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Question: What are the symptoms of alpha thalassemia major?

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Context 1: Thalassaemia minor | definition of Thalassaemia minor by Medical dictionary
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Thalassemia describes a group of inherited disorders characterized by reduced or absent amounts of hemoglobin, the oxygen-carrying protein inside the red blood cells  There are two basic groups of thalassemia disorders: alpha thalassemia and beta thalassemia  These conditions cause varying degrees of anemia, which can range from insignificant to life threatening 
All types of thalassemias are considered quantitative diseases of hemoglobin, because the quantity of hemoglobin produced is reduced or absent  Usual adult hemoglobin is made up of three components: alpha globin, beta globin, and heme  Thalassemias are classified according to the globin that is affected, hence the names alpha and beta thalassemia  Although both classes of thalassemia affect the same protein, the alpha and beta thalassemias are distinct diseases that affect the body in different ways 
Beta thalassemia may be the most best-known type of thalassemia and is also called Cooley's anemia  It is caused by a change in the gene for the beta globin component of hemoglobin  Beta thalassemia causes variable anemia that can range from moderate to severe, depending in part on the exact genetic change underlying the disease  Beta thalassemia can be classified based on clinical symptoms  Beta thalassemia major usually causes severe anemia that can occur within months after birth  If left untreated, severe anemia can result in insufficient growth and development, as well as other common physical complications that can lead to a dramatically decreased life-expectancy  Fortunately, in developed countries beta thalassemia is usually identified by screening in the newborn period, before symptoms have developed  Children who are identified early can be started on ongoing blood transfusion therapy as needed  Although transfusion therapy prevents many of the complications of severe anemia, the body is unable to eliminate the excess iron contained in the transfused blood  Over time, the excess iron deposits in tissues and organs, resulting in damage and organ failure  Another medication must be administered to help the body eliminate the excess iron and prevent iron-over-load complications  Beta thalassemia intermedia describes the disease in individuals who have moderate anemia that only requires blood transfusions intermittently, if at all 
Alpha thalassemia is the result of changes in the genes for the alpha globin component of hemoglobin  There are two main types of alpha thalassemia disease: hemoglobin H disease and alpha thalassemia major  The two diseases are quite different from beta thalassemia as well as from one another  Individuals with hemoglobin H disease can experience events of hemolytic anemia—anemia caused by the rapid breakdown of the red blood cells  These events are thought to be triggered by various environmental causes, such as infection and/or exposure to certain chemicals  Hemoglobin H disease is in most cases milder than beta thalassemia  It does not generally require transfusion therapy  Alpha thalassemia major is a very serious disease that results in severe anemia that begins even before birth  Most affected babies do not survive to be born or die shortly after birth 
The thalassemias are among the most common genetic diseases worldwide  Both alpha and beta thalassemia have been described in individuals of almost every ancestry, but the conditions are more common among certain ethnic groups  Unaffected carriers of all types of thalassemia traits do not experience health problems  In fact, the thalassemia trait is protective against malaria, a disease caused by blood-borne parasites transmitted through mosquito bites  According to a widely accepted theory, most genetic changes—mutations—that cause thalassemia occurred multiple generations ago  Coincidentally, these mutations increased the likelihood that carriers would survive malaria infection  Survivors passed the mutation onto their offspring, and the trait became established throughout areas where malaria is common  As populations migrated, so did the thalassemia traits 
Beta thalassemia trait is seen most commonly in people with the following ancestry: Mediterranean (including North African, and particularly Italian and Greek), Middle Eastern, Indian, African, Chinese, and Southeast Asian (including Vietnamese, Laotian, Thai, Singaporean, Filipino, Cambodian, Malaysian, Burmese, and Indonesian)  Alpha-thalassemia trait is seen with increased frequency in the same ethnic groups  However, there are different types of alpha thalassemia traits within these populations  The frequency of hemoglobin H disease and alpha thalassemia major depends on the type of alpha thalassemia trait  The populations in which alpha thalassemia diseases are most common include Southeast Asians and Chinese (particularly Southern Chinese) 
It is difficult to obtain accurate prevalence figures for various types of thalassemia within different populations  This difficulty arises due to testing limitations in determining exact genetic diagnoses, as well as the fact that many studies have focused on small, biased hospital populations 
Two studies reflect prevalence figures that can be helpful counseling families and determining who to screen for beta thalassemia  Between the years of 1990 and 1996, the State of California screened more than 3 1 million infants born in the state for beta thalassemia  Approximately 1 in 114,000 infants had beta thalassemia major, with prevalence rates being highest among Asian Indians (about one in 4,000), Southeast Asians (about one in 10,000), and Middle Easterners (about one in 7,000)  Another type of beta thalassemia disease, E/beta thalassemia, was represented in approximately one in 110,000 births, all of which occurred in families of Southeast Asian ancestry  Among Southeast Asians, the prevalence of E/beta thalassemia was approximately one in 2,600 births  This is in keeping with the observation that hemoglobin E trait carrier rates are relatively high within the Southeast Asian population: 16% in a study of 768 immigrants to California, and up to 25% in some specific Southeast Asian populations such as Cambodians  While these California studies address some of the limitations of earlier population studies, the pattern observed in California is expected to be different in other areas of the United States and the world  For example, Italians are underrepresented in this population when compared to the population of the East Coast of the United States 
Determining prevalence figures for alpha thalassemia is even more difficult due to increased limitations in diagnostic testing  All types of alpha thalassemia disease are most common among people of Southeast Asian and Chinese descent, for reasons that become clearer with an understanding of the underlying genetics of alpha thalassemia  One study of 500 pregnant women in Northern Thailand estimated a frequency of one in 500 pregnancies affected by alpha thalassemia major, for example  Prevalence of alpha thalassemia disease is significantly lower in the United States primarily because of immigration patterns; although at least one state, California, has observed growing hemoglobin H disease incidence rates that are high enough to justify universal newborn screening for the condition 
Humans normally make several types of the oxygen-carrying protein hemoglobin  An individual's stage in development determines whether he or she makes primarily embryonic, fetal, or adult hemoglobins  All types of hemoglobin are made of three components: heme, alpha (or alpha-like) globin, and beta (or beta-like) globin  All types of thalassemia are caused by changes in either the alpha- or beta-globin gene  These changes cause little or no globin to be produced  The thalassemias are, therefore, considered quantitative hemoglobin diseases  All types of thalassemias are recessively inherited, meaning that a genetic change must be inherited from both the mother and the father  The severity of the disease is influenced by the exact thalassemia mutations inherited, as well as other genetic and environmental factors  There are rare exceptions, notably with beta thalassemia, where globin gene mutations exhibit a dominant pattern of inheritance in which only one gene needs to be altered in order to see disease expression  Scientists continue to study the causes  For instance, a new mutation for alpha-thalassemia was discovered for the first time among Iranian patients in 2004 
BETA-THALASSEMIA  Most individuals have two normal copies of the beta globin gene, which is located on chromosome 11 and makes the beta globin component of normal adult hemoglobin, hemoglobin A  There are approximately 100 genetic mutations that have been described that cause beta thalassemia, designated as either beta0 or beta + mutations  No beta globin is produced with a beta0 mutation, and only a small fraction of the normal amount of beta globin is produced with a beta + mutation 
When an individual has one normal beta globin gene and one with a beta thalassemia mutation, he or she is said to carry the beta thalassemia trait  Beta thalassemia trait, like other hemoglobin traits, is protective against malaria infection  Trait status is generally thought not to cause health problems, although some women with beta thalassemia trait may have an increased tendency toward anemia during pregnancy 
When two members of a couple carry the beta thalassemia trait, there is a 25% chance that each of their children will inherit beta thalassemia disease by inheriting two beta thalassemia mutations, one from each parent  The clinical severity of the beta thalassemia disease—whether an individual has beta thalassemia intermedia or beta thalassemia major—will depend largely on whether the mutations inherited are beta0 thalassemia or beta + thalassemia mutations  Two beta0 mutations generally lead to beta thalassemia major, and two beta+ thalassemia mutations generally lead to beta thalassemia intermedia  Inheritance of one beta0 and one beta + thalassemia mutation tends to be less predictable 
Although relatively uncommon, there are other thalassemia-like mutations that can affect the beta globin gene  Hemoglobin E is the result of a substitution of a single nucleotide  This change results in a structurally altered hemoglobin that is produced in decreased amounts  Therefore, hemoglobin E is unique in that it is both a quantitative (i e  thalassemia-like) and qualitative trait  When co-inherited with a beta thalassemia trait, it causes a disease that is almost indistinguishable from beta thalassemia disease  Large deletions around and including the beta globin gene can lead to delta/beta thalassemia or hereditary persistence of fetal hemoglobin (HPFH)  Interestingly, delta/beta thalassemia trait behaves very similarly to beta thalassemia trait in its clinical manifestations  However, HPFH trait does not tend to cause hemoglobin disease when co-inherited with a second thalassemia or other beta globin mutation 
ALPHA-THALASSEMIA  Most individuals have four normal copies of the alpha globin gene, two copies on each chromosome 16  These genes make the alpha globin component of normal adult hemoglobin, which is called hemoglobin A  Alpha globin is also a component of fetal hemoglobin and the other major adult hemoglobin called hemoglobin A2  Mutations of the alpha globin genes are usually deletions of the gene, resulting in absent production of alpha globin  Since there are four genes (instead of the usual two) to consider when looking at alpha globin gene inheritance, there are several alpha globin types that are possible 
Absence of one alpha globin gene leads to a condition known as silent alpha thalassemia trait  This condition causes no health problems and can be detected only by special genetic testing  Alpha thalassemia trait occurs when two alpha globin genes are missing  This can occur in two ways  The genes may be deleted from the same chromosome, causing the 'cis' type of alpha thalassemia trait  Alternately, they may be deleted from different chromosomes, causing the 'trans' type of alpha thalassemia trait  In both instances, there are no associated health problems, although the trait status may be detected by more routine blood screening 
Hemoglobin H disease results from the deletion of three alpha globin genes, such that there is only one functioning gene  Typically, this can occur when one parent carries the silent alpha thalassemia trait, and the other parent carries the 'cis' type of the alpha thalassemia trait  In this situation, there is a 25% chance for hemoglobin H disease in each of such a couple's children 
Hemoglobin H disease-like symptoms can also be a part of a unique condition called alpha thalassemia mental retardation syndrome  Alpha thalassemia mental retardation syndrome can be caused by a deletion of a significant amount of chromosome 16, affecting the alpha globin genes  This is usually not inherited, but rather occurs sporadically in the affected individual  Affected individuals have mild hemoglobin H disease, mild-to-moderate mental retardation, and characteristic facial features  This syndrome can also occur as a sex-linked form in which a mutation is inherited in a particular gene on the X-chromosome  This gene influences alpha globin production, as well as various other developmental processes  Individuals affected with this form of the syndrome tend to have more severe mental retardation, delayed development, nearly absent speech, characteristic facial features, and genital-urinary abnormalities  The remaining discussion will focus only on aspects of hemoglobin H disease 
Alpha thalassemia major results from the deletion of all four alpha globin genes, such that there are no functioning alpha globin genes  This can occur when both parents carry the 'cis' type of the alpha thalassemia trait  In this situation, there is a 25% chance for alpha thalassemia major in each of such a couple's children 
Beta thalassemia major is characterized by severe anemia that can begin months after birth  In the United States and other developed countries beta thalassemia is identified and treated early and effectively  Therefore, the following discussion of symptoms applies primarily to affected individuals in the past and unfortunately in some underdeveloped countries now  If untreated, beta thalassemia major can lead to severe lethargy, paleness, and delays in growth and development  The body attempts to compensate by producing more blood, which is made inside the bones in the marrow  However, this is ineffective without the needed genetic instructions to make enough functioning hemoglobin  Instead, obvious bone expansion and changes occur that cause characteristic facial and other changes in appearance, as well as increased risk of fractures  Severe anemia taxes other organs in the body—such as the heart, spleen, and liver—which must work harder than usual  This can lead to heart failure, as well as enlargement and other problems of the liver and spleen  When untreated, beta thalassemia major generally results in childhood death, usually due to heart failure  In 2004, the first known heart attack associated with beta thalassemia major was reported  Fortunately, in developed countries diagnosis is usually made early, often before symptoms have begun  This allows for treatment with blood transfusion therapy, which can prevent most of the complications of the severe anemia caused by beta thalassemia major  Individuals with beta thalassemia intermedia have a more moderate anemia that may only require treatment with transfusion intermittently, such as when infections occur and stress the body  As a person with beta thalassemia intermedia gets older, however, the need for blood transfusions may increase to the point that they are required on a regular basis  When this occurs their disease becomes more similar to beta thalassemia major  Other genetic and environmental factors can influence the course of the disease as well  For example, co-inheritance of one or two alpha thalassemia mutations can tend to ameliorate some of the symptoms of beta thalassemia disease, which result in part from an imbalance in the amount of alpha- and beta-globin present in the red blood cells 
Hemoglobin h disease
Absence of three alpha globin genes causes an imbalance of alpha and beta globin proteins in the red blood cells  The excess beta globin proteins tend to come together to form hemoglobin H, which is unable to release oxygen to the tissues  In addition, hemoglobin H tends to precipitate out in the cells, causing damage to the red blood cell membrane  When affected individuals are exposed to certain drugs and chemicals known to make the membrane more fragile, the cells are thought to become vulnerable to breakdown in large numbers, a complication called hemolytic anemia  Fever and infection are also considered to be triggers of hemolytic anemia in hemoglobin H disease  This can result in fatigue, paleness, and a yellow discoloration of the skin and whites of eyes called jaundice  Usually, the anemia is mild enough not to require treatment  Severe anemia events may require blood transfusion, however, and are usually accompanied by such other symptoms as dark feces or urine and abdominal or back pain  These events are uncommon in hemoglobin H disease, although they occur more frequently in a more serious type of hemoglobin H disease called hemoglobin H/Constant Spring disease  Individuals effected with this type of hemoglobin H disease are also more likely to have enlargement of and other problems with the spleen 
Alpha thalassemia major
Because alpha globin is a necessary component of all major hemoglobins and some minor hemoglobins, absence of all functioning alpha globin genes leads to serious medical consequences that begin even before birth  Affected fetuses develop severe anemia as early as the first trimester of pregnancy  The placenta, heart, liver, spleen, and adrenal glands may all become enlarged  Fluid can begin collecting throughout the body as early as the start of the second trimester, causing damage to developing tissues and organs  Growth retardation is also common  Affected fetuses usually miscarry or die shortly after birth  In addition, women carrying affected fetuses are at increased risk of developing complications of pregnancy and delivery  Up to 80% of such women develop toxemia, a disturbance of metabolism that can potentially lead to convulsions and coma  Other maternal complications include premature delivery and increased rates of delivery by cesarean section, as well as hemorrhage after delivery 
Thalassemia may be suspected if an individual shows signs that are suggestive of the disease  In all cases, however, laboratory diagnosis is essential to confirm the exact diagnosis and to allow for the provision of accurate genetic counseling about recurrence risks and testing options for parents and affected individuals  Screening is likewise recommended to determine trait status for individuals of high-risk ethnic groups 
The following tests are used to screen for thalassemia disease and/or trait:
hemoglobin electrophoresis with quantitative hemoglobin A2 and hemoglobin F
free erythrocyte-protoporphyrin (or ferritin or other studies of serum iron levels)
A complete blood count will identify low levels of hemoglobin, small red blood cells, and other red blood cell abnormalities that are characteristic of a thalassemia diagnosis  Since thalassemia trait can sometimes be difficult to distinguish from iron deficiency, tests to evaluate iron levels are important  A hemoglobin electrophoresis is a test that can help identify the types and quantities of hemoglobin made by an individual  This test uses an electric field applied across a slab of gel-like material  Hemoglobins migrate through this gel at various rates and to specific locations, depending on their size, shape, and electrical charge  Isoelectric focusing and high-performance liquid chromatography (HPLC) use similar principles to separate hemoglobins and can be used instead of or in various combinations with hemoglobin electrophoresis to determine the types and quantities of hemoglobin present  Hemoglobin electrophoresis results are usually within the normal range for all types of alpha thalassemia  However, hemoglobin A2 levels and sometimes hemoglobin F levels are elevated when beta thalassemia disease or trait is present  Hemoglobin electrophoresis can also detect structurally abnormal hemoglobins that may be co-inherited with a thalassemia trait to cause thalassemia disease (i e , hemoglobin E) or other types of hemoglobin disease (i e , sickle hemoglobin)  Sometimes DNA testing is needed in addition to the above screening tests  This can be performed to help confirm the diagnosis and establish the exact genetic type of thalassemia 
Diagnosis of thalassemia can occur under various circumstances and at various ages  Several states offer thalassemia screening as part of the usual battery of blood tests done for newborns  This allows for early identification and treatment  Thalassemia can be identified before birth through the use of prenatal diagnosis  Chorionic villus sampling (CVS) can be offered as early as 10 weeks of pregnancy and involves removing a sample of the placenta made by the baby and testing the cells  CVS carries a risk of causing a miscarriage that is between 0 5%-1%  Amniocentesis is generally offered between 15 and 22 weeks of pregnancy, but can sometimes be offered earlier  Two to three tablespoons of the fluid surrounding the baby is removed  This fluid contains fetal cells that can be tested  The risk of miscarriage associated with amniocentesis ranges from 0 33-0 5%  Pregnant woman and couples may choose prenatal testing in order to prepare for the birth of a baby that may have thalassemia  Alternately, knowing the diagnosis during pregnancy allows for the option of pregnancy termination  Preimplantation genetic diagnosis (PGD) is a relatively new technique that involves in-vitro fertilization followed by genetic testing of one cell from each developing embryo  Only the embryos unaffected by sickle cell disease are transferred back into the uterus  PGD is currently available on a research basis only and is relatively expensive 
Individuals with beta thalassemia major receive regular blood transfusions, usually on a monthly basis  This helps prevent severe anemia and allows for more normal growth and development  Transfusion therapy does have limitations, however  Individuals can develop reactions to certain proteins in the blood—called a transfusion reaction  This can make locating appropriately matched donor blood more difficult  Although blood supplies in the United States are very safe, particularly relative to the past and to other areas of the world, there remains an increased risk of exposure to such blood-borne infections as hepatitis  Additionally, the body is not able to get rid of the excess iron that accompanies each transfusion  An additional medication called desferoxamine is administered, usually five nights per week over a period of several hours, using an automatic pump that can be used during sleep or taken anywhere the person goes  This medication is able to bind to the excess iron, which can then be eliminated through urine  If desferoxamine is not used regularly or is unavailable, iron overload can develop and cause tissue damage and organ damage and failure  The heart, liver, and endocrine organs are particularly vulnerable  Desferoxamine itself may rarely produce allergic or toxic side effects, including hearing damage  Signs of desferoxamine toxicity are screened for and generally develop in individuals who overuse the medication when body iron levels are sufficiently low  Overall, however, transfusion and desferoxamine therapy have increased the life expectancy of individuals with the most severe types of beta thalassemia major to the 4th or 5th decade  This can be expected to improve with time and increased developments in treatment, as well as for those with more mild forms of the disease 
New treatments offer additional options for some individuals with beta thalassemia major  There are various medications that target the production of red blood cells (i e  erythropoeitin) or fetal hemoglobin (i e  hydroxyurea and butyrate)  Their effectiveness in ameliorating the severity of beta thalassemia is currently being investigated  Another promising new treatment is bone marrow transplantation, in which the bone marrow of an affected individual is replaced with the bone marrow of an unaffected donor  If successful, this treatment can provide a cure  However, there is an approximately 10-15% chance the procedure could be unsuccessful (i e  the thalassemia returns); result in complications (i e  graft-versus-host disease); or result in death  The risk for specific individuals depends on current health status, age, and other factors  Because of the risks involved and the fact that beta thalassemia is a treatable condition, transplant physicians require a brother or sister donor who has an identically matched tissue type, called HLA type  HLA type refers to the unique set of proteins present on each individual's cells, which allows the immune system to recognize "self" from "foreign " HLA type is genetically determined, so there is a 25% chance for two siblings to be a match  Transplant physicians and researchers are also investigating ways to improve the safety and effectiveness of bone marrow transplantation  Using newborn sibling umbilical cord blood—the blood from the placenta that is otherwise discarded after birth but contains cells that can go on to make bone marrow—seems to provide a safer and perhaps more effective source of donor cells  Donors and recipients may not have to be perfect HLA matches for a successful transplant using cord blood cells  Trials are also underway to determine the effectiveness of "partial transplants," in which a safer transplant procedure is used to replace only a percentage of the affected individual's bone marrow  Other possible treatments on the horizon may include gene therapy techniques aimed at increasing the amount of normal hemoglobin the body is able to make 
Hemoglobin H disease is a relatively mild form of thalassemia that may go unrecognized  It is not generally considered a condition that will reduce one's life expectancy  Education is an important part of managing the health of an individual with hemoglobin H disease  It is important to be able to recognize the signs of severe anemia that require medical attention  It is also important to be aware of the medications, chemicals, and other exposures to avoid due to the theoretical risk they pose of causing a severe anemia event  When severe anemia occurs, it is treated with blood transfusion therapy  For individuals with hemoglobin H disease, this is rarely required  For those with the hemoglobin H/Constant Spring form of the disease, the need for transfusions may be intermittent or ongoing, perhaps on a monthly basis and requiring desferoxamine treatment  Individuals with this more severe form of the disease may also have an increased chance of requiring removal of an enlarged and/or overactive spleen 
Anemia — A blood condition in which the level of hemoglobin or the number of red blood cells falls below normal values  Common symptoms include paleness, fatigue, and shortness of breath 
Bilirubin — A yellow pigment that is the end result of hemoglobin breakdown  This pigment is metabolized in the liver and excreted from the body through the bile  Bloodstream levels are normally low; however, extensive red cell destruction leads to excessive bilirubin formation and jaundice 
Bone marrow — A spongy tissue located in the hollow centers of certain bones, such as the skull and hip bones  Bone marrow is the site of blood cell generation 
Bone marrow transplantation — A medical procedure used to treat some diseases that arise from defective blood cell formation in the bone marrow  Healthy bone marrow is extracted from a donor to replace the marrow in an ailing individual  Proteins on the surface of bone marrow cells must be identical or very closely matched between a donor and the recipient 
Desferoxamine — The primary drug used in iron chelation therapy  It aids in counteracting the life-threatening buildup of iron in the body associated with long-term blood transfusions 
Globin — One of the component protein molecules found in hemoglobin  Normal adult hemoglobin has a pair each of alpha-globin and beta-globin molecules 
Heme — The iron-containing molecule in hemoglobin that serves as the site for oxygen binding 
Hemoglobin — Protein-iron compound in the blood that carries oxygen to the cells and carries carbon dioxide away from the cells 
Hemoglobin A — Normal adult hemoglobin that contains a heme molecule, two alpha-globin molecules, and two beta-globin molecules 
Hemoglobin electrophoresis — A laboratory test that separates molecules based on their size, shape, or electrical charge 
Hepatomegaly — An abnormally large liver 
HLA type — Refers to the unique set of proteins called human leukocyte antigens  These proteins are present on each individual's cell and allow the immune system to recognize 'self' from 'foreign'  HLA type is particularly important in organ and tissue transplantation 
Hydroxyurea — A drug that has been shown to induce production of fetal hemoglobin  Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin  Higher-than-normal levels of fetal hemoglobin can ameliorate some of the symptoms of thalassemia 
Iron overload — A side effect of frequent blood transfusions in which the body accumulates abnormally high levels of iron  Iron deposits can form in organs, particularly the heart, and cause life-threatening damage 
Jaundice — Yellowing of the skin or eyes due to excess of bilirubin in the blood 
Mutation — A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted to offspring 
Placenta — The organ responsible for oxygen and nutrition exchange between a pregnant mother and her developing baby 
Red blood cell — Hemoglobin-containing blood cells that transport oxygen from the lungs to tissues  In the tissues, the red blood cells exchange their oxygen for carbon dioxide, which is brought back to the lungs to be exhaled 
Screening — Process through which carriers of a trait may be identified within a population 
Splenomegaly — Enlargement of the spleen 
Because alpha thalassemia major is most often a condition that is fatal in the prenatal or newborn period, treatment has previously been focused on identifying affected pregnancies in order to provide appropriate management to reduce potential maternal complications  Pregnancy termination provides one form of management  Increased prenatal surveillance and early treatment of maternal complications is an approach that is appropriate for mothers who wish to continue their pregnancy with the knowledge that the baby will most likely not survive  In recent years, there have been a handful of infants with this condition who have survived long-term  Most of these infants received experimental treatment including transfusions before birth, early delivery, and even bone marrow transplantation before birth, although the latter procedure has not yet been successful  For those infants that survive to delivery, there seems to be an increased risk of developmental problems and physical effects, particularly heart and genital malformations  Otherwise, their medical outlook is similar to a child with beta thalassemia major, with the important exception that ongoing, life-long blood transfusions begin right at birth 
As discussed above, the prognosis for individuals with the most serious types of thalassemia has improved drastically in the last several years following recent medical advances in transfusion, chemo-, and transplantation therapy  Advances continue and promise to improve the life expectancy and quality of life further for affected individuals 
"First Known Heart Attack Associated With Beta-thalassemia Major Reported " Heart Disease Weekly February 22, 2004: 10 
"Novel Alpha-thalassemia Mutations Identified " Hematology Week January 26, 2004: 19 
Children's Blood Foundation  333 East 38th St , Room 830, New York, NY 10016-2745  (212) 297-4336  cfg@nyh med cornell edu 
Cooley's Anemia Foundation, Inc  129-09 26th Ave  #203, Flushing, NY 11354  (800) 522-7222 or (718) 321-2873  http://www thalassemia org 
March of Dimes Birth Defects Foundation  1275 Mamaroneck Ave , White Plains, NY 10605  (888) 663-4637  resourcecenter@modimes org  http://www modimes org 
National Heart, Lung, and Blood Institute  PO Box 30105, Bethseda, MD 20824-0105  (301) 592-8573  nhlbiinfo@rover nhlbi nih gov  http://www nhlbi nih gov 
National Organization for Rare Disorders (NORD)  PO Box 8923, New Fairfield, CT 06812-8923  (203) 746-6518 or (800) 999-6673  Fax: (203) 746-6481  http://www rarediseases org 
Bojanowski J  "Alpha Thalassemia Major: The Possibility of Long-Term Survival " Pamphlet from the Northern California Comprehensive Thalassemia Center  (1999) 
Children's Hospital Oakland, Northern California Comprehensive Thalassemia Center website  http://www thalassemia com 
Cooley's Anemia Foundation, Inc  website  http://www thalassemia org/gohome html 
Joint Center for Sickle Cell and Thalassemic Disorders website  http://cancer mgh harvard edu/medOnc/sickle htm 
[thal″ah-se´me-ah]
a heterogeneous group of hereditary hemolytic anemias marked by a decreased rate of synthesis of one or more hemoglobin polypeptide chains, classified according to the chain involved (α, β, δ); the two major categories are α- and β-thalassemia 
α-thalassemia (alpha-thalassemia) that caused by diminished synthesis of alpha chains of hemoglobin  The homozygous form is incompatible with life, the stillborn infant displaying severe hydrops fetalis  The heterozygous form may be asymptomatic or marked by mild anemia 
β-thalassemia (beta-thalassemia) that caused by diminished synthesis of beta chains of hemoglobin  The homozygous form is called t  major and the heterozygous form is called t  minor 
thalassemia ma´jor the homozygous form of β-thalassemia, in which hemoglobin A is completely absent; it appears in the newborn period and is marked by hemolytic, hypochromic, microcytic anemia; hepatosplenomegaly; skeletal deformation; mongoloid facies; and cardiac enlargement 
thalassemia mi´nor the heterozygous form of β-thalassemia; it is usually asymptomatic, but there may be mild anemia 
sickle cell–thalassemia a hereditary anemia involving simultaneous heterozygosity for hemoglobin S and thalassemia 
thal·as·se·mi·a
, thalassanemia (thal'ă-sē'mē-ă, thă-las-ă-nē'mē-ă),
Any of a group of inherited disorders of hemoglobin metabolism in which there is impaired synthesis of one or more of the polypeptide chains of globin; several genetic types exist, and the corresponding clinical picture may vary from barely detectable hematologic abnormality to severe and fatal anemia 
[G  thalassa, the sea, + haima, blood]
/thal·as·se·mia/ (thal″ah-se´me-ah) a heterogeneous group of hereditary hemolytic anemias marked by a decreased rate of synthesis of one or more hemoglobin polypeptide chains, classified according to the chain involved (α, β, δ); the two major categories are α- and β-thalassemia 
α-thalassemia that caused by diminished synthesis of alpha chains of hemoglobin  The homozygous form is incompatible with life, the stillborn infant displaying severe hydrops fetalis  The heterozygous form may be asymptomatic or marked by mild anemia 
β-thalassemia that caused by diminished synthesis of beta chains of hemoglobin  The homozygous form is called t  major and the heterozygous form is called t  minor 
thalassemia ma´jor the homozygous form of &#x03B2;, in which hemoglobin A is completely absent; it appears in the newborn period and is marked by hemolytic, hypochromic, microcytic anemia, hepatosplenomegaly, skeletal deformation, mongoloid facies, and cardiac enlargement 
thalassemia mi´nor the heterozygous form of &#x03B2;, usually asymptomatic, although there is sometimes mild anemia 
(thăl′ə-sē′mē-ə)
An inherited form of anemia occurring chiefly among people of Mediterranean descent, caused by faulty synthesis of part of the hemoglobin molecule  Also called Mediterranean anemia 
thal′as·se′mic adj 
[thal′əsē′mē·ə]
Etymology: Gk, thalassa, sea, a + haima, without blood
production and hemolytic anemia characterized by microcytic, hypochromic red blood cells  Thalassemia is caused by inherited deficiency of alpha- or beta-globin synthesis  See also hemochromatosis, hemosiderosis 
Beta thalassemia, clinical thalassemia, Cooley's anemia, Mediterranean anemia, thalassemia major Hematology A group of genetic diseases by underproduction of hemoglobin due to mutations in the beta globin gene, which is more common in Mediterraneans Heredity Parents are carriers–heterozygotes; one in 4 children is homozygous for the mutation and thus has full-blown disease Clinical See Anemia  Cf Sickle cell anemia 
α-thalassemia
Hemoglobin Barts Hematology An inherited condition caused by a defect in the synthesis of the Hb α chain; Hb Barts hemoglobinopathy is characterized by the presence of 4 gamma chains; it is more common in southeast Asians; the most severe form of alpha thalassemia causes stillbirth due to hydrops fetalis Heredity Parents are carriers–heterozygotes; one in 4 children is homozygous for the mutation and thus has full-blown disease Clinical Pallor, fatiguability, FTT, fever, infections, diarrhea Management Transfusions
Thalassemia major Hematology A hemoglobinopathy caused by a defect in the synthesis of Hb β chain Clinical Pallor, fatigability, FTT, fever due to infections, diarrhea, bone deformities, hepatosplenomegaly Management Transfusions, but iron overload can damage the heart, liver, and endocrine systems, ergo iron chelation–early use of deferiprone, deferoxamine ↓ transfusion-related iron overload and may protect against DM, cardiac disease, early death
δ-thalassemia
Hematology A condition characterized by a defect of Hb A2–α2δ2; because Hb A2 comprises only 3% of the circulating Hb, even its complete absence; δ-thalassemia has little clinical or hematologic impact
γ-thalassemia
Hematology A condition characterized by a defect of gamma–γ Hb chains found in Hb F–α2γ2; because Hb F is present primarily in the fetus and newborns, it is rarely seen outside of the neonatal period, but may cause transient neonatal hemolytic anemia 
, thalassanemia (thal'ă-sē'mē-ă, -ă-să-nē'mē-ă)
Any of a group of inherited disorders of hemoglobin metabolism in which there is impaired synthesis of one or more of the polypeptide chains of globin; several genetic types exist, and the corresponding clinical picture may vary from barely detectable hematologic abnormality to severe and fatal anemia  People of Mediterranean, extraction are more often affected than others by this type of anemia 
Synonym(s): thalassaemia, thalassanaemia 
Any of a group of inherited disorders of hemoglobin metabolism with impaired synthesis of one or more polypeptide chains of globin; several genetic types exist 
<a href="https://medical-dictionary thefreedictionary com/Thalassaemia+minor">thalassemia</a>
Barts hemoglobin
beta hemoglobinopathy
beta-delta thalassemia
beta-thalassaemia
Bite Cell
black gallstone
I know of a couple, totally unrelated and unbeknownst to them, who are silent carriers of Thalassaemia minor 
Pakistan: Genetic factor: All in the genes
But, unfortunately, when one person with thalassaemia minor carrier happens to marry another with the same diagnosis, there is a strong possibility that their child would be thalassaemia major, as happened in the case of Taneja 
' My life depends upon a monthly blood transfusion '
0] thalassaemia demonstrates variable severity, ranging from a condition similar to [beta] thalassaemia minor to something approaching thalassaemia major 
A retrospective review of homozygous haemoglobin E patients
Thal, Alan P 
thalame
thalamencephalic
thalamencephalon
thalamic
thalamic fasciculus
thalamic nucleus
thalamic pain syndrome
thalamic peduncle
thalamic radiation
thalamo-
thalamocoele
thalamocortical
thalamocortical fibers
thalamogeniculate artery
thalamolenticular
thalamoperforating artery
thalamostriate radiation
thalamotuberal artery
Thalassaemia minor
thalassaemiaor Cooley's disease
thalassemic facies
thalasso-
Thalassobacter
Thalassobacter utilis
thalassoplankton
thalassoposia
thalidomide neuropathy
Thalidomider
thallium poisoning
Thalarctos
THALAS
Thalasaemia
Thalassaemia Association of Malaysia
thalassaemia major
Thalassaemias
thalassaemic
thalassanaemia
Thalassemia Action Group
Thalassemia Clinical Research Network
thalassemia syndrome
Context 3: \section{Introduction}

The publicly available XMM-Newton slew data covers to date around 35\%
of the sky  The soft band (0 2$-$2 keV) sensitivity limit of the slews
(6$\times10^{-13}$\,ergs cm$^{-2}$ s$^{-1}$) is close to that of the
ROSAT All-Sky Survey (RASS; Voges et al \ 1999), and in the medium
(2$-$12 keV) band, the slew data goes significantly deeper
(4$\times10^{-12}$\,ergs cm$^{-2}$ s$^{-1}$) than all other previous
large area surveys  Over 7700 individual sources have so far been
detected to a positional accuracy of 8\arcsec   For details on the
the construction and
characteristics of the first released XMM-Newton slew survey
catalogue, see Saxton et al  (2008)  For details of the initial
science results from the slew survey, see Read et al  (2006) 

The comparison of XMM-Newton slew data with the RASS is now giving,
for the first time, the opportunity to find exotic, extreme
high-variability X-ray bursting objects, e g  tidal disruption
candidates (Esquej et al  2007), and also Galactic novae, flare stars,
and flaring white dwarfs, plus eclipsing binaries, AGN and blazars  It
is only with such a large-area survey as the XMM-Newton Slew Survey,
that transient events as these have a chance of being caught 

One such rare event, XMMSL1~J060636 2-694933, which we here show to be
a new Classical Nova, was discovered in an XMM-Newton slew from 18th
July 2006 at a very high count rate of 23 3\,ct s$^{-1}$ (EPIC-pn:
0 2$-$2\,keV)  

Classical novae (see Bode \& Evans 2008 for a review) occur in
interacting binary systems consisting of a white dwarf primary star
and a lower-mass secondary star  The nova itself is a cataclysmic
nuclear explosion caused by the accretion of material (via Roche Lobe
overflow or wind accretion) from the secondary star onto the surface
of the white dwarf; here the pressure and temperature at the base of
the accreted material becomes sufficient to trigger a thermonuclear
runaway  A recent review of the thermonuclear processes powering
classical novae can be found in Starrfield et al \ (2008)   The
accreted material is partially expelled, obscuring the X-ray emission
from the surface of the white dwarf  At later stages, the ejected
material expands further and becomes optically thin, revealing the
nuclear burning on the surface of the white dwarf   This emission
peaks in the soft X-ray regime and it is known as the super-soft
source (SSS) state (Krautter 2008)  Models of the classical nova SSS
state can be found in Tuchman \& Truran (1998) and Sala \& Hernanz
(2005) 

Though many classical novae have been observed in X-rays in their SSS
states (Ness et al \ (2007) for example discuss several examples observed with
Swift), it is in the optical band, early in their outbursts, that
classical novae are almost always discovered  This is because they are
intrinsically optically bright and easily found in inexpensive
wide-area shallow surveys   XMMSL1~J060636 2-694933 is very unusual
therefore in that it has been discovered, as we shall see, later in
its evolution, in the SSS X-ray state 

In this paper we describe the XMM-Newton slew observations
(Section~2), and the follow-up X-ray observations by the Swift XRT
(Section~3) and XMM-Newton (Section~4)  Multiwavelength observations
with Swift-UVOT, Magellan and ASAS are described in Section~5  We then
present a discussion of the results (Section~6), and conclusions 



\begin{table*}[t]
  \caption[]
  {Details of the four XMM-Newton Slew observations and the single (Rev \,1378) 
    dedicated XMM-Newton pointed observation  XMM-Newton revolution, date and observation ID 
    are tabulated, together with the 0 2$-$2 0\,keV X-ray properties of XMMSL1~J060636 2-694933;  
    position, background-subtracted counts, exposure, count-rate, and detection likelihood  For the 
    Rev \,1378 dedicated observation, these properties are given for all the EPIC cameras combined   
    For the slew observations, only the EPIC-pn values are given  In the first two slews the source 
    was not detected, and upper limits are shown in the table }
  \centering
\begin{tabular}{lccccrrrr}
\hline
Rev  & Date & Obs \,ID & RA(J2000)   & Dec(J2000) & Counts         & Exposure & Count rate  & Lik  \\ 
     & (UT) &        &     &            &                & (s) & (s$^{-1}$)  &      \\ \hline 
 351 (slew) & 07/11/01 &  9035100003  &        &               & $<$3 6     & 8 8 & $<$0 41 & $<$$\sim$8      \\
 750 (slew) & 12/01/04 &  9075000003  &        &               & $<$3 2     & 17 3 & $<$0 18 & $<$$\sim$8      \\  
1210 (slew )& 18/07/06 &  9121000003  & 06:06:36 2 & -69:49:33 & 228 8$\pm$14 1 & 9 8 & 23 4$\pm$1 4 & 1777 1   \\ 
1246 (slew) & 28/09/06 &  9121460003  & 06:06:36 5 & -69:49:38 &  12 9$\pm$2 4  & 3 4 &  3 8$\pm$0 7 &   54 7   \\
\vspace{-3 5mm}\\
\hline 
1378 (pointed) & 19/06/07 &  0510010501  & 06:06:36 5 & -69:49:37 & 1511 0$\pm$44 8 & 8940 0 &  0 20$\pm$0 01 & 4630 4          \\
\hline
\end{tabular}
\label{slewtable}
\end{table*}

\section{XMM-Newton slew observations}

XMMSL1~J060636 2-694933 was discovered in XMM-Newton slew 9121000003
from revolution 1210 on 18th July 2006  Details of the standard
XMM-Newton slew data reduction and analysis used, plus the
source-searching and catalogue cross-correlation etc , are presented
in Saxton et al   (2008) 

The source passed through the EPIC-pn detector in 14\,s, at a small
off-axis angle, such that an effective vignetting-corrected soft band
(0 2$-$2\,keV) exposure time of 9 8\,s was achieved   A total of 229
source counts lie within a radius of 20\arcsec, yielding a (EPIC-pn:
0 2$-$2\,keV) count rate of 23 4\,ct s$^{-1}$ 

The source is seen to have no cross-correlation identifications in the
RASS, and no other multiwavelength candidates within 30\arcsec\ in
Simbad\footnote{http://simbad u-strasbg fr/simbad/},
NED\footnote{http://nedwww ipac caltech edu/index html}, and
HEASARC\footnote{http://heasarc gsfc nasa gov/}  The position of the
source in the sky is such that it lies apparently at the outer eastern
edge of the LMC 

XMM-Newton has slewed over this region of sky a number of times, and
though nothing was detected in previous slews from 7th November 2001
and 12th January 2004, the source was seen again on 28th September
2006 (rev \,1246, 72 days after the rev \,1210 discovery), at the same
position, but at a reduced flux level (3 8\,ct s$^{-1}$; EPIC-pn:
0 2$-$2\,keV)   i e  it had reduced in flux by a factor of $\approx$6
in 72 days  XMM-Newton has not slewed over this area of sky since
rev \,1246  Details of the relevant XMM-Newton slews, together with
the (0 2$-$2\,keV) EPIC-pn source position, detected source counts,
count rate and detection likelihood are given in
Table~\ref{slewtable} 

The fact that XMMSL1 J060636 2-694933 is detected in the total-band
(0 2$-$12\,keV) and the soft-band (0 2$-$2\,keV), whilst effectively
zero counts are seen in the hard-band (2$-$12\,keV), is immediately
indicative of the source being very soft  

The moderately high count rate indicates that the spectrum is affected
by pile-up (the on-axis limit is 6\,ct s$^{-1}$ for EPIC-pn full-frame
mode
\footnote{http://xmm esac esa int/external/xmm\_user\_support/documentation
  /uhb\_2 5/index html})  This distorts the spectrum and makes
quantitative spectral analysis of the slew data difficult  We
minimized these effects by following the standard procedure, i e 
ignoring the central part of the Point Spread Function (PSF), and
extracted an event spectrum (containing single and double events) of
the source from within an annulus of 5\arcsec$-$30\arcsec\ radius,
centred on the source position  Unresolved problems associated with
the motion of sources across the detector still exist within slew
data, and approximations currently have to be made when calculating
the associated effective area and detector response matrix files  In
order to perform qualitative spectral analysis, an effective area file
was generated by averaging the individual core-removed effective area
files at 9 different positions along the detector track made by the
source  This accounts for the removal of the piled-up core, and takes
the vignetting and PSF variations into account to a good
approximation   Individual BACKSCAL values have been set by hand, as
have the EXPOSURE values, estimated by calculating the distance
travelled by the source in detector coordinates and finding the time
taken to do this, given a 90\,deg\,hr$^{-1}$ slew speed, then
subtracting the appropriate fractions for chip gaps and bad pixels 
For the response matrix, we used the equivalent canned detector
response matrix for the vignetting-weighted average source position,
for single plus double events and for full-frame mode:
epn\_ff20\_sdY6\_v6 9 rmf  A background spectrum was extracted from a
much larger circular region close to the source and at a similar
off-axis angle 

To fit the slew spectral data, and indeed all the high-energy spectra
in the present paper, the
XSPEC\footnote{http://heasarc gsfc nasa gov/docs/xanadu/xspec/}
spectral fitting package has been used  As $\chi^2$ minimization is
not valid when fitting spectra of low statistical quality, for the
fitting of the slew spectrum (and all the spectral fitting in the
present paper), C-statistics have been used  To take into account the
absorbing column along the line of sight, the {\em wabs} model with
the {\em wilm} cosmic abundance table (Wilms et al \ 2000) has been
used throughout the paper  All the errors quoted in the present paper
are 90\% confidence intervals, unless otherwise stated 

The rev \,1210 slew spectrum shows that the source is very soft, and
appears consistent with a 63$_{-10}^{+12}$\,eV black body, absorbed by
a hydrogen column density of
8 2$_{-4 1}^{+5 4}\times10^{20}$\,cm$^{-2}$  The fit is good, with a
P-statistic value of 0 11, obtained via the XSPEC {\em goodness}
command for this fit, based on 5000 random simulations  The best-fit
hydrogen column is equal to the full Galactic hydrogen column in the
direction of the source (8 0$\pm{1 1}\times10^{20}$\,cm$^{-2}$; Dickey
\& Lockman, 1990, calculated via the FTOOL {\em
  nh}\footnote{http://heasarc gsfc nasa gov/lheasoft/ftools/fhelp/nh txt}) 
The slew spectrum, plus the best fit simple black body model and the
deviations from the model, are shown in Fig \,\ref{slewspec}  The
observed count rate corresponds to a (0 2$-$2\,keV) flux, corrected
for the removal of the saturated PSF core, of
4 8$^{+2 7}_{-1 6}\times10^{-11}$\,ergs cm$^{-2}$ s$^{-1}$ (an
increase in flux over the RASS upper limit, assuming the same spectral
model, by a factor of more than 500) 

Simple power-law, thermal Bremmstrahlung, and other optically thin hot
plasma models are unable to fit the spectrum adequately well   Given
that we later are able to identify the source as a nova (Section~5 2),
then the black-body model will likely be a good approximation 
Furthermore, as we have obtained here a moderate number of slew
counts, the more physically realistic, though more complex atmosphere
model for CO white dwarfs of MacDonald \& Vennes (1991), provided by
K \,Page (private communication), was attempted   This model, used
e g  to model the nova V1974 Cyg (Balman et al \ 1998), yielded a
marginal fit (and not formally a more statistically significant fit;
P-statistic = 0 03, based on 5000 random simulations), with an
effective temperature of 70$^{+8}_{-6}$\,eV, an $N_{\rm H}$ of
3 7$^{+3 2}_{-2 5}$$\times$$10^{20}$\,cm$^{-2}$, and a PSF-corrected
(0 2$-$2\,keV) flux of 4 5$^{+1 3}_{-1 8}\times10^{-11}$\,ergs
cm$^{-2}$ s$^{-1}$  Note that a smaller $N_{\rm H}$ (though perhaps
still consistent with the full Galactic hydrogen column) is now
obtained using the white dwarf atmosphere model  (Note that the
MacDonald \& Vennes (1991) ONe white dwarf atmosphere model was also
attempted, but yielded a marginally worse fit than the CO white dwarf
atmosphere model; only the CO atmosphere model has been used in the
subsequent analysis) 

It is well known (e g  Krautter et al \ 1996) that, because of the
energy-dependent opacity in the white dwarf atmosphere, fits to super
soft source novae spectra with black body models give larger fluxes
and lower temperatures than atmosphere models fit to the same spectra,
and this is seen in the present case  Thus the black body model
requires a larger $N_{\rm H}$ to fit the same data than the atmosphere
model, as is seen  

The model normalizations, corrected for the removal
of the saturated PSF core, can be used to derive an approximate
distance to the source   If we assume a typical emitting region for
the white dwarf atmosphere to be of spherical radius 10$^{9}$\,cm,
then, for the black body model, this distance turns out to be
20$^{+31}_{-10}$\,kpc  The effects discussed above however can lead to
usage of the black body model giving rise to an underestimation of the
distance   For the white dwarf atmosphere model, a larger distance of
71$^{+27}_{-23}$\,kpc is obtained  Both estimates are consistent with
the distance to the LMC ($\sim$50\,kpc, see Section~6), and assuming a
distance of 50\,kpc, the black body derived flux corresponds to a
(pile-up corrected) 0 2$-$2\,keV X-ray luminosity of
1 4$^{+0 8}_{-0 5}\times10^{37}$\,ergs s$^{-1}$ 


\begin{figure}
\centering
\includegraphics[bb=100 20 575 700,clip,width=6 0cm,angle=270]{12082f1 ps}
\caption{XMM-Newton Slew spectrum of XMMSL1 J060636 2-694933 from
  XMM-Newton revolution 1210   The data points (crosses; adjacent data
  bins having been grouped together for the plot to have a significance of at least
  3) have been fitted with a black body model (kT=63\,eV; see text) 
  The solid line shows the best fit to the spectrum  The ratio of the
  data to the best fit model is shown in the lower panel }
\label{slewspec}
\end{figure}


\section{Swift XRT X-ray observations}

We requested and received a prompt observation with Swift of this
source before it moved out of the Swift visibility window in April
2007  We received over 14\,ksec of Swift-XRT time in 7
separate observations and the details of these observations are listed
in Table~\ref{xrttable}  All of the observations were in photon
counting mode and none of the observations showed any times of
significant high-BG flux  In none of the observations did the source
position coincide with any of the dead (micrometeorite-induced)
detector columns  The analysis has been performed using HEASOFT
v6 1 2  The individual XRT observations were astrometrically-corrected
and then stacked to ascertain a best Swift-XRT position $-$ this was
found to be 06 06 37 00 -69 49 33 9 (with a 90\% error radius of
4 0\arcsec)  Source counts were then extracted from each observation
from a circle of radius of 40\arcsec\ at this position  Background
counts were extracted from each observation from large-radius
off-source circles close to the source position  Source counts and
count rates for the individual XRT observations are given in
Table~\ref{xrttable} 


\begin{table}
  \caption[]{Details of the Swift-XRT observations (observation ID, observation date and 
    cleaned exposure time) are tabulated, together with the total (0 2$-$2 0\,keV) background-subtracted 
    counts and count rate from XMMSL1 J060636 2-694933 (see text) }
  \centering
\begin{tabular}{ccrrr}
\hline
ID          & Date     & Exp  & Counts       & Count rate       \\ 
            &   (UT)   &  (s) &              & (s$^{-1}$)        \\ \hline 
00030895001 & 28/02/07 & 1955 & 23 9$\pm$5 1 & 0 0122$\pm$0 0026  \\
00030895002 & 07/03/07 & 1796 & 15 8$\pm$4 2 & 0 0088$\pm$0 0024 \\
00030895003 & 08/03/07 & 1651 & 10 9$\pm$3 6 & 0 0066$\pm$0 0022 \\
00030895004 & 08/03/07 & 2547 & 20 6$\pm$4 8 & 0 0081$\pm$0 0019 \\
00030895005 & 10/03/07 & 2550 & 29 5$\pm$5 7 & 0 0116$\pm$0 0022 \\
00030895006 & 20/03/07 &  552 &  8 6$\pm$3 2 & 0 0156$\pm$0 0057 \\
00030895007 & 22/03/07 & 3391 & 24 4$\pm$5 4 & 0 0072$\pm$0 0016 \\
\hline
\end{tabular}
\label{xrttable}
\end{table}

The observation naturally fell into three time-separated groups, those
of obs \,1, obs \,2-5 and obs \,6-7  A similar analysis applied to
these groups (where the statistics are improved) gives rise to source
counts and count rates of 76 7$\pm$9 3\,counts and
0 0090$\pm$0 0011\,ct~s$^{-1}$ (for obs \,2-5), and
33 0$\pm$6 2\,counts and 0 0084$\pm$0 0016\,ct~s$^{-1}$ (for
obs \,6-7)  (Analysis of all the data together yields
133 6$\pm$12 3\,counts and 0 0092$\pm$0 0009\,ct~s$^{-1}$)  

A spectrum was extracted from all the Swift-XRT data from a 40\arcsec\
radius circle, using grades 0$-$12, centred on the Swift-XRT position 
A background spectrum was extracted again from all the Swift-XRT data,
from large-radius off-source circles close to the source position  An
ARF file was created using {\em xrtmkarf} and the appropriate RMF
(swxpc0to12\_20010101v008 rmf) from the Swift-XRT Calibration Database
was obtained 

Standard spectral models were again fit to the spectral data using
XSPEC  Again, C-statistics were used, as was the {\em wabs} absorption
model with the {\em wilm} cosmic abundance table  It was again 
obvious that only a very soft spectrum would be appropriate for the
data, and the only simple model that was able to fit the data
adequately was a black-body model of temperature
$kT$=$59^{+14}_{-10}$\,eV, with an absorbing hydrogen column of
9 5$^{+5 0}_{-3 9}$$\times$$10^{20}$\,cm$^{-2}$  No sufficiently constrained parameters could
be obtained using the CO white dwarf atmosphere model (MacDonald \&
Vennes 1991)  The Swift-XRT spectrum, together with the best-fit black
body model is shown in Fig \,\ref{xrtspec}  The corresponding
(0 2$-$2 0\,keV) flux is 2 7$^{+0 7}_{-1 2}\times10^{-13}$\,ergs
cm$^{-2}$ s$^{-1}$ (i e  a reduction by more than a factor 100 from
the XMM-Newton slew discovery flux), and the X-ray luminosity, for the
assumed distance of 50\,kpc, is 8 0$^{+2 2}_{-3 5}\times10^{34}$\,ergs
s$^{-1}$ 

\begin{figure}
\centering
\includegraphics[bb=100 15 580 710,clip,width=6 0cm,angle=270]{12082f2 ps}
\caption{Swift-XRT spectrum from XMMSL1 J060636 2-694933  The data
  points (crosses; adjacent data bins having been grouped together for
  the plot to have a significance of at least 3) have been fitted with
  a black body model (kT=59\,eV; see text)  The source has faded by a
  factor of $>100$ since the XMM-Newton revolution 1210 slew
  discovery  The solid line show the best fit to the spectra   The
  ratio of the data to the best fit model is shown in the lower panel 
}
\label{xrtspec}
\end{figure}

A cautious estimate of the size of the emitting region can be obtained
from the model normalization; the assumed distance of 50\,kpc yields a
maximum radius of 4 5$\times$10$^{8}$\,cm (the fit normalization is
essentially unconstrained at the lower bound)   Though great care
should be taken in interpreting this result, as the black body model
is possibly overestimating the luminosity, this obtained radius is
still consistent with that of moderately massive ($>$1 1$M_{\odot}$)
white dwarfs (Hamada \& Salpeter 1961), i e \,the whole white dwarf
surface may still be emitting at 59\,eV 

\section{Dedicated XMM-Newton observations}

We were granted an XMM-Newton Target of Opportunity (ToO) observation,
once the source became again visible to XMM-Newton, and a 10\,ks
XMM-Newton EPIC observation was made on 19th June 2007 (see
Table~\ref{slewtable})  All the XMM-Newton EPIC data, i e   the data
from the two MOS cameras and the single pn camera, were taken in
full-frame mode with the thin filter in place   These data from the
three EPIC instruments have been reprocessed using the standard
procedures in XMM-Newton SAS (Science Analysis System) $-$ v 7 1 0 
Periods of high-background, of which there were very few, were
filtered out of each dataset by creating a high-energy 10$-$15\,keV
lightcurve of single events over the entire field of view, and
selecting times when this lightcurve peaked above 0 75\,ct s$^{-1}$
(for pn) or 0 25\,ct s$^{-1}$ (for MOS)  This resulted in
$\approx$9 4(8 0)\,ks of low-background MOS(pn) data  Details of this dedicated
XMM-Newton observation, together with source position, and
(0 2$-$2\,keV) all-EPIC combined (pn, MOS1, MOS2) detected source
counts, count rate and detection likelihood are given in
Table~\ref{slewtable} 

Source spectra, containing single and double events, were extracted
from the datasets from circles (none of the data were now piled up)
centred on the source position  An extraction radius, estimated from
where the radial surface brightness profile was seen to fall to the
surrounding background level, was set to 30\arcsec  Background spectra
were extracted from each cleaned dataset from a 40\arcsec$-$80\arcsec\
annulus centred on the source position  Point sources seen to
contaminate these larger-area background spectra were removed from the
background spectra to a radius of 60\arcsec  ARF files were created
for the source spectra, and were checked to confirm that the correct
extraction area calculations had been performed  Finally RMF response
files were generated 
 
Standard spectral models were again fit to the spectral data using
XSPEC  Once again it was obvious that only a very soft model would fit the data; the only
simple model that was able to fit the data well (a P-statistic = 0 17,
based on 5000 random simulations) was a black-body model of
temperature $kT$=70$^{+3}_{-4}$\,eV, with an absorbing hydrogen column
of 6 9$^{+1 0}_{-1 6}\times10^{20}$\,cm$^{-2}$  The spectrum, together with this best-fit
model are shown in Fig \,\ref{xmmspec}  The corresponding
(0 2$-$2 0\,keV) flux is only marginally less than the Swift-XRT value
at 2 2$^{+0 8}_{-0 9}\times10^{-13}$\,ergs cm$^{-2}$ s$^{-1}$ and the
X-ray luminosity (for the assumed distance of 50\,kpc) is
6 7$^{+2 5}_{-2 8}\times10^{34}$\,ergs s$^{-1}$ 

\begin{figure}
\centering
\includegraphics[bb=110 15 570 705,clip,width=6 0cm,angle=270]{12082f3 ps}
\caption{XMM-Newton ToO spectrum from XMMSL1 J060636 2-694933  The
  data points (crosses; adjacent data bins having been grouped
  together for the plot to have a significance of at least 3)) have
  been fitted again with a black body model (kT=70\,eV) (see text) 
  EPIC-pn data is shown in black, with EPIC-MOS1 in red and EPIC-MOS2
  in green  The solid lines show the best fit to the spectra   The
  ratios of the data to the best fit model are shown in the lower
  panel }
\label{xmmspec}
\end{figure}

Given that, in this XMM-Newton ToO observation, we had obtained a
larger number of counts ($\raisebox{-1mm}{$\stackrel{>}{\sim}$}$1500 over the 3 EPIC cameras), the
physically more realistic CO white dwarf atmosphere model (MacDonald \&
Vennes 1991) was also attempted  This yielded a marginal fit (and formally
a no more statistically significant fit; P-statistic = 0 04, based on
5000 random simulations), with an effective temperature of
73$^{+3}_{-2}$\,eV, and an $N_{\rm H}$ of
3 4$^{+0 8}_{-0 8}$$\times$$10^{20}$\,cm$^{-2}$  Again, usage of the black body model results
in a larger fitted $N_{\rm H}$ and a lower fitted temperature than
with the atmosphere model  


As before, the model normalization can be used to obtain a cautious
estimate of the size of the emitting region  For the assumed distance
of 50\,kpc, then the black body model returns an emitting region
radius of only 1 3$\pm$0 2$\times$10$^{8}$\,cm   Again care should be
taken, as this may be an overestimation, the black body model having
perhaps overestimated the luminosity  For the white dwarf atmosphere
model, a smaller radius of 0 4$\pm$0 1$\times$10$^{8}$\,cm is
obtained  Note further that the assumption of a larger distance (see
Section~6) would result in a proportionally larger emitting radius 
The range in allowed radius therefore is quite large, and it is not
impossible for for the whole of the white dwarf surface to be emitting
at 70\,eV  If this is the case, then the white dwarf would have to be
at the high end of the mass range ($>$1 2$M_{\odot}$; Hamada \&
Salpeter 1961)  It may be the case then that we are at this point at,
or close to the end of the SSS phase, where the effective temperature
has reached a maximum (Sala \& Hernanz 2005), as is tentatively seen
in the spectral fitting results, and where the photospheric radius has
reached a minimum, close to the white dwarf radius 


\subsection{X-ray variability}

The full (XMM-Newton slew plus Swift-XRT plus XMM-Newton ToO) X-ray
lightcurve of XMMSL1 J060636 2-694933 is shown in
Fig \,\ref{lightcurve}  The calculated (0 2$-$2 0\,keV) flux values
are shown plotted against the number of days since the rev \,1210
XMM-Newton Slew discovery  The first two data points are the
rev \,1210 and the rev \,1246 XMM-Newton Slew observations  Then the
three nested Swift-XRT points are shown and finally the XMM-Newton ToO
observation  The level of RASS upper limit is shown to the bottom
left  The (0 2$-$2 0\,keV) X-ray flux is seen to have dropped by more
than two orders of magnitude in 230 days since the discovery, but is
then seen to have levelled off for the next 120 days, at a level still
$\approx$3 times that of the RASS  Finally, no evidence for any
short-term variability (using time bins down to 100\,s) is seen in the
highest statistic continuous X-ray lightcurve (the $\approx$8 0\,ksec
background-filtered EPIC-pn lightcurve) obtained from the 19/06/07
XMM-Newton observation 

\begin{figure}
\centering
\includegraphics[bb=60 60 550 454,clip,width=8 7cm]{12082f4 ps}
\caption{The full X-ray lightcurve of XMMSL1 J060636 2-694933  Plotted
  are the calculated (0 2$-$2 0\,keV) flux values versus time  The
  first point is the rev \,1210 XMM-Newton Slew observation, then the
  rev \,1246 XMM-Newton Slew observation  The three nested Swift-XRT points
  are shown next and finally the XMM-Newton ToO observation  The RASS upper
  limit is shown bottom left  }
\label{lightcurve}
\end{figure}


\section{Multi-wavelength Follow-up}

\subsection{Swift UVOT}

For the Feb/Mar 2007 Swift observations, we arranged for both the
Swift UVOT-B filter and the UVOT-UVW2 filters to be used in an
approximate exposure time ratio of 1:5, thus ensuring roughly equal
numbers of counts in the two bands (though there is a spectral type
dependency here)  Swift UVOT images in these two filters of the area
of sky around XMMSL1 J060636 2-694933 are shown in Fig \,\ref{uvot} 

Prior to the Swift UVOT observations, a `best-guess' to the possible
candidate optical/IR counterpart would have been the USNO-A2 0 source
0150-04066298 (B~mag: 17 4, R~mag: 16 1), seen 4\arcsec\ south of the
XMM-Newton slew position  The UVOT images however immediately showed
that the optically fainter source at position RA, Dec (J2000) = 06 06
36 4, -69 49 34 3 (error radius: ~0 5\arcsec) was a very strong UVW2
source and very blue, and was very likely the true counterpart to
XMMSL1~J060636 2-694933  (The UVW2 filter spans approximately
800\AA\,, centred at $\approx$1900\AA)

\begin{figure}
\centering
\includegraphics[bb=-82 210 695 585,clip,width=8 7cm]{12082f5 ps}
\caption{Swift UVOT images of the field around XMMSL1 J060636 2-694933 from observation
  00030895002  Left shows the UVOT B-filter and right shows the the
  UVOT UVW2-filter  The large circle is a 20\arcsec\ radius circle around
  the XMM-Newton Slew position  The small circle in the UVW2 image around the
  bright source is reproduced in the B image, indicating that a faint
  optical source is also visible at this position }
\label{uvot}
\end{figure}

The Swift UVOT pipeline processed data were analysed using the UVOT
photometry package {\em uvotsource} released with
FTOOLs\footnote{http://heasarc nasa gov/lheasoft/ftools/ftools\_menu html} 
This package performs aperture photometry on pre-specified source and
background regions, accounting for photometric- (via PSF fitting) and
coincidence loss- effects using the UVOT calibration files  Source
counts were extracted using a 5\arcsec\ radius aperture centred on the
source, while for the background we used a 10\arcsec\ radius aperture
located in a nearby source-free region   We used a larger background
aperture to effectively smooth over the modulo-8 fixed pattern noise
present in UVOT observations and to improve the statistics of the
background counts  Source counts were converted to UVOT UV-magnitudes
using the UVW2 zero-point calibration released with version~2 8 (Build
22) of the CALDB  The source is seen (see Fig \,\ref{uvotlc}) to be
roughly constant over the short duration of the Swift observations,
with a suggestion of a decline towards the end  This is in keeping
with the general form of the X-ray lightcurve (Fig \,\ref{lightcurve})
at this time 

\begin{figure}
\centering
\includegraphics[bb=80 70 535 380,clip,width=8 7cm]{12082f6 ps}
\caption{Variation of the UVW2 magnitude of the bright UV source
  during the Swift observations  The same time axis as
  Fig \,\ref{lightcurve} has been used to aid comparison, and a zoom
  is also shown  The UVW2 filter was only employed during observations
  00030895002, 00030895004, 00030895005, 00030895006 \& 00030895007
  (hence the points span the dates 07/03/07 to 22/03/07)  The errors here are 1-$\sigma$  }
\label{uvotlc}
\end{figure}

It is possible to include the UVOT-detected flux with the XRT spectrum
described in Section~3  UVOT files, created using {\em uvot2pha} for
the five observations (00030895002, 00030895004, 00030895005,
00030895006 \& 00030895007) where the UVW2 filter was employed, were
incorporated into {\em xspec}, along with the appropriate response
file (swuw2\_20041120v104 rsp) from the Swift-XRT Calibration
Database  We attempted to fit a single black-body spectrum to the
Swift-XRT+UV data (again using C-statistics, the {\em wabs} absorption
model and the {\em wilm} cosmic abundance table, plus the inclusion of
the {\em xspec-redden} component to model the absorption in the UV
band)  The best fit however, with a much lower temperature of
$kT$=$36^{+3}_{-4}$\,eV, is a very poor fit to the data; we obtain a
{\em goodness} P-statistic value of 0 00, based on 5000 random
simulations  This notwithstanding, a flux in the UVW2
(1 57$-$7 77\,eV) band of 3 5$\pm{0 2}\times10^{-13}$\,ergs cm$^{-2}$
s$^{-1}$ can be obtained, corresponding to a UVW2 luminosity, for the
assumed distance of 50\,kpc, of 1 0$\pm{0 1}\times10^{35}$\,ergs
s$^{-1}$ 

The very poor single black-body fit above, plus the large change in
fitted temperature is strongly suggestive that a model other than, or
in addition to the XRT-derived kT=59\,eV black body model (Section~3)
should be used to describe the UVW2 data  As we have no UV data other
than in the UVW2 filter, all that can be done is to apply the
XRT-derived black body model to the UVW2+XRT data, and in doing this,
a large flux excess with respect to the XRT-derived black body model
is seen in the UVW2 band  This is shown in Fig \ref{xrtuvotspec}  This
excess in UV emission (most of the $10^{35}$\,ergs s$^{-1}$ discussed
above) is likely due to a combination of residual post-nova nuclear
burning on the surface of the white dwarf, plus accretion in the disk,
including from emission lines  The situation is likely to be rather
complex, depending on the structure of both the ejecta and the
accretion disk, and is beyond the scope of the present work, where we
only have sparse UV data   For a review of the UV emission from
classical novae, see Shore (2008) 


\begin{figure}
\centering
\includegraphics[bb=100 15 580 710,clip,width=6 0cm,angle=270]{12082f7 ps}
\caption{Swift-XRT spectrum (black) from XMMSL1 J060636 2-694933, plus
  the best-fit black-body model to this spectrum (Section~3; Fig \,2),
  but extending into the UV to the Swift-UVOT UVW2 flux points (coloured)
  (see text)  The data points are plotted such that adjacent data
  bins have been grouped together to have a significance of at least
  3  The solid line show the best fit to the Swift-XRT spectrum  The
  ratio of the data to the best fit model is shown in the lower
  panel }
\label{xrtuvotspec}
\end{figure}


\subsection{Magellan optical observations}

On Nov ~13, 14, and 15, 2007, XMMSL1~J060636 2--694933 was observed
with the Low--Dispersion Survey Spectrograph 3 (LDSS3) mounted on the
Magellan Clay telescope  Images were obtained through the Sloan
$g^\prime$, $r^\prime$ and $i^\prime$ filters  On Nov ~15, 2007
conditions were photometric and the Landolt field RU 149A was observed
to flux calibrate the data in the $g^\prime$, $r^\prime$ and
$i^\prime$--bands   The Landolt (1992) magnitudes of the standards
were converted to Sloan magnitudes using the transformations presented
in Smith et al \ (2002)  All the images were debiased and flatfielded
using dome flatfield frames  We applied aperture photometry on each of
the images using DAOPHOT in \textsc{IRAF}\footnote{\textsc {iraf} is
  distributed by the National Optical Astronomy Observatories} to
compute the instrumental magnitudes of the stars  Differential
photometry of the optical counterpart to XMMSL1~J060636 2-694933
(marked by an arrow in Fig ~\ref{magellan}) was performed with respect
to the field star (marked with a `c' in Fig ~\ref{magellan})  This was the
brightest isolated and unsaturated star common to all frames   The
calibrated brightness of this comparison star is $g'= 18 42 \pm 0 04$,
$r'= 17 85 \pm 0 06$ and $i'=17 58 \pm 0 07$ 

\begin{figure}
\centering
\includegraphics[bb=35 215 575 575,clip,width=8 7cm]{12082f8 ps}
\caption{Magellan Clay LDSS3 finder chart  The counterpart to
  XMMSL1~J060636 2-694933 (and the bright Swift-UVOT UVW2-filter
  source; Figs \ref{uvot}\&\ref{uvotlc}) is marked with an arrow  The comparison star is
  shown marked with a 'c' }
\label{magellan}
\end{figure}

In addition to the imaging observations described above, we have
obtained spectroscopic observations on Nov ~13, 14, and 15, 2007 using
the VPH All grism, which has 660 lines per mm, and employing a
1\arcsec\ wide slit  This set-up provides a mean dispersion of 2\AA\,
per pixel  For a slit width of 1 arcsecond and a mean seeing close to
1\arcsec, the mean spectral resolution is $\approx$10\AA  On Nov ~13, 2007
we took 4 exposures of 450\,s each, on Nov ~14, 2007 we took 2
exposures of 900\,s each, and on Nov ~15, 2007 we took one 1200\,s
exposure with the slit at the parallactic angle  The spectra were bias
and flatfield corrected, and extracted in \textsc{IRAF}  The
instrumental response was corrected using the spectrophotometric flux
calibrators LTT 3218 (Nov ~13), H600 (Nov ~14) and LTT 9293 (Nov ~15) 
Significant differences in the flux around H$\alpha$ are apparent with
the flux being 50\% higher during the Nov ~15, 2007 with respect to
the Nov ~13, 2007 observations  Since there is no evidence for
brightening in the $r^\prime$ images we attribute the difference to
the fact that the source was not observed at the parallactic angle on
Nov ~13 and 14, 2007  We exported the one dimensional spectra to the
spectral analysis software package \textsc{molly} for further
analysis 

\begin{figure}
\centering
\includegraphics[bb=70 30 600 800,clip,width=6 8cm,angle=270]{12082f9 ps}
\caption{Magellan Clay averaged optical spectrum of the optical source
  associated with XMMSL1 J060636 2-694933  The flux scaling is
  approximate  The prominent strong emission lines are marked (see
  text)  }
\label{optspec}
\end{figure}

We have averaged all spectra (see Fig ~\ref{optspec})  We find several
strong emission lines  The strongest of these emission lines are best
interpreted as due to [OIII] 4958 9\AA\, and 5006 9\AA\,, He~II at
4685 8\AA\, and a blend of the H$\alpha$ plus the [NII] at 6548 1\AA\,
and 6583 4\AA\,, lines found often in novae (Williams 1992)  In this
case the main [OIII] lines appear redshifted by approximately 2000\,km
s$^{-1}$  We interprete this as due to clumpy outflows in the nova
shell  The integrated light from different outflowing parts can also
explain the substructure that is present in the [OIII] lines  The
outflow velocities that we obtain for the H$\alpha$ and H$\beta$ lines
is $\approx$350\,km s$^{-1}$, hence less than that for the [OIII]
lines   Note that, if XMMSL1~J060636 2-694933 does reside within the
LMC, then the systematic line-of-sight recession velocity of the LMC,
262$\pm$3 4\,km~s$^{-1}$ (van der Marel et al \ 2002), should be taken
into account; i e \,a good fraction of the observed H$\alpha$ and H$\beta$
recession would then be due to the recession of the LMC itself 

\subsection{Long-term Optical light curve}

Analysis of archival robotic optical survey data from 3-minute CCD
exposures (pixel size 14\arcsec 8), obtained with a 70\,mm (200\,mm
focal length) f/2 8 telephoto lens in the course of the All Sky
Automated Survey (ASAS; Pojmanski 2002) show that the visual magnitude
of this source rose from m$_{V}\raisebox{-1mm}{$\stackrel{>}{\sim}$}$14 to m$_{V}$$\approx$12 between
Sep ~18, 2005 and Sep ~30, 2005, and then declined rapidly thereafter (see
Fig \ref{optlc})  ASAS did not detect any significant emission from
the source after around November 2005, the source having dimmed below
the limiting magnitude of ASAS 

The decline from the brightest data point ($\approx$2 2 magnitudes in
10 days, then a further $\sim$1 3 magnitudes in 46 days) suggests that
this is a nova of the 'very fast' speed class (Warner 1995, Downes
et al \ 2001)  We estimate that the time that the light curve takes to
decline 2 magnitudes below maximum observed brightness is
8$\pm$2\,days (see Section~6) 

\begin{figure}
\centering
\includegraphics[bb=30 78 453 549,clip,width=7 8cm,angle=270]{12082f10 ps}
\caption{All Sky Automated Survey V-band magnitudes of the optical counterpart 
to XMMSL1~J060636 2-694933, during outburst (late September 2005) and afterwards }
\label{optlc}
\end{figure}



\section{Discussion}

The optical spectrum, showing lines of [OIII] 4958 9\AA\, and
5006 9\AA\,, He~II at 4685 8\AA\, and a blend of the H$\alpha$ plus
[NII] at 6548 1\AA\, and 6583 4\AA\, suggests that
XMMSL1~J060636 2-694933 was a nova, observed (in Nov 2007) in the late
A$_{0}$ auroral phase  The fact that the observed [OIII] lines are not
in the more usual, optically thin 3:1 ratio, can be explained in terms
of a clumpy outflow scenario, whereby individual clumps of both
rest-frame and redward-shifted material are observed, and the
superposition of these account for the observed [OIII] ratio (note
further that density enhancements can change observed [OIII] ratios to
more like $\sim$1:1)  Clumps of material are often seen in nova ejecta
(e g  Shara et al \ 1997), and outflows of speeds around 2000\,km
s$^{-1}$ are not uncommon in novae (e g  in nova LMC 1991; Schwartz
et al \ 2001) 

XMMSL1~J060636 2-694933 was likely at its onset (in Oct 2005) a very
fast, Fe~{\sc ii} nova (Section~3 and Williams et al \ 1991; Williams
et al \ 1994)  An accurate classification now however is not possible,
so late after maximum brightness  The soft ($kT_{\rm
  eff}$$\approx$60--70\,eV) X-ray spectrum indicates that the nova was
in a super-soft source (SSS) state (Krautter 2008) during its
discovery (in July 2006), and throughout its X-ray decline (by more
than two orders of magnitude) in the observations of Sept 2006, March
2007 and June 2007   Such a state originates from nuclear burning on
the surface of the white dwarf, and measurements of the intensity,
duration, and temperature can be used to estimate the distance to the
nova and the mass of the white dwarf (e g  Balman et al \ 1998; Lanz
et al \ 2005)  Indeed, we believe (Section~4) that the white dwarf
within XMMSL1~J060636 2-694933 may be quite massive
($>$1 2$M_{\odot}$) 

As discussed earlier, classical novae are almost always discovered
optically in the early phases of their outbursts 
XMMSL1~J060636 2-694933 is very unusual therefore in that it has been
discovered first in X-rays  As such, it is useful to compare it with
XMMSL1~J070542 7-381442 (also known as V598 Pup; Read et al \ 2008),
another nova recently discovered (in X-rays) in the XMM-Newton slew
survey  With a peak $m_{V}$ of $\ltsim12$, XMMSL1~J060636 2-694933 is
not a particularly bright nova (c f  V598 Pup, which reached an
m$_{V}$ of $\raisebox{-1mm}{$\stackrel{<}{\sim}$}$4), and so it is not surprising that it went
unnoticed, only being discovered in X-rays during the later (here
291\,days after the outburst), optically thin nebular phase, when
classical novae are typically observed as soft X-ray sources  Though
this delay should be taken as a upper limit, it is long when compared
to V598 Pup ($\raisebox{-1mm}{$\stackrel{<}{\sim}$}$127 days), but may instead be more similar to the
delays of $\sim$200 days seen in V1974 Cyg (Krautter et al \ 1996),
$\sim$6 months of V382 Vel (Orio et al \ 2002), and 6$-$8 months of
V1494 Aql (Drake et al \ 2003)  In their X-ray monitoring of optical
novae in M31, Pietsch et al \ (2007) detect 11 out of 34 novae in
X-rays within a year after their optical outbursts  Seven novae are
seen to be X-ray bright, several (3$-$9) years after outburst, and
three novae showed very short X-ray outbursts, starting within
50\,days of outburst, but lasting only two to three months 
XMMSL1~J060636 2-694933 therefore is not particularly unusual 

A method to estimate the distance to the nova is to use the relation
between the absolute magnitude at maximum brightness and the time that
the light curve takes to decline 2 magnitudes below maximum
brightness, $t_{2}$ (Della Valle \& Livio 1995)  We have no
information over the 12 days between the data point of maximum
brightness and the lower limit prior to this (Fig \,\ref{optlc}), and
therefore we have no exact outburst date, nor exact apparent
magnitude at outburst   Assuming for the moment though that we have
caught the outburst exactly in the Sep ~30, 2005 observation, then we
can estimate (Sect ~5 3) $t_{2}$ to be 8$\pm$2\,days, and using this,
we can estimate (Della Valle \& Livio 1995) the absolute magnitude at
maximum brightness $M_{V}$ to be --8 7$\pm$0 6  An absolute magnitude
of $M_{V}$=--8 7 implies a peak luminosity $\sim$7 times the Eddington
luminosity for a 1\,$M_{\odot}$ white dwarf  This is quite typical of
novae 

With $A_{V}$=0 39$^{+0 05}_{-0 09}$ (90\% error), as derived (Predehl
\& Schmitt 1995) from $N_{\rm
  H}$=6 9$^{+1 0}_{-1 6}\times10^{20}$\,cm$^{-2}$ (from the highest
statistic spectral fit; the XMM-Newton ToO observation), and with
$M_{V}$=--8 7$\pm$0 6, and a peak $m_{V}$ of 12 0, we can derive a
distance to XMMSL1~J060636 2-694933 of 115$^{+43}_{-30}$\,kpc   As
discussed above however, we are unsure as to the exact outburst date
and the maximum brightness at outburst  Our assumed peak $m_{V}$ of
12 0 is almost certainly an underestimation  Although we have no
information in the 12 days prior to Sep ~30, 2005, a simple linear
extrapolation of the early October lightcurve back prior to Sep ~30,
2005 suggests that the actual peak $m_{V}$ was somewhere between 9 and
12  The corresponding distance estimates are then between 29 and
115\,kpc (with a mid-point $m_{V}$=10 5 value yielding a distance
estimate of 58\,kpc)  Many methods have been used to estimate the
distance to the LMC (e g   Kovacs 2000, Nelson et al \ 2000), but a
value of around 50\,kpc appears to be quite robust  Our distance
estimate is certainly consistent with that of the LMC, though the
errors are quite large   It does appear to be the case however, that
our distance estimate places the source far outside of our own Galaxy 
This, together with the source's position on the sky (at the eastern
edge of the LMC) and the sizable ($\sim$Galactic) X-ray hydrogen
column densities obtained from the spectral fits, suggest strongly
that XMMSL1~J060636 2-694933 lies within the LMC itself   Note further
that the (pile-up corrected) spectral model normalizations to the
initial Slew discovery data (Sect ~2) also imply an approximate
distance to XMMSL1~J060636 2-694933 of $\sim$50\,kpc 

The source had, at the time of the slew detection, an absorbed
(0 2$-$2\,keV) X-ray flux of 4 8$^{+2 7}_{-1 6}\times10^{-11}$\,ergs
cm$^{-2}$ s$^{-1}$, corresponding to a 0 2$-$2\,keV X-ray luminosity
(at 50\,kpc) of 1 4$^{+0 8}_{-0 5}\times10^{37}$\,ergs s$^{-1}$ 
Assuming instead for the moment a distance more like 100\,kpc (though
this is thought to be well beyond the LMC, e g  Kovacs 2000), then the
(0 2$-$2\,keV) X-ray luminosity of
5 7$^{+3 0}_{-1 9}\times$$10^{37}$\,erg s$^{-1}$ obtained is at the high end of the X-ray luminosities of
classical SSS-phase novae discussed e g \,in Orio et al \ (2002) and
Ness et al \ (2007)  As discussed though, we have very likely missed
the outburst peak, and as such, our more probable assumed distance of
50\,kpc gives rise to a more typical SSS-phase X-ray luminosity   The
luminosities of 7$-$8$\times$$10^{34}$\,erg s$^{-1}$, obtained during
the Swift and pointed XMM-Newton observations, are more typical of
novae at later times, when the emission can also sometimes be
described by a thermal plasma, rather than a black-body type spectrum,
or a more mixed spectrum, due to the complex structure of the ejecta
and the accretion disk (Krautter 2008, Shore 2008) 


\section{Conclusions}

A bright X-ray source, XMMSL1~J060636 2-694933, was detected in an
XMM-Newton slew on 18 July 2006 at a position where no previous X-ray
source had been seen  The XMM-Newton slew data, plus follow-up dedicated
XMM-Newton and Swift observations, plus optical imaging and
spectroscopic data acquired with the Magellan Clay telescope and 
All-Sky Automated Survey (ASAS) data were used to classify the new object
as a nova, and to examine its properties  The primary conclusions are
as follows:

  \begin{itemize}

  \item The soft X-ray spectrum indicates that the nova was in a
    super-soft source (SSS) state at its discovery in July 2007
    (XMM-Newton slew) and through its X-ray decline (by over two
    orders of magnitude) in September 2006 (XMM-Newton slew), March
    2007 (Swift) and June 2007 (XMM-Newton) 

  \item The Magellan optical spectrum (Nov 2007) of the source
    indicates that it was very likely then a nova in the late
    A$_{0}$ auroral phase 

  \item The very fast optical decline (ASAS) during the nova's onset
    (Oct 2005), indicates that the initial nova was likely of speed class
    'very fast' 

  \item The very fast speed, together with the absolute magnitude at
    maximum brightness and the X-ray absorption, give rise to a
    distance to the source far beyond our own Galaxy  The large
    distance, together with the source's position in the sky, at the
    eastern edge of the LMC, and the spectral information from the
    X-ray data, are very suggestive that the nova is situated within
    the LMC itself 

  \item Analysis of XMM-Newton slew data is continuing to provide a
    powerful means of finding new X-ray transient objects 

\end{itemize}

\begin{acknowledgements}

  The XMM-Newton project is an ESA Science Mission with instruments
  and contributions directly funded by ESA Member States and the USA
  (NASA)  The XMM-Newton project is supported by the Bundesministerium
  f\"ur Wirtschaft und Technologie/Deutsches Zentrum f\"ur Luft- und
  Raumfahrt (BMWI/DLR, FKZ 50 OX 0001), the Max-Planck Society and the
  Heidenhain-Stiftung  AMR and PE acknowledge the support of STFC
  funding, and PGJ of the Netherlands Organisation for Scientific
  Research  The ASAS project is supported by the N2030731/1328 grant
  from the MNiSzW  We thank the referee (G \,Sala) for very useful
  comments and several references that have improved the paper
  notably  We thank Kim Page for providing the white dwarf atmosphere
  model, and we thank her and Graham Wynn for useful discussions  The
  use of the spectral analysis software package \textsc{molly} written
  by Tom Marsh is also acknowledged  MM acknowledges support by a
  Miller Institute Research Fellowship during the time in which part
  of the work was completed 

\end{acknowledgements}





ground_truth: Severe anemia that begins even before birth.

prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: What experimental techniques were used to study the quantum dot structures in this research?

Read the following text and answer briefly.

Context 2: \section{Introduction}

Despite the rise of graphene and other 2D materials, semiconducting single-walled carbon nanotubes (SWNT) are still regarded as strong candidates for the next generation of high-performance ultrascaled transistors~\cite{Cao_IBM_2015,IBM_2017,3D_CNT_FET} as well as for opto-electronic devices~\cite{Review_Avouris,CNT_photonics} such as chip-scale electronic-photonic platforms~\cite{Pernice_2016} or low-threshold near-infrared tunable micro-lasers~\cite{Graf_2017}  
Engineering a quantum dot (QD) along a (suspended) semiconducting SWNT foreshadows promising opportunities in the field of quantum information processing and sensing through recently proposed schemes such as detection and manipulation of single spins via coupling to vibrational motion~\cite{Palyi_2012}, optomechanical cooling~\cite{Wilson_Rae_2012} as well as all optical manipulation of electron spins~\cite{Galland_all_optical_2008}  Furthermore, the quasi one-dimensional geometry of SWNTs allows for defining tunable p-n junctions induced by electrostatic doping through local gates~\cite{Buchs_JAP,tunable_pn_2011}  Combining a well-defined QD within such a p-n junction structure could constitute a crucial building-block for the realization of highly desirable electrically driven, on-demand single photon emitters operating at telecom wavelength, based $e g $ on a turnstile device architecture~\cite{turnstile_1994,turnstile_1999} 
In practice, QDs in carbon nanotubes have been reported predominantly for two different confinement structures: i) Engineered tunneling barriers at metal-nanotube contacts~\cite{Pablo04nat} and/or by gate electrodes, used \emph{e g } to manipulate single electron spins~\cite{Laird:2015}, ii) Unintentional localization potentials stemming from environmental disorder~\cite{Hofmann_2016}, allowing for single-photon emission mediated by localization of band-edge excitons to QD states~\cite{CNT_photonics,Hoegele_2008,Walden_Newman_2012,Hofmann_2013,Pernice_2016_2}  Both types of structures are usually operated at cryogenic temperature due to small energy scales ranging from a few to few tens of millielectronvolts 
\\
\indent Another technique for achieving confinement in SWNTs makes use of artificial defects such as covalently bound oxygen or aryl functionalization groups on the side walls of semiconducting SWNTs, inducing deep exciton trap states allowing for single-photon emission at room temperature~\cite{Htoon_2015,tunable_QD_defects}  Also, carrier confinement between defect pairs acting as strong scattering centers has been reported for mechanically induced defects~\cite{Postma_SET} as well as for ion-induced defects with reported level spacings up to 200 meV in metallic SWNTs~\cite{Buchs_PRL}  The latter technique, combined with recent progress in controlling defects structure and localization~\cite{Robertson_2012,Yoon_2016,Laser_writing_2017} offers a high potential for engineering a broad set of SWNT-based quantum devices operating at room temperature  
\\
\indent Here, we demonstrate confinement of electrons and holes in sub-10 nm QD structures defined by ion-induced defect pairs along the axis of semiconducting SWNTs  Using low temperature scanning tunneling microscopy and spectroscopy (STM/STS), bound states with level spacings of the order of 100 meV and larger are resolved in energy and space  By solving the one-dimensional Schr\"odinger equation over a piecewise constant potential model, the effects of asymmetric defect scattering strength as well as the influence of the Au(111) substrate such as terrace edges on the bound states structure are remarkably well reproduced  By means of ab-initio calculations based on density functional theory and Green's functions, we find that single (SV) and double vacancies (DV) as well as chemisorbed nitrogen ad-atoms are good candidates to produce QDs with the experimentally observed features  These simulations also allow to study the scattering profile as a function of energy for different defect combinations 

\section{Experimental section}

The experiments have been performed in a commercial (Omicron) low temperature STM setup operating at $\sim5$~K in ultra high vacuum  Topography images have been recorded in constant current mode with a grounded sample, using mechanically cut Pt/Ir tips  Differential conductance $dI/dV$ spectra, proportional in first approximation to the local density of states (LDOS)~\cite{Tersoff85} have been recorded using a lock-in amplifier technique  The LDOS spatial evolution along a nanotube axis is obtained by $dI/dV(x,V)$ maps built by a series of equidistant $dI/dV$ spectra  Spatial extent mismatches between topography images and consecutive $dI/dV(x,V)$ maps have been systematically corrected~\cite{Buchs_Ar}, and the metallic nature of the tip has been systematically checked on the gold substrate to prevent any tip artefacts before recording STM or/and STS data sets  
\\
\indent Nanotube samples were made of extremely pure high-pressure CO conversion (HiPCo) SWNTs~\cite{Smalley01} with a diameter distribution centered around 1 nm, FWHM $\sim$ 0 3 nm~\cite{Buchs_conf}  The measured intrinsic defect density was below one defect every 200 nm  SWNTs were deposited on atomically flat Au(111) surfaces from a 1,2-dichloroethane suspension, followed by an in-situ annealing process~\cite{Buchs_APL_07,Buchs_Ar} 
\\
\indent Local defects in SWNTs have been created in-situ by exposure to: (i) Medium energy $\sim$ 200 eV argon ions (Ar$^{+}$) produced by an ion gun \cite{Buchs_Ar,Buchs_PRL}, (ii) Low energy (few eV's) nitrogen ions (N$^{+}$) produced by a 2 45 GHz ECR plasma source~\cite{Buchs_APL_07,Buchs_NJP_07}  In both cases, the exposure parameters have been calibrated to reach an average defect separation along the SWNTs of about 10 nm~\cite{Buchs_Ar,Buchs_APL_07} 

\section{Results and discussion}
\subsection{Experimental LDOS patterns}
\begin{figure}
  \includegraphics[width=8cm]{Figure_1 pdf}
  \caption{\label{exp_data_1} (a)-(b) 3D topography images (processed with WSXM~\cite{WSXM}) of SWNT I with Ar$^{+}$ ions-induced defects, with sample-tip bias voltage ($V_\mathrm{S}$) 1 V and tunneling current $I_\mathrm{S}$ 0 1 nA  (c) Corresponding $dI/dV(x,V)$ map recorded along the horizontal dashed lines in (b), with $V_\mathrm{S}=1$ V, $I_\mathrm{S}=0 2$ nA  Spatial resolution $\sim$ 0 3 nm  (d) 3D topography image of SWNT II with N$^{+}$ ions-induced defects, with $V_\mathrm{S}=1$ V, $I_\mathrm{S}=128$ pA  (e) Corresponding $dI/dV(x,V)$ map recorded along the horizontal dashed lines in (d), with $V_\mathrm{S}=1 5$ V, $I_\mathrm{S}=0 3$ nA  Spatial resolution $\sim$ 0 2 nm }
\end{figure}
In Fig ~\ref{exp_data_1} (a) and (b), we show 3D STM images of the same semiconducting SWNT (referred as SWNT I in the following) with Ar$^{+}$ ions-induced defect sites labeled $d1-d5$   Panel (d) shows a 3D STM image of a second semiconducting SWNT (referred as SWNT II) with N$^{+}$ ions-induced defect sites labeled $d6-d7$  In both cases, defect sites typically appear as hillock-like protrusions with an apparent height ranging from 0 5~{\AA} to 4~{\AA} and an apparent lateral extension varying between 5~{\AA} and 30~{\AA}~\cite{Buchs_NJP_07,Buchs_Ar,Thesis_Buchs}  
\\
\indent The resulting $dI/dV(x,V)$ maps recorded along the horizontal dashed line drawn in the STM images (b) and (d) are displayed in panels (c) and (e) in Fig ~\ref{exp_data_1}, respectively  Defect signatures in the LDOS in both cases are characterized by deep in-gap states at the defects positions  This is consistent with the expected defect structures, $i e $ mainly SVs, DVs and combinations thereof for collisions with Ar$^{+}$ ions~\cite{Buchs_Ar} and bridgelike N ad-atom for collisions with N$^{+}$ ions~\cite{Thesis_Buchs,Nitrogen_prb_07}  Note that gap states at energy levels $\sim$~0 2 eV and $\sim$~0 05 eV in panels (c) and (e), respectively, are shifted to the right from $d3$ by about 1 nm and to the right from $d6$ by about 2 nm  This indicates the presence of intrinsic or ion-induced defects on the lateral or bottom side wall of the SWNTs~\cite{Kra01prb}, not visible in the topographic images  These defects are labelled $d3'$ and $d6'$, respectively   
\\
\begin{figure}
  \includegraphics[width=12cm]{Figure_2 pdf}
  \caption{\label{exp_data_Ar} (a)-(b) QD I detailed $dI/dV(x,V)$ maps in conduction and valence bands  Lower subpanels contain QD states linecut profiles and stationary wave-like fits in left and right QD parts  Right subpanels contain experimental energy dispersion relation data sets $k_\mathrm{n}(E_\mathrm{n})$ and tight-binding calculations  (c)-(d) Resulting LDOS calculated from a one-dimensional piecewise constant potential model featuring potential barriers and a potential step (gray area), with position of the potential step: 5 09 nm from the right barrier's center, potential step heigth: $U_\mathrm{C}=V_\mathrm{L}-V_\mathrm{R}=60$ meV, barrier heights: $V_\mathrm{d3'}=1$ eV, $V_\mathrm{d4}=0 85$ eV, barrier widths: $a_\mathrm{d3'}=a_\mathrm{d4}=3 4$ nm   Valence band: $V_\mathrm{d3'}=-0 4$ eV, $a_\mathrm{d3'}=a_\mathrm{d4}=2 5$ nm, $V_\mathrm{d4}=-0 4$ eV  $E_\mathrm{g}$ stands for bandgap energy }
\end{figure}
\begin{figure}
  \includegraphics[width=12cm]{Figure_3 pdf}
  \caption{\label{exp_data_N} (a) QD II detailed $dI/dV(x,V)$ map  Lower subpanels contain QD states linecut profiles and stationary wave-like fits in the left and right QD parts  Right subpanel contains experimental energy dispersion relation data sets $k_\mathrm{n}(E_\mathrm{n})$ and tight-binding calculations  (b) Resulting LDOS calculated from a one-dimensional piecewise constant potential model featuring potential barriers and a potential step (gray area) with position of the potential step: 4 7 nm from the right barrier's center, potential step heigth: $U_\mathrm{C}=V_\mathrm{L}-V_\mathrm{R}=60$ meV, barrier heights: $V_\mathrm{d6'}=0 6$ eV, $V_\mathrm{d7}=0 6$ eV, barrier widths: $a_\mathrm{d6'}=1 5$ nm, $a_\mathrm{d7}=2 6$ nm }
\end{figure}
\indent Remarkably, the $dI/dV(x,V)$ maps in Fig ~\ref{exp_data_1} exhibit several broad discrete states in the conduction bands of SWNT I, II (white dashed boxes in panel (c) and (e), respectively) and in the valence band of SWNT I (white dashed box in panel (c)), characterized by a modulation of the $dI/dV$ signals in the spatial direction between pairs of consecutive defect sites $d3'-d4$ and $d6'-d7$  Enlarged plots of these boxed regions are displayed in Fig ~\ref{exp_data_Ar}(a)-(b) and Fig ~\ref{exp_data_N}(a) for SWNTs I and II, respectively  In the conduction bands, cross-sectional curves recorded along the black horizontal dashed lines labelled m1--m3 in Fig ~\ref{exp_data_Ar}(a) and m1--m4 in Fig ~\ref{exp_data_N}(a) are plotted below the LDOS panels  These clearly reveal one to three and respectively one to four spatially equidistant maxima  The number of maxima increases for increasing $\left|V_\mathrm{bias}\right|$ and the measured level spacings between consecutive discrete states is of the order of 100 meV and larger for both cases  This indicates that defect sites $d3'-d4$ and $d6'-d7$, respectively separated by 12 1 nm and 11 2 nm, act as strong scattering centers able to confine carriers in semiconducting SWNTs~\cite{Buchs_PRL,Bercioux_prb_2011}  Such intrananotube QD structures will be referred as QD I (in SWNT I) and QD II (in SWNT II) in the following  We estimated the level spacings in the conduction band of QD I to 98 meV (m1-m2) and 116 meV (m2-m3)  For QD II, we measured 122 meV (m1-m2), 185 meV (m2-m3) and 210 meV (m3-m4) 
\\
\indent In the valence band of SWNT I, discrete states with level spacings of the order of 80-90 meV, with one clear maximum at the level m-1, can also be distinguished between defect sites $d3'-d4$ in Fig ~\ref{exp_data_Ar}(b)  The discretization of the states indicates that this QD structure also confines holes  Discrete states starting from m-2 and lower show less well defined structures compared to the conduction band states  In the case of SWNT II, no clear discrete states are observed in the valence band (see supplementary information)  These observations are most probably the result of an energy dependent scattering strength of the defects, respectively $d3'$-$d4$ and $d6'$-$d7$, leading here to a weaker confinement in the valence band  Such energy dependence is well known for metallic SWNTs~\cite{Chico96,vac_2007,mayrhofer:2011,Bockrath_Science01} and is corroborated by our ab-initio calculations  Note that mixing effects with defect states and substrate-induced effects~\cite{substrate_effects} cannot be ruled out 
\\
\indent Another remarkable feature in the LDOS is the strong spatial asymmetry of the lowest energy states m1 and m-1 in QD I and m1 in QD II  In QD I, m1 is shifted to the right side of the dot while m-1 is shifted to the left side  Higher states m2 and m3 show more symmetry in terms of position of the maxima relative to the center of the QD  In QD II, m1 is shifted to the right side of the QD  We attribute the observed lowest energy states asymmetry (for electrons as well as for holes) in part to their strong sensitivity to weak potential modulations within the QD structure (as we will show in section \ref{1D})  For QD I, this assertion is supported by the observation of a 0 25 nm high Au(111) terrace edge located around the center of the QD, leading to a supported-suspended interface (see white dashed lines in Fig ~\ref{exp_data_1}(b) and more topographic details in Fig ~S2(a)-(d) in supplementary information)  Such configurations have been reported to induce a rigid shift in the SWNT bands~\cite{Clair_2011}, for instance here a down-shift in the right side of QD I corresponding to the "suspended" portion between two terraces  In QD II, we attribute the spatial shift of m1 to a potential modulation induced by a layer of disordered impurities, most probably residua from the 1,2-dichloroethane suspension, lying between the gold substrate and the SWNT (see Fig ~\ref{exp_data_1}(d) and Fig ~S2(e)-(h) in supplementary information)  
\\
\indent Also, the LDOS in QD I and II (Fig ~\ref{exp_data_Ar}(a) and Fig ~\ref{exp_data_N}(a), respectively) reveals asymmetric patterns with curved stripes oriented from top left to bottom right for QD I and from bottom left to top right for QD II  These are characteristic signatures for defect pairs with different scattering strengths~\cite{Bercioux_prb_2011,Buchs_PRL}  For instance here, the left defect in QD I ($d3'$) has a larger scattering strength than the right one ($d4$), while the right defect in QD II ($d7$) has a larger scattering strength than the left one ($d6'$)  
\\
\indent The exact atomic structure of the defects could in principle be determined from a comparison of $dI/dV$ spectra with simulated first-principle LDOS signatures of expected defect types  In reality, this is hampered by the large number of possible geometries to simulate, including complex multiple defect structures~\cite{Buchs_Ar}, together with the large unit cells of the semiconducting chiral SWNTs studied here 
\\
\subsection{1D piecewise constant potential model}
\label{1D}
To better understand the physical origins of the non-trivial signatures of the quantized states, we model the experimental $dI/dV$ maps by solving the time independent one-dimensional Schr\"odinger equation over a piecewise constant potential model of QD I and QD II  The scattering centers are approximated by semi-transparent rectangular tunneling barriers leading to a square confinement potential~\cite{Laird:2015}  This is supported by previous results on defect-induced confinement in metallic SWNTs using the same experimental conditions~\cite{Buchs_PRL} and is consistent with ab-initio simulations presented later in this work  The potential modulation within the QD is approximated by a potential step  The resulting potential geometries are illustrated with gray shaded areas in Fig ~\ref{exp_data_Ar} (c) and (d) and Fig ~\ref{exp_data_N}(b)  Dispersion relations $E(k)$ can be extracted experimentally from the quantized states wavefunctions by measuring the energy and corresponding momenta in the left and right sides of the QDs  The wavevectors $k$ are determined using stationary wave-like fitting functions~\cite{Buchs_PRL} displayed with dashed red curves in Figs ~\ref{exp_data_Ar}(a)-(b) and ~\ref{exp_data_N}(a))  From this procedure, the potential step height and position can be estimated (see supplementary information)  The experimental data sets $E(k)$ are plotted in the right panels of Figs ~\ref{exp_data_Ar}(a) and \ref{exp_data_N}(a) together with dispersion relations from a third-nearest neighbor tight-binding calculation closely approximating ab-initio results~\cite{Reich_TB_2002}  These chirality-dependent tight-binding dispersion relations, calculated within an extended Brillouin zone resulting from the defect-induced breaking of the translation invariance~\cite{Bercioux_prb_2011}, are used in the Hamiltonian of our one-dimensional model  Taking into account the measured chiral angle, diameter distribution~\cite{Buchs_conf} and measured bandgaps, we find the best match with chiralities $(7,6)$ for QD I and $(11,1)$ for QD II (see supplementary information)  
\\
\indent Once chiralities together with potential step heights and positions are optimized, one can fit the height and width of the rectangular tunneling barriers in order to reproduce the experimental level spacings and general LDOS patterns  On a qualitative ground, a symmetric double barrier system results in the formation of spatially symmetric discrete bound states  Increasing both barrier heights simultaneously shifts the bound state energy levels and level spacings up  This leads to sharper bound states as the confinement in the QD is made stronger thus increasing the lifetime of the confined electrons  Increasing the barrier thickness with constant inner edge separation does not affect much the level spacings but further sharpens the bound states  Any asymmetry introduced by a change in the width or height of one single barrier leads to broader bound states  The presence of a potential step modifies the LDOS in lifting the levels of the bound states, with a more pronounced effect on the lower states  In QD I and II, the center of each barrier is aligned with the center of the gap states ($d3'$-$d4$ for QD I and $d6'$-$d7$ in QD II) and the width ratio is kept proportional to the ratio of the spatial extent of the gap states  Thus, by increasing the width of the barriers, we decrease the length of the QD leading to higher level spacings, and vice versa  The experimental level spacings can then be approximated by tuning both barrier widths in the same ratio and the heights individually, knowing that the scattering strength of $d3'$ ($d7$) is larger than $d4$ ($d6'$) according to the observed asymmetry in the LDOS described above \footnote{The transmission probability through a rectangular tunneling barrier is given by $T=\left( 1+\frac{V^{2}\sinh^{2}\left( a \cdot \sqrt{2m^{*}(V-E)}/\hbar \right)}{4E(V-E)} \right)^{-1}$, where $V$ and $a$ are respectively the barrier height and width  For the argument in the $\sinh$ sufficiently small such that $\sinh(x)\simeq x$, it can be shown that $a$ and $V$ can be coupled such that the transmission probability becomes a function of the area under the barrier $A=a\cdot V$, with $T=\left( 1+ \frac{m^{*}A^{2}}{2\hbar^{2}E} \right)^{-1}$  In our case, this condition is not satisfied and thus the barrier geometries are tuned empirically to fit the experimental level spacings }  
\\
\indent For QD I, we find a good match in the conduction band for the barrier heights $V_\mathrm{d3'}=1$ eV and $V_\mathrm{d4}=0 85$ eV, widths $a_\mathrm{d3'}=a_\mathrm{d4}=$ 3 4 nm,  and potential step $V_\mathrm{L}-V_\mathrm{R}=60$ meV  With these parameters, the spatial profile of the obtained quantized states (see lower subpanels in Fig ~\ref{exp_data_Ar}(a) and (c)) reproduces the experimental modulation features remarkably well  Also, the simulated LDOS displays a pattern with curved stripes oriented from top left to bottom right, as observed experimentally, due to a left barrier with a larger scattering strength  In the valence band, although modes m-2 and lower do not show a well defined structure in the spatial direction, thinner barriers with dimensions $a_\mathrm{d3'/d4}=2 5$ nm, $V_\mathrm{d3'/d4}=-0 4$ eV, leading to a slightly longer QD length (9 6 nm compared to 8 7 nm in the conduction band) can reproduce the measured level spacings very well  
\\
\indent For QD II, we observed that the measured energy levels are overestimated by a factor $\alpha\sim1 29$, presumably due to a voltage division effect induced by the impurity layer mentioned above (see details in supplementary information)  We find a good agreement with the experimental LDOS with the parameters: $V_{d3'}=V_{d4}\simeq$ 0 47 eV, $a_\mathrm{d6'}=1 5$ nm, $a_\mathrm{d7}=2 6$ nm and $U_\mathrm{C}=V_\mathrm{L}-V_\mathrm{R}\simeq 47$ meV  Note that in Fig ~\ref{exp_data_N}(b) the barrier and potential heights are multiplied by $\alpha$ to allow a direct comparison with the experimental LDOS  The simulated LDOS shows a pattern with curved stripes oriented from bottom left to top right, as observed experimentally, due to a right barrier exhibiting a larger scattering strength  Also, the spatial profile of the obtained bound states (see lower subpanels in Fig ~\ref{exp_data_N}(a) and (b)) reproduces the experimental features quite well  Note also that one can distinguish an isolated state in the experimental LDOS at an energy level between m1 and m2, about in the middle of the QD  This state that prevented an accurate fit of the state m2 in the right QD part is attributed to a spatial feature visible in the STM topography image in Fig ~\ref{exp_data_Ar}(d) (see also supplementary information, Fig S2(f)), probably a physisorbed impurity which does not affect the LDOS significantly 
\\
\subsection{Ab-initio calculations}
\begin{figure}
  \includegraphics[width=16cm]{Figure_4 pdf}
  \caption{\label{num_data} (a)-(c) LDOS ab-initio simulations of a semiconducting $(16,0)$ SWNT with combinations of vacancies defects separated by 11 1 nm  Subpanels display QD state linecut profiles  (d) Tight-binding (black curve) and ab-initio dispersion relations (green circles) for a pristine $(16,0)$ SWNT with $E_\mathrm{n}(k_\mathrm{n})$ data sets extracted from (a)-(c)  (e)-(g) LDOS ab-initio simulations of a semiconducting $(17,0)$ SWNT with combinations of N ad-atoms and vacancies defects separated by 10 7 nm  (h) Tight-binding (black curve) and ab-initio dispersion relations (green circles) for a pristine $(17,0)$ SWNT with $E_\mathrm{n}(k_\mathrm{n})$ data sets extracted from (e)-(g) }
\end{figure}
In order to elucidate the physical nature of the electron/hole confining scattering centers, we performed ab-initio simulations based on a combination of density functional theory~\cite{pbe,paw,vasp_paw,VASP2}, maximally localized Wannier orbitals~\cite{transportwannier90} and Green's functions (see supplementary information)  Without loss of generality, we have simulated short unit cell semiconducting zigzag SWNTs with different combinations of the most probable defect structures  Results for vacancy defects likely being induced by 200 eV Ar$^{+}$ ions, separated by about 11 nm in a $(16,0)$ SWNT are shown in Fig ~\ref{num_data}(a)-(c) with DV-DV, DV-SV and SV-SV pairs, respectively  The LDOS displays midgap states at the defect positions as expected as well as defect states in the valence band~\cite{Buchs_Ar}  Most importantly, clear quantized states with a number of maxima increasing with energy are observed between the defects in the conduction band, emphasizing the ability of SVs and DVs to confine carriers  For the asymmetric configuration DV-SV, one can distinguish faint curved stripe patterns oriented from top left to bottom right, indicating a larger scattering strength for DVs compared to SVs  This is consistent with observations in transport experiments~\cite{Gomez05nm}  On the other hand, the patterns in the valence band strongly depend on the defect types  Discrete states can be distinguished for the DV-DV case, with m-2 being mixed with defect states  For the DV-SV case, clear curved stripe patterns oriented from bottom left to top right indicate again a stronger scattering strength for DV  Also, broader states are observed, indicating that the scattering strength of DVs and SVs is weaker in the valence band compared to the conduction band 
\\
\indent More insight on the energy dependent scattering strength for each defect pair configuration can be obtained by extracting the wavevector $k_\mathrm{n}(E_\mathrm{n})$ for each resonant state  This data set is plotted in Fig ~\ref{num_data}(d) for the conduction and valence bands together with the $(16,0)$ dispersion relations calculated from the third-nearest neighbor TB model and from the ab-initio calculation for the pristine nanotube  A first observation is the excellent agreement between TB and ab-initio results, further validating the method used in Figs ~\ref{exp_data_Ar}(a)-(b) and ~\ref{exp_data_N}(a)  The vertical dashed lines indicate the limiting $k_\mathrm{n,\infty}=\frac{\pi \cdot n}{L}$ values corresponding to the closed system (infinite hard walls potential) with $L=11 1$ nm being the defect-defect distance  In the conduction band, we find that $k_\mathrm{n}(E_\mathrm{n})=\frac{\pi \cdot n}{L_\mathrm{eff}(n)} < k_\mathrm{n,\infty}$, indicating that the effective lengths $L_\mathrm{eff}(n)$ of the QD are larger than $L$ ($i e $ the resonant states wavefunctions are characterized by penetrating evanescent modes inside the defect scattering potential), as expected for an open system  The shortest $L_\mathrm{eff}(n)$ are obtained for the DV-DV configuration with 12 1 nm (m1), 13 1 nm (m2) and 12 9 nm (m3), which we attribute to wider scattering potential profiles for DVs compared to SVs  In the valence band, we find that $k_\mathrm{n}(E_\mathrm{n})=\frac{\pi \cdot n}{L_\mathrm{eff}(n)} > k_\mathrm{n,\infty}$, with $L_\mathrm{eff}(n)$ values between 7 9 nm (DV-DV, m-1) and 9 66 nm (DV-SV, m-2)  We attribute this pronounced QD shortening to wider scattering potential profiles of both DVs and SVs in the valence band, probably due to mixing with wide spread defect states in the valence band 
\\
\indent Ab-initio calculations for different defect pairs combinations containing at least one N ad-atom, $i e $ N-DV, N-SV and N-N, are presented in Fig ~\ref{num_data}(e)-(h) for a $(17,0)$ SWNT, along with details on the defects geometries  Remarkably, clear QD states are generated for all three configurations, underlining the potential of N ad-atoms to confine carriers in semiconducting SWNTs and thus to generate intrananotube QDs  
\\
\indent In order to demonstrate the scattering strengths of the different defects, we calculated the energy dependent conductance in addition to the LDOS for the different combinations of the QD defining scattering defects on the $(16,0)$ and $(17,0)$ SWNTs, see supplementary information  Generally we can observe strong conductance modulation of the order of 30-40\% with regard to the pristine CNT for all three tested defects (double vacancies DV, single vacancies SV and chemisorbed C-N) with the DVs having the largest scattering strength in the CB and VB   
\\
\indent Note that the choice of the zigzag SWNT chiralities in the two different ab-initio scenarios is motivated by the different effective masses of both chiralities ($m^{*}_{(17,0)}>m^{*}_{(16,0)}$) which is typical for chirality families $(3n-1,0)$ and $(3n-2,0)$~\cite{ZZ_families}  Taking advantage of recent reports on SWNT chirality control~\cite{chirality_control_EMPA,chirality_control_chinese,chirality_chemistry}, this property could be used in practice to design QDs with different level spacings for the same QD length  From an application point of view, however, QDs generated by DVs will have far superior stability at room temperature due to their high migration barrier above 5 eV ($\sim$~1 eV for single vacancy)~\cite{Kra06vm}  This value drops down by at least 2 eV for N ad-atoms depending on their chemisorption configuration~\cite{Nitrogen_prb_07,Yma05nitr} 
\\
\indent Our ab-initio simulations do not take into account any substrate effect  In the experimental case, the carriers can decay through the substrate, thus limiting their lifetime  This leads to state broadening, measured between about 60 meV up to 120 meV in QD I and II, while the quantized states widths in ab-initio simulations vary between about 5 meV and 45 meV  This suggests that a better contrast of the experimental quantized states, especially in the valence band, could be achieved by lowering the nanotubes-substrate interaction through $e g $ the insertion of atomically thin insulating NaCl films~\cite{Ruffieux_Nature_2016}  This would allow to gain more insight on the electronic structure of the QDs as well as in the associated scattering physics at the confining defects~\cite{Buchs_PRL}  

\section{Conclusions and outlook}
In summary, using low-temperature STM/STS measurements supported by an analytical model and ab-initio simulations, we have demonstrated that intrananotube quantum dots with confined electron and hole states characterized by energy level spacings well above thermal broadening at room temperature can be generated in semiconducting SWNTs by structural defects such as vacancies and di-vacancies, as well as nitrogen ad-atoms  These results, combined with recent progresses in type and spatial control in the formation of defects~\cite{Robertson_2012,Yoon_2016,Laser_writing_2017} as well as chirality control~\cite{tunable_QD_defects}, hold a high potential for applications in the design of SWNT based quantum devices  These include $e g $ electrically driven single-photon emitters operating at room temperature and telecom wavelength  In this context, the observation of quantum confinement effects in the emitted light of cut, sub-10 nm, semiconducting SWNTs~\cite{Dai_2008} shall be seen as an additional motivation for investigating the optical properties of our "QD with leads" building-blocks  These would include $e g $ studying optical transitions selection rules for different types and configurations of defect pairs~\cite{sel_rules_2006} associated with experimental studies such as photoluminescence~\cite{Lefebvre06} combined to $g^{(2)}$ correlation measurements~\cite{Hofmann_2013} in suspended SWNT devices as well as photocurrent imaging~\cite{Buchs_Nat_comm} and spectroscopy~\cite{Gabor_2009} 

\section*{Acknowledgements}
The authors thank Ethan Minot, Lee Aspitarte, Jhon Gonzalez, Andres Ayuela, Omjoti Dutta and Arkady Krasheninnikov for fruitful discussions 
The work of DB is supported by Spanish Ministerio de Econom\'ia y Competitividad (MINECO) through the project  FIS2014-55987-P and by the (LTC) QuantumChemPhys  LM acknowledges support from the BMBF-project WireControl (FKZ16ES0294) and computing time for the supercomputers JUROPA and JURECA at the J\"ulich Supercomputer Centre (JSC) 


\clearpage

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Tsurushima, H  and Yuan, X  and Dillehay, L  E  and Leong, K  W , Radioresponsive tumor necrosis factor-related apoptosisinducing ligand (TRAIL) gene therapy for malignant brain tumors, Cancer Gene Therapy, vol  14 no  8 (2007), pp  706-716 [abs]
Chai, C  and Leong, K  W , Biomaterials approach to expand and direct differentiation of stem cells, Molecular Therapy, vol  15 no  3 (2007), pp  467-480 [abs]
Zhang, Y  and Chai, C  and Jiang, X  S  and Teoh, S  H  and Leong, K  W , Fibronectin immobilized by covalent conjugation or physical adsorption shows different bioactivity on aminated-PET, Materials Science & Engineering C-Biomimetic and Supramolecular Systems, vol  27 no  2 (2007), pp  213-219 [abs]
Song, R  J  and Liu, S  Q  and Leong, K  W , Effects of MIP-1 alpha, MIP-3 alpha, and MIP-3 beta on the induction of HIV Gag-specific immune response with DNA vaccines, Molecular Therapy, vol  15 no  5 (2007), pp  1007-1015 [abs]
Yim, E  K  F  and Liao, I  C  and Leong, K  W , Tissue compatibility of interfacial polyelectrolyte complexation fibrous scaffold: Evaluation of blood compatibility and biocompatibility, Tissue Engineering, vol  13 no  2 (2007), pp  423-433 [abs]
Sharma, B  and Williams, C  G  and Kim, T  K  and Sun, D  N  and Malik, A  and Khan, M  and Leong, K  and Elisseeff, J  H , Designing zonal organization into tissue-engineered cartilage, Tissue Engineering, vol  13 no  2 (2007), pp  405-414 [abs]
Chua, K  N  and Tang, Y  N  and Quek, C  H  and Ramakrishna, S  and Leong, K  W  and Mao, H  Q , A dual-functional fibrous scaffold enhances P450 activity of cultured primary rat hepatocytes, Acta Biomaterialia, vol  3 no  5 (2007), pp  643-650 [abs]
Chua, K  N  and Chai, C  and Lee, P  C  and Ramakrishna, S  and Leong, K  W  and Mao, H  Q , Functional nanofiber scaffolds with different spacers modulate adhesion and expansion of cryopreserved umbilical cord blood hematopoietic stem/progenitor cells, Experimental Hematology, vol  35 no  5 (2007), pp  771-781 [abs]
Yim, E  K  F  and Pang, S  W  and Leong, K  W , Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage, Experimental Cell Research, vol  313 no  9 (2007), pp  1820-1829 [abs]
Chew, S  Y  and Mi, R  F  and Hoke, A  and Leong, K  W , Aligned protein-polymer composite fibers enhance nerve regeneration: A potential tissue-engineering platform, Advanced Functional Materials, vol  17 no  8 (2007), pp  1288-1296 [abs]
Tsurushima, H  and Yuan, X  and Dillehay, L  E  and Leong, K  W , Radio-responsive gene therapy for malignant glioma cells without the radiosensitive promoter: Caspase-3 gene therapy combined with radiation, Cancer Letters, vol  246 no  1-2 (2007), pp  318-323 [abs]
Dang, J M  and Leong, K  W , Myogenic induction of aligned mesenchymal stem cell sheets by culture on thermally responsive electrospun nanofibers, Advanced Materials, vol  19 no  19 (2007), pp  2775-2779
Dai, H  and Jiang, X  and Tan, G  C  and Chen, Y  and Torbenson, M  and Leong, K  W  and Mao, H  Q , Chitosan-DNA nanoparticles delivered by intrabiliary infusion enhance liver-targeted gene delivery, International Journal of Nanomedicine, vol  1 no  4 (2006), pp  507-522 [abs]
Le Visage, C  and Kim, S  W  and Tateno, K  and Sieber, A  N  and Kostuik, J  P  and Leong, K  W , Interaction of human mesenchymal stem cells with disc cells - Changes in extracellular matrix biosynthesis, Spine, vol  31 no  18 (2006), pp  2036-2042
Ong, S  Y  and Dai, H  and Leong, K  W , Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture, Biomaterials, vol  27 no  22 (2006), pp  4087-4097
Bright, C  and Park, Y  S  and Sieber, A  N  and Kostuik, J  P  and Leong, K  W , In vivo evaluation of plasmid DNA encoding OP-1 protein for spine fusion, Spine, vol  31 no  19 (2006), pp  2163-2172
Yim, E  K  and Wan, A  C  and Le Visage, C  and Liao, I  C  and Leong, K  W , Proliferation and differentiation of human mesenchymal stem cell encapsulated in polyelectrolyte complexation fibrous scaffold, Biomaterials, vol  27 no  36 (2006), pp  6111-22 [abs]
Luong-Van, E  and Grondahl, L  and Chua, K  N  and Leong, K  W  and Nurcombe, V  and Cool, S  M , Controlled release of heparin from poly(epsilon-caprolactone) electrospun fibers, Biomaterials, vol  27 no  9 (2006), pp  2042-2050
Dang, J  M  and Leong, K  W , Natural polymers for gene delivery and tissue engineering, Advanced Drug Delivery Reviews, vol  58 no  4 (2006), pp  487-499
Li, J  and Li, X  and Ni, X  P  and Wang, X  and Li, H  Z  and Leong, K  W , Self-assembled supramolecular hydrogels formed by biodegradable PEO-PHB-PEO triblock copolymers and alpha-cyclodextrin for controlled drug delivery, Biomaterials, vol  27 no  22 (2006), pp  4132-4140
Yim, E  K  F  and Wen, J  and Leong, K  W , Enhanced extracellular matrix production and differentiation of human embryonic germ cell derivatives in biodegradable poly(epsilon-caprolactone-co-ethyl ethylene phosphate) scaffold, Acta Biomaterialia, vol  2 no  4 (2006), pp  365-376
Chew, S  Y  and Hufnagel, T  C  and Lim, C  T  and Leong, K  W , Mechanical properties of single electrospun drug-encapsulated nanofibres, Nanotechnology, vol  17 no  15 (2006), pp  3880-3891
Zhang, Y  and Chai, C  and Jiang, X  S  and Teoh, S  H  and Leong, K  W , Co-culture of umbilical cord blood CD34(+) cells with human mesenchymal stem cells, Tissue Engineering, vol  12 no  8



ground_truth: 4.5x10^8 cm.