At the same time, the fact and rhetoric used in this case is also worrisome by senior state officials in the Government of the Republic of Bulgaria (for example, the Minister of Defense, Mr. Karakachanov), directs his hate speech towards Roma from this state, only encourages an even more extreme charge against this population.
We are all aware that it is necessary to abide by the legal regulations and respecting the laws themselves, but it is also necessary to take into consideration the important human aspect. In times when weather conditions do not allow it, and actions are taken to leave literally in the street, women, children, elderly and feeble people are an indication that it is not really a policy that is advocated by a country that is part of the European family and fights against all forms of discrimination, segregation, intolerance and other activities that violate basic human rights.
This is more like a form where, from one group, party, leader or sympathizers of one political option, they achieve their pre-election promises and gain political points than any state strategy.
There are forms and ways of resolving possible problems, which we believe that Bulgaria has democratic instruments for their resolution. It can also be done through various adopted state strategies for solving problems such as housing, employment, education and social inclusion.
Here we believe also the numerous civil society organizations that can solve painful and favorable solutions in order to solve these problems together with the state.
Therefore, the IRU appeals to all relevant international organizations and institutions such as the European Union, the Council of Europe, the European Parliament, the UN, the OSCE, the ODIHR, the Helsinki Committee and others to take immediate actions and respond to this type of discrimination and intolerance to fight its effective elimination of such phenomena.
At the same time, the IRU, which has its own Plan and Program, a resolution and similar documents available to all the above mentioned institutions to cooperate in finding optimal solutions, are in the spirit of respecting fundamental human rights. At the same time, IRU together with the Bulgarian state bodies can work in finding optimal solutions that will benefit all stakeholders.
Once again, the IRU, appeal to all international institutions and organizations to take steps and actions for the elimination of this kind of undemocratic actions.


Most patients with diabetes type 2 eventually need insulin, due to progressive decline in the production of insulin by pancreatic beta cells.
The question before every type 2 diabetes is when to start the insulin therapy and what is the appropriate insulin regime?
Anti-diabetic treatment is an evolving field with many new drugs: oral drugs, injectable analogues of glucagon-like peptide-1 (GLP1) and insulin formations.
Does a diabetes type 2 is really in need of insulin therapy?
Patients with type 2 diabetes on oral diabetes medication may need insulin therapy for a while when they are sick or have surgery. At these instances, diabetes pills may not work as expected in lowering your blood-glucose level, thus need insulin therapy.
If triple-therapy (diabetes treatment with three different classes of drugs) of maximum dosage does not produce a result (i.e., A1C of 7% or FBG of 130 mg/dl or 7.223 mmol/l), then you need to initiate insulin therapy along with one class of diabetes drug.
Most people with diabetes type 2 are having much fear, as they have advised to go on insulin. Even though there is numerous oral medications available in the market to treat diabetes type 2, insulin is the only one capable of not only lowering and even normalizes your blood glucose level.
In adequate management of diabetes for a long time may lead to diabetes complications such as nerve damage, diabetic eye problems, kidney failure, impotence, heart attack and stroke. Insulin therapy can prevent all these complications, so why still panic about insulin treatment. Start insulin treatment and keep yourself away from diabetes complications.
Fear of Needles - Now they are painless.
A person with type 2 diabetes normally has fear of needles. However, there are ultra-thin short needles are available to inject insulin under your skin. These needles are far less painful (almost painless) than a lancet (used to prick the skin for the blood test). They are painless to an extent that you may have to do visually check if you actually have pierced the skin and injected the insulin.
The important thing to make your injection painless is to choose a very thin needles, 30 or 31 gauge, and use a shortest needle suitable for your body size, maybe 5/16 inch will do.
When should I start the insulin therapy?
At the early stages, patients can be able to manage with diabetes lifestyle modification and oral diabetes drug or injection of a GLP1 analogue, either alone or in combination. However, most patients at the later stages need insulin therapy, similar to diabetes type 1 for effective management of blood-glucose and for prevent diabetes complications.
If lifestyle changes along with a combination of diabetes oral medication failed to produce the expected result; that is A1C of less than 7%, or fasting blood-glucose level of less than 130mg/dl or 7.223 mmol/l.
When your blood-glucose is very high over 250 mg/dl (13.89 mmol/l), you need to begin insulin therapy. Once your diabetes is in control then you might stop insulin and can manage with oral medication.
If you are elderly, having heart diseases or kidney problems, then insulin therapy is considering as the safest diabetes treatment.
If cost of treatment is bothering, you can consider changing to insulin therapy, because it is the least expensive, effective and safest diabetes treatment available.
About one in three individuals with diabetes type 2 requires insulin therapy when their diabetes age crossed 10 to 15 years.
How do you motivate for insulin therapy?
In 1990's doctors ignored strict blood-glucose control and allowed their diabetes patients with an A1C of 12 % or higher by putting them in ineffective oral drugs. They put their patient on insulin only when their blood glucose became so high, which are perfectly not responding to oral medications. Before this time, diabetes can make enough irreversible damage. This leads to diabetes complications and numerous patients experiencing vision losses, amputations, kidney failures, heart attacks and strokes.
Most of the patients on insulin, feel better once their blood-glucose levels are under good control. This is a major motivation for initiating and adhering to insulin therapy. The anticipated reduction of risk for diabetic complications further enhances the compliance.
Including basal insulin to the existing oral glucose-lowering medication can help achieve good glycemic control in the majority of diabetes type 2; however, few may require a twice-daily dosage. You can initiate your insulin therapy with either once-daily NPH insulin or a long-acting insulin analog. They should target fasting plasma glucose less than equal to 100 mg/dl (or 5.6 mmol/l) can safely achieve an A1C of 7.0%.
For several reasons, NPH insulin is considering as the preferred option. The relative benefit of the long-acting insulin analogs is limited to a reduction in (nocturnal) hypoglycemia.
The best timing for once-daily basal insulin injection is in the evening as compared with morning.
Combination therapy of insulin with metformin indeed produces a better glycemic control; fewer episodes of hypoglycemic and fewer weight gains than treatment with insulin alone.
What is the reasonable blood-glucose target?
Patients should try to achieve their best possible blood-glucose control with fewest adverse effects. Proper diet with a regular mealtime and predictable carbohydrate intake helps to avoid or minimize the two important insulin side effects (i.e., weight gain and hypoglycemia).
For most A1C of below 7% and FPG of 130 mg/dl or 7.223 mmol/l is considering as a reasonable target; a less stringent goal may be an A1C of less than 7.5% and FPG of 140 mg/dl or 7.779 mmol/l.
Several factors influence your decision in fixing the target; willingness to follow complex insulin treatment (basal-bolus therapy), lifestyle factors, how long you have diabetes, other coexisting medical conditions, hypoglycemia frequency, hypoglycemia awareness, age, life expectancy, and cost factors.
The target should be relaxed in difficult to treat individuals; those with frequent hypoglycemia, hypoglycemia unawareness, and widely fluctuating in blood-glucose levels in patients with advance stage of diabetes.
What are the drawbacks of insulin therapy in type 2 diabetes patients?
The two major drawbacks of insulin therapy in type 2 diabetes are increased hypoglycemia episodes and weight gain.
Intensive glucose-lowering therapy inevitably leads to an increased hypoglycemia episode. Hypoglycemia hampers stringent glycemic control and is considering as the restricting factor in diabetes control. In type 2 diabetes, the frequency of hypoglycemia is generally lower compared to type 1 diabetes. Type 2 diabetes is having protection against hypoglycemia by internally secreted insulin & glucagon, insulin resistance, higher glycemic thresholds for counter regulatory and symptomatic responses to hypoglycemia.
The two to four kg weight gain is associating with increased energy intake due to insulin therapy.
Extremely low blood glucose is called as hypoglycemia is always possible with insulin therapy. However, overtime you can learn to manage or change the insulin dosage with respect to your blood-glucose level, food intake, physical activity you undergo, and the symptoms you are experiencing.
Risk of hypoglycemia is high if you are in alcohol use, smoking, advanced age, intensive therapy, low body mass index, long diabetes duration, low-carb meals, fasting, delayed meals, vigorous exercise (without carb to compensate), and medical conditions (such as depression, sleep disorder, cerebrovascular disorder, liver failure, malnutrition, renal insufficiency, hypothyroidism).


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Q: Lock User and Enforce Password change via wp-cli Via wp-cli I want on automated installation scripts to either:

*

*"lock" and send an email to enforce to follow a "forgotten password" link via a custom email.

*Enforce a user on first login to change his/her password.

So I can apply an user policy via automation scripts for my custom docker solution such as this one.
So do you have any idea how to do that?

A: Would wp user reset-password {username} work for your purposes? The docs are a little thin, but I gather it sets the password for {username} to a random string, then emails that string to the email address on record for {username}.

redpajama_set_name: RedPajamaStackExchange


The problem in this research is the low of mathematics learning result of grade V student of SD Negeri 6 Metro Utara. The purpose of this research was to know the influence of realistic mathematics education (RME) approach to the result of V grade student mathematics. The type of the research was experiment research. The design used in this research was quasi experimental design. Population research is all of students V grade, the sample consists 26 students VA class and 27 student VB class. The determination of research sample used purposive sample. Data collection tools used questionnaires and cognitive tests. The data analysis was used t-test pooled varians. The learning results of this research was limited only to the cognitive domain. The result showed that there was a significant influence on the application of realistic mathematics education (RME) approach to the students' mathematics learning outcomes.
Agus, Ria Noviana. 2016. Efektivitas Pembelajaran Matematika Melalui Pendekatan Realistics Mathematics Education (RME) dengan Pemecahan Masalah Ditinjau dari Gaya Belajar Siswa. JIP STKIP Kusuma Negara. Vol. 7, No. 2, Juni 2016.
BSNP. 2006. Standar Isi untuk Satu-an Pendidikan Dasar dan Me-nengah. Jakarta. BNSP.
Fadillah. 2014. Implementasi Kuriku-lum 2013. Yogyakarta. Ar-Ruzz Media.
Özdemir, Burçin Gökkurt. 2017. Mathematical Practices In A Learning Environment Designed by Realistic Mathematics Education: Teaching Experiment About Cone and Pyramid. European Journal of Education Studies. Vol. 5, Issue 2, 2017.
Ricks, Thomas E. 2010. Mathematics is Motivating. The Mathematics Educator. Vol. 19, No. 2, September 2010.
Rinayanti, Ni Luh. 2014. Pendekatan Pendidikan Matematika Rea-listik Berbantuan Media Grafis Berpengaruh Terhadap Hasil Belajar Matematika Siswa Kelas V Sd Gugus 1 Mengwi. e-Journal Mimbar PGSD Universitas Pendidikan Ganesha. Vol. 2, No. 1, 2014.
Savickienė, Izabela. 2010. Conception of Learning Outcomes In The Bloom's Taxonomy Affective Domain. Lithuania. Vytautas Magnus University.
Sugiyono. 2010. Metode Penelitian Pendidikan. Bandung. Alfa-beta.
Susanto, Ahmad. 2016. Teori Belajar dan Pembelajaran di Sekolah Dasar. Jakarta. Prenadamedia Group.
UU RI No.20 Tahun 2003. Undang-Undang SISDIKNAS 2003. Jakarta. Sinar Grafika.
Widyastuti, Nur Sri, dkk. 2014. Pengaruh Pendidikan Mate-matika Realistik Indonesia (PMRI) terhadap Pemahaman Konsep Dan Berpikir Logis Siswa. Jurnal Prima Edukasia. Vol. 2, No. 2, 2014.
Word Economic Forum. 2017. The Inclusive Growth and Development Report. Geneva. Word Economic Forum.
Zulkardi, dkk. 2014. Pengembangan Materi Pembelajaran Bilangan Berdasarkan Pendidikan Mate-matika Realistik untuk Siswa Kelas V Sekolah Dasar. Jurnal Pendidikan Matematika. Vol. 3, No. 1, Januari 2009.


New Delhi: Board of Control for Cricket in India (BCCI) Acting Secretary Amitabh Chaudhary on Monday said a bilateral series with Pakistan is possible if the government gives the go-ahead.
"We are not averse to a bilateral series with Pakistan. But everything depends on whether the government gives the clearance," Chaudhary told a news channel.
"The series will not be possible without approval from the government," he added.
The two arch-rivals last participated in a bilateral series in December 2012 when Pakistan visited India for a limited overs series that included three One Day Internationals and two Twenty20 Internationals.


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History Warship Brittany
France to relaunch search for 16th-century shipwrecks
The coast off Finistère where the Cordelière warship was sunk during a 16th-century battle Julien Carnot/Wikimedia/CC
French researchers will this summer resume the search for the Cordelière, a huge warship that was sunk during a 16th-century battle with the Regent, the biggest vessel in the English fleet -- which also foundered in the clash.
The Cordelière, pride of Anne of Brittany's navy, exploded off the coast of Brest in 1512 after Henry VIII's armada surprised her France-Brittany fleet during the War of the League of Cambrai.
"What we have under the water here are two of the most significant museums of the 16th century's maritime history," Michel L'Hour, head of France's marine archeology department, said at a press conference.
"An underwater Pompeii"
The search, set to run from 20 June to 14 July, will cover about 25 square kilometres stretching from the port at Brest to the promontory at Saint-Mathieu, which would later give its name to the battle.
Discovering the arrival of the much larger English armada on 10 August 10, 1512, the bulk of Queen Anne's fleet raced to safety in port.
But the Cordelière, a 40-metre-long vessel armed with 200 canons, turned to take on the Regent, fending it off for several hours before an explosion of unknown origin engulfed the French vessel, sinking both ships.
Nearly 1,500 people died, and the sacrifice by the Cordelière's captain and crew acquired mythic status in Brittany's cultural history.
The simultaneous destruction of the Cordelière and the Regent warships Pierre-Julien Gilbert/Wikimedia/CC
"As is often the case with ships, the Cordelière was thrust into History just as it disappeared," L'Hour said.
A series of searches were carried out from 1996 to 2001 without success, but the new effort is based on a new analysis of archival documents as well as a revised interpretation of possible tidal movements.
The André Malraux research vessel will use sonar and magnetometric sensors to map the seafloor, with potential anomalies investigated by divers or robotic devices.
"We might find something on the first day, or nothing for five years. But I am firmly convinced, one day we will find it," L'Hour said.
Bone discovery revives century-old …
Far-right targets France's mixed-race …
France to loan Bayeux Tapestry to UK
Turkey clears RSF representative of 'terror propaganda'
Five key holes at the British Open

redpajama_set_name: RedPajamaCommonCrawl


Drop by our homepage and take this week's poll question, which considers miles-traveled taxation as a potential boon to state revenue.
New poll: The investment group that owns the Chicago Skyway recently put it up for sale after having it for just over a decade. Is this a bad sign for P3s in the U.S.?


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Frontline Coffee
Supporting Through Coffee
365 days a year, 24 hours a day our frontline services provide an unparalleled life saving service, that's why through the sales of our premium hand roasted coffee we donate 100% of our profits to charities that are there for them.
We proudly support the following charities:
RNLI - SAVING LIVES AT SEA
We are the RNLI: the charity that saves lives at sea. Every day of every year, people of all backgrounds get into danger in the water. It's a problem that we're here to tackle.
NHS CHARITIES TOGETHER
NHS charities are charities that are dedicated to supporting the NHS. They exist for the benefit of current and future NHS patients. There are over 250 of them across the UK. NHS Charities Together is the national association that individual charities belong to.
THE AMBULANCE STAFF CHARITY
We are the leading UK charity providing support to all present and past ambulance staff and their families in time of need, both in the NHS and independent sector.
POLICE CARE UK
Every day the police find themselves in harm's way protecting the public. We're the organisation that serving and former police officers, staff, volunteers, and their families, can turn to
THE FIREFIGHTERS CHARITY
Whether injured, ill or in need of psychological support we exist to support the everyday heroes of the UK fire community.
We are proud to announce that in the coming months we will be launching coffees dedicated to supporting HM Coastguard, Independent Lifeboats, Air Ambulance and Independant Rescue Teams including Mountain Rescue and Lowland Rescue.
We have raised £3177 for NHS, RNLI and emergency service charities so far!
© 2020, Frontline Coffee


We are pleased to say the event raised £2067 for the Fakenham Community Centre, so it's nice to see the Fakenham community supporting this community event.
We are very grateful for everyone's support: from the sponsors, the visitors and the volunteer helpers. Thank you.


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Paediatrics (RCH)
Paediatrics (RCH) - Theses
Curlis, Yvette M. 1 GIBSON, ANNE-MARIE 1 Opat, Annette 1
Bronchopulmonary dysplasia 1 consent 1 decision-making 1 genetic counselling 1 guidelines 1
Masters Research thesis
Type: Masters Research thesis × Start date: 2009 × End date: 2009 ×
Respiratory function tracking in survivors of prematurity and low birth weight
GIBSON, ANNE-MARIE ( 2009)
INTRODUCTION: To investigate longitudinal 'tracking' in lung growth, decline or stability of adult preterm/very low birth weight survivors over the study period. To investigate whether those who have clinically abnormal lung function fall further behind their contemporaries or demonstrate evidence of 'catch-up' growth. METHODS: 210 babies born ≤34 weeks' gestation and with birth weights ≤ 1500g in 1977-1982 were followed up at 8, 11, 14, 18 and 25 years of age. Respiratory outcome was evaluated using Spirometry. Spirometry was performed at each of the follow-up periods. Mixed model regression was used to assess longitudinal lung function trajectories and the influence of Bronchopulmonary dysplasia, being small for gestational age and abnormal lung function. Restricted maximum likelihood modelling was used for longitudinal FEV1 z-score as it allows for analysis of data from different time points that are not necessarily evenly spaced, without being affected by missing data. RESULTS: 137 VLBW children completed lung function testing at 8 years of age. Twenty VLBW children (14.6%) had abnormal FEV1 z-scores and 26 (21.0%) [Defined as >2 standard deviation's below the mean]. VLBW survivors showed minimal 'catch-up' in FEV1 z-score over the 13 years of the study; those without BPD (Bronchopulmonary dysplasia) FEV1 improved 0.034 (p=0.014) z-scores, those with BPD FEV1 improved 0.033 (p=0.039) z-scores. VLBW with BPD survivors did not return to within normal limits; those with abnormal FEF25-75 z-scores did not show significant 'catch-up' growth (p=0.41) and remained abnormal. CONCLUSIONS: Mixed models do not reveal any significant effects from being born with VLBW and its interaction with age; it does lead to a reduction in FEV1/FVC mean z-score. Although those VLBW individuals who were small for gestational age had significantly reduced FEV1, FVC and FEV1/FVC mean z-scores and these small for gestational age individuals show evidence of 'catch-up' growth in terms of lung function, with the exception of FEV1/FVC z-score which falls further from their contemporaries. This effect on FEV1 and FVC z-scores may suggest some protective element or compensatory mechanism of being born small for gestational age. Reassuringly, Bronchopulmonary dysplasia as a neonate did not significantly affect lung function variables as these individuals as they age. Those with clinically abnormal lung function show a progressive failure to achieve optimal lung function whether or not they had Bronchopulmonary dysplasia.
Attitudes towards newborn screening for Pompe disease among affected adults, family members and parents of 'healthy' children
Curlis, Yvette M. ( 2009)
Pompe disease is a rare autosomal recessive condition caused by a deficiency in lysosomal alpha glucosidase. It is a progressive and often fatal muscular disease with wide variation in clinical presentation. Two broad clinical categories of Pompe disease have been identified; infantile- and late- onset. In the past decade, enzyme replacement therapy has shown promising results in treating the underlying pathology, resulting in improved clinical outcome. Clinical trials indicating that initiation of treatment at an earlier disease stage leads to a higher chance of preventing permanent damage have led to the proposition of introducing newborn screening for Pompe disease. All forms of Pompe disease are caused by the same pathology, and thus newborn screening has the potential to identify those affected with the more severe infantile-onset form as well as those with late-onset disease who may not present with symptoms until late in life. The aim of this study was to investigate attitudes towards newborn screening for Pompe disease among affected adults, their family members and parents of 'healthy' children. Affected adults were recruited through support groups in Australia, the United Kingdom and United States; family members of affected adults were recruited from Australia; and parents of 'healthy' children were recruited through maternal child health clinics in Victoria, Australia. Participants completed questionnaires exploring their experiences of Pompe disease and/or newborn screening and their attitudes towards newborn screening for Pompe disease. Support for newborn screening for Pompe disease was high among adults with Pompe disease (85.4%), parents of 'healthy' children (93.9%) and all three family members of affected adults who participated in this study. However, when offered a theoretical screening test that would only identify infantile-onset Pompe disease, 42.1% of adults with Pompe disease and 53.1% of parents of 'healthy' children preferred this screen, indicating that these stakeholders have some concerns regarding detection of late-onset disease in infancy. Factors influencing attitudes were investigated and support for newborn screening in affected adults was highly correlated with age of onset of disease; a preference to have been diagnosed in infancy; a belief that an earlier diagnosis would have made symptoms easier to cope with; and a stronger confidence in the efficacy of enzyme replacement therapy. Potential benefits of diagnosis of late-onset disease in infancy were identified as being able to avoid the diagnosis odyssey, access enzyme replacement therapy at the optimal time, and allow individuals to make appropriate life choices. Participants identified increased anxiety in parents and the potential for over-protectiveness, in addition to possible discrimination, as harms of newborn screening for Pompe disease. Families in which an infant is identified with the potential for late-onset Pompe disease will need assistance to adapt to and manage this diagnosis, so that anxiety is minimised and unnecessary limitations are not placed on the child. Whilst potential medical and psychosocial benefits can result from newborn screening, it is important to carefully consider the potential for harm and the resources required to appropriately manage these so that ultimately benefit outweighs harm.
Exploring the experiences of people who have consented to tumour testing for a hereditary disposition to cancer
Opat, Annette ( 2009)
Due to the costly and technically challenging nature of genetic testing, methods have been developed to target more specifically those who are at increased risk of carrying the Hereditary Non-Polyposis Colorectal Cancer (HNPCC) mutation. HNPCC is an inherited colorectal cancer syndrome. Testing of tumour material (which has previously been removed during surgery) for features of HNPCC has been found to be an effective and economic method of identifying those at higher risk of having a mutation. Only those at higher risk of having a mutation will undergo genetic testing. This practice of "tumour testing" has become widespread. There is currently no clarity about requirements for consent prior to testing of stored tumour tissue. The person giving consent to tumour testing does not always have an appointment with a genetics service prior to giving consent. This can be contrasted to genetic testing on blood samples where laws and guidelines state that informed consent is required prior to genetic testing and that comprehensive genetic counselling and support should be provided as part of this process. Protocols for genetic testing have been developed as a result of extensive research around the impact and implications of genetic testing. Consumer opinion and participation through research is an important aspect of health policy and guideline development. Accordingly the purpose of this study was to contribute to such development by gaining insight into the experiences, understandings, decision making processes and opinions of those who had given consent to have their own or their relatives tumour tested. Seventeen people who had given consent for tumour testing either for themselves, or on behalf of a deceased relative were recruited through a Familial Cancer Centre and in-depth interviews conducted. The interviews were transcribed and analysed using thematic analysis. Some participants had no memory of consenting to tumour testing. Others remembered basic concepts. Negative implications of testing were unknown or viewed as unimportant. Participants did not understand the difference between tumour testing and germline testing. Despite lack of memory or understanding participants did not want additional or more detailed pre-test information although they did want more follow-up and support after receipt of results. The decision to consent to testing was made as soon as participants were informed of the availability of tumour testing - the major reason being to provide information for the family that would aid in cancer prevention. Participants were more concerned with accessibility to testing than pre test information and counselling. Findings in this study indicated participants made decisions heuristically rather than systematically and this as well as participants' opinions and other decision-making research has implications for the traditional view of informed consent around genetic related decisions. This in turn has implications for policy and guidelines in the area. Implications for current practise as a result of findings from this study include ensuring participants understand negative implications of testing and follow up and support of those with negative as well as positive results to tumour testing.


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UPI Photos
"Mad Men's" season seven premiere held in Los Angeles
Cast members Kiernan Shipka Jessica Pare, Elisabeth Moss, Jon Hamm, January Jones, and Christina Hendricks (L-R) attend the season seven premiere of the television drama series "Mad Men" at the ArcLight Cinerama Dome in the Hollywood section of Los Angeles on April 2, 2014. Storyline: A drama about one of New York's most prestigious ad agencies at the beginning of the 1960s, focusing on one of the firm's most mysterious but extremely talented ad executive, Donald Draper (Jon Hamm). UPI/Jim Ruymen
OTR:
LAP20140402104
MAD MEN SEASON SEVEN
"Mad Men", season seven, executive, 1960's, New York, advertising, advertising agency, AMC, Lionsgate, ArcLight Cinerama Dome, Hollywood, Los Angeles
Supplemental Codes:
Entertainment/Arts/Culture, People
© 2022 United Press International, Inc. All Rights Reserved.


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Stock Market Analysis and Prediction
What New Virus Strain Means for Traders
A new Covid-19 variant has been found in South Africa and Botswana. The World Health Organization named it 'omicron' and added it to the variants of concern. Many countries have closed their borders for travellers from South Africa amid concerns that omicron can trigger another Covid-19 resurgence.
What are the risks?
Researchers don't know for sure yet whether the current vaccines are sufficiently effective against omicron or not. Investors concern that it may slow down the reopening of economies and force central banks to switch back to the dovish policy.
What was the market reaction?
On Friday, markets fell sharply on news of a new coronavirus variant detected in South Africa that might pause the global economic recovery.
What to buy now?
With the market uncertainty and possible travel restrictions, it's a good idea to brush off the list of companies that outperformed their peers amid the pandemic last year. Let's then do it!
Amazon (AMZN), eBay (EBAY), and Walmart (WMT) can gain from both the return of Covid-19 restrictions and the upcoming New Year holidays.
Companies with a strong balance sheet
Companies with solid balance sheets and regular dividend payments will grow no matter what: with or without Covid. Among them are Microsoft and Google (Alphabet).
Biotech companies whose vaccines show the best efficacy against the new mutations of the virus will win. For example, Moderna has already announced that an omicron variant vaccine could be ready in early 2022! Will we see it at $400 soon again?
Don't know how to trade stocks? Here are some simple steps.
First of all, be sure you've downloaded FBS Trader app or Metatrader 5. FBS allows you to trade stocks only through this software.
Open an account in FBS Trader or the MT5 account in your personal area.
Start trading!
FBS Analyst Team
24.01.2023 11:09 TESLA Earnings Report Outcome Forecast
In a call scheduled for January 25, 00:30 am GMT+2, the Tesla Inc. team will publish the company's earnings for the final quarter of 2022 and comment on the results, projections, and outlook for the nearest future of the company.
18.01.2023 11:08 Will NETFLIX surprise investors?
The Netflix stock (NFLX), with a market cap of $145.17B and a whooping 10 000+% rise since its inception 16 years ago, experienced some turbulence for a short period last year while trading around the $250 share price. However, the NFLX stock quickly recovered and rose to over $300 towards the end of the previous quarter of 2022.
16.01.2023 12:01 Q4 2022 Earnings Report
The Q4 earnings season has been interesting, mainly because of the turbulent global economic outlook. On this premise, analysts forecast a disappointing performance for several stocks ahead of the Q4 earnings report publishing.


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The Itinerant Coach - The Footballing Life and Times of Steve Darby
Style Paperback E-Book
Paperback E-Book
Author: Antony Sutton
From growing up in the backstreets around Anfield as a football-crazy but nonetheless diligent and studious young man, to an adventure on the other side of the globe to Tasmania - not Tanzania as he thought - then onwards throughout Australia and south-east Asia, Steve Darby has had a remarkable life as a goalkeeper turned itinerant coach.
Along the way, he's met princes, sultans, some of the greats of the game, football administration VIPs as well as players and fans who, like so many around the world, just love the game.
The story of this popular, well-traveled itinerant coach is charmingly told by author Antony Sutton.
ISBN: 978-1-925914-25-2, 978-1-925914-26-9 (ePub)
Imprint: Fair Play Publishing
We will accept new, unopened items with 14 days of delivery for a full refund. We do not provide refunds on e-books. For more information, see our store policies, including details on shipping.


Basically, you may want to convert PDF to Word DOC or DOCX so that you can edit the document. Unless you have a professional-grade Adobe Acrobat IX or higher software, you can't easily make corrections or introduce changes on a PDF file directly. Once you are through with the editing, you may want to convert the revised document from Word DOC or DOCX to PDF for purposes of security, better portability and ease of storage.
There are two ways of converting Adobe files to Microsoft Word DOC or DOCX files. One is by availing of online file conversion services. The other is by using an installed standalone desktop PDF converter software. In both cases, there are top-of-the-line proprietary versions, the more affordable alternative commercial versions and the freeware versions. Which one you select will depend on the volume, frequency and extent of regularity by which you have to convert and edit PDF files.
There are now several cloud-based services for for converting and editing PDF files, including Google Docs. If you have a Google account, just sign in and proceed to your Google Docs. Upload your PDF file to your Google Drive either by dragging and dropping it to the page or by clicking on the Select a file from your computer button on the menu. Once uploaded to your Google Drive, the file will be displayed on the Google Doc window. On the File button in the menu, click on the Download as option. Select Microsoft Word (docx). Wait for the PDF file to download to your computer as an editable Word document file. Of course, the downside with using most of these free cloud-based resources is that they can convert only one PDF file at a time. Often too, it takes a long time to wait for the conversion process to be completed. In the case of ZamZar, you will even have to give them your email address where they will send you the converted file later once they are ready.
If you have to process tons of large files quickly and on a fairly regular basis, you may need to install a desktop PDF to Word converter application directly on your computer. With such a dedicated app, the file conversion process can be done locally and instantly on your machine. There are many free PDF converter desktop apps that comes to mind. Of course, these freeware desktop apps arent as powerful nor sophisticated as the file conversion tools that are used by the cloud-based services, even if also free. In terms of quality, the converted files youll get from these apps will likely be a notch or so lower than those youd get from the online resources, or from the branded softwares like Adobe Acrobat and its more affordable commercial alternatives.
After youre done editing, converting a Word file to PDF is fairly easy. Using Microsoft's own basic Word software application, or for that matter, any modern word processor, you can just click on either the Save as or the Export options shown in the File scroll-down menu to convert your edited DOC or DOCX document back to PDF.


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Sara Ramirez Just Came Out For A Great Cause
By Lucas Molandes October 10, 2016 at 5:00 pm
CREDIT: TRUE COLORS FUND/ YOUTUBE
It should come as no surprise that nearly 40 percent of homeless youths identify as lesbian, gay, bisexual or transgender. Coming of age is already awkward enough when you're straight, but when you're living in a society where you see people maliciously targeted because of their gender identity, it can forever shatter your own self-image and lead to strong feelings of isolation and alienation, feelings that can lead beautiful people to suffer on fringes of society. It doesn't have to be like that. This past weekend, with the help of True Colors Fund's 40 to None Summit, Sara Ramirez came out as bisexual to let LBGTQ youths know something very important: you're not alone.
"I am deeply, deeply invested in projects that allow our youths voices to be heard," Ramirez explained to the True Colors Fund's 40 to None Summit audience.
From my speech at #40ToNoneSummit #SharingMyTruth #ThankYou @truecolorsfund for your support.
A photo posted by Sara Ramirez (@therealsararamirez) on Oct 8, 2016 at 10:12am PDT
CREDIT: THEREALSARARAMIREZ / INSTAGRAM
Sara's coming out came during a heartfelt speech covering the conflicts she felt in her own life as a result of her gender identity. Sara's story is not too different from the hundreds of thousands of youths who confront neglect, abuse and shame at the hands of societal bias and ignorance. Thanks to the platform the True Colors Fund provided, Sara was able to spread her message to the LBGTQ community who need compassion the most. She also set an example by using her high profile to bring awareness to this great cause. If people learn from her example, the True Colors Fund will have an fighting chance to lower homelessness in the LBGTQ community, a goal that benefits all of us. Please check out the True Colors Fund website for more information.
READ: CBS Is Producing A Show With A Latino Lead With Issues That Will Hit Home
Tags: LBGTQ, Sara Ramirez, Grey's Anatomy
Show Your Pride And Allyship With These Colorful And Fun Rainbow Outfits
By Samantha Chavarria May 30, 2019 at 12:16 pm
June is PRIDE month which means cities all over the world will be holding major events to celebrate our LBGTQ communities. Between festivals, parades, mixers, and other big happenings, our calendars will be jam-packed the first month of summer. That means we need to start getting our PRIDE wardrobes established asap.
No matter where you fall on the spectrum, you're going to want a look that embraces the freedom and spirit of PRIDE. Thanks to Instagram, we've got all the vision we'll need. Here are some fashion-forward examples to spark some inspiration your PRIDE looks.
1. Handmade with Love and Pride
Instagram / @nina_dashl
Some of the best PRIDE looks we'll see are handmade by creative artisans. Created by @mikaliias, this incredible two-piece denim outfit is adorned with embellishments and beads. We love this look because it manages to be a versatile statement-maker without being gaudy or too over the top.
2. Everything's Coming Up Rainbow
Instagram / @teseesays
If you're going to dress head to toe for PRIDE, be sure to get shoes that live up to the challenge. These rainbow platforms are fun and fashionable with the added advantage of being hella unique. After all, how often do you slap see-through vinyl on your patas?
3. A Fashionable Foursome
PRIDE is all about community and community is the feeling you get when surrounded by your amigas y comadres. Your BFFs are practically an accessory so don't be afraid to try a group look. Go for a theme or — if all else fails to impress — wear shorts and shades to help inspire those summertime feels.
4. This Rainbow Goth Look is Everything
Instagram / @saracha_boho
Just because it's PRIDE, it doesn't mean you have to ditch your usual aesthetic for a more colorful one. Why not just combine them? Brilliant eye makeup paired with this witchy harness and spike ensemble has us falling in love with the Rainbow Goth aesthetic.
5. Proud and Body Positive
Instagram / @johodaniels
PRIDE is fundamentally all about inclusivity and this includes bodies of all sizes. Body positivity isn't always celebrated when sported by fat bodies, but we fully support our bigger babes in taking up space and showing off their killer style. Every PRIDE-goer should be comfortable in their own skin when they join the party.
6. Somewhere Over the Rainbow
Instagram / @life.of.lauren
The rainbow is the official symbol of the LBGTQ community so you're going to see it a lot of it this month. You might as well embrace colorful motif now. This mix of vibrant striped bottoms with a pegasus and rainbow top is exactly what we want to see at PRIDE.
7. Just Add Glitter
Instagram / @clararaararra
Not sure what to wear to your PRIDE event? Just add glitter. Seriously, that's all you need. Glitter can glam up any outfit you choose and costs next to nothing. Just make sure your sparkly addition is the environmentally friendly kind before you embrace this quick glo-up.
8. Pride — and Fashion — is For Everyone
Instagram / @svngre_seca
For too long, the LGBTQ community was viewed as perverse and not suitable for kids. Luckily, that has changed as the world has become more educated and empathetic. PRIDE now has many family-friendly events. which means you can take the little ones with you to celebrate. Just don't forget the matching outfits.
9. Serving Pride Head to Toe
Instagram / @kawaii_fetus
You're going to see hundreds of fierce PRIDE looks this month so feel free to make a statement with your own. That's what cosplayer @kawaii_fetus did with her vividly cute outfit. It's raver girl meets pastel goth meets Rainbow Brite and we love it.
10. Born This Way
Instagram / @nycpride
There's nothing better than embracing who you are while being surrounded by people who are doing the same. No matter what you wear this PRIDE season, make sure you're feelin' yourself. You're beautiful, you're bold and you're not going to hide it.
11. They/Them
Instagram / @qadir.el
This year, we're done with apologizing for who we are. A statement shirt like this one is a powerful way to declare that as well as what you stand for. What's even better is that it's easy to style this look with a bold face of makeup or dress it down with a pair of jeans.
12. Teach Them Young to be Proud of Who They Are
We're raising a generation of kids who won't feel the need to hide; a generation who can be proud of who they are. The kids in our community are super heroes who will make it even better for the generation that follows them. That's every reason to celebrate PRIDE.
13. D-I-V-A
If you can't be a DIVA at PRIDE, where can you be one? Drag stars have long been the entertainers and artists of our communities so they're the perfect people to draw inspiration from. Skin-tight clothing, feathers, and rhinestones go a long way in your search for the perfect PRIDE aesthetic.
14. Biker Babe Chic
Bikers and those who love leather have always been a part of PRIDE parades. So, if you ride, it's time to dust off your chaps and hit the road. Add someone snuggling behind you on the backseat to fully emulate the Biker look.
15. He came to SLAY
Confidence is the thing that really sells an outfit. That means that if you believe you look good then you do look good. Whether you wear an elaborate show girl-esque number or just your favorite jeans, you better come to PRIDE ready to slay!
16. Neon & Glitter & Tassels — Oh My!
In case you didn't know, over the top doesn't exist during PRIDE month. If it is in your personal taste to glitz it up in something fabulous, don't feel like you'll be the only one. Chances are you'll meet plenty of people who get you and your look.
17. Frida Would be Proud
Instagram / @love_is_love_collection
The iconic Mexican artist Frida Kahlo was famous for wearing flower crowns and she also just so happened to be bisexual. From what we know about the colorful woman, she would have adored PRIDE month. Celebrate your queerness and pay homage to Frida herself with your own brilliant flower crown.
18. Paint With All The Colors
Instagram / @alexisevelynbeauty
Once you get your clothes straight, it's time to deck your face out for PRIDE. Look to your favorite beauty blogger's work for inspiration or try to free-hand with the use of your own imagination. You have every color of the rainbow to work with so neutral tones need not apply.
19. The Best Accessory is a Flag
Instagram / @lisaluong_
If all else fails, a PRIDE flag is all that you need to make a radiant fashion statement. The traditional rainbow flag, the lesbian flag, and the bi flag are just a few options to try and prove that simple can be just as impactful.
20. To Love and Be Loved
When all is said, this month is a celebration of love. The love of ourselves, the love of our families and the love of those we choose are what makes the festivities possible. No matter what you wear, remember that PRIDE is a joyous time. Stand tall, smile and face the month with a full heart.
Tags: fashion, Gay Pride, LBGTQ, Pride, Pride 2019, pride month
'Grey's Anatomy' Got Real Emotional In Episode About Undocumented Immigrants And Family Separation
Grey's Anatomy / ABC
By Araceli Cruz May 7, 2019 at 2:19 pm
For the past 14 years, "Grey's Anatomy" has been delivering the goods on love, death, and everything in between. However, it's only been in the past couple of years that the show has been touching on Latino issues and traditions including Day of the Dead. Last week's episode, which aired on May 4, hits close to home given the current immigration crisis,
The latest episode of "Grey's Anatomy" featured a storyline about an undocumented father and daughter.
The episode titled "What I Did for Love," had a little girl named Gabby who was brought into the hospital by her father because she was complaining about a pain in her stomach.
The audience learns that the father and daughter were separated at the border and that he is seeking asylum.
The father, played by Omar Leyva, hadn't seen his daughter in four months. When they were finally reunited, it is clear that his daughter is sick and wasn't getting proper treatment while in custody. The doctors told him that his daughter will need surgery, but he informs the doctors that he doesn't have insurance. The doctors then try to get him some assistance, but he doesn't qualify for that either because he makes too much money.
Meredith Grey is desperate to get this little girl help, so she commits insurance fraud to give her the medical attention she needs.
"The system failed him," Grey said after her boss reprimands her for breaking the law. Grey says that the undocumented man pays taxes, works and yet he cannot afford insurance.
He came all this way to make her life better, and yet he cannot pay for the insurance that he needs to care for his daughter. Ultimately, Grey wins and is allowed to do the surgery and help the family in their time of need.
The entire staff comes through for this little girl and her father giving us a glimpse at the compassion in this country.
This is not the first time "Grey's Anatomy" has dealt with the issue of immigration and undocumented immigrants. Last season, surgical intern, Sam Bello (played by Jeanine Mason) disclosed that she was a DREAMer.
While the DREAMer episode was good at bringing awareness to immigration, the intern has whisked away to Switzerland in order to avoid deportation, which is not reality. At least this episode shows the harsh realities that undocumented people have to face when it comes to medical care and insurance.
READ: "Grey's Anatomy" Celebrated Dia De Los Muertos And I Cried The Entire Time
Tags: Undocumented Parents, Grey's Anatomy, Immigrant Rights, undocumented immigrants, immigration
Just When You Thought It Couldn't Get Worse: A 3-Year-Old Was Told To Pick Which Parent To Be Separated From
This year has seen so much of what we would have never even imagined just a little over four years ago. Thanks to the strict and cruel policies under our current presidential administration, we've seen families separated from their underaged children at border stops, kids held in cages and women sexually assaulted and harassed by […]
An undocumented mother posted a video on Twitter of one woman threatening her with her immigration status during an argument at her door.
Places Of Worship In The US Are Sheltering Undocumented Immigrants And Here's How They Can Do That
Places of worship have a long history of protecting communities under attack and now religious leaders are stepping up to protect undocumented immigrants.


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Highly sensitive, with high temporal resolution, detection of ethanol concentrations in discrete brain regions of rats voluntarily accessing ethanol would represent a source of greatly desirable data in studies devoted to understanding the kinetics of the neurobiological basis of ethanol's ability to impact on behaviour. In the present study we present a series of experiments aiming to validate and apply an original high-tech implantable device, consisting of the coupling, for the first time, of an amperometric biosensor for brain ethanol detection, with a sensor for detecting the micro vibrations of the animal. This device allows the real-time comparison between the ethanol intake, its cerebral concentrations, and their effect on the motion when the animal is in the condition of voluntary drinking. To this end, we assessed in-vitro the efficiency of three different biosensor designs loading diverse alcohol oxidase enzymes (AOx) obtained from three different AOx-donor strains: Hansenula polymorpha, Candida boidinii and Pichia pastoris. In-vitro data disclosed that the devices loading Hansenula polymorpha and Candida boidinii were similarly efficient (respectively, LRS: 1.98±0.07 and 1.38±0.04 nA mM−1) but significantly less than the Pichia pastoris-loaded one (LRS: 7.57±0.12 nA mM−1). The in-vivo results indicate that this last biosensor design detected the rise of ethanol in the nucleus accumbens shell (AcbSh) after 15 minutes of voluntary 10% ethanol solution intake. At the same time, the micro-vibration sensor detected a significant increase in the rat's motion signal. Notably, both the biosensor and micro-vibration sensor described similar and parallel time-dependent U-shaped curves, thus providing a highly sensitive and time-locked high-resolution detection of the neurochemical and behavioural kinetics upon voluntary ethanol intake. The results overall indicate that such a dual telemetry unit represents a powerful device which, implanted in different brain areas, may boost further investigations on the neurobiological mechanisms that underlie ethanol-induced motor activity and reward.
Simultaneous wireless and high-resolution detection of nucleus accumbens shell ethanol concentrations and free motion of rats upon voluntary ethanol intake / Rocchitta, G.; Peana, A. T.; Bazzu, G.; Cossu, A.; Carta, S.; Arrigo, P.; Bacciu, A.; Migheli, R.; Farina, D.; Zinellu, M.; Acquas, E.; Serra, P. A.. - In: ALCOHOL. - ISSN 0741-8329. - 78:(2019), pp. 69-78. [10.1016/j.alcohol.2019.04.002]
Simultaneous wireless and high-resolution detection of nucleus accumbens shell ethanol concentrations and free motion of rats upon voluntary ethanol intake
Rocchitta, G.
;Peana, A. T.
Writing – Original Draft Preparation
;Bazzu, G.
;Cossu, A.;Carta, S.;Arrigo, P.
Membro del Collaboration Group
;Bacciu, A.
;Migheli, R.
;Farina, D.
;Zinellu, M.
;Acquas, E.;Serra, P. A.
Writing – Review & Editing


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Michael Anthony Arbib (born May 28, 1940) is an American computational neuroscientist.  He is an Adjunct Professor of Psychology at the University of California at San Diego and professor emeritus at the University of Southern California; before his 2016 retirement he was the Fletcher Jones Professor of computer science, as well as a professor of biological sciences, biomedical engineering, electrical engineering, neuroscience and psychology.

Early life and education
Arbib was born in England on May 28, 1940, the oldest of four children.  His parents moved to New Zealand when he was about 7, and on to Australia when he was about 9.
Arbib was educated in New Zealand and at The Scots College in Sydney, Australia.  In 1960 he took a BSc (Hons) at the University of Sydney, with the University Medal in Pure Mathematics.

Arbib received his PhD in Mathematics from the Massachusetts Institute of Technology in 1963. He was advised by Norbert Wiener, the founder of cybernetics, and Henry McKean. As a student, he also worked with Warren McCulloch, the co-inventor of the artificial neural network and finite-state machine.

Career
Following his PhD, Arbib moved to Stanford for a postdoc with Rudolf E. Kálmán.  Arbib spent five years at Stanford, before moving to become becoming the founding chairman of the Department of Computer and Information Science at the University of Massachusetts Amherst in 1970. He remained in the Department until 1986, when he joined the University of Southern California.  He retired and was granted emeritus status in 2016.

Arbib's collected papers from the period 1960 through 1985 are held by the University of Massachusetts Amherst.

Awards and honors
In 1992, Arbib was elected a Fellow of the Association for the Advancement of Artificial Intelligence for "his work in schema theory and neural networks to provide a linking methodology between distributed artificial intelligence and brain theory."
In 2008, Arbib was elected a Fellow of the American Association for the Advancement of Science.

Selected bibliography

Authored and co-authored books
 (1968) Algebraic Theory of Machines, Languages and Semigroups
 (1969) Theories of abstract automata Prentice-Hall
 (1973) with Louis Padulo System Theory. A Unified State-space Approach to Continuous and Discrete Systems Saunders
 (1975) with Ernest G. Manes Arrows, Structures, and Functors: The Categorical Imperative Academic Press
 (1978) with Suad Alagic The Design of Well-Structured and Correct Programs Springer
 (1981) with A.J. Kfoury and Robert N. Moll A Basis for Theoretical Computer Science Springer
 (1982) with A.J. Kfoury and Robert N. Moll A Programming Approach to Computability Springer
 (1984) Computers and the Cybernetic Society Second Edition" Academic Press  (First edition 1977)
 (1985) In Search of the Person: Philosophical Explorations in Cognitive Science UMass
 (1986) with Ernest G. Manes Algebraic Approaches to Program Semantics Springer
 (1986) with Mary B. Hesse The Construction of Reality CUP
 (1987) with E. Jeffrey Conklin and Jane C. Hill From Schema Theory to Language OUP
 (1987) Brains, Machines, and Mathematics Second Edition Springer  (First edition McGraw-Hill 1964 LC 63-21473)
 (1988) with Robert N. Moll and A.J. Kfoury An Introduction to Formal Language Theory Springer
 (1989) The Metaphorical Brain Second Edition" Wiley  (First edition Wiley 1972
 (2005) Beyond the Mirror: Biology and Culture in the Evolution of Brain and Language OUP
 (2012) How the Brain Got Language: The Mirror System Hypothesis OUP

Edited books
 (1982) with David Caplan and John C. Marshall Neural Models of Language Processes Academic Press
 (1984) with Oliver G. Selfridge and Edwina L. Rissland Adaptive Control of Ill-Defined Systems Plenum Press  (Proc. Nato Conference Series. II, Systems Science, V. 16, June 21–26, 1981 Devon, England)
 (2003) The Handbook of Brain Theory and Neural Networks 2nd Edition MIT  (First edition MIT 1995 0-262-01148-4)
 (2005) with Jean-Marc Fellous Who Needs Emotions: The Brain Meets the Robot OUP

Other publications

 Dynamic Interactions in Neural Networks: Models and Data (Research Notes in Neural Computing) by Michael A. Arbib, Shun-Ichi Amari (1 January 1989)
Vision, Brain, and Cooperative Computation by Michael A. Arbib (Editor), Allen R. Hanson (Editor) (24 January 1990)
Natural and Artificial Parallel Computation by Michael A. Arbib (Editor), J. Alan Robinson (Editor) (Hardcover – 21 December 1990)
Neuroscience: From Neural Networks to Artificial Intelligence : Proceedings of a US-Mexico Seminar Held in the City of Xalapa in the State of Verac (Lecture Notes in Mathematics) by Pablo Rudomin, et al. (1 June 1993)
Neural Organization: Structure, Function, and Dynamics by Michael A. Arbib, Péter Érdi and János Szentágothai et al. (31 October 1997)
Neuroscience and the Person: Scientific Perspectives on Divine Action (Scientific Perspectives on Divine Action Series) by Robert J. Russell, et al. (1 January 2000)
Computing the Brain: A Guide to Neuroinformatics by Michael Arbib, Jeffrey S. Grethe (15 March 2001)
The Neural Simulation Language: A System for Brain Modeling by Alfredo Weitzenfeld, et al. (1 July 2002)
Visual Structures and Integrated Functions (Research Notes in Neural Computing, No 3) by Michael A. Arbib, Jorg-Peter Ewert
Visuomotor Coordination: Amphibians, Comparisons, Models, and Robots by Jorg Peter Ewert, Michael A. Arbib

References

External links

1940 births
Living people
American cognitive scientists
British emigrants to the United States
University of Massachusetts Amherst faculty
University of Southern California faculty

redpajama_set_name: RedPajamaWikipedia


text:
Rainbow rocks
> Applejack123rainbowrock
Flash123. Alvin and the chipmunks. Star wars. Heroes. Athrodite. Hector2. Roald Dahl - Biography - Author. Children's author Roald Dahl wrote the kids' classics Charlie and the Chocolate Factory and James and the Giant Peach, among other famous works. He was married to actress Patricia Neal. Synopsis Roald Dahl was born on September 13, 1916, in Llandaff, South Wales. In 1953, he published the best-selling story collection Someone Like You and married actress Patricia Neil.
He published the popular book James and the Giant Peach in 1961. Early Life Famed children's author Roald Dahl was born in Llandaff, South Wales, on September 13, 1916. The young Dahl received his earliest education at Llandaff Cathedral School. And that he did. Lusting for yet more adventure, in 1939, Dahl joined the Royal Air Force. Early Writing Career While in Washington, D.C., Dahl met with author C.S.
Dahl wrote his first story for children, The Gremlins, in 1942, for Walt Disney. Personal Life Dahl told his children nightly bedtime stories that inspired his future career as a children's writer. Children's Books Death. Roald Dahl. Cocoa Beans Plants - Facts for Kids. Do you like chocolate?
Most people do. The smooth, brown candy is deliciously sweet. Not all chocolate tastes exactly alike, but it all tastes like chocolate, doesn't it? That's because it all comes from the cocoa bean. What is a cocoa bean Cocoa beans are little beans found in the pods that grow on cacao (cocoa) trees. When the pods are ready to be picked, they are cut open so the beans inside can be taken out and roasted (baked). Roasting the beans dries them so they can be crushed into cocoa (chocolate powder). Growing cocoa beans Since cocoa beans grow on trees, you might be thinking you want to plant a few in your yard. Cocoa trees grow slowly. A tree produces about one thousand cocoa beans every year. Think about this… Every year, people all over the world eat or drink 2 BILLION pounds of chocolate every year. My favriout from winx club. Roald Dahl. Charlie.and.the.Chocolate.Factory.2005.8BRO.COM.mkv. Roald Dahl Biography - life, childhood, children, parents, story, school, mother, young, book.
Born: September 13, 1916 Llandaff, South Wales Died: November 23, 1990 Oxford, England Welsh author A writer of both children's fiction and short stories for adults, Roald Dahl is best known as the author of the 1964 children's book Charlie and the Chocolate Factory (he also wrote the script for the 1971 movie version).
Dahl has been described as a master of story construction with a remarkable ability to weave a tale. A young troublemaker Roald Dahl was born September 13, 1916, in Llandaff, South Wales, United Kingdom, to Norwegian parents. He spent his childhood summers visiting his grandparents in Oslo, Norway. After his father died when Dahl was four, his mother followed her late husband's wish that Dahl be sent to English schools. The birth of a writer After graduating from Repton, Dahl took a position with the Shell Oil Company in Tanganyika (now Tanzania), Africa.
Teeth. Commercials. Anmie. Purdys Chocolatier - Science of Chocolate. Winx club. Kids Zone: Chocolate Tree/Cacao. Chocolate Tree/Cacao Theobroma cacao Have you ever wondered where chocolate from?
Did you know that the chocolate in the candy bars that you buy at the grocery store actually come from a tree in the middle of the rainforest? Chocolate comes from a tree called the Cocoa tree, or in Spanish, Cacao. The cocoa tree or chocolate tree, is found in the Upper Amazon Basin where it can reach over fifty feet high. The fruit is thick and oval shaped, usually yellow or red, and can sometimes grow as big a as a football. The pulp around the seed is actually there to attract animals that will eat the seed and then serve as seed dispensers after the seed goes through their digestive track.
Cacao is an important crop in the Amazon region because it is sold to countries all over the world so that children just like you can eat all forms of chocolate: liquid in your hot cocoa, and solid in your candy bar. Lego ninjago episodes. How-To Videos. Matchstalk Men & Matchstalk Cats & Dogs ~ Top of The Pops 1978. The Roald Dahl Museum. Five nights at fredies. Gangstar vegas. Gta. Flash123. Video game types. Marvel avenjers. Super heroe videos. Games. Songs.
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'Tis the season! The holidays are upon us and that means decking your halls to celebrate the whole host of festive celebrations November and December have to offer! If you are looking for some simple inspiration for your home, here are a few favorite decorating ideas from ASP Windows for this holiday season.
Holiday decorations tend to be a little over the top. Think Clark Griswold in National Lampoon's Christmas Vacation.
Decorating doesn't have to be flashy or excessive. By keeping it understated, you can add a subtle, yet elegant holiday theme to any room. Instead of loads of lights, try placing a few Christmas, Hanukah, or other holiday-themed decorations on a coffee table, along with some festive colored votive candles. You can even give it a South Florida feel to add some Miami sizzle to a classic North Pole style.
Candles used to be the only way to add light to a house after dark. Nowadays, the candle is less of a necessity for lighting the home, but that doesn't mean you should abandon them. Using candles to add a soft glow is a great way to set the festive mood. Also, adding some candlelight, especially in front of mirrors, adds a charming, understated warmth to a room – perfect for a relaxing evening with some hot cocoa.
Candlesticks may seem like a small part of your interior decorating plans, but just this one little swap can have a big impact on your festive designs! Try swapping out those plain old white candles for more festive red, green or blue ones. This will add a little extra spark to your holiday designs and liven up any table setting.
Another great idea to literally spruce up your home this holiday season is to add a few sprigs of evergreen trees to pillows and other fabric surfaces. By tying a sprig of spruce or pine to pillows with ribbons, you can add little splashes of festive cheer throughout your home.
Living in Miami is an amazing experience, but fun in the sun is offset by an occasional hurricane or tropical storm that can stop the festive holiday season. Fortunately, that is where ASP Windows comes in. At ASP Windows, we want you to be worry free when the next storm comes. Fully licensed, insured, and Ygrene certified, we offer no down payment and 100 percent financing until December 2019 on new impact windows and installation. Contact us today at (888) 782-8342 for a free in-home estimate on our extensive range of fully customizable windows, doors, and glass. So, if you're stuck thinking of the perfect present for yourself – or someone else in South Florida – think ASP Windows. After all, safety and peace of mind are the best gifts!


Do you dream of becoming a rock star but don't know where to begin? Muzichunters can teach you how to make rock music for beginners. A typical rock band consists of a drummer, a bass guitar player, a guitarist and a singer. In many cases, the singer will be playing the guitar or bass as well. You might have 2 or 3 guitars in your band, perhaps a good keyboard player. It depends on who you find and what style of music you play. Make sure that they can actually play something, have a basic knowledge of musical theory, and are actually interested in playing and performing. Maybe a drummer, and 3 guitarists, and nobody sings. Put the worst trumpet player on tuba. The part is so easy, that the student will be playing perfectly. Also, singing comes with maturity. Make sure everyone has an instrument to use. You can purchase a guitar or bass for some dollars. Drum sets can be about 300 dollars and you also need amps for everyone. They usually come in starter packs, but you can get a small one for 100 for guitar or bass. Percussionists play drums. Get someone who has played music in a previous band, or really knows how to keep time while playing. Whoever works the percussion lays the backbeat for everyone else, so they have to be consistent.
Mics usually go into a PA system in a concert hall or club or anywhere they have music normally. For practices, it can be a pain. It's not going to be loud enough, but plug it in to a bass amp or a stereo system that you might have for Cd's. You just need the right adapter.
Now it's time to try and play a song. In the beginning, try a simple session. Have the drummer do a simple beat, and have the bassist play quarter notes on E. Then have the guitarist strum an E chord in either quarter notes or eighth notes. If there is another guitar or whatever, have he or she solo in the pentatonic E scale. It sounds hard, but the best part is that it's very hard to be bad. Just play E G A B D E in different orders, in different rhythms.
It's time to write a song.
All you have to do is write a quality poem. It doesn't have to rhyme, though it sounds better when it does. Try to pick a good topic, like running to the store or going on vacation or something. Or it could be random, and not make any sense whatsoever. Then, once you make lyrics, come up with a simple chord progression. Many times, the 4 and 5 chords are used. For instance, if you were playing a song in G, maybe the chords would be G D A C, or 1 5 2 4. Then, try and come up with a little guitar lick or some kind or little melody to play in between the verses and chorus and stuff.
That is the basic part of your song. Then: (Lead Part) (Verse 2) (Chorus) (Bridge) (Chorus) (Ending) this is typical of a rock song. Once you've practiced that enough, try to make a few more songs and learn some easy covers. Your first performance should be in front of people you know. From there, move on to battle of the bands competitions. You do not have to win, just get experience and so people know you exist. Over time, your band will get better. You'll lose your members and gain new members. You'll upgrade your music equipment. You might get a PA and Massive amps. You might get a record deal and go on tour.


In order to combine the advantages of fluorescence and surface-enhanced Raman spectroscopy (SERS) on the same chip platform, a nanostructured gold surface with a unique design, allowing both the sensitive detection of fluorescence light together with the specific Raman fingerprint of the fluorescent molecules, was established. This task requires the fabrication of plasmonic arrays that permit the binding of molecules of interest at different distances from the metallic surface. The most efficient SERS enhancement is achieved for molecules directly adsorbed on the metallic surface due to the strong field enhancement, but where, however, the fluorescence is quenched most efficiently. Furthermore, the fluorescence can be enhanced efficiently by careful adjustment of the optical behavior of the plasmonic arrays. In this article, the simultaneous application of SERS and fluorescence, through the use of various gold nanostructured arrays, is demonstrated by the realization of a DNA detection scheme. The results shown open the way to more flexible use of plasmonic arrays in bioanalytics.
Fluorescence spectroscopy and microscopy is one of the most important analytical techniques in the life sciences and medicine. Due to its extreme sensitivity, fluorescence allows investigations on a single-molecule level . Fluorescence in bioanalytics is mostly used for tracking intrinsic fluorophors (autofluorescence) or special fluorescence labels, which selectively bind to special cellular functional groups, such as proteins or nucleic acids [2,3]. However, the broad emission spectrum of the fluorescence reporter molecules prevents the parallel detection of several fluorescent dye labels by fluorescence microscopy.
Raman spectroscopy, i.e., the excitation of vibrational modes through inelastic light scattering, allows one to obtain highly specific molecular fingerprint information without the need for external labels. The drawback of the intrinsically small Raman scattering cross sections not allowing for trace analytics and fast detections times can be overcome by applying surface-enhanced Raman spectroscopy (SERS). The enhancement of the inherently small Raman cross sections by applying SERS is based on the strong plasmonic field enhancement at rough metallic surfaces. Since SERS combines the unique fingerprint specificity of Raman with trace level sensitivity, it is a very active topic in (bio)analytics [4-13].
(1) Periodically patterned arrays with homogenous signal enhancement must be prepared, because difficulties in the fabrication of metallic surfaces with reproducible signal enhancement hamper the routine application of SERS as a (bio)analytical tool . (2) A patterned plasmonic active film is essential for detecting both fluorescence and SERS signals through a single plasmonic array, since the optimum distance between the (fluorescent) molecules and the metallic surface, for gaining the maximum signal intensity, is different in the two cases. The most efficient SERS enhancement is achieved for molecules within the first layer of the metallic surface, where the fluorescence signal will be quenched most efficiently. Thus, a parallel detection of fluorescence and SERS is prevented when applying a continuously nanostructured metallic layer, such as roughened metal electrodes, as a sensor array. (3) A further requirement which has to be fulfilled is the realization of large-scale production capacity for applications in (bio)analytics.
One of the most common type of periodically patterned plasmonic arrays is based on the formation of a polystyrene or silicon dioxide bead mask during the production process, such as in nanosphere lithography (NSL) [15,16], film over nanospheres (FON) [17,18], and sculpted SERS substrates . Here, the arrays are tunable by varying the size of the monodisperse polystyrene or silicon dioxide beads. Unfortunately, frequently occurring constructional defects within the mask are transferred to the nanostructured metallic surface. Furthermore, electron beam lithography (EBL)  is a promising production technique for periodically patterned plasmonic arrays. We have recently shown that gold nanorhomb arrays produced by EBL  provide a homogenous signal enhancement across a large area . By virtue of the patterning process, the optical parameters are tunable by varying both the size of the nanoparticles and the period of the array , which leads to design and fabrication strategies of SERS arrays developed to gain a maximum SERS enhancement .
Furthermore, the use of our gold nanorhomb arrays fabricated on a quartz wafer allows the binding of analyte molecules also through direct attachment to the quartz surface. Thus, molecule–surface distances from zero to several tens of nanometers (depending on interparticle distances) can be obtained, hence allowing both fluorescence and SERS detection. Finally, once optimized, plasmonic arrays produced by electron beam lithography can also be prepared through nanoimprint techniques, an inexpensive method to manufacture large quantities. Therefore, we report here on the application of such a nanorhomb array on a quartz wafer biochip platform for DNA detection by fluorescence and SERS readout. By doing so, fluorescence microscopy allows for a fast detection of any positive or negative binding event within several seconds. Moreover SERS provides detailed molecular fingerprint information of fluorescence reporter molecules. This work contributes to the development of the more flexible usage of different optical detection schemes on the same chip surface.
The work presented in the following reports on the design and application of biosensors based on periodically patterned plasmonic arrays, which can be read out by both fluorescence and Raman spectroscopy, thus utilizing the unique sensitivity of fluorescence spectroscopy and the molecular selectivity of Raman spectroscopy. Therefore, chip surfaces with gold as the plasmonic material and with clearly defined arrays in the range of 200 × 200 µm2 were fabricated. The number and position of the plasmonic arrays across the entire sensor chip can be adjusted to the particular research and application of interest. In Figure 1A, the SEM image of a section of the periodically patterned plasmonic array is depicted. Rhombic structures with interparticle distances of ~100 nm were fabricated on a quartz wafer. The size of the single rhomb-shaped gold nanoparticles of the plasmonic arrays used in this study was 50–240 nm along the short axis and 100–750 nm along the long axis. The shape and size of the nanoparticles of the plasmonic array define its optical properties.
Figure 1: Schematic illustration of gold nanorhombs as plasmonic substrate. (A) The SEM image shows the periodically patterned gold surface. (B) Due to the interaction of the incident light with a metallic nanoparticle, surface plasmons are generated on the metal dielectric interface yielding a strong electromagnetic field with an evanescent decay on the nanoparticle surface. The strong electromagnetic field enhancement is employed for the effective enhancement of the Raman cross section (SERS) and the fluorescence (SEF), as indicating by the arrows.
In order to illustrate potential applications of these plasmonic arrays for bioanalytics, the arrays were tested for DNA detection. Therefore, capture oligonucleotides were immobilized on the chemically modified quartz surface between the gold nanorhombs. The nonspecific interaction of the DNA strands with the gold surface, through the nitrogen atoms of the DNA bases, was prevented by the formation of an octanethiol SAM as a lipophilic protection layer. Dye-labeled target DNA was incubated on the chip surface and bound efficiently to the complementary capture sequences during the hybridization process. Figure 1B highlights the different readout methods, utilizing the properties of the periodically patterned plasmonic arrays. The excitation of localized surface plasmon resonances (LSPR) at the metal dielectric interface induces a strong electromagnetic field with evanescent decay on the metal surface. This strong field enhancement by the evanescent field can be employed for an effective enhancement of the weak Raman cross section (surface-enhanced Raman spectroscopy – SERS)  and also of the fluorescence signal (surface-enhanced fluorescence – SEF) . However, the signal enhancement in SERS and SEF is characterized by different dependencies on the distance between the analyte and metal surface. In order to establish rules for an analyte–metal-surface, distance dependent, signal enhancement, scanning probe microscopy (SPM)-based measurements in combination with an optical readout were performed by several research groups: Roth et al. applied distance dependent tip-enhanced Raman spectroscopic (TERS) measurements, where SERS is combined with the SPM technique AFM (atomic force microscopy). These distance dependent TERS studies revealed that the highest signal intensities can be found for the smallest distance between tip and surface and moreover that the enhancement decays on a length scale of approximately 10 nm . Furthermore, Anger et al. investigated the distance dependent enhancement of single-molecule fluorescence. The most efficient fluorescence enhancement was detected for distances in the range of 3–7 nm, whereas for shorter distances the molecular fluorescence was quenched . Since the plasmonic behavior of a SPM probe for tip-enhanced near-field optical microscopy is comparable with that of a single metallic nanoparticle, the usage of periodically ordered plasmonic arrays should allow the application of SERS readout for molecule–metal surface distances up to 10 nm and SEF for analyte–metal distances of around 5 nm (Figure 1B). For distances of more than 20 nm the molecule remains more or less unaffected by the strong electromagnetic field enhancement, so normal fluorescence should be detectable.
In order to test the simultaneous application of fluorescence readout and SERS measurements on one common biochip platform, a DNA detection scheme based on the usage of a well-known fluorescence dye label (cyanine dye Cy3.5) was performed. In doing so, complementary and noncomplementary (here: negative control) capture DNA was immobilized on the sensor surface. Furthermore, the biochip was treated with dye-labeled target DNA, which binds to its complementary sequence. In a first test, fluorescence spectroscopy as one of the standard methods in bioanalytics was performed for a fast and easy control of the biochemical binding process: In the complementary case a bright fluorescence signal was detected, whereas under the same conditions no fluorescence signal was found for the noncomplementary case (Figure 2A). In order to gain more detailed information, SERS was employed as a readout technique for the same biosensor. The detected mean value SERS spectra, shown in Figure 2B, are dominated by contributions of the Cy3.5 label (see therefore the reference spectrum in ). The detected background signal, which can be attributed among others factors to the fluorescence emission of the dye, was subtracted from all SERS spectra for better visibility. An intense SERS signal of the reporter molecule Cy3.5 was detected due to the double helix formation in the complementary case. By insertion of mismatches within the DNA strand, the binding efficiency of the dye labeled target DNA and moreover the SERS signal was decreased for the noncomplementary case (Figure 2C). Thus, the established biosensor allowed the distinction between a complementary and a noncomplementary binding of target DNA through both a fluorescence and SERS detection scheme. This will be useful for the flexible usage of the same biochip platform in applying different detection schemes.
Figure 2: Application of the same plasmonic array for fluorescence and SERS readout. (A) Here, the fluorescence signal is shown in the upper-left and lower-right, for the complementary and noncomplementary capture and dye-labeled target DNA sequences, respectively. A bright fluorescence signal was detected for the complementary case due to the effective formation of the DNA double helix. (B) Raman signature (background-corrected mean value spectrum) of the Cy3.5 label, which is attached to the target DNA. (C) As more dye-labeled DNA molecules are attached to the surface in the complementary case, due to the double helix formation, the Raman signal is more intense.
In order to achieve a maximum SERS enhancement, the excitation wavelength should lie within the plasmonic absorption. As shown in Figure 3A the optical transmission minimum at around 700 nm indicates the surface plasmon excitation along the short rhomb axis. Thus the Raman excitation wavelength of 633 nm is in resonance with the short wavelength tail of the plasmon band. However, the emitted Stokes Raman-scattered light of modes that are also in resonance with the surface plasmon will also be enhanced due to the plasmon resonance of the nanoantenna. This effect is described as the second part of the electromagnetic SERS mechanism [30,31]. Recently we  investigated this contribution of secondary emission enhancement to the overall SERS signal, utilizing the anisotropic character of gold nanorhomb arrays. Since the signal enhancement follows the plasmonic profile, fabrication strategies were developed for the vis and NIR spectral region. Here, the geometry of the gold nanorhombs was optimized by numerical calculations to efficiently improve the emission enhancement process. In Figure 3B a typical SERS spectrum is depicted for the complementary case concerning the capture and dye-labeled target DNA. The background-corrected fingerprint signature is dominated by contributions from the dye-label Cy3.5. In order to investigate the mismatch specificity of the binding process on the biochip surface, capture DNA was immobilized on the free quartz surface with the complementary sequence (NS150), one mismatch (NS151), three mismatches (NS153), and the noncomplementary sequence (N7), with respect to the Cy3.5-labeled target DNA. Figure 3C shows the Raman signal intensity of three prominent Raman modes, as determined by their peak areas. The mean values of the signal intensities are plotted for each of the tested capture DNA sequences. The largest signal intensities were found for the complementary case (NS150) due to the most specific interaction between the capture and target molecule. The Raman signal intensities for the mismatch (NS151, NS153) cases are lower than for the complementary (NS150) case, thus demonstrating the mismatch specificity of the used protocol. In addition, the signal intensity for the negative control (N7) is significantly lower than for the complementary case. Thus the established biochip is an appropriate tool for sequence specific SERS investigation and application to DNA analytics.
Figure 3: Mismatch-selective SERS investigation. (A) Transmission minimum at around 700 nm indicates the surface plasmon excitation along the short rhomb axis (inset: SEM image of periodically distributed nanorhombs). The excitation wavelength of 633 nm and the Raman interval matches the plasmonic profile. (B) The background-corrected Raman spectrum is dominated by contributions from the dye-label Cy3.5. The target DNA sequence is complementary to that of the capture DNA. (C) In order to illustrate the sequence-specific Raman intensity of three different Raman bands (marked in Fig. B), capture DNA with the complementary sequence (NS150), one mismatch (NS151), three mismatches (NS153), and the non-complementary sequence (N7) with respect to the Cy3.5-labeled target DNA were immobilized on the biochip surface. The strongest Raman signal intensity was detected for the complementary case, which indicates the efficient double helix formation.
Due to the strong electromagnetic field enhancement, the fluorescence intensity of chromophores can also be enhanced in close vicinity to the metallic nanoparticles (SEF) [32,33]. In order to verify the amount of fluorescence signal enhancement that is due to coupling with a strong electromagnetic field, various plasmonic arrays were used for this study. The SEM images are depicted in Figure 4A. As mentioned above, the plasmonic samples were arrays of gold nanorhombs mounted on a quartz wafer, with interparticle distances in the range of 100 nm. The fluorescent dye was bound to DNA strands on the free quartz surface. Binding to the gold layer was hindered by a lipophilic protection layer. Thus the detected fluorescence intensity was strongly correlated with the area of free quartz surface per unit cell (Figure 4B). The lower the density of gold per unit cell, the higher the fluorescence intensity should be. Furthermore, the fluorescence enhancement is locally confined to nanosized areas with strong electromagnetic field enhancement, which correspond to the edges of the short rhomb axis when using visible excitation wavelengths . The perimeter of the nanorhomb plays no prominent role in the electromagnetic field enhancement. Due to the large distances between the gold nanoparticles, the fluorescence intensity of molecules bound on the quartz surface remains mainly unaffected by the excitation of the LSPR. Therefore, the detected fluorescence intensity was normalized with respect to the free quartz surface area per unit cell of the various plasmonic arrays.
Figure 4: Various plasmonic arrays, which were used for a fluorescence comparison study. (A) SEM images of the used plasmonic arrays illustrate the nanoparticle size and the interparticle distance, which is in the range of 100 nm. (B) Estimation of the free quartz surface area per unit cell.
Capture DNA was immobilized on the free quartz wafer. The dye-labeled target DNA bound to its complementary capture sequence. Thus, the formation of the DNA double helix was indicated by the fluorescence signal of the Cy3.5 label. The absorption and emission spectra of the fluorophore Cy3.5 and moreover the plasmonic profiles of the used gold nanorhomb arrays are depicted in Figure 5A for comparison. Since the various plasmonic arrays are characterized by a different size of the individual gold nanorhombs (Figure 4A), the transmission minimum, indicating the excitation of the LSPR, shifts to higher wavelengths with increasing size of the gold nanorhombs. Thus the LSPR peak overlaps with the absorption and emission spectra differently, which may have an influence on the fluorescence intensity. The normalized fluorescence intensity (detected fluorescence/free quartz surface area per unit cell, illustrated in Figure 5B) of sample 2 is surprisingly higher than that for the other plasmonic samples, whereas sample 3 and 4 exhibit comparable signal intensities. The observed fluorescence enhancement with sample 2 opens the way towards systematic SEF investigations with tunable plasmonic arrays. Furthermore, these results provide insight into the fluorescence enhancement mechanism. Due to the spectral overlap of the plasmonic profile with the absorption spectrum of the dye, an enhanced excitation rate may be reached. Thus the fluorescence intensity is enhanced because the fluorophore is excited more often . This mechanism may be the explanation for the signal increase seen with sample 1 and 2 for fluorescence measurements of Cy3.5. A further contribution to SEF is described as an enhanced decay rate that improves the quantum yield of the fluorophore and decreases the lifetime, which should allow the fluorophore to undergo more excitation–de-excitation cycles before photobleaching occurs [26,32].
Figure 5: Observation of enhanced fluorescence intensity. (A) Absorption and emission spectrum of the dye-label Cy3.5, attached to a DNA strand, in comparison to the transmission spectra of various plasmonic arrays. The transmission minima (indicating the LSPR excitation) overlap with the absorption and emission spectra differently. (B) The detected fluorescence intensity is normalized with respect to the free quartz surface area per unit cell. The highest signal intensity was detected for sample 2, which may be attributed to a fluorescence enhancement mechanism.
In this paper, the application of a sensor platform employing fluorescence and SERS detection was introduced. Since the signal intensity is known to show a strong dependence on the distance between the molecules of interest and the metallic surface of the plasmonic active particle [27,28], an array of periodically patterned gold nanostructures mounted on a quartz wafer was preferred for these multimodal readout applications, due to the feasibility of binding molecules to the quartz layer, resulting in different distances to the metallic surface. In studying the example of a DNA detection scheme with a Cy3.5 dye label, fluorescence spectroscopy was applied, due to its fast detection time of several seconds, in order to detect the binding event of complementary DNA on the biochip surface. Additionally, SERS provides fingerprint information of the dye-label and the results illustrate the mismatch selectivity. By careful adjustment of the plasmonic behavior, the fluorescence intensity of the dye-label was significantly increased. As a result, the tuning of the optical behavior of plasmonic arrays allows studies of the fluorescence and SERS enhancement mechanism in future work. Finally, this study is a contribution towards the development of more flexible applications of the same biochip platform, through the performance of both fluorescence and SERS microscopy.
Fabrication process of periodically patterned gold nanorhomb arrays. The geometry of the plasmonic array was optimized for maximum signal enhancement by finite element method (FEM) simulations (COMSOL Multiphysics). Periodically patterned SERS arrays were fabricated by means of electron beam lithography and Argon ion beam etching. Quartz wafer was coated with 20 nm of gold by vacuum evaporation, followed by spin-coating of a 120 nm thick PMMA (polymethyl methacrylate) resist layer onto the metal film. The resist layer was exposed by a commercial e-beam writer (LION LV-1, Vistec Electron Beam GmbH) operating at 20 keV. After the development in organic solvents (60 s in MIBK:IPA = 1:1 solution), the unprotected gold layer was removed by Argon ion beam etching. Finally, the entire process was completed with oxygen plasma cleaning. The fabrication process was described in detail previously [21-23,34]. Based on the concept of the crossed exposure of two gratings of lines in the resist layer, regularly patterned gold surfaces were produced. The gold surfaces were characterized by means of SEM and optical far-field transmission measurements (Lambda-950 Perkin Elmer).
Sample preparation (DNA immobilization). The regularly patterned gold nanorhomb arrays were treated with oxygen plasma under gentle conditions (35 W, 30 s) before usage. To prevent nonspecific interactions of the DNA strands with the metallic surface through the DNA bases, the plasmonic arrays were incubated in a 10 mM ethanolic solution of octanethiol, providing a lipophilic protection layer (here: Self assembled monolayer (SAM)) on the gold surface . For the binding of the amino-modified capture DNA, the quartz surface was modified with 3-glycidyloxypropyl trimethoxysilane (GOPS) as described elsewhere . The capture DNA (complementary sequence NS150: amino-link-5'-TTT TTT CAG CAT GTG CTC CTT GAT TCT ATG-3'; one mismatch sequence NS151: amino-link-5'-TTT TTT CAG CAT GGG CTC CTT GAT TCT ATG-3'; three mismatch sequence NS153: amino-link-5'-TTT TTT CAG CAT TAT CTC CTT GAT TCT ATG-3'; negative control N7 5'-ACT GAC TGA CTG ACT GAC TGA CTG GGC GGC GAC CT-3'-amino-link) was prepared as a 1 µM solution in 5× phosphate buffered saline (PBS). To deposit small volumes (here: 4 nL) of the capture DNA solution, a Nano-Plotter NP 2.0 (GeSiM mbH, Großerkmannsdorf, Germany) was used. After the drops dried up, the complete immobilization of the capture DNA strand was ensured by an UV linking process  (5 min at 254 nm). Finally, the chips were thoroughly washed to remove all unbound capture DNA. Before the hybridization, the dye-labeled target DNA (50 nM Cy3.5-labeled sequence: Cy3.5-5'-CAT AGA ATC AAG GAG CAC ATG CTG AAA AAA-3') was suspended in 5× saline–sodium citrate (SSC) and 0.1% sodium dodecyl sulphate (SDS). Droplets of approximately 10 μL of the target DNA were added onto the chip and incubated for 1 h at 40 °C in a humidity chamber. Afterwards, the substrates were washed for 5 min each in 2× SSC and 0.1% SDS, 2× SSC and 0.2× SSC. Finally, the chips were dried under a stream of nitrogen.
Fluorescence measurements. Fluorescence images were recorded by means of an Axio Imager A1m microscope with an AxioCam MRc5 camera (Carl Zeiss Jena GmbH, Germany). The correct settings of excitation and emission wavelength for the samples were realized by the special filter set 77HE (Carl Zeiss Jena GmbH, Germany), which contains a through-hole bandpass filter with specific excitation wavelengths in the range of 483 nm, 564 nm and 642 nm. Excitation and emission spectra of the fluorescent dye Cy3.5 were measured with a Jasco FP-6200 spectrofluorometer (JASCO Germany).
SERS set-up. The Raman spectra were recorded with a micro-Raman setup (HR LabRam invers, Jobin-Yvon-Horiba). The spectrometer has an entrance slit of 100 µm, a focal length of 800 mm, and is equipped with a 300 line mm−1 grating. The 633 nm line of a He–Ne laser (Coherent) with a laser power of ~600 µW incident on the sample was used for excitation. The Raman scattered light was detected by a CCD camera operating at 220 K. A Leica PLFluoar ×100 objective (NA 0.75) was used for focusing the laser light onto the samples (focus size ~1 µm) and collecting the Raman signal.
Funding of research project "Jenaer Biochip Initiative (JBCI)" within the framework "Unternehmen Region – InnoProfile" and "Photonic Nanomaterials (PhoNa)" within the framework "Spitzenforschung und Innovation in den Neuen Ländern" from the Federal Ministery of Education and Research, Germany (BMBF) is gratefully acknowledged. K. W. gratefully acknowledges financial support by "Carl-Zeiss-Stiftung". The authors thank Jörg Petschulat and Thomas Pertsch for providing the transmission spectra. Further, D.C. thanks Keiko Munechika, Yeechi Chen and David Ginger for helpful discussions during the stay at Ginger Research Lab (University of Washington) in summer 2009.
© 2011 Cialla et al; licensee Beilstein-Institut.