Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
femoral and humeral bones of balb / c mouse embryos were removed aseptically on 18.5  dpc , and they were microdissected into esz and growth plate ( egp ) under a stereomicroscope ( zeiss stemi 2000-c , carl zeiss microimaging ) .
each region was minced and gently digested with 2  mg / ml of collagenase ( wako pure chemical ) at 37  c for 2  h. they were cultured in growth medium composed of iscove 's modified dulbecco 's medium ( invitrogen ) supplemented with 15% fetal bovine serum , and subjected immediately to retroviral infection .
fli1 was introduced into the pmys - ires - gfp vector . the full length ews
the per cell normalization method ( percellome method ) was applied to esz and egp samples .
a 10  l aliquot of each lysate was treated with dnase - free rnase a ( nippon gene inc . ,
japan ) for 30  min at 37  c , followed by proteinase k ( roche diagnostics gmbh .
usa ) was added to each well , shaken for 10  s four times and then incubated for 2  min at 30  c .
dna concentration was measured using a 96 well fluorescence plate reader with excitation at 485  nm and emission at 538  nm .
usa ) was used as standard . as reported previously , the grade - dosed spike cocktails ( gscs ) made of the bacillus subtilis rnas corresponding to the sequences in the affymetrix genechip arrays ( affx - thrx-3_at , affx - lysx-3_at , affx - phex-3_at , affx - dapx-3_at , and affx - trpnx-3_at ) were prepared , and gscs were added to the sample homogenates in proportion to their dna concentrations .
the genechip mouse genome 430 2.0 array ( affymetrix ) was hybridized with the crna generated from esz and egp cells , and murine ewing 's sarcoma tissue ( table  1 ) . after staining with streptavidin
phycoerythrin conjugates , arrays were scanned using an affymetrix genechip scanner 3000 and analyzed using affymetrix genechip command console software ( agcc , affymetrix ) and genespring gx 11.0.2 ( agilent technologies ) as described previously .
the expression data for esz and egp cells were converted to percellome data , i.e. , absolute copy numbers of mrna per one cell , by the homemade software scal4 ( spike calculation version 4 ) .
response linearity of the five gsc spikes and the location of spike probe sets in the histogram of all probe sets ( fig .
n  =  3 ) , all the pairs were plotted to a scatter graph as red ( expression above detection level ) or green dots ( below detection level ) with the data of five yellow spike probe sets ( fig .
if any samples did not draw a symmetric scatter plot with yellow dot on the diagonal line , the sample were rejected for evaluation , and they were subjected to additional analyses .
homemade software named rsort ( roughness sort )   was used . this program sorts the probe sets as upward or downward peaks in a 3d isobologram ( fig .  2 ) . to avoid biologically nonsense
probe sets such as ones with expression below the detection level , the data were visually checked for their 3d isobologram shape .
femoral and humeral bones of balb / c mouse embryos were removed aseptically on 18.5  dpc , and they were microdissected into esz and growth plate ( egp ) under a stereomicroscope ( zeiss stemi 2000-c , carl zeiss microimaging ) .
each region was minced and gently digested with 2  mg / ml of collagenase ( wako pure chemical ) at 37  c for 2  h. they were cultured in growth medium composed of iscove 's modified dulbecco 's medium ( invitrogen ) supplemented with 15% fetal bovine serum , and subjected immediately to retroviral infection .
fli1 was introduced into the pmys - ires - gfp vector . the full length ews
the per cell normalization method ( percellome method ) was applied to esz and egp samples . briefly
a 10  l aliquot of each lysate was treated with dnase - free rnase a ( nippon gene inc . ,
japan ) for 30  min at 37  c , followed by proteinase k ( roche diagnostics gmbh .
usa ) was added to each well , shaken for 10  s four times and then incubated for 2  min at 30  c .
dna concentration was measured using a 96 well fluorescence plate reader with excitation at 485  nm and emission at 538  nm .
usa ) was used as standard . as reported previously , the grade - dosed spike cocktails ( gscs ) made of the bacillus subtilis rnas corresponding to the sequences in the affymetrix genechip arrays ( affx - thrx-3_at , affx - lysx-3_at , affx - phex-3_at , affx - dapx-3_at , and affx - trpnx-3_at ) were prepared , and gscs were added to the sample homogenates in proportion to their dna concentrations .
the genechip mouse genome 430 2.0 array ( affymetrix ) was hybridized with the crna generated from esz and egp cells , and murine ewing 's sarcoma tissue ( table  1 ) . after staining with streptavidin
phycoerythrin conjugates , arrays were scanned using an affymetrix genechip scanner 3000 and analyzed using affymetrix genechip command console software ( agcc , affymetrix ) and genespring gx 11.0.2 ( agilent technologies ) as described previously .
the expression data for esz and egp cells were converted to percellome data , i.e. , absolute copy numbers of mrna per one cell , by the homemade software scal4 ( spike calculation version 4 ) .
response linearity of the five gsc spikes and the location of spike probe sets in the histogram of all probe sets ( fig .
n  =  3 ) , all the pairs were plotted to a scatter graph as red ( expression above detection level ) or green dots ( below detection level ) with the data of five yellow spike probe sets ( fig .
if any samples did not draw a symmetric scatter plot with yellow dot on the diagonal line , the sample were rejected for evaluation , and they were subjected to additional analyses .
homemade software named rsort ( roughness sort )   was used . this program sorts the probe sets as upward or downward peaks in a 3d isobologram ( fig .  2 ) . to avoid biologically nonsense probe sets such as ones with expression below the detection level ,
we describe a unique dataset of mouse embryonic cartilage with or without the ewing 's sarcoma fusion oncogene , ews  fli1 .
the dataset was used in the study published recently   and was informative to understand the tumorigenic mechanisms of ewing 's sarcoma .

Answer:
ewing 's sarcoma is a rare bone tumor that affects children and adolescents .
 we have recently succeeded to induce ewing 's sarcoma - like small round cell tumor in mice by expression of ews  ets fusion genes in murine embryonic osteochondrogenic progenitors .
 the ewing 's sarcoma precursors are enriched in embryonic superficial zone ( esz ) cells of long bone . to get insights into the mechanisms of ewing 's sarcoma development , gene expression profiles between ews
 fli1-sensitive esz cells and ews
 fli1-resistant embryonic growth plate ( egp ) cells were compared using dna microarrays .
 gene expression of esz and egp cells ( total , 30 samples ) was evaluated with or without ews
 fli1 expression 0 , 8 or 48  h after gene transduction .
 our data provide useful information for gene expression responses to fusion oncogenes in human sarcoma .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
oral myiasis is a rare condition that refers to the invasion of tissue of the oral cavity by fly larvae .
the term myiasis ( greek : myia= fly , iasis = disease ) was coined by hope in 1840 and it was first described by laurance in 1909 .
zumpt defined myiasis as the infestation of live human and vertebrate animals with dipterous larvae , which feed on living or necrotic tissues , liquid body substances , or ingested food .
human myiasis is reported mainly in developing countries such as asian countries and very rarely from western countries .
myiasis can be classified depending on the condition of the involved tissue as i ) accidental myiasis  when larvae get ingested along with food , ii ) semi - specific myiasis  when the larvae are laid on necrotic tissue of the wound and iii )
. based on anatomic site , it can be classified as i ) cutaneous myiasis , ii ) myiasis of external orifices and iii ) myiasis of internal organs .
primary myiasis is caused by biophagous larvae ( feed on living tissues ) and also called as obligatory myiasis .
secondary myiasis is caused by the necrobiophagous larvae ( feed on dead tissues ) and also called as facultative myiasis .
the most common anatomical sites for myiasis are the nose , eyes , skin wounds , sinuses , ears , lungs , gut , gall bladder , vagina , nasal cavities , and rarely , the mouth . whereas cutaneous myiasis involves invasion of the skin through the wounds .
the common predisposing factors are incompetent lips , poor oral hygiene , severe halitosis , anterior open bite , mouth breathing during sleep , facial trauma , extraction wounds , ulcerative lesions and carcinoma .
most of the patients are senile , alcoholics , mentally handicapped , cerebral palsied,[121416 ] and also those living in poor conditions , with no age limitation .
droma etal . reported that incidence of myiasis is more in anterior maxillary region and men are more affected than women .
traumatic wounds in orofacial region , when neglected by patients themselves as well as care takers , can lead to development of myiasis .
the present report describes a case of oral myiasis in a 14 year old boy with a history of trauma to the maxillary anterior region and it was neglected by him and parents .
a 14 year old boy with learning disability presented to department of pedodontics and preventive dentistry , sjm dental collegeand hospital , chitradurga , with a chief complaint of upper lip swelling and itching sensation on the right side of the face since more than 2 weeks [ figure 1 ] .
the patient gave a history of trauma to maxillary anterior dentoalveolar region and it was neglected for many days . on examination , there was swelling of the face on the right side , which extended from infraorbital region to upper lip [ figure 1 ] .
intraoral examination revealed a deep lacerated wound which was infected and maggots were noticed on the upper vestibule and the nasal floor .
the patient had an incompetent lip , swollen upper gingiva , and poor oral hygiene , and general symptoms like pain , fever and malaise were present .
a cotton swab impregnated with turpentine was placed near the upper vestibule ( wound ) area for 510 minutes .
many of the maggots came out from the nose , which were then removed one by one with the help of curved artery forceps [ figures 2 , 3 ] . during the 3 days interval ,
the length of the each maggot ranged from 6 to17 mm [ figure 6 ] .
then , the wound was irrigated with hydrogen peroxide , antiseptic betadine solution and broad - spectrum antibiotics , and analgesics were prescribed .
the patient was recalled for regular follow - up for wound debridement and the wound healed uneventfully .
swelling of the right side of the face and the upper lip arrow shows larvae coming out from the nose number of maggots removed from this area collected larvae from the lesion each maggot was measured
myiasis is an uncommon disease in humans and common in rural areas compared to urban areas .
the most common sites are the nose , eye , ear , anus , vagina , and rarely , the oral cavity .
predisposing factors are extraction wounds , poor oral hygiene , psychiatric patients , mouth breathing during sleep , facial trauma , open neglected wounds , necrotic tissues , suppurative lesions , severe halitosis , senility , cerebral palsy , mental retardation , hemiplegia and factors that favor persistent non - closure of the mouth.[121416 ] primary oral myiasis commonly affects the anterior part of the mouth .
the patient reported here was residing in a rural area , with low socioeconomic background .
the life cycle of a house fly begins with the egg stage followed by the larva , the pupa , and finally the adult fly .
the conditions required for egg laying and survival of the larvae are moisture , necrotic tissue and suitable temperature .
the larval stage lasts from 6 to 8 days , in which period they are parasitic to human beings .
they are photophobic , and therefore tend to hide deep into the tissues , which also helps them to secure a suitable niche to develop into pupa . in the present case also , the larvae were present deep into the tissue and the nasal floor .
proteolytic enzymes released by the surrounding bacteria decompose the tissue and the larvae feed on this rotten issue .
oral myiasis can also be classified as- 1 ) larvae living outside the body , 2 ) larvae burrow into unbroken skin and develop under it .
4 ) eggs or young larvae are deposited in the wounds or natural cavities in the body .
when there are multiple larvae and in advanced stages of development and there is tissue destruction , local application of various agents like turpentine oil , larvicidal drug like negasunt , ethyl chloride , ether , mercuric chloride , creosote , saline , iodoform , chloroform , clove oil , calomel , phenol mixture , olive oil , gentian violet , alcoholic solution in association with tobacco , camphor , sodium hypochlorite can be used for complete removal of all larvae .
these agents asphyxiate the aerobic larvae and force them to a superficial position and these larvae are removed with less damage to tissues and larvae as well .
the rupture of the larvae might cause allergic or foreign body reaction and secondary infection , so care must be taken not to rupture the maggots . in the present case , maggots were removed completely in 3 days interval by using turpentine oil .
myiasis of orofacial region can be prevented by educating the people from rural areas and low socioeconomic groups about personal hygiene , taking care of any wound , control of fly population and maintenance of sanitation of the surroundings .
we , the dentists , must educate parents / guardians to make them aware of the conditions , and the parents should bring children as early as possible for dental intervention to prevent further complications .

Answer:
oral myiasis is a rare condition in humans and is associated with poor oral hygiene , severe halitosis , mouth breathing during sleep , mental handicap , cerebral palsy , epilepsy , anterior open bite , incompetent lips , and other conditions . in this report , a 14 year - old boy who had an orofacial trauma in the maxillary dentoalveolar region , which was neglected , has been described .
 there was a deep lacerated wound on the upper vestibule which was infected and maggots were found on the same wound .
 the clinical features , management , treatment are discussed and relevant literature is reviewed .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
overweight and obesity are conditions that have been increasing in the united states and these risk factors for diseases are estimated to affect more than one - half of those over the age of 20 . over the last few years
obesity is a major public health concern because it increases the risk for many chronic conditions , such as cardiovascular diseases , particularly diabetes , hypertension , coronary artery disease , and cancer [ 1,811 ] .
public health officials have begun to monitor the health status of school - aged children because it is believed that many of them exhibit risk factors that create the potential for developing chronic disease as adults . in 1994 ,
10.4% among 2 to 5-year - old children , compared to 11.3% and 7.2% respectively for the same age groups in 1988 .
this increase in overweight children has underscored the challenges faced by young people as they grow into an adult group where over 50% are overweight , and at significant risk for developing cardiovascular and other metabolic disorders [ 1 , 12 ] .
effective management of risk factors among the youth , such as reducing / eliminating improper dietary practices and incorporating adequate physical activity , must become a universal health priority in order to effectively precipitate any noticeable decline in the adult morbidity and mortality statistics .
childhood obesity is also associated with several immediate health risk factors , such as orthopedic , neurological , pulmonary , gastroenterological , and endocrine conditions .
obesity has been linked to negative psychosocial outcomes in children , such as low self - esteem and depression [ 1523 ] , making obesity indirectly linked to academic performance and adverse social outcomes over time [ 2429 ] .
cardiovascular disease is not only the leading cause of death , but also the single greatest contributor to excess mortality in african - americans .
unhealthy eating contributes to at least 300,000 preventable deaths each year , and is one of the most identifiable contributors to premature death , second only to tobacco use .
premature deaths due to cardiovascular disease remain higher for african americans than any other group [ 3137 ] .
the highest rates of premature coronary heart disease in adults age 3564 occurred in the rural southern region of the united states .
the rate of cvd for african americans in mississippi was deemed serious enough to compel the national institutes of health ( nih ) to initiate the jackson heart study to focus on identifying risk factors for the development of cvd in african - americans . among the known risk factors for cvd
according to tom walden of the north american association for the study of obesity , schools can play a key role in preventing the risk behaviors by providing instruction on proper nutrition and physical activity .
based on this premise , this study was designed to examine the students possible role in changing their own negative practices , by first assessing their perceptions of the obstacles to positive dietary practices and increased physical activity .
the study also solicited students recommendations for reducing the negative practices that are associated with the rise in obesity and the development of cardiovascular diseases .
the implementation of the study was intended to grant the students an opportunity to provide their own ideas , suggestions and recommendations for what they feel could be done to improve their quality of life and to prevent premature morbidity and mortality .
the sample for this study included 300 students from a high school , located in rural , mississippi .
the high school under investigation in this study educates students in grades 912 , and all students enrolled in the health and physical education courses comprised the sample for this project .
students were first asked to complete an assent form and to have their parents sign a consent form before they could participate in the survey .
only students who returned completed assent and consent forms were permitted to participate in the study .
the data for the study were obtained from the administration of the project health high school survey ( phhss ) , which was a modification of the mississippi youth risk behavior survey ( yrbs ) that was developed by the centers for disease control and prevention ( cdc ) .
the phhss was designed to measure the prevalence of risk behaviors associated with leading causes of illness and death .
the survey was modified to include three additional questions that served to fulfill the objectives of this study .
these questions specifically asked students to respond about their perceptions , and were the following :
what do you think is keeping you or other students from eating more nutritious , healthier foods ?
  what do you think is preventing you or other students from taking part in daily physical activity ?   what suggestions do you have that would help students to start eating better and exercising more ?  these were open - ended questions and the students had the freedom to think and enumerate their perceptions .
the students were assured that their responses would be confidential and their honest responses could shed some light on a perplexing health dilemma that currently faced public health officials .
all students enrolled in health and physical education classes , which included students in the 912 grades , were administered the phhss survey during the regular classroom session by the regular health and physical education teacher .
the students responses on each of these issues were recorded and analyzed to fully understand their perceptions and recommendations .
this descriptive study sought to ascertain the students perceptions through the use of questions that were presented in the form of a self - administered questionnaire . upon completion of the survey ,
the statistical package for the social sciences ( spss ) was used to evaluate the student responses .
the high school students perceptions about current practices and possible solutions were calculated and presented in the tables that follow .
the students perceptions on each of the areas under investigation were recorded and reported based on the rankings ( highest number of responses received and recorded ) from highest to lowest .
completed phhss surveys were returned for 126 students which represented 42% of the 300 students enrolled in the health and physical education classes .
all of the students were between the ages of 14 and 18 , and they were all enrolled in grades 912 .
the breakdown according to race was as follows : 94.9% were african american ; 2.5% were hispanic ; 1.3% were asian ; and 1.3% were native americans , the participants were 69% female and 31% male .
students at the high school were asked to respond to the question  what do you think is keeping you or other students from eating better ( more nutritious foods ?  figure 1 provides a graphical image of the students responses about this issue .
love of sweets , junk food and fatty foods occupied the highest ranked reason selected by 19.8% of the students .
the students also admitted that most of them ate what they were accustomed to eating .
they ate what they liked to eat , and the decision about what to eat was made because of the taste of the food without regard for any health consequence or negative health outcomes .
the number two reason for not eating healthy was that students believed that the food they were served in the school s cafeteria was of poor quality : 15.7% of the students responses supported this view .
the number three reason given for not eating more nutritious foods was family background , family customs and family heritage : 14.1% of the students acknowledged that they ate the way they did simply because they inherited those patterns from their family .
in other words , they ate what their parents could afford to buy and prepare for meals .
many of them asserted that they were simply not accustomed to eating nutritious foods daily .
these students stated that they buy the types of food they want , and , in some instances , they want the fast foods more than anything else .
the students placed fast food restaurants as number five among the reasons why they found it difficult to practice positive eating habits .
ranked number six as a factor that inhibits them from healthy eating habits is the easy access to junk foods and other unhealthy foods : 6.6% of them blamed the easy accessibility of junk foods as a perpetrator of the unhealthy dietary choices and practices .
another 6.6% of the students cited lack of care and guidance from responsible adults as a factor that prevents them from practicing good dietary habits .
these students admitted that pressure from videos and corporate advertisements helped to steer them in the wrong direction in reference to the choices they make .
the negative influences perpetrated by famous actors , sports personalities and performers usually project the wrong messages and oftentimes influence many students to act spontaneously and without proper judgment . as a result ,
many of them make the decision to eat daily at fast food restaurants , where they often consume an over abundance of unhealthy meals . several students reported that there was no one in their life to motivate them with positive messages or inspiration , and not many people cared enough .
the number eight ranked reason for students not practicing positive eating habits was the presence of snack machines at school , laden with junk food .
about 5.0% of the students cited this as a possible obstacle to good eating practices .
approximately 19.8% of the students did not express an opinion about what is keeping them and other students from eating better ( more nutritious foods ) .
the students were also asked  what do you think is keeping you or other students from taking part in sufficient exercise ( daily physical activity ) ?
the number one reason offered by students for inadequate participation in physical activity is laziness .
some students insisted that there are many students who believe that they are too  cute  to dress in workout gear , and do not want to sweat during physical activity .
approximately 38.9% of the students perceived that as the main reason why many students do not participate in activities today .
the next reason cited by 14.3% of the students was that they preferred to hang out with friends rather than participate in physical activity . since it is not required daily
many of them would prefer to attend parties , talk on the telephone , ride around in cars or watch television , rather than participate in physical activity . and , besides , as some of them insisted , the school has not been helpful in encouraging them to look at the positive benefits of daily exercising .
the third ranked reason was that they simply have no desire to take part in physical activity ( see figure 2 ) .
about 6.3% of the students cited self esteem issues and the feeling of embarrassment as a major contributing factor .
the number five ranked reason for non - participation was the volume of homework assignments they have .
these students felt that they just do not have the time to participate in physical activity .
approximately 3.2% of the students explained that their inadequate participation is due to a lack of adequate mixture of games available at school .
health problems were cited by 2.4% of the students as obstacles , and 1.6% of them indicated that disagreements with the gym teacher resulted in their non - participation .
a small number of students believe that being fat or overweight was a contributing factor to their failure to participate in physical activity . there were approximately 19.0% of the students who had no opinion about what was keeping them and other students from taking part in sufficient exercise ( daily physical activity ) .
the students also responded to the question  what do you think is needed to help students to start eating better and exercising more ?
 the number one suggestion given by students for improving their quality of life was that the school should provide better and more nutritious cafeteria food ( see figure 3 ) .
this was equaled in number by the need for guidance by school personnel and parents in the area of healthy eating practices .
they felt that the adults should show more interest and concern , and do more to provide adequate instruction and direction , possibly implementing new programs or activities and increased time in health class to address these important issues .
they also believed that the parents have a major responsibility to lead the way by providing positive alternatives .
this was followed by the need for more encouragement and motivation , as expressed by 14.1% of the students .
about 11.3% of the students felt that the school should increase the volume of physical activity and exercise offered to students daily .
number five among the students suggestions was the recommendation that the school make exercise mandatory for students .
the students felt that , as incentives , school officials should use prizes , grades or money to encourage students to participate .
another 6.3% of the students suggested that school should make exercise and nutrition programs more fun to encourage students to participate .
some students concluded that increased conversation about the topic would lead to heightened motivation among students to participate in activities that are offered in their health and physical education classes .
about 4.2% of the students believed that parents and teachers do not care enough to provide them with adequate guidance and opportunity .
the students felt that the school needs to implement a healthy life program within its curriculum .
approximately 4.2% of the students indicated that the students themselves should eliminate junk food and fast foods from their daily lunch menus .
another group of students suggested that more positive advertising of nutritious foods should be encouraged and should be a major part of the plan to improve the students quality of life .
students felt that they should be constantly apprised of the dangers of negative practices regarding poor eating practices and inadequate physical activity .
this would facilitate their change to healthier daily practices which could possibly add years to their lives .
approximately 11.3% of the students said they did not know the answer and could not present any suggestions .
the major limitation of this study was the fact that only 42% of the total number of students eligible to participate in the study provided surveys that could be analyzed .
. however , their responses are valuable enough to shed some light on obstacles to good health and possible solutions to improve the quality of life and develop ways of helping them to eliminate negative practices and reduce risk factors .
the major limitation of this study was the fact that only 42% of the total number of students eligible to participate in the study provided surveys that could be analyzed .
. however , their responses are valuable enough to shed some light on obstacles to good health and possible solutions to improve the quality of life and develop ways of helping them to eliminate negative practices and reduce risk factors .
the interpretation of the students responses to these critical health issues identifies certain urgent needs that could and should be addressed by the academic institutions .
many students understand that there may be negative consequences resulting from the daily choices that they make .
it is clear that culture and family customs have a great influence on the direction students take in their dietary practices , as well as their involvement in physical activity .
the convenience and easy accessibility of low nutritious foods is also seen as a contributing factor , as are the negative influences that are presented through advertising of non - nutritious foods .
it is evident that adequate support and guidance from adults are not available often enough to facilitate the kind of learning and training that could ensure that students are afforded the opportunity to acquire knowledge to help them make positive responsible choices and decisions .
so children have little desire to take the initiative to make improvements in their daily practices .
the students suggested that modifying the schools curriculum to address student risk behaviors should become an embedded characteristic of their educational systems .
the current absence of learning strategies to adequately address and educate students about the pitfalls of negative dietary and physical behaviors is a major shortcoming of the school s education system .
recommendations for future studies should involve examining the responses of students enrolled in predominantly white institutions with those of the predominantly african american canton public school district . studies could also be designed to compare the responses of students from urban schools and rural schools to determine what their perceptions and recommendations are concerning risk factors and ways of reducing them .

Answer:
this study was designed to assess students perceptions of the obstacles to positive dietary practices and increased physical activity and to solicit the students recommendations for addressing and possibly reducing the negative practices that are associated with the rise in obesity and the development of cardiovascular diseases .
 data for the study were obtained from the administration of the 2005 project health high school survey ( phhss ) which measured the students perceptions regarding obstacles to eating more nutritious , healthier foods and obstacles to participating in daily physical activity .
 the reasons for students lack of interest in practicing more life - healthy behaviors are ranked and recorded .
 some of the students indicated that they usually ate what they liked to eat , and the decision about what to eat was made because of the taste of the food without regard for any health consequence or negative health outcomes .
 finding ways to reach these students at their young ages is the key to successfully combating the high prevalence of obesity and the development of other chronic diseases in childhood , as well as in adulthood .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
pmds is a rare form of male pseudo - hermaphroditism characterized by the presence of mullerian duct structures in an otherwise phenotypically , as well as genotypically , normal man .
it is characterized by the persistence of the uterus , fallopian tubes and upper vagina in otherwise normally virilized boys . despite the normal male genotype ( 46 xy ) and the subsequent normal development of fetal testes , mllerian structures do not regress either due to absence of mllerian inhibiting substance ( mis ) or lack of response to it .
the persistence of a large uterus - like paramesonephric duct in a man is in itself clinically unusual , but when it forms a part of the contents of a hernial sac , it must be considered a rarity .
we report the case of a 70 year old man with unilateral cryptorchidism on the right side and left obstructed inguinal hernia containing uterus and fallopian tube ( that is , hernia uteri inguinalis ; type i male form of pmds ) coincidentally detected during an operation for an obstructed left inguinal hernia with right cryptorchidism .
a 70 year old man presented to our hospital with a painful left - sided inguinal swelling of one day duration . the patient gave history of asymptomatic left inguinal swelling from past 20 years and absence of the right testis since birth .
he had been married for fifty years and was having 4 children , the youngest one being 38 year old female .
general physical examination revealed a man of sub - average built with well developed secondary sexual characters . his urethra and penis
were fully developed with a poorly developed right hemi - scrotum and no palpable right testis in the scrotum or inguinal canal .
there was a non - reducible , tender swelling measuring approximately 10    8  cm in the left inguinal region with absent cough impulse .
exploration of the inguinal canal revealed an indirect inguinal hernia containing a globular structure resembling uterus , fallopian tubes with an atrophic right testis embedded in the broad ligament and attached to pelvis with a thick fibrous band [ figs . 1 and 2 ] .
total excision of the uterus with fallopian tubes and atrophic right testis was performed and the operation was completed with left inguinal hernioplasty [ figs . 3 and 4 ] .
grossly , the specimens removed were identified as a uterus with patent endometrial and endocervical linings and two fallopian tubes .
the right testis measuring 2    1    1  cm , was atrophic and embedded in the right broad ligament .
the specimen was sent for histopathological examination which revealed uterine muscular tissue with its cavity lined by endometrial tissue and congested fallopian tubes .
male pseudo - hermaphroditism is a condition in which the gonads are testes but the internal genitalia are not completely virilized .
pmds is a rare form of internal male pseudo - hermaphroditism in which mullerian duct derivatives are seen in men .
the exact cause of pmds is not known , however it is thought to result from a defect of the synthesis or release of mif , or from defects in the mif receptor .
defects in the mif gene lead to the persistence of a uterus and fallopian tube in males .
it is likely that remnant mullerian structures lead to cryptorchidism by hindering the normal testicular descent mechanism .
patients with pmds usually have normal development of external genitalia and secondary sexual characteristics . the typical patient with pmds
has unilateral or bilateral cryptorchidism and is assigned to the male sex at birth without hesitation , as they have normal male genotypes and phenotypes .
the male form is encountered in 8090% of cases , characterized by unilateral cryptorchidism with contralateral inguinal hernia , and can be one of the two types : the first type is hernia uteri inguinalis , which is characterized by one descended testis and herniation of the ipsilateral corner of uterus and fallopian tube into the inguinal canal .
the second type is crossed testicular ectopia , which is characterized by herniation of both testes and the entire uterus with both fallopian tubes .
clinically , the persistence of a uterus and fallopian tubes leads to either cryptorchidism or inguinal hernia depending on whether or not mullerian derivatives can be mobilized during testicular descent .
if the uterus and fallopian tube are mobile , they may descend into the inguinal canal during testicular descent .
pmds is usually coincidently detected during surgical operation , as in our patient 's case .
however pre - operative ultrasonography , computerized tomography and mri allow possible pre - operative diagnosis .
an element of deciding on intervention is largely based on reducing risk of malignancy , while maintaining maximum reproductive function . in pmds patients with undescended testes ,
the rate of testicular cancer is about 12% which is comparable to the rate seen in undescended testes not associated with pmds .
several authors have asserted that the mullerian structures should not be removed as there is minimal risk associated with their retention , and excision of the mullerian structures risks damaging primary blood supply to the pmds testis via the internal spermatic and deferential arteries .
however most recent reports have demonstrated rare malignancies including adenocarcinomas of the mullerian duct associated with retained mullerian structures .
pmds is a rare form of male pseudo - hermaphroditism characterized by the presence of mullerian duct structures in an otherwise phenotypically , as well as genotypically , normal man .
since patients are phenotypically male , the diagnosis is usually not suspected until surgery is performed for cryptorchidism or hernia repair .
hernia uteri inguinalis is type i of the male form of pmds , characterized by one descended testis and the herniation of the ipsilateral corner of the uterus and fallopian tube into the inguinal canal . in order to prevent further complications such as infertility and malignant change
, the surgeon should be aware of pmds while dealing with patients who present with unilateral or bilateral cryptorchidism . in summary , in cases of unilateral or bilateral cryptorchidism associated with hernia , as in our patient 's case ,
a written informed consent was obtained from the patient for publication of the case report and various images which may be used with the same .
the patient being a major gave a written consent of the same after assuring him that name and hospital mrd no of the patient will not appear in the case report .
all the authors have contributed either as being part of surgical and anaesthesia team or helping in the photography , paper writing , submission etc . afak yusuf sherwani , abdul qayoom shah , abdul majeed wani , farooq ahmad sofi and ashfaq amin wani were in the surgical team .
bashir a chalkoo , bashir a khan and ab hamid sherwani in the anaesthesia team .
wasim lone , mehmood a sheikh and raj reshi sharma did photography and paper writing .

Answer:
introductionpersistent mullerian duct syndrome is a rare form of male pseudo - hermaphroditism characterized by the presence of mullerian duct structures in an otherwise phenotypically , as well as genotypically , normal man ; only a few cases have been reported in the worldwide literature .
 a great variety of organs have been found in indirect inguinal hernial sacs.presentation of casewe report a case of 70 year old man , father of 4 children with unilateral cryptorchidism on the right side and left - sided obstructed inguinal hernia containing uterus and fallopian tube ( that is , hernia uteri inguinalis ; type i male form of persistent mullerian duct syndrome ) coincidentally detected during an operation for an obstructed left inguinal hernia.discussionpmds is usually coincidently detected during surgical operation , as was in our case .
 however pre - operative ultrasonography , computerized tomography and mri allow possible pre - operative diagnosis.3conclusionin cases of unilateral or bilateral cryptorchidism associated with hernia , as in our patient 's case , the possibility of pmds should be kept in mind .


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
A visible-light mediated three-component radical process using dithiocarbamate anion catalysis

Paper sections:
Introduction

Multicomponent reactions (MCRs) are important in synthetic chemistry because they allow the rapid construction of complex molecules from simple substrates and in a single step. 1 While chemists have predominantly developed methods based on polar pathways, radical reactivity provides a powerful alternative. 2,3 However, methods to initiate radical MCRs have traditionally required unstable initiators or stoichiometric oxidants or reductants (Fig. 1a). 4 These relatively harsh conditions for generating open-shell intermediates (high temperatures, toxic reagents or strong redox-active reagents) signicantly affect the selectivity and the functional group tolerance of the overall radical cascade processes. Recently, the eld of photoredox catalysis 5 has overcome some of these limitations, offering effective tools to trigger radical MCRs under mild conditions while avoiding the need for stoichiometric metals or harsh atom abstractors. 6 However, this radical generation strategy mainly activates substrates via single-electron transfer (SET) pathways, thus relying on their redox properties. 7 This intrinsic feature poses a voltage-gated limit to the generality of the radical precursors that can be used.

In this context, our laboratory recently reported a unique photochemical catalytic strategy, which harnesses different physical properties of the substrates to generate radicals (Fig. 1b). 8 Specically, we designed the readily available and air-  and moisture-stable dithiocarbamate (DTC) 9 anion catalyst A, which is adorned with an indole chromophoric unit. This organic catalyst is nucleophilic enough 10 to activate alkyl electrophiles by displacing a variety of leaving groups via an S N 2 pathway. The resulting photon-absorbing intermediates I afford radicals upon excitation by visible light and homolytic cleavage of the weak C-S bond. 11 This catalytic S N 2-based strategy, which is not reliant on the redox properties of the radical precursor, grants access to open-shell intermediates from substrates that would be incompatible with or inert to classical radicalgenerating strategies, including photoredox catalysis.

Here, we demonstrate how this photochemical strategy can be translated into the realm of radical MCRs to design cascades that would be difficult to implement with other methods. Specically, we report a three-component reaction mediated by the DTC potassium salt catalyst A that uses difficult-to-reduce alkyl chlorides 1 as radical precursors and couples them with readily available maleimides 2 and heteroaromatic fragments 3 (Fig. 1c). This carbo-difunctionalization of maleimides 12 combines two sequential intermolecular radical-based bondforming processes to afford complex products 4 containing a succinimide moiety. This structural element is found in numerous biologically active molecules. 13 Importantly, the method's redox neutral conditions and high functional group tolerance allow us to easily adorn products 4 with a variety of biologically relevant N-heterocycles, 14 which would not be compatible with strong redox-active reagents.

Mechanistic plan

The specic mechanistic details of our proposed photochemical radical MCR are outlined in Fig. 2. We envisioned a catalytic cycle where the DTC catalyst A would activate alkyl chlorides 1 upon S N 2 attack. 10 The resulting intermediate I possesses a weak C-S bond, which would be cleaved by low-energy photons (blue LEDs) to generate the target carbon radical II and the dithiocarbonyl radical III. 11 The nucleophilic open-shell intermediate II would initiate the radical cascade upon interception from maleimide 2, which forges a new C-C bond. The emerging electrophilic radical IV would in turn participate in a second trapping event with an electron-rich heteroaromatic compound, affording the open-shell intermediate V. This crucial intermediate would act as a reductant to turn over catalyst A upon SET reduction of the dithiocarbonyl radical III. 15 Overall, this net redox-neutral transformation would deliver the functionalized cascade product 4. 8

Results and discussion

To test the feasibility of our strategy, we selected the commercially available N-(chloromethyl)phthalimide 1a as precursor of a nucleophilic radical, N-methylmaleimide 2a as the radical trap, and N-methylpyrrole 3a as the terminal electron-rich heteroaromatic trap (Table 1). The experiments were conducted at 60 C in DCE using blue LEDs emitting at 465 nm, 20 mol% of the DTC catalyst A and a large excess of 3a. These conditions furnished the cascade product trans-4a in good chemical yield and with excellent diastereoselectivity (dr > 20 : 1, entry 1). Under these conditions, we did not observe any byproduct arising from either a pyrrole alkylation radical path with 1a or a polar addition of 3a to maleimide 2a. Variations of the initial conditions, including a lower catalyst amount and temperature (entries 3 and 4), led to poorer results. Control experiments established that both catalyst A and light are necessary to trigger the three-component radical process (entries 5 and 6), thus excluding an alternative polar pathway for the formation of 4a.   a Reactions performed on a 0.1 mmol scale at 60 C for 20 h using 0.2 mL of solvent under illumination by blue LED strip (l max ¼ 465 nm) and using catalyst A (20 mol%), 1.5 equiv. of 1a, and 10 equiv. of 3a. b Yield of 4a determined by 1 H NMR analysis of the crude mixture using trichloroethylene as the internal standard; value in parenthesis refers to the yield of isolated 4a. DCE: 1,2-dichloroethane; AcOEt: ethyl acetate; NPhth: phthalimide.

Interestingly, no product formation was observed when replacing catalyst A with the strongly reducing fac-Ir(ppy) 3 photoredox catalyst (E 1/2 Ir(IV)/Ir(III*) ¼ À1.73 vs. SCE), 16 which highlights the inability of photoredox catalysis to trigger the radical MCR process (entry 7). 17 Using the optimized conditions described in Table 1, entry 1, we turned our attention to exploring the generality of the photoinduced radical cascade process (Fig. 3). The method is amenable to synthetically useful purposes, since a high efficiency was maintained when running the reaction on a 5 mmol scale. This experiment did not require any modication of the standard experimental set-up (see ESI † for details), and it afforded product 4a in good yield and with complete diastereoselectivity (0.91 g, 52% yield, >20 : 1 dr). We then explored the scope of the radical precursors 1 could be activated by the DTC catalyst A. Our approach displayed a high degree of tolerance towards N-heterocycles, as the cascade products 4 could be readily adorned with triazole (4b), pyrazole (4c), isoxazole (4d), benzothiazole (4e), and thiazole (4f) scaffolds. Other heterocyclic moieties, such as furan (4g) and thiophene (4h), were also tolerated. These common motifs are typically found in drug molecules. However, they generally represent a signicant tolerability challenge for synthetic methods. 14a The corresponding MCR products 4 were obtained with good yields and complete diastereoselectivity. Importantly, the reduction potentials of the heterocyclic-containing substrates 1, evaluated by cyclic voltammetry, are sufficiently negative (E red < À2.0 V vs. Ag/AgCl, see ESI †) to remain out of reach of most commonly used photoredox catalysts. 5 Therefore, SET-based reduction methods to generate the target radicals and trigger this MCR process would require strong reductants, greatly limiting functional group compatibility.

Fig. 3 Reaction scope: reactions performed on 0.5 mmol scale using 1.5 equiv. of 1, 10 equiv. of 3, and 1.0 mL of 1,2-dichloroethane; yields of products 4 refer to isolated material after purification. a NMR yield determined using 1,1,2-trichloroethylene as the internal standard. b The corresponding bromides 1 were used as radical precursors. c 3 equiv. of 1; NPhth: phthalimide.

Benzylic radical precursors, bearing both electron-rich and electron-poor aryl substituents, were also competent substrates, affording the complex products in moderate to high chemical yields (4i-4s, 28-72% yield). Reactive functional groups, including an aryl iodide (4m), a boron ester (4o), an amide (4p), and a free alcohol (4q), were all tolerated activated exclusively at the desired benzylic position. Regarding the diastereoselectivity, full control was achieved with electron-rich benzyl systems, while the presence of electron-withdrawing moieties affected the relative stereocontrol (4i-k, 4n). In addition, prenyl chloride, which delivered an allylic radical upon activation, could be successfully used in the MCR (product 4t), albeit with reduced diastereoselectivity. The N-protecting group of the maleimide 2 was found to be important for stereocontrol, as unprotected maleimide resulted in low diastereoselectivity (product 4u). Substrates 2 bearing more encumbered protecting groups were well tolerated (adducts 4v, 4w), and thiophene was found to be an alternative terminal radical trap (4x and 4y). A complete list of moderately successful and unsuccessful substrates for this radical MCR strategy is reported in Section D, Fig. S5 of the ESI. † To showcase the system's synthetic utility, we used this strategy to prepare highly functionalized pyrroles, which are relevant motifs found in natural products, pharmaceuticals, and materials. 18 Specically, we envisioned an assembly line protocol that combines two sequential radical processes, governed by the DTC catalyst A and visible light, to achieve a 2,5difunctionalization of a commercial pyrrole building block (Scheme 1a). First, the photochemical activation of chloroacetonitrile 5 by A generates an electrophilic radical, which is readily intercepted by N-methyl pyrrole to deliver the functionalized intermediate 6 in 92% yield. 8 By exploiting the residual nucleophilic character of C5, the pyrrole 6 was then used in the MCR process with N-(chloromethyl)phthalimide 1a and Nmethylmaleimide 2a to rapidly assemble the difunctionalized pyrrole 7 from commercially available substrates.

Finally, we demonstrated that the succinimide moiety within the MCR products 4 can be readily transformed into a pyrrolidine, which is a synthetically and biologically relevant framework. 19 As highlighted in Scheme 1b, the reduction of adduct 4w with LiAlH 4 affords the corresponding trans-3,4-disubstituted pyrrolidine 8. This transformation further testies to the potential of this MCR strategy to cover biologically relevant chemical space.

Conclusions

We have developed a visible-light-mediated three-component radical strategy, which couples readily available alkyl chlorides, maleimides, and heteroaromatic fragments to rapidly generate complex products. The MCR is founded upon an S N 2based radical-generation strategy, which is not reliant on the redox properties of the radical precursors and therefore overcomes the limitations of photoredox chemistry. The redox neutral conditions of this process make it tolerant of redoxsensitive substrates and allow the installation of multiple biologically relevant heterocycles within the products. These ndings, along with the experimental simplicity and the low cost of the catalyst, suggest that this method can inspire the design of other voltage-independent radical applications and would be amenable to interrogating new chemical space in medicinal chemistry.

Conflicts of interest

There are no conicts to declare.

Answer: We report a photoinduced three-component radical process, which couples readily available alkyl chlorides, maleimides, and heteroaromatic fragments to rapidly generate complex chiral products with high diastereocontrol. This method generates radicals via an S N 2-based photochemical catalytic mechanism, which is not reliant on the redox properties of the precursors. It therefore grants access to open-shell intermediates from substrates that would be incompatible with or inert to classical radicalgenerating strategies. The redox-neutral conditions of this process make it tolerant of redox-sensitive substrates and allow the installation of multiple biologically relevant heterocycles within the cascade products.


Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Chiral Br\xc3\xb8nsted Acid from a Cationic Gold(I) Complex: Catalytic Enantioselective Protonation of Silyl Enol Ethers of Ketones

Paper sections:

Over the past decade gold catalysis has attracted significant attention from synthetic community.1 More recently, notable progress has been made in asymmetric catalysis using homogenous gold(I) complexes. In general, enantioselective reactions have relied on the ability of cationic gold(I) complex π-donor ligands such as alkynes, allenes, and alkenes and activate them toward nucleophilic attack.2–4 In contrast, similar σ-complexes of cationic gold complexes with σ-donor ligands have been little explored in asymmetric catalysis, although there have been several reports of reactivity differences in gold catalysis in the presence of protic additives.5 Very recently, we found that alcoholic additive have a dramatic effect on the regio- and enantioselectivity in gold-catalyzed hydroamination of 1,3-dienes.6 For example, in the absence of alcohol, 1,2-addition products were obtained as exclusive products with very poor enantioselectivity, whereas in the presence of an alcohol additive 1,4-addition products were obtained in good yields and high enantioselectivity (eq 1).

(1)

We hypothesized that in the absence of alcohol, the cationic gold(I) directly activates the 1,3-diene towards nucleophilic attack leading to the 1,2-addition products. On the other hand, in the presence of alcohol, cationic gold(I) forms σ-complex with alcohol to generate chiral Brønsted acid activated by complexation with gold; a so called, Lewis acid activated Brønsted acid (LBA).7 Based on these observations, we envisioned that a new chiral Brønsted acid could be generated by complexation of alcohol with cationic gold, significantly enhancing the acidity of the original alcohol. Herein we describe the development of a chiral LBA derived from cationic gold complex and its application to enantioselective protonation reaction of silyl enol ethers of ketones.8–11

We began our investigation by examining the protonation reaction of silyl enol ether 4a, catalyzed by 3 mol% (R)-DTBM-SEGPHOS(AuCl)2 activated by 3 mol% AgBF4, in isopropanol as a solvent. Under these conditions, the desired protonation product 5a was obtained in quantitative yield and 87% ee (Table 1, entry 1). Encouraged by this initial result, we examined other chiral diphosphine(bis)gold complexes as catalysts for the enantioselective protonation reaction (entries 1–6). Among the gold(I) complexes tested, the (R)-BINAP-derived complex proved to generate the most selective catalyst for the asymmetric protonation reaction (entry 5).

With BINAP as the diphosphine ligand on gold, we next examined the effect of counterions on the protonation reaction (entries 4, 7–11). Generation of the cationic gold(I) complex proved essential for the protonation reaction, as no protonation was observed without AgBF4 (entry 12), or when a more coordinating counterion was used (entry 7). On the other hand, reactive catalysts were generated from non-coordinating anions (entries 4, 8–11), with tetrafluoroborate providing the protonation adduct with highest enantioselectvity. Furthermore, the catalyst derived from the monocationic gold(I) complex proved more selective than the one from dicationic gold complex (entries 5 and 13). We also investigated the possibility of protonation catalyzed by a Brønsted acid derived from AgBF4·BINAP complex; however, this silver-based Brønsted acid was not reactive enough to protonate silyl enol ether 4a (entry 14).12 Finally, the enantioselectivity could be further increased by changing the solvent from isopropanol to ethanol (entry 15).13

With these optimized conditions, we first investigated the scope of the gold-catalyzed enantioselective protonation reaction of silyl enol ethers of cyclic ketones (Table 2). Various silyl enol ethers from 2-aryl cyclic ketones could be employed in the enantioselective protonation reaction and the corresponding ketones were obtained with excellent yields and high enantioselectivities (entries 1–5). The cationic gold(I)-derived LBA could be further applied to the protonation reaction of silyl enol ethers of 2-alkyl cyclic ketones (entries 6–7). Tetralone and indanone analogs bearing a methyl group at the 2-position were obtained in quantitative yields and excellent enantioselectivity. It is noteworthy that the ring size of cyclic ketones had little effect on reactivity and high levels of enantioselectivity were obtained regardless of ring size (entries 1 vs 5, 6 vs 7).

Although several examples of Brønsted acid-catalyzed enantioselective protonation reactions of silyl enol ethers of cyclic ketones have been reported,9–11 to the best of our knowledge, there have been no reports of Brønsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic ketones.14,15 Therefore, we next examined the use of our gold(I)-based catalytic system in the enantioselective protonation of these more challenging substrates. The first anticipated challenge with acyclic substrates is the stereochemistry of starting silyl enol ethers. In contrast to cyclic ketones having only one isomer of silyl enol ethers, acyclic ketones can generate both (E) and (Z) silyl enol ethers. Since the transition states for the protonation of the diastereomeric silyl enol ether are different, we anticipated that it might be important to diastereoselectively generate the silyl enol ethers.8e Furthermore, the acyclic substrates generally have more conformational flexibility than the corresponding cyclic ones, which can also lead to lower asymmetric induction.

With these challenges in mind, we examined our LBA-catalyzed asymmetric protonation reactions of silyl enol ethers of acyclic substrates (Table 3). First, we attempted to synthesize stereochemically pure silyl enol ether 6a of 2-phenyl propiophenone. After several unsuccessful attempts to obtain stereochemically pure silyl enol ether of 2-phenyl propiophenone,16 we decided to apply a mixture of (E) and (Z) silyl enol ethers to enantioselective protonation reaction under the standard condition developed for protonation reaction of cyclic substrates. To our surprise, the protonation product was obtained in nearly quantitative yield and 92 % ee despite a 2:1 isomeric ratio of the silyl enol ether substrate (entry 1, Table 3).

With this rather unexpected result in hand, we moved our attention to other acyclic substrates under those reaction conditions. Several other silyl enol ethers from 2-aryl propiophenones were prepared were prepared as a mixture of E/Z isomers. Protonation products, however, were obtained in excellent yields and high enantioselectivities regardless of the ratio of E/Z in the starting silyl enol ethers (entries 2–8). Electronic effects had little impact on enantioselectivity (entries 1–4), although electron-withdrawing substituents required somewhat longer reaction times (entry 4). Acyclic ketones bearing bulky aryl groups at the alpha-position, such as ortho-substituted aryl group, are tolerated, albeit with slightly lower enantioselectivity (entries 6–8). We further examined the effect of substituents on the aromatic ring of 2-phenyl propiophenene (entries 1, 9–11). Substituents on the phenyl ring have little effect on enantioselectivity (entries 1,9–10), although the silyl enol ether with an electron-withdrawing substituents decreased reacted more slowly in the protonation reaction (entry 11). Furthermore, alkyl substituted silyl enol ether 6l could also be employed in the gold-catalyzed protonation reaction with only slightly lower enantioselectivity (entry 12). The catalyst system was also effective for the protonation of the silyl enol ether of 2-phenyl butyrophenone (6m), providing the desired ketone in 91% yield and 85% ee (entry 13). However, the silyl enol ether possessing two alkyl groups at the α-position provided the protonation product in poor enantioselectivity (entry 14).17

Several experiments were conducted in order to gain insight into the reaction mechanism. First, we tested the possibility that the reaction proceeded by protonation of a gold enolate18,19 generated transmetallation of the silyl enol ether; however, silyl enol ether 6a remained intact and we could not detect any gold enolate formation on treatment the cationic gold complex in the absence of alcohol. A second possible scenario is selective protonation of a rapidly equilibrating mixture of silyl enol ether isomers, in which the isomerization is catalyzed by either protonation or the cationic gold complex.20 However, we did not observe any isomerization between silyl enol ethers by either LBA or the cationic gold complex and the ratio of E/Z isomers did not remain constant during the protonation reaction (Figure 1). The third scenario is that the gold-derived LBA discriminates both isomers and approaches both silyl enol ethers from the same prochiral face, which results in very high enantioselectivity regardless of a ratio of (E) and (Z) silyl enol ethers. This scenario is consistent with the observation that the enantioselectivity of the reaction remains constant, despite the changing ratio of olefin isomers (Figure 1). Similarly, protonation of the silyl enol ether of 2-phenyl propiophenone with different E/Z ratios, produced ketone 7a with comparable the yields and enantioselectivities (eq 2).

(2)

In conclusion, we have developed the first gold-catalyzed enantioselective protonation reaction. The chiral Brønsted acids derived from cationic gold-complexes and an alcohol were applied to enantioselective protonation reaction of silyl enol ethers of ketones. Various silyl enol ethers from cyclic ketones could be applied to this catalytic system and the desired protonation products were obtained in excellent yields and high enantioselectivities. Furthermore, the catalytic system could be extended to the first enantioselective protonation reactions of silyl enol ethers of acyclic ketones. The silyl enol ethers of acyclic ketones afforded the corresponding ketones in high enantioselectivities even with a mixture of (E) and (Z) isomers of silyl enol ethers. Mechanistic studies suggest that a gold-derived LBA selectively protonates silyl enol ethers from the same prochiral face regardless of their stereochemistry.

Answer: A chiral Br\xc3\xb8nsted acid has been developed from cationic gold(I) disphosphine complex in the presence of alcoholic solvent and applied to enantioselective protonation reaction of silyl enol ethers of ketones. Various optically active cyclic ketones were obtained in excellent yields and high enantioselectivities including cyclic ketones bearing aliphatic substrates at the \xce\xb1-position. Furthermore, the application of this Br\xc3\xb8nsted acid was extended to the first Br\xc3\xb8nsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic substrates, regardless of their E/Z ratio.


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
in the last two decades , a large research effort has been devoted to quantum dots ( qds ) , the quantum wires , qd chains , nanoholes and pits [ 1 - 8 ] due to their modified density of states , fascinating optoelectronic properties and device applications for lasers , photodetectors and other electronic devices . among quantum dots , pits and wires fabrication techniques , the self - organized stranski
krastanow method   is an important one by which dislocation - free dots , elongated islands and wires can be produced . indeed , above a certain critical thickness , the growth mode switches from the conventional layer - by - layer ( i.e. , two - dimensional , 2d ) to a 3d growth mode due to the accumulation of the elastic energy in the strained layer that , first , partially relaxes by spontaneously nucleating small islands of strained material and , later , by creating misfit dislocations .
the elastic strain caused by lattice mismatch can also be relaxed by the formation of undulations , pits and their combination [ 5 - 8 ] .
depending on the growth conditions , the elastic strain can be relaxed by the formation of either quantum wires and quantum dots , or even unique island
extensive experimental results suggest that surface morphologies are relying on growth conditions and matrix materials . on the basis of an atomistic model
, it is shown that the energy change due to the step formation is negative or positive depending upon the sign of the misfit
. the step formation energy can even be negative for compressive misfit stress in the heterolayer , while it is definitely positive for tensile misfit stress .
this conclusion is in contrast to the classical model where the step energy is always positive and independent of the sign of the misfit .
the step formation energy influences the critical thickness and the energy barrier for dislocation nucleation . using a simple atomistic simulation
, it is shown that the critical thickness depends upon the sign of the misfit .
for example , it changes from 4 nm for ge films on si(100 ) substrates to 6 nm for si films on ge(100 ) substrates having the same misfit .
the investigations of the surface morphology evolution of strained inas / gaas films at different growth conditions   demonstrated that there are at least three different strain relaxation mechanisms for the same material system .
that is , depending on the growth conditions , the elastic strain can be relaxed by the formation of either quantum wires or quantum dots , or even unique island  pit pairs .
. both the island height and the pit depth can be much greater than the average layer thickness .
this suggests that considerable mass transport from substrate into the islands is taking place during the growth .
however , during heteroepitaxy , when the layer becomes sufficiently thick , the pits are eventually filled up either by the lateral overgrowth or by the expanding islands , forming nearly pure island morphology at the surface .
the detailed analysis of the surface dynamics during phase transitions of gaas(100 )   and unusual role of the substrate at droplet - induced gaas / algaas qd pairs growth   also confirm this assumption . from the industrial point of view , the narrow band gap iii
v semiconductor materials like inas , gasb , insb and their ternary and quaternary alloys are particularly interesting and useful since they are potentially promising to access mid - infrared and far infrared wavelength regions .
these materials would provide the next generation of leds , lasers and photodiodes for applications such as infrared gas sensors , for molecular spectroscopy , thermal imaging , photovoltaic ( pv )   and thermo - photovoltaic cells ( tpv ) .
the application of the inassbp and other similar quaternary materials opens up interesting physical and technological prospects for the dirigible growth of qds , the pits and dots  pits cooperative systems .
independent variations of the third and fourth components provide corresponding sign of the misfit ; i.e. , providing the tensile or compressive misfit stress .
at the first case , elastic strain will be relaxed by the formation of qds , but at the second one  by the pits . in this article , an example of inassbp quaternary qds , the pits and dots  pits cooperative structure growth on inas(100 ) substrates by lpe , as well as the interaction and surface morphology of the dots  pits combinations are presented and investigated .
the samples are grown by lpe using a slide - boat crucible . to ensure a high purity of the epitaxial layers ,
the inas(100 ) substrates have a 11 mm diameter are undoped , with a background electron concentration of n = 2  10 cm .
the inas0,742 sb0,08 p0,178 quaternary alloy used here as basis composite is conveniently lattice - matched to inas .
the lpe growth solution components  undoped inas , undoped inp and sb ( 6 n ) are solved in a in ( 7 n ) solution that has been first homogenized for 1 h at t = 580 c and then 3 h at the initial growth temperature of t = 550 c to equilibrate the system thermodynamically . to expect the strain - induced qds and pits formation , the undoped and supersaturated by antimony and phosphorus liquid phase was used to provide a different sign of lattice mismatch up to 4% between the inas substrate and inassbp epilayer . to initiate the growth of qds and pits ,
an oversaturation of the liquid phase is developed by decreasing the initial growth temperature up to 2 c at the slower ramp rate .
the high - resolution scanning electron microscope ( sem - edxa  fei nova 600dual beam ) is used to study the strain - induced inassbp qds
1 ) that the pits ( large and small ) like the islands primarily formed into truncated  reverse  pyramids . the edxa measurements shown that , at first , either islands or pits edges have a quaternary composition and that on average , they are enriched by antimony and by phosphorus , respectively . in our inassbp quaternary experimental system , the nucleation mechanism of qds and the exposure of wetting layer ( and inas substrate ) at pits are quite interesting , but very complicated for explanation result . from a physical perspective
, we have assumed that simultaneous nucleation of the islands and pits are occurring due to variable curvature ( the tensile or compressive local perturbations ) of the wetting layer .
we suggest that at the perturbed sites , the wetting layer surface is strained , and the depositing material will prefer not to remain at these sites , but rather diffuse away .
after that occurs , the strain relaxation is performed at the adatoms ( sb and p ) surface diffusion in opposite directions , leaving behind the islands and the pits on the surface . in this scenario , corners or edges of the pits and islands
are the most preferred sites to attach newly deposited materials , because at these regions , the strain energy is most relieved .
the islands ( or pits ) at these relaxed regions will grow rapidly at the expense of the material around the pits ( or dots ) .
the fact that the  large  pits are deeper ( up to 100 nm and more ) than the wetting layer thickness implies that the arsenic atoms are also  pumped  out from the substrate and probably replaced by the phosphorus atoms . the similar cooperative nucleation of the dots  pits pairs was detected at the growth of inas qds on gaas substrate , gaas / algaas qd pairs   and at the growth of in 0.53 ga0.47 as layers on inp(001 ) substrate .
the effect of island density on pit nucleation in in0.27 ga0.73 as films grown on gaas(001 ) substrate is discussed in .
large  pits banded by the quantum wires in order to be confident , we calculated the gibbs free energy of inassbp quaternary alloy , as well as separately of inas - insb , inas - inp and insb - inp ternary alloys .
we found that at t = 550 c ( our growth temperature ) , the gibbs energy has the minimal value at x = 0.39 for inas1xsbx and at y = 0.52 for inas1ypy alloys .
otherwise , for the insb1zpz ternary alloy at the same temperature , the sufficiently wide immiscibility gap is exist at 0.05 < z < 0.97 . in this concentration range , the gibbs energy increases ( from the both sides ) and the mixing of these binary compounds becomes energetically not preferable .
this result marginally proves our assumption that at the nucleation of inassbp quaternary dots and pits , the surface diffusion of the antimony and phosphorus in opposite direction has to be energetically more preferable .
in addition , note that with the increasing of the liquid phase initial concentration , the islands and pits shape transformation from the truncated pyramids to ellipsoidal and globe shape was detected .
figure 2a displays the sem and afm images of the inassbp unencapsulated dots  pits cooperative structure in plain view for the surface area of s = 4 m . in this figure
the qds and pits are clearly visible and quite uniformly distributed over the substrate surface .
figures 1b , 1c and 2b2d show that cooperative nucleation of the dots  pits structures is occurring . in
pits are banded by quantum wires and that the qds are banded by pits ( in the form of  nano - camomile  ) .
b , c and d  enlarged view of the mentioned by red , blue and green ovals related regions .
white ovals  qds , black ovals  pits our statistical explorations show that the  small  qds average density ranges from 0.8 to 2  10 cm , with heights and widths dimensions from 2 to 20 nm and 5 to 45 nm , respectively .
the average density of the  small  pits is equal to ( 610 )  10 cm with dimensions of 540 nm in width and depth .
surface density of the  large  dots and pits is less by almost on two orders of magnitude .
small  qds and pit amount , and surface density versus their average diameter calculated from the surface of s = 4 m is detected and displayed in fig .
dependence of the inassbp strain - induced qds and pits amount ( a , b ) and surface density ( c , d ) versus their average diameter ( s = 4 m ) .
 slezov approximations we used the fourier transform infrared spectrometry ( ftir  nicolet / nexus ) to investigate the transmission spectra ( see fig .
4 ) of an unencapsulated inassbp dots  pits cooperative structure at room temperature . as a test sample
the result shows the displacement of the absorption edge toward the long wavelength region from  = 3.44 m ( for test sample ) to    = 3.85 m , as well as the enlargement of the absorption spectrum up to  = 2.75 m short wavelength region .
we assume that this effect is the result of the absorption by the qds through the permitted energy sub - band .
pits cooperative structure grown on inas(100 ) substrate schematic diagram showing the type ii inassbp / inas qds is presented in fig .
1 . whereis the planck constant , is the light holes effective mass , is the average diameter of qds andis the integer .
the similar approach was applied in . for our experimental system ( at light holes confinements ) ,   ( at ) ,   ( at ) , sub - band depth .
numerical value for the light holes effective mass for our inas1xysbxpy quaternary system was calculated by the linear approximation of the corresponding values for binary compounds at x = 0.04 and y = 0.08 .
schematic view of the zone diagram showing the type ii inassbp / inas qds  pits cooperative structure .
numerical values for b , c , d and e energies are approximate and based on ftir measurements and calculations finally , note that at the growth of diode heterostructures with the quantum dots and pits inside p  n junction spatial charge region , the main challenge to overcome is providing the lateral overgrowth of the pits ( providing  reverse  qds ) and keeping the dots size during epitaxy of the cap epilayer .
we assume that by using step - cooling lpe , the growth of the cap epilayer from the strongly cooled liquid phase will address this problem .
thus , we have presented an example of the inassbp quaternary qds , pits and dots  pits cooperative structures growth on the inas(100 ) substrates by lpe . the interaction and surface morphology of the dots  pits combinations were investigated .
lifshits  slezov - like distribution for the amount and surface density of  small  qds , and pits versus their average diameter was experimentally detected .
application of the inassbp and other similar quaternary materials opens up interesting physical and technological prospects for the dirigible growth of qds , pits and dots  pits cooperative systems . by the corresponding and independent variations of the v - group elements concentrations ,
the results of our study can be also used for producing controlled arrays of strain - induced qds , which is very important for the fabrication of wide - band photodiodes , thermo - photovoltaic cells and other inas - based mid - infrared devices .
this work was carried out in the frame of armenian national governmental program for nano - electronics and istc grant a1232 .
this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .
this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .

Answer:
an example of inassbp quaternary quantum dots ( qds ) , pits and dots  pits cooperative structures growth on inas(100 ) substrates by liquid phase epitaxy ( lpe ) is reported .
 the interaction and surface morphology of the dots  pits combinations are investigated by the high - resolution scanning electron microscope .
 bimodal growth mechanism for the both qds and pits nucleation is observed .
 cooperative structures consist of the qds banded by pits , as well as the  large  pits banded by the quantum wires are detected .
 the composition of the islands and the pits edges is found to be quaternary , enriched by antimony and phosphorus , respectively .
 this repartition is caused by dissociation of the wetting layer , followed by migration ( surface diffusion ) of the sb and p atoms in opposite directions . the  small  qds average density ranges from 0.8 to 2  109 cm2 , with heights and widths dimensions from 2 to 20 nm and 5 to 45 nm , respectively .
 the average density of the  small  pits is equal to ( 610 )  109 cm2 with dimensions of 540 nm in width and depth . lifshits  slezov - like distribution for the amount and surface density of both
 small  qds and pits versus their average diameter is experimentally detected .
 a displacement of the absorption edge toward the long wavelength region and enlargement toward the short wavelength region is detected by the fourier transform infrared spectrometry .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the term was used by hallopeau in 1889 and is derived from the greek ; thrix - hair , tillein - pull out and mania - madness .
scalp is the most common site for pulling hair although other hair bearing areas may be involved . in less severe forms
diagnosis is mainly by history and clinical examination , nevertheless , sometimes it is very difficult to differentiate it from other causes of noncicatricial alopecia .
trichoscopy , dermoscopy hair and scalp , is a noninvasive technique for differential diagnosis of various hair and scalp diseases . here
authors evaluated trichoscopic patterns in ttm and authors believe that these patterns are specific to ttm , which can aide in early diagnosis of this chronic condition .
this study was carried out on 10 patients attending department of dermatology in a tertiary hospital attached to s. nijalingappa medical college at bagalkot , south india between january 2014 and july 2014 .
ten patients with clinical features of ttm were subjected for a complete history and dermatological examination .
demographic data such as age and gender and clinical variables in terms of site of lesions and disease duration were documented .
dermlite 3 dermoscope ( 10 magnifications ) with both polarized and nonpolarized lights was employed in the study .
sony camera ( digital , 14 mega pixels ) was attached to save the images .
initially , ultrasound gel was applied either on the faceplate of dermoscopy or on the skin lesions and then lesions were observed through the eyepiece of dermoscopy .
although polarized dermoscopy was employed , ultrasound gel was applied for clarity of images and to lessen distortions associated with light .
this study was carried out on 10 patients attending department of dermatology in a tertiary hospital attached to s. nijalingappa medical college at bagalkot , south india between january 2014 and july 2014 .
ten patients with clinical features of ttm were subjected for a complete history and dermatological examination .
demographic data such as age and gender and clinical variables in terms of site of lesions and disease duration were documented .
dermlite 3 dermoscope ( 10 magnifications ) with both polarized and nonpolarized lights was employed in the study . however , only polarized light version was used in our study .
sony camera ( digital , 14 mega pixels ) was attached to save the images .
initially , ultrasound gel was applied either on the faceplate of dermoscopy or on the skin lesions and then lesions were observed through the eyepiece of dermoscopy .
although polarized dermoscopy was employed , ultrasound gel was applied for clarity of images and to lessen distortions associated with light .
mean age of the patients was 34 years ( minimum age 13 years and maximum age 55 years ) .
mean duration of disease was 19 months ( minimum 2 months and maximum 36 months ) .
most common symptom was patchy loss of hair over the scalp ( 100% ) especially in the frontal area [ figure 1 ] and one patient ( 10% ) had tonsure pattern of hair loss .
four patients agreed to knowingly pulling of hair , and one patient ( 10% ) gave a history of eating them ( trichophagia ) .
the most common trichoscopic pattern observed in all patients was decreased hair density and hairs broken at different lengths ( 100% ) [ figure 2 ] .
excoriations are also seen on the forehead trichoscopy showing decreased hair density , trichoptilosis ( yellow arrows ) , tulip hairs ( red arrows ) and perifollicular whitish areas ( red stars ) short hair with trichoptilosis (  split ends  ) [ figures 25 ] , irregular coiled hairs [ figure 3 ] and upright re - growing hairs were demonstrated in 8 patients ( 80% ) each .
the novel diagnostic signs like black dots and flame hair [ figure 4 ] , v - sign [ figure 3 ] , follicular hemorrhages [ figure 5 ] were observed in 3 patients ( 30% ) each .
tulip hair and hair powder [ figure 6 ] patterns were observed in 1 ( 10% ) patient each .
all patients ( 100% ) had the noninflammatory alopecia with follicles having distorted and collapsed inner root sheath [ figure 7 ] in histopathology .
trichoscopy showing coiled hairs ( red arrows ) and v - hairs or v - sign ( yellow arrows ) trichoscopy showing flame hairs ( red arrows ) and black dots ( yellow arrows ) trichoscopy showing decreased hair density , follicular hemorrhage ( black arrow ) and trichoptilosis ( red arrows ) trichoscopy showing tulip hairs ( red arrows ) and hair powder ( yellow arrows ) histopathology showing diffuse , noninflammatory alopecia , missing hair shafts ( black stars ) and inward collapse of outer root sheath ( black arrows ) .
few unaffected follicles are also seen ( yellow arrows ) ( h and e , 4 ) histopathology showing an irregular , deformed and pigmented shaft characteristic of trichomalacia ( h and e , 40 )
trichotillomania is a chronic impulse control disorder characterized by repetitive hair pulling resulting in alopecia . in young children , it is usually a habit that resolves spontaneously or with minimal treatment . in older age groups , adolescents and adults ,
seen predominantly in females and evidence of some form of psychological or behavioral stress is often apparent .
the favorite site is the easily reached fronto - parietal region of the scalp followed by eyelashes , eyebrows , pubic hair , body hair and facial hair .
this results in patchy loss of hair , often in a bizarre or angular pattern , in which the hairs are twisted and broken at various distances from the clinically normal scalp .
a hairball , trichobezoar , is a rare accompaniment of ttm in those who also eat the plucked hair ( trichophagia ) . in our study ,
most of the patients belonged to adolescent , and middle age group and most of them were females .
all of them presented with patchy hair loss over the scalp , none of the patients gave a history of hair loss in other areas .
only one patient had a history of eating of pulled hairs , but there were no signs and symptoms of trichobezoar in her .
the diagnosis of ttm is often difficult as other hair loss diseases appear similar in clinical manifestations .
this difficulty is encountered especially with alopecia areata ( aa ) . as ttm often coexists with aa
trichoscopy is a novel diagnostic technique , both simple and noninvasive , can be used as a handy bed side tool for diagnosing common hair and scalp disorder .
several common trichoscopy features of ttm were identified . decreased hair density , hairs broken at different lengths , short hairs with trichoptilosis ( " split ends " ) are described in the literature as diagnostic of ttm .
authors observed these findings in all the patients , and this is due to irregular and repetitive pulling of hairs leading to damage to the cuticle . irregular coiled hairs and upright re - growing hairs are also reported to be seen in ttm . in this study , these findings were demonstrated in 80% of patients . coiled hair results from hair shaft fracture and coiling of the remaining proximal part which is fixed to the scalp .
black dots are believed to be remnants of hair shafts arising from tapering hairs , broken hairs , and bent hairs . in a study conducted by shim et al .
rakowska et al . observed that black dots tend to be uniform in size and shape in aa , whereas in ttm and tinea capitis they are variable in diameter and round , oval , irregular in shape .
it presents as a red dot corresponding to follicular ostia capped or stuffed with the blood clot and suggests a history of traumatic forced plucking .
recently , flame hairs , v - sign , tulip hairs , and hair powder are described , and authors claim these signs are specific only for ttm .
flame hairs are semi - transparent , wavy and cone - shaped hair residues , which develop as a result of severe mechanical hair pulling and shredding .
v - sign is created when two or more hairs emerge from one follicular ostium , which are pulled simultaneously and break at the same length above scalp surface .
when hair shafts are almost totally damaged by mechanical manipulation , only a sprinkled hair residue is visible .
this finding is referred to as  hair powder .  in the present study , these trichoscopic patterns were demonstrated in variable frequency . in aa , the common trichoscopic findings are yellow dots , uniform black dots , broken hair , trichoptilosis , upright re - growing hair , and vellus hair .
as some of the trichoscopic features are overlapping in ttm and aa , histopathology plays a corroborative role in definitive diagnosis .
the histopathological features of ttm include empty follicles , incomplete disrupted follicular anatomy , trichomalacia , and pigment casts without significant inflammation .
collapsed inner root sheath and missing hair shaft indicate the extraction of the hair follicle due to forcible hair pulling . partially extracted and distorted root sheath material with fragments of pigment can be identified as
the germinative follicular epithelium may produce abnormally formed , diminished and distorted hair shaft with irregular pigmentation as a result of trauma .
a new trichoscopic pattern was observed by the authors in one patient , in the form of perifollicular whitish areas [ figure 2 ] .
authors believe these whitish areas represent hyperkeratosis that is due to perifollicular damage as a result of repeated hair pulling
trichotillomania is often chronic and difficult to treat . patients may attempt to disguise the condition due to its social implications . hence
trichoscopy , being a noninvasive and in vivo diagnostic technique , can be utilized in this condition as it plays a vital role in the diagnosis of this condition by demonstrating specific trichoscopic patterns .
further studies on trichoscopic patterns correlating with duration of disease and histopathology of ttm are suggested .

Answer:
introduction : trichotillomania ( ttm ) is characterized by patchy alopecia of hair bearing areas . this is because of compulsive urge to pull the hair .
 scalp is the most common site for pulling hair .
 usually , patients may have only small areas of baldness , in severe forms , tonsure pattern of baldness is observed .
 diagnosis is by history and clinical examination .
 however , it is difficult to differentiate from other causes of noncicatricial alopecia . here , authors observed trichoscopic patterns and evaluated their importance in the diagnosis of ttm.materials and methods : this study was conducted in s. nijalingappa medical college , bagalkot , from january 2014 to july 2014 .
 ten patients with clinically suspected ttm were included in the study .
 informed consent was taken and ethical clearance was obtained .
 dermlite3 dermoscope was used with sony camera attachment to save the images .
 histopathological examination was conducted in all the patients to confirm the diagnosis.results:ten patients were included in the study .
 mean age of the patients was 34 years .
 most common symptom was patchy loss of hair in the frontal area ( 100% ) .
 common trichoscopic feature was decreased hair density and broken hairs .
 trichoptilosis ( split ends ) and irregular coiled hairs were seen in 80% patients .
 novel diagnostic signs like black dots , flame hair , v - sign , follicular hemorrhages , were seen in 30% each .
 tulip hair and hair powder were observed in 10% of patients .
 all patients had the noninflammatory alopecia with distorted and collapsed inner root sheath in histopathology.conclusion:trichotillomania is often chronic and difficult to treat . hence
 , early diagnosis and treatment is necessary .
 authors believe that the trichoscopy plays a vital role in the diagnosis of this condition by demonstrating specific trichoscopic patterns .