Sarah Rotta will become the new head softball coach at Ferris State," said Weisenburger. "When we began this search process we identified specific qualities that were imporant to us. We wanted someone who is a demonstrated teacher and coach of the game, someone with an understanding of college softball and a passion to build and maintain a winning program, and most importantly someone who will commit to this team and program and provide Ferris State with the championship stability that we want. We found that person in Coach Rotta."
While at Michigan-Dearborn, Rotta was responsible for the development of softball as a varsity sport at the collegiate level. She coached 10 first team All-Wolverine Hoosier Athletic Conference (WHAC) performers along with 19 honorable mention selections in addition to 24 academic all-conference awardees and six NAIA All-American Scholars.
"As a team, we're looking forward to Coach Rotta's leadership," said senior student-athlete and returning two-time All-Great Lakes Intercollegiate Athletic Conference (GLIAC) honoree Amy Dunleavy. "We wanted someone to come in who's passionate about Ferris State and the softball program. She's certainly displayed that to us and will bring a great drive and motivation to help us succeed."
"Sarah will bring a great deal of experience and passion for softball to Ferris State University," said Dawn Thompson, who has been a key member of the Bulldog coaching staff for the last five years and has served most recently as the program's interim head coach since Foster's departure. "She is excited to work with our student-athletes in their pursuit of excellence both on and off the field and I believe she'll prove to be an outstanding leader for Bulldog Softball."
During her tenture at UM-Dearborn, the Michigan native received the WHAC Champion of Character Coach Award in 2012 and registered her 300th career victory in April of 2011. Her team qualified for the conference tournament in the program's first year of competition and posted a third-place 17-11 conference finish in her second campaign.
"I'm very excited to become part of the Ferris State and Big Rapids community," said Rotta. "Everyone treated me so well during the interview process and I'm looking forward to being part of an outstanding organization. A great deal of credit goes to Dawn Thompson, who has been tremendous to talk with and a person who's been extremely committed to the program and growth of the student-athletes.
"During the process, I found a team really looking for a coach who can bring consistency and one that wants to win a championship so I couldn't be more happy being the choice to help make that happen," she added.
As a head coach at her previous stop, Rotta directed and oversaw all aspects of the softball program such as game strategy, recruiting, budget, travel and scheduling. She also coordinated fundraising activities, which was essential to the UM-Dearborn softball program.
In addition to serving as the head softball coach at UM-Dearborn, Rotta also was the academic coordinator for the school's athletics program. Among her key initiatives was designing and implementing the START (Successful Team Academic Round Tables) Program for academic support of student-athletes.
Rotta began her collegiate head coaching career guiding Macomb Community College where she built a highly-reputable and nationally-recognized program. She claimed Michigan Community College Athletic Association (MCCAA) State Coach of the Year laurels twice and was the Eastern Conference Coach of the Year four times. She also received National Junior College Athletic Association (NJCAA) Region XII Coach of the Year honors in both 2001 and 2003 in addition to the Region IX "Real Sport" Award in 1999. Her team finished seventh in the country at the 2001 NJCAA National Tournament and won a regional title under her direction.
She also supervised a successful academic support program at Macomb CC while helping improve the athlete degree completion rate to three times the national average for JUCO student-athletes. Prior to her collegiate coaching career, Rotta served as a paramedic for 10 years for the Universal Macomb Ambulance in Sterling Heights.
As a collegiate student-athlete, Rotta was a member of the University of Detroit softball team from 1988 to 1990. She earned a liberal arts degree from Macomb CC where she also claimed team MVP accolades. She later earned a degree in business communication from Rochester College and is currently working towards a masters degree in coaching and athletic administration from Concordia University in Irvine, Calif.
Overall, Ferris State has made five trips to the NCAA Tournament since 2005. Last spring, the Bulldogs reached the NCAA Tournament for the eighth time in school history and it represented the 10th consecutive year in which FSU won at least 24 games in a season. The Bulldogs finished as the GLIAC runner-up in regular-season play with a 20-6 league record in 2013.


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Opening period dooms Flyers in loss to Leafsby Staff Writer / Philadelphia Flyers
LONDON, Ont. -- Nazem Kadri and Mason Raymond each had a goal and an assist Sunday as the Toronto Maple Leafs opened the NHL pre-season schedule with a 4-3 victory over the Philadelphia Flyers.
Kadri, who signed a new two-year deal on the eve of training camp, is expected to produce, while Raymond is with the Leafs on a tryout basis after 374 games with the Vancouver Canucks.
Performing in his hometown, it was Kadri opening the offence as the Leafs scored three in 3:05 for an early 3-0 advantage.
Kadri, who also starred in the Budweiser Gardens for the Ontario Hockey League's London Knights, began a two-on-one rush inside his own blue-line. Kadri used a drag move to awkwardly put Philadelphia defenceman Hal Gill out of position before snapping the puck past Steve Mason.
Troy Bodie, who split his AHL time between Portland and Norfolk last year and was inked as a free agent by Toronto in July, made it 2-0 by beating Mason in close. Bodie received his pass on the doorstep from 2013 first-round pick Frederik Gauthier.
The third Toronto goal displayed the speed of Raymond as he scored short-handed on a breakaway after stealing the puck at his own blue-line and out-raced Philadelphia's Erik Gustafsson down the right wing.
Philadelphia rebounded quickly with three goals from Doug Clarkson in the first period and Brayden Schenn and Nick Cousins early in second.
The Cousins goal was started by a Gill point shot that went wide of Leafs goaltender James Reimer's net and bounded out the other side for Cousins to flip in a backhand.
After netminder changes by both clubs, Toronto's Paul Ranger welcomed Anthony Stolarz by converting a rebound on a give-and-go effort by Kadri and David Broll.
The final period was scoreless.
In 28 minutes of work, Reimer stopped 14 of 17, while counterpart Mason stopped 12 of 15. Maple Leafs' Christopher Gibson didn't allow a goal in 32 minutes and was credited with 13 saves, while the Flyers' Anthony Stolarz was beaten in his first minute, but settled down to make 14 saves on 15 shots.
Six former or current London Knights dressed including Kadri, Dave Bolland and Ryan Rupert for Toronto, and Mason, Stolarz and Zac Rinaldo for the Flyers.
The two clubs meet again on Monday at Air Canada Centre in Toronto. The Leafs tune-up schedule includes eight games over 14 days before opening the campaign Oct. 1 in Montreal.
The Flyers open their regular season versus Toronto at home Oct. 2.


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|January 25, 2013
12:00 AM to 11:59 PM
|Martin Luther King Jr. Arena
|Ticket prices vary.
|Be a part of circus history Jan. 23-27 as The Greatest Show On Earth harnesses the energy of the audience to power the performers. Witness superhuman stunts so close, you can feel it! Experience the excitement as Ringling Bros. transforms energy and power into megawatts of thrills. Imaginations ignite for children of all ages. For more information and a list of show times, go to http://www.savannahga.gov/ index.aspx?NID=604.


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Additional Credits
Photographer Statement
To license this work for editorial, creative, or other uses, click on the OZMO logo above.
This will take you to the Ozmo website retro toys where you can review the cost and license for the photographs in this exhibit.
You will need to create an account with both Amazon payments and with the Ozmo website as described on the Ozmo website.
Affiliated NGO
Contact Photographer
Nadia Todres
(917) 734-4838
Death in Haiti
Photographer: Nadia Todres
Exhibit Title: Death in Haiti
Location: Haiti
Death in Haiti comes easily. It comes to many. Young and old. Poor and Poorer. It comes without explanation. Those who mourn do so, often loudly, sometimes wildly and always beautifully adorned. They walk roads, rubble and countryside, climbing down steep slopes, they cry, play music and walk beside one another. Bearing witness to their process is a privilege and an honor; of which I am grateful for each time I am invited. The images I make of death in Haiti are the images I relate to the most.They speak to me, in ways others cannot. They are alive in ways that others are not. They scream out in ways that others can not. They are the images I most want the world to see; for Haiti overflows with pain, most of which is hidden, beneath their tents and torn tarps, in the darkness of the night, in everything they lack. But when death comes, we see it, in all it's starkness. Loud and wild, bursting at the seams and we can't help but listen.
Nadia Todres
(917) 734-4838
Make Comment/View Comments


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Canadian Gay Man Opens Up About Alleged Anti-Gay Attack
A gay man from St. John's, Newfoundland, Canada, who was beaten last week, took to social media sites to open up about the alleged anti-gay attack, the Huffington Post Canada reports.
"It's really scary when somebody tells you that if you weren't found 10 minutes before you would've bled out and died," Pattrick Blackburn said in a YouTube video, which has since been removed. According to Canada.com, a YouTube user commented on the video, claiming to be Blackburn's close friend and said he took down the clip because of "malicious acts of sabotage towards his Youtube and Facebook accounts."
Blackburn, 30, says that a group of men followed him and that he heard one of the attackers use an anti-gay epithet before he was beaten last Thursday. Blackburn suffered injuries to his left eye and needed 18 stitches for other injuries. He's also suffering from short-term memory loss, he says in the video.
"I never thought that something like this could happen in Newfoundland. But it's still going on," Blackburn added.
Soon after the alleged attack, he wrote on Facebook, saying, "Almost died last night from an attack - here are the photos - Thans you again Sheldon Steven Burke for saving my life. I have short term memory loss - Im only going by what i was told when Sheldon found me about to bleed to death. - I phone stolen (again) & $ in wallet - i wont have a phone for a long while - so please get in touch with me through here. Thank you so much."
He later added, "Thanks for everyones concern, means a lot - Again Sheldon Steven Burkesaved my life a jumping last night - I have short term memory loss - I dont remember NOTHING - a police report has been made on my behalf - I remember walking home seeing 3 guys and waking up in a hospital where the doctors said I lost a lot of blood and i came in unconscious - Battered and brusied and have a HUGE gash on my forehead - I was released shirtly after i woke up..Thanks to staff! Im in a lot of pain and I cannot answer anymore questions about police, hospital, or the assailants. I'm sorry when this comes back to me i'lll let you know. ALSO i could kill for some company..im afraid to close my eyes :("
HuffPo Canada spoke with the Royal Newfoundland Constabulary who said they were still investigating the attack and do not have details to release.
Blackburn told Canada.com that he does not remember a weapon being used.
Newfoundland's LGBT community has been on edge since the incident, however. President of St. John's Pride, Noah Davis-Power, said he's never heard anything like this "happening in St. John's."
"It rattles everybody," he said. "It makes you wonder; am I going to get beat up when I go downtown if I dress a bit more flamboyantly, or if I'm holding my partner's hand."
Davis-Power said that he wants to plan an event for Blackburn but is waiting for him to recover. Additionally, Queer Ottawa is holding a fundraiser for Blackburn this week. Another fundraiser will be held in Halifax.
As Canada.com reports, Blackburn describes himself as an out gay man with "a passion for fitness and cosmetics" but is not an LGBT activist.
He said there has been "so much love from friends and strangers worried about me."
"I love them all dearly, they are helping me get back on my feet. The human heart is not lost, I swear. It's not lost," Blackburn added.


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NH Supreme Court orders indictment restored for offender who failed to report MySpace account
CONCORD, N.H. (AP) � The New Hampshire Supreme Court says a sex offender who failed to report creation of a MySpace account can be prosecuted.
The court is reversing a trial judge's order dismissing the felony indictment against 40-year-old Thomas White of Manchester. The trial court ruled that because White created the MySpace account using his real name and an email address already on file that he had satisfied the reporting requirements.
But the Supreme Court ruled Friday that creation of the social media account falls squarely within the statute's requirement that convicted sex offenders must report any online identifiers and user profile information.
White was convicted in 1994 of aggravated felonious sex assault on a child and related felonies.
His lawyer did not immediately return a call seeking comment.


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Linked by Thom Holwerda on Mon 25th Mar 2013 21:09 UTC
Late last week, Nokia dropped what many consider to be a bomb on the WebM project: a list of patents that VP8 supposedly infringes in the form of an IETF IPR declaration. The list has made the rounds around the web, often reported as proof that VP8 infringes upon Nokia's patents. All this stuff rang a bell. Haven't we been here before? Yup, we have, with another open source codec called Opus. Qualcomm and Huawei made the same claims as Nokia did, but they turned out to be complete bogus. As it turns out, this is standard practice in the dirty business of the patent licensing industry.
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What would be really cool about this patent mess, is to simply change some rules :
1- Claiming you have patents under the hood and keeping them secret shouldn't be enough. Each time a company claims for holding a patent, they should open it for review.
2- If the claim was wrong, the patent is automatically invalidated and thrown into public domain : never leave a robber with its weapon !
3- If some FUD was successful in the past, some anti-litigation contracts signed, and the patent is finally found to be invalid, let's the tolling company payback the fees... twice !
These simple 3 rules would make the claiming companies a bit more accurate before making great noise.
Edited 2013-03-26 10:13 UTC


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FRESNO, Calif. – If the Masumoto family has done its job, you may never think about peaches the same way.
The Masumotos – a fourth-generation Fresno County, Calif., farming family – have written a 167-page book, "The Perfect Peach."
Released on June 11, the book includes essays detailing the dynamics of farming, a primer on peaches, and most of all, recipes celebrating the love of this juicy, sweet-tasting summertime fruit.
Already, interest in the book appears strong. A preview of the book was prominently featured on six-pages of the June issue of Country Living magazine.
"We wanted this book to be for people who enjoy peaches and are interested in cooking with them," says David Mas Masumoto, who co-authored the book with wife Marcy and daughter Nikiko. "But at the same time, this is for the people who want to know about the back story of the farm and where their food comes from."
Nestled on 80 acres in the southeast Fresno County community of Del Rey, the Masumotos grow peaches, nectarines and grapes for raisins. The farm has been in the family since the 1940s and is known for producing the beloved Suncrest Peach, an old-time peach with full flavor.
The Masumotos have carefully cultivated a following for their fruit. Fueling that interest has been David's writing. He wrote the award-winning "Epitaph for a Peach," along with several other books. And the family launched an adopt-a-tree program several years ago that draws people from throughout the state to pick tree-ripe fruit.
Although the family had talked for years about creating a recipe book, they wanted the project to be more than just about food. They wanted it to be an honest reflection of their lives, from the joy of tasting a tree-ripe peach to the sadness of losing a loved one.
Each of the recipes is prefaced with a short explanation of how the recipe came about or who inspired it. Woven throughout the book are essays by David and Nikiko. In one passage, Nikiko fondly recalls how her baachan, Japanese for grandmother, would "put up" her peaches in a simple syrup, freezing them in bulging plastic pouches.
"They tasted so good in my oatmeal," Nikiko says.
An entire section of the book deals with how to preserve peaches, including frozen, in jams, jars and even dried.
"To us, good preserved peaches are better than bad fresh peaches," Marcy says.
In the book, preserving peaches serves as a useful metaphor for how the Masumotos are working to preserve their farm and lifestyle.
Nikiko, who represents the fourth generation of the Masumoto family, admits that while farming has many rewards, it can be hard, back-breaking work.
"There is a real raw side to farming where you have to dig deep and say I can do this," Nikiko says. "And in a way, farming is like getting a tattoo. It can be painful. But you also get to the point where you decide that this is something that is really you, something that belongs with you for the rest of your life."
David would not have it any other way. He still enjoys solving the riddles that farming sometimes poses. And while he was excited about writing the book with his family, it also concerned him.
This book represents our family going public and in a way that is scary," he says. "What if people see us as a fragmented family?"
His fears were unfounded. When he saw the book for the first time, he cracked it open and breathed a sigh of relief.
"This is who we are," he says. "We'll see if the public accepts it or not, but this is who we are and it's authentic."
"The Perfect Peach" by Marcy, Nikiko & David Mas Masumoto (Ten Speed Press, $22)
©2013 The Fresno Bee (Fresno, Calif.)
Visit The Fresno Bee (Fresno, Calif.) at www.fresnobee.com
Distributed by MCT Information Services
PHOTO (from MCT Photo Service, 202-383-6099): PEACH-COOKBOOK
Topics: t000027855,t000003142,t000009275,t000009276,t000002537,t000040148,t000045025,c000214847


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Archived Publications
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WDFW Publications
Eelgrass/Macroalgae Habitat Interim Survey Guidelines
Habitat - Guidelines
Date Published: June 16, 2008
Number of Pages: 6
DESCRIPTION:WDFW has developed revised survey guidelines for eelgrass and macroalgae habitat to improve protection of these important habitats in Puget Sound and coastal waters. Guidelines for both preliminary and advanced surveys are contained in the revised protocols to facilitate evaluation of potential impacts to these habitats at project sites with various conditions. Statistical considerations are an integral part of the advanced surveys and a sample size calculator has been included to aid in determining the appropriate number of samples to be taken at a particular site.
Under the Washington Administrative Code (WAC), eelgrass and macroalgae are defined as saltwater habitats of special concern (WACs 220-110-250 (3)(a, b)). In administering the Hydraulic Project Approval (HPA) process, the Washington Department of Fish and Wildlife (WDFW) requires proponents for projects to: 1) avoid impacting eelgrass and macroalgae, 2) minimize unavoidable impacts, and 3) mitigate for any impacts.
Mitigation for the loss of eelgrass typically entails providing eelgrass enhancement away from the project footprint. Because establishment of new eelgrass for mitigation is often unsuccessful, project proponents need to address this uncertainty by increasing the scope of their mitigation effort, such as planting an area larger than the project impact footprint. For macroalgae mitigation measures, the WDFW Area Habitat Biologist (AHB) shall be consulted.
In known or suspected eelgrass areas, proponents shall survey to delineate the spatial extent of eelgrass and macroalgae presence in the project area. If the project cannot be moved or redesigned to avoid direct eelgrass and macroalgae impacts, surveys are required for quantifying potential impacts. Surveys shall be conducted by divers/biologists who are qualified to identify the predominant eelgrass and macroalgae species in the project area. Deviations from the survey guidelines shall be approved by the AHB prior to conducting eelgrass or macroalgae surveys. Survey results and interpretation will be subject to WDFW approval.
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As we observe Veteran's Day this November we must pay homage and respect to the veterans of all of our American Armed Forces who served and continue to serve to protect our country and keep our liberties safe and sacred. There are those who gave and continue to give the supreme sacrifice of their lives in order that we and our children are able to continue to live in the land of the free and the home of the brave.
Locally we wish to sincerely thank our veterans from Bayonne and throughout Hudson County who are in active military service in all parts of the world. When we see a serviceman or servicewoman in our streets in uniform we should address that person with the utmost respect and state to them in a voice filled with gratitude, "thank you for your service." We recognize the sacrifices made by these fine and brave people, stationed in all parts of the world and away from their families and loved ones to protect our liberties.
I join with all people to stand up proudly, shoulder to shoulder with our heads up high and be thankful each day that we live in this fine country. God Bless the veterans past and present and most certainly God Bless America.


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Little Hands Build Big Dreams
by Bryan Bergeron, Editor
January 2010
If you're a robotics enthusiast, you don't need to be convinced of the importance of developing mechanical skills, including a hands-on familiarity with various materials, hardware components, and assembly techniques. In robotics, fluency in basic programming and mechanical engineering principles is necessary but insufficient to design and develop anything new.
Consider that robotic control algorithms that work on simulated robots often don't run on the real thing because of real-world issues such as friction, imperfect motor startup characteristics, and other factors not typically represented in the simulation — that is, unless the programmer has experience with the real thing. In robotics, there's no substitute for a physical platform to build on and test real components, and to develop real world skills.
As a kid growing up in a town on the gulf coast that serviced the offshore industry, I assumed that everyone on the planet owned or had access to a metal lathe, welding machine, milling machine, and master mechanics tool set. Today, living in Boston, I happen to own a miniature milling machine and fairly extensive tool collection, but I'm certain my neighbors don't. In fact, given that Boston is a typical college town, machining and other blue-collar skills are not highly regarded. After all, technicians and factory workers build things with their hands, engineers design things, and physicists theorize what's possible. In short, hands-on, blue-collar skills are not what we aspire to, for ourselves or for our children.
Transition to our front cover, featuring John Ratzenberger, perhaps best known for his roles as Cliff, the postman in Cheers, and the host of the Travel Channel show John Ratzenberger's Made in America. I had the pleasure of speaking with John about his charity organization Nuts, Bolts, and Thingamajigs Foundation (NBT), which is dedicated to inspiring the next generation of welders, plumbers, carpenters, and others who work with their hands and minds, one tinker at a time. John is convinced that the backbone of civilization is manufacturing, and the future belongs to those who know how to use their hands.
John's conviction stems from both firsthand knowledge and those intimately familiar with the American workforce. John worked as a journeyman carpenter throughout New England prior to becoming an actor. He started NBT about 2-1/2 years ago following his work with the Made in America show. During his travels for the show, he frequently encountered CEOs alarmed that the US is running out of people who can build and make things with their hands.
As an actor, John is attuned to the role of the general public's attitude towards the loss of manufacturing jobs in the US. He pointed out that in movies, those who work with their hands are portrayed as geeks, but they're really the heroes. As such, one of his goals is to improve the image of those who work with their hands to make things. And he's going about it by taking strategic, direct action.
For example, guidance counselors often steer students away from careers in manufacturing because they perceive the jobs as low paying, with grimy work conditions reminiscent of the factories portrayed in 1930's movies. To confront this misperception head on, NBT took busloads of counselors on tours of manufacturing plants. They were shown that the plants are clean, that the workers make a good living, and that most have nice homes. As a result, these counselors now encourage students to consider careers that involve mechanical skills.
John's quick to point out that more has to be done in the American educational system. For example, shop classes — once popular — are now rare. As a result, most students who finish high school are functionally illiterate when it comes to basic mechanical skills such as the ability to read a ruler. He also related a complaint that many employers have of new engineering graduates. Apparently, they often can't build anything because they don't know how things are made. Theoretical knowledge alone just doesn't cut it on the shop floor. To compound the problem, there's a shortage of engineers. According to John, American universities awarded twice as may degrees in sports management than in engineering last year. John Ratzenberger certainly has his work cut out for him, and, of course, he can't do it alone. Fortunately, Nuts and Bolts recently merged with the Fabricators & Manufacturers Association of America, which works on multi-level platforms to promote American manufacturing, including grants and scholarships to nonprofits that provide day or overnight camps to children who want to learn the manual arts. To learn more about John and Nuts, Bolts, and Thingamajigs, and how you too can help, log onto http://www.nutsandboltsfoundation.org.
Through his charity (Nuts, Bolts, and Thingamajigs Foundation), John has committed his resources to introducing America's youth to the pleasures of 'tinkering' – getting away from their video games and TV sets and into the backyard building things. In that way, we will create the next generation of artisans, inventors, engineers, repairmen, and skilled workers — in short, a self-sufficient, self-sustaining society. John's tag line has become "Little hands build big dreams. Give children tools and watch them build America."
John is an outspoken advocate for American-made products and the companies that keep Americans working. In 2007, John embarked on a yearlong commitment with the Association for American Manufacturing and US Steelworkers to create a Presidential Town Hall Tour. The Town Hall series brought attention to issues that American voters were demanding to hear about — a real commitment from presidential candidates to ensure a strong manufacturing industry. During the town hall events, John encouraged voters to ask the presidential candidates what specific policies they would enact to strengthen the American manufacturing base, which is vital to our economic and national security.
John was invited to address Congress and its Manufacturing Caucus that same year, for which he prepared his oft-quoted speech "The Industrial Tsunami Heading Our Way." He continues to work with politicians on both sides of the aisle to ensure that the American manufacturing industry has a voice in Washington.
During his free time, John is an avid sailor, fisherman, and billiard player. He enjoys international travel, fencing, and collecting antiques. He plays the drums and belongs to a bagpipe band, as part of the Emerald Society. Sports such as karate, yoga, and skeet shooting keep him active. He has one son and one daughter and lives outside of Los Angeles, but spends as much time as possible on his boat, cruising up and down the east coast. SV


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C'mon todd, all you have to do is take human behavior/reaction out of any plan/theory and it will work perfectly. Don't you get it? Only a socialist could possibly "get it" about Economics 101.
I had planned to address the many errors in bis's many analyses when I had time, but I can see right now it would be fruitless.
And to bis, claiming you understand a lot about economics doesn't make it so. It's merely an unsupported assertion (like many of your points). It becomes even less supported the more you spout about the theory absent of human interaction within it.
Posted by bistiza on 11/26/2012 2:59:00 PM (view original):This isn't a case of one person versus "everybody else" or anything even remotely close to that. There are plenty of people who support both sides of the capitalism versus socialism debate, whether or not they happen to be willing to voice their opinion here. So there is no "everybody else is wrong" because there isn't an "everybody else" in the first place.
Honestly though I understand how frustrating it is for people to disagree with me on this type of subject and actually argue their points because this is an area where I excel. You think you know what's right in your opinion, and you're entitled to have your own opinion , but it's not going to be easy to argue with someone who has far greater knowledge and experience than you do in that area.
So if you can't effectively argue your opinion against someone whose knowledge and experience makes them an expert compared to you, don't resort to fallacies to try to compensate. Don't make personal attacks. Don't try to argue that more people agree with you or certain people here do. Just accept you won't win the argument and be done with it.
I'm sure you have more knowledge than I do in some area, so it isn't a terrible thing when it goes the other way. We all have areas of expertise and areas we're not as good at, and there is always someone who is better than we are even in the areas we're good at.
That's why knowing when to cut your losses is perhaps one of the best skills anyone can have.
C'mon todd, all you have to do is take human behavior/reaction out of any plan/theory and it will work perfectly.
I had planned to address the many errors in bis's many analyses when I had time, but I can see right now it would be fruitless.
And to bis, claiming you understand a lot about economics doesn't make it so. It's merely an unsupported assertion (like many of your points). It becomes even less supported the more you spout about the theory absent of human interaction within it.
So your "proper framework" of an effective socialist economy is just a theory, with no empirical evidence to support it how effective it really would work in practice.
Without the empirical evidence of a successful implementation, what exactly is giving you "enough support"?
If you think I'm "cutting my losses" because I'm "defeated, you should think again. The biggest reason I'm deciding against engaging with you and your opinion is the complete arrogance on this topic. You may know a lot about economics. All you've demonstrated in this and other threads is opinion and unsupported assertions. You've mostly refused to support your opinions with fact, but only with further opinions - as if those opinions are in and of themselves proof.
When I go back to some of the original questions, such as a fair share, a target tax rate for the rich, etc., I'm the one pointing you to a thread with actual bona fide numbers and facts in it, fully available to anyone, yet you're the one who supposedly is the enlightened one. I would think one as far above the uneducated masses like us as you are could give us a clue as to what a fair share is or an idea of what tax rate for the rich would be the best. You might be able to show examples as to how your point of view would work in real life. What the implications are for people and businesses when you change their variables. You might want to show the moral reasoning serving as a foundation for allowing those in power to confiscate something from someone to give it to someone else, especially when it approaches a majority-rule (or potentially mob rule). I would think someone as enlightened as you are would have ready and convincing answers.
I'll give you a hint about something that I'm sure you don't need: if you want to "win a debate" in any fashion other than in your own mind, you should be willing to concede a point or two. A real intellectual should always be open to persuasion, or to be able to validate another's point of view. As you might notice, I have never even a single time tried to claim "victory" in this one, or claim that I know more than someone else (as you have). You may think it's self-evident by you claiming it so, but you would probably be alone, except among your socialist friends. Your obvious disdain for people with wealth shows in your discriminatory language in dealing with them and it serves to discredit your point of view. (My opinion, not claimed as fact - I'll let other readers judge the merit of that statement if they choose).
If you cared about your credibility with anyone here, which I'm sure you don't, I would recommend you try real hard to get over yourself and discuss the merits of your positions.
Here are a few specific questions regarding that support:
What general incentives do you suppose work in each of the two competing theories?
Why would socialist incentives work better than capitalist incentives (knowing that both systems likely share a fair number of these incentives)?
Is freedom a valuable component in one or the other (or both)?
Back to the "fairness issue":
Are you willing to give a target as to the rich's fair share?
If they paid 100% of the taxes, would it be enough?
If you raised their rates, and the rich's burden went down, would you be willing to lower their rates in order for the burden to go up? (BTW, this is demonstrated in the numbers so you can see the effects of human behavior)
How much of your earnings would it ever be moral for me to take for my needs (or to have the government in its benevolence do so)?
If you have a number in mind, would you give it willingly?
I think capitalism (as flawed as it can be) better recognizes human behavior and incentives than socialism does and this has been demonstrated in history. America's version of it is far from perfect, but there is a reason people don't have to be born with wealth here in order to attain it. First, the pie isn't finite, and second, freedom is everything.
But go ahead and claim you're the smartest. I don't mind.
Claim the rich need to pay more. Don't bother to tell anyone how much more.
Claim victory. Have at it.
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[- -]
There are 3 lakes in Africa (Monoun and Nyos in Cameroon, and Kivu in the limit of Rwanda and Congo) that concentrate in its depth large quantities of CO2 and Methane. These gases, highly mortal and harmful for our skin, are emitted due to volcanic activity, earthquakes or detachments of land. The gas comes from the lake and moving up to 2 meters of height from the level of the soil it can manage to cover approximately 30 kilometers to the semibreve of the affected lake.
The presence of this gas can extend for near 24 hours. The last disaster of this type happened in 1986 had near 2000 mortal victims. The great danger is more than 2 million persons live in the surroundings of these 3 lakes. When one of these events happens (and since the gases are invisible) alarms that alert the population are activated, but its exodus becomes impossible by the great existing volume of people and animals, and for the lack of effective means of transport.
In these areas life depends of the coexistence of man and animal. The solution consists of a refuge of double skin (leather), capable of sheltering an average family and its cattle separately (in average 5 heads of cattle or 15 heads of sheep). This refuge is totally hermetic in a height of 5 meters and has in its higher part a mouth that allows the entrance of pure and breathable air.
SHELTER ME/YZlAB


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For Immediate Release: August 14, 2009
Monday, August 17 – Public Information Session for On-Site Assessment of Sheriff's Office
The Alexandria Sheriff's Office will undergo an on-site assessment by the Commission on Accreditation for Law Enforcement Agencies, Inc. (CALEA). As part of the on-site assessment, Sheriff's Office employees, members of the community and the media are invited to offer comments at a public information session on Monday, August 17 at 3 pm. in Courtroom #3 of the Alexandria Courthouse, 520 King St. Individuals may submit comments anonymously by calling 703.746.4351 on Sunday, August 16 from 2 p.m. to 4 p.m. All comments are limited to ten minutes and must address the agency's ability to comply with the Commission's standards. A copy of the standards is available for review at the Alexandria Sheriff's Office's two locations: 2003 Mill Rd. and 520 King St. For more information, contact Commander Mondre' Kornegay at 703.746.5009 or e-mail email@example.com.
Monday, August 17 – Deadline for Alexandria Marketing Fund Applications
Applications are now being accepted for the Alexandria Marketing Fund, a program administered by the Alexandria Marketing Committee. The program is designed to foster projects that enhance the long-range marketing priorities of the City; increase awareness, while expanding the quality, of Alexandria's diverse retail, dining, hospitality, cultural attractions and other businesses; promote Alexandria to specific target audiences, including residents and visitors; and generate additional business sales and tax revenues in Alexandria. For more information or to apply, visit alexandriava.gov/marketingfund.
Call for Artists Announced for Charles Hamilton Houston Memorial
The City of Alexandria is announcing a Call for Artists for the Charles Hamilton Houston Memorial to be located at the Charles Houston Recreation Center, 901 Wythe St. The City will conduct the search for qualified applicants through a Request for Qualifications (RFQ). The deadline for submission is October 1, 2009, at 4 p.m. EDT. The anticipated installation date of the Charles Hamilton Houston Memorial is April 2011. For more information, visit www.alexandriava.gov/arts.


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States' animal health officials vigilant against illness at fairs
EPA withdraws proposed rule to garnish non-federal wages
By MATTHEW D. ERNST
Missouri Correspondent
WASHINGTON, D.C. — The U.S. EPA last week withdrew a wage garnishment rule, proposed July 2. The withdrawal came after the proposal received adverse comments, including a formal letter of opposition from three Republican senators.
Notice of the EPA's withdrawal came in a July 17 announcement in the Federal Register. The proposed rule, "Administra-tive Wage Garnishment," would have given the EPA wage garnishment power under provisions of the Debt Collection Improvement Act (DCIA).
"The direct final rule will allow the EPA to garnish non-federal wages to collect delinquent non-tax debts owed the U.S. without first obtaining a court order," stated the proposal. A "direct final rule" can be implemented only if the proposing agency receives no adverse comments.
Republican Sens. David Vitter of Louisiana and Mike Enzi and John Barrasso of Wyoming issued a formal adverse comment in a July 10 letter to EPA Administrator Gina McCarthy. "We believe the direct rule represents an inappropriate effort to avoid preliminary judicial scrutiny of EPA garnishment proceedings," they wrote.
Republican House members also submitted comments of opposition. Adverse comments to the EPA proposal were inevitable, said Roger McOewen, director of the Iowa State University Center for Agricultural Law and Taxation.
"Of course they will receive many negative comments, especially from the agricultural sector," said McOewen, before the withdrawal. Crop farmers, rural landowners and livestock operations could potentially be affected under the rule, he said.
The Republican senators made farming and land rights concerns a focus of their letter. "EPA's decision to give itself the authority to garnish wages without first obtaining a court order compounds the challenge for individuals who face ruinous fines from the agency," they said.
They cited well-publicized examples of a West Virginia farmer receiving possible civil fines for alleged stormwater runoff contamination, as well as a Wyoming landowner facing possible EPA fines for a pond construction.
An EPA spokesperson defended the proposed rule this month, stating the proposal met legal stipulations.
"Under the administrative wage garnishment provisions of the DCIA, federal agencies may garnish administratively up to 15 percent of the disposable pay of a debtor to satisfy a delinquent non-tax debt owed to the United States," stated the EPA in its Federal Register announcement.
The adverse comments from the senators did not dispute the authority given the EPA by the 1996 law. Rather, they objected to the potential bypass of due process rights that might occur when the EPA garnished wages.
McOewen said the proposed rule would have given EPA power to garnish wages before an appeal of any adverse determination and other court processes. "Not even IRS can do that," he noted.
An agency receiving adverse comments to a "direct final rule" can respond to the comments during the standard administrative rulemaking process. The EPA's intent to pursue its former proposal under the standard process is not yet known.