<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is System and can you explain it in depth? [/INST] A system is a group of interacting or interrelated elements that act according to a set of rules to form a unified whole. A system, surrounded and influenced by its environment, is described by its boundaries, structure and purpose and expressed in its functioning. Systems are the subjects of study of systems theory and other systems sciences.
Systems have several common properties and characteristics, including structure, function(s), behavior and interconnectivity.

Etymology
The term system comes from the Latin word systēma, in turn from Greek σύστημα systēma: "whole concept made of several parts or members, system", literary "composition".

History
According to Marshall McLuhan,

"System" means "something to look at". You must have a very high visual gradient to have systematization. But in philosophy, prior to Descartes, there was no "system". Plato had no "system". Aristotle had no "system".

In the 19th century the French physicist Nicolas Léonard Sadi Carnot, who studied thermodynamics, pioneered the development of the concept of a system in the natural sciences. In 1824 he studied the system which he called the working substance (typically a body of water vapor) in steam engines, in regards to the systems ability to do work when heat is applied to it. The working substance could be put in contact with either a boiler, a cold reservoir (a stream of cold water), or a piston (on which the working body could do work by pushing on it). In 1850, the German physicist Rudolf Clausius generalized this picture to include the concept of the surroundings and began to use the term working body when referring to the system.
The biologist Ludwig von Bertalanffy became one of the pioneers of the general systems theory. In 1945 he introduced models, principles, and laws that apply to generalized systems or their subclasses, irrespective of their particular kind, the nature of their component elements, and the relation or forces between them.Norbert Wiener and Ross Ashby, who pioneered the use of mathematics to study systems, carried out significant development in the concept of a system.In the 1980s John Henry Holland, Murray Gell-Mann and others coined the term complex adaptive system at the interdisciplinary Santa Fe Institute.

Concepts
Environment and boundaries
Systems theory views the world as a complex system of interconnected parts. One scopes a system by defining its boundary; this means choosing which entities are inside the system and which are outside—part of the environment. One can make simplified representations (models) of the system in order to understand it and to predict or impact its future behavior. These models may define the structure and behavior of the system.Natural and human-made systems
There are natural and human-made (designed) systems. Natural systems may not have an apparent objective but their behavior can be interpreted as purposeful by an observer. Human-made systems are made with various purposes that are achieved by some action performed by or with the system. The parts of a system must be related; they must be "designed to work as a coherent entity" — otherwise they would be two or more distinct systems.
Theoretical framework
Most systems are open systems, exchanging matter and energy with their respective surroundings; like a car, a coffeemaker, or Earth. A closed system exchanges energy, but not matter, with its environment; like a computer or the project Biosphere 2. An isolated system exchanges neither matter nor energy with its environment. A theoretical example of such system is the Universe.Process and transformation process
An open system can also be viewed as a bounded transformation process, that is, a black box that is a process or collection of processes that transform inputs into outputs. Inputs are consumed; outputs are produced. The concept of input and output here is very broad. For example, an output of a passenger ship is the movement of people from departure to destination.System model
A system comprises multiple views. Man-made systems may have such views as concept, analysis, design, implementation, deployment, structure, behavior, input data, and output data views. A system model is required to describe and represent all these views.Systems architecture
A systems architecture, using one single integrated model for the description of multiple views, is a kind of system model.

Subsystem
A subsystem is a set of elements, which is a system itself, and a component of a larger system. The IBM Mainframe Job Entry Subsystem family (JES1, JES2, JES3, and their HASP/ASP predecessors) are examples. The main elements they have in common are the components that handle input, scheduling, spooling and output; they also have the ability to interact with local and remote operators.
A subsystem description is a system object that contains information defining the characteristics of an operating environment controlled by the system. The Data tests are performed to verify the correctness of the individual subsystem configuration data (e.g. MA Length, Static Speed Profile, …) and they are related to a single subsystem in order to test its Specific Application (SA).

Analysis
There are many kinds of systems that can be analyzed both quantitatively and qualitatively. For example, in an analysis of urban systems dynamics, A .W. Steiss defined five intersecting systems, including the physical subsystem and behavioral system. For sociological models influenced by systems theory, Kenneth D. Bailey defined systems in terms of conceptual, concrete, and abstract systems, either isolated, closed, or open. Walter F. Buckley defined systems in sociology in terms of mechanical, organic, and process models. Bela H. Banathy cautioned that for any inquiry into a system understanding its kind is crucial, and defined "natural" and "designed", i. e. artificial, systems.
It is important not to confuse these abstract definitions. For example, natural systems include subatomic systems, living systems, the Solar System, galaxies, and the Universe, while artificial systems include man-made physical structures, hybrids of natural and artificial systems, and conceptual knowledge. The human elements of organization and functions are emphasized with their relevant abstract systems and representations.
Artificial systems inherently have a major defect: they must be premised on one or more fundamental assumptions upon which additional knowledge is built. This is in strict alignment to the Gödels incompleteness theorems. The Artificial system can be defined as a "consistent formalized system which contains elementary arithmetic". These fundamental assumptions are not inherently deleterious, but they must by definition be assumed as true, and if they are actually false then the system is not as structurally integral as is assumed (i.e. it is evident that if the initial expession is false, then the Artificial system is not a "consistent formalized system"). For example, in geometry this is very evident in the postulation of theorems and extrapolation of proofs from them.
George J. Klir maintained that no "classification is complete and perfect for all purposes", and defined systems as abstract, real, and conceptual physical systems, bounded and unbounded systems, discrete to continuous, pulse to hybrid systems, etc. The interactions between systems and their environments are categorized as relatively closed and open systems. It seems most unlikely that an absolutely closed system can exist or, if it did, that it could be known by man. Important distinctions have also been made between hard systems – technical in nature and amenable to methods such as systems engineering, operations research, and quantitative systems analysis – and soft systems that involve people and organisations, commonly associated with concepts developed by Peter Checkland and Brian Wilson through Soft Systems Methodology (SSM) involving methods such as action research and emphasis of participatory designs. Where hard systems might be identified as more "scientific", the distinction between them is often elusive.

Cultural system
A cultural system may be defined as the interaction of different elements of culture. While a cultural system is quite different from a social system, sometimes both together are referred to as a "sociocultural system". A major concern of the social sciences is the problem of order.

Economic system
An economic system is a mechanism (social institution) which deals with the production, distribution and consumption of goods and services in a particular society. The economic system is composed of people, institutions and their relationships to resources, such as the convention of property. It addresses the problems of economics, like the allocation and scarcity of resources.
The international sphere of interacting states is described and analysed in systems terms by several international relations scholars, most notably in the neorealist school. This systems mode of international analysis has however been challenged by other schools of international relations thought, most notably the constructivist school, which argues that an over-large focus on systems and structures can obscure the role of individual agency in social interactions. Systems-based models of international relations also underlies the vision of the international sphere held by the liberal institutionalist school of thought, which places more emphasis on systems generated by rules and interaction governance, particularly economic governance.

Applications
Systems modeling is generally a basic principle in engineering and in social sciences. The system is the representation of the entities under concern. Hence inclusion to or exclusion from system context is dependent on the intention of the modeler.
No model of a system will include all features of the real system of concern, and no model of a system must include all entities belonging to a real system of concern.

Information and computer science
In computer science and information science, system is a hardware system, software system, or combination, which has components as its structure and observable inter-process communications as its behavior. Again, an example will illustrate: There are systems of counting, as with Roman numerals, and various systems for filing papers, or catalogues, and various library systems, of which the Dewey Decimal Classification is an example. This still fits with the definition of components which are connected together (in this case to facilitate the flow of information).
System can also refer to a framework, aka platform, be it software or hardware, designed to allow software programs to run. A flaw in a component or system can cause the component itself or an entire system to fail to perform its required function, e.g., an incorrect statement or data definition

Engineering and physics
In engineering and physics, a physical system is the portion of the universe that is being studied (of which a thermodynamic system is one major example). Engineering also has the concept of a system referring to all of the parts and interactions between parts of a complex project. Systems engineering is the branch of engineering that studies how this type of system should be planned, designed, implemented, built, and maintained. Expected result is the behavior predicted by the specification, or another source, of the component or system under specified conditions.

Sociology, cognitive science and management research
Social and cognitive sciences recognize systems in human person models and in human societies. They include human brain functions and mental processes as well as normative ethics systems and social/cultural behavioral patterns.
In management science, operations research and organizational development (OD), human organizations are viewed as systems (conceptual systems) of interacting components such as subsystems or system aggregates, which are carriers of numerous complex business processes (organizational behaviors) and organizational structures. Organizational development theorist Peter Senge developed the notion of organizations as systems in his book The Fifth Discipline.
Organizational theorists such as Margaret Wheatley have also described the workings of organizational systems in new metaphoric contexts, such as quantum physics, chaos theory, and the self-organization of systems.

Pure logic
There is also such a thing as a logical system. The most obvious example is the calculus developed simultaneously by Leibniz and Isaac Newton </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hyperandrogenism and can you explain it in depth? [/INST] Hyperandrogenism is a medical condition characterized by high levels of androgens. It is more common in women than men. Symptoms of hyperandrogenism may include acne, seborrhea (inflamed skin), hair loss on the scalp, increased body or facial hair, and infrequent or absent menstruation. Complications may include high blood cholesterol and diabetes. It occurs in approximately 5% of women of reproductive age.Polycystic ovary syndrome accounts for about 70% of hyperandrogenism cases. Other causes include adrenal hyperplasia, hirsutism, insulin resistance, hyperprolactinemia, Cushings disease, certain types of cancers, and certain medications. Diagnosis often involves blood tests for testosterone, 17-hydroxyprogesterone, and prolactin, as well as a pelvic ultrasound.Treatment depends on the underlying cause. Symptoms of hyperandrogenism can be treated with birth control pills or antiandrogens, such as cyproterone acetate or spironolactone. Other palliative measures may include hair removal techniques.The earliest known description of the condition is attributed to Hippocrates.In 2011, the International Association of Athletics Federations (now World Athletics) and IOC (International Olympic Committee)  released statements restricting the eligibility of female athletes with high testosterone, whether through hyperandrogenism or as a result of a difference in sex development (DSD). These regulations were referred to by both bodies as hyperandrogenism regulations and have led to athletes with DSDs being described as having hyperandrogenism. They were revised in 2019 to focus more specifically on DSDs.

Signs and symptoms
Hyperandrogenism affects 5–10% of women of reproductive age. Hyperandrogenism can affect both men and women but is more noticeable in women since elevated levels of androgens in women may facilitate virilization. Because hyperandrogenism is characterized by elevated male sex hormone levels, symptoms of hyperandrogenism in men are often negligible. Hyperandrogenism in women is typically diagnosed in late adolescence with a medical evaluation. The medical evaluation usually consists of a pelvic exam, observation of external symptoms, and a blood test measuring androgen levels. Symptoms may include the following:

Women
Hyperandrogenism, especially high levels of testosterone, can cause serious adverse effects if left untreated. High testosterone levels are associated with other health conditions such as obesity, hypertension, amenorrhea (cessation of menstrual cycles), and ovulatory dysfunction, which can lead to infertility. Prominent signs of hyperandrogenism are hirsutism (unwanted growth of hair, especially in the abdominal region and on the back), adult acne, deepening of the voice, and alopecia (balding).Hyperandrogenism has also been observed to increase insulin tolerance, which can lead to type two diabetes and dyslipidemia, such as high cholesterol. These effects may have psychological impacts, sometimes leading to social anxiety and depression, especially in adolescent girls and young women. Paired with obesity and hirsutism, it can cause the individual to have low self-esteem.

Men
Administration of high-dose testosterone in men over a course of weeks can cause an increase in aggression and hypomanic symptoms, though these were see in only a minority of subjects. Acute high-dose anabolic-androgenic steroid administration in males attenuates endogenous sex hormone production and affects the thyroid hormone axis. Effects on mood and aggression observed during high-dose anabolic-androgenic steroid administration may occur secondarily to hormonal changes. Many of the same signs and symptoms that are seen in women, such as alopecia and acne, may also be found in men. Enlargement of the prostate may also occur.

Causes
While hyperandrogenism in women can be caused by external factors, it can also appear spontaneously.

Polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by an excess of androgens produced by the ovaries. It is estimated that approximately 90% of women with PCOS demonstrate hypersecretion of these hormones. The cause of this condition is unknown. Speculations include genetic predisposition; however, the gene or genes responsible for this remain unidentified. The condition may have a hereditary basis. Other possible causes include elevated insulin production. Most cases of PCOS involve insulin resistance. It is thought that adipose tissue dysfunction plays a role in the insulin resistance seen in PCOS. Insulin can induce excess testosterone secretion from the ovaries. A complication associated with polycystic ovary syndrome is high cholesterol, which is treated with statins. In a meta-analysis, atorvastatin was shown to decrease androgen concentrations in people with hyperandrogenism.Elevated insulin leads to lower production of sex hormone binding globulin (SHBG), a regulatory glycoprotein that suppresses the function of androgens. High blood levels of insulin also work in conjunction with ovarian sensitivity to insulin to cause hyperandrogenemia, the primary symptom of PCOS. Obese individuals may be more biologically inclined to PCOS due to markedly higher insulin. This hormonal imbalance can lead to chronic anovulation, in which the ovaries fail to release mature eggs. These cases of ovulatory dysfunction are linked to infertility and menstrual disturbances. A post hoc analysis from a randomized, placebo-controlled, multi-centre study carried out at 11 secondary care centres, as well as a longitudinal single-centre study on pregnant women in Norway, also determined that metformin had no effect on maternal androgens in pregnancies occurring in the setting of PCOS.One systemic review suggested that polymorphisms in the vitamin D receptor gene are associated with the prognosis of polycystic ovary syndrome, though this is based on small sample sizes and is debated. Studies have shown benefits for vitamin D supplementation in women with vitamin D deficiency and PCOS.Hyperinsulinemia can increase the production of androgens in the ovaries. One context in which this occurs is HAIR-AN syndrome, a rare subtype of PCOS.

Hyperthecosis and hyperinsulinemia
Hyperthecosis occurs when the cells of the ovarian stroma transition from interstitial cells, located between other cells, into luteinized theca cells. Theca cells are located in the ovarian follicles and become luteinized when the ovarian follicle bursts and a new corpus luteum is formed. The dispersal of luteinized theca cells throughout the ovarian stroma — in contrast to their distribution in PCOS, in which luteinized theca cells occur around cystic follicles only — causes women with hyperthecosis to have higher testosterone levels and virilization) than women with PCOS. Elevated insulin is also characteristic of hyperthecosis. Hyperthecosis most commonly develops in postmenopausal women and is linked to acne, hirsutism, growth of the clitoris, baldness, and voice deepening.Obesity can play a role in insulin resistance. It makes thecal cells more responsive to luteinizing hormone. Therefore, obesity increases ovarian androgen production. Additionally, obesity elevates inflammatory adipokines which leads to not only adipogenesis, but also heightened insulin resistance.

Cushing’s syndrome
Cushings syndrome develops as a result of long-term exposure to the hormone cortisol. Cushings syndrome can either be exogenous or endogenous, depending on whether it is caused by an external or internal source, respectively. The intake of glucocorticoids, a type of corticosteroid, is a common cause for the development of exogenous Cushings syndrome. Endogenous Cushings syndrome can occur when the body produces excess cortisol. This occurs when the hypothalamus of the brain signals to the pituitary gland with excess corticotropin-releasing hormone, which in turn secretes adrenocorticotropin hormone (ACTH). ACTH then causes the adrenal glands to release cortisol into the blood. Signs of Cushings syndrome include muscle weakness, easy bruising, weight gain, male-pattern hair growth (hirsutism), coloured stretch marks, and an excessively reddish complexion in the face. Cushings syndrome can cause androgen excess and hence the signs and symptoms of hyperandrogenism.

Congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders that cause a lack of an enzyme necessary for the production of cortisol and/or aldosterone, steroid hormones produced by the adrenal cortex. Most cases of CAH are due to 21-hydroxylase deficiencies. The heightened androgen levels seen in congenital adrenal hyperplasia affect the hypothalamic–pituitary–gonadal axis. Heightened androgen levels can also affect the ovaries, which can lead to infertility as well as chronic anovulation.Since CAH consists of multiple disorders, the signs, symptoms and severity of hyperandrogenism may stem from a variety of specific mutations. Genotyping is therefore critical to verify diagnoses and to establish prognostic factors for individuals. Genotyping is also crucial for people seeking to use genetic counselling as an aid to family planning.In women, CAH causes ambiguous genitals at birth and excessive pubic hair, enlargement of the clitoris, and hirsutism in adolescence. Although CAH causes rapid growth in childhood, adult women with CAH are shorter than average due to early puberty and closure of the growth plates in the long bones. Symptoms in males include early showings of pubic hair, enlargement of the penis, and rapid musculoskeletal growth.

Tumors
Adrenocortical carcinoma and tumors
Adrenocortical carcinoma occurs rarely; the average incidence rate is estimated to be 1–2 cases per million annually.  The disease involves the formation of cancerous cells within the cortex of one or both of the adrenal glands. Although these tumors are identified in fewer than two percent of patients diagnosed with hyperandrogenism, the possibility must be considered within this population. In one study, more than half of tumor-affected patients had elevated levels of the androgens androstenedione, dehydroepiandrosterone sulfate, and testosterone. The elevation of androgens caused by adrenocortical carcinomas often causes patients to develop Cushings syndrome, primary aldosteronism, and hyperandrogenism. The molecular basis of the disease has yet to be elucidated.

Adenoma of the adrenal gland
Adrenal adenomas are benign tumors of the adrenal gland. In most cases, the tumors display no symptoms and require no treatment. In rare cases, however, some adrenal adenomas may become activated. When activated, the adenoma begins to produce hormones in much larger quantities than what the adrenal glands would normally produce, leading to health complications including primary aldosteronism and hyperandrogenism.

Arrhenoblastoma
Arrhenoblastoma is an uncommon tumor of the ovary.  It is composed of sterol cells, Leydig cells, or some combination of the two. The tumor can produce male or female hormones and may cause masculinization. In a prepubescent child, a tumor may cause precocious puberty. Malignant arrhenoblastoma accounts for 30% of cases of arrhenoblastoma, the other 70% being largely benign and curable with surgery.

Hilar cell tumor
A hilar cell tumor is an androgen-producing ovarian tumor that is most commonly found in older women and often leads to the development of male sex characteristics. The tumor tends to occur around the region of the ovary where the blood vessels enter the organ, known as the hilum. This type of tumor tends to be small in size and in most cases can be entirely removed and its symptoms reversed through surgery.

Krukenberg tumor
A Krukenberg tumor is a quickly developing malignant tumor found in one or both ovaries. In most cases, the tumor primarily originates from tissues in the stomach, pancreas, gallbladder, colon, or breast. It colonized the ovary by spreading through the peritoneal cavity. These tumors cause virilization. Increased androgen production due to elevations in human chorionic gonadotropin is hypothesized as the main cause of hyperandrogenism in people with Krukenberg tumors.

Menopause
The end of ovulation and the beginning of menopause can result in hyperandrogenism. During this transition, the body stops releasing estrogen at a faster rate than it stops releasing androgens. In some cases, the difference between the lower estrogen levels and higher androgen levels can produce hyperandrogenism. A decrease in sex hormone levels while the free androgen index increases can also contribute to this process.

Drugs
Many drugs can provoke symptoms of hyperandrogenism. These symptoms include, but are not limited to hirsutism, acne, dermatitis, androgenic alopecia, irregularities in menstruation, clitoral hypertrophy, and the deepening of the voice. Drugs most frequently implicated in hyperandrogenism include anabolic steroids, synthetic progestins, and antiepileptics; however, many other drugs may also cause hyperandrogenism. This can happen through one of five mechanisms: the direct introduction of androgens to the body, the binding of the drug to androgen receptors (as is the case with anabolic-androgenic steroids), a reduction of sex hormone-binding globulin plasma concentration that leads to an increase in free testosterone, interference with the hypothalamic–pituitary–ovarian (HPO) axis, or an increase in the release of adrenal androgens. Certain drugs cause hyperandrogenism through mechanisms that remain unclear. For example, the molecular basis by which valproate induces hyperandrogenism and polycystic ovary syndrome has yet to be determined. However, one study showed that women taking valproic acid had higher testosterone levels and incidences of hyperandrogenism compared to women who were not taking valproic acid.

Heredity
Hyperandrogenism can appear as a symptom of many different genetic and medical conditions. Some of the conditions with hyperandrogenic symptoms, including PCOS, may sometimes be hereditary. Additionally, it is thought that epigenetics may contribute to the pathogenesis of polycystic ovary syndrome.One potential cause of PCOS is maternal hyperandrogenism, whereby hormonal irregularities in the mother can affect the development of the child during gestation, resulting in the passing of polycystic ovary syndrome from mother to child. However, no androgen elevations in were found in the umbilical cord blood of children born to mothers with PCOS.

Diagnosis
Diagnosing hyperandrogenism can be complex due to the wide variety and severity of signs and symptoms that may present. It is most often diagnosed by checking for signs of hirsutism according to a standardized method that scores the range of excess hair growth.Girls may show symptoms of hyperandrogenism early in life, but physicians become more concerned when the patient is in her late teens or older.Checking medical history and a physical examination of symptoms are used for an initial diagnosis. Patient history assessed includes age at thelarche, adrenarche, and menarche; patterns of menstruation; obesity; reproductive history; and the start and advancement of hyperandrogenism symptoms. Patterns of menstruation are examined since irregular patterns may accompany hyperandrogenism. Other conditions that may present alongside hirsutism that can contribute to diagnosis include androgenic alopecia and acne. If hyperandrogenism is severe, virilization may occur.Family history is also assessed for occurrences of hyperandrogenism symptoms or obesity in other family members.Laboratory tests can measure FSH, luteininzing hormone, DHEAS, prolactin, 17α-hydroxyprogesterone, and total and free testosterone in the blood. Abnormally high levels of any of these hormones help in diagnosing hyperandrogenism.

Prevention
Since risk factors are not known and vary among individuals with hyperandrogenism, there is no sure method to prevent the condition. Accordingly, more long-term studies are needed to find a cause of the condition before a sufficient method of prevention can be established.Despite this, there are a few things that can help avoid long-term medical issues related to hyperandrogenism and PCOS. Getting checked by a medical professional for hyperandrogenism — especially if one has a family history of the condition, irregular periods, or diabetes — can be beneficial. A healthy weight and diet may reduce the chances, as continued exercise and a healthy diet lead to an improved menstrual cycle, decreased insulin levels, and lowered androgen concentrations.

Treatment
There is no definitive treatment for hyperandrogenism as it varies with the underlying condition that causes it. As a hormonal symptom of PCOS, menopause, and other endocrine conditions, it is primarily treated as a symptom of these conditions. Drugs may be considered only in women who do not plan on becoming pregnant in the near future. Some effective drugs for facial hirsutism includes eflornithine, which may cause birth defects in pregnant women. Retinoids and antibiotics can be used for acne and minoxidil for alopecia. Systemically, it is treated with antiandrogens such as cyproterone acetate, flutamide and spironolactone to reduce androgenic signaling. For hyperandrogenism caused by late-onset congenital adrenal hyperplasia (LOCAH), treatment is primarily focused on providing the patient with glucocorticoids to combat the low cortisol production and the corresponding increase in androgens caused by the increase in size of the adrenal glands. Estrogen-based oral contraceptives are used to treat both LOCAH- and PCOS-associated hyperandrogenism. These hormonal treatments reduce the androgen excess and suppress adrenal androgen production, bringing about a significant decrease in hirsutism.Hyperandrogenism is often managed symptomatically. Hirsutism and acne both respond well to the hormonal treatments described above, with 60–100% of patients reporting an improvement in hirsutism. Androgenic alopecia however, does not show an improvement with hormonal treatments and requires other treatments, such as hair transplantation.Supplementation can also contribute to the managing the symptomatic effects of hyperandrogenism. In a meta-analysis, high-dose vitamin D supplements given to women with vitamin D deficiency due to PCOS improved glucose levels, insulin sensitivity, and cholesterol levels, as well as lowering testosterone, sex hormone-binding globulin, and the free androgen index, all of which are associated with hyperandrogenism. Vitamin D supplementation in women with vitamin D deficiency but without PCOS did not show the same results.

Targeting insulin resistance and obesity
Lifestyle modifications are the first-line treatment for PCOS. They help improve body composition, insulin resistance, and hyperandrogenism. However, it is unclear whether they help improve mood, quality of life, and reproductive outcomes </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Mucositis and can you explain it in depth? [/INST] Mucositis is the painful inflammation and ulceration of the mucous membranes lining the digestive tract, usually as an adverse effect of  chemotherapy and radiotherapy treatment for cancer. Mucositis can occur anywhere along the gastrointestinal (GI) tract, but oral mucositis refers to the particular inflammation and ulceration that occurs in the mouth. Oral mucositis is a common and often debilitating complication of cancer treatment.Oral and gastrointestinal (GI) mucositis affects almost all patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT), 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary tract mucositis increases mortality and morbidity and contributes to rising health care costs.For most cancer treatment, about 5–15% of patients get mucositis. However, with 5-fluorouracil (5-FU), up to 40% get mucositis, and 10–15% get grade 3–4 oral mucositis. Irinotecan is associated with severe GI mucositis in over 20% of patients. Seventy-five to eighty percent of bone marrow transplantation recipients experience mucositis, of which oral mucositis is the most common and most debilitating, especially when melphalan is used. In grade 3 oral mucositis, the patient is unable to eat solid food, and in grade 4, the patient is unable to consume liquids as well.Radiotherapy to the head and neck or to the pelvis or abdomen is associated with Grade 3 and Grade 4 oral or GI mucositis, respectively, often exceeding 50% of patients. Among patients undergoing head and neck radiotherapy, pain and decreased oral function may persist long after the conclusion of therapy. Fractionated radiation dosage increases the risk of mucositis to > 70% of patients in most trials. Oral mucositis is particularly profound and prolonged among HSCT recipients who receive total-body irradiation.

Signs and symptoms
Cancer patients undergoing chemotherapy usually become symptomatic four to five days after beginning treatment, reaching a peak at around day 10, and then slowly improving over the course of a few weeks. Mucositis associated with radiotherapy usually appears at the end of the second week of treatment and may last for six to eight weeks.As a result of cell death in reaction to chemo- or radio-therapy, the mucosal lining of the mouth becomes thin, may slough off and then become red, inflamed and ulcerated. The ulcers may become covered by a yellowish-white fibrin clot called a pseudomembrane. Peripheral erythema is usually present. Ulcers may range from 0.5 cm to greater than 4 cm. Oral mucositis can be severely painful.  The degree of pain is usually related to the extent of the tissue damage.  Pain is often described as a burning sensation accompanied by reddening. Due to pain, the patient may experience trouble speaking, eating, or even opening the mouth.Dysgeusia, or an alteration in taste perception, is common, especially for those who are receiving concomitant radiation therapy to the neck and mouth area. "Taste blindness", or an altered sense of taste, is a temporary condition that occurs because of effects on taste buds that are mostly located in the tongue. Sometimes, only partial recovery of taste occurs. Common complaints are of food tasting too sweet or too bitter or of a continuous metallic taste.

Complications
Sores or ulcerations can become infected by virus, bacteria or fungus. Pain and loss of taste perception makes it more difficult to eat, which leads to weight loss. Ulcers may act as a site for local infection and a portal of entry for oral flora that, in some instances, may cause septicaemia (especially in immunosuppressed patients). Therefore, oral mucositis can be a dose-limiting condition, disrupting a patient’s optimal cancer treatment plan and consequentially decreasing their chances of survival.

Pathophysiology
The pathophysiology of mucositis is complex and multifactorial. Currently, Sonis five phase model is the accepted explanation for the process. The 5 stages are:

Initiation phase. Free radicals are produced due to DNA damage caused by chemo- or radiotherapy.
Primary damage response. Chemotherapy, radiotherapy and free radicals all contribute to the activation of transcription factors, such as NF-κB. This results in the upregulation of pro-inflammatory cytokines, ceramide, nitric oxide and matrix metalloproteinases. The consequence of this is mucosal destruction, caused by thinning of the epithelium due to tissue injury and cell death.
Signal amplification. Positive or negative feedback loops involving some of the molecules in the previous phase can exacerbate or prolong tissue injury. For example, the pro-inflammatory cytokine TNF-α can positively feedback on NF-κB thus inducing more pro-inflammatory cytokine production.
Ulceration. Bacteria colonise ulcers and their cell wall products infiltrate the submucosa. This leads to activation of tissue macrophages, which causes further production of pro-inflammatory cytokines. In addition, bacteria-mediated immune signalling via Toll-like receptors (TLRs) ambiguously shapes chemotherapy-induced genotoxic damage in the gastrointestinal tract.
Healing. Signalling from the extracellular matrix of the submucosa results in epithelial proliferation and differentiation, and thus a thickening of the epithelium. The local oral flora are reinstated.

Diagnosis
Diagnosis is based on the symptoms the patient is experiencing and the appearance of the tissues of the mouth following chemotherapy, bone marrow transplants or radiotherapy. Red burn-like sores or ulcers throughout the mouth is enough to diagnose mucositis.The severity of oral mucositis can be evaluated using several different assessment tools.
Two of the most commonly used are the World Health Organization (WHO) Oral Toxicity score and the National Cancer Institute Common Toxicity Criteria (NCI-CTC) for Oral Mucositis. While the NCI system has separate scores for appearance (erythema and ulceration) and function (pain and ability to eat solids, liquids, or nothing by mouth), the WHO score combines both elements into a single score that grades the severity of the condition from 0 (no oral mucositis) to 4 (swallowing not possible such that patient needs supplementary nutrition). Another scale developed in 1999, the Oral Mucositis Assessment Scale (OMAS) has been shown to be highly reproducible between observers, responsive over time, and accurate in recording symptoms associated with mucositis.   The OMAS provides an objective assessment of oral mucositis based on assessment of the appearance and extent of redness and ulceration in various areas of the mouth.

Prevention
A 2015 Cochrane systematic review assessing the prevention of chemotherapy-induced oral mucositis concluded that oral cryotherapy leads to large reductions in the incidence of oral mucositis of all severities in adults receiving 5-FU treatment for solid cancers. The evidence also indicates a reduction of oral mucositis in adults receiving high-dose melphalan-based cancer treatment prior to haematopoietic stem cell transplantation, although there is uncertainty regarding the size of the reduction in this instance. No evidence was found for use of this preventive measure in children. Oral cryotherapy involves the placement of rounded ice chips in the mouth, which cools the oral tissues and causes vasoconstriction. This decreases blood flow to the region and, hence, also restricts the amounts of the chemotherapy drugs delivered to the tissues.

Treatment
Treatment of mucositis is mainly supportive. Oral hygiene is the mainstay of treatment; patients are encouraged to clean their mouth every four hours and at bedtime, more often if the mucositis becomes worse.Water-soluble jellies can be used to lubricate the mouth. Salt mouthwash can soothe the pain and keep food particles clear so as to avoid infection. Patients are also encouraged to drink plenty of liquids, at least three liters a day, and avoid alcohol. Citrus fruits, alcohol, and foods that are hot are all known to aggravate mucositis lesions. Medicinal mouthwashes may be used such as Chlorhexidine gluconate and viscous Lidocaine for relief of pain. However, care should be taken as the high doses of viscous lidocaine my cause adverse effects. A study reported that lidocaine has a potential toxicity; when it was tested on patients with oral mucositis who underwent a bone marrow transplant, lidocaine anesthetic mouthwash was found to be systemically absorbed.Palifermin is a human KGF (keratinocyte growth factor) that has shown to enhance epithelial cell proliferation, differentiation, and migration. Experimental therapies have been reported, including the use of cytokines and other modifiers of inflammation (e.g., IL-1, IL-11, TGF-beta3), amino acid supplementation (e.g., glutamine), vitamins, colony-stimulating factors, cryotherapy, and laser therapy.Symptomatic relief of the pain of oral mucositis may be provided by barrier protection agents such as concentrated oral gel products (e.g. Gelclair). Caphosol is a mouth rinse which has been shown to prevent and treat oral mucositis caused by radiation and high-dose chemotherapy. MuGard is a FDA-cleared mucoadhesive oral protectant, developed by Access Pharmaceuticals, Inc., that is designed to form a protective hydrogel coating over the oral mucosa while a patient is undergoing chemotherapy and/or radiotherapy cancer treatments to the head and neck </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hermansky–Pudlak syndrome and can you explain it in depth? [/INST] Heřmanský–Pudlák syndrome (often written Hermansky–Pudlak syndrome or abbreviated HPS) is an extremely rare autosomal recessive disorder which results in oculocutaneous albinism (decreased pigmentation), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin). It is considered to affect around 1 in 500,000 people worldwide, with a significantly higher occurrence in Puerto Ricans, with a prevalence of 1 in 1800. Many of the clinical research studies on the disease have been conducted in Puerto Rico.
There are eight classic forms of the disorder, based on the genetic mutation from which the disorder stems.

Signs and symptoms
There are three main disorders caused by Hermansky–Pudlak syndrome, which result in these symptoms:

Albinism and eye problems: Individuals will have varying amounts of skin pigment (melanin).  Because of the albinism there are eye problems such as light sensitivity (photophobia), strabismus (crossed eyes), and nystagmus (involuntary eye movements).  Hermansky–Pudlak syndrome also impairs vision.
Bleeding disorders: Individuals with the syndrome have platelet dysfunction. Since platelets are necessary for blood clotting, individuals will bruise and bleed easily.
Cellular storage disorders: The syndrome causes a wax-like substance (ceroid) to accumulate in the body tissues and cause damage, especially in the lungs and kidneys.It is also associated with granulomatous colitis,, an inflammation of the colon, and with pulmonary fibrosis, a potentially fatal lung disease.

Causes
HPS can be caused by mutations in several genes: HPS1, HPS3, HPS4, HPS5, HPS6 and HPS7.HPS type 2, which includes immunodeficiency in its phenotype, is caused by mutation in the AP3B1 gene.HPS type 7 may result from a mutation in the gene coding for dysbindin protein.Hermansky–Pudlak syndrome is thought to be inherited as an autosomal recessive genetic trait. The defective gene, called HSP, responsible for this disorder is located on the long arm of chromosome 10 (10q2). Some research suggests that an abnormality of lysosomal function may be responsible for the development of the disease.
HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1 and  Biogenesis of Lysosome-related Organelles Complex (BLOC1, BLOC1S2 and BLOC3) are associated with Hermansky–Pudlak syndrome.In autosomal recessive disorders, the condition does not appear unless a person inherits two copies of the defective gene responsible for the disorder, one copy coming from each parent.  If an individual receives one normal gene and one gene for the disorder, the person will be a carrier for the disease, but usually will not show symptoms.  The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent.  Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait).  The risk is the same for each pregnancy.

Pathophysiology
The mechanism of Hermansky–Pudlak syndrome indicates that platelets in affected individuals accumulate abnormally with thrombin, epinephrine, and adenosine diphosphate, furthermore platelets in these individuals have a lower amount of dense bodies

Diagnosis
The diagnosis of HPS is established by clinical findings of hypopigmentation
of the skin and hair, characteristic eye findings, and demonstration of absent
dense bodies on whole mount electron microscopy of platelets.  Molecular
genetic testing of the HPS1 gene is available on a clinical basis for
individuals from northwestern Puerto Rico.  Molecular testing of the HPS3 gene
is available on a clinical basis for individuals of central Puerto Rican or
Ashkenazi Jewish heritage.  Sequence analysis is available on a clinical basis
for mutations in HPS1 and HPS4.  Diagnosis of individuals with other types of
HPS is available on a research basis only.

Treatment
While there is no cure for HPS, treatment for chronic hemorrhages associated with the disorder includes therapy with vitamin E and the antidiuretic dDAVP.

Considerations for patients
A preoperative pulmonology consultation is needed. The anesthesia team should
be aware that patients may have postoperative pulmonary complications as part
of the syndrome.Preoperative hematology consultation is advisable prior to elective ocular
surgeries. Since patients with the syndrome have bleeding tendencies,
intraoperative, perioperative, and postoperative hemorrhages should be
prevented and treated </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Vehicle and can you explain it in depth? [/INST] A vehicle (from Latin: vehiculum) is a machine that transports people or cargo.  Vehicles include wagons, bicycles, motor vehicles (motorcycles, cars, trucks, buses, mobility scooters for disabled people), railed vehicles (trains, trams), watercraft (ships, boats, underwater vehicles), amphibious vehicles (screw-propelled vehicles, hovercraft),  aircraft (airplanes, helicopters, aerostats) and spacecraft.Land vehicles are classified broadly by what is used to apply steering and drive forces against the ground: wheeled, tracked, railed or skied. ISO 3833-1977 is the standard, also internationally used in legislation, for road vehicles types, terms and definitions.

History
The oldest boats found by archaeological excavation are logboats, with the oldest logboat found, the Pesse canoe found in a bog in the Netherlands, being carbon dated to 8040 - 7510 BC, making it 9,500–10,000 years old,
a 7,000-year-old seagoing boat made from reeds and tar has been found in Kuwait.
Boats were used between 4000 -3000 BC in Sumer, ancient Egypt and in the Indian Ocean.
There is evidence of camel pulled wheeled vehicles about 4000–3000 BC.
The earliest evidence of a wagonway, a predecessor of the railway, found so far was the 6 to 8.5 km (4 to 5 mi) long Diolkos wagonway, which transported boats across the Isthmus of Corinth in Greece since around 600 BC. Wheeled vehicles pulled by men and animals ran in grooves in limestone, which provided the track element, preventing the wagons from leaving the intended route.
In 200 CE, Ma Jun built a south-pointing chariot, a vehicle with an early form of guidance system.
Railways began reappearing in Europe after the Dark Ages. The earliest known record of a railway in Europe from this period is a stained-glass window in the Minster of Freiburg im Breisgau dating from around 1350.
In 1515, Cardinal Matthäus Lang wrote a description of the Reisszug, a funicular railway at the Hohensalzburg Fortress in Austria. The line originally used wooden rails and a hemp haulage rope and was operated by human or animal power, through a treadwheel.
1769 Nicolas-Joseph Cugnot is often credited with building the first self-propelled mechanical vehicle or automobile in 1769.
In Russia, in the 1780s, Ivan Kulibin developed a human-pedalled, three-wheeled carriage with modern features such as a flywheel, brake, gear box and bearings; however, it was not developed further.
1783 Montgolfier brothers first balloon vehicle
1801 Richard Trevithick built and demonstrated his Puffing Devil road locomotive, which many believe was the first demonstration of a steam-powered road vehicle, though it could not maintain sufficient steam pressure for long periods and was of little practical use.
1817 Push bikes, draisines or hobby horses were the first human means of transport to make use of the two-wheeler principle, the draisienne (or Laufmaschine, "running machine"), invented by the German Baron Karl von Drais, is regarded as the forerunner of the modern bicycle (and motorcycle). It was introduced by Drais to the public in Mannheim in summer 1817.
1885 Karl Benz built (and subsequently patented) the first automobile, powered by his own four-stroke cycle gasoline engine in Mannheim, Germany
1885 Otto Lilienthal began experimental gliding and achieved the first sustained, controlled, reproducible flights.
1903 Wright brothers flew the first controlled, powered aircraft
1907 First helicopters Gyroplane no.1 (tethered) and Cornu helicopter (free flight)
1928 Opel RAK.1 rocket car
1929 Opel RAK.1 rocket glider
1961 Vostok vehicle carried the first human, Yuri Gagarin, into space
1969 Apollo Program first crewed vehicle landed on the moon
2010 The number of road motor vehicles in operation worldwide surpassed the 1 billion mark – roughly one for every seven people.

Types of vehicles
There are over 1 billion bicycles in use worldwide. In 2002 there were an estimated 590 million cars and 205 million motorcycles in service in the world. At least 500 million Chinese Flying Pigeon bicycles have been made, more than any other single model of vehicle. The most-produced model of motor vehicle is the Honda Super Cub motorcycle, having passed 60 million units in 2008. The most-produced car model is the Toyota Corolla, with at least 35 million made by 2010. The most common fixed-wing airplane is the Cessna 172, with about 44,000 having been made as of 2017. The Soviet Mil Mi-8, at 17,000, is the most-produced helicopter. The top commercial jet airliner is the Boeing 737, at about 10,000 in 2018. At around 14,000 for both, the most produced trams are the KTM-5 and Tatra T3. The most common trolleybus is ZiU-9.

Locomotion
Locomotion consists of a means that allows displacement with little opposition, a power source to provide the required kinetic energy and a means to control the motion, such as a brake and steering system. By far, most vehicles use wheels which employ the principle of rolling to enable displacement with very little rolling friction.

Energy source
It is essential that a vehicle have a source of energy to drive it. Energy can be extracted from external sources, as in the cases of a sailboat, a solar-powered car, or an electric streetcar that uses overhead lines. Energy can also be stored, provided it can be converted on demand and the storing mediums energy density and power density are sufficient to meet the vehicles needs.
Human power is a simple source of energy that requires nothing more than humans. Despite the fact that humans cannot exceed 500 W (0.67 hp) for meaningful amounts of time, the land speed record for human-powered vehicles (unpaced) is 133 km/h (83 mph), as of 2009 on a recumbent bicycle.The most common type of energy source is fuel. External combustion engines can use almost anything that burns as fuel, whilst internal combustion engines and rocket engines are designed to burn a specific fuel, typically gasoline, diesel or ethanol.
Another common medium for storing energy is batteries, which have the advantages of being responsive, useful in a wide range of power levels, environmentally friendly, efficient, simple to install, and easy to maintain. Batteries also facilitate the use of electric motors, which have their own advantages. On the other hand, batteries have low energy densities, short service life, poor performance at extreme temperatures, long charging times, and difficulties with disposal (although they can usually be recycled). Like fuel, batteries store chemical energy and can cause burns and poisoning in event of an accident. Batteries also lose effectiveness with time. The issue of charge time can be resolved by swapping discharged batteries with charged ones; however, this incurs additional hardware costs and may be impractical for larger batteries. Moreover, there must be standard batteries for battery swapping to work at a gas station. Fuel cells are similar to batteries in that they convert from chemical to electrical energy, but have their own advantages and disadvantages.
Electrified rails and overhead cables are a common source of electrical energy on subways, railways, trams, and trolleybuses.
Solar energy is a more modern development, and several solar vehicles have been successfully built and tested, including Helios, a solar-powered aircraft.
Nuclear power is a more exclusive form of energy storage, currently limited to large ships and submarines, mostly military. Nuclear energy can be released by a nuclear reactor, nuclear battery, or repeatedly detonating nuclear bombs. There have been two experiments with nuclear-powered aircraft, the Tupolev Tu-119 and the Convair X-6.
Mechanical strain is another method of storing energy, whereby an elastic band or metal spring is deformed and releases energy as it is allowed to return to its ground state. Systems employing elastic materials suffer from hysteresis, and metal springs are too dense to be useful in many cases.Flywheels store energy in a spinning mass. Because a light and fast rotor is energetically favorable, flywheels can pose a significant safety hazard. Moreover, flywheels leak energy fairly quickly and affect a vehicles steering through the gyroscopic effect. They have been used experimentally in gyrobuses.
Wind energy is used by sailboats and land yachts as the primary source of energy. It is very cheap and fairly easy to use, the main issues being dependence on weather and upwind performance. Balloons also rely on the wind to move horizontally. Aircraft flying in the jet stream may get a boost from high altitude winds.
Compressed gas is currently an experimental method of storing energy. In this case, compressed gas is simply stored in a tank and released when necessary. Like elastics, they have hysteresis losses when gas heats up during compression.
Gravitational potential energy is a form of energy used in gliders, skis, bobsleds and numerous other vehicles that go down hill. Regenerative braking is an example of capturing kinetic energy where the brakes of a vehicle are augmented with a generator or other means of extracting energy.

Motors and engines
When needed, the energy is taken from the source and consumed by one or more motors or engines. Sometimes there is an intermediate medium, such as the batteries of a diesel submarine.Most motor vehicles have internal combustion engines. They are fairly cheap, easy to maintain, reliable, safe and small. Since these engines burn fuel, they have long ranges but pollute the environment. A related engine is the external combustion engine. An example of this is the steam engine. Aside from fuel, steam engines also need water, making them impractical for some purposes. Steam engines also need time to warm up, whereas IC engines can usually run right after being started, although this may not be recommended in cold conditions. Steam engines burning coal release sulfur into the air, causing harmful acid rain.

While intermittent internal combustion engines were once the primary means of aircraft propulsion, they have been largely superseded by continuous internal combustion engines: gas turbines. Turbine engines are light and, particularly when used on aircraft, efficient. On the other hand, they cost more and require careful maintenance. They can also be damaged by ingesting foreign objects, and they produce a hot exhaust. Trains using turbines are called gas turbine-electric locomotives. Examples of surface vehicles using turbines are M1 Abrams, MTT Turbine SUPERBIKE and the Millennium. Pulse jet engines are similar in many ways to turbojets, but have almost no moving parts. For this reason, they were very appealing to vehicle designers in the past; however their noise, heat and inefficiency has led to their abandonment. A historical example of the use of a pulse jet was the V-1 flying bomb. Pulse jets are still occasionally used in amateur experiments. With the advent of modern technology, the pulse detonation engine has become practical and was successfully tested on a Rutan VariEze. While the pulse detonation engine is much more efficient than the pulse jet and even turbine engines, it still suffers from extreme noise and vibration levels. Ramjets also have few moving parts, but they only work at high speed, so that their use is restricted to tip jet helicopters and high speed aircraft such as the Lockheed SR-71 Blackbird.Rocket engines are primarily used on rockets, rocket sleds and experimental aircraft. Rocket engines are extremely powerful. The heaviest vehicle ever to leave the ground, the Saturn V rocket, was powered by five F-1 rocket engines generating a combined 180 million horsepower (134.2 gigawatt). Rocket engines also have no need to "push off" anything, a fact that the New York Times denied in error. Rocket engines can be particularly simple, sometimes consisting of nothing more than a catalyst, as in the case of a hydrogen peroxide rocket. This makes them an attractive option for vehicles such as jet packs. Despite their simplicity, rocket engines are often dangerous and susceptible to explosions. The fuel they run off may be flammable, poisonous, corrosive or cryogenic. They also suffer from poor efficiency. For these reasons, rocket engines are only used when absolutely necessary.Electric motors are used in electric vehicles such as electric bicycles, electric scooters, small boats, subways, trains, trolleybuses, trams and experimental aircraft. Electric motors can be very efficient: over 90% efficiency is common. Electric motors can also be built to be powerful, reliable, low-maintenance and of any size. Electric motors can deliver a range of speeds and torques without necessarily using a gearbox (although it may be more economical to use one). Electric motors are limited in their use chiefly by the difficulty of supplying electricity.Compressed gas motors have been used on some vehicles experimentally. They are simple, efficient, safe, cheap, reliable and operate in a variety of conditions. One of the difficulties met when using gas motors is the cooling effect of expanding gas. These engines are limited by how quickly they absorb heat from their surroundings. The cooling effect can, however, double as air conditioning. Compressed gas motors also lose effectiveness with falling gas pressure.Ion thrusters are used on some satellites and spacecraft. They are only effective in a vacuum, which limits their use to spaceborne vehicles. Ion thrusters run primarily off electricity, but they also need a propellant such as caesium, or more recently xenon. Ion thrusters can achieve extremely high speeds and use little propellant; however they are power-hungry.

Converting energy to work
The mechanical energy that motors and engines produce must be converted to work by wheels, propellers, nozzles, or similar means.
Aside from converting mechanical energy into motion, wheels allow a vehicle to roll along a surface and, with the exception of railed vehicles, to be steered. Wheels are ancient technology, with specimens being discovered from over 5000 years ago. Wheels are used in a plethora of vehicles, including motor vehicles, armoured personnel carriers, amphibious vehicles, airplanes, trains, skateboards and wheelbarrows.
Nozzles are used in conjunction with almost all reaction engines. Vehicles using nozzles include jet aircraft, rockets and personal watercraft.  While most nozzles take the shape of a cone or bell, some unorthodox designs have been created such as the aerospike. Some nozzles are intangible, such as the electromagnetic field nozzle of a vectored ion thruster.Continuous track is sometimes used instead of wheels to power land vehicles. Continuous track has the advantages of a larger contact area, easy repairs on small damage, and high maneuverability. Examples of vehicles using continuous track are tanks, snowmobiles and excavators. Two continuous tracks used together allow for steering. The largest vehicle in the world, the Bagger 288, is propelled by continuous tracks.
Propellers (as well as screws, fans and rotors) are used to move through a fluid. Propellers have been used as toys since ancient times, however it was Leonardo da Vinci who devised what was one of the earliest propeller driven vehicles, the "aerial-screw". In 1661, Toogood & Hays adopted the screw for use as a ship propeller. Since then, the propeller has been tested on many terrestrial vehicles, including the Schienenzeppelin train and numerous cars. In modern times, propellers are most prevalent on watercraft and aircraft, as well as some amphibious vehicles such as hovercraft and ground-effect vehicles. Intuitively, propellers cannot work in space as there is no working fluid, however some sources have suggested that since space is never empty, a propeller could be made to work in space.Similarly to propeller vehicles, some vehicles use wings for propulsion. Sailboats and sailplanes are propelled by the forward component of lift generated by their sails/wings. Ornithopters also produce thrust aerodynamically. Ornithopters with large rounded leading edges produce lift by leading-edge suction forces. Research at the University of Toronto Institute for Aerospace Studies  lead to a flight with an actual ornithopter on July 31, 2010.
Paddle wheels are used on some older watercraft and their reconstructions. These ships were known as paddle steamers. Because paddle wheels simply push against the water, their design and construction is very simple. The oldest such ship in scheduled service is the Skibladner. Many pedalo boats also use paddle wheels for propulsion.
Screw-propelled vehicles are propelled by auger-like cylinders fitted with helical flanges. Because they can produce thrust on both land and water, they are commonly used on all-terrain vehicles. The ZiL-2906 was a Soviet-designed screw-propelled vehicle designed to retrieve cosmonauts from the Siberian wilderness.

Friction
All or almost all of the useful energy produced by the engine is usually dissipated as friction; so minimising frictional losses is very important in many vehicles. The main sources of friction are rolling friction and fluid drag (air drag or water drag).
Wheels have low bearing friction and pneumatic tyres give low rolling friction. Steel wheels on steel tracks are lower still.Aerodynamic drag can be reduced by streamlined design features.
Friction is desirable and important in supplying traction to facilitate motion on land. Most land vehicles rely on friction for accelerating, decelerating and changing direction. Sudden reductions in traction can cause loss of control and accidents.

Control
Steering
Most vehicles, with the notable exception of railed vehicles, have at least one steering mechanism. Wheeled vehicles steer by angling their front or rear wheels. The B-52 Stratofortress has a special arrangement in which all four main wheels can be angled. Skids can also be used to steer by angling them, as in the case of a snowmobile. Ships, boats, submarines, dirigibles and aeroplanes usually have a rudder for steering. On an airplane, ailerons are used to bank the airplane for directional control, sometimes assisted by the rudder.

Stopping
With no power applied, most vehicles come to a stop due to friction. But it is often required to stop a vehicle faster than by friction alone: so almost all vehicles are equipped with a braking system. Wheeled vehicles are typically equipped with friction brakes, which use the friction between brake pads (stators) and brake rotors to slow the vehicle. Many airplanes have high performance versions of the same system in their landing gear for use on the ground. A Boeing 757 brake, for example, has 3 stators and 4 rotors. The Space Shuttle also uses frictional brakes on its wheels. As well as frictional brakes, hybrid/electric cars, trolleybuses and electric bicycles can also use regenerative brakes to recycle some of the vehicles potential energy. High-speed trains sometimes use frictionless Eddy-current brakes; however widespread application of the technology has been limited by overheating and interference issues.Aside from landing gear brakes, most large aircraft have other ways of decelerating. In aircraft, air brakes are aerodynamic surfaces that provide braking force by increasing the frontal cross section thus aerodynamic drag of the aircraft. These are usually implemented as flaps that oppose air flow when extended and are flush with aircraft when retracted. Reverse thrust is also used in many aeroplane engines. Propeller aircraft achieve reverse thrust by reversing the pitch of the propellers, while jet aircraft do so by redirecting their engine exhaust forwards. On aircraft carriers, arresting gears are used to stop an aircraft. Pilots may even apply full forward throttle on touchdown, in case the arresting gear does not catch and a go around is needed.Parachutes are used to slow down vehicles travelling very fast. Parachutes have been used in land, air and space vehicles such as the ThrustSSC, Eurofighter Typhoon and Apollo Command Module. Some older Soviet passenger jets had braking parachutes for emergency landings. Boats use similar devices called sea anchors to maintain stability in rough seas.
To further increase the rate of deceleration or where the brakes have failed, several mechanisms can be used to stop a vehicle. Cars and rolling stock usually have hand brakes that, while designed to secure an already parked vehicle, can provide limited braking should the primary brakes fail. A secondary procedure called forward-slip is sometimes used to slow airplanes by flying at an angle, causing more drag.

Legislation
Motor vehicle and trailer categories are defined according to the following international classification:
Category M: passenger vehicles.
Category N: motor vehicles for the carriage of goods.
Category O: trailers and semi-trailers.

European Union
In the European Union the classifications for vehicle types are defined by:
Commission Directive 2001/116/EC of 20 December 2001, adapting to technical progress Council Directive 70/156/EEC on the approximation of the laws of the Member States relating to the type-approval of motor vehicles and their trailers
Directive 2002/24/EC of the European Parliament and of the Council of 18 March 2002 relating to the type-approval of two or three wheeled motor vehicles and repealing Council Directive 92/61/EECEuropean Community, is based on the Communitys WVTA (whole vehicle type-approval) system. Under this system, manufacturers can obtain certification for a vehicle type in one Member State if it meets the EC technical requirements and then market it EU-wide with no need for further tests. Total technical harmonization already has been achieved in three vehicle categories (passenger cars, motorcycles, and tractors) and soon will extend to other vehicle categories (coaches and utility vehicles). It is essential that European car manufacturers be ensured access to as large a market as possible.
While the Community type-approval system allows manufacturers to benefit fully from internal market opportunities, worldwide technical harmonization in the context of the United Nations Economic Commission for Europe (UNECE) offers a market beyond European borders.

Licensing
In many cases, it is unlawful to operate a vehicle without a license or certification. The least strict form of regulation usually limits what passengers the driver may carry or prohibits them completely (e.g., a Canadian ultra-light license without endorsements). The next level of licensing may allow passengers, but without any form of compensation or payment. A private drivers license usually has these conditions. Commercial licenses that allow the transport of passengers and cargo are more tightly regulated. The most strict form of licensing is generally reserved for school buses, hazardous materials transports and emergency vehicles.
The driver of a motor vehicle is typically required to hold a valid drivers license while driving on public lands, whereas the pilot of an aircraft must have a license at all times, regardless of where in the jurisdiction the aircraft is flying.

Registration
Vehicles are often required to be registered. Registration may be for purely legal reasons, for insurance reasons or to help law enforcement recover stolen vehicles. Toronto Police Service, for example, offers free and optional bicycle registration online. On motor vehicles, registration often takes the form of a vehicle registration plate, which makes it easy to identify a vehicle. In Russia, trucks and buses have their licence plate numbers repeated in large black letters on the back. On aircraft, a similar system is used where a tail number is painted on various surfaces. Like motor vehicles and aircraft, watercraft also have registration numbers in most jurisdictions, however the vessel name is still the primary means of identification  as has been the case since ancient times. For this reason, duplicate registration names are generally rejected. In Canada, boats with an engine power of 10 hp (7.5 kW) or greater require registration, leading to the ubiquitous "9.9 hp (7.4 kW)" engine.
Registration may be conditional on the vehicle being approved for use on public highways, as in the case of the UK and Ontario. Many US states also have requirements for vehicles operating on public highways. Aircraft have more stringent requirements, as they pose a high risk of damage to people and property in event of an accident. In the US, the FAA requires aircraft to have an airworthiness certificate. Because US aircraft must be flown for some time before they are certified, there is a provision for an experimental airworthiness certificate. FAA experimental aircraft are restricted in operation, including no overflights of populated areas, in busy airspace or with unessential passengers. Materials and parts used in FAA certified aircraft must meet the criteria set forth by the technical standard orders.

Mandatory safety equipment
In many jurisdictions, the operator of a vehicle is legally obligated to carry safety equipment with or on them. Common examples include seat belts in cars, helmets on motorcycles and bicycles, fire extinguishers on boats, buses and airplanes and life jackets on boats and commercial aircraft. Passenger aircraft carry a great deal of safety equipment including inflatable slides are rafts, oxygen masks, oxygen tanks, life jackets, satellite beacons and first aid kits. Some equipment such as life jackets has led to debate regarding their usefulness. In the case of Ethiopian Airlines Flight 961, the life jackets saved many people but also led to many deaths when passengers inflated their vests prematurely.

Right-of-way
There are specific real-estate arrangements made to allow vehicles to travel from one place to another. The most common arrangements are public highways, where appropriately licensed vehicles can navigate without hindrance. These highways are on public land and are maintained by the government. Similarly, toll routes are open to the public after paying a toll. These routes and the land they rest on may be government or privately owned or a combination of both. Some routes are privately owned but grant access to the public. These routes often have a warning sign stating that the government does not maintain the way. An example of this are byways in England and Wales. In Scotland, land is open to un-motorised vehicles if the land meets certain criteria. Public land is sometimes open to use by off-road vehicles. On US public land, the Bureau of Land Management (BLM) decides where vehicles may be used. Railways often pass over land not owned by the railway company </s>