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Saturday, May 25, 2013

Chocolate and citrus marmelade cupcakes

Enjoy and feel free to comment!

for the cupcake batter:
- 1 cup AP flour
- 1 cup flour
- 1/2 cup unsweetened cocoa powder
- 1/4 tsp salt
- 1/2 tsp baking powder
- 1/2 tsp baking soda
- 1 egg
- 1 stick butter, at room temperature
- 1/2 cup milk
- a splash of vanilla extract
- zest of 1 orange

for the frosting:
- 2 cups of confectionner sugar
- 1/2 cup unsweetened cocoa powder
- 1/4 cup orange juice
- zest of 1 orange
- 1 stick of butter
- a splash of vanilla extract
- a splash of grapefruit flavored vodka, optionnal

prepare the batter first:
- preheat your oven at 350F
- cream the sugar and butter until fluffy

- mix the milk and orange juice

- let cool completely on a rack until ready to frost

prepare the frosting:
- mix the butter, zest, confectionner sugar and cocoa powder

- add the orange juice and mix until smooth

Try not to eat the paper liner... ;)

Sunday, May 12, 2013

Quick and easy couscous fish cakes

Have you ever felt completely uninspired in the kitchen?

Ever asked yourself "what am I ever going to make for lunch??", "what I am going to do with a half a cup of couscous?!" or "why oh why did I buy 5 lbs of frozen fish?!?"

Well I have... And this recipe is what came out :D

Not only does it use freezer and pantry items, but you can even make it into a 3-in-1 serving it with cooked veggies leftover.

Oh, and it's healthy too!

INGREDIENTS (yields about 12 patties):
- 4 frozen flounder filets, thawed and drained (you can use any fish you like, this just happens to be what I had in my freezer)
- 3 frozen haddock filets, thawed and drained. Make sure to squeeze out any residual liquid or the patty mixture will be too moist.
- 1/2 cup leftover cooked couscous (or any cooked grains or cereals like quinoa, grits, rice, barley. Mashed potatoes will work too)
- 1 cup panko breadcrumbs (or dry instant oats, regular breadcrumbs, crushed saltines, AP flour, basically anything to adjust moisture of the patty mix)
- salt, pepper, dried thyme (or any seasoning you feel like)
- the juice of half a lemon
- 1 clove of garlic
- olive oil for cooking

- put the fish filets in a food processor and pulse-puree until almost smooth

Note: I like my fish cakes to still have a few pieces of fish for texture
- season with salt, pepper, lemon juice, grated garlic and crushed thyme and pulse quickly once more

- transfer the fish mixture in a bowl and add the cooked couscous and half of the panko. Mix well using your hands and adjust the moisture level with panko until satisfied

- form 12 flat round patties

- heat the olive oil in a wide frying pan and cook the patties over medium heat until golden and crispy (about 3 minutes on each side)

- serve with any veggie side you like. I served my fish cakes with a side of chilled Bohémienne (a ratatouille-like eggplant and tomato stew) and a slice of lemon.

- Bon app!

Saturday, May 4, 2013

Meyer lemon curd pie

Lemon curd pie is my absolute favorite dessert ever. Eh. Vah.

I used Jamie Oliver's recipe for inspiration, and mixed Meyer lemons with regular lemons for a little something extra.

Perfect balance of sweet and tart. Melts in your mouth...

for the crust (2 servings, you will only use one for the pie but you can freeze the other half and you'll have pie crust ready for next time!):
- 2 whole eggs
- 250g butter, at room temperature (about 2 1/4 sticks)
- 200g confectioner sugar
- a splash of vanilla extract
- 1/4 cup cold milk (I used fat free, but any milk is fine)
- 500g AP flour
- zest of 1 Meyer lemon
- a pinch of salt

for the filling (1 serving):
- 7 whole eggs
- 7 yolks (you can keep the whites for a meringue topping, or macarons)
- 380g caster sugar
- juice and zest of 4 Meyer lemons and 4 regular lemons (you can use just regular lemons if you cannot find Meyer lemons)
- 320g very cold butter, diced in 1/2 inch cubes (about 2 3/4 sticks)

1) prepare the crust:
- preheat your oven at 350F
- cream the butter and confectioner sugar together until fluffy and smooth

- add the lemon zest and vanilla extract

- add the flour and eggs, alternating and mixing well between each addition until it looks a bit dry and crumbly

Note: the dough should look dry, but when pressed together it should form a ball and stick together
- form a flat patty, wrap and refrigerate for at least an hour

Note: it is important to shape the dough into a flat patty and not just a ball, because you want the dough to cool down uniformly. If it is in a ball, the center of the ball will not cool as much as the surface.
- after the dough has rested an hour and feels harder to the touch, cut the patty in half. Keep one half for today and freeze the rest, wrapped in plastic.
- crumble the dough (or coarsely grate it) directly in a buttered and floured pie form and pat it down until it forms a uniform layer in the bottom and on the sides of the form. Trim the excess and refrigerate for at least 30 minutes in the fridge or 10 minutes in the freezer before baking.

- bake dry for 15 minutes at 350F (place a sheet of aluminum foil on top of the dough and weigh down with baking weights, or dry beans or rice you keep only for that purpose). After baking for 15 minutes, take out of the oven and let rest while you prepare the filling

2) prepare the filling:
- add the sugar, lemon juice and zest to the eggs and yolks and beat until sugar is dissolved

- transfer to a pot and stir continuously on very low heat (even better to use a double boiler, but I just did not have one at hand)

Note: it is crucial to stir all the time: trust me, you do not want to have scrambled eggs in the bottom of your pan!
- after a few minutes, when the mixture is warm and starting to thicken a little, you can start adding the very cold butter, a few cubes at a time. Stir, stir, stir!!!

- cook on very low heat until the curd thickens and covers a wooden spoon evenly, and strain the curd through a fine sieve to remove any clumps that may have formed and gritty zest

- pour the filling in the cooled crust

Note: it may still look a bit liquid while hot, but as it cools down, it will set into a soft yet sturdy filling :)
- refrigerate for at least 3 to 4 hours before serving
- serve with fresh fruit (raspberries, blackberries, strawberries, kiwi, whatever you feel like!) and strong coffee.


Security expert says look for out of the norm behaviors to spot Tad Cummins

HUNTSVILLE, Ala. –Tad Cummins could be anywhere with Elizabeth Thomas at this point. Authorities believe they are staying off the grid, and possibly not even in the vehicle first reported anymore. But, there are still things the public can look for to identify the two.

“That’s really what we’re looking for, is something out of the norm,” said Shane Hammett, Vice President of Cyber Operations for All Points LLC.

Hammett knows not everyone is trained to notice those things. He said for the public to identify someone like Tad Cummins, reading body posture is a big help.

“Not making eye contact is an example of those kinds of things, and so looking for those unique identifiers like that,” he explained.

He said being vigilant can be as easy as looking for unorthodox patters of behavior in the people around you.

“Never going to work and not seemingly having a disability, or erratic time of leaving the house may be another example of it,” he said.

Even if they are off the grid, Cummins could be posing with Thomas as anything. If they do make an appearance in public, a big tell for identifying individuals like them would be the absence of technology.

“You know not having that cell phone with you on a regular basis where the majority of the U.S. tends to have that on a regular basis,” said Hammett.

He thinks Cummins is very much aware of his surroundings.

“Identifying social media, looking for trends along those lines, looking at local news, is going to certainly be a pattern of his behavior,” said Hammett.

So, spotting anyone paying too much attention to things like that is another good indicator. Paying close attention to anyone around you is always helpful.

“I think that’s why it’s important for individuals to engage and have a conversation, and get to know their neighbors in that situation,” said Hammett.

He said if you know who your neighbors are, you’ll notice when something’s out of the norm, and that’s the key.


How to economically achieve a 365-day calving interval for suckler cows – Teagasc

Analysis carried out in 2014 found that the annual cost of keeping a suckler cow on Irish beef farms ranged from €550 to €700.

This was for farms with high levels of management and where the length of the grazing season was approximately 220 days.

The range in suckler cow costs on these farms was primarily a reflection of differences in feed, replacement heifer and breeding costs.

Where levels of management are lower and/or the length of the grazing season is shorter than this, then it is likely that suckler cow costs are greater.

Although farmers can adopt management strategies to reduce suckler cow costs (e.g. calving close to the onset of the grazing season so that feed costs are minimised), these costs are likely to remain the predominant cost for suckler beef farms.

Thus, the objective for suckler systems is to minimise costs while producing a healthy and heavy weanling annually so that suckler cow costs per calf or kilogram of weight weaned is minimised.

The quality (muscularity) is also important, particularly for farms selling weanlings. One of the key measures determining the cost and annual output of suckler beef cows is the calving interval.

Calving interval describes the number of days between successive calvings. The target calving interval for a suckler cow is 365 days; where the calving interval is greater than 365 days this means that it takes longer than one year for a cow to produce successive calves.

The overall effect of longer calving intervals is to reduce profitability for suckler beef farms for the following reasons:

  • For spring calving cows, which represent the vast majority of our suckler herd, the length of the indoor winter feeding period is longer since cows are normally not turned out to grass until after calving. This is a critical issue for our seasonal calving production systems where the objective must be to maximise grazing season lengths and thus, the proportion of grazed grass in the annual feed budget. Thus, longer calving intervals increase total feed costs.
  • Where weaning occurs on a fixed date, weaning weights of the later-born calves are lower. For example, if a cow calves on March 1 and the calf is weaned on October 1, then the age at weaning is 7 months. If this cow then calves on April 1 the following year (representing a calving interval of 396 days) and the weaning date remains October 1 then the calf is only 6 months of age at weaning and correspondingly, 30kg to 40kg lighter.
  • The likelihood of a cow with a longer calving interval becoming pregnant and remaining in the herd is reduced. This is because later calving cows have a shorter duration prior to breeding or indeed may be calving when the breeding season has already commenced. The overall effect of this is lower pregnancy rates and higher cow replacement costs, a considerable cost in suckler beef systems.

There are also health risks (mixing of calves of different ages and levels of disease exposure), marketing difficulties (selling uneven batches of calves) and management/labour challenges (for example, repetition of husbandry tasks such as disbudding and castration as calves reach suitable ages on different dates).

It is also important to consider that costs are typically expressed on an annual basis but if calving intervals are greater than 365 days then the cost of maintaining suckler cows per calf weaned is greater than the annual cost.

Take the example of a cow with an annual cost of €600 and has a calving interval of 396 days (one year and one month) – in effect the cost of this cow per calf produced is €650.

In short, higher calving intervals reduce output and increase costs per calf or per kilogram of weight weaned.

The overall cost of longer calving intervals, taking into account the above factors, has been quantified as €2.20 per day change in calving interval. Data from Irish Cattle Breeding Federation (ICBF) indicates that the average calving interval for suckler cows in Ireland is 403 days.

Using this cost estimate and the national average calving interval and applying it to a herd of 50 cows, total farm costs are increased by almost €4,200 (50 cows x 38 days longer calving interval x €2.20/day), a considerable cost particularly in the context of suckler beef systems where margins are low.

Indeed across the national suckler cow herd of approximately one million cows, this represents a cost of almost €85m to the industry.

Overall it is clear that the length of calving intervals on suckler beef farms is an important factor influencing profitability.

The three most important factors controlling reproductive performance are level of management, herd health and genetics.

Attention to all of these factors is required for high levels of reproductive performance, short calving intervals and profitable suckler beef systems.

Paul Crosson, Research Officer, Teagasc, Grange


Hackerrank: Count Luck

Ron and Hermione are deep in the Forbidden Forest collecting potion ingredients, and they’ve managed to lose their way. The path out of the forest is blocked, so they must make their way to a portkey that will transport them back to Hogwarts.

Consider the forest as an grid. Each cell is either empty (represented by .) or blocked by a tree (represented by ). Ron and Hermione can move (together inside a single cell) LEFT, RIGHT, UP, and DOWNthrough empty cells, but they cannot travel through a tree cell. Their starting cell is marked with the character , and the cell with the portkey is marked with a . The upper-left corner is indexed as .

In example above, Ron and Hermione are located at index and the portkey is at . Each cell is indexed according to Matrix Conventions

Hermione decides it’s time to find the portkey and leave. Each time they are able to move in more than one direction, she waves her wand and it points to the correct direction. Ron is betting that she will have to wave her wand exactly times. Can you determine if Ron’s guesses are correct?

Note: It is guaranteed that there is only one path from the starting location to the portkey.

Input Format

The first line contains an integer, , the number of test cases.

Each test case is described as follows:
The first line contains space-separated integers, and , respectively, denoting the forest matrix.
The subsequent lines each contain a string of length describing a row of the forest matrix.
The last line contains an integer, , denoting Ron’s guess as to how many times Hermione will wave her wand.

  • There will be exactly one and one in the forest.
  • Exactly one path exists between and .

Output Format

On a new line for each test case, print if Ron impresses Hermione by guessing correctly; otherwise, print .

Sample Input

Sample Output

For each test case , denotes the number of times Hermione waves her wand.

Case 0: Hermione waves her wand at , giving us . Because , we print on a new line.
Case 1: Hermione waves her wand at , , and , giving us . Because , we print on a new line.
Case 2: Hermione waves her wand at , , and , giving us . Because and , and we print on a new line.

这个题是个深搜，只不过需要在途中数valid的neighbor的个数。需要注意的细节是：1. 起始位置没有设为’X’而是’M’，在开始搜索的时候也没有改变其值，因此在isValid函数中需要加一个判断是否是’M’，或者就直接在开始的时候将其改为’X’；2. 只有在valid的path中的岔路口才计入最后的count中。


leaders training center

Oil Field Exploration and Evaluation

Course outline
Participants will be exposed to the basic concepts of acreage management, exploration geology, petroleum geophysics, rotary drilling, and economics and risk assessment:
· Acreage acquisition and legal aspects
· How exploration groups are put together (joint ventures, floats, operators, non-operators)
· How companies acquire exploration acreage (permits, gazettals, open acreage, bidding, work programs, farmins, joint ventures)
· Legal obligations and moral responsibilities (legislation, environmental controls)

Petroleum geology
· Why companies explore where they do (rock types and properties, geological models, prospectivity)
· Where oil and gas come from (source, seal, reservoir, generation, migration, trapping mechanisms)
· How oil and gas fields are found (basin analysis, regional studies, play concepts, prospect generation)

Petroleum geophysics
· How explorers determine what it looks like below the surface of the earth (remote sensing)
· How seismic works (acquisition, processing, 2D and 3D surveys)
· What seismic tells us (interpretation, mapping, hydrocarbon indicators)

Exploration drilling
· Types of drilling rigs (land rigs, jackups, drill ships, semi-submersibles)
· How rotary wells are drilled (hoisting, rotating, circulation, control)
· Information obtained from wells (cuttings, cores, logs, well seismic)
· What happens after the well is drilled (abandon, suspend, test)


Industrial Internet Now

7 amazing technologies we’ll see by 2030

Via IoT Business Insider

Join the conversation!

Your email address will not be published.

How Industrial IoT enables the factory of the future

Trillion-dollar projections on the expanding size of the market are urging companies to capitalize on the Industrial IoT. For many, however, it remains unclear how industries should apply IIoT to begin making the hyper-efficient and agile factory of the future a reality. Fabio Bottacci, founder and CEO of VINCI Digital and Industrial IoT Expert Contributor at the World Economic Forum and at the Brazilian Development Bank (BNDES), shares his insights on how Industrial IoT is already increasing operational efficiency, saving time and reducing cost.

As the Fourth Industrial Revolution transforms manufacturing and material handling, enterprises continue to look for ways to create value from converging technologies. But what are the steps that companies need to take to put together an effective agenda of action? Fabio Bottacci finds it essential that the implementation of industrial internet is incorporated into the company’s strategy and business development. In other words, chief executives must embrace change. “In order to advance decision-making on the correct level, CEOs must be included from the very beginning, possibly as initiative main sponsor. IT officers alone cannot drive real digital transformation,” says Bottacci.

Bottacci advises manufacturers to initiate the transformation by defining a specific set of goals, to be assessed and validated initially on a pilot project, before the implementation at scale of an end-to-end Industrial IoT solution. The next step is to deploy an industrial internet pilot in one facility, or on a specific production line, which will be used as a case study for learning how IoT works in this particular industrial environment. The pilot facility is then reworked and developed according to observations. After the test phase, it is easy for a company to apply the same principles, with proper adjustments, at scale to other facilities.

Bottacci uses the concept of flexible infrastructure to refer to how transformation can be simpler in certain contexts. “It is easier to justify large investments in industrial internet in environments where industrial internet is incorporated into production by transitioning directly to automated, advanced IIoT environments. The transition phase is less complicated when the existing infrastructure is light, because there are fewer things that must be accounted for in applying new solutions,” he explains.

A case in point is Romania, where the internet infrastructure is now top of the class in Europe. The Romanian infrastructure was created rather recently compared to more affluent European countries, and therefore, the entire web is more modern than that in Finland, for example.

Industrial internet in practice

“IIoT coupled with AI or ML turns maintenance into a dynamic, rapid and automated task.”

Bottacci emphasizes that applications of industrial IoT are already a reality. According to him, there are dozens of different use cases of IIoT in enterprises. “Companies are already developing IoT applications that work, and they have started making a difference. For example, transportation and warehousing benefit from automated vehicles and asset tracking. In manufacturing, predictive maintenance and asset performance management are key areas where industrial internet boosts value creation.”

Predictive maintenance keeps assets up and running, decreasing operational costs and saving companies millions of dollars. Data from IIoT-enabled systems – sensors, cameras, and data analytics enabled by powerful artificial intelligence (AI) or machine learning (ML) algorithms – helps to better plan maintenance, allowing manufacturers to service equipment before problems occur. “Data streaming from sensors and devices can be used to quickly assess current conditions, recognize warning signs, deliver alerts and automatically trigger appropriate maintenance processes. IIoT coupled with AI or ML thus turns maintenance into a dynamic, rapid and automated task,” Bottacci explains.

“Other potential advantages include increased equipment lifetime, increased plant safety and fewer accidents with negative impact on environment,” he adds.

The importance of edge analytics

“Companies have been proactive in moving the processing of IIoT to cloud services,” Bottacci notes. However, in his opinion, it is not necessarily a wise move to have everything in the cloud. During critical stages of the manufacturing process it is crucial that decisions can be made instantaneously. Here, manufacturers can benefit from edge analytics.

“Edge computing enables real-time analytics. Edge analytics is an approach to data collection and analysis where automated analytical computation is performed on data at a sensor, network switch or other device instead of waiting for the data to be sent back to a centralized data store. IIoT can be supplemented with Arduino-based, open-source computer hardware and software applications that allow some of the processing to take place on site, at the edge of the network and near the source of the data. Edge computing helps ensure that the right processing takes place at the right time, in the right place,” Bottacci explains. “Edge computing is a preferable option for the cloud in terms of security, as proprietary data is kept within the company firewall. Moreover, edge computing becomes vital when you need real-time analysis and automated action to save critical-mission production lines or facilities from potential heavy damages.”

Creating value with Industrial IoT

“There’s no value in the data without advanced algorithms of machine learning.”

Bottacci says that value can be created in surprisingly simple ways by putting data to work. As an example of enhancing safety and efficiency in material handling, he refers to a fleet management system in Silicon Valley. “Peloton Tech’s truck platooning system is a case study that illustrates how IIoT is already creating value. The system uses vehicle-to-vehicle communication to connect the braking and acceleration between two trucks. The lead truck controls the simultaneous acceleration and braking of the whole fleet, reacting faster than a human or even a sensor system could. What follows is a reduction in aerodynamic drag, which leads to companies saving around seven per cent in fuel cost. In terms of annual savings, this is a remarkable number,” says Bottacci.

In Europe, trucking companies such as Scania and Volvo Trucks have adopted IIoT fleet thinking. “It still takes courage to adopt innovations like these,” Bottacci admits. However, he recommends getting started quickly by building a case study of industrial internet and then working towards expanding IIoT to cover more and more of the industrial realm. “Companies should start seeing emerging technology like Industrial IoT not as a threat but as the only way to survive in a matter of a few years. That’s two or three years if you are an optimist, five to ten if you are more conservative,” estimates Bottacci.

In Bottacci’s view, the simple capacity of devices to seize data is not what the Industrial Internet of Things is essentially about. “Even if you have all the infrastructure and the technology to get the data – sensors, WiFi, the gateway, the cloud – and the capacity of analyzing the data, there’s no value in it without AI, more specifically advanced algorithms of machine learning.”

“IIoT is about AI or ML analyzing data in real time so as to make decisions and act, most of the times several days or even weeks before a potential issue. This process results in actual business outcomes,” Bottacci states. “Prescriptive analytics react autonomously, real-time: In a mission-critical situation, a prescriptive system will autonomously decide what to do. This is where edge analytics is imperative,” he explains. “My point is: You can’t consider industrial internet standalone. The real value comes from how companies use AI and ML-enabled IIoT solutions in analyzing and processing data.”

Fabio Bottacci works as an independent advisor. He is founder and CEO of VINCI Digital and an Industrial IoT Expert Contributor at the World Economic Forum and at BNDES, the Brazilian Development Bank.

Interview w/ Fabio Bottacci

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The need to connect legacy devices to the IIoT

Pre-internet assets lack the connectivity of newer pieces of equipment. These legacy devices, however, still have years of remaining value if they can be linked to the cloud, enabling their data to be analyzed and revealing actionable insights that could perhaps potentially transform business. Wael Elrifai, Sr. Director of Enterprise Solutions at Pentaho, offers insights on how older systems can be made to work with current ones, and talks about the human side of machine learning.

Businesses that have operated for a considerable amount of time will have accumulated several legacy systems over that period. While they have long life-spans, few of these machines will be immediately compatible with one another. The cost of replacing these pre-internet assets to facilitate communication could easily outweigh foreseeable production benefits. What steps must plant managers then take to combine AI capabilities with legacy infrastructure?

Wael Elrifai, Sr. Director of Enterprise Solutions at Pentaho, begins with this premise. “I usually like to remind people that we talk as though data was not generated in the past on these systems. Remember, however, that there’s a lot of robotics involved already, and these systems have sensors that have been producing data for decades. The truth of the matter is that systems such as PLCs (programmable logic controllers) and SCADA (Supervisory Control and Data Acquisition) have already been capturing that data. What you need to do now is to pull the data off those systems. Things like data integration tools are built for that,” he says.

According to Elrifai, predictive maintenance – a technology that drives value in modern manufacturing – isn’t new either. “The difference today is, because the cost of computing and the cost of storage have dramatically reduced, you can do more with it. It’s been a nice positive feedback cycle: Where you can capture more data, you can do more computing work – applied mathematics, machine learning and AI, among others. This then makes capturing data more valuable.”

Conversely, in situations where it’s entirely mechanical and no data or robotics are involved, he suggests looking for proxies for that data. Elrifai adds that while some retrofitting may be required, from his experience a lot of data is already there and is not being used, so it would be best to begin with that.

IIoT implementation across industries

Some industries are more advanced when it comes to IIoT implementation, while others lag. To convince traditional manufacturing companies of the economic benefits of AI investments, Elrifai offers the following examples.

“The ports industry is already using complex machine learning techniques. The most common one for logistics companies is simulated annealing, a method for schedule optimization that sees to it that cranes are doing the right thing at the right time, and containers are moved according to the right schedule.” Elrifai believes that for some container terminals, it’s mostly about the integration of the larger supply chain.

On the other hand, he recalls a visit to a steel factory that wanted to improve its efficiency. “A couple of times a day, they experienced a very specific kind of failure. This cost about 10 percent of their productivity, and in the steel industry that figure is enormous,” Elrifai explains. Furthermore, the way they knew there was a problem was rather unusual: The control room would start shaking.

While the company wanted to reduce this through predictive maintenance techniques, what they didn’t know was that they were capturing all this data already. Elrifai says like many other companies, this particular steel factory would only look at five, ten or 20 variables, the ones that were in their SCADA system.

“What they didn’t do is integrate this with thousands of other sources. The statistical techniques that factories are doing today are low-dimensionality ones,” he continues, adding that trying to convince groups to do more is a matter of explaining to them that it’s just an evolution of what they are already doing.

Where humans fit in

Another dimension to machine learning and AI is the human factor. As far as the supply chain is concerned, Elrifai is of this opinion. “If you are talking about supervised learning – just prediction, basically – oftentimes the baseline data that you use to train these systems is from humans. And you want these systems to evolve, because systems evolve, factories evolve,” he says. “I think humans are always going to be there, helping to state what the ground truth is. Or, at least for the foreseeable future, they will be doing that.”

In addition, Elrifai points out that in certain cases in factories, several different algorithms are voting whether something is going to fail or not, and a human expert is doing that as well.

“With these kinds of methods – ensembles, if you will – you end up with better outcomes. For instance, the machine by itself might produce 75% accuracy and the human on his or her own might produce 68% accuracy.  When you put them together, you end up with greater performance, say 80% or 85%,” he states. “I think there’s still a lot of room for cooperation. I don’t think the algorithms are taking over just yet.”

How to solve new problems

“The common problem people have with technology is that they search for problems. That makes no sense. Solution? Start with use cases.”

Finally, Elrifai – with his background in data science – offers this essential piece of advice to companies that plan to connect legacy equipment to the IIoT. “The common problem people have with technology is that they search for problems. That makes no sense,” he emphasizes. His solution? Start with use cases.

“I think there’s a sense that this is extremely expensive to do. However, all you really are doing is putting up a basic data engineering or basic machine learning infrastructure – this is low-cost. There’s a lot of automation available now around machine learning,” states Elrifai. “In the data world, when you try to build models, about 80-90% of the effort that is put in is made up of data engineering, feature engineering, preparing data, filtering – all the easy stuff.”

Elrifai believes that a lot of the data prep for data engineering can be done in an automated fashion. “I don’t think people recognize that. They are trying to use old tools to solve new problems,” he concludes.

Wael Elrifai is an author and speaker. He works as Sr. Director of Enterprise Solutions at Pentaho, a data integration and business analytics company with an enterprise-class, open source-based platform for diverse big data deployments.

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Implementing AI in Europe’s Businesses, Beyond the Hype

AI Business set out to find out how AI is transforming business today and how it will evolve in the future. They surveyed the C-Suite executives in the UK & Europe’s 300 largest businesses on how they see AI impacting their organizations, understanding their current and future AI projects, concerns and overall strategy. Georgios Kipouros, Research Director at AI Business, writes about the findings of the survey on techUK.

The majority of the leaders thought AI will transform their industry and saw it essential for their organization. Over 80% compared the impact of AI to that of the Internet. The leaders perceived AI as a way to improve efficiency, reduce overall costs, and also a way to enhance accuracy in their operations. Over 80% of Europe’s leading organizations were investing in machine/deep Learning technologies, expecting to spend an average of 4 million Euros per AI project within the next 2 years.

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Securing IIoT systems still a contractual no man’s land

The industrial internet is a continuously evolving and layered infrastructure built on connected machinery – a large proportion of which has not previously been linked to the internet. The fact that these machines can now be accessed online brings new challenges for IoT service providers as well as their clients. Furthermore, questions remain regarding responsibilities, says Pasi Vilja, Chief Information Security Officer at Konecranes.

Last year, a massive distributed denial-of-service (DDoS) attack swept through the globe and nearly disrupted the entire internet. Experts called it the largest attack of its kind in history. Afterwards, close investigation revealed that the assault had been orchestrated completely through IoT devices. A huge number of web cameras were left unprotected, and this offered an easy opportunity for hackers to mount a large-scale attack via the internet.

“This is a great example of the vulnerabilities born out of millions of unprotected devices suddenly being connected to the internet. As the number of internet connected devices continues to grow, new vulnerabilities also arise, bringing forth questions about internet safety which we haven’t faced before,” Vilja says.

The need for shared solutions to these questions is growing increasingly dire as more and more machines – many of which were designed before the advent of the IoT era – are connected into the internet, and operated in ways which couldn’t have been considered at the time they were made.

Implementing security measures in the era of IoT

According to Vilja, security in the context of the industrial internet can be implemented mainly through the same types of practices already used in securing computer networks. Keeping up a proper firewall, requiring identification, and constantly surveying and reacting to problems that arise quickly are important, as is updating software.

“The same principles work in both an ordinary IT context and an IoT environment. On the software level, there isn’t that much of a difference in how the systems can be kept safe in either setting. Still, the industrial context adds a layer of complexity to the equation,” Vilja says.

One of the greatest differences in terms of web security in an industrial context is the machinery’s long lifecycle, which brings forth new questions on service providers’ responsibility to offer their clients updates for extended periods.
“Some machinery in industrial use still run on Windows XP or even NT. For the former, support ended in 2014 –  and for the latter, in 2004. How are we going to ensure that systems will be kept secure when some of the machines have lifecycles of 50 years? These are still questions to be discussed,” Vilja says.

Another issue comes up with the variety of machines being connected to the web. Industrial companies might have a combination of old, non-connected machinery which is now being connected to the web, point-to-point connected machines, and newer internet connected machines. When they open all these machines gradually to the internet, questions arise on how to make sure that no gaps are left between the different ways to connect.

Discussions about responsibilities still underway

Who has the ultimate responsibility regarding the IoT solutions in use and keeping them up to date? Is it the service providers? And if so, then how long and how actively do they have to ensure that the security is current? According to Vilja, these questions are still open for discussion, and no concrete best practices have surfaced yet.

“This is very much a discussion still to be had. Service providers must take responsibility to ensure that the services they offer are maintained to protect against new security threats. But only the clients know their full set-up and probably don’t want automatic updates from multiple providers. And how knowledgeable are the clients about the relevant security features or risks? This is still a contractual no man’s land,” Vilja says.

Another concern is that in highly specialized systems that have been tweaked or integrated by clients, the updates could cause interruptions – or even shutdowns –  in their operations. On the other hand, refraining or neglecting to update their systems could also end up leaving their entire systems vulnerable.

According to Vilja, in order to form proper guidelines, open discussion and continuous surveillance are essential. Eventually, the best practices will be formed, and they are likely to follow precedents from the computer market.

Ultimately, the same rules apply to web cameras and smart refrigerators as for industrial sensors – basic security measures go a long way, and they must actually be implemented in order to ensure operational safety.

Pasi Vilja is the Chief Information Security Officer at Konecranes.

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Abdus Salam Quotes 1

Abdus Salam photo Physicist

Mohammad Abdus Salam NI, SPk, KBE, was a Pakistani theoretical physicist. A major figure in 20th century theoretical physics, he shared the 1979 Nobel Prize in Physics with Sheldon Glashow and Steven Weinberg for his contribution to the electroweak unification theory. source

1 most famous quotes by Abdus Salam (Physicist)

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The New Dredging Project on the Saco River: Another Highway Widens to Biddeford / Saco

130 years ago, the Saco River served as a primary commercial delivery route for the mills and the region. The massive piers and moorings on both sides of the river served the schooners, barges and tugs that delivered raw materials to the mill. The same boats loaded on finished products to ship out to the market. Coal arrived to fire the endless appetite of the massive boiler plants, making steam for heat and process throughout the 3,000,000 square foot mill complex. Cotton, the primary raw material for making textiles, arrived in barge loads, delivered in 1000 lbs. compressed bales. Finished cotton “drill” fabric, wrapped in burlap and stamped with the familiar Laconia Griffon logo was packed in into schooners, ready for the trip down the river and across the world.

The schooners built for open ocean travel had deep keels for rough water stability. Those schooners required 12’ to 15’ in water depth. 130 years ago, the Saco River was deep enough to accommodate these delivery boats.

Through the natural process of siltation, over time the sands and sediments filled in the river bed, slowly blocking the pathways of nautical delivery.

Luckily for the mills, the modes of commercial transportation evolved away from ocean travel to ways of railroads and trucking.

Today the river is in the process of becoming an ocean travel way again. Through a joint effort by Biddeford and Saco, federal funding has been procured to dredge the river, returning it to the depths of its past. It is no coincidence that recently a major marina and townhouse project has been announced for Saco Island.

The waterfront of Saco/Biddeford comes alive once again.

Continued Market Growth in Biddeford

When Starbuck’s looks for their next retail location, they look at trending demographics. They also look at the growth potential of the area market. They use research tools to assess when real estate becomes available to determine if the location will be able to support the volume they need to profitably operate their store. The fact that Starbuck’s choose their new 5 corners location validates the PMC’s non-scientific prediction that Biddeford is an up and coming market.

If you live or work at the mill you recognize the daily site of DHL, FED EX and UPS. The trucks arrive with their characteristic reverse alarms, stopping daily at 5 locations at the Pepperell Mill Campus. With 136 commercial and 100 residential leases, there is a constant cycle of products being shipped out and shipped in. This ebb and flow on campus demonstrates real economic impact in our community.

With roughly 60% of the 1.1 million square feet of leasable space here on campus re-developed and occupied we are ahead of that non-scientific prediction’s schedule. Come join the downtown revival, and feel the buzz and benefit of being part of a community of startups, small businesses, and residents.

Biddeford Mills Museum

On the cultural front, the Biddeford Mills Museum is in the process of building exhibit space and refining their extensive on-site tours.

Perhaps the greatest historical aspect of the mill is hidden under ground. Beneath the mill lies a network of tunnels and lagoons that once carried and controlled all of the water used to power the mill’s machinery back in the late 1800s. This was the original source of power for the mill, and the reason why the mill was developed along the Saco River falls. The lagoon (photo below) was the epicenter of water power, and controlled the distribution of power for all of the machinery at the mill.lagoon

During the era of steam power, several steam engines were in service at the mill. Steam power replaced the mill’s original mode of power, river water.

This is a photo of the new timeline mural in the lobby of the Pepperell Center. The timeline follows the history of the mill from it’s inception in the early 1800s.23380308_10155151948557362_8771920208047621304_n

The museum is a great cultural addition to the campus. The story of Biddeford – Saco mill history is critical, as the buildings and the industrial innovations developed were at the fore front of the American Industrial Revolution.

Saco River Falls

When the Saco River rages as it does in this video, the river is either draining the White Mountains during the spring thaw, or a great weather event has just occurred. We are all painfully aware of the recent weather event.

The awesome strength of the falls reminds us of why the mills are here in the first place. It was the power of the water that drove the machinery that made these mills the most successful textile operation of its time.

What made this mill so uniquely productive, was the difference in elevation between the top of the falls and the bottom of the falls. That difference is 42 feet. It all comes down to gravity and head pressure. Large quantities of water dropping 42 feet was the force that consistently drove the water wheels that ran the various machinery, processes and looms to produce cloth.

The mill developers in the early 1840s saw this potential and commenced the construction of a network of tunnels to harness the water’s power. Then they built the mill buildings on top of the tunnels, and the machines started spinning. The mill was one of the greatest early advances of the American Industrial Revolution, and it was all based on a very simple principle: gravity.


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Chinese Medicine - The Healing Art of Qi Gong

Chinese medicine dates back to the late Shang Dynasty, 1000 years before the birth of Christ. Beginning even in those ancient times, Chinese medicine has focused not on treating individual symptoms, but rather on understanding the collection of symptoms and the context in which they occur. This holistic approach is based on the recognition for the need for harmony and balance. Treating only the symptom, as is common in Western medicine, ignores the underlying imbalance which produced the illness.

The core secret of Chinese healing is Qi (pronounced Chee), the natural energy found in each of our bodies. Qi flows along well defined lines called meridians. Disruptions in the flow of Qi is the source of many ills. Restoring the smooth flow of Qi is essential to restoring health. Blockages in Qi disrupt the body’s natural balance making, reduce our ability to combat stress, increase tension and make us more likely to fall sick. By releasing blockages and stimulating the flow of Qi, the body is brought into harmony and balance. This balance will reduce stress, relieve tension and improve our health.

As people everywhere become more aware of Acupuncture and Oriental Medicine a less well-known, but no less important Oriental healing art is emerging: QiGong (Chi Kung). The word itself means "Cultivating Vitality." This broad category of breath and movement exercises also refers to a form of direct healing work with others. Along with acupuncture and herbal medicine, it is one of the fundamental traditional practices you can use to achieve and maintain health and quality of life.

The Practice of Qi Gong

Personal practice of Qigong promotes balanced, radiant health. Simple, enjoyable movements, like the elegant Eight Treasures of Qi Gong, done regularly can:

  • Improve all aspects of physical, emotional and mental health. Most involve a kind of smooth, slow activity - a bit like moving underwater - combined with specific breathing patterns. Virtually anyone can practice Qigong.
  • Clear energy and rejuvenate, which is especially useful at the end of a busy day. People who practice Qigong get back some of the energy "lost" during the day and sleep more soundly.

It can be done almost anywhere. Commonly you will practice once or twice a day, generally in the morning and/or evening. It can take as little as 15 minutes. Qigong is one of the original forms of "preventive medicine" for healthy living.

There are many types of Qigong, but they all have a common goal: balancing and increasing the energy flow within the body. This means better health, deeper and more restful sleep and increased quality of life.

An interesting aspect of practicing Qigong is it's subtlety. There is a saying that if an exercise looks big on the outside, it is small on the inside, and if it's small on the outside, it's big on the inside. This means that flashy, broad movements may not be the most profound in their effects, while more subtle ones probably are. Some of the most advanced exercises have virtually no movement visible on the outside.


Clergy members proclaim the words of God to the people.
Clergy members proclaim the words of God to the people.

In the Greek Orthodox church, the three main clerical officers -- bishops, priests and deacons -- are ordained through the sacrament called Holy Orders. These clergy members represent Christ's presence with his people. The Church also teaches that the clergy is exclusively male and receives its authority from the Apostles of the New Testament. Clergy members are directly or indirectly responsible to teach, administer sacraments and perform administrative duties in the Church and local parishes.

Apostolic Succession

Orthodoxy teaches that the first leaders of the Church were Jesus' twelve apostles, as referenced in St. Luke 6:13: “And when it was day, He called unto Him his disciples: and of them He chose twelve, whom also He named apostles.” The Church also believes Jesus taught the mysteries of the faith to the apostles in the 40 days after he was raised from the dead. According to Church teaching, the apostles could ordain their own successors, in the same way Christ had promised to send the Holy Spirit to the apostles to remain with them until the end of the world. Apostolic succession permits the Church to continue from one generation to the next.

The Greek Orthodox Church teaches that because bishops are successors to the apostles charged to maintain the unity and truth of the Orthodox faith, they have the authority to ordain deacons, priests and other bishops. The word bishop, episkopos in Greek, means overseer; accordingly, bishops are in charge of a geographical area known as a diocese. The bishop over the national church holds the title of patriarch. Bishops are servants and are not considered to be infallible; they are required to be either a widower or unmarried.

Orthodox priests, also called pastors or presbyters, are ordained Church officials who are in charge of the daily management of local parishes. The priests teach and preach in the local parish; they also administer sacraments such as communion and baptism. The Orthodox Church believes priests have administrative duties, as stated in 1 Peter 5: 1-2: “So I exhort the presbyters among you, as a fellow presbyter and witness to the sufferings of Christ and one who has a share in the glory to be revealed. Tend the flock of God in your midst, [overseeing] not by constraint but willingly, as God would have it, not for shameful profit but eagerly. ” Priests can marry, as long as it is the first marriage for him and his wife.

Bishops ordain deacons for service in the Orthodox church. Deacons assist pastors and bishops in administering the sacraments but do not independently administer the sacraments. Deacons assist in the celebration of the liturgy and at other church services. Deacons are often chosen from among local parishioners and, in present-day Orthodoxy, engage in hospital visitation, form youth groups, lead educational ministries and carry out missionary work. Deacons can marry, but like Orthodox priests, the marriage must be the first for both persons.


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Our Physiotherapists work with kids who are diagnosed to have Cerebral Palsy, Muscular Dystrophy, Down’s syndrome, Developmental Coordination Disorder and Autism. These kids may have difficulties with balance, coordination, movement, gait patterns, increased/decreased muscle tone and muscle strength. They evaluate and provide treatment addressing these issues as well as to achieve age appropriate developmental motor milestones.

Various approaches, techniques and activities are implemented in the treatment sessions to enable them to improve their functional and performance levels thereby improving their quality of life. They also collaborate with other professionals providing recommendations for the betterment of the child.


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Amyotrophic lateral sclerosis: cell vulnerability or system vulnerability?

  • Kevin Talbot

    Corresponding author
    1. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
    • Correspondence

      Kevin Talbot, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK. E:

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Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with clinical, pathological and genetic overlap with frontotemporal dementia (FTD). No longer viewed as one disease with a single unified cause, ALS is now considered to be a clinicopathological syndrome resulting from a complex convergence of genetic susceptibility, age-related loss of cellular homeostasis, and possible environmental influences. The rapid increase in recent years of the number of genes in which mutations have been associated with ALS has led to in vitro and in vivo models that have generated a wealth of data indicating disruption of specific biochemical pathways and sub-cellular compartments. Data implicating pathways including protein misfolding, mRNA splicing, oxidative stress, proteosome and mitochondrial dysfunction in the pathogenesis of ALS reinforce a disease model based on selective age-dependent vulnerability of a specific population of cells. To the clinical neurologist, however, ALS presents as a disease of focal onset and contiguous spread. Characteristic regional patterns of involvement and progression suggest that the disease does not proceed randomly but via a restricted number of anatomical pathways. These clinical observations combined with electrophysiological and brain-imaging studies underpin the concept of ALS at the macroscopic level as a ‘system degeneration’. This dichotomy between cellular and systems neurobiology raises the fundamental questions of what initiates the disease process in a specific anatomical site and how the disease is propagated. Is the essence of ALS a cell-to-cell transmission of pathology with, for example, a ‘prion-like’ mechanism, or does the cellular pathology follow degeneration of specific synaptic networks? Elucidating the interaction between cellular degeneration and system level degeneration will aid modeling of the disease in the earliest phases, improve the development of sensitive markers of disease progression and response to therapy, and expand our understanding of the biological basis of clinical and pathological heterogeneity.

Introduction: Clinical and pathological features indicate that ALS is a system failure

The first clinicopathological descriptions of ALS by Jean-Martin Charcot in Paris in the mid-19th century are contemporaneous with the evolution of the concept of upper and lower motor neurons and the recognition of the anatomical role both of the anterior horn cells of the spinal cord in the actualisation of voluntary movement and of the corticospinal tracts in conveying descending modulation and control (Charcot & Joffroy, 1869). Amyotrophic lateral sclerosis is the commonest form of motor neuron disease, and the third most frequent neurodegenerative disease after Alzheimer's disease and Parkinson's disease. The annual population incidence is 2/100 000 per year, and there appears to be a uniform geographical incidence of ‘sporadic’ forms of ALS, although monogenic forms, which account for 5–10% of cases, show variation in incidence between populations, presumably due to founder effects (Byrne et al. 2011; Chio et al. 2013). The malignant nature of the disease progression is indicated by the fact that the median survival is approximately 2 years from diagnosis and 3 years from symptom onset (Chio et al. 2011). However, there is considerable clinical variation, with a long ‘tail’ in the survival curve; approximately 10% of patients are still alive at 10 years after onset. A better understanding of the biological underpinning of this variation in outcome could shed considerable light on the nature of ALS.

There is a general consensus among neurologists who specialise in ALS that the condition has a focal clinical onset. The overwhelming majority of patients are clearly able to describe alteration in motor function in one body region at a specific time, typically within a timescale of weeks to months. Approximately 30% of cases begin in one upper limb, 35% in one lower limb and 30% in the muscles of speech and swallowing, with the remainder accounted for by initial respiratory failure or various forms of axial weakness (head-drop or truncal weakness). Where the onset is characterised by weakness in more than one body region at presentation, this is generally a manifestation of rapidly progressive disease with a poor prognosis. Furthermore, the disease does not progress randomly, but through a discrete number of recognisable patterns of clinical evolution (Chio et al. 2011). The fact that such patterns do not vary between populations with different genetic backgrounds implies that progression is an inherent feature or an emergent property of the way in which the corticomotorneuronal system promoting voluntary movement fails.

Although classical ALS is conventionally divided into spinal (limb) or bulbar (speech and swallowing) onset, this simple dichotomy fails to capture accurately the clinical heterogeneity of the condition. A more useful approach to classification, allowing more accurate prognostication and also proactive management of nutrition and respiration, is to consider the site of symptom onset, the intrinsic rate of progression (e.g. the slope of functional decline using a validated clinical measure such as the ALS Functional Rating Scale), whether symptoms remain regionally localised or rapidly spread to other anatomical segments, the timing of involvement of respiratory and bulbar muscles, and the age of the patient. Older age is an independent variable predicting short survival, which may reflect a higher burden of co-morbidities, an age-related lack of functional reserve in the motor system, or that an age-related neurodegenerative process is likely to be more aggressive in the aged brain. The most robust predictor of survival is the latency from symptom onset to confirmed diagnosis in a specialist clinic. A firm diagnosis of ALS requires involvement of more than one anatomical region (bulbar, upper limb, lower limb); weakness and wasting initially confined to one limb is the commonest presentation of ALS, but has a broad differential diagnosis. Slowly progressive forms of ALS are often atypical in presentation, increasing diagnostic uncertainty and requiring more ancillary diagnostic tests.

Pathologically, ALS is characterised in the majority of cases by ubiquitinated inclusions, which stain for the protein TDP-43 (Neumann et al. 2006). Careful studies correlating regional distribution of pathology with the clinical burden of disease in life suggests that there is a radial gradient of involvement from an initial clinical and pathological focus, and that this proceeds in a non-random fashion across contiguous anatomical segments (Ravits et al. 2007). Furthermore, there is evidence of simultaneous involvement of the corticospinal tract and spinal motor neuron circuits. Although there are many patients with clinical features showing upper or lower motor neuron predominance, it is the combination of the two that is so characteristic of ALS, particularly in its most aggressive forms.

In addition to the undoubted contribution of aging as a critical co-factor in the development of ALS, attention has also focused on the possible role of developmental factors in neurodegenerative diseases like ALS. It is clear that Alzheimer's disease and Parkinson's disease are the clinical endpoints of degenerative system failures that begin decades before (Bateman et al. 2012). It is possible that the way in which the corticomotorneuronal system is established in development varies significantly between individuals and that this variation is governed partly by genetic influences. The observation that patients with ALS are more likely to have a high level of physical fitness, a lower body-mass index and to have fewer other co-morbidities suggests that the disease might be more likely to affect a population of individuals with a motor system with specific characteristics (Veldink et al. 2005; Turner et al. 2011).

Direct corticomotorneuronal connections to anterior horn cells appears to be a recent evolutionary development, unique to higher primates. Human neocortical evolution over the last 200 000 years has been rapid and is presumably under strong selection pressure. The number of fibres in the corticospinal tract has increased by about 30–40% in the 5 million years since a common human-chimpanzee ancestor (Lemon, 2008). It has been suggested that this rapid and recent evolution of the motor system, in large part driven by the development of language and manual dexterity, while advantageous at a species level, may have come with an inherent penalty of increasing the possibility of system level failure in individuals with the appropriate genetic susceptibility profile (Eisen, 2009). For example, the clinical phenomenon of the ‘split hand syndrome’ in which there is preferential wasting of the thenar eminence, has been proposed to be a reflection of the corticomotorneuronal representation and input for fractionated thumb movement (Weber et al. 2000).

Although the clinical association between ALS and frontotemporal dementia has been known for decades, it has only been the subject of serious research activity in the last 10 years. It is now clear that up to 50% of patients with ALS show impairments on psychological tests of executive function (planning, attention and reasoning) if tested in sufficient detail, and in approximately 5% of cases FTD is the dominant clinical feature (Phukan et al. 2012). The neuropathology of ALS and FTD cases characterised by ubiquitin stained inclusions is identical at the cellular level, demonstrating TDP-43 inclusions and loss of nuclear staining, and varies only by distribution. With some notable exceptions (e.g. SOD1, see below) mutations in the genes associated with ALS can also cause FTD. Remarkably, in families with an identified genetic mutation, individuals can manifest ALS, FTD or combined ALS-FTD, suggesting that other events, or multiple ‘hits’, interact with a genetic mutation to determine the manifestation of the disease within the confines of a specific neuroanatomical pathway. An understanding of why two apparently different and unconnected neuroanatomical networks (corticomotorneuronal and frontotemporal) are involved in the same disease, and often combined in the same patient, is a priority for clinical and pathological research.

The cellular basis of motor neuron vulnerability in ALS

In addition to neuropathology, the most important biological insights in recent decades have come from the identification of genes associated with monogenic forms of ALS. Approximately 5% of patients have other affected first degree or second degree relatives and are considered to have familial ALS. There are now more than 10 genes for which there is general consensus of mutations having a direct causal relationship with ALS and others in which there is incomplete evidence (Al-Chalabi et al. 2012). Depending on the population studied, 35–45% of the familial cases are explained by a dynamic hexanucleotide expansion mutation in the C9orf72 gene on chromosome 9 (DeJesus-Hernandez et al. 2011; Renton et al. 2011), 20% of fALS by mutations in SOD1 (Rosen et al. 1993) and 4–5% each by mutations in TDP-43 or FUS/TLS (Sreedharan et al. 2008; Vance et al. 2009). Therefore, approximately 25% of genetic cases are yet to be explained. Importantly, although there are some observable trends and clinical clues such as the co-occurrence of FTD in families with C9orf72 mutations, it is not possible to distinguish reliably familial from sporadic ALS on clinical features alone (Byrne et al. 2012). This suggests that research into genetically determined cases of ALS would yield information of general relevance for the much commoner sporadic ALS. In fact, for each of the genes identified as causing fALS, mutations have been identified in apparently sporadic cases, at a low level (< 1%) for SOD1, TDP-43 and FUS, but remarkably in 5–7% of sporadic cases in populations of European descent for C9orf72 (Majounie et al. 2012). This indicates that that the strict distinction between familial and sporadic cases is an artificial dichotomy with genetic factors more likely to operate as a continuum, encompassing familial cases with high penetrance at one extreme, and true sporadic cases at the other (Talbot, 2011).

The number of individual upstream genetic factors contributing to ALS is therefore great and attempts to use the known functions of these genes to form functional groups that might give insights into motor neuron vulnerability are only partially successful. These are reviewed in detail elsewhere (Robberecht & Philips, 2013) but can be summarised under a number of broad themes:

  1. Both TDP-43 and FUS are RNA-binding proteins. Evidence suggests that each protein regulates the processing of non-overlapping subsets of transcripts by binding to conserved intronic motifs, which are possibly commoner in neurons. In each case the number of identified gene targets is greater that 5000 (Lagier-Tourenne et al. 2012). In keeping with this apparently generalised splicing function, inactivation of TDP-43 or FUS by gene targeting or RNAi knockdown is lethal to cells. It is therefore difficult to envisage that loss of function mutations can be the sole mechanism of motor neuron degeneration in ALS, though aggregation and mislocalisation may be the final trigger to cell death. In keeping with this, loss of TDP-43 from its normal location in the nucleus is a pathological hallmark of ALS in 95% of cases (Neumann et al. 2006) (Fig. 1). This suggests that the cellular ‘lesion’ in TDP-43-associated ALS is a shift in the cellular compartment from nuclear to cytoplasmic, presumably induced by age-related cellular stress. When this has reached a critical level, the nucleus is depleted of TDP-43, and this presumably triggers cell death (Igaz et al. 2011). A number of other RNA-binding proteins are mutated in ALS and also non-ALS motor neuron diseases such as spinal muscular atrophy (Baumer et al. 2010a) but given the diversity of function of such proteins no overarching mechanism has yet emerged to explain this relatively cell-selective degeneration. Mutations in C9orf72, the commonest cause of ALS and also frontotemporal dementia, may lead to disruption of RNA-binding proteins through aberrant interaction with the expanded hexanucleotide repeat, but other mechanisms have also been proposed.
  2. Proteins involved in the maintenance of cellular protein homeostasis form a second group. These include ubiquilin-2, sequestome-1, optineurin and VCP, mutations in which have been described at a low frequency in ALS (1–2% of familial cases). As protein aggregation is a common feature of neurodegenerative diseases, this pathway is a mechanistically plausible point of vulnerability in ALS. However, as with RNA-binding proteins, there is currently no clear explanation for the selective vulnerability of motor neurons over other CNS cells. SOD-1, which until the discovery of mutations in C9orf72 was the commonest and most studied cause of familial ALS, appears to be a protein with an unusual propensity to misfold and can be tentatively considered to be in this pathway.
  3. A range of proteins functioning in axonal transport (including neurofilament subunits, peripherin, VAPB and others) have been implicated in rare families with motor neuron diseases. Although these can be classified within the ALS spectrum, there are some atypical features such as lower motor neuron predominance and slow progression (Robberecht & Philips, 2013).
Figure 1.

Primary motor neurons cultured from a transgenic mouse harbouring an ALS-associated TDP-43 mutation (M337V) (a, unstressed; b, treated with 0.5 mm sodium arsenite), demonstrating that under conditions of cellular stress TDP-43 (red) moves from the nuclear to cytoplasmic compartment, where it partially co-localises with stress granules (green) and also travels down the axon. (Courtesy of Dr David Gordon, Nuffield Department of Clinical Neurosciences, University of Oxford).

Even in apparently simple monogenic forms of ALS it is necessary to invoke a multiple hit mechanism in which aging is a critical co-factor. Although the median age of onset of fALS cases is approximately 10 years earlier than sALS cases, the majority of familial cases, especially those due to C9orf72 mutations, still occur in the same age group (55–75 years) where most sALS cases arise. The putative age-related changes in cells which after many years lead to loss of tolerance of genetic mutations, many of which are highly toxic in cell culture models, include damage from oxidative stress exceeding the buffering capacity of the cell, damage to the genome and to sub-cellular organelles and alterations in the functional capacity of the proteasome.

How and when does ALS begin and how does ALS spread?

The latency between first symptoms and a formal diagnosis of ALS in a neurology specialist clinic varies, but averages 1 year (Chio et al. 2011). What is happening in the nervous system prior to the point of symptom onset is currently a matter of speculation. Although clinical observation suggests that such patients have been functioning normally right up until symptom onset, and a limited longitudinal neurophysiological study in SOD1 mutation carriers indicates that the number of motor units is normal up to few months prior to first symptoms (Aggarwal & Nicholson, 2001), the idea that ALS might arise abruptly from a normal nervous system is only one possibility. If ALS, in common with AD and PD, has a prolonged period of system dysfunction without obvious clinical manifestation, this has important implications, as a pre-clinical phase is likely to be the best target for therapeutic trials.

Most neurodegenerative diseases appear to have three phases (Fig. 2). During normal development of the nervous system, genetic variation between individuals may be an important influence in determining later life susceptibility to degeneration, but there is no evidence of dysfunction. In the pre-clinical phase, susceptible individuals are likely to have abnormal neuronal function, at a network or individual synapse level, but this does not lead to clinical symptoms either because the system in question has intrinsic reserve capacity or because there are other compensatory mechanisms in operation. It is therefore only when the reserve is exceeded or the compensatory mechanisms break down, that patients develop symptoms and the clinical phase begins.

Figure 2.

Patients with ALS present to a specialist neurological clinic on average 1 year after the onset of symptoms. It is likely that this occurs when functional reserve in the motor system has been used up (vertical dotted line). Whether this occurs as an explosive loss of motor neurons on the background of normality (green line) or after a steady loss of cells over decades (blue line) is unclear. However, by analogy with other neurodegenerative diseases, it remains plausible that people who develop ALS have a period of life in which they are normal but susceptible (based on their genetic profile) followed by a period of uncertain duration in which there is system dysfunction but no clinical manifestation, either due to functional reserve within the motor system or the recruitment of active compensatory pathways.

The apparent focal onset of ALS in clinical terms might suggest that a precise ‘event’ located in time and in anatomical space triggers the disease. However, it is just as likely that the whole corticomotorneuronal system is in a state of partially compensated decline and the ‘site of onset’ simply reflects stochastic events that determine where a generalised disease rises above the ‘clinical horizon’. In this case, studying the clinical heterogeneity of ALS and stratifying patients according to extremes of phenotype, even if it is important for clinical management, might not provide much meaningful insight into the biological basis of the motor neuron degeneration. An intriguing observation in support of this possibility comes from families in which a single genetic mutation can give rise to almost every possible clinical sub-type of ALS (Fig. 3). In this family a single genetic mutation manifests as typical spinal or bulbar onset ALS, a slowly progressive lower limb variant that is lower motor neuron predominant or as an upper motor neuron predominant form described as ‘stiff limbs’. This degree of heterogeneity is not uncommon in genetically determined ALS, although there are some general trends with different genetic subtypes. For example, SOD1-related ALS almost never causes significant cognitive impairment (Wicks et al. 2009), FUS-associated ALS can be an aggressive form with onset in young adulthood (Baumer et al. 2013) and there are some broad pointers to a C9orf72 mutation such as a strong family history of dementia (Byrne et al. 2012).

Figure 3.

In this family, affected by ALS due to autosomal dominant inheritance of the I113T SOD1 mutation the index case (arrow) presented with typical ALS with limb onset, progression to bulbar and respiratory weakness and death within 3 years. Other family members presented with typical bulbar onset, respiratory onset or ‘creeping paralysis’, an old term for slowly progressive lower limb predominant (‘flail-leg’) ALS which typically has a survival of 5–8 years. As is common with this particular mutation, there are obligate carriers who did not develop ALS (reduced penetrance).

While understanding the initiating steps of ALS is likely to be important for the development of therapies, of equal relevance could be understanding the mechanism of disease propagation and finding ways to halt this. A hypothesis that has received much attention recently is that neurodegeneration may spread from cell to cell by a mechanism akin to that seen in prion diseases (Nonaka et al. 2013). A number of ALS-associated proteins (principally TDP-43 and FUS) contain ‘prion-like’ domains, which in principle could promote protein aggregation. However, as well as the fact that even in classical prion diseases such as Creutzfeldt–Jakob disease (CJD) the method of spread has not been well characterised, there is only indirect evidence that TDP-43 actually undergoes prion-like aggregation, a process which is defined as permissive templating of native protein by a conformationally altered, mutant form of protein. Furthermore, other classical features of prion diseases such as evidence of infectivity are currently lacking.

There are a range of other possible mechanisms with equal explanatory power, such as transynaptic spread of mutant protein, spread through adjacent glia or even through circulating factors. Finally, the higher order network organisation of the corticomotorneuronal system, which is incompletely understood, could provide an explanation for how the disease appears to spread through anatomically contiguous segments if the equilibrium of inter-related sub-networks of fibres is altered by cell death in an adjacent region. The elucidation of such mechanisms will require new and more sophisticated approaches to the analysis of animal models and to human biomarker studies.

Conclusions: new opportunities to integrate cellular and systems based research in ALS

Since its initial description in the late 19th century, ALS has been recognised by clinical neurologists as a relatively stereotyped diagnostic entity and treated, for the purposes of clinical enquiry and clinical trials, as a single disease. In the modern era of molecular and cellular biology this concept is no longer tenable and has been replaced by a view of ALS as a clinicopathological syndrome with multiple upstream causes. However, the clinically stereotyped nature of the disease progression, and emerging evidence from multimodal brain imaging studies, suggests that a system level vulnerability is an important aspect of the biological underpinning of ALS. The recent discovery that approximately 10% of all ALS cases, and a similar number of FTD cases, are due to an expanded hexanucleotide repeat in the C9orf72 gene provides an important new departure for ALS research. Much has been learned about the pre-clinical phase of disorders such as Huntington's disease by longitudinal multimodal studies of gene carriers (Tabrizi et al. 2013). The large number of potential subjects who could be recruited from ALS clinics, both those with early disease and pre-symptomatic carriers of the mutation, will for the first time allow studies of the pre-symptomatic phase of ALS that may contribute to a complete understanding of the relationship between a genetic mutation and the corticomotorneuronal system in which the disease reveals itself.

Work in Professor Talbot's laboratory is supported with funding from the MND Association.


Maine Revised Statutes

§3606. Mass picketing to prevent maintenance or movement of perishables

It shall be unlawful for any person, acting individually or in concert with others, by mass picketing, force, coercion, physical obstruction at the entrance to any place of employment or physical obstruction in any street, sidewalk or railway, to prevent or attempt to prevent the delivery to any public, commercial or industrial enterprise of any supply, commodity or service necessary for the proper maintenance of any of the buildings, equipment, machinery or fixtures constituting such enterprise or necessary to keep any of such buildings, equipment, machinery or fixtures from deteriorating or being damaged by fire, freeze-up or other casualties, or the harvesting, the storing, the transportation to storage and market of a perishable food product. For the purpose of this section, "person" means any individual, corporation or unincorporated association, including partnerships and labor organizations. Whoever violates this section shall be punished by a fine of not more than $250 or by imprisonment for not more than 30 days, or by both.


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A green-tea croissant or a sesame éclair, anyone?
Japanese cake guru,

delicious) cakes in Paris.

Tables are available if you want to eat in. In January and February, don’t miss his ‘galette des rois’ filled with matcha, black sesame and azuki paste!


Big things are in store for the Lost Language label. One reason being they are getting their main man back in charge after an extended hiatus. That’s right; Ben Lost is returning and in doing so he is mixing the fifth installment of the Exhibition series. March 10th is where the release date has been set for this colossal compilation/mix package.

Ben Lost

The compilation will feature artists like Manmachine, Ovnimoon and Superpsychics with a total of fourteen tracks overall. There is a lot of talent packed into this project and given Ben’s return to his A&R position, you can assume this one will be a game-changer. There are no previews currently, but the full tracklist as been released and you may find that below.

1: Bernie Allen: Late Reflections (Manmachine Remix)
2: Space Manoeuvres: Stage One (Guy J Remix)
3: Barraka: Song To The Siren (Jaap Ligthart Vocal Mix)
4: Amir Abbasi: Angelus Sine Sensu (Hazem Beltagui Remix)
5: Miro: Paradise (Mindwave Dub Remix)
6: Dj Orion & J Shore: Brotherhood (Taucher Adult Mix)
7: Miro: By Your Side (Ovnimoon Remix)
8: Freesoup: We Who Have
9: Manmachine : Where’s Cynthia?
10: Filteria: Perpetually Delayed Voyage (Sonic Entity Remix)
11: Sonic Entity: Genome Evolution
12: Superpsychics: Coheena (Cosmithex Remix)
13: Accadia : Blind Visions (Neptune Project’s Third Eye Remix)
14: C.M: Dream Universe (Activa Remix)


Random Act Artist Bria Skonberg hails from Chilliwack, B.C. and a musical family; she now resides in New York City. With her memorable compositions and compelling vocals,Bria brings a modern flair to traditional jazz. Her unique combination of style, skill, taste and swing positions her as one of the most versatile and imposing musicians of her generation. She performs at clubs such as Birdland and Iridium in New York, and at festivals and venues around the world. Whether leading her own bands or performing with others, Bria’s rare beauty shines through her sublime trumpet playing, angelic singing and heartfelt compositions. Her debut as a Random Act Artist So Is The Day came out in April 2012. Her most recent effort, INTO YOUR OWN, showcases her own vocal harmonies, her touring band and the legendary percussionist MINO CINELU. Roll down the windows and turn up the sounds: Let Bria take you on a journey through Life and Love.


The 'DineHero' Network App Encourages Collaborative Dining

The 'DineHero' network app aims to help users "never dine alone again" by enabling them to find others nearby that are open to grabbing a table and eating together. Designed as an app to help professionals find other professionals to dine with, 'DineHero' hopes to turn online networking into real-life interactions and relationships. It's ideally created for those who are new to a certain location or job, business travelers or even foodies looking to try out a new restaurant.

The number of people who are working independently or in small teams is on the rise, which can sometimes limit the networking capabilities. The 'DineHero' network app aims to help users broaden their professional social groups and connect people over a meal with up to three other people.


Time For An Update

When it comes time for the GDP, what counts?

August 25, 2002|By Robert Costanza. Robert Costanza is director of the University of Vermont Institute for Ecological Economics.

Enron, WorldCom, and other corporations have violated basic good accounting principles. They have hidden costs and inflated profits in order to make their operations look better than they were. But these scandals are small potatoes compared to the analogous accounting errors inherent in the U.S. government's National Income Accounts, which paint a dangerously misleading picture of how well the economy as a whole is doing.

The most commonly used measure of national economic performance, Gross Domestic Product, does not adequately distinguish costs from benefits, inflates profits, and therefore makes the operation of the economy look better than it actually is. Fraudulent corporate accounting cost shareholders billions and shook the markets. The GDP counts over a trillion dollars in costs as revenues.

To understand how this can be, one needs to understand what the GDP is measuring, why it is no longer an appropriate measure of economic performance, and what some of the alternatives are.

GDP measures marketed economic activity or gross income. It was never intended as a measure of economic welfare, and it functions very poorly as a welfare measure. Yet it is inappropriately used as a national welfare measure in far too many circumstances. Just check the headlines: "GDP up = good; GDP down = bad" is the unambiguous message.

What are the problems with the GDP as an economic-welfare measure?

First, it counts everything as a positive. It does not separate desirable, welfare-enhancing activity from undesirable welfare-reducing activity. For example, an oil spill increases GDP because someone has to clean it up, but it obviously detracts from welfare.

From the perspective of GDP, more crime, more sickness, more war, more pollution, more fires, storms and pestilence are all potentially good things, because they can increase marketed activity in the economy.

Second, GDP leaves out many things that do enhance welfare but are outside the market. For example, the unpaid work of mothers caring for their own children at home doesn't show up, but if these same mothers decide to work outside the home to pay for child care, GDP suddenly increases.

The non-marketed work of nature in providing clean air and water, food, natural resources, and other ecosystem services don't adequately show up in GDP, but if those services are damaged and we have to pay to fix or replace them, then GDP suddenly increases.

Third, GDP takes no account of the distribution of income among individuals. But it is well-known that an additional $1 worth of income produces more welfare if one is poor rather than rich. Doubling Bill Gates' income would do far less toward enhancing his welfare than doubling the income of the countless people worldwide currently working for a dollar a day would do for theirs, and at lower cost.

These problems are not invisible, and several researchers have proposed alternatives that try to separate the positive from the negative components of marketed economic activity, add in non-marketed goods and services, and adjust for income-distribution effects.

These include William Nordhaus and John Tobin's MEW (Measure of Economic Welfare), developed in 1972; Herman Daly and John Cobb's ISEW (Index of Sustainable Economic Welfare), developed in 1989; and Redefining Progress' more recent variation of ISEW, the GPI (Genuine Progress Indicator: www.rprogress.org/projects/gpi/).

For example, the Gross Progress Indicator shows that while GDP has steadily increased since 1950, with the occasional recession, GPI peaked in about 1975 and has been decreasing ever since. Thus, from the perspective of economic welfare, rather than mere activity, the U.S. economy has been in recession since 1975.

This also is more consistent with survey-based research on people's stated life-satisfaction, which has been decreasing rather than increasing over the last several decades. We are now in a period of what Daly has called "un-economic growth," where further growth in economic activity (GDP) is actually reducing welfare (on balance) rather than enhancing it.

How can we reverse this situation and get out of the real recession in economic welfare that we have been in since 1975? Several policies have been suggested that would help to turn things around, including:

- Shifting our primary national policy goal from increasing marketed economic activity (GDP) to maximizing economic welfare (GPI or ISEW).

- Using the tax system to send the right incentives by taxing negatives (pollution, depletion of natural capital, overconsumption) rather than positives (labor, savings, investment). Recent tax reforms decrease welfare by promoting a greater income gap, natural resource depletion and increased pollution.

- Reforming international trade to promote economic welfare over GDP growth. This implies subjugating trade to greater environmental protection, labor rights and democratic self-determination rather promoting trade rules that ride roughshod over all other societal values.

- Further reforming campaign finance laws so that the needs and welfare of individuals are more fully and accurately expressed in the democratic process, rather than the needs and welfare of those who currently fund political campaigns.

Ultimately, getting out of the 25-year welfare recession we are currently in will require that people first recognize how bad the current system is at tracking welfare.

We must not allow deceptive accounting practices (analogous to those that caused the Enron and WorldCom debacles) to paint an inaccurate and ultimately destructive picture of how well the economy is doing.

Alternatives are available, but they need significant further research, discussion and funding. With nothing less than our current and future welfare at stake, we can certainly afford much greater effort devoted to figuring out how to adequately measure it.

Ultimately, if we want the things that really matter to our welfare to count, we have to learn how to count them.


Fresh Toones is a web site dedicated to fostering the creativity of all those individuals who struggle on their own with little or no public support to explore and produce.Whether it be music, animation, song writing, painting or any creative endeavor, there is much for us to share and much more for us to discover.

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Yann Perreau

A singer-songwriter and notorious showman, Yann Perreau will launch his 5th album of original songs, Le fantastique des astres, on April 15th, 2016. With this project, Yann is in full command of his songwriting, and his music is more infectious and hypnotic than ever.

Website | www.yannperreau.com