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Helping The Philippines Heal
As we take stock of the impact of the horrific tragedy in the Philippines following Super Typhoon Haiyan, Americans inside and outside of government are rushing to help those less fortunate. These values of compassion and generosity have long been part of what makes us Americans, as seen in 2010 during the U.S. response to the devastating earthquake in Haiti and 2004 tsunami in East Asia.
American NGO's have already jumped in to provide relief and there have been calls from President Obama for more Americans to get involved and help those in need in the Philippines. This includes USGLC members like the American Jewish Joint Distribution Committee, American Refugee Committee, CARE, Catholic Relief Services, ChildFund International, Habitat for Humanity, the International Medical Corps, International Relief and Development, International Rescue Committee, Lutheran World Relief, Mercy Corps, Oxfam America, Plan International, Save the Children, and World Vision. Save the Children and World Vision are already working to assist on the ground by supporting temporary school tents and hygiene kits, while USAID has partnered with organizations like Catholic Relief Services to support relief logistics and distribute supplies, as well as participating in water, sanitation, and hygiene activities in some of the hardest hit provinces.
Equally important is the work of our civilian agencies funded by the International Affairs Budget to get on the ground quickly and assist Filipinos with the recovery from the super typhoon. The American response to the natural disaster has been "swift" and so far the U.S. has given $20 million of humanitarian assistance. The U.S. tends to be one of the first nations on the ground in natural disasters to offer humanitarian relief and this time was no different. According to Secretary of State John Kerry, "A U.S. disaster assistance response team was among the first international groups to reach Leyte province, one of the hardest-hit regions." The U.S. is continuing to work closely with partners in the Philippines to respond to the disaster.
Like in Haiti, the United States has pulled together partners across the government to provide the most effective assistance. This includes U.S. military forces attached to U.S. Pacific Command providing logistical support to the State Department and USAID to deliver emergency shelter, food, water, and sanitation supplies to Filipinos hit by this tragedy. The coordinated efforts of USAID and PACOM were praised by members of the development community recently. According to Former USAID Administrator Andrew Natsios, "AID and PACOM have worked together for 30 years on these sort of things and they do a very good job when they are left to get their work done and there is no political interference." As we saw in Haiti, when Americans stand up first and work together to help those tragically affected by natural disasters, it can go a long way in the recovery efforts.
Our hearts go out to the victims of the typhoon and we hope they will soon feel a sense of relief from the hardship they are enduring. But, while we look stunned at the devastation, we also look to the future. Already, careful voices are calling for learning lessons from past disaster relief efforts, paying attention to coordination and sustainability. Through initiatives like the USAID Resilience Strategy and the Partnership for Growth partnership between the U.S. and the Philippines, the U.S. should be in a strong place to coordinate its assistance and help provide the Philippines with the tools it needs to rebuild.


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Latest Stories
Sci-Fi TV Shows That Should Be Remade
February 4, 2010
Whoops, it doesn't look like we have any episodes for this season! Try clicking on another season above!
About This Show
- Summary
Invasion: Earth was a BBC sci-fi series about alien saucers being shot down in 1944.
Genre: Sci-Fi
Network: BBC One
Status: Ended
Original Air Date: May 8, 1998
Finale: Jun 12, 1998

subset: commoncrawl


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Drought-stricken areas of the United States continue to carefully monitor their water resources and examine the state of their water infrastructure as supplies dwindle, impacting nearly every corner of the regions affected. In California, residents voted drought as its top concern over other issues such as the economy and employment, according to a 2015 poll commissioned by the California Water Foundation. The survey also indicated residents were willing to pay more to fund infrastructure improvements. With mandated water usage restrictions in place, communities must work to ensure water resources are managed efficiently and wisely.
There are a variety of approaches and methods available to help water utilities combat the effects of extreme drought in their communities. This publication, fittingly titled the Drought Handbook, highlights solutions that can help your organization monitor water networks, detect pipeline leaks of varying sizes before they swell to expensive proportions, assess the state of your water infrastructure and supplies, and more. With improvements to infrastructure cited as vital in much of these drought-affected areas, it is important to take a look at your water network and gauge areas where you can rein in costs, reduce non-revenue water and manage resources effectively. The more tools utilities can have in their arsenal, the more they can combat drought and keep precious water systems intact.
Copyright © 2015 Mueller Co. LLC. All Rights Reserved. Trademarks and patents and patent applications covering products marked with a § symbol are owned by Mueller Co. LLC or its affiliates. For details, visit www.mwppat.com.
A water balance, or water audit, is a method of identifying and tracking the abstraction, treatment and distribution of water for sale to a utility's customers, and identifying where and why any losses of water are occurring in addition to the volume and value of the losses.
Just like any business, a city needs to know how much product (water) is produced and placed into the system for sale to the customers, so the revenue can be used to operate and maintain components of the water system. In developing a water balance, all components and operational areas where losses, such as leakage and metering errors, can occur are identified and evaluated. Strategies are then developed to efficiently reduce the impact of these losses and to increase revenue recovery and reduce operational costs.
Yes, the U.S. Environmental Protection Agency (EPA) Drinking Water State Revolving Funds (DWSRF) are one source of loans and financing for non-revenue water studies, which are one component of water conservation, sustainable infrastructure and water efficiency programs. Recently the DWSRF allowed the inclusion of the purchase of leak detection equipment, water meters, AMR/AMI systems, and water mains rehabilitation and/or replacement. The funds have a category called "Green Project Reserves" that are to be specifically used for water audits, replacement of malfunctioning meters, leak detection studies and water use efficiency baseline studies.
A utility's water infrastructure is a delicate, difficult system to manage, with much of the equipment—water mains, hydrants, meters and more—operating underneath cities and out of sight. Tracking water distribution and usage becomes a particularly important task, especially in times of drought, to ensure meter readings and billings are accurate and efficient. Traditional data collection and reporting, often through automatic meter reading (AMR) systems, are giving way to smart advanced metering infrastructure (AMI), enabling two-way communications across utility networks. With AMI systems, processes can be automated and devices linked throughout the entire infrastructure, giving utilities more control over how and where their water is being distributed and helping to reduce non-revenue water.
In Washington, the Nob Hill Water Association has been serving customers in the Yakima Valley since 1908. Most of its infrastructure is located underground, making it a challenge for managers to gauge water distribution. But with the use of a two-way AMI system, operations have become more streamlined for both utility officials and customers alike.
Nob Hill Water utilizes the Mi.Net Mueller Infrastructure Network, which provides two-way meter communication and control across its water system, one of the largest in the Yakima region. The AMI allows Nob Hill Water to gain more information in the field in real time, says Nob Hill Water manager Zella West, who calls it "vital" for the utility to know what's going on. The technology links meters, distribution sites and control devices in a single, highly efficient data network.
Since implementing Mi.Net, billing processes were cut down from two weeks to about three days, and the ability to pull data from the system within a few hours has given Nob Hill Water the opportunity to discover issues that otherwise could have cost them exorbitant amounts of non-revenue water. The system helps Nob Hill prioritize resources and optimize efficiency, a clear example of just how important automated tracking and reporting of data has become for water utilities.
The Mi.Net Mueller Infrastructure Network for Utilities from Mueller Systems is a true two-way advanced metering infrastructure (AMI) system that fully automates the meter-reading-to-billing process through its wireless fixed network and mesh configuration. Ongoing access to customer data and information allows utilities to receive readings and vital alerts faster than before.
The Mi.Net system uses Mi.Node tranceivers on water and energy metering devices to collect and store information to area Mi.Hub collectors, or gateways that upload the data to either the utility's server or Mueller's hosted server. The benefits of implementing the Mi.Net system include improving water and energy management, identifying leaks and outages, offering flexible billing capabilities to customers, and more.
Early leak detection is vital for distribution systems, with the ability to identify system failure points before they impact customer levels of service. When water resources are limited, early detection is a valuable tool in reducing non-revenue water and extending pipe asset life. A fixed leak detection technology, Echologics' EchoShore®-DX platform, is changing the way water main leaks are identified and repaired.
Pennsylvania American Water in Liberty, PA, was field-testing the new technology when it located a growing leak in a susceptible portion of the distribution system. After two attempts to detect leaks with conventional ground sounding equipment, a third inspection—this time accompanied by Echologics specialists—exposed a long crack in the bottom of the pipe, beginning in the spigot's end, that was saturating the soil at 5 gallons per minute (GPM).
"I've never seen anything like this, where a leak was identified so early in its history—almost immediately after it occurred," said David Hughes of American Water. "This leak would have gone undetected with our traditional equipment, and it likely would have become a catastrophic failure similar to pipes that literally burst apart, creating costly property damage and substantial water loss."
West Virginia American Water in Charleston, WV, which typically produces 25 million gallons per day (MGD), credits the EchoShore-DX platform with reducing water loss by 2.3 MGD in the first four months of operation. Another 2 MGD of water loss was recovered from a transmission main leak, picked up by the DX system through ground vibration.
American Water has been piloting and implementing the automated acoustic monitoring system, which is capable of detecting noise signatures of potential leaks and other problems within the system. The EchoShore-DX platform uses sophisticated sensors and processing algorithms that analyze data from events detected by two or more nodes, which are installed and fixed onto existing fire hydrants, to identify and locate potential leaks or flow issues. The nodes collect essential data on the pipeline and is readily available for analysis by water operators, giving utilities like those in Liberty and Charleston the chance to find potentially costly—and difficult-to-detect—leaks.
The LeakFinderST correlator offers leak detection crews the opportunity to increase efficiencies with rapid and accurate correlation times on a variety of pipe materials, including PVC, pre-stressed concrete cylinder pipe (PCCP), asbestos cement, ductile and cast iron, and steel. It enables operators to locate "quiet" narrow band, low frequency leaks that may have previously identified as background leakage on water mains. The compact system is easy to use, with a simple software-based platform and streamlined interface developed in collaboration with end users, and can quickly and effectively locate quiet leaks that are long running and previously undetectable.
The EchoShore®-TX monitoring platform plays a central role in the Las Vegas Valley Water District (LVVWD) leak monitoring program. Part of the Global City Teams Challenge sponsored by the U.S. Department of Commerce's National Institute of Standards and Technology, the project has LVVWD teaming up with Echologics and several other innovative partners to ensure round-the-clock monitoring of the 30-in. diameter underground water main running beneath the Las Vegas Strip—no easy task when considering the multitude of resorts operating 24/7 above it.
The EchoShore-TX platform uses sophisticated acoustic sensors and proprietary processing algorithms to detect potential leaks in large-diameter pipelines long before they become detectable by conventional means. The importance of detecting such leakages early and before they become too serious and costly to fix—and more importantly, before they rupture and cause catastrophic damage—is emphasized by Charles Scott, engineering project manager for the LVVWD.
"This type of pipe doesn't just catastrophically fail all of a sudden," he says. "Rather, it fails by having a very small leak, which develops into a larger leak, eventually becoming a sinkhole. This technology enables us to monitor the pipe on a continuous basis, detect those small leaks before they get to be big leaks, and schedule repairs as needed—enabling us to significantly extend the life of our pipes."
Using wireless connectivity provided by Global City Teams Challenge partner AT∓T, the 12 EchoShore-TX nodes installed in Las Vegas collect data about the pipeline and regularly upload it to a secure server, where advanced algorithms search for leak signals within the data and generate reports that can be easily viewed on a customized user interface. The system also sends alerts to the mobile devices of utility operators, enabling them to react to any detected leaks or problems immediately.
The entire deployment of the EchoShore-TX system—a noninvasive process encompassing installation, commissioning, testing and activation—was completed in a little over two weeks on the Las Vegas Boulevard, without interruption to water service or aboveground traffic. The city is already known for its efforts to conserve water and has reached one of the lowest rates of water loss in the country at 5-6%; implementation of the EchoShore-TX technology serves to strengthen its mission to bring water loss as close to zero as possible.
"This kind of advanced technology opens up a whole new world for water utilities," says David Johnson, LVVWD deputy general manager. "It gives us a new set of eyes and ears within our underground water distribution network, enables us to fully optimize the life cycles of our pipelines and helps us become more fiscally responsible."
Once detected, pipeline water leaks should be addressed and repaired to prevent further water from escaping infrastructure systems, particularly those in areas hit hard by drought. There are a variety of technologies available to repair leaks, depending on their location within the system and their size. According to the EPA, the most significant portion of leak repair cost and time is due to the work involved in uncovering pipelines and dewatering sites. Because of this, the optimum solution for leak repair requires minimal disruption to pipeline locations.
One common approach is the repair clamp, which is a collar that can be fitted around the outside of the pipe. The clamp patches over the hole or break with a gasket that is compressed onto the surface of the pipe, providing a pressure-tight fitting to contain the leak. Mike Lent, superintendent for the Apple Valley Ranchos Water Company, discussed his use of Mueller's pipe repair products:
Mike Lent: We're a large system that covers 59 square miles and has almost 20,000 service connections, serving 65,000 people in Apple Valley, CA. Because of our elevation changes we have 16 different pressure zones, so we're serviced by tanks, wells, booster pumps and mostly gravity feed.
Lent: We've used them for small service line leaks, from ¾-in. PE pipe all the way up to 12-in. welded steel pipes, and they seem to make it easier for us to fix the leak under pressure. With the age of our system we don't like to shut the water mains down, so just about everything we do is live. It helps us get the leak repaired in a cost-efficient, timely and also safe manner.
Lent: The ease of use, and they have so many applications that we try to stock everything that we might need. If we don't have it, our distributor will have it for us the next day. We use everything from a 3-in. clamp all the way up to a 30-in. clamp for our bigger pipes.
Lent: It's made it that much more cost effective to get the water leaks repaired and get them repaired in a timely fashion, and when you have customers standing there looking over your repairs, it makes it easier to have the right product for the job.
|Pipe Couplings
|Unrestrained couplings connect any two pieces of pipe of similar size without disassembly.
|Repair Clamps
|Stainless steel clamps repair holes, leaks, splits, circumferential breaks and cracks, as well as correct pulled or leaking service connections.
Click the Registration button below to select the drought response topics that interest your team, and a Mueller Water Products expert will contact you to confirm the details.
Pressure management throughout the distribution system is vital for maintaining system reliability. Fluctuations in pressure can negatively impact the physical integrity of pipes. A loss of pressure can result in groundwater contamination, while surges can create leaks and main breaks, all of which have a dramatic impact on the life of the infrastructure. By continuously monitoring pressure throughout the system, utilities in drought-stricken locations can be proactive by completing repairs or replacements before damage and water loss become costly.
A November 2014 survey conducted by American Water revealed major gaps in the actions utilities have taken to address pressure. Of the 36 utilities surveyed, most had minimum-pressure requirements in place, but 56% had no maximum-pressure requirements. Sixty-seven percent of systems surveyed did not manage peak pressures, and only 13% conducted pressure monitoring at critical locations.
Many utilities only employ continuous monitoring at the distribution inlets and outlets, with limited monitoring in between. Of the systems surveyed in the American Water study, the most common areas for monitoring include pump stations, pressure-reducing valve stations, water production facilities and storage tanks—all utility-owned locations. Without systemwide pressure monitoring in between, it is difficult to pinpoint problem areas where leaks or pipe bursts could potentially occur.
Remote wireless pressure monitoring is the ideal solution and helps a utility continually monitor pressure and prevent unnecessary water loss, repairs or service interruptions. These systems typically consist of a sensor to collect and analyze data; a remote server for data acquisition and analysis; a browser interface to allow user interaction; and a method of transmitting and receiving wireless data. The systems are also integrated with existing network infrastructure and generally allow for customizable pressure and condition alerts for personnel.
By monitoring actual pressures throughout the entire distribution system, utilities can analyze pump operations and better manage water quality while reducing operations and maintenance costs. Through continuous monitoring, contamination, leaks and main breaks can all be minimized or avoided, decreasing non-revenue water loss and aiding a utility in its water conservation efforts.
The Mueller™ remote pressure monitoring system helps utilities reduce water main breaks and customer complaints by monitoring pressure throughout the distribution system. The system can be deployed virtually anywhere in a network, by either saddle or direct tap into the distribution main or at the meter vault.
The system features a remote telemetry unit with optional lock; lightweight composite valve box; sensor transducer rated at 250 or 300 psi; low-lead ball valve; and bronze service saddle. The system also includes a five-year battery and one year of cellular service with a renewable annual contract.
A designated system administrator will receive credentials to log into the secure Web portal to view data from all deployed pressure sensor devices. Captured data and high- and low-pressure alerts can be transmitted to a smartphone, desktop computer or SCADA system via cellular communication.
As part of a distribution system maintenance program, hydrant flushing is the traditional method for clearing water lines and ensuring water quality. Typically performed annually, the process utilizes thousands of gallons of water per flush, resulting in non-revenue water loss for the sake of maintenance. In areas of drought, this water is a scarce resource and flushing makes conservation difficult.
In Birmingham, AL, routine flushing combined with resident complaints about poor water quality and the city's difficulty maintaining the required chlorine residual resulted in the city performing frequent flushing. In some cases, flush points would run for hours at a time, leading to a significant loss of non-revenue water. Furthermore, drought conditions caused the city to restrict routine flushing to save water, which made maintaining the chlorine residual even more difficult.
To meet these challenges, the city installed nearly 90 automated flushing units, which helped reduce water loss, man-hours and costs, while meeting chlorine residual requirements. Mac Underwood, general manager of the Birmingham Water Works Board, spoke about the experience:
Mac Underwood: Birmingham is located at the foothills of the Appalachian Mountains and we have a total of 28 different gradients that we have to serve in a hilly area. We have a lot of flushing points and a lot of high-pressure zones, so we were looking to slow down or control water loss.
Underwood: We went through an evaluation process back in 2004 and were looking for some automatic flushing units. We chose the Hydro-Guard® HG-2 unit.
Underwood: Underwood: The Hydro-Guard units have helped us reduce our costs by about $2,500 per unit; we have nearly 100 units installed. Those units are able to turn on in the middle of the night and flush for a certain period of time. It helps control chlorine residual and disinfectant byproducts, so we think the units work really well for us. In total we save about $2,500 per unit per year. That ends up being somewhere close to about $300,000 savings on an annual basis.
Underwood: Our water loss, at one point, was really high and with using the Hydro-Guard units and some additional metering for fire hydrant use, we've been able to cut that in half. It's at about 12% right now; at one point it was up to about 28%. With Hydro-Guard and metering the fire hydrants, we've been able to reduce our water loss significantly.
The Hydro-Guard HG-6 hydrant automatic flushing system allows for automatic and programmable flushing of a water distribution system wherever a fire hydrant is available. The system monitors water quality in distribution piping and automatically initiates flushing as necessary to help a municipality maintain water quality and meet required disinfectant residual levels. The portable and adjustable system can be connected to the hose nozzle of any brand of hydrant.
Maintaining hydrant integrity is vital to protecting a distribution system from vandalism and water theft, as well as unintentional damage from traffic accidents. These incidents lead to massive amounts of water lost in short periods of time. The effects are felt especially hard in areas of drought
Keeping a hydrant secure can mean protecting water assets from a number of variables. Security is compromised when vandals or thieves attempt to break into a hydrant to cause intentional damage or steal water. While these acts can be major monetary losses to utilities, the water taken from the hydrants is equally valuable. An unsecure hydrant can also be an access point for someone seeking to contaminate the public water supply. Defending these assets is vital, as the city of Bozeman, MT, learned.
In the winter of 2003, the city faced an act of vandalism that led to more than 3 million gallons of lost water over a three-day period. The vandals improperly opened 13 hydrants, leading to costly damage throughout the city in addition to the enormous water loss. It took the city more than a week to regain the lost water.
After the incident, the city acted by installing Mueller® Hydrant-Defender® security devices in vulnerable areas of town. Soon after, the devices became part of the city's standard specifications. Today, when someone buys a fire hydrant to place into the city's distribution system, the Hydrant-Defender is included as part of the package. John Alston, operations superintendent for the city of Bozeman, said that since installing the devices, the city has not experienced any measurable water loss from hydrant tampering.
Occasionally hydrant water loss occurs not from an intentional act but as a result of a traffic accident. In Southern California, where drought runs rampant, these accidents can waste enormous quantities of valuable water in a short period of time. In one hit-and-run incident in Sand City, CA, a car backed over a hydrant, causing a 40-ft geyser of water to shoot in the air for more than an hour. Not only did the accident lead to thousands of gallons of lost water, it also flooded neighborhood businesses and prompted area evacuations due to electrocution concerns.
When struck by a vehicle, unprotected wet barrel fire hydrants—commonly found in warm, drought-prone climates—will break, creating a geyser. Response time by emergency personnel can vary, but with the speed at which this water is lost, every second counts. By installing a device such as Jones Tell-Tail break-off check valves onto these wet barrel hydrants, municipalities still can be visually alerted of breaks while minimizing water loss.
Protecting hydrants from these potentially devastating events can save a municipality thousands of dollars and countless gallons of water—both valuable resources in today's water climate.
The Hydrant-Defender security device provides protection to hydrants at two levels. The heavy stainless steel straps prevent unauthorized access to the nozzles and operating nut and offer visible evidence of tampering. When the device is securely locked, the nozzles and operating nut can only be accessed by cutting through the heavy straps or barrel lock. In case of emergency, fire personnel can quickly and easily remove the straps and access the hydrant. The recommended stainless steel barrel lock features keys that are uniquely coded for the purchaser.
Jones Tell-Tail break-off check valves are designed to minimize water loss associated with vehicular traffic accidents. When a hydrant is hit, the safety flange breaks, releasing the hydrant from the check valve. The hydrant and adapter plate are released from the lower barrel and the check valve closes, releasing only a small, vertical stream of water to indicate that the hydrant has been damaged, but not enough water to lead to a substantial loss.
During a drought, emphasis on water conservation is at a high. While utilities aim to reduce non-revenue water, customers are encouraged to use less billed water. Additional expenses—such as the energy required to pump water to these water-scarce regions, as well as regular infrastructure maintenance—can add up, leading to an overall loss of revenue.
To combat this issue, utilities should analyze their capital improvement programs (CIP) to identify areas in which spending cuts can be made. Performing a pipeline condition assessment can help determine whether pipe rehabilitation or replacement projects are necessary. Deferring or canceling these projects can help a utility cope with a revenue shortfall in a time of drought.
John Marciszewski, director of business development for Echologics, explained the pipeline condition assessment process and how it benefits the utility's infrastructure, as well as its bottom line:
John Marciszewski: The goal of condition assessment is to help utilities (owners) make more informed decisions about pipeline renewal decisions. Condition assessment data helps utilities to target their capital more effectively and mitigate risks of failure, particularly for critical pipelines.
Marciszewski: New Jersey American Water, for example, explored a number of rehabilitation technologies for their cast iron pipes, and found their suitability was predicated on the structural condition of the host pipe and other factors. They used acoustic wall thickness testing, and associated remaining service life data, to determine whether pipeline renewal is best served by replacement, structural lining, semi-structural lining or non-structural (cement mortar) lining. New Jersey American Water saved 23% on their first pilot project using this approach, and have since continued the program into multiple other communities.
Tacoma Water has more than 110 miles of asbestos cement (AC) pipe within its water system. As part of the Dumas Bay replacement project, Tacoma Water planned to replace 6,000 linear ft of AC pipe at an estimated cost of $1.4 million. The utility needed a means to assess the condition of this pipe and determine how much life was left in it. The utility chose the Echologics ePulse® acoustic condition assessment technology to perform this analysis. After performing the assessment, it was discovered that only 1,933 linear ft of pipe needed to be replaced, at a cost of $625,000.
"Echologics provided a quick, noninvasive technique to assess the condition of the pipe [and] understanding how much effective wall thickness we had left in our pipe," says Ryan Flynn, senior principal engineer for Tacoma Water. "Then we were able to insert that information into our economic model and assess the remaining life and understand the condition and overall priority of main segments in our system."
Overall, the utility has had three contracts with Echologics, assessing a total of 45 miles of AC and cast iron pipe throughout its system.
"As a manager of your assets it gives you greater peace of mind, that you're not replacing mains before they actually need to be replaced," Flynn said. "You're preserving that value that your ratepayers have paid for, and really mining that value out of the existing assets."
Broken water mains, water loss and property damage—why let a preventable problem cost large sums of money and damage your reputation?
While it often starts with a leak, historically many utilities have waited until there is an evident problem or rupture to react. Today's utilities have a cost-effective and easy-to-deploy monitoring option.
Imagine being immediately notified about a problem in a transmission main. The EchoShore®-TX platform will call, text or email you promptly after detecting a leak or anomaly.
Through monitoring and notification, your response time can be significantly reduced to help mitigate the risk and cost of operating critical transmission mains.
The EchoShore-TX platform provides a high level of operation insight and can simultaneously monitor several parameters including:


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Friendships, Winners Abound For Marty Garey
Thursday, February 10, 2011 - by Mark Ratzky, Publicity -- Cal Expo
Marty Garey has been a fan of the trotters and pacers since he was a
teenager in his native New York, joining the ranks of owner as part of a
partnership in 1977, some two years after moving to California.
While he has campaigned some very nice horses, including California champion Knead To Shine with Wayne Short and the current sharp customer Ivegotwhatuneed with trainer and co-owner Bob Johnson, he relates that it's the lasting friendships he's established in the game that provide the most satisfaction.
"It started out with a few friends that I had made out here who were also fans and we pooled our money to claim a horse," Garey explained. "Through Alan Horowitz, we were introduced to trainer Jack Olsen and claimed a mare named Prairie Sunshine, and she ended up winning enough to cover her training bills.
"When her racing days were over, Prairie Sunshine became a broodmare and her second foal was Knead To Shine. He was the California 3-year-old of the year in 1986, and I remember Annette Funicello was in the audience at the ceremony, because she was married to trainer Glen Holt. Knead To Shine won over $300,000 and also went back East at one point and won at Yonkers and Freehold at a class just below the Open."
Fast forward some 25 years and Garey has his name listed under three performers.
"One of the my original partners I started out with in 1977, Hank Wieseneck, remains my good friend and we're partners on Myra's Hi Ho and Giles L S Hanover, and I also own Ivegotwhatuneed with Bob Johnson, who trains all three.
"Over the years, Hank and I and in some cases a few other friends and partners have also had horses at various times with Jack and Ruth Olsen, Wayne and Diane Short, Jim Lackey, Rick Plano, Bob Ritchie, Carolyn Lyons, Walter Bickford and Bob Wiley. Many have become good and long-standing friends."
Garey has high praise for current conditioner Johnson.
"I had known Bob to be one of the top trainers for a long time, but didn't have any horses with him until the last few years when I became partners in a few horses with David Neumeister. I've come to know Bob as a man of unquestioned honesty, integrity and work ethic.
"What actually sets Bob apart for me from trainers I've had on either coast is his skill at communication. Living 400 miles from Sacramento, but liking to stay closely involved and sometimes just talk horses as much as I do, a trainer that is easy to communicate with is very important. Bob answers the phone when I call, returns messages when I miss him, and calls himself to keep me informed and discuss things that are happening."
One other important friendship that Marty wants to acknowledge is the one he has with Cal Expo track announcer Scott Ehrlich.
"Scott is an outstanding announcer, and soon after he came to California, we were introduced by a mutual friend and we've been close friends ever since."
It must be nice to have a friend calling your horse down the stretch, especially when that one has it's mojo working.
Cal Expo Featured Pace On Saturday Brings Out Ivegotwhatuneed
Ivegotwhatuneed, coming off three bang-up efforts resulting in two wins and a game second, is the one to beat at Cal Expo in Saturday night's (February 12) $4,500 main event for the pacers.
An 8-year-old son of Givemewhatineed, Ivegotwhatuneed goes about his business for Marty Garey and Bob Johnson, with Johnson the conditioner and Lemoyne Svendsen in his usual position in the sulky. He has $255,000 in his bank account and a 1:52 career standard that was established two years ago.
The dark-hued performer was a 10-1 upsetter at this level on January 22, riding live cover to a half-length score in 1:54.3, then proved clearly best at 9-5 the following week over a sloppy track. He carved out all the fractions last time, but was unable to contain the pocket-sitting Haggin Oaks that evening.
Cycle Power was an eye-catching winner over these in coast-to-coast fashion last month, but has been a beaten favorite in his last three trips to the post while recording two thirds and a fourth. Nathalie Tremblay owns and trains the Cambest offspring with Steve Wiseman at the controls. He could easily apologize this time around.
Biggest Big Bertha (Rick Plano) and Red Star Ruffles (Jim Lackey) represent the mares in the cast; Nittany Linebacker has Rich Wojcio and is always dangerous with his best mile; and ML Jackhammer rounds out the field from the inside with Tim Maier giving directions.
Live racing resumes at Cal Expo on Thursday (February 10) and continues through Saturday (February 12). Post-time on Thursday is 5:30 p.m. (PST). Post-Time on Friday (February 11) & Saturday is at 6:00 p.m. On Thursday and every live card, Cal Expo offers free admission, as well as free preferred & general parking after 4:30 p.m. Also on Thursday night from 6:00 p.m. to 8:30 p.m., Cal Expo offers a complete Lasagna dinner, which includes salad and bread, for just $3.00. Additionally on Thursday, beer & wine can be purchased for $3.00 each as well.
On Saturdays, Cal Expo offers a reduced 15 percent takeout rate on both the Early & Late Pick-4 wagers with both Pick-4's having a $10,000 gross guaranteed pool. Additionally, on Saturdays, for winning wagers made on the Late Pick 4 online at TwinSpires.com or on track at Cal Expo, a bonus payout of 17.65 percent of the gross Late Pick 4 mutuel payoff will be paid.


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Federico Iovino, Disa L. Hammarlöf, Genevieve Garriss, Sarah Brovall, Priyanka Nannapaneni, Birgitta Henriques-Normark
Nitric oxide (NO) production is critical for the host defense against intracellular pathogens; however, it is unclear whether NO-dependent control of intracellular organisms depends on cell-intrinsic or cell-extrinsic activity of NO. For example, NO production by infected phagocytes may enable these cells to individually control their pathogen burden. Alternatively, the ability of NO to diffuse across cell membranes might be critical for infection control. Here, using a murine ear infection model, we found that, during infection with the intracellular parasite
Romain Olekhnovitch, Bernhard Ryffel, Andreas J. Müller, Philippe Bousso
Development of host protective immunity against
Roanne Keeton, Nasiema Allie, Ivy Dambuza, Brian Abel, Nai-Jen Hsu, Boipelo Sebesho, Philippa Randall, Patricia Burger, Elizabeth Fick, Valerie F.J. Quesniaux, Bernhard Ryffel, Muazzam Jacobs
An enigmatic feature of Lyme disease is the slow resolution of musculoskeletal symptoms that can continue after treatment, with some patients developing an inflammatory arthritis that becomes refractory to antibiotic therapy. Using intravital microscopy and the mouse model of Lyme borreliosis, we observed that Borrelia burgdorferi antigens, but not infectious spirochetes, can remain adjacent to cartilage for extended periods after antibiotic treatment. B. burgdorferi was not recovered by culture or xenodiagnosis with ticks after antibiotic treatment of WT mice and all but one of the immunodeficient mice with heightened pathogen burden due to impaired TLR responsiveness. Amorphous GFP+ deposits were visualized by intravital microscopy in the entheses of antibiotic-treated mice infected with GFP-expressing spirochetes and on the ear cartilage surface in sites where immunofluorescence staining detected spirochete antigens. Naive mice were not infected by tissue transplants from antibiotic-treated mice even though transplants contained spirochete DNA. Tissue homogenates from antibiotic-treated mice induced IgG reactive with B. burgdorferi antigens after immunization of naive mice and stimulated TNF-α production from macrophages in vitro. This is the first direct demonstration that inflammatory B. burgdorferi components can persist near cartilaginous tissue after treatment for Lyme disease. We propose that these deposits could contribute to the development of antibiotic-refractory Lyme arthritis.
Linda K. Bockenstedt, David G. Gonzalez, Ann M. Haberman, Alexia A. Belperron
Biofilms are surface-attached agglomerations of microorganisms embedded in an extracellular matrix. Biofilm-associated infections are difficult to eradicate and represent a significant reservoir for disseminating and recurring serious infections. Infections involving biofilms frequently develop on indwelling medical devices in hospitalized patients, and Staphylococcus epidermidis is the leading cause of infection in this setting. However, the molecular determinants of biofilm dissemination are unknown. Here we have demonstrated that specific secreted, surfactant-like S. epidermidis peptides — the β subclass of phenol-soluble modulins (PSMs) — promote S. epidermidis biofilm structuring and detachment in vitro and dissemination from colonized catheters in a mouse model of device-related infection. Our study establishes in vivo significance of biofilm detachment mechanisms for the systemic spread of biofilm-associated infection and identifies the effectors of biofilm maturation and detachment in a premier biofilm-forming pathogen. Furthermore, by demonstrating that antibodies against PSMβ peptides inhibited bacterial spread from indwelling medical devices, we have provided proof of principle that interfering with biofilm detachment mechanisms may prevent dissemination of biofilm-associated infection.
Rong Wang, Burhan A. Khan, Gordon Y. C. Cheung, Thanh-Huy L. Bach, Max Jameson-Lee, Kok-Fai Kong, Shu Y. Queck, Michael Otto
Sickle cell disease (SCD) is characterized by intravascular hemolysis and inflammation coupled to a 400-fold greater incidence of invasive pneumococcal infection resulting in fulminant, lethal pneumococcal sepsis. Mechanistically, invasive infection is facilitated by a proinflammatory state that enhances receptor-mediated endocytosis of pneumococci into epithelial and endothelial cells. As statins reduce chronic inflammation, in addition to their serum cholesterol-lowering effects, we hypothesized that statin therapy might improve the outcome of pneumococcal infection in SCD. In this study, we tested this hypothesis in an experimental SCD mouse model and found that statin therapy prolonged survival following pneumococcal challenge. The protective effect resulted in part from decreased platelet-activating factor receptor expression on endothelia and epithelia, which led to reduced bacterial invasion. An additional protective effect resulted from inhibition of host cell lysis by pneumococcal cholesterol-dependent cytotoxins (CDCs), including pneumolysin. We conclude therefore that statins may be of prophylactic benefit against invasive pneumococcal disease in patients with SCD and, more broadly, in settings of bacterial pathogenesis driven by receptor-mediated endocytosis and the CDC class of toxins produced by Gram-positive invasive bacteria.
Jason W. Rosch, Angela R. Boyd, Ernesto Hinojosa, Tamara Pestina, Yunming Hu, Derek A. Persons, Carlos J. Orihuela, Elaine I. Tuomanen
Intracellular pathogens survive by evading the host immune system and accessing host metabolic pathways to obtain nutrients for their growth. Mycobacterium leprae, the causative agent of leprosy, is thought to be the mycobacterium most dependent on host metabolic pathways, including host-derived lipids. Although fatty acids and phospholipids accumulate in the lesions of individuals with the lepromatous (also known as disseminated) form of human leprosy (L-lep), the origin and significance of these lipids remains unclear. Here we show that in human L-lep lesions, there was preferential expression of host lipid metabolism genes, including a group of phospholipases, and that these genes were virtually absent from the mycobacterial genome. Host-derived oxidized phospholipids were detected in macrophages within L-lep lesions, and 1 specific oxidized phospholipid, 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphorylcholine (PEIPC), accumulated in macrophages infected with live mycobacteria. Mycobacterial infection and host-derived oxidized phospholipids both inhibited innate immune responses, and this inhibition was reversed by the addition of normal HDL, a scavenger of oxidized phospholipids, but not by HDL from patients with L-lep. The accumulation of host-derived oxidized phospholipids in L-lep lesions is strikingly similar to observations in atherosclerosis, which suggests that the link between host lipid metabolism and innate immunity contributes to the pathogenesis of both microbial infection and metabolic disease.
Daniel Cruz, Andrew D. Watson, Christopher S. Miller, Dennis Montoya, Maria-Teresa Ochoa, Peter A. Sieling, Miguel A. Gutierrez, Mohamad Navab, Srinivasa T. Reddy, Joseph L. Witztum, Alan M. Fogelman, Thomas H. Rea, David Eisenberg, Judith Berliner, Robert L. Modlin
Candida parapsilosis is a major cause of human disease, yet little is known about the pathogen's virulence. We have developed an efficient gene deletion system for C. parapsilosis based on the repeated use of the dominant nourseothricin resistance marker (caSAT1) and its subsequent deletion by FLP-mediated, site-specific recombination. Using this technique, we deleted the lipase locus in the C. parapsilosis genome consisting of adjacent genes CpLIP1 and CpLIP2. Additionally we reconstructed the CpLIP2 gene, which restored lipase activity. Lipolytic activity was absent in the null mutants, whereas the WT, heterozygous, and reconstructed mutants showed similar lipase production. Biofilm formation was inhibited with lipase-negative mutants and their growth was significantly reduced in lipid-rich media. The knockout mutants were more efficiently ingested and killed by J774.16 and RAW 264.7 macrophage-like cells. Additionally, the lipase-negative mutants were significantly less virulent in infection models that involve inoculation of reconstituted human oral epithelium or murine intraperitoneal challenge. These studies represent what we believe to be the first targeted disruption of a gene in C. parapsilosis and show that C. parapsilosis–secreted lipase is involved in disease pathogenesis. This efficient system for targeted gene deletion holds great promise for rapidly enhancing our knowledge of the biology and virulence of this increasingly common invasive fungal pathogen.
Attila Gácser, David Trofa, Wilhelm Schäfer, Joshua D. Nosanchuk
Mucormycosis causes mortality in at least 50% of cases despite current first-line therapies. Clinical and animal data indicate that the presence of elevated available serum iron predisposes the host to mucormycosis. Here we demonstrate that deferasirox, an iron chelator recently approved for use in humans by the US FDA, is a highly effective treatment for mucormycosis. Deferasirox effectively chelated iron from Rhizopus oryzae and demonstrated cidal activity in vitro against 28 of 29 clinical isolates of Mucorales at concentrations well below clinically achievable serum levels. When administered to diabetic ketoacidotic or neutropenic mice with mucormycosis, deferasirox significantly improved survival and decreased tissue fungal burden, with an efficacy similar to that of liposomal amphotericin B. Deferasirox treatment also enhanced the host inflammatory response to mucormycosis. Most importantly, deferasirox synergistically improved survival and reduced tissue fungal burden when combined with liposomal amphotericin B. These data support clinical investigation of adjunctive deferasirox therapy to improve the poor outcomes of mucormycosis with current therapy. As iron availability is integral to the pathogenesis of other infections (e.g., tuberculosis, malaria), broader investigation of deferasirox as an antiinfective treatment is warranted.
Ashraf S. Ibrahim, Teclegiorgis Gebermariam, Yue Fu, Lin Lin,, Mohamed I. Husseiny, Samuel W. French, Julie Schwartz, Christopher D. Skory, John E. Edwards Jr., Brad J. Spellberg
Philipp C. Rittershaus, Talar B. Kechichian, Jeremy C. Allegood, Alfred H. Merrill, Mirko Hennig, Chiara Luberto, Maurizio Del Poeta
The study of regulatory networks in human pathogens such as Cryptococcus neoformans provides insights into host-pathogen interactions that may allow for correlation of gene expression patterns with clinical outcomes. In the present study, deletion of the cryptococcal copper-dependent transcription factor 1 (Cuf1) led to defects in growth and virulence factor expression in low copper conditions. In mouse models, cuf1Δ strains exhibited reduced dissemination to the brain, but no change in lung growth, suggesting copper is limiting in neurologic infections. To examine this further, a biologic probe of available copper was constructed using the cryptococcal CUF1-dependent copper transporter, CTR4. Fungal cells demonstrated high CTR4 expression levels after phagocytosis by macrophage-like J774.16 cells and during infection of mouse brains, but not lungs, consistent with limited copper availability during neurologic infection. This was extended to human brain infections by demonstrating CTR4 expression during C. neoformans infection of an AIDS patient. Moreover, high CTR4 expression by cryptococcal strains from 24 solid organ transplant patients was associated with dissemination to the CNS. Our results suggest that copper acquisition plays a central role in fungal pathogenesis during neurologic infection and that measurement of stable traits such as CTR4 expression may be useful for risk stratification of individuals with cryptococcosis.
Scott R. Waterman, Moshe Hacham, Guowu Hu, Xudong Zhu, Yoon-Dong Park, Soowan Shin, John Panepinto, Tibor Valyi-Nagy, Craig Beam, Shahid Husain, Nina Singh, Peter R. Williamson
Pseudomonas aeruginosa, an important cause of opportunistic infections in humans, delivers bacterial cytotoxins by type III secretion directly into the host cell cytoplasm, resulting in disruption of host cell signaling and host innate immunity. However, little is known about the fate of the toxins themselves following injection into the host cytosol. Here, we show by both in vitro and in vivo studies that the host ubiquitin ligase Cbl-b interacts with the type III–secreted effector exotoxin T (ExoT) and plays a key role in vivo in limiting bacterial dissemination mediated by ExoT. We demonstrate that, following polyubiquitination, ExoT undergoes regulated proteasomal degradation in the host cell cytosol. ExoT interacts with the E3 ubiquitin ligase Cbl-b and Crk, the substrate for the ExoT ADP ribosyltransferase (ADPRT) domain. The efficiency of degradation is dependent upon the activity of the ADPRT domain. In mouse models of acute pneumonia and systemic infection, Cbl-b is specifically required to limit the dissemination of ExoT-producing bacteria whereas c-Cbl plays no detectable role. To the best of our knowledge, this represents the first identification of a mammalian gene product that is specifically required for in vivo resistance to disease mediated by a type III–secreted effector.
Priya Balachandran, Leonard Dragone, Lynne Garrity-Ryan, Armando Lemus, Arthur Weiss, Joanne Engel
Enteropathogenic E. coli (EPEC) is a major cause of infantile diarrhea, but the pathophysiology underlying associated diarrhea is poorly understood. We examined the role of the luminal membrane Cl–/OH– exchange process in EPEC pathogenesis using in vitro and in vivo models. Cl–/OH– exchange activity was measured as OH– gradient–driven 36Cl– uptake. EPEC infection (60 minutes–3 hours) inhibited apical Cl–/OH– exchange activity in human intestinal Caco-2 and T84 cells. This effect was dependent upon the bacterial type III secretory system (TTSS) and involved secreted effector molecules EspG and EspG2, known to disrupt the host microtubular network. The microtubule-disrupting agent colchicine (100 μM, 3 hours) also inhibited 36Cl– uptake. The plasma membrane expression of major apical anion exchanger DRA (SLC26A3) was considerably reduced in EPEC-infected cells, corresponding with decreased Cl–/OH– exchange activity. Confocal microscopic studies showed that EPEC infection caused a marked redistribution of DRA from the apical membrane to intracellular compartments. Interestingly, infection of cells with an EPEC mutant deficient in espG significantly attenuated the decrease in surface expression of DRA protein as compared with treatment with wild-type EPEC. EPEC infection in vivo (1 day) also caused marked redistribution of surface DRA protein in the mouse colon. Our data demonstrate that EspG and EspG2 play an important role in contributing to EPEC infection–associated inhibition of luminal membrane chloride transport via modulation of surface DRA expression.
Ravinder K. Gill, Alip Borthakur, Kim Hodges, Jerrold R. Turner, Daniel R. Clayburgh, Seema Saksena, Ayesha Zaheer, Krishnamurthy Ramaswamy, Gail Hecht, Pradeep K. Dudeja
Grace Soong, Amanda Muir, Marisa I. Gomez, Jonathan Waks, Bharat Reddy, Paul Planet, Pradeep K. Singh, Yukihiro Kanetko, Matthew C. Wolfgang, Yu-Shan Hsiao, Liang Tong, Alice Prince
Increasing multidrug resistance in Enterococcus faecalis, a nosocomial opportunist and common cause of bacterial endocarditis, emphasizes the need for alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In an earlier study, we demonstrated the presence of antibodies in E. faecalis endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall–anchored proteins; of these, we have now characterized an in vivo–expressed locus of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using mutation analyses and complementation, we demonstrated that both the ebp (encoding endocarditis and biofilm-associated pili) operon and srtC are important for biofilm production of E. faecalis strain OG1RF. In addition, immunogold electron microscopy using antisera against EbpA–EbpC proteins as well as patient serum demonstrated that E. faecalis produces pleomorphic surface pili. Assembly of pili and their cell wall attachment appeared to occur via a mechanism of cross-linking of the Ebp proteins by the designated SrtC. Importantly, a nonpiliated, allelic replacement mutant was significantly attenuated in an endocarditis model. These biologically important surface pili, which are antigenic in humans during endocarditis and encoded by a ubiquitous E. faecalis operon, may be a useful immunotarget for studies aimed at prevention and/or treatment of this pathogen.
Sreedhar R. Nallapareddy, Kavindra V. Singh, Jouko Sillanpää, Danielle A. Garsin, Magnus Höök, Stanley L. Erlandsen, Barbara E. Murray
Many respiratory pathogens, including Hemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa, express neuraminidases that can cleave α2,3-linked sialic acids from glycoconjugates. As mucosal surfaces are heavily sialylated, neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors. However, in contrast to neuraminidase produced by the influenza virus, a role for bacterial neuraminidase in pathogenesis has not yet been clearly established. We constructed a mutant of P. aeruginosa PAO1 by deleting the PA2794 neuraminidase locus (Δ2794) and tested its virulence and immunostimulatory capabilities in a mouse model of infection. Although fully virulent when introduced i.p., the Δ2794 mutant was unable to establish respiratory infection by i.n. inoculation. The inability to colonize the respiratory tract correlated with diminished production of biofilm, as assessed by scanning electron microscopy and in vitro assays. The importance of neuraminidase in biofilm production was further demonstrated by showing that viral neuraminidase inhibitors in clinical use blocked P. aeruginosa biofilm production in vitro as well. The P. aeruginosa neuraminidase has a key role in the initial stages of pulmonary infection by targeting bacterial glycoconjugates and contributing to the formation of biofilm. Inhibiting bacterial neuraminidases could provide a novel mechanism to prevent bacterial pneumonia.
Grace Soong, Amanda Muir, Marisa I. Gomez, Jonathan Waks, Bharat Reddy, Paul Planet, Pradeep K. Singh, Yukihiro Kanetko, Matthew C. Wolfgang, Yu-Shan Hsiao, Liang Tong, Alice Prince
The fungal pathogen Candida albicans has a multilayered cell wall composed of an outer layer of proteins glycosylated with N- or O-linked mannosyl residues and an inner skeletal layer of β-glucans and chitin. We demonstrate that cytokine production by human mononuclear cells or murine macrophages was markedly reduced when stimulated by C. albicans mutants defective in mannosylation. Recognition of mannosyl residues was mediated by mannose receptor binding to N-linked mannosyl residues and by TLR4 binding to O-linked mannosyl residues. Residual cytokine production was mediated by recognition of β-glucan by the dectin-1/TLR2 receptor complex. C. albicans mutants with a cell wall defective in mannosyl residues were less virulent in experimental disseminated candidiasis and elicited reduced cytokine production in vivo. We concluded that recognition of C. albicans by monocytes/macrophages is mediated by 3 recognition systems of differing importance, each of which senses specific layers of the C. albicans cell wall.
Mihai G. Netea, Neil A.R. Gow, Carol A. Munro, Steven Bates, Claire Collins, Gerben Ferwerda, Richard P. Hobson, Gwyneth Bertram, H. Bleddyn Hughes, Trees Jansen, Liesbeth Jacobs, Ed T. Buurman, Karlijn Gijzen, David L. Williams, Ruurd Torensma, Alistair McKinnon, Donna M. MacCallum, Frank C. Odds, Jos W.M. Van der Meer, Alistair J.P. Brown, Bart Jan Kullberg
Recent studies have shown that fine structural modifications of Mycobacterium tuberculosis cell envelope lipids mediate host cell immune activation during infection. One such alteration in lipid structure is cis-cyclopropane modification of the mycolic acids on trehalose dimycolate (TDM) mediated by proximal cyclopropane synthase of α mycolates (pcaA), a proinflammatory lipid modification during early infection. Here we examine the pathogenetic role and immunomodulatory function of mycolic acid cyclopropane stereochemistry by characterizing an M. tuberculosis cyclopropane–mycolic acid synthase 2 (cmaA2) null mutant (ΔcmaA2) that lacks trans-cyclopropanation of mycolic acids. Although titers of WT and ΔcmaA2 organisms were identical during mouse infection, ΔcmaA2 bacteria were hypervirulent while inducing larger granulomas than WT M. tuberculosis. The hypervirulence of the ΔcmaA2 strain depended on host TNF-α and IFN-γ. Loss of trans-cyclopropanation enhanced M. tuberculosis–induced macrophage inflammatory responses, a phenotype that was transferable with petroleum ether extractable lipids. Finally, purified TDM lacking trans-cyclopropane rings was 5-fold more potent in stimulating macrophages. These results establish cmaA2-dependent trans-cyclopropanation of TDM as a suppressor of M. tuberculosis–induced inflammation and virulence. In addition, cyclopropane stereochemistries on mycolic acids interact directly with host cells to both positively and negatively influence host innate immune activation.
Vivek Rao, Feng Gao, Bing Chen, William R. Jacobs, Michael S. Glickman
The pathogenic fungus Cryptococcus neoformans infects humans upon inhalation and causes the most common fungal meningoencephalitis in immunocompromised subjects worldwide. In the host, C. neoformans is found both intracellularly and extracellularly, but how these two components contribute to the development of the disease is largely unknown. Here we show that the glycosphingolipid glucosylceramide (GlcCer), which is present in C. neoformans, was essential for fungal growth in host extracellular environments, such as in alveolar spaces and in the bloodstream, which are characterized by a neutral/alkaline pH, but not in the host intracellular environment, such as in the phagolysosome of macrophages, which is characteristically acidic. Indeed, a C. neoformans mutant strain lacking GlcCer did not grow in vitro at a neutral/alkaline pH, yet it had no growth defect at an acidic pH. The mechanism by which GlcCer regulates alkali tolerance was by allowing the transition of C. neoformans through the cell cycle. This study establishes C. neoformans GlcCer as a key virulence factor of cryptococcal pathogenicity, with important implications for future development of new antifungal strategies.
Philipp C. Rittershaus, Talar B. Kechichian, Jeremy C. Allegood, Alfred H. Merrill, Mirko Hennig, Chiara Luberto, Maurizio Del Poeta
Panton-Valentine leukocidin (PVL) is a pore-forming toxin secreted by Staphylococcus aureus that has recently been associated with necrotizing pneumonia. In the present study, we report that in vitro, PVL induces polymorphonuclear cell death by necrosis or by apoptosis, depending on the PVL concentration. PVL-induced apoptosis was associated with a rapid disruption of mitochondrial homeostasis and activation of caspase-9 and caspase-3, suggesting that PVL-induced apoptosis is preferentially mediated by the mitochondrial pathway. Polymorphonuclear cell exposure to PVL leads to mitochondrial localization of the toxin, whereas Bax, 1 of the 2 essential proapoptotic members of the Bcl-2 family, was still localized in the cytosol. Addition of PVL to isolated mitochondria induced the release of the apoptogenic proteins cytochrome c and Smac/DIABLO. Therefore, we suggest that PVL, which belongs to the pore-forming toxin family, could act at the mitochondrion level by creating pores in the mitochondrial outer membrane. Furthermore, LukS-PV, 1 of the 2 components of PVL, was detected in lung sections of patients with necrotizing pneumonia together with DNA fragmentation, suggesting that PVL induces apoptosis in vivo and thereby is directly involved in the pathophysiology of necrotizing pneumonia.
Anne-Laure Genestier, Marie-Cécile Michallet, Gilles Prévost, Gregory Bellot, Lara Chalabreysse, Simone Peyrol, Françoise Thivolet, Jerome Etienne, Gérard Lina, François M. Vallette, François Vandenesch, Laurent Genestier
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Posts Tagged 'tummy tuck after weight loss'
Exactly what are Some Tummy Tuck Drawbacks?
When hunting into receiving a abdominoplasty treatment www.drshermak.com/procedures/body/tummy-tuck/, it truly is normal to dwell on every one of the approaches the process goes to improve your daily life. You will glimpse incredible as part of your bikini, you might be significantly less self-conscious, you might search such as you did when you have been 18, and you'll blow your spouse absent with how beautiful you seem. Having said that, it's crucial that you spend as much time considering the drawbacks of a tummy tuck when you do the benefits, so as to have got a clear head when building the decision to experience using an elective beauty surgery.
Numerous women of all ages have difficulties getting rid of pounds inside their belly area no matter how a lot of sit-ups they are doing, or how significantly they run, or the amount of days they take in very little but broccoli. Receiving a abdominoplasty is often a brief take care of to obtain the flat, toned stomach you have got been dreaming of due to the fact you had your final child. Having said that, that is definitely particularly just what the tummy tuck process is, a "quick fix". When gals shed weight the previous vogue way, as a result of workout and dieting, they generate a schedule for by themselves; a practice they should stick with day to day to help keep the weight off. On the other hand, when girls (or guys) get yourself a tummy tuck, these are receiving the benefits of month's really worth of exercising and dieting, right away! They skip the action of creating a balanced physical exercise and food plan routine, and infrequently periods this has destructive consequences on their bodies following the operation. You may have to commit by yourself to some healthier life style post-surgery to receive one of the most benefits out of your surgical treatment.
Very first of all, sufferers must adhere to your guidelines presented to them by their surgeon to ensure that their physique has the perfect time to mend effectively. Regardless if clients abide by all of their doctor's directions, issues can occur, like infections. A drawback of your abdominoplasty surgical procedures is the fact that there may be in essence no technique to predict how the body will respond to your operation. The surgery could quite possibly generate intensive scarring, relying on how your whole body reacts and just how you take care of you post-surgery. Moreover, sufferers who've been through, or are considering of going through an abdominoplasty need to do not forget that doing exercises and obtaining a nutritious life-style are important to maintaining the sculpted, toned search which was realized with the tummy tuck.


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Observations From Years of Experience
"A flat-fee arrangement also encourages clients to call us or schedule appointments at our St. George office without worrying about being 'on the clock,' as they might with an attorney."
Eliminating Surprises
We believe that a flat fee for the services provided puts the risk on us, rather than on our clients. It prevents invoice surprises when the amount of work exceeds the estimates that occur with an hourly fee. With our arrangement, we absorb the cost of surprises.
A flat-fee arrangement also encourages clients to call us or schedule appointments at our St. George office without worrying about being "on the clock," as they might with an attorney.
A popular arrangement offered by advisors and planners is taking a percentage of the assets under management. It is our opinion that this is not always an equitable arrangement. At times, a client with more assets may pay substantially more than one with lesser assets, yet the services provided are not commensurate with the amount of the additional fee.
The fee we quote is not based on your net worth. Rather, it is based on the amount of work that we believe is required by our St. George staff to complete your planning process. There might be more work involved with a more substantial estate, but that is not always the case. There are instances where a client with a net worth of $2 million requires more work than another client with a net worth of $3 million.
No Busy Work
At anytime during the Initial Meeting or Data Gathering Interview, if we determine that we are not going to be able to provide you with a substantial improvement in your financial situation, we will bow out of the process and decline to offer a fee quote. We want to enter into engagements only when we can add value for both Utah clients and those located in other states (we are experienced in working with out-of-area clients).


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Early Ford Spindles -- Bolt Patterns
I have a set of early Ford spindles and I pretty much thought the hole pattern for the backing plates was all about the same. The right spindle has two tie rod end holes. I've already made wheel bearing spacers and caliper mounting brackets for GM calipers and rotors for these spindles.
I just bought Chassis Engineering forged steering arms and discover they are a different mounting bolt pattern then my spindles.
Is there information or drawings somewhere to help me determine what I have now and before I buy CE's forged spindles?
1937 to 1948 Ford spindles have the same backing plate pattern. That is the most popular ... and what the CE ones are also.
What year do you think your spindles are ??
early Ford spindles -- bolt pattrens
I think you have a pair of '35 or '36 spindles. Have you cut the steering arms off the spindles? If you haven't, you can heat and reshape the arms. That's the good news. If you've cut the arms off, well I don't know of any after market arms for these spindles. If you've made bearing adapters and caliper mounts, I would think you would be skilled enough to whip up a set of steering arms. You already have half of the figuring done with the arms from CE.
Youngster, you're right.
I can make steering arms.
The other problem I didn't mention is the fact on my spindles - we'll assume they're 35-36 is, there isn't enough room between the axle end and spindle for the bearing.
Looking at this last night with a glass of Chardoney, I think I can mill about .375 off the spindle top king pin lug and a little off the axle end to get the bearing in. I'm not looking forwrd to having to set up the spindles in a mill to cut them. I just don't like milling steelas much as I love milling aluminum. Let the chip fall where they may.
The arms are still on the spindles so I can heat and bend them.
I guess I'll put the Chassis Eng. arms on ebay or look around for some later spindles or step up to a pair of Chassis Eng spindles.
Early Ford Spindles--Bolt Patterns
Doug... The reason there isn't enough room for the bearing is because on the '35 - '36 spindles, the bearing was between the top boss on the spindle and the cup for the brake shaft on the king pin. Personally, I would call Jim at CE and order a pair of spindles to go with the arms you have from them.
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1. Where do I go to get my driver license?
WYDOT has 29 driver license examiner stations around the state.
2. What documents do I need to get my driver license?
Security regulations require documents to verify your identity, residence and Social Security number.
3. Where do I go to get my license plates?
Vehicle registration and license plates are handled by county treasurer offices in Wyoming.
4. Where do I get my vehicle titled?
Vehicle titling is handled by county clerk offices in Wyoming.
5. Where can I find road condition and closure information?
WYDOT's 511 Travel Information Service provides information on road and weather conditions, highway closures and advisories via the Internet and telephone by dialing 511.
6. Where can I find Web camera views of conditions on Wyoming highways?
Web camera views of 148 highway sections can be found on the 511 Travel Information Service site.
7. Why is the highway closed when the Web cameras show good conditions?
Web cameras show conditions on only a small fraction of the highways. Conditions only a few miles away may be completely different and not safe for travel. Wyoming's weather patterns are unique. Localized wind events can stretch for a few miles or tens of miles, and are not always visible from cameras or closure gates. WYDOT's plow drivers are out in that weather, working to open the road as soon as possible. However, when there is zero visibility, continued maintenance efforts become fruitless.
8. Why don't I see any snowplows on the highway?
WYDOT has a Snow Control Priority Plan that determines the hours of service on each highway section in the state. The more traffic a highway carries, the higher priority it is for clearing snow and ice. Some highways that carry very little traffic only get plowed after the busier highways have been cleared.
9. What kinds of chemicals does WYDOT use to clear snow and ice from highways?
A mixture of sand and salt is still the option WYDOT uses most frequently to improve traction on snowy and icy highways. However the department also uses a variety of other chemical treatments whenever conditions indicate they will help traffic move safely. In some cases the sand-salt mixture is sprayed with liquid magnesium chloride or brine to help it stick to the road. Maintenance crews also use brine and beet juice and sometimes a combination of the two to help prevent the formation of ice on the road or help break up ice already on the road.
10. How does WYDOT award contracts for highway construction projects?
The department seeks sealed bids from qualified contractors for completing the needed work. The Wyoming Transportation Commission then awards the contract for the project to the qualified contractor submitting the bid to do the work for the lowest cost.
11. Why does WYDOT award contracts for work on Wyoming highways to contractors from other states?
Federal law requires contracts for work on federally-funded highway projects be awarded to the qualified contractor submitting the bid to complete the work for the lowest price. On state-funded projects, state law allows WYDOT to give Wyoming contractors a 5 percent preference when determining the lowest qualified bidder. In other words, a Wyoming contractor can get the contract, even if its bid is 5 percent higher than the lowest bid from an out-of-state contractor.


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While our jointer planer reviews will help you find the right jointer planer to buy, a review cannot help you understand how to use it safely. Every year there are thousands of people who don't know how to use their tools properly, and they end up getting hurt.
Here are some basic safety tips on using your jointer planer:
Average Customer Rating:
3.25 inch hand planer design that incorporates lightweight components and a powerful 7.5AMP motor that rotates at 16,000 RPM for the closest and deepest levelling. The JET-JPM-13CS can manage up to 5/32 inch deep and 3-14 inch wide cuts in a single pass. Designed to be ergonomic, this hand planer comes with depth adjustment on the handle and a rubberized grip with a front base that together with the rest of the body is made from aluminum housing.
Pros: Long five year warranty, precision assured and dependable construction.
Cons: Expensive and not meant for enthusiastic woodworkers, it is solely for professionals.
Average Customer Rating:
When you get two benefits in one go, isn't it a wonderful feeling? To bring this joy to your woodworking workshop bring the Jet JJP-12 without any delay. A 12 x 55" jointer planer, it is compact and ergonomically designed with a 13amp powerful motor. Switching from one mode to another is extremely easy, sturdily built with easy adjustments and simple mechanisms; the auto lock system takes care of the safety aspect.
Pros: Solid construction, easy transition between operation modes, dust-collector, heavy-duty motor, auto-lock system.
Cons: Rough table surface, fairly heavy.
Average Customer Rating:
A fully functional, 3HP 220 Volt rated single phase motor jointer planer, the Shop Fox W1742 is ideal for heavy duty planer and jointer activities. It comes with a table measuring 15 by 42 inches and has wings too. Two operational speeds of 16 and 30 FPM help tackle both soft and hard woods along with pedestral mounted controls and a thermal safety switch with overload protection.
Pros: Good construction, reliable and economical considering its purpose.
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Thursday, January 10, 2008
The Passive Voice is Found in Your Query Letter
Now that I'm an agent, I know that the truth is even more serious: the passive voice is ready to kill your query letter.
What, ask you, is the passive voice? Good question. Here's a website that will explain it better than I can, but basically it's a way of writing a sentence without attributing an action to an actor.
Here are some examples:
Spencer called me on his homeboy phone. -- normal sentence
Calls were made on Spencer's homeboy phone. -- passive voice
The monkey's bananas were stolen. -- passive voice
Spencer stole the monkey's bananas. -- normal sentence
Make sense? It basically kills a sentence by making it vague and dull since the actions aren't attributed to a person or thing.
Well, some people manage to write nearly their entire query letter in the passive voice. It goes something like this:
Vengeance will be found. Mistakes will be punished. When his dreams are shattered, Spencer is compelled to find the enemies who have caused his life to be destroyed...
This makes me pound my head on my desk. Vengeance will be found HOW? Mistakes will be punished HOW? HOW were his dreams shattered? WHO are the enemies? HOW are they destroying his life? WHY don't you just go ahead and rip my hair out for me?
So watch out for the passive voice, the silent killer of query letters, and of writing in general. A novel is not a place where things happen, a novel is a place where characters do things.
34 comments:
- Demon Hunter said...
Do you see passive voice quite a bit in the queries you receive? I would think that most people would know to summarize the novel in a paragraph. Your examples were on point. :*)
- January 10, 2008 at 1:09 PM
- Nathan Bransford said...
demon hunter-
Sadly, the passive voice is found in many query letters these days. And it is causing many headaches.
- January 10, 2008 at 1:11 PM
- Adaora A. said...
You make everything so easy for people who want to query you Nathan. Thanks alot for that. I'll be sure not to keep you medicated on advil liquid gels and cold packs to the head. :::Re edits query letter::
- January 10, 2008 at 1:33 PM
- Mark Terry said...
My question:
Why do 99.9% of all writers say:
She was wearing...
Rather than
She wore...
??? Inquiring minds want to know.
- January 10, 2008 at 1:53 PM
- cyn said...
hurrah! keep these gems coming! =D
- January 10, 2008 at 2:00 PM
- D. Robert Pease said...
Thanks Nathan. I don't know how many times I will need to be hit over the head to get this concept. Umm... I mean... I don't know how many times fine Agents as yourself will hit me over the head with... I mean... Oh never mind.
- January 10, 2008 at 2:02 PM
- sex scenes at starbucks said...
A novel is not a place where things happen, a novel is a place where characters do things.
That should go in bold print on the top of every website and book on writing.
was wearing is a misuse of past progressive. PP indicates a "continuing action" while another action happens. So technically, she "was wearing" clothes while doing something else works (unless she got nekkid first).
Hmmm. Nekkid.
Sorry. Got distracted.
Misuse occurs when there is no other action, or when the reader naturally understands that she is still wearing clothes while the new action occurs.
I find a search and destroy on WAS solves many verb issues, not just the past progressive ones.
- January 10, 2008 at 2:35 PM
- Dwight's Writing Manifesto said...
I'm a Tech Writer by trade, so passive voice is rampant in my neck of the literary woods. Object have sh!t happen to them all the time, as far as Engineers are concerned.
People speak in passive voice because it's perceived as being more polite. (Ambiguity = polite. Go figure.)
Unfortunately, people write in passive voice because they hear it in their head.
I maintain it is THE hardest writing habit to break. It's the last of the grammar hurdles. I promise you that you can pick up any best seller on the table at BookWorld and find three examples of passive voice in less than two minutes.
But for the love of God, get it out of your query letter and all other business correspondence.
- January 10, 2008 at 2:40 PM
- Michael Reynolds said...
A guy who writes the query that way probably hasn't completed his book. He's sending a query, hoping you'll bite on the concept, figuring he'll rush the book out if you say yes.
- January 10, 2008 at 2:48 PM
- Dave F. said...
Dorothy Parker is reputed to have said:
"The Passive Tense should not be used."
- January 10, 2008 at 3:28 PM
- Erik said...
I advise learning German. Passive voice practically does not exist in that language, so once you think a bit bilingually the passive voice will be purged from your speech patterns.
I also reccomend avoiding the Midwest, where passive voice is rather standard. That could be seen as a good idea, you bet.
- January 10, 2008 at 3:43 PM
- Demon Hunter said...
Oh no, Nathan! I'll send you virtual Tylenol and chocolates. Those people obviously have not read your blog or the retired Miss Snark! :*)
My query and synopsis are fine, it's just my polishing that's draining the life from me now, but it's worth it. A saleable novel is what I am working towards.
- January 10, 2008 at 3:48 PM
Once, as a joke, I wrote an entire bank robbery scene in passive voice. It was amazing how it gave the sense of a huge hole in the middle of the scene, because the people taking actions simply weren't on the page.
Passive voice is useful for somethings: If you don't know who committed a murder, then "Bob was killed while trying the crash the set of THE HILLS" works just fine. If the person receiving the action is the most important thing at the moment, then "Bruce Willis was hit in the leg by a sniper's bullet" does the job.
Most times, though, Active sounds better.
- January 10, 2008 at 3:54 PM
- Josephine Damian said...
Not just novels and queries but short stories as well.
I'm a screening judge in a national short story contest, and PV is a big reason for my not letting a story advance to the semi-finalist round.
- January 10, 2008 at 4:13 PM
- bitterhermit said...
I was under the impression that the space monkeys stole the bannanas. Yes, we have none today.
As a former TA myself, I applaud this post above most others. Such writing is useful for politics and social sciences, but I've always recommended against it nonetheless. Good writing is good communication. We write well when we communicate effectively.
However . . . is great writing more important than great story-telling?
Have a super day!
- January 10, 2008 at 4:39 PM
- Ghost Girl said...
Amen, Nathan!
- January 10, 2008 at 5:08 PM
- Kim Stagliano said...
Gah! Passive voice! Also a killer on resumes. But the all time, hands down favorite of politicians who need to say something without assuming any blame. The old, "mistakes were made." Lord I hate that.
And Dave K - I have a cocktail napkin that I picked up at The Algonquin just last week that reads, "I love a Martini - but two at the most. Three I'm under the table; Four, I'm under the host." Dorothy Parker. She will be missed.
- January 10, 2008 at 5:13 PM
But Nathan, what if you extend the passive voice?
Veronica killed Jake. <- active
Jake was killed by Veronica. <- passive
'By' is a trademark word of the passive voice.
Obviously, an entire query letter written like that would be annoying, but the same could be said about a query written only using active. Shouldn't we mix it up a little? :)
- Steph
- January 10, 2008 at 5:28 PM
- Adaora A. said...
@Steph- I'm not Nathan but he seems to have made it very clear that all intending to query him must avoid passive voice like the plague. Perhaps it is another way of him forcing the personal letter out of us all - thereby preventing a heart attack...and insomnia.
I see a definite pattern here.
- January 10, 2008 at 5:54 PM
- Nathan Bransford said...
I wouldn't rule out that the occasional use of the passive voice could be well-placed (such as, say, if one were writing dialogue for an evasive character), but I don't really think it would be possible to write an effective letter in the passive voice. It's just vague by definition, and vague has no place in a query letter.
- January 10, 2008 at 5:59 PM
- Adaora A. said...
I have a question which is admittedly off of the passive voice subject matter but I've wanted to ask.
You've said you like humor in query letters, but how much is too much?
- January 10, 2008 at 6:50 PM
- Nathan Bransford said...
adaora, you read my mind. I'm going to post on humor in queries... hopefully next week.
- January 10, 2008 at 6:53 PM
- Julie Weathers said...
Well, I'm thoroughly depressed now. Just when you think you have something figured out someone turns on the light.
- January 10, 2008 at 6:58 PM
I agree, Nathan, that the passive voice should be avoided, especially in queries. As for the MS, I offer a small "however" as someone recently sold and not seeking representation :-))) If you make a list of all the "don't's"--never use passive voice, never use gerunds, never use adverbs, writers will drive themselves MAD trying to adhere to all the rules and may end up editing all the personality from their work. Sit down and WRITE. Do your best to avoid the don'ts, but don't make yourself crazy trying to make it perfect.
Love your blog! I read every day and this is the first comment I've made.
- January 10, 2008 at 7:11 PM
- Adaora A. said...
Thanks Nathan, it is something I've been itching to ask for some time now.
- January 10, 2008 at 7:11 PM
- A Paperback Writer said...
I learned what passive voice is by learning Spanish. I wasn't aware that German doesn't make much use of it, either.
Dave F.,
Nathan's right: it's not a tense; it's a voice.
Mark Terry,
"Was wearing" is past progressive tense. "Wore" is past tense." The English language loves progressive tenses almost as much as it does the passive voice. Progressive tenses suggest a continuum, whereas the past tense suggests finality or an "of the moment" sense. It's all about connotations of the choice.
Yes, passive voice removes one from the immediate drama of the scene. Consider the passive voice phrase "I was born in July." The active voice alternative is "My mother bore me in July," which just really brings up a much more graphic picture that most people wish to avoid. (Yes, we can use "gave birth to," but that uses a different verb.) Personally, I'm sticking with passive voice when it's appropriate; none of my characters will be saying that their mothers bore them on a certain date.
This is why learning grammar is really not such a bad thing, folks. When you know the rules, you can use or break them without worrying about making mistakes you don't understand.
- January 10, 2008 at 8:48 PM
- Bija Andrew Wright said...
In addition to passive voice, I sometimes see troubles with passive constructions. A good sentence has the right subject and the right verb. A sentence with the wrong subject or the wrong verb can seem passive, even if it is grammatically in active voice.
When I was revising my book, I cringed every time I read a sentence with the subject "thing" and the verb "to be." It's my worst writing habit. "The first thing to remember is..." "One thing I noticed was..." "The most important thing is..."
- January 10, 2008 at 10:42 PM
- Stephanie said...
Thank you so much for your blog. Lots of good info. Writers can fix passive voice if they just pay attention. Good reminder though.
- January 10, 2008 at 11:17 PM
- Rose Green said...
Good point on how prolific the passive is in queries.
Uh, I do have to say that the passive is alive and kicking in German. It's especially used as a way around the sometimes unsure situation of whether to address someone with Sie or du. (See, even talking about it throws me all into passive.) Das ist ziemlich oft benutzt!
- January 11, 2008 at 12:59 AM
- Chris Redding said...
Just remember not all "wases" are passive voice.
The sky was blue is not passive. Not a great sentence. Not even interesting, but not passive voice.
I also search for "had" to make my sentences more active.
- January 11, 2008 at 6:32 AM
Vengeance will be found HOW?
By looking down the back of the settee and finding it's next to the tv remote?
- Britbeat
- January 11, 2008 at 8:05 AM
- Chris said...
Back when I was in university, we had to use passive voice for all our lab notes for the specific reason that it's not *who* does the experiment that's important but *what* happened.
On the plus side, I now find it quite easy to root out the passive stuff and concentrate on the active.
- January 11, 2008 at 9:40 AM
- Teens with a Vision: Nourishing Kids in Poverty said...
Ahh!! My brain is being hurt by all the passive voice!
Still love your blog though.
- January 11, 2008 at 7:34 PM
- Stella said...
YES!!! And thanks for the reminder.
- January 11, 2008 at 8:35 PM


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