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CHARMER
A burned out middle-age accountant and a young daredevil woman form an improbable alliance on a dangerous rescue-mission to Mexico. First Place, Screenplay Festival, 2017.
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1. Tres Banditos
By Thomas Leupp.
After running afoul of his shady underworld creditors, a washed-up athlete becomes involved in an outlandish scheme to steal the most famous trophy in the world.
(Posted: 06/08/2019; Updated: 07/07/2019)
Script Excerpt
2. HAT TRICK
By Robert Gately.
A retired police officer goes to the current-day Army/Navy football game with his two wacky friends intending to jump onto the field and score a touchdown he should've scored decades ago when he fumbled during the same football classic as time ran out, only this time dozens of security guards await him, and it'll be a friggin' miracle if he succeeds.
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3. FULL CONTACT
By Dave Kraft.
While battling a vengeful extortionist's scheme, an All-Pro linebacker with anger issues works to rebuild a life, his character and a career that spirals out of control after his fierce play on-field injures his estranged best friend. .
4. Boo Hoo Flanagan
A black correctional officer coaches a prison basketball team and finds the motivation he needs, in life and on the job, in Boo Hoo Flanagan, an aging, white, crippled inmate who shoots 3-point baskets better than anyone has ever seen.
5. The Comeback
By Dallas Gibson.
With everything on the line a college quarterback will get the shot she's always dreamed of. A shot to silence all the doubters, critics and naysayers. Once and for all she'll get the opportunity to lead, The Comeback.
Format: Short Screenplay
6. Pole Position
By Shannonn Kelly.
A TransWoman stakes a claim for female empowerment by starting a strip club in the secret heart of corporate America: Charlotte, North Carolina; where the headquarters of Bank of America and Wells Fargo do business with the NFL, NBA and NASCAR. Greed, virility, politics and sex simmer under the glow of red neon, crisp bills, aged bourbon and refined manners. Enter the Sodom and Gomorrah of Dixie…
Format: TV Pilot
7. The Color Of The Puck
By Mark Golik.
Amidst the backdrop of the American civil rights movement, Canadian Willie O'Ree overcomes racial prejudice and a career-threatening injury to become "the Jackie Robinson of hockey," the first black man to play in the National Hockey League.
8. The Umpire Has No Balls
By Debbie Bolsky.
A fiery young woman who has baseball running through her blood and can call the game better than anyone starts her journey through the umpire ranks to achieve her one goal in life – becoming a major league baseball umpire. Her problem? No woman has ever broken through the stainless-steel ceiling of this male dominated sport.
9. Six Hours to Santa Monica
A failed NASCAR driver looking for redemption uncovers a sinister plot involving his ex-girlfriend. With the help of a prototype car, he defies the odds to get her back.
10. 3rd and Goal
By Vicky Neal.
Against all odds, the first female quarterback drafted into the NFL battles prejudices and personal tragedy as she attempts to lead her longtime losing team in the quest for a playoff berth.
11. Life & Death
By Lisa Hagen.
Six, potty mouthed volleyball players finally grow up when one accidentally donates an organ to save another.
12. Dellwood
By Jonathan LaPoma.
A successful but unhappy novelist reluctantly returns to his childhood town to attend a friend's funeral and reminisces about his experiences playing basketball on a city court to escape his abusive home. [Ranked 7th in the Urban category of MovieBytes.com's "Top 10 Contest Winning Scripts"]
13. Free Sports Radio
By James Palmer.
They're commercial free. They're free to talk. They work for free. There's not enough money to make them go away. They're on a mission… to free sports radio.
Synopsis Script Excerpt
14. Hammond
A group of troubled but charismatic boys in a tough Buffalo, NY neighborhood play basketball at a local park and dream of winning a state high school championship. Driven by raw talent and killer instinct, they dominate the court, but everywhere else, they feel like losers.
Format: Novel
15. Purple Aces
By Kyle B. Dietz.
In 1977, the University of Evansville and its small Indiana community are struck by tragedy when a plane crash claims the lives of the entire men's basketball team. Hoping to bring healing to the community, the university forms a new team and hires Coach Dick Walters. Haunted by the past and their own self-doubt these Aces find themselves in the team's first ever NCAA Tournament appearance.
16. DOUBLE STEED
By Christine J. Whitlock.
When a teen girl has to take over the care and training of her competitor's new horse, her compassion and companionship with the two horses wins her a dressage competition.
17. One Nation Under Par
By mark nemcek.
A gambling talk show host places a million dollar bet that an honest pro golfer, sided by his exotic hooker wife and her pornographic pet parrot, will beat an unscrupulous congressman in the upcoming presidential election.
18. ME & JACKIE
By Justine Cowan.
Story of an unlikely friendship between a junk-yard hermit with guilt he can't shake and a young latchkey teenager from a poor Baltimore neighborhood.
19. The Complex
By BRIAN J. WILSON.
A famous athlete tries to balance fame and family with the secrets that will destroy his success. His relationship with a dynastic organization and a beleaguered public force him to question the motives of both. When he finds himself in life and death circumstances he must act to save himself.
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Lies, Hamburgers, And Cufflinks
To save his life, a guy held hostage by the Russian mafia must find out who ordered the robbery of a 4 million dollar pair of cufflinks.
Operation Brother Sam
During the Cold War, an aging Intelligence Officer addicted to anxiolytics must lead a rogue team of spies to investigate a US ambassador involved in a conspiracy in Brazil.
Hapless Fu
A lovable Asian fool in Los Angeles bumbles through life unable to get anything right, then is thrust into a position of being the only man who can save the world from nuclear holocaust.
When a troubled girl's visions of her classmates' murders start coming true, she suspects her father is the killer.
The Meat Eaters
A college-age fast food manager's virginity makes him a target of a cult of "living meat" eaters masquerading as workers.
Noticing how many marriages around them fall apart as soon as the kids leave home and fearing that their own marriage has an expiration date, a married couple spends the final year before their impending empty nest discovering who they want to be for the next act in their lives.
When a bullied teenager seeks refuge by an Irish castle, he travels to a magical world he never knew existed where his long-lost father turns out to be king.
After her parents are brutally murdered, the last dragon whisperer — a 16 yr old grieving teenager named Luana — goes on an epic quest to avenge their deaths and rescue her village from blood-thirsty banshees.
When Doves Cry
In 1991, a group of high school seniors navigate the treachery of young adulthood, while seeking the ultimate Minneapolis experience, seeing the legendary Prince perform live at First Avenue on Halloween night, when a freak blizzard threatens their plan.
Anatomy Of A Town
The Chief of Police investigates the murder of a young woman while confronting the Sheriff, who blocks his every move for jurisdiction, in order to protect himself from the Chief finding out about his ties to both the murder victim and the killer.


A disquieting finding of The State of Food Security and Nutrition in the World 2017, Building Resilience for Peace and Food Security, or (SFSN2017), Rome, is that, in 2016, the number of chronically undernourished people in the world increased to 815 million, up from 777 million in 2015 although still lower than about 900 million in 2000. Similarly, while the prevalence of undernourishment rose to 11 per cent in 2016, this is still well below the level attained a decade ago. Whether this recent rise in hunger and food-insecurity levels signals the beginning of an upward trend, or whether it reflects an acute transient situation calls for a close scrutiny.
Undernourishment is associated with lower productivity. More importantly, in an agrarian economy with surplus labour and efficiency wages, a weather or market shock could result in rationing out of those lacking adequate physical stamina and dexterity from the labour market. This could perpetuate the poverty of the undernourished, often referred to as nutrition-poverty trap.
By contrast, other indicators of food security have registered improvement. Stunting refers to children who are too short for their age. It is a reflection of a chronic state of undernutrition. When children are stunted before the age of two, they are at higher risk of illness and more likely than adequately nourished children to lack cognitive skills and learning abilities in later childhood and adolescence. Globally, the prevalence of stunting of children under five years fell from 29.5 per cent to 22.9 per cent between 2005 and 2016. The global average of the prevalence of anaemia in women of reproductive age increased slightly between 2005 and 2016. When anaemia occurs during pregnancy, it causes fatigue, lowered productivity, increased risk of maternal and perinatal mortality, and low birth weight babies.
Has Asia's experience been different? It is argued below on the basis of Table 1 that it has been more mixed.
Although proportion of undernourished in different sub-regions of Asia varied within a narrow range in 2004-06, it became narrower in 2014-16. In all sub-regions, the proportion of undernourished fell during this period but slowly, as in Asia as a whole. Under-five stunting is a key indicator of child malnutrition. The range was large in 2005, with a high of 44.6 per cent in Southern Asia and a low of 9.4 per cent in Central Asia. The range became narrower in 2016 but Southern Asia continued to have the highest prevalence of over 34 per cent (but lower than in 2005) and Eastern Asia the lowest of 5.5 per cent (substantially lower than in 2005). So except for Central Asia which witnessed a slight rise, all other sub-regions recorded reductions in stunting. Prevalence of anaemia among women of reproductive age was widespread with a high of 50 per cent in Southern Asia and a low of about 19 per cent in Eastern Asia in 2005. While the prevalence of anaemic women fell in Southern Asia from 50 per cent to 43.7 per cent in 2016, this sub-region still had the highest prevalence.
Eastern Asia saw a more than moderate rise, South Eastern Asia experienced a negligible reduction, and Central Asia a small reduction. As a result, there was a bunching of high prevalence rate in Central Asia, Eastern Asia and South Eastern Asia, and a consequent rise in prevalence of anaemic women from a high of 33.3 per cent to 36.6 per cent.
SFSN (2017) attributes much of the worsening in food security - especially in Sub-Saharan Africa - to frequency of conflicts, droughts, and fragility of governance, but the analysis is largely conjectural.
As Asia was not so prone to conflicts, we sought to unravel the relationship between these indicators of food security and income growth, allowing for unobservable country-level heterogeneity and residual time effect. Whether the political regime of a country is more inclined to protect the poor and vulnerable - especially children and women in the reproductive age-group - against the risks of undernourishment from weather and market shocks is unobservable but crucial for isolating the effect of income.
Our analysis shows that there are robust relationships between these indicators and per capita income (PPP2011) and the residual time effect. Assessing the effect of income in terms of elasticities, proportionate change in say prevalence of undernourishment/proportionate change in income, we find that the elasticity of undernourishment to income is -0.28, implying that a 1.0 per cent higher income will lower prevalence of undernourishment by 0.28 per cent. A related finding is that the elasticity (in absolute value) rose substantially during 2005-16, implying that a 1.0 per cent higher income will be far more effective in curbing undernourishment. Moreover, there was a substantial negative residual time effect, implying that controlling for income, other time related factors led to reduction in prevalence of undernourishment.
The elasticity of under-five stunting with respect to income was also robust, with an elasticity of -0.045, implying that a 1.0 per cent higher income will translate into a reduction of stunting by -0.045 per cent. Compared to the elasticity of undernourishment with respect to income, this is considerably lower. This is not surprising given that stunting is the result of persistent undernourishment over time. In addition, there was a significant negative residual time effect, implying presumably better hygiene and sanitary conditions. The elasticity (in absolute value) rose more than moderately between 2005 and 2016, implying greater sensitivity of under-five stunting to income. Finally, the elasticity of prevalence of anaemia among women in reproductive phase with respect to income was negative but also low (-0.075). So a 1.0 per cent higher income is likely to be associated with a reduction in prevalence of anaemia of 0.075 per cent. The (absolute) elasticity rose slightly between 2005 and 2016. The residual time effect was negative, implying better access to medical services, hygiene and sanitary conditions for women in reproductive phase over time.
Although limited in scope, our analysis confirms that income growth is key to food security in Asia. This is not to suggest that other factors (e.g. social safety nets, greater nutritional awareness-especially among women-and education) do not matter. They matter too but call for a broader investigation.
Geetika Dang is an independent researcher; and Raghav Gaiha is currently (Hon.) Professorial Research Fellow, Global Development Institute, University of Manchester, England, and Visiting Scientist, Department of Global Health, Harvard School of Public Health (2015 and 2016).


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Home NewsHuntsville awarded grant for jail restoration
Huntsville awarded grant for jail restoration
August 29, 2018| News| benwgarrett@gmail.com
Photo: Huntsville Mayor Dennis Jeffers (left) chats with Tennessee Tourism Commissioner Kevin Triplett and State Senator Ken Yager during a grant presentation at the Huntsville Municipal Building on May 29, 2018.
HUNTSVILLE — The Town of Huntsville's efforts to restore the old Scott County Jail received a shot in the arm Monday, when the State of Tennessee announced that a $75,000 grant has been awarded for the project.
The Tourism Enhancement Grant was awarded by the Tennessee Department of Economic & Community Development and the Tennessee Department of Tourism. Local officials learned last week that they had received the grant, while the formal announcement was made jointly by State Sen. Ken Yager, R-Kingston, and State Rep. Kelly Keisling, R-Byrdstown, on Monday.
Application for the grant was made by the Industrial Development Board of Scott County, which partnered with the Town of Huntsville on the project. It marked the second time in three years that Scott County was awarded the grant. In the last cycle, it was used to restore the historic O&W Railroad bridge in the Big South Fork National River & Recreation Area.
"It is an honor to be able to work with our local municipalities and serve as a conduit to help obtain grant funding for projects that will benefit all of us," said ID Board Chairman Jim Swann.
Ownership of the old jail, which was built in 1906 and is listed on the National Register of Historic Places, was obtained by the town last year, after Mayor Dennis Jeffers approached Scott County Commission to ask that the facility be given to his town in exchange for a pledge that it would be restored and made available to the public in some fashion.
Work has since begun to renovate the dilapidated structure, which had set vacant for 10 years after the county moved its inmates to the new Scott County Justice Center in 2007.
"I have long been a supporter of preservation and restoration of the historic Scott County Jail," Yager said. "I was happy to support the grant application. The tourism grant will provide needed funds to start the restoration. Restored, the historic jail will serve as a magnet for historians, preservationists and tourists."
Keisling called the jail a "fixture" in the community. "These grant dollars will ensure that the facility's rich history is preserved so that future generations know its significance in our local narrative," he said.
Jeffers has stated in the past that he hopes to have the jail restoration complete and ready for the public to explore by October, when the Scott County Chamber of Commerce's Fall on the Mall takes place on the courthouse mall adjacent to the jail.
The preceding article first appeared in the Oneida Independent Herald. Reprinted with permission.

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As you look into the purchase of a new home, don't just assume that everything is going to be in tip-top shape once construction is complete. By asking Oregon home builders the right questions, you can have a pleasant purchasing experience and peace of mind knowing that the contractor is experienced and reputable.
Is home construction your specialization? Oregon home builders that specialize in house construction have better knowledge regarding residential building codes and the respective industry best practices and standards.
How long have you been in the business? A good builder is forthcoming about the company's track record, regardless of the amount of time it's been in business. When companies are young, Portland home builders should tell you about their training, professional experience and capabilities.
Are you a member of any builders' associations? Membership in an association shows a company's commitment to the industry and its own success.
What type of warranty comes with the home? Good Portland home builders back their new homes with a warranty. If there is a warranty, ask about what's covered, the length of the warranty and deductibles.
Do the appliances in the home have their own warranties? Some appliance warranties last longer than home warranties.
Does your company provide any type of after-sales service? These services can help you connect with interior designers, local utility companies, landscapers, area schools and the like.
Can you give me some references? A builder who is proud of is his work is more than happy to give you the names of clients.
Do you sell to investors? When a builder sells homes to investors and homeowners, you may find yourself in an empty neighborhood if there's an economic scare.
Is there a deadline for choosing my own home upgrades? In some cases, if you don't request your own appliances and upgrades by a certain deadline, the builder may choose them for you.
What are your quality control practices? A reputable builder is one who has nothing to hide. He should be able to walk you through how the home was constructed and the measures taken to ensure a quality build, like steps to prohibit moisture intrusion, product failures and more.
When you buy a new home, the builder is just as important as the structure. By asking the right question, you can purchase a new home with confidence.


Usually covers educational expenses, living expenses and dependent child expenses too.
Fellowships to women from developing countries to pursue PhD or Post-doctorate studies in STEM disciplines at leading universities worldwide.
30 fellowships each year for PhD in the aerospace field.
For women with a focus on cybersecurity or information assurance.
What are the best scholarships for women?
Are there any scholarships for women?
How do I get a scholarship to study abroad?
How do I get a scholarship to study in European countries?
How to get an international scholarship for women?
What are a few scholarships for women?
Is there any scholarships for women provided by India for studying in the USA?
Why is the postgraduate scholarship for women?
What scholarships are available for women in computer science?
Is there any scholarship/fellowship for married women?
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Can a Masters of Pharmacy student apply for these scholarships if they want to do P. hd in abroad?
Mam, I am doing B. A programme in the combination of history and Spanish. Any Scolarship for me??


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Meet the insurgents who are likely future Assembly members
Zohran for Assembly
Zohran Mamdani emerged victorious over incumbent Assembly Member Aravella Simotas.
Seven progressive challengers have toppled longtime Democratic incumbents.
By REBECCA C. LEWIS
Two years after the 2018 left-wing reckoning for many Democratic incumbents in the state Senate, this year is the Assembly's turn.
Across New York City, progressive insurgents have unseated longtime members of the Assembly in hotly contested races. Unlike the state Senate, which flipped from Republican to Democratic control in the 2018 blue wave, the Assembly has long been a Democratic stronghold. The party holds a supermajority in the chamber, but progressive activists were frustrated by reluctance in the chamber to back some ambitious reforms in the last legislative session, including public campaign financing. More conservative incumbents were warned to expect progressive primaries.
As serious challenges to incumbents have become increasingly common, and the state Senate becoming the progressive trendsetter in the Legislature, several mainstream Democrats have now lost their primaries to upstarts demanding fresh voices and new representation in the people's chamber.
Each is expected to win their November elections in their overwhelming Democratic districts. Here's what you need to know about the likelyfuture Assembly members.
Marcela Mitaynes
Mitaynes defeated Assembly Member Félix Ortiz in the 51st District, which includes most of Sunset Park and Red Hook, Brooklyn. Not only has Ortiz served in the Assembly for over two decades, he is a member of leadership and effectively serves as Assembly Speaker Carl Heastie's right hand as assistant to the speaker. Ortiz garnered criticism in 2019 when one of his staffers was arrested for embezzling $80,000 in campaign cash over seven years, with some calling for the Assembly member's resignation. Mitaynes is a member of the Democratic Socialists of America's New York City chapter and received the group's endorsement. She also had the support of the Working Families Party, Rep. Alexandria Ocasio-Cortez and New York Communities for Change. A tenant organizer and immigrant from Peru, housing reform is at the top of Mitaynes' agenda, including the passage of the so-called "good cause" eviction bill considered the cornerstone of universal rent control. She also supports DSA criminal justice reforms like defunding the police, not building new jails, eliminating cash bail and taxing the rich.
Jessica González-Rojas
González-Rojas bested Assembly Member Michael DenDekker in the 34th Assembly District in Western Queens. Although DenDekker is white, he has represented the largely Hispanic, Asian American and Black neighborhoods of Jackson Heights and East Elmhurst for over a decade. González-Rojas is a DSA member, although she didn't receive the group's endorsement, but she did run to the left of DenDekker and was backed by several notable progressives, including Tiffany Cabán and New York City Public Advocate Jumaane Williams, and organizations such as the Working Families Party and Make the Road Action. She ran on a platform of LGBTQ rights and passing the New York Health Act to create a single-payer system. She also supports the cancellation of rent in light of the coronavirus pandemic, no rollbacks for bail reform and taxing the rich.
Jenifer Rajkumar
Rajkumar defeated Assembly Member Michael Miller in the 38th Assembly District in southwest Queens. A win in November would make her the first South Asian lawmaker in the Assembly, and only the second in the state Legislature. (State Sen. Kevin Thomas is the first.) Unlike most other insurgents this cycle, Rajkumar is not a DSA member and did not receive endorsements from prominent left-wing and progressive groups. She presented herself as a progressive, but did not campaign mainly on issues like single-payer health care or universal rent control, though she has stated on a candidate questionnaire that she supports both. The district has become more progressive, although not as much so other parts of Western Queens, as it has grown more racially diverse. It has a significant Asian American population. Miller, a white man, also has a more conservative record than many other insurgents, so Rajkumar didn't have to heavily campaign on the far left to still be considered a progressive alternative.
Emily Gallagher
Gallagher bested Assembly Member Joseph Lentol, who has been serving in the Assembly for nearly 50 years, in the 50th District in Brooklyn. Like Mitaynes, Gallagher's victory was an upset. On election night, Gallagher was about 1,700 votes behind Lentol, but as absentee ballots were counted, the gap closed until her vote total had comfortably surpassed his. Gallagher did not get the support of the DSA, despite initially seeking it. Interestingly, the WFP also did not endorse Gallagher, and in fact backed Lentol in the race, based in part on his longtime record of supporting criminal justice reform. However, Gallagher had support from progressive groups like New York Communities for Change and Our Progressive Future. An environmental activist and tenant rights organizer, she campaigned on issues like investing in public, low-income and supportive housing, and opposing any new fossil fuel pipelines.
Phara Souffrant Forrest
In another victory for the NYC-DSA, Forrest declared victory over Assembly Member Walter Mosley in the race for the 57th District in Central Brooklyn. On election night, she trailed him by about 600 votes, but according to Souffrant Forrest's campaign, she led him by more than 2,500 after most absentee ballots had been counted. She was backed by the DSA and also had endorsements from Rep. Alexandria Ocasio-Cortez, Our Progressive Future and New York Communities for Change. The WFP did not back her, instead supporting Mosley. Souffrant Forrest is a nurse and supports safe staffing ratios in hospitals and passing the New York Health Act. She also organized tenants in her own building in the past and campaigned strongly on housing issues like universal rent control. Like many other progressive insurgents and DSA candidates, she supports redirecting state funds away from police and into social services.
Zohran Mamdani
In Western Queens, Mamdani emerged victorious over incumbent Assembly Member Aravella Simotas. He had a tight lead in the election night results, one that held as the counting of absentee ballots concluded. In a tweet declaring victory, Mamdani said that he held a 300-vote lead over Simotas, enough not to trigger a recount. Mamdani was backed by the NCY-DSA, although he was the only candidate from the slate not to have the endorsement of Ocasio-Cortez. He also did not get the WFP's backing, which stayed out of the race entirely, despite having supported Simotas in the past. Mamdani campaigned strongly on housing rights and affordability, inspired by his work helping immigrant homeowners avoid foreclosure. If he wins in November, he would be only the second South Asian ever elected to the state Senate and the third Muslim in the state Legislature as a whole.
Amanda Septimo
In the South Bronx, Amanda Septimo unseated longtime Assembly Member Carmen Arroyo before voters even headed to the polls. Unlike other insurgents this cycle, she won the Democratic nomination unopposed when a judge ruled that Arroyo had gathered fraudulent petition signatures and kicked her off the ballot. Septimo, a labor organizer, was supported by the Working Families Party in her second challenge for the seat after the party backed her unsuccessful 2018 bid. This time around, Septimo is almost guaranteed to be headed to Albany as the Democratic Party's pick, where she wants to ensure that historically underserved neighborhoods in the South Bronx get the resources they need. She campaigned on issues like making subway and bus service free, repairing public housing and making sure that all students have access to after-school programs regardless of income.
Correction: González-Rojas is a DSA member.
New York's 2020 congressional primary election results
By ANNIE MCDONOUGH, JEFF COLTIN, REBECCA C. LEWIS
Suburban NY backs Black congressional candidates
By ANNIE MCDONOUGH
Rebecca C. Lewis
is a staff reporter at City & State.
@_rebeccaclewis
The coronavirus in New York, by the numbers
The endorsements for NYC mayoral candidates
By JEFF COLTIN
Wait, why is indoor dining reopening again?
By AMANDA LUZ HENNING SANTIAGO
The 2021 Health Power 100


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Kariba Dam Rehabilitation Project
Zambezi Valley Development Fund
Our Value Aligning Activities
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Home / Opportunities / Tenders
Technical Advisor for the Development of the Batoka Gorge Hydro - Electric Scheme
The Zambezi River Authority ("the Authority") intends to employ a firm for the provision of Technical Advisory Consulting Services to the Zambezi River Authority, ZESCO Limited and ZESA Holdings for the development of the Batoka Gorge Hydro -Electric Scheme (BGHES). The BGHES will be developed on a Build, Operate and Transfer (BOT) mode.
The Authority is a corporate body jointly and equally owned by the Governments of Zambia and Zimbabwe ("Contracting States") and is mandated with the management of the Kariba Complex and the stretch of the Zambezi River (from Kazungula to Kanyemba) forming a common border between the two Contracting States.
The scope for the development of the BGHES shall include but not limited to;
175m high, 720m long rolled compacted concrete gravity arch dam;
Radial gated crest type spillway;
Two surface power plants, one on either side of the river bank, each having a capacity of 1,200MW, with a combined capacity of 2,400MW;
6 x 200MW turbines in each powerhouse;
Four intakes in the reservoir which will take the water through 4 tunnels (each approximately 0.5km in length) to the two surface power plants downstream of the dam;
Diversion tunnels
Switchyards for both power plants
Transmission lines connecting the Project to the grid in Zambia and in Zimbabwe:
BGHES to Mukuni substation (2 x 330kV x 22km,) in Zambia;
BGHES to Muzuma in Choma (1 x 330kV x 152km) in Zambia;
Muzuma to Nambala substation (1x 330kV, 230km) in Zambia
Batoka North and Batoka South Interconnector (2 x 330kV)
BGHES to Hwange (2 x 400kV x 70km) in Zimbabwe; and
BGHES to Chakari (2 x 400kV x 400km) in Zimbabwe.
The above Transmission scope may change depending on the outcome of the network studies to be undertaken by the Developer.
Construction of access roads on both sides of the two contracting countries (approx. 90Km);
Construction of the operational staff townships and office complex for the Authority and the Power Utilities on both sides of the river banks with social amenities
The high-level scope of the consulting services ("the Services") to be implemented over a period of approximately seven (7) years shall include but not limited to;
Assist with the contract negotiations with the Developer: The Consultant will be expected to participate in all contract negotiations with the developer and offer Technical advice to the Zambezi River Authority, ZESCO Limited and ZESA Holdings until Financial close;
Technical Advisory services during project Construction: The Consultant shall offer Technical Advice to the Zambezi River Authority, ZESCO Limited and ZESA Holdings with respect to the Civil, Hydro-Mechanical, Electro-Mechanical and Transmission and Distribution Infrastructure works during construction and follow-up of the Zambezi River Authority, ZESCO Limited and ZESA Holdings' training of staff by the Developer.
The Draft Terms of Reference for the Consulting Services can be inspected on the Authority's website: www.zambezira,org
The Authority now invites consulting firms ("Consultants") with similar and specific experience to express their interest in providing the said services. Interested Consultants should provide information demonstrating that they have the required qualifications and relevant experience to perform the Services.
Consultants may associate with other firms in the form of a joint venture or a sub consultancy to enhance their qualifications.
A Consultant will be selected in accordance with the Quality and Cost Based Selection method set out in the Authority's Procurement Policy and Procedures.
The shortlisting criteria is;
The firms core business being in the area of the proposed assignment,
General experience of the firm (clearly demonstrating the scope, cost and duration),
Specific experience of the firm in the provision of Technical Advisory Services for the Development of Hydro-electric Power schemes in the last twenty (20) years,
Specific Experience of the firm in at least One Public Private Partnership, Independent Power Producer or Build, Operate and Transfer Projects in the energy sector in the last twenty (20) years.
Specific Experience of the firm in provision of Consultancy services in at-least two Hydro Power Projects with minimum installed capacity of 500MW in the last twenty (20) years
Experience in similar conditions or sub Saharan Africa region, and
Suitability of the qualifications and experience of the Consultants core staff, such as principals or directors who may not at all be proposed subsequent to short listing to be among the key staff of the consultants who may be proposed to undertake the assignment. Specific Key Experts requirements will be considered in the Request for Proposal Stage.
Further information can be obtained at the address below during working hours from 0800 to 1630 hours local time.
Expressions of interest must be delivered by E-MAIL in PDF on or before 27th September 2019, 1600hrs on the following E-mail addresses;
Email: Langton Pfaira: langton. pfaira@zambezira.org
cc: Avitol Nkweendenda: avitol.nkweendenda@zambezira.org
The Expressions of interest must be addressed to;
The Chief Executive
Kariba House
32 Cha Cha Cha Road
Lusaka, Zambia.
Tel.: +260 211 227970-3
Att: Manager Procurement
Draft TORS Technical Advisor
Advert - Technical Advisor BGHES rev an.pdf
Launch Date:
Copyright 2020 Zambezi River Authority. All Rights Reserved | Disclaimer | Privacy | Contact Us


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Prior to Workday, SSO used role assignments from the various HR/Payroll applications to require some employees to use two-factor authentication. The System Office decided to delay switching to the equivalent Workday roles in order to get past Workday go-live before adding that requirement for additional employees. The System Office is now ready to make that switch and wanted to make you aware of the timeline. The switch will occur on the morning of June 25 and will result in 312 employees system-wide newly required to use two-factor when logging in through SSO.
Please let Brad Blair, Mark Schulz or Carol Manthei know if you have questions or concerns.
Come Join The Texas A&M University System Technology Summit's Project Management Virtual Half-Day Event.
Want to learn more about how to manage IT projects? The Texas A&M University System Technology Summit and the TAC 216 Working Group are holding a project management virtual event on June 7. Captioning will be available during the event.
Join us for discussion and networking as we hear from our opening speaker, Mr. Patrick Perry, CIO, California State University System discussing the challenges facing CSU as they realign principal strategies and set key priorities to support the Graduation Initiative 2025 – an ambitious goal of accelerating student success and degree completion.
Joining the Summit on the 14th will be Mr. Jeff Kline, Program Director of Statewide Electronic Information Resources and Accessibility, who will provide an overview of the Texas Department of Information Resources and engage attendees on the awareness of accessibility regulations and standards.
Space is limited so register soon!
No trips scheduled for this week.


On the football field former NFL Quarterback Troy Aikman led the Dallas Cowboys to three Super Bowl championships, but in the troubled world of high-end real estate Aikman may soon be taking a financial beating.
Aikman's swank five bedroom, six bathroom mansion in a posh high-end Dallas neighborhood just had its priced slashed $3 million to an asking price of $24 million. The Mediterranean style mansion is more than 10,000 square feet covering most of its 1.5 acre estate in Highland Park.
The three story house was built at the height of the real estate bubble in 2005 and is the largest residential listing in all of "Big D" as the locals call Dallas. The estate is accompanied by a four car garage, three fireplaces with a large living room, sitting areas for warm Texas evenings and a massive family room.
The property surrounding the home is heavily treed with all sorts of other vegetation.
The estate is apparently being sold as part of Aikman's announced divorce from his wife of ten years to settle financial affairs, and is priced $8 million above the next highest priced home in the Dallas area currently on the market.
Somehow you have to feel sorry for Aikman, who despite his successes on and off the field is likely to take a real financial beating in the hard hitting world of high end estate real estate these days.
Maybe Fox sports will sign him to a bigger announcer's contract for next football season to make up for some of his losses.


text:
Home » Trending » Man Kicked & Strangled His Shepherd Puppy To Death 'Because He Had Mange'
Man Kicked & Strangled His Shepherd Puppy To Death 'Because He Had Mange'
A Dayton, Texas man has been arrested by the Montgomery County Sheriff's Office and sentenced to prison after he admitted to abusing and killing his German Shepherd puppy.
35-year-old Joseph Dewayne Lloyd pleaded guilty to cruelty to a non-livestock animal, a third-degree felony, and was sentenced to two years in prison, including 238 days that he has already served.
gomagoti/Flickr
Lloyd's neighbors heard banging sounds followed by cries of a young puppy. They later found the puppy's discarded dead remains in a nearby dumpster.
Lloyd allegedly kicked and strangled the puppy to death because the dog was "suffering from mange." But his neighbors say the puppy was happy and healthy, would run and play with them, and did not have mange.
Montgomery County Sheriff's Office via Houston Chronicle
"The unwarranted and unjustified pain and suffering caused by the defendant is unacceptable," prosecuting Montgomery County Assistant District Attorney Tiana Sanford said. "We will continue to work with law enforcement and other stakeholders in our community to protect and care for the vulnerable among us. This includes our animals in Montgomery County."
H/T to Houston Chronicle.
Little Girls Lose Dad In Tragic Accident, Then 2 Dogs Turn Their Lives Around
Pack Of Dogs Won't Leave Blanket And Man Walking By Hears Crying
He Set Up A Hidden Cam To Prank A Shelter, But Seconds Later A Truck Pulled Up
Man Prepares Food For 80 Homeless Dogs Each Day In A Mission To Help Them Survive
Foolish Tourist Attempts To Pet A Lion While On Safari, Nearly Loses An Arm
Baby English Bulldog Knows How to Strut Her Stuff!


text:
7:30 p.m. at Nashville SC • FSN, 1500-AM
Preview: Sent home from midsummer's MLS is Back Tournament without playing a game because of a coronavirus outbreak, expansion Nashville SC has not scored more than one goal in any game other than a 4-2 victory over Atlanta United on Sept. 12. Despite that, it is 3-1-4 in its past eight games, the only loss coming to mighty Columbus. Overall, Nashville SC is 10th in the East — right above the cut line to make the playoffs — with a 4-5-5 record. It is 3-1-2 at home. … Loons starting left back Chase Gasper is suspended because of yellow-card accumulation after he received another one in Saturday's 2-0 home victory over FC Cincinnati. … Injuries that caused the Loons to make 2017 No. 1 overall pick Abu Danladi available in last November's expansion draft have followed him to Nashville. He has started three of 10 games he has played and has scored a goal, but he hasn't played since he started that Sept. 12 victory over Atlanta United. … The Loons' Saturday victory ended a four-game winless streak. They're fourth in the West with a 6-5-4 record, five points behind first-place Seattle.
Injuries: MF Ethan Finlay has trained and is aimed toward returning from a shoulder injury, while coach Adrian Heath said defensive midfielder Ozzie Alonso (hamstring) probably won't return until Sunday's game at Dallas. GK Tyler Miller (hip surgery, out for season), D Ike Opara (undisclosed), F Luis Amarilla (ankle) and GK Greg Ranjitsingh (knee) all remain out.
JERRY ZGODA
Local 'We have a lot to lose': 16 Minn. cities declare climate emergency
Local Minn. infectious disease director Kris Ehresmann to retire Feb. 2
'We have a lot to lose': 16 Minn. cities declare climate emergency
The U.S. Department of Education has opened a civil-rights investigation into how LGBTQ students are disciplined at Brigham Young University, a private religious school.
NCAA member schools voted to ratify a new, streamlined constitution Thursday, paving the way for a decentralized approach to governing college sports that will hand more power to schools and conferences.
The U.S. Olympic top doctor says all of the 200-plus athletes heading to Beijing for the Olympics next month are fully vaccinated, and not a single one asked for a medical exemption.
An arbitrator has ruled that UConn improperly fired former men's basketball coach Kevin Ollie and must pay him more than $11 million, Ollie's lawyer said Thursday.
Loons' Gregus will miss time while playing for Slovakia national team
Blaine workouts will mark start of Loons' trek to season opener • Loons
Loons start anew in 2022 without some familiar faces • Loons
Soccer's 'Honey Badger' comes to Minnesota as United trades for Alonso • Loons
Loons updates: Chase Gasper's USMNT debut 'everything you dream about' • Loons
'Great day for the club.' Loons fell Timbers, reach Open Cup title match • Loons


text:
Q: past simple or present perfect for an action connected to the future
My friends told me that they planned to see me next Sunday before going back home. I told  them that it was very nice but completely forgot to add that I won't be there next Sunday,  the day they planned to see me.

Is past simple a good choice for "plan"  or would it be better to use present perfect for the second "planned"  because they may change  the date.

A: What you are dealing with here is reported speech.
The assumption is that your friends told you this:

We are planning to see you next Sunday before going back home.

Therefore, if we report that speech the way you did, that becomes:

My friends told me that they were planning to see me next Sunday
  before going back home.

(Tenses shift from present continuous to past continuous. If you do not know how reported speech works you can find a pretty good explanation here.)
Now to review your second sentence:

I told them that it was very nice but completely forgot to add that I won't be there next Sunday the day they planned to see me.

You should never use "planned". Because they didn't "plan". You would never say "I plan to see you.", instead you'd say "I am planning to see you".
The best tense to use in this scenario would be past perfect continuous, because they had been planning before you told them that it was very nice, and past perfect is used to express that something happened before something. If you don't quite understand that you can read this.
I don't know how you came to the conclusion that you should use present perfect. Present perfect is not used to express probability, as you suggested.

redpajama_set_name: RedPajamaStackExchange


text:
Q: How to map Product entity so that it is managed by Doctrine? I am trying to build a module under PS 1.7.6.1.
In design, I have a manyToOne relationship between a Product and a Preorder (many preorders can be associated to one product).
The Preorder object is an ORM entity:
//mymodule/src/Entity
class Preorder
{
    /**
     * @var int
     *
     * @ORM\Id
     * @ORM\Column(name="id_preorder", type="integer")
     * @ORM\GeneratedValue(strategy="AUTO")
     */
    private $id;

    /**
     * @var int
     *
     * @ORM\Column(name="id_product", type="integer")
     */
    private $productId;

    /**
     * @var string
     *
     * @ORM\Column(name="email", type="string", length=64)
     */
    private $email;

    setter and getter
}

In controller:
//src/mymodule/src/Controller

use Doctrine\DBAL\Types\TextType;
use PrestaShopBundle\Controller\Admin\FrameworkBundleAdminController;
use Doctrine\ORM\EntityManagerInterface;
use MyModule\Entity\Preoder;
use Symfony\Bridge\Doctrine\Form\Type\EntityType;
use Symfony\Component\Form\Extension\Core\Type\EmailType;
use Symfony\Component\HttpFoundation\Request;
use Product;

class PreorderController extends FrameworkBundleAdminController
{
public function createAction(Request $request){

        $preorder = new Preorder();
        $preorderForm = $this->createFormBuilder($preorder)
                ->add('email', EmailType::class)
                ->add('productId', EntityType::class, [
                    'class' => Product::class,
                ])
                ->getForm();

        $bookingForm->handleRequest($request);

// validate and persist
}}

The problem is that the  form builder doesn't recognize the Product entity. It throws a runtime exception:

Class "Product" seems not to be a managed Doctrine entity. Did you
  forget to map it?

I can't find in the core files an example where such a scenario is handled. Thank you very much in advance for guiding/helping me the resolve this issue.

A: The main issue is that product_id is not an entity so there is 0 chance that The formbuilder handle it with the EntityType::class. you need to properly define (as explained in the doc) your ManyToOne relation with objects
on the product side :
/**
 * @ORM\Entity(repositoryClass="App\Repository\ProductRepository")
 */
class Product
{
    // usual stuff

    /**
     * @ORM\ManyToOne(targetEntity="App\Entity\User", inversedBy="product", cascade={"persist"})
     */
    private $preorders;
}

and on the preorder side:
/**
 * @ORM\Entity(repositoryClass="App\Repository\ProductRepository")
 */
class Product
{
    // usual stuff

    /**
     * @ORM\OneToMany(targetEntity="App\Entity\Product", mappedBy="preorders")
     */
    private $product;
}

In your formBuilder, product will be an entity and recognize by as such by the EntityType::class
EDIT
If your product is a legacy class unmapped by the ORM then you can use the dataTransformer to help your formBuilder recognize the legacy entity.
namespace App\DataTransformer;

class ProductToIdTransformer implements DataTransformerInterface
{
    public function transform($product)
    {
        if (null === $product) {
            return '';
        }

        return $product->getId();
    }

    public function reverseTransform($product_id)
    {
        if (!$product_id){
            return;
        }

        //your db logic to retrieve the product

        if (null === $field){
            throw new TransformationFailedException(sprintf("the product '%s' does not exist!", $product_id));
        }

        return $product;

    }
}

Then in your formbuilder you'll use a CollectionType instead:
$preorderForm = $this->createFormBuilder($preorder)
    ->add('email', EmailType::class)
    ->add('product', CollectionType::class, [
        'class' => Product::class,
        //some logic to adapt the different choices to your needs
    ])
;

$preorderForm
    ->get('product')
    ->addModelTransformer(ProductToIdTransformer::class)
;

$preorderForm = $preorderForm->getForm();


We depend on volunteers to help in many ways. At the Valley City Wetland Management District, a volunteer is anyone who assists the district staff with projects, daily tasks, or programs. We can help to build a volunteering experience around you and your needs and wants. Volunteers can commute from local communities to help within the district, or may stay and reside in a bunkhouse for an extended period if available.


How do I enroll as a Reward Points Member?
Enrollment is fast and free. If you are not registered then click here to sign up. Upon completion of registration you will start receiving reward points after each purchase.
PLEASE NOTE THAT YOU MUST BE REGISTERED ON OUR SITE AND LOGGED IN (MY ACCOUNT) PRIOR TO COMPLETING YOUR PURCHASE TO GET POINTS.
How much will I save by enrolling as a Reward Points Member?
Our Rewards Points Program is designed to provide discounts to our loyal customers.
How do I check my Reward Points balance?
To check your Reward Points balance you need to log into your account with your username and password. Once you have logged you can go to My Account located at the top right of the homepage to see all your account details including your Reward Points balance.
Registration – If you register for an account on our site you will earn 25 points.
Shopping – If you make a purchase you will receive 1 point for every $1 spent.
Product Reviews – If you write a product review you will earn 10 points. Maximum of 5 reviews per month.
How do I apply my points to a purchase?
If you are logged in you will see your points balance at the time of checkout. You can apply points at the time of your purchase or they can be saved for a future date.
Reward points are redeemable up to 180 from the date of your purchase. After 180 days your points balance will expire if unused. You will receive an email reminder 30 days prior to the expiration of your points.


What things have gone wrong with the car? There are no weaknesses to this car. It is really great. You get wg=hat you pay for.
General comments? overall this car is fun to drive, has a nice V6, and can outperform any Accord, Maxima, Malibu, Mazda 626, etc. out there. Dont let the price fool you, because it is worth much more that I payed for. I timed myself and got this Camry to go from 0-60MPH in about 7.8sec. I would definatly pay more for this car if I had to. And if you have a late model Camry, such as a 1997, my friend says that there is a big difference between the 1997, and the 2001, and he's gonna trade his old one in for a new one. He says that Toyota fixed alot of things in the new ones. I am really happy with this car, and it will do good as any type of car. If your on a budget, and want more for your money, go for the Camry.
Previous car I also have a BMW 540i, and 330xi, and it is my first toyota. We use this car as a family car for long trips. It cant be compared to my other cars, but for a toyota, it is a pretty good car.


text:
Q: Let $A_1,\dots,A_k \subset \mathbb{R}^n$. If $x \in \text{conv}(A_1+…+A_k)$, then $x \in \text{conv}(A_1'+…+A_k')$, with finite $A_i' \subset A_i$.
Let $A_1,\dots,A_k \subset \mathbb{R}^n$. If $x \in \text{conv}(A_1+…+A_k)$, then $x \in \text{conv}(A_1'+…+A_k')$, with finite $A_i' \subset A_i$.

I'm trying to verify this remark. If $x$ can be bounded by a simplex in $\text{conv}(A_1+…+A_k)$, then we can use it to find such $A_1',…,A_k'$ where $x$ has a representation in $\text{conv}(A_1'+…+A_k')$. But what do I do when $x$ cannot be bounded that way? For example, take $A_1,A_2$ to be a ball and a rectangle in $\mathbb{R}^2$, and $x$ a corner in $\text{conv}(A_1+A_2)$.

A: The convex hull of a set $A$ is equivalent to the set of all convex combinations of points in $A$ (see for example Convex hull: Equivalence of definitions).
Therefore, if $x \in \operatorname{conv}(A_1+ A_2 + \cdots +A_k)$ then
$$
 x = \sum_{j=1}^N \lambda_j (a_{j, 1} + a_{j, 2} + \cdots + a_{j, k})
$$
where $\lambda_k \ge 0$ are real numbers with $\sum_{k=1}^N \lambda_k = 1$, and $a_{j, i}  \in A_i$. Then
$$
 A_i' = \{ a_{1, i}, a_{2, i}, \ldots, a_{N, i} \}
$$
are finite subsets of $A_i$, and $x \in \operatorname{conv}(A_1'+ A_2' + \cdots +A_k')$.


text:
Microbiology 15.2 How Pathogens Cause Disease
Summarize Koch's postulates and molecular Koch's postulates, respectively, and explain their significance and limitations
Explain the concept of pathogenicity (virulence) in terms of infectious and lethal dose
Distinguish between primary and opportunistic pathogens and identify specific examples of each
Summarize the stages of pathogenesis
Explain the roles of portals of entry and exit in the transmission of disease and identify specific examples of these portals
For most infectious diseases, the ability to accurately identify the causative pathogen is a critical step in finding or prescribing effective treatments. Today's physicians, patients, and researchers owe a sizable debt to the physician Robert Koch (1843–1910), who devised a systematic approach for confirming causative relationships between diseases and specific pathogens.
Koch's Postulates
In 1884, Koch published four postulates (Table 15.3) that summarized his method for determining whether a particular microorganism was the cause of a particular disease. Each of Koch's postulates represents a criterion that must be met before a disease can be positively linked with a pathogen. In order to determine whether the criteria are met, tests are performed on laboratory animals and cultures from healthy and diseased animals are compared (Figure 15.4).
(1) The suspected pathogen must be found in every case of disease and not be found in healthy individuals.
(2) The suspected pathogen can be isolated and grown in pure culture.
(3) A healthy test subject infected with the suspected pathogen must develop the same signs and symptoms of disease as seen in postulate 1.
(4) The pathogen must be re-isolated from the new host and must be identical to the pathogen from postulate 2.
Table 15.3
Figure 15.4 The steps for confirming that a pathogen is the cause of a particular disease using Koch's postulates.
In many ways, Koch's postulates are still central to our current understanding of the causes of disease. However, advances in microbiology have revealed some important limitations in Koch's criteria. Koch made several assumptions that we now know are untrue in many cases. The first relates to postulate 1, which assumes that pathogens are only found in diseased, not healthy, individuals. This is not true for many pathogens. For example, H. pylori, described earlier in this chapter as a pathogen causing chronic gastritis, is also part of the normal microbiota of the stomach in many healthy humans who never develop gastritis. It is estimated that upwards of 50% of the human population acquires H. pylori early in life, with most maintaining it as part of the normal microbiota for the rest of their life without ever developing disease.
Koch's second faulty assumption was that all healthy test subjects are equally susceptible to disease. We now know that individuals are not equally susceptible to disease. Individuals are unique in terms of their microbiota and the state of their immune system at any given time. The makeup of the resident microbiota can influence an individual's susceptibility to an infection. Members of the normal microbiota play an important role in immunity by inhibiting the growth of transient pathogens. In some cases, the microbiota may prevent a pathogen from establishing an infection; in others, it may not prevent an infection altogether but may influence the severity or type of signs and symptoms. As a result, two individuals with the same disease may not always present with the same signs and symptoms. In addition, some individuals have stronger immune systems than others. Individuals with immune systems weakened by age or an unrelated illness are much more susceptible to certain infections than individuals with strong immune systems.
Koch also assumed that all pathogens are microorganisms that can be grown in pure culture (postulate 2) and that animals could serve as reliable models for human disease. However, we now know that not all pathogens can be grown in pure culture, and many human diseases cannot be reliably replicated in animal hosts. Viruses and certain bacteria, including Rickettsia and Chlamydia, are obligate intracellular pathogens that can grow only when inside a host cell. If a microbe cannot be cultured, a researcher cannot move past postulate 2. Likewise, without a suitable nonhuman host, a researcher cannot evaluate postulate 2 without deliberately infecting humans, which presents obvious ethical concerns. AIDS is an example of such a disease because the human immunodeficiency virus (HIV) only causes disease in humans.
Briefly summarize the limitations of Koch's postulates.
Molecular Koch's Postulates
In 1988, Stanley Falkow (1934–) proposed a revised form of Koch's postulates known as molecular Koch's postulates. These are listed in the left column of Table 15.4. The premise for molecular Koch's postulates is not in the ability to isolate a particular pathogen but rather to identify a gene that may cause the organism to be pathogenic.
Falkow's modifications to Koch's original postulates explain not only infections caused by intracellular pathogens but also the existence of pathogenic strains of organisms that are usually nonpathogenic. For example, the predominant form of the bacterium Escherichia coli is a member of the normal microbiota of the human intestine and is generally considered harmless. However, there are pathogenic strains of E. coli such as enterotoxigenic E. coli (ETEC) and enterohemorrhagic E. coli (O157:H7) (EHEC). We now know ETEC and EHEC exist because of the acquisition of new genes by the once-harmless E. coli, which, in the form of these pathogenic strains, is now capable of producing toxins and causing illness. The pathogenic forms resulted from minor genetic changes. The right-side column of Table 15.4 illustrates how molecular Koch's postulates can be applied to identify EHEC as a pathogenic bacterium.
Molecular Koch's Postulates Applied to EHEC
Application to EHEC
(1) The phenotype (sign or symptom of disease) should be associated only with pathogenic strains of a species. EHEC causes intestinal inflammation and diarrhea, whereas nonpathogenic strains of E. coli do not.
(2) Inactivation of the suspected gene(s) associated with pathogenicity should result in a measurable loss of pathogenicity. One of the genes in EHEC encodes for Shiga toxin, a bacterial toxin (poison) that inhibits protein synthesis. Inactivating this gene reduces the bacteria's ability to cause disease.
(3) Reversion of the inactive gene should restore the disease phenotype. By adding the gene that encodes the toxin back into the genome (e.g., with a phage or plasmid), EHEC's ability to cause disease is restored.
As with Koch's original postulates, the molecular Koch's postulates have limitations. For example, genetic manipulation of some pathogens is not possible using current methods of molecular genetics. In a similar vein, some diseases do not have suitable animal models, which limits the utility of both the original and molecular postulates.
Explain the differences between Koch's original postulates and the molecular Koch's postulates.
Pathogenicity and Virulence
The ability of a microbial agent to cause disease is called pathogenicity, and the degree to which an organism is pathogenic is called virulence. Virulence is a continuum. On one end of the spectrum are organisms that are avirulent (not harmful) and on the other are organisms that are highly virulent. Highly virulent pathogens will almost always lead to a disease state when introduced to the body, and some may even cause multi-organ and body system failure in healthy individuals. Less virulent pathogens may cause an initial infection, but may not always cause severe illness. Pathogens with low virulence would more likely result in mild signs and symptoms of disease, such as low-grade fever, headache, or muscle aches. Some individuals might even be asymptomatic.
An example of a highly virulent microorganism is Bacillus anthracis, the pathogen responsible for anthrax. B. anthracis can produce different forms of disease, depending on the route of transmission (e.g., cutaneous injection, inhalation, ingestion). The most serious form of anthrax is inhalation anthrax. After B. anthracis spores are inhaled, they germinate. An active infection develops and the bacteria release potent toxins that cause edema (fluid buildup in tissues), hypoxia (a condition preventing oxygen from reaching tissues), and necrosis (cell death and inflammation). Signs and symptoms of inhalation anthrax include high fever, difficulty breathing, vomiting and coughing up blood, and severe chest pains suggestive of a heart attack. With inhalation anthrax, the toxins and bacteria enter the bloodstream, which can lead to multi-organ failure and death of the patient. If a gene (or genes) involved in pathogenesis is inactivated, the bacteria become less virulent or nonpathogenic.
Virulence of a pathogen can be quantified using controlled experiments with laboratory animals. Two important indicators of virulence are the median infectious dose (ID50) and the median lethal dose (LD50), both of which are typically determined experimentally using animal models. The ID50 is the number of pathogen cells or virions required to cause active infection in 50% of inoculated animals. The LD50 is the number of pathogenic cells, virions, or amount of toxin required to kill 50% of infected animals. To calculate these values, each group of animals is inoculated with one of a range of known numbers of pathogen cells or virions. In graphs like the one shown in Figure 15.5, the percentage of animals that have been infected (for ID50) or killed (for LD50) is plotted against the concentration of pathogen inoculated. Figure 15.5 represents data graphed from a hypothetical experiment measuring the LD50 of a pathogen. Interpretation of the data from this graph indicates that the LD50 of the pathogen for the test animals is 104 pathogen cells or virions (depending upon the pathogen studied).
Figure 15.5 A graph like this is used to determine LD50 by plotting pathogen concentration against the percent of infected test animals that have died. In this example, the LD50 = 104 pathogenic particles.
Table 15.5 lists selected foodborne pathogens and their ID50 values in humans (as determined from epidemiologic data and studies on human volunteers). Keep in mind that these are median values. The actual infective dose for an individual can vary widely, depending on factors such as route of entry; the age, health, and immune status of the host; and environmental and pathogen-specific factors such as susceptibility to the acidic pH of the stomach. It is also important to note that a pathogen's infective dose does not necessarily correlate with disease severity. For example, just a single cell of Salmonella enterica serotype Typhimurium can result in an active infection. The resultant disease, Salmonella gastroenteritis or salmonellosis, can cause nausea, vomiting, and diarrhea, but has a mortality rate of less than 1% in healthy adults. In contrast, S. enterica serotype Typhi has a much higher ID50, typically requiring as many as 1,000 cells to produce infection. However, this serotype causes typhoid fever, a much more systemic and severe disease that has a mortality rate as high as 10% in untreated individuals.
ID50 for Selected Foodborne Diseases4
Hepatitis A virus 10–100
Norovirus 1–10
Rotavirus 10–100
Escherichia coli, enterohemorrhagic (EHEC, serotype O157) 10–100
E. coli, enteroinvasive (EIEC) 200–5,000
E. coli, enteropathogenic (EPEC) 10,000,000–10,000,000,000
E. coli, enterotoxigenic (ETEC) 10,000,000–10,000,000,000
Salmonella enterica serovar Typhi <1,000
S. enterica serovar Typhimurium ≥1
Shigella dysenteriae 10–200
Vibrio cholerae (serotypes O139, O1) 1,000,000
V. parahemolyticus 100,000,000
Giardia lamblia 1
Cryptosporidium parvum 10–100
What is the difference between a pathogen's infective dose and lethal dose?
Which is more closely related to the severity of a disease?
Primary Pathogens versus Opportunistic Pathogens
Pathogens can be classified as either primary pathogens or opportunistic pathogens. A primary pathogen can cause disease in a host regardless of the host's resident microbiota or immune system. An opportunistic pathogen, by contrast, can only cause disease in situations that compromise the host's defenses, such as the body's protective barriers, immune system, or normal microbiota. Individuals susceptible to opportunistic infections include the very young, the elderly, women who are pregnant, patients undergoing chemotherapy, people with immunodeficiencies (such as acquired immunodeficiency syndrome [AIDS]), patients who are recovering from surgery, and those who have had a breach of protective barriers (such as a severe wound or burn).
An example of a primary pathogen is enterohemorrhagic E. coli (EHEC), which produces a virulence factor known as Shiga toxin. This toxin inhibits protein synthesis, leading to severe and bloody diarrhea, inflammation, and renal failure, even in patients with healthy immune systems. Staphylococcus epidermidis, on the other hand, is an opportunistic pathogen that is among the most frequent causes of nosocomial disease.5 S. epidermidis is a member of the normal microbiota of the skin, where it is generally avirulent. However, in hospitals, it can also grow in biofilms that form on catheters, implants, or other devices that are inserted into the body during surgical procedures. Once inside the body, S. epidermidis can cause serious infections such as endocarditis, and it produces virulence factors that promote the persistence of such infections.
Other members of the normal microbiota can also cause opportunistic infections under certain conditions. This often occurs when microbes that reside harmlessly in one body location end up in a different body system, where they cause disease. For example, E. coli normally found in the large intestine can cause a urinary tract infection if it enters the bladder. This is the leading cause of urinary tract infections among women.
Members of the normal microbiota may also cause disease when a shift in the environment of the body leads to overgrowth of a particular microorganism. For example, the yeast Candida is part of the normal microbiota of the skin, mouth, intestine, and vagina, but its population is kept in check by other organisms of the microbiota. If an individual is taking antibacterial medications, however, bacteria that would normally inhibit the growth of Candida can be killed off, leading to a sudden growth in the population of Candida, which is not affected by antibacterial medications because it is a fungus. An overgrowth of Candida can manifest as oral thrush (growth on mouth, throat, and tongue), a vaginal yeast infection, or cutaneous candidiasis. Other scenarios can also provide opportunities for Candida infections. Untreated diabetes can result in a high concentration of glucose in the saliva, which provides an optimal environment for the growth of Candida, resulting in thrush. Immunodeficiencies such as those seen in patients with HIV, AIDS, and cancer also lead to higher incidence of thrush. Vaginal yeast infections can result from decreases in estrogen levels during the menstruation or menopause. The amount of glycogen available to lactobacilli in the vagina is controlled by levels of estrogen; when estrogen levels are low, lactobacilli produce less lactic acid. The resultant increase in vaginal pH allows overgrowth of Candida in the vagina.
Explain the difference between a primary pathogen and an opportunistic pathogen.
Describe some conditions under which an opportunistic infection can occur.
Stages of Pathogenesis
To cause disease, a pathogen must successfully achieve four steps or stages of pathogenesis: exposure (contact), adhesion (colonization), invasion, and infection. The pathogen must be able to gain entry to the host, travel to the location where it can establish an infection, evade or overcome the host's immune response, and cause damage (i.e., disease) to the host. In many cases, the cycle is completed when the pathogen exits the host and is transmitted to a new host.
An encounter with a potential pathogen is known as exposure or contact. The food we eat and the objects we handle are all ways that we can come into contact with potential pathogens. Yet, not all contacts result in infection and disease. For a pathogen to cause disease, it needs to be able to gain access into host tissue. An anatomic site through which pathogens can pass into host tissue is called a portal of entry. These are locations where the host cells are in direct contact with the external environment. Major portals of entry are identified in Figure 15.6 and include the skin, mucous membranes, and parenteral routes.
Figure 15.6 Shown are different portals of entry where pathogens can gain access into the body. With the exception of the placenta, many of these locations are directly exposed to the external environment.
Mucosal surfaces are the most important portals of entry for microbes; these include the mucous membranes of the respiratory tract, the gastrointestinal tract, and the genitourinary tract. Although most mucosal surfaces are in the interior of the body, some are contiguous with the external skin at various body openings, including the eyes, nose, mouth, urethra, and anus.
Most pathogens are suited to a particular portal of entry. A pathogen's portal specificity is determined by the organism's environmental adaptions and by the enzymes and toxins they secrete. The respiratory and gastrointestinal tracts are particularly vulnerable portals of entry because particles that include microorganisms are constantly inhaled or ingested, respectively.
Pathogens can also enter through a breach in the protective barriers of the skin and mucous membranes. Pathogens that enter the body in this way are said to enter by the parenteral route. For example, the skin is a good natural barrier to pathogens, but breaks in the skin (e.g., wounds, insect bites, animal bites, needle pricks) can provide a parenteral portal of entry for microorganisms.
In pregnant women, the placenta normally prevents microorganisms from passing from the mother to the fetus. However, a few pathogens are capable of crossing the blood-placental barrier. The gram-positive bacterium Listeria monocytogenes, which causes the foodborne disease listeriosis, is one example that poses a serious risk to the fetus and can sometimes lead to spontaneous abortion. Other pathogens that can pass the placental barrier to infect the fetus are known collectively by the acronym TORCH (Table 15.6).
Transmission of infectious diseases from mother to baby is also a concern at the time of birth when the baby passes through the birth canal. Babies whose mothers have active chlamydia or gonorrhea infections may be exposed to the causative pathogens in the vagina, which can result in eye infections that lead to blindness. To prevent this, it is standard practice to administer antibiotic drops to infants' eyes shortly after birth.
Pathogens Capable of Crossing the Placental Barrier (TORCH Infections)
T Toxoplasmosis Toxoplasma gondii (protozoan)
O6 Syphilis
Fifth disease (erythema infectiosum) Treponema pallidum (bacterium)
Varicella-zoster virus (human herpesvirus 3)
Hepatitis B virus (hepadnavirus)
Parvovirus B19
R Rubella (German measles) Togavirus
C Cytomegalovirus Human herpesvirus 5
H Herpes Herpes simplex viruses (HSV) 1 and 2
At the clinic, a physician takes down Michael's medical history and asks about his activities and diet over the past week. Upon learning that Michael became sick the day after the party, the physician orders a blood test to check for pathogens associated with foodborne diseases. After tests confirm that presence of a gram-positive rod in Michael's blood, he is given an injection of a broad-spectrum antibiotic and sent to a nearby hospital, where he is admitted as a patient. There he is to receive additional intravenous antibiotic therapy and fluids.
Is this bacterium in Michael's blood part of normal microbiota?
What portal of entry did the bacteria use to cause this infection?
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Following the initial exposure, the pathogen adheres at the portal of entry. The term adhesion refers to the capability of pathogenic microbes to attach to the cells of the body using adhesion factors, and different pathogens use various mechanisms to adhere to the cells of host tissues.
Molecules (either proteins or carbohydrates) called adhesins are found on the surface of certain pathogens and bind to specific receptors (glycoproteins) on host cells. Adhesins are present on the fimbriae and flagella of bacteria, the cilia of protozoa, and the capsids or membranes of viruses. Protozoans can also use hooks and barbs for adhesion; spike proteins on viruses also enhance viral adhesion. The production of glycocalyces (slime layers and capsules) (Figure 15.7), with their high sugar and protein content, can also allow certain bacterial pathogens to attach to cells.
Biofilm growth can also act as an adhesion factor. A biofilm is a community of bacteria that produce a glycocalyx, known as extrapolymeric substance (EPS), that allows the biofilm to attach to a surface. Persistent Pseudomonas aeruginosa infections are common in patients suffering from cystic fibrosis, burn wounds, and middle-ear infections (otitis media) because P. aeruginosa produces a biofilm. The EPS allows the bacteria to adhere to the host cells and makes it harder for the host to physically remove the pathogen. The EPS not only allows for attachment but provides protection against the immune system and antibiotic treatments, preventing antibiotics from reaching the bacterial cells within the biofilm. In addition, not all bacteria in a biofilm are rapidly growing; some are in stationary phase. Since antibiotics are most effective against rapidly growing bacteria, portions of bacteria in a biofilm are protected against antibiotics.7
Figure 15.7 Glycocalyx produced by bacteria in a biofilm allows the cells to adhere to host tissues and to medical devices such as the catheter surface shown here. (credit: modification of work by Centers for Disease Control and Prevention)
Once adhesion is successful, invasion can proceed. Invasion involves the dissemination of a pathogen throughout local tissues or the body. Pathogens may produce exoenzymes or toxins, which serve as virulence factors that allow them to colonize and damage host tissues as they spread deeper into the body. Pathogens may also produce virulence factors that protect them against immune system defenses. A pathogen's specific virulence factors determine the degree of tissue damage that occurs. Figure 15.8 shows the invasion of H. pylori into the tissues of the stomach, causing damage as it progresses.
Figure 15.8 H. pylori is able to invade the lining of the stomach by producing virulence factors that enable it pass through the mucin layer covering epithelial cells. (credit: modification of work by Zina Deretsky, National Science Foundation)
Intracellular pathogens achieve invasion by entering the host's cells and reproducing. Some are obligate intracellular pathogens (meaning they can only reproduce inside of host cells) and others are facultative intracellular pathogens (meaning they can reproduce either inside or outside of host cells). By entering the host cells, intracellular pathogens are able to evade some mechanisms of the immune system while also exploiting the nutrients in the host cell.
Entry to a cell can occur by endocytosis. For most kinds of host cells, pathogens use one of two different mechanisms for endocytosis and entry. One mechanism relies on effector proteins secreted by the pathogen; these effector proteins trigger entry into the host cell. This is the method that Salmonella and Shigella use when invading intestinal epithelial cells. When these pathogens come in contact with epithelial cells in the intestine, they secrete effector molecules that cause protrusions of membrane ruffles that bring the bacterial cell in. This process is called membrane ruffling. The second mechanism relies on surface proteins expressed on the pathogen that bind to receptors on the host cell, resulting in entry. For example, Yersinia pseudotuberculosis produces a surface protein known as invasin that binds to beta-1 integrins expressed on the surface of host cells.
Some host cells, such as white blood cells and other phagocytes of the immune system, actively endocytose pathogens in a process called phagocytosis. Although phagocytosis allows the pathogen to gain entry to the host cell, in most cases, the host cell kills and degrades the pathogen by using digestive enzymes. Normally, when a pathogen is ingested by a phagocyte, it is enclosed within a phagosome in the cytoplasm; the phagosome fuses with a lysosome to form a phagolysosome, where digestive enzymes kill the pathogen (see Pathogen Recognition and Phagocytosis). However, some intracellular pathogens have the ability to survive and multiply within phagocytes. Examples include Listeria monocytogenes and Shigella; these bacteria produce proteins that lyse the phagosome before it fuses with the lysosome, allowing the bacteria to escape into the phagocyte's cytoplasm where they can multiply. Bacteria such as Mycobacterium tuberculosis, Legionella pneumophila, and Salmonella species use a slightly different mechanism to evade being digested by the phagocyte. These bacteria prevent the fusion of the phagosome with the lysosome, thus remaining alive and dividing within the phagosome.
Following invasion, successful multiplication of the pathogen leads to infection. Infections can be described as local, focal, or systemic, depending on the extent of the infection. A local infection is confined to a small area of the body, typically near the portal of entry. For example, a hair follicle infected by Staphylococcus aureus infection may result in a boil around the site of infection, but the bacterium is largely contained to this small location. Other examples of local infections that involve more extensive tissue involvement include urinary tract infections confined to the bladder or pneumonia confined to the lungs.
In a focal infection, a localized pathogen, or the toxins it produces, can spread to a secondary location. For example, a dental hygienist nicking the gum with a sharp tool can lead to a local infection in the gum by Streptococcus bacteria of the normal oral microbiota. These Streptococcus spp. may then gain access to the bloodstream and make their way to other locations in the body, resulting in a secondary infection.
When an infection becomes disseminated throughout the body, we call it a systemic infection. For example, infection by the varicella-zoster virus typically gains entry through a mucous membrane of the upper respiratory system. It then spreads throughout the body, resulting in the classic red skin lesions associated with chickenpox. Since these lesions are not sites of initial infection, they are signs of a systemic infection.
Sometimes a primary infection, the initial infection caused by one pathogen, can lead to a secondary infection by another pathogen. For example, the immune system of a patient with a primary infection by HIV becomes compromised, making the patient more susceptible to secondary diseases like oral thrush and others caused by opportunistic pathogens. Similarly, a primary infection by Influenzavirus damages and decreases the defense mechanisms of the lungs, making patients more susceptible to a secondary pneumonia by a bacterial pathogen like Haemophilus influenzae or Streptococcus pneumoniae. Some secondary infections can even develop as a result of treatment for a primary infection. Antibiotic therapy targeting the primary pathogen can cause collateral damage to the normal microbiota, creating an opening for opportunistic pathogens (see Case in Point: A Secondary Yeast Infection).
A Secondary Yeast Infection
Anita, a 36-year-old mother of three, goes to an urgent care center complaining of pelvic pressure, frequent and painful urination, abdominal cramps, and occasional blood-tinged urine. Suspecting a urinary tract infection (UTI), the physician requests a urine sample and sends it to the lab for a urinalysis. Since it will take approximately 24 hours to get the results of the culturing, the physician immediately starts Anita on the antibiotic ciprofloxacin. The next day, the microbiology lab confirms the presence of E. coli in Anita's urine, which is consistent with the presumptive diagnosis. However, the antimicrobial susceptibility test indicates that ciprofloxacin would not effectively treat Anita's UTI, so the physician prescribes a different antibiotic.
After taking her antibiotics for 1 week, Anita returns to the clinic complaining that the prescription is not working. Although the painful urination has subsided, she is now experiencing vaginal itching, burning, and discharge. After a brief examination, the physician explains to Anita that the antibiotics were likely successful in killing the E. coli responsible for her UTI; however, in the process, they also wiped out many of the "good" bacteria in Anita's normal microbiota. The new symptoms that Anita has reported are consistent with a secondary yeast infection by Candida albicans, an opportunistic fungus that normally resides in the vagina but is inhibited by the bacteria that normally reside in the same environment.
To confirm this diagnosis, a microscope slide of a direct vaginal smear is prepared from the discharge to check for the presence of yeast. A sample of the discharge accompanies this slide to the microbiology lab to determine if there has been an increase in the population of yeast causing vaginitis. After the microbiology lab confirms the diagnosis, the physician prescribes an antifungal drug for Anita to use to eliminate her secondary yeast infection.
Why was Candida not killed by the antibiotics prescribed for the UTI?
List three conditions that could lead to a secondary infection.
Transmission of Disease
For a pathogen to persist, it must put itself in a position to be transmitted to a new host, leaving the infected host through a portal of exit (Figure 15.9). As with portals of entry, many pathogens are adapted to use a particular portal of exit. Similar to portals of entry, the most common portals of exit include the skin and the respiratory, urogenital, and gastrointestinal tracts. Coughing and sneezing can expel pathogens from the respiratory tract. A single sneeze can send thousands of virus particles into the air. Secretions and excretions can transport pathogens out of other portals of exit. Feces, urine, semen, vaginal secretions, tears, sweat, and shed skin cells can all serve as vehicles for a pathogen to leave the body. Pathogens that rely on insect vectors for transmission exit the body in the blood extracted by a biting insect. Similarly, some pathogens exit the body in blood extracted by needles.
Figure 15.9 Pathogens leave the body of an infected host through various portals of exit to infect new hosts.
4 Food and Drug Administration. "Bad Bug Book, Foodborne Pathogenic Microorganisms and Natural Toxins." 2nd ed. Silver Spring, MD: US Food and Drug Administration; 2012.
5 M. Otto. "Staphylococcus epidermidis--The 'Accidental' Pathogen." Nature Reviews Microbiology 7 no. 8 (2009):555–567.
6 The O in TORCH stands for "other."
7 D. Davies. "Understanding Biofilm Resistance to Antibacterial Agents." Nature Reviews Drug Discovery 2 (2003):114–122.
Section URL: https://openstax.org/books/microbiology/pages/15-2-how-pathogens-cause-disease


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