International A-class catamaran
The A-Class Catamaran abbreviated to A-Cat, is a development class sailing catamaran for singlehanded racing. The class was founded during the 1960s and was part of the 4-tier IYRU approach to divide up the sports catamaran sailing scene into 4 separate groups; these A, B, C and D classes were governed by a small set of class rules to which each design had to comply. In the beginning it was just: Maximum hull length Maximum overall width Maximum sailareaAll boats designed and built to these specs would be grouped into one fleet and race each other for crossing the finish line first; the A-Class is the largest remaining of those 4 main classes. The B-Class splintered into a score of sub classes like the Hobie 16's, Formula 18's and other classes that contain far more and far stricter class rules; the C-Class developed into the high tech and vanguard boats that were used in the Little America's Cup. These require immense investments of money to race; as a result, this class is small but still maintains its status as the ultimate sailing catamaran designs.
The D class never got off the ground in earnest. The official organisation for the A-Class catamaran is the IACA; the A-Class rules were expanded over time to prevent the cost of these boats from rising too high and to ensure fairness in racing. The main A-Class rules are: Min overall boat weight: 75 kg / 165.3 lbs Max overall boat length: 5.49 m / 18.3 ft Max overall boat width: 2.30 m / 7.5 ft Max sail area incl. Mast: 13.94 m2 / 150.0 ft2 In handicap racing, the A-Class catamaran uses a Portsmouth Yardstick of 681 in the UK or a D-PN of 64.5 in the USA. The A-Class design has over time converged to a single sail rig using a lightweight carbon mast of about 9 meters length and using lightweight pentex or Kevlar sailcloth; the hulls and beams are made out of carbon fibre as well. This single sail rig allows these boats to excel when sailing upwind, their lightweight and time tested sailing techniques make these boats fast on reaches and downwind legs as well. They were unbeatable on the race course and only with the introduction of the asymmetic spinnaker on other catamarans have they lost this position a little bit.
In the decades since their foundation the A-Class has gathered a significant international following and it has class organisations in many countries around the globe. Their world championships attracts around 100 boats and sailors, it is a class that still contains a significant portion of homebuilders, although their numbers are decreasing with every year due to the skills required to make a competitive boat. However, nearly all A-Class sailors tinker with their boats; as it is a developmental class and the rules do allow so much variation, it is paramount that a top sailor keeps experimenting with new setups and tries to improve the design more. Because of this general character of the class, the A-Class is leading over other catamaran classes in terms of design development. Over time these other classes copy new findings for their own setups. Examples of such developments are: the carbon mast, the squaretop mainsail, the wave-piercer hull design and in general the use of exotic materials.
Apart from the list below of some of the commercial builders, the A-Class catamaran can be home-built: Bimare Aicher-Egner Technologie GmbH Marstrom Performance Catamarans Scheurer Design & Eng. Scheurer Bootswerft AG VectorWorks Sail Wingfox DNA Vision Nikita Exploder International A-Division Catamaran Association —National A-Catamaran Organisations: Australia Austria Belgium Brazil Denmark Germany Great Britain France Italy New Zealand Netherlands Poland Sweden Switzerland Spain United States of America List of multihulls
Human acetyl-coA cholesterol acyltransferase gene produces a chimeric mRNA through the interchromosomal processing of two discontinuous RNAs transcribed from chromosomes 1 and 7. This chimeric mRNA uses AUG as a translation initiation codon to produce the normal 50-kDa ACAT1 protein but used an alternative translation initiation codon, GGC, to produce the novel enzymatically active 56-kDa isoform. Mutagenesis and mass spectrometry identified the alternative initiation codon as the start codon for the novel 56-kDa protein and its location was mapped to a region located upstream of the AUG initiation codon. Three stem loop structures have been predicted to surround the GCC initiation codon and are known as SL1 to SL3. Mutations that disrupted these stem-loop structures showed that SL1 and SL2 as required for translation initiation from the GGC codon but SL3 has no effect on translation efficiency. Translation initiation from the GGC codon was shown to be is mediated by an internal ribosome entry site which requires SL1 located upstream of the IRES and SL2 located downstream.
This study showed that SL3 influences the choice of downstream AUG translation initiation codons that will produce the normal 50-KDa human ACAT1 protein. Page for ACAT1 at Rfam
Risk management is the identification and prioritization of risks followed by coordinated and economical application of resources to minimize and control the probability or impact of unfortunate events or to maximize the realization of opportunities. Risks can come from various sources including uncertainty in financial markets, threats from project failures, legal liabilities, credit risk, natural causes and disasters, deliberate attack from an adversary, or events of uncertain or unpredictable root-cause. There are two types of events i.e. negative events can be classified as risks while positive events are classified as opportunities. Several risk management standards have been developed including the Project Management Institute, the National Institute of Standards and Technology, actuarial societies, ISO standards. Methods and goals vary according to whether the risk management method is in the context of project management, engineering, industrial processes, financial portfolios, actuarial assessments, or public health and safety.
Strategies to manage threats include avoiding the threat, reducing the negative effect or probability of the threat, transferring all or part of the threat to another party, retaining some or all of the potential or actual consequences of a particular threat, the opposites for opportunities. Certain aspects of many of the risk management standards have come under criticism for having no measurable improvement on risk. For example, one study found. A used vocabulary for risk management is defined by ISO Guide 73:2009, "Risk management. Vocabulary."In ideal risk management, a prioritization process is followed whereby the risks with the greatest loss and the greatest probability of occurring are handled first, risks with lower probability of occurrence and lower loss are handled in descending order. In practice the process of assessing overall risk can be difficult, balancing resources used to mitigate between risks with a high probability of occurrence but lower loss versus a risk with high loss but lower probability of occurrence can be mishandled.
Intangible risk management identifies a new type of a risk that has a 100% probability of occurring but is ignored by the organization due to a lack of identification ability. For example, when deficient knowledge is applied to a situation, a knowledge risk materializes. Relationship risk appears. Process-engagement risk may be an issue; these risks directly reduce the productivity of knowledge workers, decrease cost-effectiveness, service, reputation, brand value, earnings quality. Intangible risk management allows risk management to create immediate value from the identification and reduction of risks that reduce productivity. Risk management faces difficulties in allocating resources; this is the idea of opportunity cost. Resources spent on risk management could have been spent on more profitable activities. Again, ideal risk management minimizes spending and minimizes the negative effects of risks. According to the definition to the risk, the risk is the possibility that an event will occur and adversely affect the achievement of an objective.
Therefore, risk itself has the uncertainty. Risk management such as COSO ERM, can help; each company may have different internal control components. For example, the framework for ERM components includes Internal Environment, Objective Setting, Event Identification, Risk Assessment, Risk Response, Control Activities and Communication, Monitoring. For the most part, these methods consist of the following elements, more or less, in the following order. Identify, characterize threats assess the vulnerability of critical assets to specific threats determine the risk identify ways to reduce those risks prioritize risk reduction measures The International Organization for Standardization identifies the following principles of risk management:Risk management should: create value – resources expended to mitigate risk should be less than the consequence of inaction be an integral part of organizational processes be part of decision making process explicitly address uncertainty and assumptions be a systematic and structured process be based on the best available information be tailorable take human factors into account be transparent and inclusive be dynamic and responsive to change be capable of continual improvement and enhancement be continually or periodically re-assessed According to the standard ISO 31000 "Risk management – Principles and guidelines on implementation," the process of risk management consists of several steps as follows: This involves: the social scope of risk management the identity and objectives of stakeholders the basis upon which risks will be evaluated, constraints.
Defining a framework for the activity and an agenda for identification developing an analysis of risks involved in the process mitigation or solution of risks using available technological and organizational resources After establishing the context, the next step in the
Thiolases known as acetyl-coenzyme A acetyltransferases, are enzymes which convert two units of acetyl-CoA to acetoacetyl CoA in the mevalonate pathway. Thiolases are ubiquitous enzymes that have key roles in many vital biochemical pathways, including the beta oxidation pathway of fatty acid degradation and various biosynthetic pathways. Members of the thiolase family can be divided into two broad categories: degradative thiolases and biosynthetic thiolases; these two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase. 3-ketoacyl-CoA thiolase has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as beta-hydroxybutyric acid synthesis or steroid biogenesis; the formation of a carbon–carbon bond is a key step in the biosynthetic pathways by which fatty acids and polyketide are made.
The thiolase superfamily enzymes catalyse the carbon–carbon-bond formation via a thioester-dependent Claisen condensation reaction mechanism. Thiolases are a family of evolutionarily related enzymes. Two different types of thiolase are found both in eukaryotes and in prokaryotes: acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase. 3-ketoacyl-CoA thiolase has a broad chain-length specificity for its substrates and is involved in degradative pathways such as fatty acid beta-oxidation. Acetoacetyl-CoA thiolase is specific for the thiolysis of acetoacetyl-CoA and involved in biosynthetic pathways such as poly beta-hydroxybutyrate synthesis or steroid biogenesis. In eukaryotes, there are two forms of 3-ketoacyl-CoA thiolase: one located in the mitochondrion and the other in peroxisomes. There are two conserved cysteine residues important for thiolase activity; the first located in the N-terminal section of the enzymes is involved in the formation of an acyl-enzyme intermediate. Mammalian nonspecific lipid-transfer protein is a protein which seems to exist in two different forms: a 14 Kd protein and a larger 58 Kd protein.
The former is involved in lipid transport. The C-terminal part of SCP-x is identical to SCP-2 while the N-terminal portion is evolutionary related to thiolases. Thioesters are more reactive than oxygen esters and are common intermediates in fatty-acid metabolism; these thioesters are made by conjugating the fatty acid with the free SH group of the pantetheine moiety of either coenzyme A or acyl carrier protein. All thiolases, whether they are biosynthetic or degradative in vivo, preferentially catalyze the degradation of 3-ketoacyl-CoA to form acetyl-CoA and a shortened acyl-CoA species, but are capable of catalyzing the reverse Claisen condensation reaction, it is well established from studies on the biosynthetic thiolase from Z. ramigera that the thiolase reaction occurs in two steps and follows ping-pong kinetics. In the first step of both the degradative and biosynthetic reactions, the nucleophilic Cys89 attacks the acyl-CoA substrate,leading to the formation of a covalent acyl-CoA intermediate.
In the second step, the addition of CoA or acetyl-CoA to the acyl–enzyme intermediate triggers the release of the product from the enzyme. Each of the tetrahedral reaction intermediates that occur during transfer of an acetyl group to and from the nucleophilic cysteine have been observed in X-ray crystal structures of biosynthetic thiolase from A. fumigatus. Most enzymes of the thiolase super family are dimers. However, monomers have not been observed. Tetrameters are observed only in the thiolase subfamily and, in these cases, the dimers have dimerized to become tetramers; the crystal structure of the tetrameric biosynthetic thiolase from Zoogloea ramigera has been determined at 2.0 Å resolution. The structure contains a striking and novel ‘cage-like’ tetramerization motif, which allows for some hinge motion of the two tight dimers with respect to each other; the enzyme tetramer is acetylated at Cys89 and has a CoA molecule bound in each of its active-site pockets. In eukaryotic cells in mammalian cells, thiolases exhibit diversity in intracellular localization related to their metabolic functions as well as in substrate specificity.
For example, they contribute to fatty-acid β-oxidation in peroxisomes and mitochondria, ketone body metabolism in mitochondria, the early steps of mevalonate pathway in peroxisomes and cytoplasm. In addition to biochemical investigations, analyses of genetic disorders have made clear the basis of their functions. Genetic studies have started to disclose the physiological functions of thiolases in the yeast Saccharomyces cerevisiae. Thiolase is of central importance in key enzymatic pathways such as fatty-acid and polyketide synthesis; the detailed understanding of its structural biology is of great medical relevance, for example, for a better understanding of the diseases caused by genetic deficiencies of these enzymes and for the development of new antibiotics. Harnessing the complicated catalytic versatility of the polyketide synthases for the synthesis of biologically and medically relevant natural products is an important future perspective of the studies of the enzy
Stephen William Hawking was an English theoretical physicist and author, director of research at the Centre for Theoretical Cosmology at the University of Cambridge at the time of his death. He was the Lucasian Professor of Mathematics at the University of Cambridge between 1979 and 2009, his scientific works included a collaboration with Roger Penrose on gravitational singularity theorems in the framework of general relativity and the theoretical prediction that black holes emit radiation called Hawking radiation. Hawking was the first to set out a theory of cosmology explained by a union of the general theory of relativity and quantum mechanics, he was a vigorous supporter of the many-worlds interpretation of quantum mechanics. Hawking achieved commercial success with several works of popular science in which he discusses his own theories and cosmology in general, his book A Brief History of Time appeared on the British Sunday Times best-seller list for a record-breaking 237 weeks. Hawking was a Fellow of the Royal Society, a lifetime member of the Pontifical Academy of Sciences, a recipient of the Presidential Medal of Freedom, the highest civilian award in the United States.
In 2002, Hawking was ranked number 25 in the BBC's poll of the 100 Greatest Britons. In 1963, Hawking was diagnosed with an early-onset slow-progressing form of motor neurone disease that paralysed him over the decades. After the loss of his speech, he was still able to communicate through a speech-generating device through use of a hand-held switch, by using a single cheek muscle, he died on 14 March 2018 after living with the disease for more than 50 years. Hawking was born on 8 January 1942 in Oxford to Isobel Eileen Hawking. Hawking's mother was born into a family of doctors in Scotland, his wealthy paternal great-grandfather, from Yorkshire, over-extended himself buying farm land and went bankrupt in the great agricultural depression during the early 20th century. His paternal great-grandmother saved the family from financial ruin by opening a school in their home. Despite their families' financial constraints, both parents attended the University of Oxford, where Frank read medicine and Isobel read Philosophy and Economics.
Isobel worked as a secretary for a medical research institute, Frank was a medical researcher. Hawking had two younger sisters and Mary, an adopted brother, Edward Frank David. In 1950, when Hawking's father became head of the division of parasitology at the National Institute for Medical Research, the family moved to St Albans, Hertfordshire. In St Albans, the family was considered intelligent and somewhat eccentric, they lived a frugal existence in a large and poorly maintained house and travelled in a converted London taxicab. During one of Hawking's father's frequent absences working in Africa, the rest of the family spent four months in Majorca visiting his mother's friend Beryl and her husband, the poet Robert Graves. Hawking began his schooling at the Byron House School in London, he blamed its "progressive methods" for his failure to learn to read while at the school. In St Albans, the eight-year-old Hawking attended St Albans High School for Girls for a few months. At that time, younger boys could attend one of the houses.
Hawking attended two independent schools, first Radlett School and from September 1952, St Albans School, after passing the eleven-plus a year early. The family placed a high value on education. Hawking's father wanted his son to attend the well-regarded Westminster School, but the 13-year-old Hawking was ill on the day of the scholarship examination, his family could not afford the school fees without the financial aid of a scholarship, so Hawking remained at St Albans. A positive consequence was that Hawking remained close to a group of friends with whom he enjoyed board games, the manufacture of fireworks, model aeroplanes and boats, long discussions about Christianity and extrasensory perception. From 1958 on, with the help of the mathematics teacher Dikran Tahta, they built a computer from clock parts, an old telephone switchboard and other recycled components. Although known at school as "Einstein", Hawking was not successful academically. With time, he began to show considerable aptitude for scientific subjects and, inspired by Tahta, decided to read mathematics at university.
Hawking's father advised him to study medicine, concerned that there were few jobs for mathematics graduates. He wanted his son to attend University College, his own alma mater; as it was not possible to read mathematics there at the time, Hawking decided to study physics and chemistry. Despite his headmaster's advice to wait until the next year, Hawking was awarded a scholarship after taking the examinations in March 1959. Hawking began his university education at University College, Oxford, in October 1959 at the age of 17. For the first 18 months, he was bored and lonely – he found the academic work "ridiculously easy", his physics tutor, Robert Berman said, "It was only necessary for him to know that something could be done, he could do it without looking to see how other people did it." A change occurred during his second and third year when, according to Berman, Hawking made more of an effort "to be one of the boys". He developed into a popular and witty college member, interested in classical music and science fiction.
Part of the transformation resulted from his decision to join the college boat club, the Univ