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BBDUSHM Lucknow
Babu Banarasi Das University's School of Hotel ...
Uttar Pradesh
Total Students
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Babu Banarasi Das University's School of Hotel Management is situated at Babu Banarasi Das University, BBD City, Faizabad Road,Lucknow, Uttar Pradesh - 226028, India in Lucknow.
Courses Offered
- 4 Years
- Bachelor of Hotel Management & Catering Technology-B.H.M.C.T.
- Hospitality / Aviation / Tourism
- Rs. 30000 (Per Semester)
- 3 Years
- Bachelor of Science-B.Sc.
- Management - BBA / MBA / Diploma
Babu Banarasi Das University's School of Hotel Management - BBDUSHM Lucknow - BBDUSHM
The College Mission is to "To provide an open opportunity to the young generation for evolving their core competencies for building up their career as World class professional with broad based foundation, in depth knowledge and versatile personality to meet the challenges of Hospitality Industry".Our Vision is to Our emphatic global curriculum churns the students into versatile hospitality professional.We at Babu Banarsi Das University provide the skills, knowledge, and hands-on training for professional development. Hotel management training gives a valuable opportunity to get ahead in the resort and hospitality industry. Hotel management degree program can be obtained through our regular Bachelors Degree course. After completion of our Bachelor of Hotel Management course potential Hotel managers may work as convention and Event Planners, Front Office Managers, or General Managers where they oversee all operations. Resort, Hotel, and Motel management positions require hotel managers to work with a variety of staff members including reservations, event planners, and culinary departments. Hotel management training can provide the skills and professional development needed for leadership, training, and general administrative functions in operations. Our Group organizes in campus and off campus recruitment for final year students by leading 5 star hotels chains.Food Service Management and Banquet Service Management often involve Catering Management opportunities.
Why join Babu Banarasi Das University's School of Hotel Management
The college's infrastructure is well furnished with all modern facilities.
2 Type Courses Available
- 2 UG Courses
Babu Banarasi Das University's School of Hotel Management Placements
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At Babu Banarasi Das University's School of Hotel Management (BBDUSHM) the students are endowed with all convenient amenities that make their life 'go easy' in college hours, alongside make learning more interesting. Some of the facilities include well ventilated classrooms, recreational areas, hostel facility for boys and girls, indoor and outdoor games, stocked library, seamless internet/wifi connectivity, medical facilities etc.
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Impressions of beauty change over time, as do our faces when we age. Smoothing out folds and wrinkles or enhancing lips with Restylane® injections by adding volume can make an enormous difference in one's appearance. Among fillers, there is a wide variety of methods and substances that may enhance facial features. Restylane® and Perlane™ contain the body's own natural material, hyaluronic acid, which is present in all living organisms. In the skin it creates volume by binding water to hydrate the skin and resulting in a healthy and vital appearance. Restylane® or Perlane® are cosmetic dermal fillers that replace lost volume and restore youthful contours to the skin to smooth away moderate to severe facial wrinkles and folds, such as the lines from your nose to the corners of your mouth (nasolabial folds). Restylane® is the world's most used and most studied dermal filler, and has been used in over 70 countries and over 15 million procedures have been performed.
After Restylane® treatment you may experience some swelling, tenderness and redness. This is a normal result of the injection and the above symptoms generally disappear in two to four days. Restylane® injections are fast and safe and leave no scars. The results are immediate.
Restylane® and Perlane™ are biodegradable which means that they will gradually be absorbed. As the gel breaks down, water takes its place, and when totally absorbed, the Restylane® gel disappears from the body. How long a Restylane® treatment lasts is individual. This depends on many factors, such as your age, skin type, lifestyle, and muscle activity, as well as on the injection technique and location. Clinical trials of Restylane® show that Restylane® and Perlane™ are effective for up to six months after lip augmentation and up to twelve months after facial contouring.
$530.00 per syringe
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Contact us 24/7: 1 800 638680
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- - This item's measurements are:
- Depth 8cm
- Height 12cm
- Max. Strap Length 138cm
- Min. Strap Length 119cm
- Width 16cm
Saint Laurent's 'Loulou' bag is made from supple leather and quilted with the brand's signature 'Y' stitching. Hung from a polished silver chain strap, it's sized to hold essentials – think phone, keys and compact. The three card slots and pocket mean you can forgo a wallet.
Shown here with: Saint Laurent Top, Saint Laurent Skirt, Saint Laurent Boots.
- - Black leather (Calf)
- - Zip fastening along top
- - Comes with dust bag
- - Weighs approximately 1.1lbs/ 0.5kg
- - Made in Italy
Product Code: 812078
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Is pepper spray illegal in nyc?
Pepper spray is legal in all 50 states, including New York. Residents who have no felony convictions and are at least 18 years old are permitted to carry the personal defense weapon, but they must ...
Read More »
Is pepper spray illegal?
Pepper spray, which is often used as a protective spray by consumers as well as by law enforcement agents, induces an involuntary reaction but is not permanently harmful. Pepper spray is legal for...
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Is pepper spray illegal in New Jersey?
In the State of New Jersey, pursuant to criminal code 2C:39-9, it is not illegal for citizens to carry pepper spray as long as "the device is for the purpose of personal self-defense, is pocket-siz...
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Is pepper spray illegal in Australia?
Pepper spray is legal in Western Australia for defense, but only if the user believes he or she might have need to use it. All other parts of Australia prohibit pepper spray.References:Code 3 Tacti...
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Is pepper spray illegal in New Hampshire?
It is legal to carry and own pepper spray in New Hampshire, but when traveling by air, the Transportation Security Administration restricts pepper spray in hand luggage, and only allows up to 4 oz....
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Ever since this 3.0 update I can nolonger delete anything from the Inventory.
3 Replies
· · ·
Aug 19, 2008 at 2:12 UTC
Go into an Inventory category and use the Edit button on the button bar and select Delete from there. You will get a list of devices with checkboxes, select the ones you want to get rid of and then click the Delete button at the bottom of the list.
· · ·
Aug 19, 2008 at 2:23 UTC
Please also have a look at the 3.0 known issues list:
· · ·
Aug 25, 2008 at 12:10 UTC
Um... yeah... took me a while to figure that out... "If at first you don't succeed, READ the directions!" LOL


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The Munch & Move program offers free training to educators working in centre-based early childhood services in NSW.
If you answered 'yes', then the Munch & Move program is what your service needs!
Munch & Move training is delivered via a 'live' webinar series. More information including the dates and times of each webinar series is on the page below.
Training Dates
Support is available for Munch & Move services through your Local Health District Health Promotion Service.
Local Health District Contacts
The Kit assists educators who have attended Munch & Move training to share their learning with other staff at their service.
Staff Development Kit
An online refresher training module for educators and/or services that have previously attended the training workshop and would like an update on the Munch & Move program and its components is now available.
5 Ways to a Healthy Lifestyle
Eat Fewer Snacks and Select Healthier Alternatives fact sheet (PDF 466KB)
Kay's top tips on how to get your kids eating well and being active.
Parent Tips article
Find out how much moderate and vigorous activity you should be doing every day.
Get Active Each Day
An initiative of NSW Ministry of Health, NSW Department of Education, Office of Sport and the Heart Foundation.


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He could be a singer, an actor or even a footballer.
But this is no mere entertainer - this is Jesus Christ and he's wearing jeans.
The 21st Century depiction of the Son of God will now welcome the modern masses at a Catholic church in Uckfield.
This week the new bronze statue was hoisted more than 100 ft to the top of the bell tower at Our Lady Immaculate and St Philip Neri Church.
Award winning sculptor Marcus Cornish, who lives in Lewes, was commissioned to make the bronze seven-foot contemporary version of Jesus.
On Sunday it will have the last accessory added – an eye-catching halo picked out in gold leaf.
Mr Cornish, whose work have been bought by the Prince of Wales, said: "The sculpture is simple and direct and I hope it sums up the feeling that Christ is always with us and that we are not to be afraid."
I must say, the sculptor is talented. It's interesting. But in the end, the Lord looks like He's playing soccer in a wind tunnel.
HT to many people to count...pic from The Deacon's Bench.


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Santini TWO QSkin Sock Men's
Giving your sock drawer a little love never hurt, in fact, we're usually unreasonably excited to head out on a ride if we know we have a new pair of socks to break in. You might look forward to your weekend ride a little more if you treat yourself to Santini's TWO QSkin Sock, made with a moisture wicking cotton and elastane blend and featuring ventilating raised dots along the Achilles tendon for increased breathability. The entirely seamless construction and supportive arch of the sock promise to make it feel virtually undetectable within your shoe, and you can depend on the sock's classic ankle height to remain in style around the volatile yearly changes in cuff length trends.
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"I want to tell vendors that in defence acquisition, there is no question of political decisions," Antony said, stressing that decisions related to defence acquisitions would never be based on political considerations.
Addressing an international seminar on defence acquisition, he said quality and price would be the only criterion for buying equipment from such firms.
"Don't try to corrupt our people... Quality and price are the only criteria in terms of acquisition. All the vendors will get level playing field," he said.
The Defence Minister also asked the sellers of defence equipment to inform the Ministry about the "corrupt and greedy persons" they come across during such deals.
"In an effort to modernise our defence forces, we are not willing to waste even one rupee of our tax payers money to corruption," Antony said.
On participation of the private sector in the acquisition process, he said, "There is a lot of space for private and public sectors to coexist. In the years to come, both public and private sectors would have to work together to meet the country's demand."
Commenting on the Defence Procurement Policy (DPP), the Minister said, "We want to strengthen defence industrial base.
The offset policy has far more potential than that has been tapped. Offsets need a greater thrust to enhance research and development, logistic capabilities and defence infrastructure."


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Hi, Ingrid,
glad to hear that you have a wonderful pellie year! Some of my seedlings from
March are now really flowering (P. barklyi) - with very long flower stalks!
They, too, have had much water during the last days, but like my haworthias
they seem to cope with this situation.
I also have my 3 sarcocaulons outside (Geraniacea - a really addictive drug!
My Mum loves Geranium (BTW: Her Adenium is flowering, too!!)and I Pelargonium
and Sarcocaulon).
About P. dimeierii "Apricot". This "alien" is in the catalogue of Stegmeier.
Following facts are my own translation from Germany, and I am not quite sure,
if they match the international Pelargonium vocabulary ;-). They are
miniature zonal pelargoniums (< 13 cm) with a simple apricot-colored flower
and intensive green leaves + zonal ring.
See You!


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Release Date: 1992
PG-13|1 hr 40 min
Plot Summary
Terminally ill Cleveland resident Phil (Jason Bateman) arranges a get-together with his closest childhood pals, Gene (C. Thomas Howell) and Rob (Jonathan Silverman). Gene and Rob had a falling out over a woman, but they put aside their differences and agree to join Phil on a trip to Los Angeles. Their goal is to land Phil a spot as a game show contestant on "Jeopardy!" Along the way they find adventure and, in the form of spirited waitress Mary (Annie Potts), a new buddy.
Cast: Jason Bateman, C. Thomas Howell, Jonathan Silverman, Annie Potts, Krista Tesreau, Kent Bateman
Director: Neal Israel
Genres: Drama


text:
Quick and Painless
This is a very personal story based on something that happened to me about a year ago. I was hit by a car while riding my bicycle, knocking me off of my bike and on to the road leaving me with a broken foot, shoulder and concussion. I was (and still am) very lucky to be alive to this day. In this story, I imagine what other things might have happened if I hadn't been so lucky... (All of the following is based on my experience. Names and places have been changed)
It was quick and painless.
Fortunately, I told myself in those last seconds, you told Catherine to wait for you at the coffee shop until you got back. At least she'll be okay and won't see this.
The thought of never seeing my family again hit me like a ton of bricks as I was thrown of my bicycle, as the minivan collided into me perpendicularly.
At this point I don't remember anything more. When I moved to "the other side", I was able to deduce that I was thrown against the windscreen of the minivan, lost consciousness and then rolled off the car onto the road. It was this 5-6ft fall from the minivan that caused my injuries and caused me to die.
Death...unpleasant word isn't it? Something so inevitable, and yet it always manages to surprise us. I prefer the term "the other side", the idea there is another place we move to after dying spiritually. There is something comforting knowing our loved ones are always there for us, even if not physically.
The remarkable thing about the human spirit is that we do realize every day could be our last, and we do try to make every moment count for something. Whether talking to a friend over coffee, calling your parents to talk to them, going on a walk with your friend we are all perpetually looking for meaning that keeps us alive. Some of my best memories were with my friends doing the most random things (one time my friend and I went canoeing just because we could).
I could go on about my life, but that's not what I want to focus on now. Rather, I want to share my family's experience and how they came to peace, seeking justice after my death. What started out as a simple accident, turned into a large-scale case of corruption and deceit.


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Endotoxin (Etx) causes excessive activation of the nuclear repair enzyme poly(ADP-ribose) synthase (PARS), which depletes cellular energy stores and leads to vascular dysfunction. We hypothesized that PARS inhibition would attenuate injury to mechanisms of pulmonary vasorelaxation in acute lung injury. The purpose of this study was to determine the effect of in vivo PARS inhibition on Etx-induced dysfunction of pulmonary vasorelaxation. Rats received intraperitoneal saline or Etx (Salmonella typhimurium; 20 mg/kg) and one of the PARS inhibitors, 3-aminobenzamide (3-AB; 10 mg/kg) or nicotinamide (Nic; 200 mg/kg), 90 min later. After 6 h, concentration-response curves were determined in isolated pulmonary arterial rings. Etx impaired endothelium-dependent (response to ACh and calcium ionophore) and -independent (sodium nitroprusside) cGMP-mediated vasorelaxation. 3-AB and Nic attenuated Etx-induced impairment of endothelium-dependent and -independent pulmonary vasorelaxation. 3-AB and Nic had no effect on Etx-induced increases in lung myeloperoxidase activity and edema. Lung ATP decreased after Etx but was maintained by 3-AB and Nic. Pulmonary arterial PARS activity increased fivefold after Etx, which 3-AB and Nic prevented. The beneficial effects were not observed with benzoic acid, a structural analog of 3-AB that does not inhibit PARS. Our results suggest that PARS inhibition with 3-AB or Nic improves pulmonary vasorelaxation and preserves lung ATP levels in acute lung injury.
- poly(ADP-ribose) synthase
- pulmonary artery
- 3-aminobenzamide
- nicotinamide
- myeloperoxidase
endotoxemia results in the increased production of both nitric oxide (13, 34) and superoxide anion (35). When both of these species are present in large amounts, the formation of peroxynitrite (ONOO−), a potent oxidant and nitrating reagent, is favored (4, 12, 34). Nitric oxide is the only known endogenous molecule produced in high enough concentrations in pathological conditions that can effectively compete with superoxide dismutase for superoxide (5). Peroxynitrite is a strong activator of DNA single-strand breaks, resulting in excessive stimulation of poly(ADP-ribose) synthase (PARS) (31). This process depletes NAD+ (23), leading to inhibition of glycolysis and decreased ATP formation (21). This mechanism of cellular injury has been proposed as a major pathway involved in the vascular dysfunction observed in endotoxic shock (32, 39, 40). Peroxynitrite formation in acute lung injury, as evidenced by 3-nitrotyrosine formation, has been found in endotoxin-treated rats (34) and in human autopsy specimens with sepsis-induced diffuse alveolar damage (15). In nonsepsis models of pulmonary inflammation, PARS inhibition prevented edema from excitatory amino acid (N-methyl-d-aspartate) toxicity in the isolated perfused rat lung (22) and improved cellular energetics in macrophages harvested from rats subjected to carrageenan-induced pleurisy (8) as well as in a human pulmonary epithelial cell line exposed to peroxynitrite (30).
Endotoxin-induced acute lung injury is characterized by lung edema, neutrophil sequestration, and increased pulmonary vascular resistance (7, 9). We and others (9, 16, 18, 25) have found that endotoxin causes dysfunction of pulmonary vasorelaxation in response to agonists that require the generation of cGMP. This endotoxin-induced dysfunction of pulmonary vasorelaxation is mediated, in part, by polymorphonuclear leukocytes; neutrophil depletion attenuates this acute lung injury in a rat model (24).
Activation of PARS in response to peroxynitrite-mediated DNA single-strand breaks may be responsible for the cellular energy depletion and vascular dysfunction associated with endotoxemia. In vivo administration of a PARS inhibitor attenuated the impairment of contractility in thoracic aortic rings (32) and improved mean arterial pressure (41) in endotoxin-treated rats. The dysfunction in endothelium-dependent relaxant responses in rat thoracic aortic rings caused by endotoxin was also ameliorated by the PARS inhibitor 3-aminobenzamide (3-AB) (27). PARS inhibition with 3-AB also reduced neutrophil recruitment and tissue edema in zymosan- and carrageenan-triggered models of local inflammation (29).
We hypothesized that in vivo inhibition of PARS would attenuate endotoxin-induced impairment of pulmonary vasorelaxation. The purpose of this study was to determine the effect of the PARS inhibitors 3-AB and nicotinamide (Nic) on endotoxin-induced, cGMP-mediated pulmonary vasomotor dysfunction. Endothelium-dependent relaxation was studied with the receptor-dependent agonist ACh and the receptor-independent agonist calcium ionophore A-23187. Endothelium-independent relaxation was examined with direct stimulation of vascular smooth muscle with the use of the nitric oxide donor sodium nitroprusside (SNP). We also examined the effect of PARS inhibition with 3-AB and Nic in endotoxemia on lung ATP levels and pulmonary arterial PARS activity. A secondary purpose of this study was to determine the effect of 3-AB and Nic on endotoxin-induced lung edema and myeloperoxidase activity as a measure of neutrophil accumulation. The results of this study demonstrate that PARS inhibition with 3-AB and Nic in endotoxemia 1) attenuates dysfunction of endothelium-dependent and -independent mechanisms of pulmonary vasorelaxation, 2) has no effect on lung myeloperoxidase activity and edema, and3) maintains lung ATP levels.
Animal care and housing.
All animals received humane care in compliance with the National Research Council's Guide for the Care and Use of Laboratory Animals. Male Sprague-Dawley rats weighing 250–300 g were quarantined in quiet, humidified, light-cycled rooms for 2–3 wk before use. Rats were allowed ad libitum access to food and water throughout quarantine.
Experimental protocol.
Rats were administered normal saline (NS; 1 ml ip), endotoxin [Etx; 20 mg/kg ip Salmonella typhimurium lipopolysaccharide (LPS) in 1 ml of NS], a PARS inhibitor alone (3-AB, 10 mg/kg ip, or Nic, 200 mg/kg ip, in 1 ml of NS), or Etx followed by 3-AB or Nic. Rats received 3-AB or Nic 90 min after Etx to avoid any potential interference with inducible nitric oxide synthase (iNOS) induction. The doses of 3-AB and Nic were chosen on the basis of multiple previous in vivo studies employing them in rats (8, 32, 33, 41). A similar set of experiments were performed with the use of a structural analog of 3-AB that does not inhibit PARS [benzoic acid (BA); 10 mg/kg ip]. Rats were provided chow and water ad libitum during the 6-h period after initial injection. No rats died during the 6-h experimental time course. A previous experiment using the same dose of Etx resulted in 15% mortality at 72 h (unpublished data).
Isolated pulmonary arterial ring preparation.
Isolated pulmonary arterial rings were harvested and prepared as previously described (9, 24). Five rats (10 rings) were studied in each group. Rats were anesthetized with pentobarbital sodium (50 mg/kg ip). Median sternotomy was performed, and heparin sulfate (500 USP units) was injected into the right ventricular outflow tract. After removal of the heart and lungs en bloc, the main pulmonary and the right and left pulmonary arteries were excised. The right and left main branch pulmonary arteries were then cut into 3-mm-wide rings; two pulmonary arterial rings were obtained from each rat. Care was taken during this process to avoid endothelial injury.
The pulmonary arterial rings were then placed on 11-mil-gauge steel wires and suspended in individual 10-ml organ chambers containing Earle's balanced salt solution, a standard physiological buffer consisting of CaCl2, 1.80 mM; MgSO4 (anhydrous), 0.83 mM; KCl, 5.36 mM; NaCl, 116.34 mM; Na2HPO4 (dibasic), 0.40 mM; d-glucose, 5.50 mM; and NaHCO3 2-5% CO2-74% N2. This produced a of 100–110 mmHg and a pH of 7.4.
Pulmonary vasorelaxation: concentration-response curves to ACh, A-23187, and SNP.
The optimal resting mechanical tension (passive load) for pulmonary rings was determined to be 750 mg in a prior study (9). Rings were suspended at 750 mg and allowed to reach a steady state for 1 h, during which time the Earle's balanced salt solution was changed every 15 min. Rings were preconstricted with phenylephrine (PE) to achieve a PE-induced ring tension between 275 and 325 mg (∼10−7 M PE). Cumulative concentration-response curves were then generated over the concentration range of 10−9to 10−6 M (ACh, A-23187, and SNP). For determination of the concentration-response curve, the ring was allowed to reach a steady state before advancing to the next higher concentration. The ring tension remaining in the rings in response to each dose of vasorelaxing agent was expressed in milligrams of tension. PE concentration-response curves were also generated to ensure that endotoxemia did not alter α-adrenergic-mediated vasoconstriction.
Lung harvest for myeloperoxidase assay, wet-to-dry weight determination, and ATP assay.
Rats were anesthetized with pentobarbital sodium (50 mg/kg ip). Median sternotomy was performed, and heparin sulfate (500 USP units) was injected into the right ventricular outflow tract. Lungs were then surgically removed, externally rinsed with saline, and blotted dry. Five lungs from five rats were studied in each group.
Lung myeloperoxidase assay.
Segments of lung weighing 400–500 g were snap frozen in liquid nitrogen for subsequent determination of myeloperoxidase (MPO) activity. Lung tissue was homogenized for 30 s in 4 ml of 20 mM potassium phosphate buffer, pH 7.4. Lung protein was quantified with the use of the Coomassie plus protein assay (Pierce, Rockford, IL). The samples were then centrifuged for 30 min at 40,000g at 4°C (Beckman L-80 Ultracentrifuge; Beckman Instruments, Palo Alto, CA). The pellet was resuspended in 4 ml of 50 mM potassium phosphate buffer, pH 6.0, containing 0.5 g/dl cetrimonium bromide. The samples were sonicated for 90 s at full power (ultrasonic homogenizer; Cole-Parmer Instrument, Chicago, IL), incubated in a 60°C water bath for 2 h, and centrifuged for 10 min at maximum speed (Eppendorf 5415C; Baxter, San Diego, CA). The supernatant (25 μl) was added to 725 μl of 50 mM phosphate buffer, pH 6.0, containing 0.167 mg/ml o-dianisidine and 5 × 10−4% hydrogen peroxide. Absorbance of 460-nm visible light was measured between 1 and 3 min (Beckman DU7 spectrophotometer; Beckman Instruments, Irvine, CA). MPO activity (units/mg lung protein) was then calculated as where A460 is the change in absorbance of 460-nm light from 1 to 3 min after the initiation of the reaction. The coefficient 13.5 was empirically determined such that 1 unit of MPO activity is the amount of enzyme that will reduce 1 μmol peroxide/min (3). Lung protein is measured in milligrams.
Lung wet-to-dry weight.
Harvested left or right lungs were weighed for determination of wet weight. In separate specimen containers, they were dried over a desiccant (Drierite, Xenia, OH) at 4°C for 5 days to a constant weight and then reweighed.
Lung ATP assay.
Lung ATP levels were determined with the use of a quantitative, enzymatic assay (Sigma Diagnostics, St. Louis, MO). Lungs were harvested as described in Lung harvest for myeloperoxidase assay, wet-to-dry weight determination, and ATP assay, and were immediately frozen with the use of liquid nitrogen. Segments of frozen lung weighing 100–200 mg were ground to a fine powder with the use of mortar and pestle and then sonicated (ultrasonic homogenizer) at full power on ice for 30 s in 1 ml of 12% TCA. (Separate segments of the same lungs were used for quantification of lung protein content as described for lung MPO assay.) The samples were allowed to stand 5 min on ice and were then centrifuged at 750g for 5 min.
The ATP assay couples a specific phosphorylation reaction requiring ATP (formation of 1,3-diphosphoglycerate) with a dephosphorylation reaction involving the oxidation of NADH. The amount of ATP originally present is equivalent on a molar basis to the amount of NAD formed, which is quantified by measuring the change in absorbance at 340 nm (Beckman DU7 spectrophotometer). The absorbance change is compared with a curve generated from standards of ATP (0, 250, 500, and 1,000 μM) to determine the amount of ATP present. Results are presented as nanomoles of ATP per milligram of lung protein.
Pulmonary arterial PARS activity.
PARS activity was measured with the use of a commercially available assay (Genzyme Diagnostics, Cambridge, MA). Four or five pairs of pulmonary arteries were studied in all groups. After dissection of the pulmonary arterial rings from the various experimental groups as for the response to Ach, A-23187, and SNP, the samples were placed on ice in 2 ml of buffer containing 50 mM Tris ⋅ Cl (pH 8.0), 25 mM MgCl2, and 0.1 mM phenylmethylsulfonyl fluoride. The samples were homogenized for 30 s and then sonicated for 20 s at full power (ultrasonic homogenizer). The suspension was centrifuged at 3,000 gfor 5 min at 4°C. The protein concentration of the supernatant was determined as described for MPO assay.
Supernatant (the volume containing 20 μg of protein), PARS buffer (10 μl), 1 mM NAD (10 μl), 2 μCi32P-labeled NAD (at 1 μCi/μl), and distilled water (the volume required to give a final reaction volume of 100 μl) were mixed in a microcentrifuge tube. The reaction was allowed to proceed at room temperature for exactly 1 min. The reaction was stopped by adding 900 μl of 20% TCA (4°C), and the samples were placed on ice. Enzyme activity was determined by measuring the incorporation of radiolabeled NAD as PARS catalyzed the poly(ADP) ribosylation of proteins. The labeled ADP present was then measured by scintillation counting after TCA precipitation onto a filter. Calculation of PARS activity proceeded as follows where units are as follows: PARS activity, nmol ⋅ min−1 ⋅ μl−1; reaction time, min; vol (volume of) sample, μl; and NAD specific activity (sp act), counts ⋅ min−1(cpm) ⋅ nmol−1. The specific activity of NAD was determined by calculating the total counts in a background control reaction containing 10 nmol of NAD. Results are expressed as picomoles per minute per microliter.
Standard reagents as well as the S. typhimurium Etx were obtained from Sigma Chemical (St. Louis, MO), with the exception of A-23187 (Calbiochem, La Jolla, CA). Fresh solutions were prepared daily with either deionized water or NS as the diluent. Concentrations are expressed as final molar concentrations in the organ chambers.
Statistical analysis.
Statistical analyses were performed on a Macintosh Quadra computer with StatView software (Brain Power, Calabasas, CA). Data are presented as means ± SE of the number of rings or lungs studied at each point of data collection. In ring experiments, comparisons between groups were made at the same concentrations. Statistical evaluation utilized standard one-way ANOVA with post hoc Bonferroni-Dunn correction.P < 0.05 was accepted as statistically significant.
Effects of PARS inhibition with 3-AB and Nic on Etx-induced impairment of cGMP-mediated pulmonary vasorelaxation.
The vasoconstriction response to the α-adrenergic agonist PE is unchanged after Etx (Fig. 1). Etx administration significantly impaired endothelium-dependent, receptor-dependent pulmonary arterial vasorelaxation (response to ACh), and PARS inhibition with 3-AB or Nic attenuated this injury (Fig.2 A). Rings from saline-treated rats were preconstricted with PE to 285 ± 16 mg tension and relaxed to 16 ± 4 mg tension at 10−6 M ACh, and rings from Etx-treated rats were preconstricted to 283 ± 16 mg tension and relaxed to 168 ± 12 mg tension. In Etx+3-AB and Etx+Nic rats, 106 ± 13 and 66 ± 7 mg PE-induced ring tension remained at 10−6 M ACh, respectively (P < 0.05 vs. Etx alone,P < 0.05 vs. control).
Endothelium-dependent, receptor-independent cGMP- mediated pulmonary vasorelaxation (response to calcium ionophore A-23187) was significantly impaired after Etx, and both PARS inhibitors were beneficial (Fig. 2 B). Control rings were preconstricted to 299 ± 13 mg tension and relaxed to 19 ± 4 mg tension at 10−6 M A-23187. Rings from Etx-treated rats were preconstricted to 280 ± 8 mg tension, and those from Etx+3-AB and Etx+Nic rats were preconstricted to 283 ± 6 and 288 ± 10 mg tension, respectively. In the Etx-treated rat group, 117 ± 9 mg tension remained in response to 10−6 M A-23187 compared with 60 ± 9 (Etx+3-AB) and 45 ± 8 (Etx+Nic) mg tension in the PARS inhibitor groups (P < 0.05 vs. Etx alone, P < 0.05 vs. control).
Endothelium-independent cGMP-mediated vasorelaxation (response to SNP) by direct stimulation of guanylate cyclase was also impaired after Etx treatment, and, again, PARS inhibition with 3-AB and Nic attenuated this dysfunction (Fig. 2 C). Control rings were preconstricted to 292 ± 8 mg tension, with 4 ± 2 mg tension remaining at 10−6 M SNP, and Etx rings were preconstricted to 292 ± 8 mg tension and relaxed to 80 ± 10 mg tension. PARS inhibition resulted in 22 ± 6 (Etx+3-AB) and 21 ± 4 (Etx+Nic) mg tension remaining at 10−6 M SNP (P < 0.05 vs. Etx alone,P < 0.05 vs. control).
Administration of the PARS inhibitor 3-AB or Nic alone did not affect cGMP-mediated vasorelaxation (data not shown). Neither endothelium-dependent (either receptor-dependent ACh or receptor-independent A-23187) nor endothelium-independent (SNP) vasorelaxation responses were different in comparison with saline-treated control rats.
Administration of BA, a compound that is similar to 3-AB but does not inhibit PARS, had no effect on cGMP-mediated pulmonary vasorelaxation in saline-treated control rats (data not shown). Responses in rings from Etx+BA rats were not different compared with those from Etx-treated rats (P > 0.05 vs. Etx) for both endothelium-dependent and endothelium-independent cGMP-mediated pulmonary vasorelaxation (Fig.3).
Effects of PARS inhibition with 3-AB and Nic on lung MPO activity in endotoxemia.
Etx increased lung MPO activity more than threefold in comparison with control rats, and PARS inhibition with 3-AB or Nic did not attenuate this effect (Fig. 4). Lung MPO in controls was 0.21 ± 0.09 units/mg protein. Endotoxemia for 6 h resulted in 0.75 ± 0.07 units MPO/mg protein (P < 0.05 vs. control). Lung MPO activity after Etx and either 3-AB (0.84 ± 0.05 units MPO/mg protein) or Nic (0.65 ± 0.10 units MPO/mg protein) was not different from that in Etx-treated rats (P > 0.05 vs. Etx).
Effects of PARS inhibition with 3-AB and Nic on lung edema after Etx.
Lung wet-to-dry weight ratios (W/D) were significantly greater after Etx treatment, and the PARS inhibitors did not demonstrate any beneficial effects (Table 1). Although endotoxemia resulted in an increase in W/D to 4.76 ± 0.03 from the control value of 4.43 ± 0.03 (P< 0.05), neither 3-AB (W/D 4.79 ± 0.03) nor Nic (W/D 4.80 ± 0.05) attenuated this injury (P > 0.05 vs. Etx).
Effect of PARS inhibition with 3-AB and Nic on lung ATP levels in endotoxemia.
The Etx-induced decrease in lung ATP levels at 6 h was prevented by PARS inhibition with 3-AB and Nic (Fig. 5). Etx reduced lung ATP from the control value of 13.39 ± 0.29 to 8.64 ± 0.31 nmol/mg protein (P < 0.05). Etx+3-AB-treated rats had lung ATP levels similar to those of control rats (12.47 ± 0.50 nmol/mg protein,P = 0.20) that were also different from those of rats treated with Etx alone (P < 0.05). The lung ATP levels of Etx+Nic-treated rats were also similar to those of saline-treated rats (13.65 ± 0.69 nmol/mg protein,P = 0.74 vs. control) and different from those of rats treated with Etx alone (P < 0.05). 3-AB or Nic alone had no effect on lung ATP levels in saline-treated rats (data not shown). The lung ATP levels of Etx+BA-treated rats (8.02 ± 0.33 nmol/mg protein) were not different from those of Etx-treated rats (P = 0.37).
Effect of PARS inhibition with 3-AB and Nic after Etx on pulmonary arterial PARS activity.
Pulmonary PARS activity increased more than fivefold after Etx treatment, and the PARS inhibitors 3-AB and Nic prevented this increase (Fig. 6). Etx increased pulmonary arterial PARS activity from the control value of 0.188 ± 0.010 pmol ⋅ min−1 ⋅ μl−1to 1.050 ± 0.047 pmol ⋅ min−1 ⋅ μl−1(P < 0.05). The pulmonary arteries from Etx+3-AB-treated rats had PARS activity similar to those of control rats (0.176 ± 0.015 pmol ⋅ min−1 ⋅ μl−1,P = 0.83) and different from rats treated with Etx alone (P < 0.05). Similarly, the pulmonary arterial PARS activity of Etx+Nic-treated rats (0.236 ± 0.27 pmol ⋅ min−1 ⋅ μl−1) was not different from control (P = 0.48) but was different from Etx alone (P < 0.05). Neither 3-AB nor Nic alone affected pulmonary arterial PARS activity in saline-treated rats (data not shown). The pulmonary arterial PARS activity of Etx+BA-treated rats (0.951 ± 0.148 pmol ⋅ min−1 ⋅ μl−1) was not different from that of Etx-treated rats (P = 0.32).
We found that PARS inhibition with 3-AB and Nic in endotoxemia attenuates the dysfunction of cGMP-mediated pulmonary vasorelaxation and does not affect lung MPO activity and edema but maintains lung ATP levels. Although other studies have demonstrated beneficial effects of PARS inhibitors on the systemic vascular dysfunction in endotoxic shock (27, 32, 39, 41), this is the first study to our knowledge that examines the effect of in vivo PARS inhibition on the Etx-induced impairment of pulmonary arterial vasorelaxation. Two distinct PARS inhibitors, 3-AB and Nic, ameliorated the Etx-induced impairment of both endothelium-dependent and -independent mechanisms of pulmonary vasorelaxation. The prototypical, competitive PARS inhibitor 3-AB does not directly scavenge peroxynitrite (32) and does not prevent the development of DNA strand breakage (40). The beneficial effects of 3-AB appear to be related to PARS inhibition as opposed to other possible pharmacological properties of this drug. Its inactive analog, benzoic acid, did not affect the Etx-induced dysfunction of pulmonary vasorelaxation. PARS generates Nic in its enzymatic catalyzation of the transfer of ADP-ribose to various proteins. Therefore, Nic can decrease PARS activity through negative feedback. Its beneficial effect may also stem from conversion back to NAD+, thus directly restoring cellular energy levels (41). Although Nic is somewhat less specific than 3-AB, both compounds are potent inhibitors of PARS activity (2). In vivo administration of 3-AB and Nic inhibited the Etx-induced increase in pulmonary arterial PARS activity as measured by a commercially available assay. Both exhibited similar beneficial effects in Etx-induced acute lung injury.
We administered the PARS inhibitors after endotoxemia was established for two reasons. This model approximates the clinical scenario of sepsis, and we also minimized any possible effect 3-AB and Nic may have on iNOS upregulation. Although it has been demonstrated that PARS acts to enhance iNOS gene transcription in vitro (19) and prevents tumor necrosis factor-α-stimulated induction of iNOS in a mouse fibroblast cell line (10), other investigators have demonstrated minimal or no effects by PARS inhibitors on in vitro (40) and in vivo (36) nitric oxide production after LPS. The PARS inhibitors 3-AB and Nic can have additional effects depending on the cell type or system studied (28). Benzamide analogs scavenge hydroxyl radical but not nitric oxide or peroxynitrite. These compounds can inhibit the expression of adhesion molecules, inhibit the cytochrome P-450 enzymes, and either stimulate or inhibit apoptosis. Nic has also been shown to scavenge oxyradicals and inhibit adhesion receptor expression (28).
In the current study, we found that PARS inhibition with 3-AB and Nic had no effect on Etx-induced lung MPO activity. Previous work in our laboratory (24) has demonstrated the importance of the neutrophil in this model of Etx-induced dysfunction of pulmonary vasorelaxation. Neutrophil depletion with the use of vinblastine or rabbit anti-rat neutrophil antiserum before Etx attenuated the impairment of the response to cGMP-mediated pulmonary vasorelaxation. However, neutrophil depletion did not totally eliminate the dysfunction of pulmonary arterial vasorelaxation. Thus there exist neutrophil-independent mechanisms of vasomotor dysfunction in Etx-induced acute lung injury, and increased PARS activity may be one of these mechanisms contributing to vascular dysfunction. Our results agree with a recent study that also found no effect of 3-AB on Etx-induced increases in rat lung and ileum MPO activity (26). In contrast to our findings, Szabo et al. (26) found a reduction in pulmonary microvascular leakage in 3-AB-treated rats. These results may be explained by the fact that a pretreatment as well as a posttreatment dose of 3-AB was utilized. Perhaps the Etx-induced increase in the lung wet-to-dry ratio is mediated by an early, PARS-dependent mechanism.
In contrast, PARS inhibition decreased neutrophil recruitment in other models of non-Etx-mediated inflammation. The PARS inhibitor 3-AB reduced myocardial neutrophil accumulation after ischemia-reperfusion injury (38), and studies in PARS −/− mice demonstrated a role for this enzyme in the regulation of the adhesion molecules P-selectin and intercellular adhesion molecule-1 (42). Szabo et al. (29) recently found that PARS inhibition with 3-AB prevented both local and systemic inflammation after carrageenan or zymosan challenge. The protective effects appeared to be more pronounced in the severe forms and delayed phase of inflammation, and inhibition of PARS increased the rate of adherent neutrophil detachment from the endothelium. In these nonendotoxemia models, PARS inhibitors were administered before the inflammatory stimulus, suggesting that an early PARS-dependent mechanism is involved in neutrophil accumulation and edema. The lack of effect by 3-AB and Nic on the Etx-induced increase in MPO activity in the current study and in the study by Szabo et al. (26) suggests that lung neutrophil recruitment in severe endotoxemia may be mediated by a PARS-independent step. Further investigation is needed to establish the effect of PARS inhibition on neutrophil accumulation and function in endotoxemia.
We further examined the role of PARS in Etx-induced acute lung injury by measuring lung ATP levels and pulmonary arterial PARS activity. The maintenance of lung tissue ATP after 3-AB treatment in endotoxemia suggests that PARS activation may be an important pathway in the reduction of cellular energy levels in this model of lung injury. However, lung ATP levels may not accurately represent pulmonary vascular energy status, but previous studies suggests that endotoxemia depletes cellular energy levels and that this energy deficit may be linked to a dysfunction of pulmonary arterial vasorelaxation. In rat aortic smooth muscle cells, the PARS inhibitors 3-AB, Nic, and PD-128763 inhibited the reduction in cellular NAD+ and ATP as well as the suppression of mitochondrial respiration in response to LPS and interferon-γ stimulation (32). Rodman et al. (20) found that inhibitors of oxidative phosphorylation reduced receptor-dependent relaxation in both aortic and pulmonary arterial rings. In vivo administration of both 3-AB and Nic prevented the Etx-induced increase in pulmonary arterial PARS activity, confirming the action of the inhibitors in the tissue with which we performed our vasorelaxation experiments. Furthermore, benzoic acid, a compound that is structurally similar to 3-AB but does not inhibit PARS, had no effect on lung ATP levels, pulmonary arterial PARS activity, or the dysfunction of pulmonary vasorelaxation in endotoxemia.
Peroxynitrite formation is the proposed initial stimulus leading to PARS activation, with subsequent impairment of cellular energetics and vascular function in endotoxemia (32, 39, 40). Although the presence of peroxynitrite in the lung has been demonstrated experimentally inEscherichia coli Etx-treated rats (34) and clinically in autopsy specimens from patients with sepsis-induced pulmonary injury (15), its role in the pulmonary circulation remains unclear. Other investigators have found that peroxynitrite itself is a direct pulmonary arterial vasodilator in the dose range of 10–100 μM (6, 37). However, this observed effect of peroxynitrite occurs at concentrations that are not physiologically relevant because peroxynitrite would remain in the nanomolar range even in disease states (17). Although PARS activity was not measured directly, Chabot et al. (6) found an inhibitory effect of 3-AB on this peroxynitrite-induced vasodilation. However, the effective dose of 3-AB was 10 mM, and a dose of 1 mM 3-AB did not affect the vasodilation to peroxynitrite. The high concentration of 3-AB needed to observe inhibition calls into question the specificity of this dose on PARS activity. The published IC50 of 3-AB is 33 μM, with 88% inhibition of PARS occurring at 1 mM (2). Although peroxynitrite may not be the stimulus for pulmonary arterial PARS activation, hydroxyl radical, a species also present in endotoxemia, can cause PARS activation and subsequent endothelial damage (1, 14). Further work is needed to define the relative roles of peroxynitrite and hydroxyl radical in PARS activation and vascular injury.
Although both pulmonary arterial PARS activity and lung ATP levels returned to control values with 3-AB administration, the Etx-induced dysfunction in cGMP-mediated vasorelaxation was only partially attenuated. PARS-independent mechanisms of vascular dysfunction may also contribute to the injury, as has been observed in other models of inflammation (11, 32). Cellular damage in oxidative stress occurs by parallel and/or synergistic pathways, which may or may not involve peroxynitrite generation and PARS activation. Indeed, inhibition of PARS represents just one potential strategy to reduce nitric oxide- or peroxynitrite-mediated cellular injury. Other agents such as specific inhibitors of iNOS, superoxide dismutase mimetics, and scavengers of peroxynitrite also offer promise in the therapy of shock and other inflammatory diseases.
In summary, we found that the PARS inhibitors 3-AB and Nic in Etx-induced acute lung injury attenuate the dysfunction of pulmonary vasorelaxation and maintain lung ATP levels but do not affect lung MPO activity and edema. The data presented here suggest that PARS activation in endotoxemia contributes to the development of pulmonary vascular dysfunction. PARS inhibition may provide a novel therapeutic approach in ameliorating the vascular dysfunction seen in sepsis and acute lung injury.
This work was supported in part by National Institute of General Medical Sciences Grant GM-49222, National Institute of Child Health and Human Development Grant HD-36256-01 (to D. D. Bensard), and an American College of Surgery Faculty Research Grant (to R. C. McIntyre, Jr.).
Address for reprint requests and other correspondence: R. C. McIntyre, Jr., Dept. of Surgery, Campus Box C-313, Univ. of Colorado Health Sciences Center, 4200 East Ninth Ave., Denver, CO 80262 (E-mail:robert.mcintyre{at}uchsc.edu).
E. J. Pulido is the Kiwanis Trauma Research Fellow.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
- Copyright © 1999 the American Physiological Society


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The capacity to produce brilliant, individualistic cricketers reaped more rewards for Sri Lanka here yesterday, taking them a step closer to a tournament success no rival would surely begrudge them.
With a 100 per cent record through the group and Super Eight stages, they advanced to the semi-finals of the World Twenty20 with a comprehensive 48-run victory over a limping New Zealand side whose elimination surprised no-one, least of all themselves.
The trauma of the Lahore shootings remains a raw memory, the unrest at home a disturbing backdrop, yet their players still present a sunny demeanour and retain the ability to bring joy with captivating cricket.
If it is not their innovative batsmanship, it is the unpredictable skills of their bowlers that unravel opponents and enthral spectators. On this occasion, while there were substantial contributions by three of their maestros at the crease, the chief destroyer of New Zealand was the rising spin bowler, Ajantha Mendis.
In a game designed to give free licence to batsmen, his three overs went for a miserly nine runs but, more than that, the 24-year-old took out two of the Kiwis' principal weapons in the space of four deliveries in a ninth over that was effectively decisive.
Having dragged Ross Taylor down the pitch to be stumped, he then beat Scott Styris's bewildered prod to knock back off-stump and leave New Zealand, who fancied they might chase down a target of 159, suddenly wobbling at 64 for 4 with much of their run-scoring potential already spent.
Mendis added Peter McGlashan, who edged to gully, to take his tally in the tournament to 10 from 18 overs at an average of 10.00 and an economy rate of 5.55. He has enhanced his reputation as a man of mystery, capable of summoning up leg-breaks, flippers, off-breaks and googlies at will, although Daniel Vettori, the beaten captain, attributed his success less to any mystical qualities as sheer brilliance.
"A lot of our guys felt they were picking him but on that pitch, with a lot of turn, he was still very difficult to play," Vettori said. "I don't think he is a mystery bowler, just a very good one."
Mendis himself is unfazed by the suggestion that batsmen are getting his measure. "He feels comfortable at the moment," his team-mate, Mahela Jayawardene said, interpreting questions on his behalf. "He says he has a few plans up his sleeve if people start to work him out."
Unorthodox batting, particularly in the form of Tillakaratne Dilshan's overhead flick shot, has been the feature of Sri Lanka's progress. This time their approach was more measured but Dilshan still hit 48, while Jayawardene, who struck a towering six off Vettori, and Kumar Sangakkara provided substance down the order.
Martin Guptill, with 43, offered the only innings of note for New Zealand, whose downfall Vettori refused to attribute to a length injury list. "We just didn't score enough runs," he said. "Sri Lanka deserve to get to the final."
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A fabulous new cherry tomato producing unique rose-pink skin with smoky overtones. Not only is the colour unusual, Tomato 'Rosella' has high levels of sweetness and acidity for a pronounced and lingering flavour. Heavy crops of thin-skinned 15g (½oz) fruits are produced from midsummer onwards, making an exciting and flavoursome addition to salads and cooked dishes. This cordon variety can be grown in the greenhouse, or in a sheltered, sunny spot outdoors. Height: 200cm (79"). Spread: 50cm (20").
Companion planting: Try growing tomatoes with French marigolds to deter whitefly, and basil, chives or mint to deter aphids and other pests.
Useful links:
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For greenhouse cultivation: sow from February to March.
For outdoor cultivation: sow from March to April.
Sow seeds on the surface of a good, free-draining, damp, seed sowing mix and cover with a fine sprinkling of compost or vermiculite. Place seed trays in a propagator at a constant temperature of around 15-20C (59-68F) until after germination, which takes 7-14 days. When seedlings gain 2 true leaves, transplant into individual 7.5cm (3") pots of compost and grow on at a minimum temperature of 15C (59F).
When growing in a heated glasshouse tomato plants may be transplanted at the end of May or when the first flowers are showing, if earlier. Allow 3 plants per growbag, or one per 25cm (10") pot, or plant tomatoes directly into the greenhouse soil.
When growing tomatoes outdoors, wait until all risk of frost has passed before transplanting tomatoes. Gradually acclimatise them to outdoor conditions over 7 - 10 days before planting out from early June when tomato plants are 20cm (8") tall. Choose a sheltered position in full sun on fertile, reliably moist, well drained soil, and transplant at a distance of 60cm (24") apart. Drive a (5') cane into the soil adjacent to each plant to support them as they grow, and tie each main stem to its support with soft garden twine.
Water tomato plants frequently, to keep the compost evenly moist. Feed tomatoes regularly with a high potash plant food once the first truss of fruit has formed.
Tie the main stems to their supports and remove any sideshoots that develop between the main stem and the leaf stems. Once the plant has produced 6 or 7 trusses, pinch out the top of the main stem. This process of 'sideshooting' and 'stopping' will increase the availability of light and air movement around the developing fruit, and focus the plants energy on producing a good crop of high quality tomatoes. Tomatoes can be harvested as they ripen from July to September.
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By Marie Farruggia 19-08-2016
Our family has always loved Sungold.........but we think Rosella tastes even better! We are growing it in a polytunnel as a cordon and it has a very heavy crop of nice-sized cherry tomatoes. The taste is superb. I will definitely be growing it again next year, and will try it outdoors as well as in the polytunnel and greenhouse.
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This is now my favourite cherry tomato. Extremely sweet jamminess. One to grow every year from now on. Highly recommended. I grew as cordon, sown under heated glass in March. First fruit in late May.
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Should I pull the trigger?
This is a discussion on Should I pull the trigger? within the Rifles forums, part of the Rifle & Shotgun Forum category; Mosin-Nagant m91/30 carbine on sale at local gander mtn--- $149 with all the accessories No shipping, no xfer fee who has one? Like it? Ammo ...


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Systems Biology Opens New Research Pathways
Systems Biologists Are Attacking the Encrypted Messages That Would Allow Us to Predict and Change the Course of Disease
Individual Tumor Profiling
Has Tumor Molecular Profiling Enabled More Effective and Less Toxic Cancer Treatment?
Top 10 Under 40
Up-and-Coming Stars Shine in Biopharma Research and Business
Podcast: FDA's New Commissioner Hits the Ground Running
Scott Gottlieb, M.D., Commits to Speeding Up Drug Reviews, and Maintaining Safety and Efficacy
Verastem Inks Separate Deals for Wnt and FAK Inhibitors
Eisai and Versatem inked a research collaboration focused on the development of small molecule Wnt inhibitors. Verastem separately reported acquiring exclusive global rights to Pfizer's Phase II-ready focal adhesion kinase (FAK) inhibitor PF-04554878. The drug, designated VS-6063 by Verastem, is being developed for the treatment of solid tumors and is projected to start in Phase II development for treating mesothelioma next year.
The new partnership with Eisai will use Verastem's salinomycin candidate VS-507 as the starting point for the development of new analogs that target cancer stem cells. Verastem has put further development of VS-507 itself on hold in order to push on with other priority candidates. Compounds identified through the Eisai collaboration will be tested using Verastem's Wnt signalling and cancer stem cell assays. The firm will retain ownership of compounds developed during the 12-month collaboration, with Eisai receiving royalties on future commercial sales of products, and retaining rights of first negotiation for development.
Under terms of the deal with Pfizer for VS-6063, Verastem takes over all responsibility for developing the candidate globally. Pfizer earns an up-front cash fee and Verastem equity, and will be eligible for development milestones, future royalties, and sales milestones.
Verastem is focused on the discovery and development of drugs that selectively target cancer stem cells. The firm has developed a engineering technology for generating large numbers of cells that stably retain a cancer stem cell state, and has established a high-throughput drug discovery approach for identifying and developing drugs that specifically target these cells.
The firm's development pipeline in addition includes a P13K/mTOR dual inhibitor VS-5584, which was licensed in from S*Bio earlier this year, and which is expected to start in clinical development in advanced solid tumors during mid-2013. Another FAK inhibitor, VS-4718, has been selected as a development candidate that started in IND-enabling toxicology studies last month. Healthy volunteer trials with the drug are projected to begin during early 2013.
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Horn Dot Threader Earrings
Free Shipping On Orders Over $85
The horn circle is the focal point for these Horn Dot Threader earrings. The handcrafted design create an effortlessly modern look!
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- Material: Brass & Horn
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Massage therapists are known for their strong hands, which means that the best way to find one is to follow a trail of open pickle jars. Find a helping hand with this Groupon.
Choose from Three Options
$69 for a 60-minute native-energy-stone massage, which applies warmed stones made of iron, magnesium, and calcium to the upper back (a $149 value)
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Serenity Spa Wellness Center
In a massage room awash in shades of plum, one of Serenity Spa Wellness Center's licensed therapists plunges deft fingers into muscular structures to weed out pesky pain points and break up congregations of tension. Increasingly relaxed breaths drift out of the private room, past cedar-colored planks, and toward the far-infrared sauna, which uses dry heat in an effort to draw toxins from the body or elicit confessions from ice-cream smugglers. Aestheticians blend ingredients for facial treatments and combine fragrant swirls of essential oils, catering to individual skin and health issues. In the reception area, hands warm around mugs from a coffee bar, and floral-patterned or zebra-print chairs cradle guests.
Customer Reviews
878 Muddy Branch Road
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The City of Johnstown owns and operates a separate sanitary sewer system serving the City of Johnstown, Cambria County, Pennsylvania. The City Sanitary Sewer Collection System consists of approximately 520,000 linear feet of gravity sewer pipe. The pipe is mostly vitrified clay pipe ranging in size from 6" to 18" in diameter. There are approximately 3,100 sanitary manholes and 20 Sanitary Sewer Overflows (SSOs) including 14 active SSOs and 6 sealed SSOs within the existing system.
The City Sanitary Sewer Collection System conveys sewage to the Johnstown Redevelopment Authority (JRA) sanitary sewer (Interceptor) system for treatment at JRA's Dornick Point Sewage Treatment Plant in West Taylor Township, Cambia County. The Dornick Point Sewage Treatment Plant treats sewage from Johnstown and 19 other municipalities in the Johnstown area.
On July 14, 2010 the City of Johnstown entered into a Consent Order and Agreement with the Commonwealth of Pennsylvania, DEP to identify and correct deficiencies within its conveyance system that cause routine sanitary sewer overflows. The DEP ordered the City to implement a plan for rehabilitation to their system, ultimately preventing the discharge of sewage to waters of the Commonwealth through wet weather overflows.
The City has determined the best course of action to eliminate wet weather overflows and comply with requirements set forth by the DEP is to reduce infiltration and inflow by separating the private storm sewer flows from the sanitary sewer systems and replacing the existing vitrified clay pipe
The City of Johnstown plans to replace their entire sanitary sewer system with new pipe by open cut and/or trenchless methods. In addition to the installation of the new collection line, all existing laterals will be replaced within the public right-of-way from the collector line to the property line, and all manholes within the system are to be replaced. The City will perform pressure testing of the new collection lines and laterals and vacuum testing of the manholes within the public owned sanitary sewer system. The City will take the appropriate steps to insure that all current customers reconnecting to a new collection line perform pressure testing of laterals to maximize the reduction of I/I from the private sector. These steps will greatly reduce the amount of I/I into the system and allow flow to be conveyed more efficiently through the sanitary sewer system. The new sanitary sewer would be installed adjacent to the existing sanitary system as much as possible, allowing the existing sanitary sewer system to remain in-place and be converted into a storm sewer system. Properties/structures with illegal storm water connections to the original sanitary sewer could remain as long as all the gray water piping and the sanitary portion is reconnected to the new sanitary system and passes the pressure test.
For more information, please check out our GIS page.


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ED Magedson – Founder
Ripoff Report
getphoneloan.comInternet USA
getphoneloan.com Harrasing and Rude Internet
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Fix it the right way.
Corporate Advocacy Program™
Ive never been harrased so much in my life. Recieved a total of 89 calls (including 1 whie i was writing this). Stay away from this website getphoneloan.com unless you really need somebody to talk to!
This report was posted on Ripoff Report on 02/14/2014 01:00 PM and is a permanent record located here: http://www.ripoffreport.com/reports/getphoneloancom/internet/getphoneloancom-harrasing-and-rude-internet-1123590. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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Need a Mold Allergy Test in Greenwood, SC? Simply order online 24/7 and get a fast, affordable Mold Allergy Test at a lab near you (Find More Locations):
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Let us know when your receive great advice so we can thank our lawyers and point others with similar questions in the right direction.Got it!
so now i have a hearing for this and i really dont know what is coming to possibly happen what you know please?
You are facing a license suspension that is seperate from the criminal case and potential use of the refusal against you in the criminal case. Whether it was a bad idea to refuse depends on what the result would have been. You should let your lawyer know about the refusal hearing as he/she may want to attend and question the officer.
I am a former federal and State prosecutor and now handle criminal defense and personal injury/civil rights cases. Feel free to check out my web site and contact me at (212) 385-8015 or via email at email@example.com. The above answer is for informational purposes only and not meant as legal advice.Ask a similar question
You need an attorney. Your license is at risk for 1 year.
It is also evidence that can be used in your criminal case.
Joseph A. Lo Piccolo, Esq.
Immediate Past President, Criminal Courts Bar Association 11'-12'
Hession Bekoff & Lo Piccolo
1103 Stewart Ave, Suite 200
Garden City, NY 11530
516-408-3666 (o) / 516-408-3833 (f)
I am a criminal defense attorney practicing in Nassau, Suffolk and New York City. The above information is not a substitution for a meeting whereas all potential legal issues can be discussed.Ask a similar question
Refusal is serious. Is it bad? Or good?
It all depends. You really want a DUI/DWI lawyer in your area to help you with this and the trial itself, assuming you did get a DWI charge. . You can lose your license before you even get to court. http://addbalance.com/duitendaywarning.htm
The field sobriety "tests" are designed so that sober people will fail them, even if they are properly done. Often, they are not properly done. Only someone with expertise in this area can recognize problems with how the tests were done. http://addbalance.com/fieldsobrietytests.htm
What to do if you are stopped when you have been drinking?
Confidential information should not be disclosed in this Internet forum. I am a Wisconsin lawyer. The laws in each jurisdiction can be very different. I cannot give legal advice over the internet nor can I establish an attorney client relationship with you. You should NOT assume or otherwise conclude that there is an attorney -client relationship between any reader and this writer or his firm. These comments are only guideposts. They are not subject to any privilege protections. Indeed, these internet communications are neither privileged nor confidential. Accordingly, those using this form of communication need to be guarded in what they write. Because of the nature of these communications the information is general only and should not be relied upon in any specific case. This internet site is public forum, where the communications are not confidential or privileged. There may very well be merit to your defense or position in this type of situation. However, there are hardly sufficient details for an attorney to provide you with some path to follow. It is imperative that ALL of the facts in a particular situation be examined. No conclusion can be drawn from the communication that you have provided. There are some matters that are just better handled by an attorney familiar with the procedures of the courts in your area. Most, if not all, legal matters should not be handled via internet communication. At best, the responders on this site can give you a few hints and guidance. To deal with a legal problem, nothing is better than to consult with a lawyer who will give you some time and advice. If you cannot afford an attorney, there should be agencies in your area that can provide discounted, or even free, legal services. Experienced Criminal Defense Lawyer in Madison, Dane County, Wisconsin http://addbalance.com Talking to the Police - Advice from Lawyers and Police: http://addbalance.com/police.htmAsk a similar question
You'll be fine. Call an attorney
Scott Gross
Former Suffolk Prosecutor
This is not a solicitation nor is it legal advice. An attorney/client relationship has not been established. The Law Offices of Scott Gross, PC 631-456-2326 Scottgrosslaw.comAsk a similar question
There are alot of factors that go into assessing whether or not it was "bad" to refuse. The fact is that you have an allegation of a refusal against you and you are facing a hearing in which you could lose your license. It is very important that you hire an attorney to appear at the hearing as they can try to save your license and it is also an important step in which the attorney can subject the arresting officer to cross examination before the prosecutor is likely to have even spoken to him.Ask a similar question
This is a specialized and technical hearing and if you lose the DMV revokes your driving privileges. You should retain counsel immediately to represent you at the proceeding.Ask a similar question
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A Drone's-Eye View of Conservation
By Lian Pin Koh | TED | December 18, 2013
We've all heard of Predator drones, but have you heard of conservation drones?
Ecologist Lian Pin Koh makes a persuasive case for using drones to protect the world's forests and wildlife. These lightweight autonomous flying vehicles can track animals in their natural habitat, monitor the health of rainforests, even combat crime by detecting poachers via thermal imaging. Added bonus? They're also entirely affordable.
This article is licensed under a Creative Commons License.
Please read our usage policy.
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Read More: Conservation, Environment, Innovation, Science, Sustainability, Technologyblog comments powered by Disqus


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jennifer rivers
niles, MI
im 4"8, and as you see in the picture im blonde, blue-green hazel eyes, for the most part you probably can only see gray by far in my photo. im a sagitarrius. im god fearing, laid back down to earth person.
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Well this story focuses on the girl Bailey Sok,a Korean girl who will move to LA. She'll meet her ex in LA, whom she is still in love with, they'll give it another shot but will it work?
This book has the other ships so don't think it'll just be about BaiKen, this has GaTi, SeaLey, GabLey,Gaycee and others they'll have their own love story in this book too, so be patient and wait for it, I promise that this story will be worth your time, thanks :)
ChelseaWels25 May 16, 2016
Is this BAIKEN? Or is this GABELY?!?!?! Cause if this was GABLEY I would not like the story


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28 reviews | 4.1 out of 5
The clock is awesome. It sets itself automatically, is highly visible, and the dual alarms are very easy to use. The radio gets poor reception and is plagued with a "feature" that drags the clock function down with it. The radio tuner is analog but with a digital display. When you tune the radio, the clock display switches to show the radio station. Then about 10 seconds after you leave it alone, it switches back to time display. But, the radio station changes at random. Sometimes if you walk past the radio, the reception degrades and goes all static. Sometimes it does this completely at random. When this happens, the radio display changes. I don't know why the digital frequency display changes if you don't move the knob, but it does. So some mornings, I lie in bed watching the display switch back and forth from 91.5, 91.4, 91.3, 91.4, 91.5, etc. And it never settles long enough to display the time. I thought maybe my radio had been damaged or something so I bought a second one, it had the exact same problem.
Just bought this a couple of days ago. I like about everything about it. The snooze button is obvious when you are half asleep and go grabbing to hit it. No worry about hitting an off button by mistake. The controls for turning one of the two alarms on or off are right on the front and easy to use. In fact, all the controls are easy to use. You don't have to turn this thing upside down to get to any unlike the other clock radio I had. Mostly, I can't say anything negative about this clock. I can read it with my glasses off. The controls work well....
But, note that the radio station dialing is not really digital, though it is connected to the display on the front. This makes tuning into a station unexacting, sort of like any dial station control. Not a big deal, but true digital would be a little easier.
Would I buy it again? You betcha!
I especially like the alarm sounds -- a soft "bip" or "bip-bip" depending on whether it is Alarm 1 or Alarm 2, gradually becoming louder, but never harsh-sounding at all. The only change I would suggest is the Alarm/Radio/Off control switch. It is not easy to manipulate, for a person with arthritis. A button-type control or sliding switch would be more user-friendly. But other than that, it is everything I want in an alarm clock.
This is the best alarm clock I have had for its value. I love that it will set the time itself. Dual alarms are great for 2 people. Alarm can be designated for certain days of the week. I love that it does not require batteries in case of a power outage. Large numbers make it easy to see the time. Mp3 jack and calendar are a nice bonus!
I have been looking for a dual alarm clock radio for a while. I even bought a couple but was disappointed and returned them. I wish I had seen this one a long time ago.
I love the automatic time setting when you plug it in. Also, the automatic Daylight Savings Time adjustment (you can turn this off if you want). The LED is easy to read even in the dark. The alarm settings and switches are right up front so you don't need to hunt for them.
A couple of things I am somewhat disappointed about. 1) The FM radio has a separate wire antenna coming out of the unit. 2) The labels of the buttons on top are gray/silver on the black case. Between the colors and the size of the print, they are a bit difficult to read. Luckily, you don't need to use these buttons too often.
These two things are the only reasons I gave this unit a 4 overall. I also would have expected a better price point from a Timex.
The time display is big enough to see across the room. The alarm buzzer starts at a softer volume and gets louder, but not blaring. The controls are easy to use. The only thing I could suggest to improve would be having a switch to set to AM or PM, so that you don't have to press the ALARM/TIME set buttons for so long to get to the time you want.
Great clock for people who work five, seven or just weekends. You can set it for Mon_Fri or Mon-Sun, and Sat and Sun only.
This alarm clock is AMAZING. I absolutely love it. I usually set it to radio wake up and it hasn't failed me yet. I also love that even when the power goes out it resets itself to the right date and time. My fiancée gets jealous that he has to keep setting his! The only issue I have with this clock is it's very bright even on dim mode, however I just turn it around and it's fine. It is also at eye level on my night stand, so that is also a contributing factor as well. I expected it to be more of a
"Glow-in-the-dark" brightness as opposed to an actual LED brightness, but that is my only complaint.
if you go to Timex you will not see this alarm clock on there support list, maybe because they wish to forget they made it. If you're already awake when the alarm goes off you might make it to work otherwise you will sleep thru the alarm since you can hardly hear it. the alarm clock does not set itself, it just happens to have a double sized lithium battery in it that they pre-set at the factory. the radio is a digital display but it is only simulated with actual analog tuning that is not error free. out of my 57 years on this earth is the second worst alarm clocks I have ever bought. I had to go out and buy another alarm clock because I could hardly hear the buzzer on this thing.
I love the sound of it. The reception is great. I haven't used it for the alarm therefore cant comment on the part of it. I needed a clock radio for my kitchen in an apartment building window and it is GREAT.
I had asked the question about whether or not this clock is digital (it is), and hoped it could pick up the new all-classical, UofH station 91.7 here in Sugar Land (south of Houston)...it can't. I am very disappointed.
It is not the stylish of clocks. I don't care for the knobs on the front of the clock. One for each alarm. I think a better design for a nicer appearance would be nice. No matter how much we try to get a clear reception for any radio station, we cannot. The LED light is bright, but there is a dimmer. The numbers are large. The plus side is this clock automatically changes time for DST. If there is a power outage, the clock will reset itself to the correct time. The main reason we purchased this clock was for the duel alarms. The alarm can be set to go off on weekdays; no need to turn the alarm off. It suits it's purpose. We looked at a few clocks and the price was pretty average. We went with this clock because of the "Timex" name.
With dual alarms and weekday/weekend settings, this alarm clock is a set it and forget it dream. If you want big speakers, this clock doesn't have them but it's as convenient and easy to use as any I've ever had. It also keeps time as well as sounding the alarm even when the powers gone out.
Had no complaints until I had it for a little over 2 months...it started to short-circuit. Now the time is always flickering. When you try to set any time, there's a delay every second so it takes twice as long to do anything. When the alarm sounds, it intermittently beeps with interrupting silence to the tune of it flickers.
The alarm clock radio gets good reception, it comes with a small wire antenna. It's easy to operate. I like the alarm mode, on weekdays off weekends. I also liked the digital station display when setting the stations. Overall the radio has everything I need.
I love the radio in this clock. But I cannot read the numbers. The numbers seem blurred. They are tall and skinny. I like the many features but not being able to easily read the numbers is the reason I will return this clock.
I have had the clock radio for only SIX DAYS. So far I like it very much. A rating after a longer period of time would be more meaningful.
Great Clock. display is large and very functional set up for controls
This clock radio works well. It has great sound and easy to handle.
Clock meets all our requirements. Leave it to Timex to get it right.


text:
ED Magedson – Founder
Ripoff Report
KOOL TELECOM, LTD-KOOLTEL AMERICA MTH, OAN, AT&T11301 W. Olympic Blvd. #314 Los Angeles, California United States of America
Does your business have a bad reputation?
Fix it the right way.
Corporate Advocacy Program™
recevied att phone bill today
kool telecom ltd, had charged my acct. for 2 mo of service @ $22.95/mo
never heard of companyor ever been to their web site, yet they say i created and oked the account.
called att and they took charges of bill and call kool telecom on 800 926 6435 # and the cancelled acct and put my number on a don't authorize list.
time will tell if they do this
\att are responsible for allowing this type of charge thru the billing sys. esp. when many have reported the scam to them.
i will goto/take to court if this continues, maybe a CLASS ACTION SUIT.
This report was posted on Ripoff Report on 08/28/2009 06:16 PM and is a permanent record located here: http://www.ripoffreport.com/reports/kool-telecom-ltd-kooltel-america-mth-oan-att/los-angeles-california-90064/kool-telecom-ltd-kooltel-america-mth-oan-att-oan-services-kooltel-america-mth-ripoff-486815. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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SUBMITTED: Monday, August 31, 2009POSTED: Monday, August 31, 2009
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Raymond Haas, Insurance Attorney
Relationship: Worked together on matter
Mark Link is an exceptional and accomplished personal injury attorney. I have had the privilege of working with Mr. Link on a number of cases. I can attest to the fact that he is knowledgeable, professional, and thorough. I would certainly recommend him!
Robert Hughes, Probate Attorney
Relationship: Worked together on matter
Mark is unquestionably one of Atlanta's best personal injury lawyers. I can highly recommend him to anyone looking to retain an attorney to insure that your rights are fully protected and your claims are fully considered by the insurance company with whom you are dealing.
Peter Zeliff, Criminal defense Attorney
Relationship: Fellow lawyer in community
Mark Link is an excellent attorney. He is dedicated to his clients and will go the extra mile to achieve the best possible results on their behalf. If you are looking for a personal injury attorney, you should meet with Mark Link.
William Kelley, Business Attorney
Relationship: Fellow lawyer in community
I endorse this lawyer's work. Mark has earned the respect of his peers and fellow members of the Georgia Trial Lawyers Association through his tireless representation of the injured in Georgia.
Shea Roberts, Family Attorney
Relationship: Fellow lawyer in community
Mark is a strong advocate for his personal injury clients. He is licensed in 3 states with extensive experience. Mark is a fellow member of the Georgia Trial Lawyers Association and I endorse this lawyer's work.
Andrew Speaker, Trucking accident Attorney
Relationship: Fellow lawyer in community
He is not only highly skilled, aggressive, and successful when it comes to helping those who receive serious personal injuries, but cares deeply about his clients. Unlike many at larger firms he personally works closely with his clients to ensure that they obtain the justice they deserve. I am happy to endorse this attorney's work.
Howard Spiva, Personal injury Attorney
Relationship: Fellow lawyer in community
Mark is an excellent attorney. "Smart" doesn't even begin to describe him. Incredibly he is licensed in Georgia, Florida and Alabama! He attended top schools including The University of Georgia and the University of Florida. He graduated at the top of his class. He is a well known published author. He generously and freely gives of his time speaking at legal seminars and answering questions on AVVO. This is reflected in his high rating.His skill and reputation are well know and respected in the legal community. He is passionate about helping people injured due to the negligence of others. He cares about his clients and he works hard to help them during difficult times in their lives. I lend Mark my personal endorsement. Howard Spiva www.spivalaw.com
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Chief executives Gökhan Bozkurt, (Matrix Reasürans Brokerlik, Istanbul) and Lee Ellis (MIRB Africa, Johannesburg), describe how Matrix is planning to lead the way forward through innovation and exceptional customer service.
What triggered your decision to join Matrix and how challenging has it been so far?
Gökhan Bozkurt: Although the broking sector is relatively new in Turkey, most of the well known international players have established local offices during the last 10 years. After almost three decades in the Turkish insurance market and in various managerial positions, I am confident that the current low, but increasing, insurance penetration in Turkey guarantees great opportunities in the near future.
The ability to observe and determine the needs of the sector combined with an international knowhow and cutting-edge initiatives, have certainly proved to be, and I believe will continue to be, very challenging. Matrix is a new broking house, entering the highly competitive Turkish market, so we have clearly set our strategy towards solutions that already have enabled us to differentiate ourselves from our competitors and have positioned Matrix as the exemplary client-oriented company.
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Gökhan Bozkurt, Lee Ellis, Matrix Reasürans Brokerlik, MIRB Africa, Asia-Pacific, Africa


text: Hello- My 2 year old $400 Acer laptop that has win 7 32 bit home edition locked up while surfing last night and I cannot get it to open. I tried safe mode it hangs up on the starting windows screen. I hit F8 and tried the launch start up repair function to no avail. What else should I try? When the laptop locked up the screen went off white like someone was trying to IM me and nothing opened. I pulled the battery out to shut the laptop down since I didn't like the look of what was happening and none of the buttons or other prompts would work. I have a current version of McAffe and was using Firefox. Any ideas areas to try? Thanks