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General / Protéus
Applying Enzymatic Synthesis for Chiral Molecules
Home Newsroom Applying Enzymatic Synthesis for Chiral Molecules
Pharma's Almanac Magazine
Advances in our understanding of enzymatic transformations and the increased availability of enzymes engineered for use in fine chemical synthesis is making biocatalysis attractive for the production of chiral pharmaceutical intermediates and APIs. Seqensis leveraging its expertise in chemo- and biocatalysis to identify cost-effective routes to increasingly complex small molecule drug substances with chiral centers.
The Importance of Chirality
Chirality is a fundamental property of organic molecules that contain asymmetric carbon atoms with four distinct binding groups, which can exist as paired stereoisomers — known as enantiomers — that form mirror images of one another. These enantiomers are often referred to as right- and left-handed. They not only rotate polarized light in opposite directions, they exhibit very different interactions with other chiral molecules.
Both the biologically active molecules targeted by small molecule drugs and their constituent building blocks (nucleic acids, amino acids) are chiral. Overwhelmingly, biological molecules exhibit strict homochirality — natural amino acids are left-handed, while DNA and sugars are right-handed.
Small molecule active pharmaceutical ingredients are also typically chiral, and classical production methods result in mixtures of paired enantiomers. Given that target molecules are homochiral, the two enantiomeric forms of a chiral API could exhibit different pharmacokinetic and pharmacodynamic behaviors — and different efficacies and toxicities. It is also possible for one enantiomer to be bioactive and the other not, or, in the most extreme cases, for one enantiomer to provide a therapeutic effect while the other is highly toxic. In some cases, the members of an enantiomer pair have been found to be effective in the treatment of very different diseases.
Regulatory agencies do not require the development of chiral drugs as single enantiomers. Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), however, require pharmaceutical companies to comprehensively evaluate the properties of each enantiomer individually as well as the racemic (50:50) mixture of a chiral API.
Consistent with the homochirality of biomolecules, the reactions catalyzed by enzymes generally exhibit high stereo- and regioselectivities, generating products highly enriched for single enantiomers.
New Way of Thinking
Small molecule drug candidates in the pipeline today are becoming more complex. It is common for an API under development today to have multiple chiral centers. The increasing complexity has driven the need for new approaches to obtaining chirally pure enantiomers. When pharmaceutical chemists first began developing routes for the preparation of single enantiomers of chiral APIs, they largely relied on separation technologies. The API was synthesized as a racemic mixture, and then the desired enantiomer was separated from the undesired one.
This approach has several disadvantages. It is often difficult to separate two enantiomers from one another. In many cases, the desired isomer remains contaminated with the undesired molecule. Even if an effective method is developed, the remaining enantiomer — often a very expensive material — becomes a waste product. As a result, this approach involves a significant waste of time and resources and is therefore very costly.
To avoid these problems, chemists began seeking methods for the selective production of single enantiomers of chiral molecules — and, to do so, they turned to catalysis. Catalysts mediate complex transformations but do not take part in them. Specially designed catalysts can mediate asymmetric transformations that result in the formation of several bonds and chiral centers, all in one step.
As an example, compared with kinetic resolutions of racemic mixtures, enzymatic desymmetrizations of meso compounds allow the synthesis of chiral derivatives with a 100% theoretical yield.
SEQENS has developed the asymmetric mono hydrolysis of the corresponding prochiral diester. After ammonolysis of the remaining ester, the corresponding amide was finally involved in a Hofmann rearrangement to afford R-baclofen (Fig. 1A).
After screening Protéus's enzyme portfolio, a hit was identified allowing the transformation of the prochiral diester with very high enanselectivity (> 99% ee). Moreover, the kinetic and thermodynamic analysis was further addressed for shedding insights into the desymmetrization process. The full R-baclofen process was then scaled-up at SEQENS's R&D center based in Porcheville.
Furthermore, SEQENS has developed an enzymatic process for manufacturing d-serine product on a multiton scale; both productivity and high enantioselectivity were achieved (Fig. 1B). Protéus by SEQENS has developed its own enzyme library, with more than 300 enzymes available off-the-shelf.
Biocatalysis vs. Chemocatalysis
Synthetic chemists have the choice of using chemo- or biocatalysts. Chemocatalysts typically are transition-metal complexes with complicated structures designed to bind in specific ways to specific substrates to achieve a desired and highly selective transformation. While most are designed to perform homogenous catalysis in solution, heterogeneous catalysts are also available. Often, there are several choices of chemocatalysts for mediating a certain type of reaction.
Like chemocatalysts, biocatalysts are designed to perform highly selective and specific chemistry, but can be composed of engineered enzymes. They have the advantage of being heavy metal free, and thus do not require the removal of metal impurities after completion of a reaction. Consistent with the homochirality of biomolecules, the reactions catalyzed by enzymes generally exhibit high stereo- and regioselectivities, generating products highly enriched for single enantiomers. Additionally, biocatalysts are highly efficient, allowing catalysis to be performed under mild reaction conditions, with reduced energy consumption and greenhouse gas emissions in comparison to chemical catalysis. Enzymatic reactions are also generally performed in water rather than organic solvents.
In addition to being used to replace chemocatalysts in straightforward asymmetric reactions, biocatalysis can sometimes be used to complete chiral transformations with significantly fewer steps. Typically, for molecules with more than one of the same type of functional group, chemocatalysts often do not selectively interact with just one of those groups. The others must first be protected, and then, after the asymmetric transformation is completed, be deprotected — potentially adding multiple steps to a synthetic route. In many cases, enzymes have the capability to selectively convert one of many similar functional groups in a molecule, reducing the overall process steps, time and cost.
There are also cases where enzymes are able to achieve transformations that cannot be performed effectively — or at all — using classical chemical methods or chemocatalysts. In many cases, biocatalysts can mediate complex transformations that generate complex intermediates or APIs with multiple chiral centers. Here, biocatalysis affords access to novel structures and can potentially have significant impacts on manufacturing time and cost.
In general, chemocatalysis and biocatalysis are complementary. Having expertise in both methodologies increases the likelihood of identifying the shortest, most efficient and cost-effective route to complex pharmaceutical compounds. The choice of catalytic technique will depend on the target molecule, the availability of different catalysts at industrial scale, the ability to develop appropriate analytical methods and, of course, cost. It is also important to remember that, in some cases, the same intermediate may not be used in a classical chemical synthesis route, as would be required for biocatalysis due to the different selectivities of certain enzymatic reactions.
While in some cases these off-the-shelf enzymes provide the required level of performance in terms of yield and selectivity for the desired isomer, it is often the case that some optimization is necessary for a specific transformation.
Growing Number of Choices
Building a comprehensive toolbox of biocatalysts is now possible due to significant advances in enzyme engineering technologies. Until recently, the number of enzymes suitable for use in the pharmaceutical industry (and available at industrial scale) was limited. In addition, the engineering of enzymes tailored to achieve a specific chiral transformation with high yield and selectivity was a lengthy process. Today, however, many different biocatalysts are available off-the shelf, and the development of customized enzymes can be achieved rapidly.
In the late 1980s, most enzymes used in the pharmaceutical industry at industrial scale were hydrolases, and most commonly lipases. These enzymes mediated the selective hydrolysis of esters. Since the 2000s, however, many additional types of biocatalysis have become available for pharmaceutical manufacturing, including nitrilases, transaminases, acyltransferases, epoxide hydrolases, ketoreductases and iminereductases, among others. The armentarium of commercially available enzymes continues to expand almost on a daily basis.
This growing array of enzyme choices allows route development chemists to consider multiple synthetic strategies and identify the best route possible. Evaluation of technical and cost considerations for the multitude of chemo- and biocatalysts available for achieving complex, yet highly stereoselective transformations helps determine the most appropriate methods for each step in an overall synthesis.
While in some cases these off-the-shelf enzymes provide the required level of performance in terms of yield and selectivity for the desired isomer, it is often the case that some optimization is necessary for a specific transformation. Given the numerous advances in rapid genome sequencing, site-specific mutagenesis, directed evolution, computational toolsand other techniques, it is now possible to rapidly and efficiently engineer robust enzymes with tailored biocatalytic activity.
The key question becomes one of lead time. If an off-the-shelf enzyme is suitable, then lead times are no different than those for purchasing other key raw materials. If an enzyme must be engineered, the lead time will be longer; once the engineering is completed, the enzyme must be produced — typically via fermentation — and downstream processed. Procedures and analytical methods must be developed to ensure that residues linked to enzyme production are purged from the catalyst.
At SEQENS, we are ideally positioned to bring together extensive expertise in enzymatic technologies and pharmaceutical route development. We have experience developing optimized enzymes for specific transformations and can even produce immobilized biocatalysts if appropriate.
Integrated Know-how in Asymmetric Synthesis
SEQENS was formed in December 2018 when Novacap took over Uetikon, PCAS, including Protéus and PCI Synthesis. With 24 manufacturing plants and three R&D centers in Europe, North America and Asia, we are an integrated global leader in pharmaceutical synthesis and specialty ingredients.
Our greatest expertise lies in developing and producing highly complex molecules using a unique skillset and a very broad continuum of technologies that encompasses both chemo- and biocatalysis. At SEQENS, we are ideally positioned to bring together extensive expertise in enzymatic technologies and synthetic route development. We have experience developing optimized enzymes for specific transformations and can even produce immobilized biocatalysts if appropriate.
As a one-stop shop, we provide support to clients from the lab and exploratory stages through route design, process development and scale-up to clinical manufacturing and commercial production for all types of APIs, including complex chiral molecules. We can produce intermediates in our non-GMP facilities and clinical and commercial materials at our GMP sites using our integrated capabilities for asymmetric synthesis and processing.
The ability to produce raw materials, intermediates and APIs within one company ensures that we develop the most cost-competitive synthetic strategies for chiral APIs, which may not be possible if raw materials and intermediates are purchased from external sources. Our in-house catalyst teams at both our non-GMP and GMP sites collaborate to identify the best synthetic routes and develop processes that are practical for implementation at commercial scale.
In addition, with respect to biocatalysis, which is still a newer technology in the pharma industry, our process development, engineering, production, analytical and regulatory groups collaborate and share their knowledge and understanding to rapidly and efficiently develop optimized, compliant manufacturing processes. The experience we have gained over the last several years, working on many different projects, gives us a real competitive advantage and directly benefits our customers.
Info Chimie: Interview with Pierre Luzeau
Pierre Luzeau was interviewed by Sylvie Latieule for Info chimie magazine (issue 553) released on February. Discover more…
Discover SEQENS' electronic activities with Francis Belanger
Discover Seqens Advanced Specialties and our activity thanks to the interview of Francis Belanger, Global Electronic Market Manager.
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This month's U.S. soybean supply and use projections for 2012/13 include lower beginning and ending stocks and reduced use. Lower beginning stocks reflect increased export and crush projections for 2011/12.
Soybean exports for 2011/12 are raised 20 million bushels to 1.335 billion bushels reflecting increased global import demand, led mainly by higher projected imports for China. Soybean crush is raised 15 million bushels mostly due to stronger domestic soybean meal use.
Soybean ending stocks for 2011/12 are projected at 175 million bushels, down 35 million. With reduced supplies for 2012/13, soybean exports are projected at 1.485 billion bushels, down 20 million. Soybean crush is also projected lower due to reduced domestic soybean meal use. Ending stocks for 2012/13 are projected at 140 million bushels, down 5 million from last month.
Soybean, meal, and oil price projections for 2012/13 are unchanged this month. The U.S. season average soybean price is projected at $12.00 to $14.00 per bushel. Soybean meal and oil prices are projected at $335 to $365 per ton and 52.5 to 56.5 cents per pound, respectively.
Global oilseed production for 2012/13 is projected at 470.8 million tons, down 0.7 million from last month, mainly due to lower soybean and cottonseed production. China's soybean production is reduced 0.5 million tons due to lower area as producers shift planting decisions toward corn. Brazil's cottonseed production is also reduced due to lower area planted to cotton as world prices have declined in recent weeks.
Other changes include reduced rapeseed production for EU-27, increased rapeseed production for Russia, increased sunflowerseed production for EU-27, and reduced cottonseed production for Australia and Egypt. Brazil's 2011/12 soybean production is increased 0.5 million tons to 65.5 million while Argentina soybean production is reduced 1 million tons to 41.5 million.


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An Expert Lifted The Floor Of An Old Mansion – And Found A Rat's Nest Glimmering With Gold
By Suzi Marsh
A lone archeologist is gingerly lifting the ancient floorboards in the dusty attic of a grand country house. And beneath, he finds centuries worth of dirt and debris – accumulated throughout a long and turbulent past. But amid the scraps and trash he discovers something incredible: a stash of historical treasure with the unmistakable glint of gold.
Archeologist Matt Champion volunteered to remain in England's Oxburgh Hall after 2020's lockdown brought life there to a halt. And it turned out to have been a pretty good decision. He discovered a wealth of history hidden within the 15th-century manor's attic rooms. Under each floorboard, another find offered a fascinating insight into the people who once called this place home.
Oxburgh Hall has been the seat of the Bedingfeld family since the Middle Ages, and it has seen many different people come and go over the years. But few could have been as curious as Champion, who meticulously recorded everything that he discovered. Yet alongside the relics of everyday life, something unexpected caught his eye.
Amid the discarded cigarette packets and newspaper scraps, Champion spotted a rats' nest shot with glittering gold. Nearby, the glint of a gilded manuscript shone through centuries-worth of debris. What treasures had he stumbled upon beneath the floorboards of this historic family home?
Like many of England's great houses, the story of Oxburgh is long and – in places – bloody. In the 13th century a man called Thomas De Wayland was the original owner of the land. Yet he was stripped of his assets as punishment for bad behavior. So in a desperate bid to salvage some of his wealth, he transferred the estate to his wife's family.
For many years, Oxburgh was owned by the Tuddenham family. Though it was eventually passed down to their descendant Sir Edmund Bedingfeld. He subsequently decided to build a grand house on the land in Norfolk, England. At the time, the nobleman was quickly establishing himself as a feature at the royal court, and he wished to build a seat that befitted his status.
In 1482 royal permission was granted to fortify the manor at Oxburgh, and this feature remains there to this day. The following year – during Richard III's coronation to the English throne – Bedingfeld was given a knighthood. And for several decades, the family's close alignment with the nation's monarchs saw their fortunes continue to grow.
Yet Bedingfeld's loyalty to the House of York did not last. In 1498 he hosted the new Tudor king Henry VII at Oxburgh. Eventually, a new heir took over the estate and continued to foster close ties with the royal line. And even though the family were Catholic, their status appears to have survived the reign of Henry VIII, who would ultimately kickstart years of persecution against the faith.
It seems, then, that the Bedingfelds – who still live at Oxburgh today – have been in favor since the Middle Ages. So might this explain the treasures uncovered in the attic of the manor? According to the records, things were not quite so simple. In fact, the family's fortunes took a dramatic turn when Elizabeth I came to the throne.
With the Act of Uniformity in 1559, Catholicism was outlawed and Bedingfeld's heir dismissed from court. And when he refused to sign the document, he was further persecuted for his beliefs. Back at Oxburgh, the family were fined and threatened with imprisonment. Yes, they had fallen very far from their previous high status.
For the next three centuries, the Bedingfelds were ostracized by society, although they refused to give up their Catholic beliefs. Instead, they constructed a priest hole at Oxburgh – allowing them to conduct their worship in secret. The family then enjoyed a brief reversal of fortune under the reign of Charles I. But the English Civil War – which began in 1642 – ended up being a disaster for them.
Parliamentary forces ransacked Oxburgh and even shot family members. Yet the Bedingfelds remained loyal to the Crown, even when the restored Charles II did little to compensate them for their losses. As a result, the family retreated from English society – often traveling abroad or taking up religious lives.
Eventually, the Bedingfelds staged a return to public life in the 18th century. But as their fortunes improved, those of the estate took a downwards turn. In 1826 the manor was let to a tenant and fell into a state of great disrepair. Luckily, the house was remodeled in the 1830s by Sir Henry Bedingfeld, who transformed it into a masterpiece of the Gothic Revival style.
Sadly, by the 1950s the family found themselves unable to meet the spiraling costs of maintaining Oxburgh Hall. It was subsequently sold to an insurance company and very nearly demolished long before Champion discovered its hidden treasures. But at the last minute, three Bedingfeld women secured the funds to buy the estate back.
Yes, the future of Oxburgh had now been secured. And the Bedingfelds subsequently gifted it to a heritage organization called the National Trust in 1952. But even today, descendants of the family continue to live in the manor house. Tens of thousands of people also visit the estate every year – drawn by the rich history of this English country home.
Even on the surface, it's easy to see why people are drawn to this stunning estate. Surrounded by a moat, the medieval manor stands as a fine example of a fortified great house, while its interior boasts historical treasures at every turn. If you visit the King's Room, for example, you'll see a commemoration of the visit of Henry VII and his wife: Elizabeth of York.
You can also catch a glimpse of the tiny crawlspace where the Catholic Bedingfelds would have hidden a priest during the depths of their persecution. But while much of Oxburgh's history is currently on display, other aspects have remained hidden over the years. Yet in 2020 some new stories have come to light.
In February that year, for example, the National Trust announced that an exciting discovery had been made at Oxburgh. Yes, thanks to an exhaustive search of the family's records, researchers had uncovered evidence suggesting that Sir Henry Arundell Bedingfeld – the third Baronet – had been a secret supporter of the Jacobite cause.
But who were the Jacobites, and where did they come from? Well, their story began after King James II of England was deposed in 1688 and replaced by his Anglican daughter Mary II. Yet there were some who wished to see a return to the Stuart dynasty and their Catholic faith. Meeting in secret, these supporters of James' grandson – known as Bonnie Prince Charlie – were dubbed the Jacobites.
And, it seems, Sir Henry was a Jacobite himself. In the records, researchers found that large sums of money had been transferred from the estate to known supporters. At the same time, they found evidence that the British government had accused the baronet of sending money to help the Stuart cause.
But arguably the most significant discovery was a drinking glass engraved with pro-Jacobite symbols. Although it was found in Scotland, the object is believed to have been commissioned by Sir Henry – further fueling suspicion about where the baronet's true loyalties lay. It also sheds light on one of the darkest periods in the history of Oxburgh.
Later that same year, a more literal sort of light was shone on the dark and dusty attic rooms at the top of the ancient manor. Back in 2016 one of Oxburgh Hall's dormer windows collapsed – revealing the poor state of the aging roof. Then in December 2019 an ambitious restoration project costing £6 million and covering different parts of the estate was launched.
Of course, staff carrying out repairs at Oxburgh had hoped that the hidden history of the house might be revealed. But when the restrictions of lockdown loomed, it seemed as if any discoveries might have to wait. Yet all that changed when Champion volunteered to continue working alone.
As the rest of the hall stood quiet and empty, Champion worked in the attic – where the floorboards had been lifted in order to expose the joists below. Without any specialist equipment, he conducted a meticulous search of the space by hand. And before long, Champion had stumbled across some fascinating finds.
In an August 2020 statement by the National Trust, project curator Anna Forrest explained that Champion was the first person to look beneath Oxburgh's attic floorboards for centuries. But what exactly did he find there? Well, the expert discovered a pattern of dust and debris which suggested that the area had lain undisturbed for many years. And in amongst it were everyday objects from throughout the ages – as well as some unexpected treasures.
In some places, cigarette packets had found their way beneath the floorboards – having been discarded by smokers in years gone by. Though crisp wrappers and fragments of newspaper also offered clues to the more mundane aspects of life at Oxburgh. At one point, Champion even discovered an old box of chocolates complete with empty wrappers – perhaps hidden away by a glutton desperate to conceal their greed.
Interestingly, some of the relics offered insights into how the Bedingfelds used the attic space over the years. For instance, the well-lit rooms once served as a place for intricate tasks such as sewing. Forrest told the National Trust in a statement, "One particular challenge was in areas with south-facing windows, where hundreds of pins were found, so Matt had to use thick gloves when searching."
Champion also found evidence that the attic rooms had once been used for correspondence. These came in the form of handwritten fragments and remnants of wax seals. And at one point, he uncovered a stash of ping pong balls – suggesting that the space had hosted games at some point in its long history.
According to Forrest, the artifacts had been kept in remarkable shape thanks to the conditions beneath the floorboards. In the statement, she explained, "The peak of each wave of dust, debris and objects was highest under the crack between the boards. [It] was often inches thick and lay on top of a layer of lime plaster, which drew out the moisture from the debris and resulted in much of it being perfectly preserved over the centuries."
But the real surprise came when a builder spotted gold glimmering in amongst the rubble of the attic. On closer inspection, the source was revealed to be a fragment of illuminated manuscript believed to date back to the 15th century. Also decorated in a luminous blue color, the parchment was still vibrant despite its time spent buried beneath layers of dust.
"It is just the most exquisite thing and to have found it in literally a pile of rubbish is probably… well it's unheard of for the National Trust, that's for sure," Forrest told The Guardian in August 2020. In the statement, she explained that the manuscript featured text from a fourth-century Latin translation of the Bible.
"The use of blue and gold for the minor initials, rather than the more standard blue and red, shows this would have been quite an expensive book to produce," Forrest continued. "It is tantalizing to think that this could be a remnant of a splendid manuscript and we can't help but wonder if it belonged to Sir Edmund Bedingfeld, the builder of Oxburgh Hall."
But the manuscript was far from the only treasure that was uncovered while exploring the historic country manor. Tucked away in the northwest corner of the attic, two rats' nests were discovered preserved beneath the boards. But these were no ordinary vermin – in fact, they were clearly fostering an expensive taste.
Woven into the nests were around 200 fragments of valuable textiles – some dating as far back as the 16th century. Among them were pieces of silk, wool, satin, leather and velvet, all of which would have been indicative of high status in years gone by. As such, the find provided a fascinating insight into the past fortunes of the Bedingfeld family.
According to reports, some of the fragments are believed to date back to the Tudor period, when the Bedingfelds enjoyed a high standing at the royal court. Others are thought to be from the Elizabethan and early Georgian eras, when the social standing of the family had taken a different turn.
According to the National Trust, the fragments may have wound up in the nests after being discarded during clothing alterations. Among the most striking are a piece of gold-accented silk, a snippet of embroidered, woven textile and a section of cloth crafted from 16th-century metallic thread. Alongside these, researchers also discovered a felted fabric that may once have formed part of Tudor stockings or a cap.
Like the illuminated manuscript, the fragments of fabric in the rats' nests had been perfectly preserved thanks to their location in the attic. Speaking to The Guardian, Forrest explained, "Because they were beneath the floor, out of the sun for centuries they are in incredible condition." Similarly, a handwritten score penned in the 16th century was still legible to modern researchers.
According to the statement, previous research had already revealed that Oxburgh was historically a musical home, and this discovery just confirms it. In fact, experts have speculated that scores such as the one uncovered in the attic may have played a role in the clandestine masses once held at the hall.
Most recently, a builder conducting work in Oxburgh's attic uncovered another hidden artifact: a psalm book also dating from the 16th century. In the statement, the estate's general manager Russell Clement explained the significance of the finds. He said, "These objects contain so many clues which confirm the history of the house as the retreat of a devout Catholic family, who retained their faith across the centuries."
In July 2020 Oxburgh reopened to visitors for the first time since renovations began. And behind the scenes, the team have been preparing to reveal the new chapters in the story of this ancient house. According to Clement, "This is a building which is giving up its secrets slowly. We don't know what else we might come across – or what might remain hidden for future generations to reveal."

redpajama_set_name: RedPajamaCommonCrawl


Yesterday I was treated to a terrific birthday surprise–fifth row seats behind home plate at the Cubs' game! Karen tricked me into thinking we were just out for a photographing exploration of a Chicago neighborhood (even sneakier because the idea was mine) when we just happened to pass by Wrigley Field an hour before game time. And then, who should appear but Jen and Anne, with a handful of tickets!
The weather was sunny, warm and beautiful, and our seats were amazing. In fact, we had better seats than Governor Blagojevich, who was sitting five rows behind us. The Cubbies gave me birthday gift of a win over Milwaukee, and I was treated to another surprise when we were all filing out, and as the governor was glad-handing everyone passing by, he shook my hand and wished me a happy birthday!
Kudos to Anne, Karen and Jen for pulling off a fantastic, fun and memorable birthday surprise. I had a great time!
You can see more photos from the day in my photo gallery.
‹ PreviousUp In the Sky! It's a Bird, It's a Plane, It's…?
Anne told us all about this great birthday surprise last night. So, this morning I knew you would have pictures up. Boy, it really is different sitting up close! And better seats than the govenor to boot!
I am soooo happy to know that you had a fantastic birthday.
How wonderful! I'm so glad you had such a thrilling day! All the best!!!
Hey! Your governor is kinda hot!
Hope ya had a shizzy b to the d.
What a great treat! You sure get the best birthdays–maybe not New Orleans this year, but fun just the same.
Happy Birthday! Have a super year and a personal winning season along with the Cubbies.


In 2007, Barack Obama had an estimated net worth of $1.3 million, while today he is worth an estimated $7 million dollars. That's an increase of 438 percent.
The average US citizen has a median income of roughly $51,000. Under President Obama, income inequality has increased dramatically.


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The woman who calls herself New Zealand's first Martian
by Sarah Lang / 26 June, 2019
In June, New Zealanders turn their eyes to the stars as we celebrate Matariki – but it's the red planet that captivates space-science communicator Haritina Mogoșanu as humanity's stepping stone to the future.
Haritina Mogoşanu calls herself Hari – and New Zealand's first Martian. In 2012, she led the "KiwiMars" team of six who spent a fortnight at the Mars Desert Research Station in Utah. At the tiny US base station, working and living conditions simulate those humans might encounter in an artificial habitat on the red planet. When the team conducted research outside, in a Mars-like terrain, they wore space suits.
Mogoşanu knew the protocols. She'd been to the station the previous year with the Romanian Space Agency, and has now been four times. "It's about making every mistake we can on Earth before humans go to Mars," she says. National and private organisations are taking major steps toward achieving this. "I'd love to go, but wouldn't leave my 11-year-old daughter."
Her day job is the newly created role of Senior Science Communicator at Space Place, which includes interactive galleries and a planetarium housed in Wellington Botanic Garden's Carter Observatory. Special events for Matariki include a dawn viewing by telescope from Mt Victoria.
Mogoşanu comes up with strategies to make space science more accessible and engaging, oversees the content communicated by other staff, leads events, talks to groups, and visits schools to run outreach programmes (some imitating her "Mars missions"). She's just held her first, sold-out stargazing course for beginners. "I'm a 'staryteller'!" she says. "It doesn't feel like work."
Inside the planetarium's dome, I watch a short animated film, We Are Aliens, about whether extraterrestrial life forms exist. Mogoşanu thinks it's highly likely, especially with astronomers detecting more earth-like planets outside our solar system in the "Goldilocks zone" that may sustain life.
"My thing is astrobiology, which combines biology, astronomy, geology, maths and engineering, and asks, 'What is life in the universe? Are there aliens? And how might we find them?'"
Mogoşanu was brought up by her mum in Bucharest, after her pilot dad crashed and died when she was a baby. "I fell for the stars aged six, after seeing a diagram of the sun's life cycle." She started stargazing, but in communist Romania, a job in space science was unlikely. Instead, she got a horticultural-engineering degree and a master's in environmental management.
In 2003, she visited New Zealand – "because it has the world's best night sky; we see the centre of the Milky Way and more stars, and have less light pollution. I didn't want to leave." She got another master's degree, in international security, and since 2005 has worked on and off at Space Place, initially as a planetarium presenter and later as visitor-experience manager. She also worked in government biosecurity from 2008 to 2018.
Mogoşanu is part of numerous space research, education and advocacy organisations, including the Mars Society's New Zealand chapter (dedicated to settling Mars). She set up the Kiwispace Foundation, which successfully lobbied for a New Zealand space agency, and is executive director of the New Zealand Astrobiology Network, which connects experts from different disciplines within academic institutions and agencies.
She's also created online magazine Milky-Way.Kiwi about space news, plus the podcast Galactic Conversations. Oh, and she's done an internship at Nasa in planetary protection. "I considered how to kill any trace of earth life that may be on Rovers: vehicles travelling across Mars." Now, she pairs New Zealand students with scientist mentors from Nasa. "I hope we'll become an interplanetary species," she says. "In a billion years, the sun will scorch the earth, and I want my species to survive beyond that. That's what I'm about."
Photo: Haritina Mogoşanu at Wellington's Space Place. This display depicts the sun as a fiery orange and red blaze, but most of her work has focused on Mars, which appears red due to the iron oxide on its surface.


A partial list of the thriving retail establishments, service businesses, restaurants, and hotels near Contraband Pointe is provided below.
Learn more about Southwest Louisiana's strong economic climate.
Prien Plaza Restaurants are listed in the Restaurant section.


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#endif

#ifdef __cplusplus
extern "C" {
#endif

/* UpdateDriverForPlugAndPlayDevices.InstallFlags constants */
#define INSTALLFLAG_FORCE                 0x00000001
#define INSTALLFLAG_READONLY              0x00000002
#define INSTALLFLAG_NONINTERACTIVE        0x00000004
#define INSTALLFLAG_BITS                  0x00000007

BOOL WINAPI
UpdateDriverForPlugAndPlayDevicesA(
  HWND  hwndParent,
  LPCSTR  HardwareId,
  LPCSTR  FullInfPath,
  DWORD  InstallFlags,
  PBOOL  bRebootRequired  OPTIONAL);

BOOL WINAPI
UpdateDriverForPlugAndPlayDevicesW(
  HWND  hwndParent,
  LPCWSTR  HardwareId,
  LPCWSTR  FullInfPath,
  DWORD  InstallFlags,
  PBOOL  bRebootRequired  OPTIONAL);

#ifdef UNICODE
#define UpdateDriverForPlugAndPlayDevices UpdateDriverForPlugAndPlayDevicesW
#else
#define UpdateDriverForPlugAndPlayDevices UpdateDriverForPlugAndPlayDevicesA
#endif /* UNICODE */

#ifdef __cplusplus
}
#endif

#endif /* __NEWDEV_H */

redpajama_set_name: RedPajamaGithub


All Stirling City homes currently listed for sale in Stirling City as of 04/19/2019 are shown below. You can change the search criteria at any time by pressing the 'Change Search' button below.
If you have any questions or you would like more information about any Stirling City homes for sale or other Stirling City real estate, please contact us and one of our knowledgeable Stirling City REALTORS® would be pleased to assist you.
"Newer home in peaceful setting, overlooking the pines in the picturesque town of Stirling City. Property features an open floorplan with bullnosed corners, knotty pine crown molding, window casings and doors. Huge kitchen with matching Kenmore stainless steel appliances, walk in pantry and lazy susan. All bedrooms are spacious with walk-in closets and ceiling fans. There is an exterior bar with lights, sink and mini fridge. Garage is fully finished with garage door opener and built-in workbenches for the craftsman in you. Don't let this property pass you by. Welcome home!"
"This is a Charming older home that has a lot to offer with its own little homestead. Enjoy Gardening in the summer with the beautiful garden beds that have been built with layered beds out of the redwoods and have strawberries galore during the spring/summer months. A place to have goats, pigs, ducks. You truly could call this your own little farm. The home boasts of ageless detail from the ceilings to the craftsmanship. She just needs some TLC to bring her back to her glory days."
"WITH JUST A LITTLE THIS WOULD MAKE A GREAT RENTAL. ALSO PERFECT FOR THE HANDYMAN. MAJOR REMODEL HAS BEEN DONE - NEW KITCHEN AND BATHROOM ALREADY IN. HOUSE NEEDS PAINT, CARPET AND SMALL FINISH WORK. NOTE THERE ARE TWO LOTS!! PROPERTY ON SEWER. HAVE A NICE HOME IN THE MOUNTAINS WITH NOT MUCH MORE WORK. BRING YOUR DREAMS AND IMAGINATION. LARGE BUILDING IN BACK. DRIVE THRU ACCESS OUT OF BACKYARD."


In his gospel, the Apostle John records Jesus' favorite pair of sisters, Martha and Mary, sending word to Jesus that their dear brother was sick. We're all familiar with what follows. Lazarus turns out to be more than just sick. In fact, by the time Jesus gets on scene, he had been dead for four days. The emotions were high, forcing even Jesus to weep with Mary and Martha. (John 11:35) Eventually, Jesus calls Lazarus out of the tomb, and miraculously, he is resurrected from the dead!
Interesting though, is the original message brought to Jesus: "Lord, the one you love is sick." Once again, John is the writer of this section of scripture, and he always referred to himself as the one whom Jesus loved. (John 13:23; 19:26; 20:2; 21:7; 21:20) And yet here, this phrase is not a reference to John, but to Lazarus. How could there be two "the one's"?
The answer is simple: because Jesus made everyone feel like "the one"!
In the world today, there is an idea floating around that everyone has someone out there – a special soul-mate! People believe that it's all about finding "the right one"! And yet, the truth is that there is no perfect one. It's about finding any "one" and making them "the one"! Jesus made everyone feel like the one whom He loved! And that's how we need to make people feel as well!


text:
5 Top Apps For Buying A Home | Top Real Estate House Hunting Apps
Leave a Comment	/ Buying Home, Cashback Card, Income opportunity, Life Insurance, Mobile, Money Saving Tips, Pet Insurance, Save Money On Travel, Saving Money, Saving money on meals out, utility bills / By HerrionThomas
(upbeat music)
(static hisses) – [Narrator] I'm here to help
because there's nothing more– (static hisses) (dogs barking) (static hisses) – Then the one next door– (static hisses) (funky music) (static popping) – I know you've seen all
those fancy commercials for the top apps that people
are using to buy a house. But which one is the best
and the most accurate? We're gonna be finding out today.
It's Take A Tip Tuesday! (soft music) Hi, my name is Kristina Smallhorn, your real estate whisperer. This week we're gonna be
talking about the apps. Everybody uses them to find a house. But which ones are the best? We're gonna be taking the
five most popular apps, one of them being zillow.com, Realtor.com, Redfin, Trulia, and Homesnap. We're gonna be going
through each one of them. We're gonna use one subject
property, this one right here, and we're gonna be
going through and seeing if the information, first
of all, is accurate. Secondly of all, is the app easy to use? And thirdly of all, does
it have any other features that the other apps don't
offer that is pretty exclusive and neat for that particular app? If you have any other
questions about these apps, make sure you put them
in the comments section so I can answer those questions. And if there's any apps
that I didn't mention in this video that you'd like
me to review in the future, please put that in the
comments section as well.
I'd love to have a conversation
and make a video for you. So let's get into it. Our first app that we're gonna
be going over is zillow.com. Everybody's used it on the laptop, and I just wanna see how the app works. So, we're gonna be using
our subject property. So we're gonna take a look to see if the information on Zillow is correct. So you're gonna be
following along with me. So, I already put in the
address, and let's see here. Immediately I notice at the bottom is the price and the square footage, but it only gives you an
estimate of square footage. It doesn't give you the
exact square footage, so I'm not really keen on that.
(buzzer blares) Next, it gives you the facts and features. Let's click on the button that says see more facts and features and
see what they have in there. And now, this is where
it gives you the accurate square footage, which
is 2,331 square feet. It doesn't give you the estimate. And I do like the fact, look, they give you that virtual tour.
I made a virtual tour
that goes to the MLS. Let's see if we click on it, if it actually goes to
the tour that I created. And it does. (bell dings)
It goes straight to it. You can play it from there, which is good. Okay. And it takes you right back to the app that it's not hard to navigate. I do like the fact that it says you can get pre-qualified,
but I strongly suggest of taking your advice of
your real estate agent or some friends and family
when it comes to mortgages. I find that the print
on here is a little hard to read, very small.
(buzzer blares) And I realize that it is a cell phone, but they could make that print a little bit bolder for people. But, all in all, this is a pretty good app if you're just trying to get just some basic information on the house.
And they actually break
down the monthly cost too with the principal and interest,
the mortgage insurance, property taxes, home insurance. These are good things to know. The homeowners association
fees are incorrect. (crowd booing) And I did include in the utilities. So this is not correct. This didn't give all the information right on this particular part when
it broke down the payment. So that's in something to note. And then it gives you
the grade of the schools, which it gives a score
from nine out of 10.
It shows you how close
it is to the property, which I do like.
(bell dings) 'Cause everybody wants
to know if their kids, how far the school is,
if it's driving-distance and how long, how much time
they're gonna have to manage in the morning to get
their kids to school. I don't know where this
is taking me, oh, okay. So it's taking you to other schools that are close to this particular home that might have higher
grades or lower grades. This is really good information. As far as usability on this one on a scale from one to
ten, I give it like a six. (bell dinging) I didn't like the fact
that the font was so small. I didn't like how you had
to click on certain buttons to get to all the information. The other thing is is that
the pictures came out good, but it kind of dominated
the whole entire screen. You get less information
the more visual pictures, and maybe they intended to do that. I also like the fact that
did show the virtual tour.
And I like that they gave
you other information about how other homes in the
area have been selling. So there was some pluses to it, but I don't think it's
like a grade-A wahoo. So let's look at the next one right now. The second most popular
app is Realtor.com. I personally have loved
Realtor.com for marketing my homes. It's probably been one
of my favorite sites as far as a national syndicated site as far as getting leads for my clients in the information that
they provide on the website.
But I haven't really
messed around with the app, so let's just see how this works. Okay, so it shows the house just like I had presented it on the MLS. The same thing. Okay, and I hadda click on that picture in order to get straight to it. I like the fact that it
does not get dominated with all the photographs
that were taken of the house. You actually can see the
information about the house first. I think the very first
thing that I noticed, right off the bat, is the
estimated monthly cost is a little bit higher than the one that zillow.com gave you, but if you remember when I looked at that app, I
said some of the information as far as the taxes,
the HOA were incorrect.
Look, see. This is what I was saying about Zillow. The font was so small it was hard to read.
(bell dings) This is so much clearer
and easier to read. Realtor.com got that right. Else, let's see the other details. The one I'm interested in is if it gives you the virtual tour. Because I'm finding
that it's very difficult to find the virtual tour
on a lot of these apps.
(buzzer blares) No, I cannot find the virtual
that I have put on the MLS. This is not on the app like
it is on the Zillow app. So that's a negative for me
on that particular thing. They give you that same
information that Zillow did too about the scoring, and it
gives you the same grades. Let's see the schools on the map. Oh! (bell dings)
I like this. Okay, so, there's the subject property. You can see it right there,
and it's highlighted in red. Right next to it is all the
schools that are around there, so it shows you exactly
how close the schools are to the subject property. That is smart. I was a fan of the Realtor.com website, but I'm definitely a fan of the app. I think this looks really nice. So the usability on this one,
I give it, I give it a nine. (bell dinging)
This is really usable.
The reason I didn't give it a 10 is it didn't show the virtual tour. I do like how user-friendly this is. I think this is a more thorough
app than the Zillow one. But we have to, we have to go
through the other apps too, so right now this one's a nine. So this one's gonna,
this one's gonna stay. Realtor.com is a good app. I just didn't like the fact that didn't put in the virtual tour.
Everybody wants to look at a virtual tour. They wanna see you with the house on the inside not just pictures. The next app we're gonna
be looking at is Redfin. I know that there's a lot
of controversy about Redfin and where they do their practices, and that's for another video. This is about their app. And I've been told their app is fantastic. A matter of fact, several
magazines named it as their number one app to use for searching for homes in as far as accuracy. So let's go ahead and put it to the test. So, it looks a lot like Realtor.com's when it comes up that top picture, not a bunch of busyness
with all the pictures in the background like Zillow. It does give the correct sales price, and the correct amount of
bedrooms and bathrooms. There's a little button
here that says street view. Let's click that. Oh, street view is not available (buzzer blares)
for this listing. Okay, well.
I'm not really loving this app already. There's a lot of busyness going on. Maybe this isn't, maybe this
isn't optimized for an iPhone. But if you notice like all the
wording is crammed on there. It is bold and easy to
read, but some of it is doesn't look right. It wasn't really optimized
(buzzer blares) for the phone. They have HOA fees correct. All this other information's correct. Let's see if the virtual tour is there. Oh, look it is. It says media external link. Let's click it. And it does take you straight
to that virtual tour. Yup, perfect. But it takes you straight out there but doesn't make it
easier for you to back. So you actually have to
click out and go back. (buzzer blares)
I don't like that. And I'm trying to get
more information, okay. This is a more touchy app. I don't know if I love it. Okay, so, their estimate for monthly costs is even higher than the last two. If you remember the one on Zillow, it said it was around $1,700.
This one is even higher still. So, the principal and interest. It gives you the HOA dues. It gives you the homeowners insurance. So, I would say, let's
just click the done button. Oh and it sends you back. Oh and it shows you exactly
when the house was listed, and how quickly it sold, which is nice. Again, it gives you that
scoring, which is identical to the last two.
(bell dings) Ah, look a the public facts though. There's nothing there. There's no public facts of
the bathrooms, anything, like, they didn't put
any of that in there.
I don't know. Okay. A walk score was eight. Let's see what that is. A walk score of eight. A walk score helps you find
the walkable place to live. A walk score is a number
between one and 100 that measures the
walkability of an address. Okay. Oh, 90 to 100 is a walker's paradise. And ours is an eight.
(bell dings) (Kristina laughs) Car-dependent. And that is 100% true. We don't have sidewalks here in Louisiana. I wish we did. But, yeah. There's no place to walk. There's not a place to really ride a bike, so I actually kind of agree with that. That is a neat feature. And then it gives you the Redfin estimate of the property's value. Their estimate is lower than
the other ones in the area. They're saying it's 339. I think these estimates
that these apps are giving don't give a good indication
of actually a home's value. So if you're concerned or wanna know more about your home's value, please check with your real estate agent.
Don't depend on any website or apps to give you an accurate
estimate of a home's value. They cannot determine a
house's condition, location, the housings around it,
the surrounding area. So don't put too much
weight on these estimates that these apps give you. It does have usability, which was a lot better than Zillow's. But there were some features
I didn't love about it. The font was easy to read, which was good, unlike the first app that we toured. The information looked right, but I don't like how they
crammed in some of the stuff where like the like
flopped onto one another. I'm kinda being nitpicky
here, but, I mean, you do wanna be able to read what that is 'cause I'm like, I don't
have that bad'a eyes. I would say that this app is equivalent to Realtor.com as far as
usability and information.
I do like the fact they
gave you an internal link, and I like the usability, so I'm kind of liking
(bell dinging) this app a little smidgen
more than Realtor.com. I don't know. I'd say they're tied right now. So let's go and take a
look at the next app. Okay, now we're gonna be looking into the fourth app, which is Trulia. It is a company that is
by Zillow, so I'm assuming that the app will be very
similar to the Zillow app. But let's just hope
that some of the things that were wrong with the Zillow
are repaired in Trulia app. So let's just take a look. It looks very similar to all
the other apps, except for the one which I was complaining
about is the font size. I noticed right away
that the estimated cost for this house as far as a mortgage is way lower than the other two apps, which it's saying it's $1,601. So I'm interested in how
they came up with that.
I'm assuming that they probably didn't put in the taxes, maybe. Uh, I don't know they
came up with that value. That seems off. They did put in the right information, and you can read the font very easily. (bell dings)
So already right off the bat, I like the way this looks way better. Oo, look at this. There's a button right here
at the top, crime statistics. (gasps) Oh, let's click on that. Oh, look, there's zero crimes. You can click on it,
it says assaults, none, arrests, (gasps) oo, vandalism. Oh, this is really good. (bell dings) Oh and look, you can just
scroll right over to schools. But it gives the, but it says that it's the St. Amant school district, which it's not St. Amant schools. It's actually Prairieville schools. (buzzer blares) So that information is incorrect. Anyways, the details of
the house are correct. Oo, look, they have virtual
tour, unlike Realtor.com. Love that. Let's see if it takes it
straight to that site. It does. It takes you straight there. Okay, and we're gonna push cancel, and it takes you back to the app.
So you don't have to close out
one app to open another app. (bell dings) As far as usability, this is really good. Let's see the monthly mortgage. This is how they came up with. See they estimated the HOA fees less, which those are not correct,
and the property taxes and home insurance they estimated less, so that's why the monthly payment on this is incorrect.
(buzzer blares) This is a good lesson learned
for anybody that's thinking that this is exact science
when it comes to these things. Always talk to your mortgage lender when it comes to coming
up with monthly payments. Don't rely on these apps. All right, let's look at
the legal protections, local legal protections, hmm. Okay, local legal protection, do legal protections exist for the LGBT community in a state-level in Louisiana? That is really interesting.
(bell dings) That's the only app that I've seen that has something like that.
So that's an interesting feature. I do like that. As far as a review, I don't like the way that they gave an estimate for how much the house
is gonna cost per month. I think it's way too low, and
I think you're getting your expectations set up too high if you think your payment's
gonna be that low. I think the second thing I
don't like about this app is that some of the information
on here was incorrect. That's why it's always good to check with your real estate agent when you're looking at these apps to
make sure that's correct. 'Cause it's saying that's a
one acre lot, and it's not. And it didn't give you
the correct schools, so I don't like that. It's easy to read. I liked the way it looked. It was easy to use. (bell dinging) But the information is super incorrect. I don't know. Yeah, mm-mm, nope. The last app we're gonna
be looking at is Homesnap.
It is a real estate app
that a lot of realtors use when it comes to helping determine value. So I'm assuming their estimates
as far as value of the house are gonna be a lot closer
than those estimates are. The other thing that this has is that it's directly piped in from the MLS
and is supported by the MLS. Our MLS. Not all MLSes are the same, so this may not be one that your MLS uses. So we're gonna go ahead and
take a look at right now. All right. I don't love the fact that soon
as you click on the property it gives you a smaller like
slideshow of the house. And it blows up the pictures really wide, so you can't see the entire house. I don't love that part of it. But it does give you
the accurate information right off the bat.
(bell dings) It's requiring you to sign in.
And I don't personally love the fact that you have to sign
in to get information. Let's see if we can get
some more summary on this. Listing details, let's show more. The main thing I'm look for on this, other than the fact
that it's easy to read, I'm looking to see if they
put in the virtual tour. (buzzer blares)
They do not. That is a big disappointment. For me as a listing agent,
I think it's very important that if you take the time to
make a beautiful listing video for your clients, it should be featured on all of these websites, especially one that's sponsored by our local MLS.
'Cause we're trying to
get these houses sold for our clients, and that is a big giant
disappointment for me. As far as local schools, this is correct. The information is correct, and it gives exact same scores as all the other apps as well.
(bell dings) The 9/10 for Prairieville Primary, the 10/10 for the middle school, and the 10/10 for the high school. So the information has not changed. Property lines. It says, walk the property lines. So let's click on that. All right, let's go for a walk, it says. First, head over to the corner
of the lot and tap I'm here to start an augmented reality.
(bell dings) (laughs) I don't know if
that part's gonna work 'cause I'm in my house. But that's an interesting
little extra feature. I like that. That's good to know, especially
if you're on a big property. We have lots of them
here in Ascension Parish. But, all and all, this
is not my favorite app.
It's easy to use. I don't like the fact
that you have to sign in. I don't like the fact that
there is no virtual tour. And I do not like the fact that they blur out some information. (bell dinging) But, all and all, it is a good app. It is accurate. I wanted this one to be
my favorite, but it's not. You decide which one you think is the best by this review, and you
tell me what'chu think. I personally have my
favorite, and you can probably tell me in the comment
section what you think which one's my favorite app. And I'll let you know if
you're correct or not. So these were the top five apps that people use when searching for a home. Which one was your favorite? Can you guess which one mine was? Let me know in the comment section. If you have any questions
about real estate or real estate apps and you
want me to make a video, just go ahead and email me at info@yourrealestatewhisperer.com.
Or you can even leave a
comment in the comment section. My name is Kristina Smallhorn, Your Real Estate Whisperer
for Ascension Parish. And I tell you all this
because you matter. Wanna watch more videos about apps? There's a fun one right here. This one's been pretty popular..


text:
Recommend, or reminisce about, film and television
by Gavin » 27 Dec 2013, 20:31
Not sure if anyone has been watching this very popular television series but my wife and I finally got into it recently and we are now up to the final season.
I just wanted to say that show generally comes across as very conservative. It shows the effect of using methanthetamine and that there are consequences (even unforeseen) of actions. The main character, Walter White, explains that he has made choices and he alone is responsible for them. The other main character, Jesse Pinkman, is a meth "cook", user and dealer who comes from a very privileged background and similarly has chosen his course in life.
Here's a documentary by Louis Theroux about meth users (or "meth-heads"). They usually look very ill and their lives are a mess. Sadly, a lot of them are women too and they usually have children. Yet these too speak of their "choice", repeatedly. Who has to tell liberal apologists before they understand?
Re: Breaking Bad
by Jonathan » 28 Dec 2013, 20:16
Ah, an excellent series. My wife and I recently finished watching the last season - no spoilers, I promise!
I agree with you that the series has a decidedly conservative slant. The most recurring motif is certainly a conservative one - that the best laid plans of mice and men oft go astray. The fear of unforseen consequences is not the most common sentiment in the liberal heart.
There's another scene which sticks in my mind, with a very damning condemnation of non-judgmentalism. It's the last time Jesse Pinkman attends the rehabilitation center support group - you should be well past it by this point.
Yes, I know just the scene you mean - that really struck me too as a perfect destruction of the liberal delusion.
by Andrea » 28 Dec 2013, 23:08
I am really enjoying the show as well. So much so that I've started reading web pages about the concepts behind it and something that the creator, Vince Gilligan (who also worked on my favourite series, The X-Files) said the following:
If religion is a reaction of man, and nothing more, it seems to me that it represents a human desire for wrongdoers to be punished. I hate the idea of Idi Amin living in Saudi Arabia for the last 25 years of his life. That galls me to no end. I feel some sort of need for Biblical atonement, or justice, or something. I like to believe there is some comeuppance, that karma kicks in at some point, even if it takes years or decades to happen. My girlfriend says this great thing that's become my philosophy as well. 'I want to believe there's a heaven. But I can't not believe there's a hell.'
I like the guy. The show is supposed to be about people choosing badly and getting their comeuppance. I think it's brilliant.
The Wikipedia has the following:
Klosterman added that the central question of Breaking Bad is "What makes a man 'bad' – his actions, his motives, or his conscious decision to be a bad person?"
Again, several main (and secondary) characters in Breaking Bad make decisions that are the wrong decisions, meaning decisions that an honest, good person would avoid. I'm always rooting for the DEA agents, not the criminals, because producing such drugs leads to a greater evil. People lead horrible lives because of meth use, but mainly, they usually chose to use these substances in the first place. I'm afraid I'm hardline against drugs. I come from a "broken home", immigrant parents, and things were hard at times, BUT, there is no excuse for a life of criminality. I like that this show reveals that criminality ultimately does not pay.
by Mike » 29 Dec 2013, 00:36
My wife has just gotten hold of the first season on DVD. I'm very much looking forward to watching it, on your recommendations!
by Gavin » 03 Jan 2014, 01:04
Finished this now. Incredibly well written, acted and produced drama. Can't say too much about it because it would give away what happens, but sure enough it is conservative, and they keep you guessing until the end.
p.s. Apparently meth is a popular drug around where I live. It looks that way when you're out and about too. The pieces of the puzzle have fallen into place for me: what I'm seeing is inbreeding plus meth addiction. Both have a terrible effect on people's physiognomy and general health. Mixed with no idea of how to live and state indulgence, the result is bleak to behold.
by Charlie » 04 Jan 2014, 17:27
My fiancée and I have been watching this recently, but we have to ration ourselves otherwise we will not get any work done!
All this talk of Breaking Bad as a conservative morality tale is interesting; especially when the series is compared to The Wire, whose creator, David Simon, could not be described as a conservative at all - quite the opposite (I learned about his political beliefs after I watched the show).
I still think that The Wire is excellent, and that Simon is a really good writer, but I think the series needs a reappraisal of sorts, at least as far as its political message is concerned. Compared to Dalrymple's thoughts on drugs, for example, I think that The Wire stands on the other side of the drugs argument without being as naïve about it as, say, Richard Branson or Russell Brand.
by Mike » 28 Jan 2014, 12:21
Two seasons in now. My wife and I are definitely hooked.
Oddly enough, despite the completely different subject matter and setting, I'm reminded a lot of Agatha Christie when watching Breaking Bad - not because there are any whodunit aspects to the show (although of course it does keep you guessing with some of the snatches at the beginning of the episodes), but because of that recurrent idea of a single moral wrong step having a ripple effect, both on the wrongdoer and on the world at large. That's a trope which goes back to Greek tragedy of course, but I've always felt that the theme of "opening a heart to evil", especially while professing philanthropic motives to oneself, is one that Christie handled particularly well (Death on the Nile and A Murder is Announced being two good examples).
by Jonathan » 29 Jan 2014, 07:50
Mike wrote: ...that recurrent idea of a single moral wrong step having a ripple effect, both on the wrongdoer and on the world at large.
I quite agree. And I don't think anyone will consider it a spoiler if I say that in the last episode of the last season (if I'm not mistaken) there is a short scene whose only purpose is to make this precise point.
by Gavin » 13 Feb 2014, 21:50
I thought this was an excellent interview with Bryan Cranston. He came across to me as a sensible, unpretentious, grateful, likeable, humble - and I might even say wise - man. Probably a rarity in Hollywood.
By the way, apparently blue meth has hit the streets of America now.. I suppose that was bound to happen, though do not think BB glamourised the drug - in fact the people who took it all seemed to be total losers. As for the people who made it.. keep watching!
by Mike » 05 Oct 2014, 13:24
Finally reached the end! It's a magnificent series in every way. The third-last episode was absolutely gut-wrenching of course, and I actually liked the way it slowed down somewhat after that.
And discussing it with my brother the other night, I again brought up the Agatha Christie parallels, and he agreed. (One other of hers that it forcibly reminded me of at times was Towards Zero - a story of a man who basically believes he hasn't gotten his just deserts in life and slowly goes off the rails as a result.)
Well, everyone is saying that it was the best thing on TV in recent years apart from The Wire, so I suppose I'll have to go back and immerse myself in that one too...
Return to Film & Television


text:
Q: Renaming columns of a pandas dataframe without column names I'm trying to name the columns of my new dataframe after the dataframe.from_dict operation.
Simply using pandas.dataframe.from_dict function:
df = pd.DataFrame.from_dict(my_dict,orient='index')

yields the dataframe without column headers.
data=pd.DataFrame.from_dict(my_dict,orient='index).rename(columns = {'name','number'})

This yields nothing an error : TypeError: 'set' object is not callable.
Does anybody have a clue?

A: If you want the index as the keys in your dict, you don't need to rename it.
df = pd.DataFrame.from_dict(dicts, orient = 'index') #index is name

df.columns = (['number']) #non-index column is number

df.index.name = 'name'

Or instead of changing the index name you can make a new column:
df = df.reset_index() #named column becomes index, index becomes ordered sequence

df['name'] = df['index'] #new column with names

del df['index'] #delete old column

A: You can probably do something like this by implicitly referring the columns names and then set new names.
data = (
  pd.DataFrame.from_dict(my_dict,orient='index')
  .rename(columns=dict(zip(df.columns,['name','number'])))
)

redpajama_set_name: RedPajamaStackExchange


text:
Ohio State Defeats Michigan State 52-12
By: Nick Manchester | December 5, 2020
Ohio State defeated Michigan State 52-12 in their first game since the nail biter against Indiana.
The Buckeyes scored on their first drive, and were in control from start to finish.
Leading up to the game, there was some debate whether Ohio State just needed to beat Michigan State, or whether the Buckeyes needed style points. Either way, the College Football Playoff committee should look at this game favorably, as the Buckeyes won by 30 points.
The final game of the regular season might fall through, but Ohio State took care of the things they could control. They needed to beat Michigan State no matter what, and they did so convincingly.
Offense, defense, and special teams came together for a complete victory. After Ohio State took down Michigan State, the quest for the playoff is back on track.
Ohio State was able to play, but were still far from full strength. Several players and one coach were still in COVID-19 protocol and unable to make the trip to East Lansing.
First and foremost, head coach Ryan Day was forced to stay in Columbus
Assistant head coach and defensive line coach Larry Johnson took the helm and earned his first win. The former head coach of TC Williams High School (the school featured in Remember the Titans) became the first African-American head coach in Ohio State history.
There was no better way to make a head coaching debut than with a 30-point win.
In addition to Day, the offensive line went without left tackle Thayer Munford, center Josh Myers, and right tackle Nicholas Petit-Frere. Harry Miller moved from left guard to center, so right guard Wyatt Davis was the only opening day starter on the offensive line playing his regular position.
Miller struggled on the first drive at center. Nearly all of his snaps were off target and he missed some of his blocking assignments. The inaccurate snaps threw off the timing of the offense, but Ohio State overcame the issues and scored a touchdown on their opening drive.
As the game progressed, Miller got more comfortable and settled in. Ironically, the first bad snap that resulted in negative yards came from the Michigan State center.
Miller's issues didn't totally disappear, though, and a bad snap cost the Buckeyes a safety in the waning moments of the fourth quarter.
Other than the quarterback/center exchanges, Ohio State's absences were hardly noticeable.
Justin Fields
Ohio State's quarterback took over the game and the biggest difference maker for the Buckeyes.
Justin Fields was 17 for 24 passing, with 199 yards and two touchdowns. He also rushed 13 times for 104 yards, a career high, and two touchdowns.
Many of Fields' rushes came when the snap was sloppy, and he turned potential disasters into positive gains.
Fields' decision making, leadership, and work ethic were on full display. One of his best plays was when he ran all the way downfield and threw a block on Trey Sermon's 64-yard touchdown run.
This was a statement about how he would respond to disappointment. After playing the worst game of his college career in his last game, he put together a gem.
Chris Olave and Trey Sermon
It's amazing how a player as talented as Chris Olave can get lost in the shuffle, but he's been playing second fiddle to Garrett Wilson this season.
Today was his day, as he had 10 receptions for 139 yards and a beautiful 41-yard touchdown. The rest of the team only had 60 receiving yards.
Sermon is the team's second leading rusher behind Master Teague this season, but this was his Buckeye breakout game. On 10 rushes, Sermon had 112 yards on the ground, including a career-long 64-yard touchdown. Even without the long run, Sermon averaged 5.3 yard per carry.
The Buckeye defense was exposed against Indiana in their last game, but they turned things around for this game.
Even though Michigan State had the lowest scoring defense in the conference entering this game, Ohio State's defense still performed well. There were fewer missed tackles, no deep balls, and four takeaways. The defense looked improved in every way.
The highlight of the day on defense was Haskell Garrett's tipped ball that resulted in an interception in the end zone. Garrett has been a pleasant surprise, and the pick-six was icing on the cake of his magical season.
Posted in Big Ten, FeaturedTagged Chris Olave, Garrett Wilson, Haskell Garrett, Justin Fields, Master Teague, Michigan State Spartans, Ohio State Buckeyes, Ryan Day, Trey Sermon


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PT Kustodian Sentral Efek Indonesia (KSEI) is a Securities Depository and Settlement Institution (LPP) in Indonesia Capital Market that was established in Jakarta on December 23, 1997 and obtained its operational license on November 11, 1998. In Indonesia Capital Market structure, KSEI is one of the Self-Regulatory Organizations (SROs), in addition to the Stock Exchange and Clearing & Guarantee Institution. KSEI, pursuant to the provisions under Law Number 8 Year 1995 regarding Capital Market, takes its role as LPP in Indonesia Capital Market by providing orderly, fair and efficient Securities Central Depository and Transaction settlement services.
KSEI started its operational activities, which is transaction settlement of Securities in script form, on January 9, 1998 by taking over the function of its kind from PT Kliring Deposit Efek Indonesia (KDEI), which once was the Clearing Depository and Settlement Institution (LKPP). Thereafter, as of July 17, 2000, KSEI, together with PT Bursa Efek Indonesia (d/h PT Bursa Efek Jakarta) and PT Kliring Penjaminan Efek Indonesia (KPEI) made a breakthrough by implementing scripless trading and central depository activities in Indonesia capital market. KSEI shares are owned by its service users, namely: the SROs (PT Bursa Efek Indonesia and PT Kliring Penjaminan Efek Indonesia), Custodian Bank, Securities Companies, and Registrars.
In accordance with its function, KSEI provides service products comprising of electronic Securities depository, Securities Account administration, Securities transaction settlement, distribution of corporate action proceeds, and other relevant services such as: Post Trade Processing (PTP) and central depository service reports.
In performing its daily operational activities, KSEI keeps providing excellent services to the service users. To assure transaction security and investors' contentment in making transaction in the capital market, all KSEI's activities are operated through Securities depository and transaction settlement system by means of high-technology book-entry, namely C-BEST (The Central Depository and Book Entry Settlement System. This system is an integrated electronic platform that supports Securities transaction settlement by book-entry in Indonesia capital market. As of June, 2002, KSEI had completed the conversion program of the overall stocks listed on the Stock Exchange, from script form into scripless.
Currently, KSEI has performed depository of various Securities types, such as: Stocks, Warrants, Exchange Traded Fund, Participation Unit of Limited Participation Mutual Fund, Corporate Bonds, Government Bonds, Sukuks, Sertifikat Bank Indonesia, Surat Berharga Syariah Negara, Medium Term Notes, Promissory Notes and Assets Backed Securities. Those Securities are actively recorded in C-BEST system.
As of September 13, 2001, KSEI has provided a back-up system called Disaster Recovery Center (DRC) to protect the operational continuity of its service products. Located in a site separated from the primary system, DRC system will secure the Central Securities Depository services during an emergency (disaster) condition or disturbance. This back-up system has a capacity and work process identical to those of the primary system enabling both systems to automatically replace one another when either one is collided with disruption. To make sure the back-up system can function well, KSEI always perform procedure testing periodically through DRC Live Test 2 (twice) a year.
To facilitate communication between KSEI and Account Holders, Private Network Provider, the combination of velocity and security factors, is applied. As of October 6, 2009, Account Holders can use 2 (two) network providers, namely PT Pasifik Satelit Nusantara dan PT First Media Tbk., for accesing C-BEST. Account Holders can choose one of the Private Network Providers to become the data network provider that linked to KSEI. It is expected that the two Private Network Providers can improve the data network quality, performance, and security of KSEI Service Users.
In line with the increasing number of Securities managed in KSEI's system and considering this extremely-high-risk security level, KSEI has invited independent party to examine the IT Security. Referring to the recommendation of such independent party, KSEI has started to perform revitalization of IT Security to protect network system from outer threat as well as to keep providing comfort to its service users.
In line with C-BEST development efforts to provide excellent services to all service users in order to cope with the international standard related data format and communication network, KSEI has officially become active member of The Society for Worldwide Interbank Financial Telecommunication (SWIFT) as of September 6, 2008. As one of supporting communication platforms for C-BEST, activation of SWIFT network enables KSEI to communicate with Account Holders of SWIFT users. Finally, information from KSEI to its service users can be delivered more easily to global investors that have linked to SWIFT, or vice versa, instruction coming from investors to service users can be easily processed and forwarded to C-BEST.
Meanwhile, to improve efficiency in daily activities of KSEI Account Holders, development has been made on C-BEST facility, Straight Through Processing (STP) Interface, enabling C-BEST to have host to host connection with back office system of KSEI Account Holders. This facility is expected not only to support the application of international standard format like SWIFT, XML Message, etc., but also to replace the semi-manual activities currently performed by Account Holders through upload and download file processes.
As part of the company asset protection effort, KSEI has already developed an effective and continual risk management system called Enterprise Risk Management (ERM). This ERM approach has enables company to identifiy and manage risk comprehensively so it can minimize the corporate risks, e.g.: strategic risk, compliance risk, financial risk and operating risk, and help the corporate objective achievement. In order to improve the continual risk management process, in the beginning of year 2010 KSEI has conducted the Policy Integration Program of Business Continuity Plan (BCP) with Risk Management Policy. Through this program, the risk management will be more compherensive and integrated in order to protect the company assets and ascertain the company's business performance.


That sent stocks falling in mainland China. After early gains, the Shanghai Composite SHCOMP, -0.51% was last down 0.9% and the smaller-cap Shenzhen Composite 399106, -1.32% was off more than 2%. Stocks in Hong Kong HSI, +0.00% gave up early gains as well, and were last up only about 0.1%. Japan's Nikkei NIK, +0.19% was up 0.6%, while South Korea's Kospi SEU, +0.17% was about flat. Benchmark indexes in Taiwan Y9999, +0.35% and Singapore STI, -0.13% were slightly lower. Australia's S&P/ASX 200 XJO, +0.95% was up about 0.1%.
Among individual stocks, SoftBank 9984, +0.31% jumped in Tokyo trading after a report that it may lead a $1 billion investment in Uber Technologies' self-driving car unit. E-commers company Rakuten 4755, -4.17% and Kobe Steel 5406, +1.25% also rose. Oil producer CNOOC 0883, +1.49% advanced in Hong Kong, while Apple AAPL, +0.38% suppliers AAC 2018, +1.48% and Sunny Optical 2382, +1.56% sank. LG Electronics 066570, +0.95% rose in South Korea while Hyundai Motor 005380, +1.49% fell. Mining and oil stocks, such as Rio Tinto RIO, +1.50% and Beach Energy BPT, +4.21% , rose in Australia.
On Wall Street, stocks secured their third straight gain on Wednesday after health care and technology companies rose. Boeing BA, +0.25% dipped briefly, but ultimately finished slightly higher, as the U.S. joined much of the world in grounding its 737 Max 8 aircraft after a fatal crash in Ethiopia on Sunday.
The broad S&P 500 index SPX, +0.24% gained 0.7% to 2,810.92. The Dow Jones Industrial Average DJIA, +0.13% added 0.6% to 25,702.89 and the Nasdaq composite COMP, +0.46% climbed 0.7% to 7,643.41.
The dollar USDJPY, +0.01% strengthened to 111.59 yen from 111.17 yen late Wednesday.


text:
English|Myanmar
About MIIT
Overview •
Origins •
Mission and Vision •
Why is MIIT special? •
Governing Council •
Senate •
Milestones •
Media •
Collaborations •
News •
Bachelor's Degree Programmes •
Postgraduate Diplomas •
Fees and Scholarships •
Master's Degree Programmes •
Courses •
Administration •
Faculty •
Staff •
Faculty Development •
Mandalay •
Campus Tour •
Facilities •
Stories •
Events •
Resources •
Explore Academics
Bachelor's Degree Programmes
Bachelor of Engineering (Honours) in Computer Science & Engineering
Bachelor of Engineering (Honours) in Electronics & Communications Engineering
Master's Degree Programmes
Postgraduate Diplomas
The bachelor's degree programmes at MIIT have been designed keeping in mind the matriculation system of school education in Myanmar. Students in Myanmar complete the Matriculation Examination in Standard X (also known as Grade XI). Thus, the students would have attended ten years of schooling before seeking admission to a university. MIIT has designed the bachelor's degree programmes in such a way that it accepts students who have matriculated, and enables them to graduate with a bachelor's degree that is equivalent to those in the USA, India, Canada, etc.
The undergraduate programmes at MIIT have a broad-based structure, with a strong foundation in mathematics, sciences, and engineering sciences, followed by a rich collection of specific, discipline courses in their designated major. The programme also offers courses from liberal studies, humanities, social sciences, and English language communication in order to cater to the overall development of the students. A wide collection of electives empowers a student to choose their specialisation based on individual career goal
Input Qualifications
Students must have passed the Matriculation Examination (or the University Entrance Examination) of Myanmar with Mathematics, Physics, Chemistry, and English as subjects in the same year in which they are seeking admission to MIIT.
Specific Programmes
B.E. (Hons.) in Computer Science & Engineering
The B.E. (Hons.) programme in Computer Science & Engineering lays great emphasis on a broad-based coverage of the hard sciences (physics, chemistry, and mathematics) and the engineering sciences. This provides the student with a strong foundation for various courses in computer science & engineering. The programme focuses on the core areas of computer science, but also offers the students the opportunity to gain substantial depth in a specific area through a rich collection of electives.
Dept. of Computer Science
5 year programme
10 semesters
B.E. (Hons.) in Electronics & Communications Engineering
The B.E. (Hons.) programme in Electronics & Communications Engineering offers a strong foundation in the hard sciences (physics, chemistry, and mathematics) and the engineering sciences. The programme has several courses that cover all the necessary fundamentals in electronics that are required to work with electronic devices & systems, embedded systems, and communications systems. These courses combine classroom and hands-on lab experiences, including, but not limited to, such topics as digital electronics, technical communication, electronic circuit design, microprocessors, signal processing, and networking technologies.
Based on the general student input level from the matriculation school system in Myanmar, the bachelor's degree is for a duration of 5 years.
Bachelor's degree programmes at MIIT follow the semester system, with courses having specific credits.
Each academic year is divided into 2 semesters of about 16 weeks and a special term of 4 weeks.
The academic year in MIIT starts with I Semester in the month of December in a given year. This is consistent with all the other universities in Myanmar.
I Semester in a specific academic year is followed by Special Term, which is then followed by II Semester.
Special Term is primarily used to offer courses from liberal studies, humanities, and social sciences, as well as scope for some independent, short-term, laboratory work.
The degree programmes are broad-based in the sense that the courses in the first four semesters of both the disciplines – CSE and ECE – are common and lay a strong foundation in mathematics, sciences, engineering sciences, technical arts, and English language communication.
Even allowing for the additional credits that a student will be enrolling for in a typical programme of 5 years, students at MIIT are required to do about 215-220 credits in an undergraduate programme. Students enrolled in these degree programmes will typically be doing far more credits than their counterparts in other universities.
Thus, to acknowledge the breadth and depth of the curriculum, as well as the significantly more credits required to graduate, MIIT offers the "Honours" degree for all its students.
MIIT emphasises outcome-based education and all courses are designed and conducted to be outcome-based.
MIIT also attaches significant importance to university-industry linkages. The courses conducted over the various semesters are designed based on inputs from the industry. The Capstone Project, undertaken towards the end of the programme, is a structured course that can be done by the students in a specific company or a research lab.
Myanmar Institute of Information Technology
73rd Street, Ngu Shwe Wah Street
Chanmyathazi Township, Mandalay
GooglePlus Profile
Copyright © 2019 Myanmar Institute of Information Technology.
Myanmar Institute of Information Technology is a technical university located in Mandalay, Myanmar. It was set up as a National Centre of Excellence in 2015.
Website by Miranj x Hamsa and others.


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text:
Macleod College
A State Prep - Year 12 School
CRICOS Provider Name: Department of Education and Training
Macleod College is situated in the well-established suburb of Macleod, just 14 km north of the city of Melbourne. The college is situated 900m from the Greensborough Highway and 3.5km from Plenty Road and although it is conveniently close to these major thoroughfares, the college has the charm of a neighbourhood school as it is tucked away in the heart of the suburb.
We are fortunate to be just a across the road from the Macleod railway station and adjacent to the local park and shopping precinct, enabling the school to form close ties with the local community.
Macleod College is easily accessible by train. Macleod railway station is a premium station with full facilities and is located only 400m from the school.
Bus route 561 runs from Coburg to Macleod station via La Trobe University and Reservoir.
By car/ on foot
Access to the school from the Greensborough Highway is via Strathallan Road or Erskine Road. From west of the railway line, use Kingsbury Drive/Ruthven Street. Melways reference: 20 B7.
Click for larger map


My name is Matilda and I write for The Travel Sisters along with my sister. I am from Chicago which is where I currently live. When I am not traveling, I am usually thinking about future trips or hanging with my family and my dog.
For many years, my sister and I talked about starting a blog chronicling our travels. We are obsessive about research and often found useful tips on other travel blogs. We figured sharing our tips might be useful to someone. Full-time jobs got in the way for a long time but we finally started our blog early 2014.
Some destinations we have covered include China, Rwanda and Japan.
We write about how to earn miles and points for almost free travel. We also try to provide some inspiration on places to travel as well as useful tips and information.
I am usually inspired to write when I can have a big block of time alone with few or no interruptions.
We have partnered with Tripeasel which is launching soon.
My blog is a part time business. I have another job so the blog is not my primary source of income however. I have monetized the blog by advertising. We would like to work on earning income with affiliate links next.


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"I always worried about my mum going into a residential home as you hear such horror stories. But since she has moved into Abbeycliffe Care Home my mum has blossomed. I have got my mum back the mum I haven't seen for quite a few years!! She is now so happy and relaxed and her wicked sense of humour has reappeared. Mum and I can't praise the staff highly enough they are so kind and caring and the meals are lovely so much so that mum has regained her appetite and actually put on weight. Abbeycliffe is the best decision we ever made."
"My mum was in Abbeycliffe Care Home from February 2014 - October 2017. She was cared for very well by all the staff and I had no complaints in the three and a half years she was there. I had peace of mind from the day she went in until the end. All her needs were met. The staff were extremely friendly and I was made to feel very welcome. I would like to say also the last few days she was poorly before she died and the staff looked after her excellently and were very caring to her and ourselves. I would not hesitate to recommend Abbeycliffe Care Home."