Embryology

The embryologist entrepreneur – BQ Live

Tell us about your businesses, Caroline.

I run two businesses. Alba SEO services provides digital marketing services to Scottish based SMEs whilst Fertility Clinics Abroad is an online portal which provides impartial information and advice to people seeking fertility treatment outside of the UK.

And how did you get from working as an embryologist to running your own business?

After completing my PhD from Edinburgh University in Mammalian Embryology followed by a two year research project, I began working as an embryologist at the London Fertility Centre Harley Street and then as a senior clinical embryologist at the IVF Unit at the Chelsea and Westminster Hospital. In 1996, I decided to move back home to Edinburgh and took up another two year research post.

The research was successful, but the project was moving to Western Australia with my research leader and I wasnt keen to move, so I began thinking about a change of career. I was looking for a more stable job with set hours lab work is great but the hours can be inconsistent.

I went back to university again and attained an MSc Diploma in Information Technology from Napier University which was a springboard to a graduate entry with the IT services department at the Royal Bank of Scotland. I had always had an interest in IT, so this was my chance to gain some experience in a new field. I got the job and ended up working at the Bank for 12 years.

I was part of a team that processed the money that went through the ATM machines, before moving to the service improvement department. Working part-time suited me as I had a young family and it fitted in with my work-life balance.

In 2011 I was made redundant and so an opportunity was opened up for me. I had been thinking about starting a business that utilised my skills in IT and my knowledge and experience in embryology and Fertility Clinics Abroad seemed like the perfect fit.

My work as a senior embryologist made me realise how little information was available to people looking into fertility options outside of the UK there was a real gap in the market for a one stop shop service where you could access all the required information from one place. When the opportunity arose to set something like this up, I felt compelled to go for it.

Once Fertility Clinics Abroad was up and running, the idea to set up a separate digital marketing company came pretty quickly. FCA is a web based platform, so I knew that I needed to improve my website ranking to attract more people to the site. I started reading and buying books about Search Engine Optimisation. I spent about a year on my own site and achieved a page one Google ranking - I thought to myself, if I can do that on my site, why can't I apply what I know to others?

So that's exactly what I did. I created another business called Alba SEO Services, built a website and proceeded to get it to the top of Google too. By doing that, I got noticed and businesses started to come to me for help. At that point Alba was officially born! Now I run FCA and Alba in conjunction with each other. In fact, FCA could be considered a client of Alba.

Was there a desire to run your own business generally?

The desire has definitely always been there. I have always craved the flexibility and freedom that comes with running your own business. There is something refreshing about managing a small business I am used to the bureaucracy of large corporations that that can be slow and cumbersome in comparison to SMEs. When you have your own business, you can introduce and test news ideas, bring in new revenue streams, experiment without any proverbial hoops to jump through. You are the master of your own destiny, if you will.

How did you learn all of the skills you need to be successful marketing, bookkeeping etc?

Most of the SEO skills I needed to set up Alba were self-taught and came about from running Fertility Clinics Abroad. I read books, did a lot of online research and learnt by testing things on my own site.

You could say my first company was the training ground for the second business I set up. Of course I also learnt a lot while working at RBS bookkeeping, processing records, team building, people management where all part of my role at the bank and put me in good steads for setting up my own company.

However I think any business owner would admit that no-one goes into business knowing everything there is an element of learning on the job. Its ok to make mistakes as long as you adapt and learn from them.

Why is there a need for your business?

Everything is online these days and most people use Google to find a business, or to buy a product or service. If your business is hidden on page two of Google, you won't get found.

So all businesses need to step up their marketing and make their websites as search friendly as possible. We are seeing demand from companies of all sizes soar everyone wants a website and everyone wants their website to be sitting at the top of Google searches.

Of course, increasing competition makes achieving this goal harder to come by, which is why companies that provide specialist SEO and digital marketing services are in big demand.

What does the future hold for your businesses?

We are hoping to grow Alba over the next few years. This time last year there were two of us, now there are four, so we are moving in the right direction. In the future, Id like to be more hands off so I can manage the business rather than implementing campaigns and getting involved with the day to day work. Id say working on the business rather than working in the business.

Im potentially looking to take someone on to take on more of the account management role to allow me to step back a little.

Regarding FCA were looking to become the number one place to go for impartial, high quality information about fertility treatment abroad key to this is having a critical mass of clinics listed so that I can give a truly representative view of the industry across Europe.

However, Im not really looking to grow in the sense of employing people or generating new revenue streams. Its more about improving the quality and quantity of information we provide

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The embryologist entrepreneur - BQ Live

Cell Biology

Use of the Quorum Cryo-SEM preparation system in microbial cell biology with electron cryotomography at the Jensen … – News-Medical.net

Quorum Technologies, market and technology leaders in electron microscopy coating and cryogenic preparation products, report on how their PP3010T Cryo-SEM preparation system is being used in the preparation of hydrated whole cells to be imaged using electron cryotomography in the Jensen Laboratory located at HHMI Caltech.

Image of fission yeast Schizosaccharomyces pombe cells prepared for TEM - by Vitrobot freezing on Quantifoil grids and Quorum PP3010T transfer for FEI Versa FIB milling.

Alasdair McDowall is the EM Center Director in the Jensen Laboratory at the Howard Hughes Medical Institute located at Caltech. Headed by Professor Grant Jensen, the Lab uses Electron Cryotomography (ECT) to study the molecular architecture of microbial cells and HIV in their native state. The focus is on the fundamentals of microbial cell biology such as cell division, movement and secretion, as well as the structure of HIV at all stages of its lifecycle.

The lab opened its doors in 2002 and continues to push the boundaries of high resolution imaging today. However, the investigation of frozen hydrated whole cells (beam and vacuum sensitive materials) in the electron microscope chamber requires new solutions. The advances in techniques for the preparation of cells by Cryo Focused Ion Beam Milling for structural characterization have recently provided a new insight of these delicate cellular architectures.

Image of fission yeast Schizosaccharomyces pombe cells prepared for TEM - by Vitrobot freezing on Quantifoil grids and Quorum PP3010T transfer for FEI Versa FIB milling.

Cryo Focused Ion Beam milling (cryo FIB milling) is a cutting-edge method for thinning vitrified biological samples that allows access to intracellular regions of thick specimens (> 1 um) with unprecedented ease and structural preservation. It provides the ability to move beyond imaging only small bacterial cells with electron cryotomography (ECT) and will allow the exploration of eukaryotic cells, tissues and microbial biofilms to the same molecular resolution that the group has achieved with individual bacterial cells for the past decade.

In addition, the ability to thin individual bacterial cells before imaging, without perturbing their structure, will provide higher contrast and resolution when necessary, even within already thin bacterial cells. Furthermore, the addition of a cryo-stage to the existing FIB mill at Caltech will allow for further development of much needed methods for correlating fluorescence microscopy and electron tomography for the targeting and identification of specific structures deep within eukaryotic cells, bacteria and tissues.

Image of fission yeast Schizosaccharomyces pombe cells prepared for TEM - by Vitrobot freezing on Quantifoil grids and Quorum PP3010T transfer for FEI Versa FIB milling.

Dr McDowall uses the Quorum PP3010T cryo sample preparation system. This is a highly automated, easy-to-use, column-mounted, gas-cooled Cryo-SEM preparation system suitable for most makes and models of SEM, FE-SEM and FIB/SEM. The Jensen group uses their prep system with an FEI Versa scanning electron microscope.

Dr McDowall

To obtain full details of Cryo-SEM preparation systems and other products available from Quorum Technologies, please visit http://www.quorumtech.com.

Acknowledgements: Quorum Technologies thanks the following for sharing their research: Professors Grant Jensen & Julia Greer and Drs Matt Swuilius, Shrawan Mageswaran & Wei Zhao.

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Use of the Quorum Cryo-SEM preparation system in microbial cell biology with electron cryotomography at the Jensen ... - News-Medical.net

Cell Biology

Bakar Fellow: Aiding cells’ strategy to survive – Phys.Org

February 6, 2017 by Wallace Ravven James Hurleys lab has determined the molecular structure of the site where production of bubble-shaped autophagosomes begins in cells organelles essential to rid the cells of debris. Credit: University of California - Berkeley

As any human biology text will tell you, enzymes in the stomach and intestine break down proteins that are locked into almost every bite we eat. The proteins' amino acid building blocks are then transported to the body's hungry cells.

There, construction begins anew as cell machinery reassembles new proteins for whatever tasks the genes call: ramping up energy production, ferrying materiel to different cell siteseven switching gene activity on or off.

But cells don't consume every protein they are offered, and leftovers can build up, clogging metabolism and threatening cell survival. Protein production can also go awry. Some must be disassembled in the cell and rebuilt, often leaving bits and pieces on the factory floor.

The Bakar Fellows Program supports research by biochemist James Hurley, professor of molecular and cell biology, to develop a new drug to boost the natural process that sweeps these threats away.

A cell's failure to clean house poses other direct threats to survival. Over the course of its life, a cell's machinery runs down. Mitochondria, the cell's powerhouses, falter and free charged atoms and molecules known as oxygen free radicals to indiscriminately destroy proteins. The cell is all but doomed.

"You don't want your cells filling up with failed mitochondria or unused protein fragments," Hurley says.

The natural, life-saving process called autophagy cleans the table, carrying out two crucial roles at the same time. It spares the cell from multiple insults, and makes leftovers available for re-usea boon when food is scarce.

The key player in autophagy is callednot surprisinglyan autophagosome. The autophagosome is a bubble-shaped sac that engulfs left-over amino acids, spent mitochondria and other materiel, and ferries them to recycling sites. An autophagosome "can fit snugly around a single mitochondrion," Hurley says.

But as in every cell function, this too can fail. Neurons are particularly at risk, possibly due to the distance autophagosomes must travel through the cells' long dendrites and axons to bring their cargoes back to the cell body.

Studies in mice show that failed or sluggish autophagy causes neuron death. Inefficient autophagy may also drive the build-up of protein aggregates in neurons that is thought to cause Parkinson's disease.

Synthesis of autophagosomes in the cell is the result of an interaction between two protein complexeseach itself made up of several proteins. Hurley's lab has used a variety of techniqueselectron microscopy, x-ray crystallography, spectroscopy and live-cell imagingto clarify the atomic-level structure of these two units and their interaction. His research suggests that autophagosome synthesis is directly related to the distance between key sites in these two units.

The structural insights have led his lab to new research, funded by the Bakar Fellows Program, to develop a drug that can change the units' 3-D shapes and bring them into the "activated" shape or conformation. This conformation, he thinks, would increase the cell's production of autophagosomes.

The approach is unusual. Most pharmaceutical interest in these complexes has focused on strategies to thwart cancer growth by preventing the two complexes from becoming activeswitching off autophagosome production.

"It's much easier to turn off the signal than turn it on," Hurley says, and the effort to do so by changing the conformation of the two protein complexes is a young field made possible by powerful structural imaging techniques.

The entire process of assembling the autophagosome takes only about ten minutes, which makes sense from an evolutionary perspective, Hurley says. Starvation can snap the cell's autophagy machinery into action, quickly yielding nutrients to sustain cells, and allow the personor mouse or whalethey reside in to hunt for more substantial food.

While nutrient need and the threat of spent materials drive autophagy, recent research has shown that other factors can trigger the process. Calorie-restriction diets and exercise trigger production of autophagosomes, Hurley says.

These recent, "optional" activities mimic starvation that threatened ancestors at some point, and, sadly, continue to do so in many cultures today. In societies with readily available food, autophagy's ability to quickly provide more nutrients is far less important than its ability to clear cells of debris.

"If neurons can't rid themselves of failing mitochondria, this defect will lead to disease, or worse," he says. "We think we can develop a drug to reverse this threat."

Explore further: Researchers identify process cells use to destroy damaged organelles, with links to diseases

Researchers at UT Southwestern Medical Center have uncovered the mechanism that cells use to find and destroy an organelle called mitochondria that, when damaged, may lead to genetic problems, cancer, neurodegenerative diseases, ...

In a recent Science Advances article, Mayo Clinic researchers show how hungry human liver cells find energy. This study, done in rat and human liver cells, reports on the role of a small regulatory protein that acts like ...

Several well-known neurodegenerative diseases, such as Lou Gehrig's (ALS), Parkinson's, Alzheimer's, and Huntington's disease, all result in part from a defect in autophagy - one way a cell removes and recycles misfolded ...

(Medical Xpress) -- New research from scientists at the University of Cambridge provides critical insight into the formation of autophagosomes, which are responsible for cleaning up cellular waste.

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The concept behind microbial fuel cells, which rely on bacteria to generate an electrical current, is more than a century old. But turning that concept into a usable tool has been a long process. Microbial fuel cells, or ...

Digging around in the dark can sometimes lead to interesting results: in the acidic waters of an abandoned coal mine in Kentucky (USA), researchers discovered ten previously unknown microbial natural products from a strain ...

Can helium bond with other elements to form a stable compound? Students attentive to Utah State University professor Alex Boldyrev's introductory chemistry lectures would immediately respond "no." And they'd be correct ...

Chemists scouring Appalachia for exotic microorganisms that could yield blockbuster drugs have reported a unique find from the smoldering remains of a coal mine fire that's burned for nearly a decade in southeastern Kentucky.

A team of scientists from the Energy Department's National Renewable Energy Laboratory (NREL) determined that surface recombination limits the performance of polycrystalline perovskite solar cells.

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Bakar Fellow: Aiding cells' strategy to survive - Phys.Org

Cell Biology

Gene therapy allows ‘deaf’ mice to hear – Wired.co.uk

Getty Images / De Agostini Picture Library / Contributor

Hearing loss affects millions of people around the world, and in around half of those cases the root cause is genetic. Now, medical researchers have been able to restore the hearing and balance in mice by inserting mutated genes into their bodies. Two papers published in the Nature Biotechnology journal describe the results.

"We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behaviour to near wild-type levels," otolaryngologists from the Harvard Medical School say in the research paper.

It says the work shows an "unprecedented recovery of inner ear function" and claims the "biological therapies to treat deafness may be suitable for translation to humans".

During the work, young mice were used to prove the method works. The mice had been artificially administered with Usher syndrome type IC, which in human children causes deafness, balance dysfunction, and blindness.

Most people born with type I and type II Usher syndrome suffer with severe to profound hearing loss as well as vision problems. Those with type III experience hearing loss later in life. The work from the Harvard medical academics focussed purely on the hearing loss aspect of the syndrome.

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To tackle the deafness, the research team injected a synthetic version of the adeno-associated virus - which has very little impact on humans - into the ears of mice. Within the virus was a normal copy of the mutated Ush1c gene, which causes deafness in the syndrome. It was the first time scientists have been able to find a virus that can enter the inner ear and deliver genes to the inner and outer hair cells needed for normal hearing ability.

"Delivery of a normal copy of the mutated gene, Ush1c, to the cochlea soon after the mice were born led to high levels of Ush1c protein in outer and inner hair cells, repair of damaged hair cell bundles, and a robust improvement in hearing and balance behaviour, enabling profoundly deaf mice to hear sounds at the level of whispers," a statement published alongside the research said.

"They can restore the hearing defect by the gene transfer," Andrew Forge an emeritus professor of auditory cell biology at University College London and author on the first Nature paper, tells WIRED.

Ruth Taylor, another UCL researcher involved in the work, tested the gene transfer method with human tissue. Using vestibular tissue the UCL academics were able to show the virus could transfer the gene to the human tissue in culture. "They did a lot of proof of concept in mice," Forge says. "The bit we did is the extra bit to show this could work in people."

He explains the work - and the field in general - is trying to answer one big question: "Can you manipulate the system to cure things that are wrong?"

Forge adds: "These kinds of therapies, if there is going to be a therapy, will be the way it is going to be working".

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Gene therapy allows 'deaf' mice to hear - Wired.co.uk

Biochemistry

Biochemistry department celebrates 50 years of interdisciplinary, scientific learning – The Wellesley News

The oldest interdepartmental program at Wellesley College, the biochemistry department (BIOC), celebrates its 50th anniversary this academic year. Founded during a time marked by dramatic discoveries in the life sciences, the department is today regarded as an interface between biology and chemistry. In light of its anniversary, the department has held two events thus far, including a kickoff event organized by Professor Don Elmore and the 4th Annual Biological Chemistry Research Retreat, which was incorporated into the celebrations.

The kickoff event, held on Dec. 13, 2016, featured panel discussions on the programs history with renowned Professors Mary Allen and Dot Widmayer, and Sonja Hicks, Professor Emerita. It also included talks by six recent alumnae: Shloka Ananthanarayanan 08, Eleanor Fleming 08, Kate Lipford 08, Natalya Maharaj 09, Tracy Wang 10 and Ruth Wangondu 07. The discussions covered various topics and perspectives related to revolutionizing research since the founding of the department at Wellesley.

To continue the celebration, the Research Retreat was held just before the beginning of the semester on Jan. 23, 2017. According to Professor T. Kaye Peterman, the director of the biochemistry department, the event was an opportunity for students to share their research with the community. It also featured a keynote address by renowned immunologist Sarah J. Schlesinger 81 on Dendritic Cells, HIV Vaccines and the Nobel Prize.

Peterman believes that BIOC is a deeply interdisciplinary field with emphasis especially on meaningful and independent undergraduate research. The discipline of biochemistry is a combination of both the physical and natural sciences. Wellesleys course offerings include classes on cellular physiology, a study of the activities that keep a cell alive, and biophysical chemistry, a study of the physical properties of biological macromolecules.

Peterman suggested that what sets this department apart from others is its ability to synthesize [the two subjects] into a unique exploration of biological structure and function at the macromolecular level. The department has explored new fields of study within biochemistry such as genomics, the study of genomes, and proteomics, the study of proteins. These disciplines continue to emerge and evolve with the help of independent research conducted by students and professors.

Like other science departments at Wellesley, the biochemistry curriculum emphasizes the need for future researchers to not only be familiar with laboratory work with complex instruments and computers, but also to have strong problem solving techniques, collaboration skills, awareness of ethical issues and the ability to think across disciplinary boundaries.

The department will continue the celebration this spring with several talks by prominent BIOC alumnae who have made impactful and lasting contributions to their fields. Details will be distributed when these events become finalized. In conjunction with the celebration of the departments 50th anniversary, students majoring in biochemistry have taken the opportunity to reflect on the discipline which they hope to concentrate in.

Hannah Jacobs 19, a sophomore considering the biochemistry major, says that she is interested in the major because it is both fascinating and challenging.

Its specialized, but it will give me a breadth of knowledge about biological systems, she said, in reference to the concentration. Jacobs advises that any students thinking of majoring in this area should plan ahead and take organic chemistry as soon as possible, as it will give [them] an idea whether the major is right for [them].

Catherine Xie 19, a sophomore double-majoring in biochemistry and French, stated that her inspiration to join this field came from her grandmother, Pan Huazhen, who was a biochemist in China. By attending summer research courses in high school and investigating subjects that interested her, she found her fascination for science.

Xie has also channeled her passion of science by being part of the organization BC2 which arranges both lectures and dessert series with professors and student research panels with current biochemistry majors. Although she wishes there were fewer requirements for the major and more flexibility in the types of courses, Xies favorite part of the department is hearing about all the amazing research that [the] faculty carries out on campus.

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Biochemistry department celebrates 50 years of interdisciplinary, scientific learning - The Wellesley News

Biochemistry

Notre Dame Researchers Study Potential Cause of Common Birth Defect – ND Newswire

Small ubiquitin-like modifier (SUMO) proteins are small peptides that get added on to other proteins to regulate their activity. While SUMO has many regulatory roles in cells, it is especially important for controlling gene expression during early development. Just a few years ago this connection between SUMO and gene regulation was relatively unknown, but now, Notre Dame researchers are exploring how a disruption to the SUMO proteins ability to regulate embryo development may be linked to congenital heart defects.

Professor Paul Huber

Paul Huber, professor of chemistry and biochemistry, and Norman Dovichi, the Grace-Rupley Professor of Chemistry and Biochemistry, are working together to understand the role of all proteins in embryo development using Xenopus laevis or the African claw frog. This species is known for having a similar gene structure to that of the human genome, meaning that findings related to this species have the potential to provide a deep understanding about human diseases.

When discussing their research, Dovichi said, In 2014, Huber and I completed a study using Xenopus laevis embryos to understand how more than 4,000 proteins fluctuate during the different stages of development. We found that certain proteins spike or lower during specific stages. For example, a number of proteins that are used during the creation of cardiovascular tissue rose during stage 13, when organs develop.

Professor Norman Dovichi

In these early experiments, Huber found that when SUMO activity was repressed, many of the embryos had two predominate phenotypes, one of which was heart defects. Then, new studiesbegan linking mutations in SUMO protein to heart failure as well as congenital heart defects. This is when the Notre Dame researchers began to develop the next steps for their research.

At the time, there was not a lot of information about the role of the SUMO protein, but our theory was that it was critical for proper development of the heart, said Huber. To study the proteins specific impact, we inhibited SUMO activity in the developing cardiovascular tissue. This will allow us to compare the proteome or all of the proteins that are expressed by a cell of the defective hearts with their normal counterparts.

To support the research, Olivia Cox, a Notre Dame graduate student, collaborated with Daniel Weeks, professor of biochemistry and pediatrics at the University of Iowa, and identified three predominate heart defects in the SUMO-deficient hearts: septal defects commonly thought of as holes in the heart abnormal turning of the outflow tract, and noncompaction cardiomyopathy.

The goal of this research is to use the proteome comparisons to specifically identify which proteins are responsible for congenital heart defects. Additionally, Huber, affiliated with the Harper Cancer Research Institute (HCRI) and the Center for Stem Cells and Regenerative Medicine, and Dovichi, affiliated with Advanced Diagnostics and Therapeutics as well as the HCRI, plan to continue exploring the SUMO proteins significance in other areas of embryo development. This research could help explain why other development defects arise, and eventually lead to a solution for increasing SUMO protein expression when a mutation occurs.

Congenital heart defects impact more than 35,000 newborns in the United States each year and is the most common type of birth defect. To learn more about congenital heart defects, please visit https://www.nhlbi.nih.gov/health/health-topics/topics/chd.

Contact:

Brandi Klingerman / Research Communications Specialist

Notre Dame Research / University of Notre Dame

bklinger@nd.edu / 574.631.8183

research.nd.edu / @UNDResearch

About Notre Dame Research:

The University of Notre Dame is a private research and teaching university inspired by its Catholic mission. Located in South Bend, Indiana, its researchers are advancing human understanding through research, scholarship, education, and creative endeavor in order to be a repository for knowledge and a powerful means for doing good in the world. For more information, please see research.nd.edu or @UNDResearch.

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Notre Dame Researchers Study Potential Cause of Common Birth Defect - ND Newswire

Anatomy

Anatomy of an Ad: Tide’s Super Bowl Stain – AdAge.com

Ambitious doesn't quite fully describe Tide's gameplan for Super Bowl LI.

Marketing executives for the Procter & Gamble brand made it clear they would rather not run a big game ad if the creative wasn't worthy of Tide's Super Bowl heritage.

This year, live commercials are dominating the pre-game buzz but Tide, in partnership with Saatchi and Saatchi, Traktor and The Mill went a completely different and costly route.

Instead of simply advertising in the game, Tide became part of the broadcast, with a little help from Fox Sports announcers Curt Menefee and Terry Bradshaw -- and a bottle of barbeque sauce.

In part one of Anatomy of an Ad: The Stain below, we look at the idea behind Tide's big gambit in the big game. The goal: to trick an audience of over 100 million into believing Mr. Bradshaw's stain is happening in real time, that his anxiety is genuine and that Tide is there to clean up the mess.

The idea is one thing. The execution is quite another. Just three weeks before the game, P&G and its army of producers, gaffers and grips descended on El Camino Community College in Torrance, Calif. to turn it into a replica of NRG Stadium in Houston, Texas, complete with Fox Sport's Super Bowl broadcast booth and the tunnel leading to the field.

They didn't count on the rain.

In Episode 2 of Anatomy of an Ad: The Stain, we look at how the Tide team overcame the deluge during filming and put the finishing touches on an unprecedented three-part campaign the brand hopes will make Super Bowl history.

Tomorrow, we will post the third installment of Anatomy of An Ad: The Stain. Our videographers Nate Skid and David Hall follow the Tide team during the Super Bowl as it monitors the ad's social impact in real time.

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Anatomy of an Ad: Tide's Super Bowl Stain - AdAge.com

Anatomy

Anatomy of a cloud project cost overrun – CIO

I recently conducted an informal survey of some cloud integration companies and found something deeply troubling. Aside from cookie-cutter or formulaic quick-start projects, more than 70 percent of cloud consulting engagements involving new customers resulted in either a 10 percent cost overrun or a change-order. The bigger the project, the more likely the overrun.

You can blame it on stupid consultants or bad estimation or nutty customers or sunspot activity, but blame does no good. Something is going wrong here, and its causing a lot of heartburn for customers and vendors alike.

In an earlier article on trends making the cloud consulting market treacherous, I mentioned that a root cause of any cloud overrun is mis-set expectations: customers believing that meeting their requirements will be simpler than it is and that it should cost less than it will. However significant that observation may be, its not particularly actionable. So lets take the next step to understand the driving specifics, and what steps we can take.

[ How to compare cloud costs between Amazon, Microsoft and Google ]

In most cloud projects, several areas are nicely contained and are unlikely to cause significant cost surprises. If setting up a function is merely a matter of system configuration, there cant be that many hours of mouse-driving involved.

We should be so lucky!

Here are the project areas where we see cost surprises on a regular basis:

This twin-headed beast can involve some very serious surprises, as its impossible to detect many of the issues until youre in the middle of draining the swamp. The cost issues scale both with the amount of data and the number of data sources.

Even if the data looks superficially clean, there may be non-printing characters, format problems, improper values, overloaded semantics and object-model ambiguities that make for a messy migration or integration. If an ongoing integration is needed, you may not realize early on that the point-to-point adaptor you originally bid needs to be replaced with a full-blown middleware system.

Solution strategy: Do a real cost-benefit analysis of the amount of data to be migrated and the number of sources to be integrated, and develop a cost model that reflects reality. Start on the migration/integration/validation tasks at the outset of the project, so the surprises come early. Expect that migration and integration can represent the single largest part of your project.

Clients often stipulate no code, out of the box functionality only as part of their project definition, and on day two of the project discover requirements that cannot be satisfied any other way. Unfortunately, too many consultants are code-happy, so they willingly nudge the client toward custom-code land. And the rich coding environment of the Salesforce.com (SFDC) platform makes it tempting for both user interface and business logic.

The problem, of course, will be developer productivity and code maintenance costs. Expect custom coding a feature to be at least an order of magnitude more expensive than configuring the standard functionality.

[ Essential CRM software features: A savvy buyer's guide ]

Solution strategy: To the degree possible, use standard system features and off-the-shelf plug-in products to meet requirements. Bend requirements to fit whats available. Push coding out of the initial delivery if possible, so coders are working on a stable platform. For items that must be built, push to streamline processes and business rules that can cause combinatorial explosions (e.g., the security model, order configurations, distribution/partner networks).

The original SFDC reporting engine strikes a nice balance between power and ease of use, but it gives spreadsheet-quality output. If you want really clever and beautiful reports, it wont take long before you run into a wall.

SFDCs Wave reporting system is both more powerful and prettier, but really leveraging its power means writing query code. For even fancier stuff with nice formatting, multi-page layouts, and automatic office-document generation third-party add-ons are needed.

But as I noted in a previous article on design work in CRM projects, if its got to be pretty, its going to be pretty expensive both to set up in the first place, and to evolve over time with your needs.

Solution strategy: Thoroughly understand and specify every variant including formats and user-specific tweaks of every single report you will need prior to putting the system out to bid. Its best to discover that you actually require 100+ reports, not the ten you thought. If you have a working report (e.g., from Access or Crystal) that you need the system to emulate, provide the vendor with a sample set of input data and the reports output, with annotations regarding format and exception conditions.

This means you, project leaders and executive champions! Things you do will contribute directly to overruns. As I discussed in an article on agile project management, distance and delay are the enemies of efficient and economical projects.

But I need to add some new Ds that are even more deadly: dithering and (unending) discovery. The first of these, dithering (a.k.a. indecisiveness) is bad enough, as it causes delay and erratic direction, which leads directly to rework. But the second, whose hallmarks are discovering that (1) the requirements werent really known up front, (2) your assumptions about how things need to work were wrong, and (3) your assumptions about how the new system features will work were wrong, is the root cause of scope creep. I cant tell you how many large projects discovered more than half of the costly requirements after formal discovery was completed.

Solution strategy: Make the discovery phase longer, and when its complete have a signoff sheet for a strict feature and data freeze. Make the project team as small and tight as it can be, and do not hire more than one consulting company (to reduce finger-pointing). Work to constantly improve trust among the team members. Kick people off the team who blame. Keep executives and bean counters as far away from the project as you can, and limit big review meetings. Focus everyones attention on business value rather than abstract or arbitrary metrics and project dashboards.

Im currently reading the book Being Wrong Adventures in the Margin of Error after having finished Wrong! Why Experts Keep Failing Us. So maybe Im a little jaded, but it sure looks to me like cost overruns are the result of bad assumptions, fragmentary information, incomplete requirements and low trust.

Interestingly, overruns are much less common for follow-on projects, where both sides have put the time in to develop good assumptions, a solid understanding of the real requirements and a trust relationship. So for initial projects, we clients and consultants have to stop the pretend-certainty about our projects.

The truth is we dont really know, and were not willing to spend the time and money to get sufficiently knowledgeable about, all the niggling details of a new project. We run off and get a budget without knowing what the project will really entail. And then we discover too many plot complications after weve reached the halfway mark in the project. For those hoping that hybrid agile techniques will solve the problem, I havent seen much help there.

In contrast, the real agile approach admits we dont know, and simply scopes the project deliverables dynamically to fit within the budget and schedule. The team discovers as they go, prioritizes as they go and focuses on maximizing business value instead of fixed (and possibly random) criteria. When done right, agile makes the bean counters happy (they can claim on time, on budget) and gets the most important stuff out to the users as soon as its done.

>> Agile project management: A beginner's guide <<

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Anatomy of a cloud project cost overrun - CIO

Anatomy

Anatomy of an All-Time Super Bowl Collapse – Monday Morning Quarterback

Entering Super Bowl 51, it seemed the Patriots bestand maybe onlychance was to keep Atlantas electrifying offense off the field. Sure enough, the Falcons finished with 46 snaps in Super Bowl 51, 18 fewer than the NFL average in 2016.

But the games biggest factor wasnt that Atlantas offense was off the field. It was that Atlantas defense was on it. A lot. For 93 snaps, to be exact. Naturally, fatigue set in. And thats the biggest reason why the Falcons suffered the greatest collapse in Super Bowl history.

Its worth examining exactly how those 93 snaps exhausted the Falcons. For starters, 93 snaps equates to playing a game and a half. Then factor in the adrenaline of that game being on the Super Bowl stage, and what happens to a players energy as that adrenaline wears off. Then add in the halftime, which is twice as long as usual. Yes, that gives your body more time to rest. But it also means your body must operate on an unfamiliar internal clock. Over your previous 18 games, your body had grown accustom to its halftime routine. Oh, and speaking of 18 games, that, too, is a lot. Its cumulative effect magnifies the toll of those 93 snaps.

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More importantly, however, was the style of snaps the Falcons were playing. As expected, they defended the Patriots primarily with man coverage. When a defender plays man-to-man, hes chasing an offensive player all over the field. Thats considerably more taxing than sitting back in zone. Furthermore, Falcons defenders often matched to specific receivers in man. With the Patriots limitless supply of formations, those defenders were often crossing the field back and forth before the snap. Because chances were, if a defenders man aligned in, say, the left slot on one play, he very well could be aligned near the right sideline on the next. The 35- to 40-yard jogs that a defender takes to follow this add up. In fact, many NFL coaches who play man coverage will implement extra snaps of zone or limit their specific man-matchup calls in order to mitigate fatigue.

Mind you, this is all just with the secondary. There are also defensive linemen, who wear down faster than any position. Theyre constantly firing off the ball and wrestling with 300-pound blockers. Thats why Dan Quinn, like the rest of the NFL, employs a deep rotation up front. But on 93 snaps, even rotating defensive linemen succumb to exhaustion.

With the D-line tiring, the pressure that had been hounding Brady (he endured five sacks and about three times as many hits) dried up. Dwight Freeney stopped eating left tackle Nate Solders lunch. Grady Jarrett, who was sensational, flashed less. Vic Beasley no longer made noise. And thats when the greatest quarterback of all time rediscovered the precision accuracy that had evaded him for the first three quarters. With Brady in a clean pocket and throwing in rhythm, the Patriots had no trouble moving the ball.

This is where people want to assign blame. Quinn played too much man coverage! Matt Ryan and Kyle Shanahan blew it in crunch time, forcing Atlantas defense back on the field! No.

THE GREATEST COMEBACK EVER:Tom Bradys season started with a four-game suspension and ended, in dramatic fashion, with his fifth championship after the Patriots overcame the largest deficit in Super Bowl history.

The man coverage had been workingthats why Quinn kept playing it. The Falcons specifically had success in man-lurk coverage, keeping a free defender (safety Keanu Neal or linebacker DeVondre Campbell) in the shallow middle. That lurker took away New Englands crossing patterns and allowed the Falcons to switch coverage assignments on the flyBrady failed to recognize one of those switches when he threw the pick-six to Robert Alford.

As for Atlantas offense, to say that Ryan and Shanahan blew it is absurd. If the Falcons had given their best performance, would they have registered more than 46 snaps? Absolutely. But understand: the game didnt flow that way, plus Ryan and Shanahan stayed aggressive late in the fourth. After Danny Amendolas touchdown made it 28-20 with just under 6:00, the Falcons called a first-down play-action deep shot. Ryan checked it down to Devonta Freeman for 39 yards. Two plays later Ryan rifled a gutsy ball into double coverage to create an incredible sideline catch by Julio Jones. But after that, unfortunately, the Patriots broke down Atlantas protection, with Trey Flowers getting inside for a late-in-the-down sack (maybe Ryan wrongly held the ball, maybe he didnt; we cant know without seeing the all-22 film) and with Chris Long drawing a hold against left tackle Jake Matthews. On previous Falcons drives, there had been protection mistakes, both physical and mental, leading to sacks and a turnover. Those arent quarterbacking or offensive coordinating issues.

FOR THE BRADY FAMILY, REDEMPTION: Tom Brady Sr. on why this victory meant so much more

The reality is Atlantas defense was simply on the field too long. It wore down. If youre a unit built almost solely on speed, thats a problem big enough to cost you a Super Bowl.

Question or comment? Email us at talkback@themmqb.com.

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Anatomy of an All-Time Super Bowl Collapse - Monday Morning Quarterback

Anatomy

Pregnant ‘Grey’s Anatomy’ Star Spoofs Beyonc in Hilarious Video – Moviefone

Camilla Luddington and fellow "Grey's Anatomy" stars Ellen Pompeo and Debbie Allen got in formation on Friday for an adorable tribute to Beyonc.

Luddington is pregnant (and her "Grey's" character Jo Wilson may or may not be pregnant as well), and we all know that Queen Bey is pregnant right now, too. So Pompeo (Meredith Grey) pressured the reluctant Luddington to recreate Bey's now iconic pose in a video directed by Allen (Catherine Avery).

The stars all captioned versions of the shoot on Instagram:

Someday, that baby is going to be able to look back on this and laugh ... or be so embarrassed about her crazy mom.

We know that's a "her" in there, since the 33-year-old "Grey's" actress also just revealed that she and her boyfriend Matthew Alan are expecting a girl. Here's what she wrote on Instagram just before the Bey photo and video:

"I am so excited to announce today that I am having a... girl! ?? I want her to grow up knowing how strong women are ??. To be a little warrior who is not afraid to use her voice and stand up for what she believes is right. To navigate through life with courage and kindness, and to be one of the girls who says "you CAN sit with us..". Special shoutout to #crystaldynamics for sending me her first #tombraider onesie."

Congrats! "Grey's Anatomy" fans are still trying to sort through what's happening with Jo and Alex, but after the midseason premiere, many fans suspect Jo is carring Alex's baby. We'll see if that's the case as Season 13 continues Thursdays at 8 p.m. on ABC.

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Pregnant 'Grey's Anatomy' Star Spoofs Beyonc in Hilarious Video - Moviefone