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 delicate catheter ablation of atrial fibrillation ( af ) involves a relevant risk of major complications although mortality is less than 1 in 2000 , , .
patients undergoing catheter ablation for af are required to lie motionless on the procedure table for several hours , and repeated stimuli from ablation are sometimes painful . for these reasons ,
the safety of deep sedation in this procedure has already been tested , and high - frequency jet ventilation during general anesthesia has also proved to be a safe technique .
aid for anesthetic management in these setting can be non - invasive ventilation ( niv ) , first used in acute respiratory failure , sometimes during sedation , subsequently used outside of the intensive care unit   and in cardio - surgical procedures , , , .
the aim of our study was to evaluate the usefulness of niv during sedation in catheter ablation of use af instead of atrial fibrillation compared to deep sedation .
in the study period ( 24 months ) , conducted in a single high - volume electrophysiology procedure center , consecutive patients undergoing catheter ablation for paroxysmal / persistent atrial fibrillation   were retrospectively revised ( fig .  1 ) .
exclusion criteria for the procedure were left ejection fraction less than 40% , moderate - to - severe mitral valve disease , severe heart failure ( new york heart association functional class iii or iv ) , expected surgery for structural heart disease , secondary af ( due to cardiac surgery , infection or hyperthyroidism ) , severe copd with concomitant respiratory insufficiency ( pao2  <  60  mmhg ) , presence of inducible myocardial ischemia or other acute illness underway , or contraindications to anesthesia . complications and recurrence of af occurring within 48  h of the electrophysiological procedure were also examined .
perioperative anesthesia visits and sedation procedures were performed according to siaarti ( societ italiana di anestesia analgesia rianimazione e terapia intensiva ) guidelines , , including pulmonary function tests in the anesthetic assessment .
routine monitoring ( electrocardiography , pulse oximetry , invasive arterial pressure , seriate arterial blood gas analysis and apnea monitor ) were performed .
sedation and niv were performed after trans - septal puncture in order to rule out left - sided emboli through neurologic assessment . midazolam
0.010.02  mg / kg iv was administered immediately before monitoring , fentanyl ( 2.55  g / kg ) was administered as analgesic and sedation was performed by propofol infusion ( bolus dose 11.5  mg / kg , maintenance 24
the infusion rate was carefully titrated to achieve a target sedation level of a ramsay sedation scale   of 23 .
mean arterial pressure was maintained above 75  mmhg during the entire procedure . during deep sedation
, the patients were breathing spontaneously and were given supplemental oxygen ( fio2 80100% ) to maintain the oxygen saturation level above 92% . in patients undergoing niv ventilation the procedure was performed with a respironic latex - free total face mask connected to garbin ventilator ( linde inc . , herrsching , germany ) in spontaneous / temporized mode applying incorporated algorithms to improve patient - ventilator synchrony by adjusting to changing breathing patterns and dynamic leaks .
i - pap , e - pap and respiratory rate were modified according to the clinical response , tolerance of the patient to obtaining exhaled tidal volume of 68  ml / kg ; fio2 requirement was 40% or less to maintain oxygen saturation above 92% .
the ventilator settings were adjusted on the basis of pulse oximetry and serial measurement of arterial blood gases .
sedation was halted when the mechanical ventilation was discontinued or at the end of the catheter ablation procedure . at the end of the procedure ,
patients were transferred , according to hospital protocol , to the intensive care unit for monitoring .
oral anticoagulation with stable international normalized ratio ( inr ) superior to 2.0 was ensured for at least 3 weeks before ablation .
transesophageal echocardiography was performed within 24  h before the procedure , to rule out the presence of left atrial thrombi . local anesthesia ( lidocaine 1% )
after septal puncture of interatrial septum , intravenous heparin was administered according to institutional standards .
minneapolis , mn , usa or carto-3 mapping system , biosense webster , diamond bar , ca , usa ) with image integration using computer tomography or magnetic resonance reconstruction of the left atrium .
catheter ablation procedure was performed using radiofrequency energy or cryoablation balloon ablation catheter ( arctic front , medtronic , minneapolis , mn , usa ) .
the electroanatomic mapping systems and the energy sources used during the procedure were selected by the electrophysiology team in relation to clinical characteristics of the patient .
categorical variables were represented as percentages , continuous variables as mean    standard deviation .
comparisons between groups were performed by unpaired samples two - sided t - test or chi - square test , with continuity correction , where appropriate .
intra - procedural changes of arterial blood gas variables were expressed as percentage variation of their basal values . a p - value less than 0.05 was considered statistically significant .
during the study period 72 electrophysiology procedures carried out in deep sedation were evaluated ; 41 ( 57% ) procedures were performed with niv ( niv group ) and the other 31 ( 43% ) with - out niv ( deep sedation group ) .
the clinical characteristics of the patients and the procedural details are shown in table 1 .
the two groups of patients showed no differences in these fields , but between the two groups , a significant variation was present in the basal paco2 ( p  =  0.008 )  with values in the physiological range  and in intra - procedural blood gas parameters ( ph p  =  0.001 , pao2
 p  =  0.004 , paco2
 p  =  0.002 respectively ( fig .
analysis of the percentage change between basal to intraprocedural blood gas parameters ( fig .
3 ) shows a statistical variation in the changing of ph and paco2 ( p  =  0.002 and 0.001 , respectively ) . during niv procedures
there were no problems due to mask - related difficulties , gastric distention , niv discomfort or significant hemodynamic alterations related to positive pressure ventilation . in the deep sedation procedure there were two episodes of respiratory complications with severe hypercapnia ( achieved a paco2 greater than 60  mmhg ) treated with application of niv .
adverse events , focused on periprocedural complications , were reported in 26 patients ( 36% ) . among the complications , vascular access complications occurred in nine cases ( iatrogenic femoral pseudoaneurysms that required percutaneous treatment   in 5 cases and femoral hematoma with decrease in hemoglobin levels greater than 2  g / dl in four cases ) ; none of these cases required transfusion support .
pleuro - pericardial effusion was documented in 8 cases ; exacerbation of bronchial asthma in three cases ; bradyarrhythmia requesting definitive pacemaker implantation in two cases ; pulmonary embolism in one case ; procedural myocardial infarction in one case ; post - procedural stroke in one case and permanent paralysis of the phrenic nerve in one case .
the recurrence of af within 48  h of the electrophysiological procedure was recorded in 21 patients ( 29% ) and was treated by electrical or pharmacological cardioversion .
deep sedation for catheter ablation of af is feasible and safe   while maintaining spontaneous ventilation . in our sedation procedures in catheter ablation of af
the niv was safe as well , and maintained ( although with respiratory parameters in the physiological range ) a better homeostasis in these parameters compared to deep sedation in breathing spontaneously . data shown in fig .  2 , fig .
3 confirmed a lower impact of niv on arterial blood gas tensions and hematic ph balance   compared to deep sedation .
while statistically significant differences were found , the absolute value differences had a clinically limited benefit ; using niv made it possible to reduce the flow of oxygen administered to the patient during the procedure and maintain better respiratory dynamics .
these conditions allowed us to maintain effective co2 elimination with minimum impact on the ph compared to the deep sedation group .
furthermore , in the 2 cases of patients who developed severe hypercapnia during deep sedation , the application of niv was effective in solving the respiratory problem without the need for endotracheal intubation .
this data shows an important and clinically relevant difference between the groups , although the small sample size does not allow to  compare this end point between the two arms of the study .
deep sedation requires frequent control and titration by anesthesiologist due to minor problems such as requiring high oxygen dose , great difference between basal and intraprocedural gas properties and occasional hypercapnia .
furthermore , niv allows to reduce the risk of hemodynamic , respiratory or neurological problems secondary to improper ventilation .
we did n't have problems related to mask - related difficulties , gastric distention , niv discomfort or significant hemodynamic alterations related to positive pressure ventilation .
also , consideration must be given to the demographic characteristics of own patients : our population had a high number of overweight patients ( overweight 39% , obese 25% ) and with a history of smoking ( 44% ) . in relation to these conditions ,
even when outside the guidelines , , our patients ' baseline respiratory function characterization was performed .
a limit of our study is the relatively small number of patients evaluated , which did not arrive at the number of patients evaluated in other studies that assessed the safety of deep sedation   or high - frequency jet ventilation . as previously described , af catheter ablation procedure has substantial procedural risks , , .
most of the complications ( 12/26 cases ) that we reported were due to the difficult balance between bleeding ( due to systemic anticoagulation ) and thrombotic ( ablation procedure and recurrence of af ) processes . in our cases
pleuro - pericardial effusion is due to the irritation of the serosa secondary to  the ablation procedure as well as paralysis of the phrenic nerve and the damage occurring to the conduction system .
incidence of major procedural complications ( 5/26 cases ) was comparable to the previous reports , , do not show differences in the two groups and are imputable to electrophysiological procedure rather than anesthetic management . of the minor complications , the only one related to anesthetic management was exacerbation of bronchial asthma .
we did not find significant differences between the two anesthetic regimens tested ( two cases in niv group vs one case in the deep sedation group ) .
these patients responded rapidly to treatment with inhaled 2-agonists and showed no alterations in chest x - ray compatible with bronchopneumonia .
own data on the early recurrence of af are in line with the literature , and this event was not related to the long - term success but was due to edema and inflammation of the myocardium subjected to ablation . in relation to the thromboembolic risk of early relapse of af , international guidelines   recommend oral anticoagulation therapy in the first few months post - ablation . in conclusion
, our study suggests that in catheter af ablation , niv proved to be a safe practice in anesthesiological management , as it can treat respiratory depression induced by sedation and maintain better respiratory homeostasis and better arterial blood gas balance when added to deep sedation .
furthermore , during the procedure patient safety was also ensured by a ventilator , which allowed continuous control of tidal volume , amount of ventilation lost to leak and effective minute ventilation .

Answer:
anesthetic management of patients undergoing pulmonary vein isolation for atrial fibrillation has specific requirements .
 the feasibility of non - invasive ventilation ( niv ) added to deep sedation procedure was evaluated.seventy-two patients who underwent ablation procedure were retrospectively revised , performed with ( 57% ) or without ( 43% ) application of niv ( respironic latex - free total face mask connected to garbin ventilator - linde inc . ) during deep sedation ( midazolam 0.010.02  mg / kg , fentanyl 2.55  g / kg and propofol : bolus dose 11.5  mg / kg , maintenance 24
 mg / kg / h).in the two groups ( niv vs deep sedation )
 , differences were detected in intraprocedural ( ph 7.37    0.05 vs 7.32    0.05 , p  =  0.001 ; pao2 117.10    27.25 vs 148.17    45.29 , p  =  0.004 ; paco2 43.37    6.91
 vs 49.33    7.34 , p  =  0.002 ) and in percentage variation with respect to basal values ( ph 0.52    0.83 vs 1.44    0.87 , p  =  0.002 ; paco2 7.21    15.55 vs 34.91    25.76 , p  =  0.001 ) of arterial blood gas parameters .
 two episodes of respiratory complications , treated with application of niv , were reported in deep sedation procedure .
 endotracheal intubation was not necessary in any case .
 adverse events related to electrophysiological procedures and recurrence of atrial fibrillation were recorded , respectively , in 36% and 29% of cases.niv proved to be feasible in this context and maintained better respiratory homeostasis and better arterial blood gas balance when added to deep sedation .


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:
melioidosis is predominantly a tropical disease and most cases are reported during the rainy season in endemic area .
it is characterized by abscess - formation in the lung , liver , spleen , skeletal muscle and prostate with the lung being the most commonly involved organ .
the clinical features are variable from rapidly progressing septicemia to chronic debilitating abscess - forming disease .
understanding about melioidosis is important in tuberculosis endemic areas , because its progression and roentgenographic findings are so similar to tuberculosis that it is not rare for melioidosis to be misdiagnosed as tuberculosis .
the patient was a 50-yr - old man who was diagnosed with melioidosis on bronchoscopic washing culture and whose symptoms improved after treatment with high dose ceftazidime .
a 50-yr - old man visited our hospital because of intermittent fever associated with cough , sputum , generalized myalgia and general weakness for about four weeks .
he had lived in indonesia for twenty years for business , and visited a local hospital in indonesia and was treated for typhoid fever without improvement of symptoms .
initial chest radiograph and computed tomography ( ct ) images showed multiple satellite nodules in the left lower and upper lobes , and judging from that roentgenographic examination , tuberculosis was the most probable diagnosis ( fig .
1 ) . bronchoscopy showed no endobronchial lesion and washing cytology and culture were also negative .
three months later we rechecked chest radiograph and ct findings , and found new infiltration in the left lower lobe and improvement of lesions in the left upper and lower lobes ( fig .
laboratory findings included white blood cell count of 5,240/l and hemoglobin value of 11.6 g / dl .
iga was 227 mg / dl ( normal range : 90 - 400 mg / dl ) and anti - neutrophilic cytoplasmic antibodies with cytoplasmic staining pattern ( canca ) was negative .
however , secretion was seen in left lower lobe , so washing cytology and culture was done .
cytology was negative but a species of bacteria grew on blood agar media ( fig .
3 ) . it was gram - negative , non - spore forming and showed as a safety pin shaped organism on microscopic examination ( fig .
api20ne strip and vitek gni card ( biomerieux , inc . , hazelwood , u.s.a . ) ,
the organism was identified as burkholderia pseudomallei ( 1 ) . on dna sequencing of 16s ribosomal rna , it was compatible with b. pseudomallei with 100% homology and formed a characteristic rugose colony on blood agar .
we prescribed ceftazidime 2 g intravenously every 8 hr and he did not complain of intermittent fever any more .
after one week of intravenous ceftazidime , he was discharged with oral amoxicillin - clavulanate ( 750 mg every 8 hr ) .
one month later the cough and sputum were almost disappeared but his general weakness persisted although it was also improving .
four months later we rechecked chest ct to show an improvement of infiltration in left lower lobe .
he said his condition was as good as his previous state before suffering from melioidosis .
one month later , we stopped administrating oral antibiotics to him , which resulted in him taking amoxicillin - clavulanate for total five months .
the endemic area includes southeast asia , north australia , madagascar , and guam ( 2 ) . in northeast
thailand , melioidosis accounts for 20% of all community - acquired septicemias , and causes death in 40% of treated patients .
melioidosis was first described by whitmore in 1911 and more than 100 cases had been reported by 1917 ( 3 ) . since then , with sporadic cases being reported during and after world war ii and many soldiers fighting in vietnam suffering from this disease , western countries began to take an interest in melioidosis .
b. pseudomallei is a motile aerobic , non - spore - forming and gram - negative bacillus .
the colonies develop a rugose appearance , and take up crystal violet dye from the medium .
although it is gram - negative bacterium , it is usually resistant to aminoglycoside , 1st & 2nd cephalosporin , macrolide , rifamycin and colistin , but is susceptible to ampicillin / sulbactam , chloramphenicol , tetracycline , bactrim , 3rd cepha and carbapenem ( 4 ) .
b. pseudomallei is a soil saprophyte and can be recovered readily from water and wet soils in rice paddy fields .
for example , in thailand the organism can be cultured readily from more than 50% of rice paddies ( 5 ) .
it presents as a febrile illness , ranging from an acute fulminant sepsis to a chronic debilitating localized infection .
the lung is the most commonly affected organ , either presenting with cough and fever resulting from a primary lung abscess or pneumonia .
seeding and abscess formation can arise in any organ , and the liver , spleen , skeletal muscle and prostate are common sites .
localized pulmonary melioidosis often can not be differentiated from tuberculosis on clinical and chest radiography findings .
first , some melioidosis cases have rapid clinical and roentgenographic progression within a few days .
second , melioidosis usually responds to treatment well and has apparent roentgenographic improvement within 1 - 2 weeks .
third , parapneumonic effusion develops in 5 - 15% of cases , but the amount is not large and associated pulmonary infiltration is always present .
in contrast , tuberculosis pleurisy in which a large amount of pleural fluid is present without underlying pulmonary infiltration is common .
diagnosis of melioidosis is made by isolation of b. pseudomallei from any site ; for example blood , sputum , abscess fluid and throat swab .
since splenic abscess is much less common in other diseases , its presence is more likely to suggest melioidosis .
the antibiotic of choice is ceftazidime ( 40 mg / kg intravenous injection every 8 hr ) , while other 3rd generation cephalosporin is less effective ( 9 ) .
four - drug combination is usually recommended as oral antibiotics , and those are chloramphenicol ( 40 mg / kg per day in four divided doses ) , doxycycline ( 4 mg / kg per day in two divided doses ) , trimethoprim - sulfamethoxazole ( 10 mg and 50 mg / kg per day , respectively , in two divided doses ) .
high dose ceftazidime followed by long term oral antibiotics is considered to be most effective treatment .
the distribution and frequency of melioidosis is probably greatly underestimated ( 10 ) . in tuberculosis endemic areas ,
it is important to understand melioidosis and differentiate this disease from tuberculosis because the treatment of the two diseases is completely different .

Answer:
melioidosis is an infection of the gram - negative bacterium burkholderia pseudomallei .
 while it is known as an important cause of sepsis or chronic abscess - forming disease in southeast asia and northern australia , no case has yet been reported in korea .
 a 50-yr - old man visited our hospital for intermittent fever associated with dry cough and sputum .
 roentgenographic examination showed migrating pulmonary infiltration .
 symptoms and chest radiograph and computed tomography ( ct ) image findings did not improve despite use of fluoroquinolone antibiotics .
 gram - negative bacteria were isolated on bronchoscopic washing culture and were identified as b. pseudomallei on dna sequencing of 16s ribosomal rna with 100% homology .
 treatment for melioidosis was commenced with high dose ceftazidime , and the patient 's fever , cough , and sputum were improved and the lesion on chest radiograph and ct almost disappeared .


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:
Copper-Catalyzed Alkylation of Aliphatic Amines Induced by Visible Light

Paper sections:

Because amines are a privileged functional group in bioactive molecules,1 the development of more versatile methods for their synthesis is an important objective.2 Whereas the alkylation of an amine by an alkyl halide via an SN2 pathway is a classic transformation, at the same time the process represents an ongoing challenge in synthesis.3 Thus, rather than the desired C–N bond formation, undesired pathways such as E2 reactions and over-alkylation often intervene. Furthermore, because SN2 reactions are sensitive to steric effects, unactivated secondary and tertiary alkyl halides oftentimes do not serve as useful electrophilic partners. Due in part to these limitations, an array of methods other than the substitution reaction of an amine with an alkyl halide have been developed in order to selectively and efficiently introduce an alkyl group to an amine.2

Whereas transition-metal catalysis has been pursued very extensively to address the challenge of effecting substitution reactions of aryl halides by nitrogen nucleophiles,4 until recently there were essentially no systematic investigations of corresponding metal-catalyzed substitution reactions of alkyl halides.5 During the past few years, this deficiency has begun to be addressed, including through our work on photoinduced, copper-catalyzed processes (carbazoles, carboxamides, and indoles as nucleophiles)6,7 and a study by Hartwig on palladium-catalyzed reactions (benzophenone imines as nucleophiles).8

Nevertheless, to date a general method for transition-metal-catalyzed substitution of an alkyl halide by an aliphatic amine, which can be regarded as the prototypical nitrogen nucleophile, has not been described. In this study, we report a photoinduced, copper-catalyzed process that achieves the selective mono-alkylation of an array of aliphatic amines with unactivated secondary alkyl halides under mild conditions (−10 °C; eq 1).

In earlier work, we have described a variety of coupling reactions of nucleophiles with organic (aryl, alkenyl, alkynyl, and alkyl) electrophiles that are induced by light and catalyzed by copper;6,9 an outline of one of the possible pathways for such processes is provided in Figure 1.10,11 To date, all of our reported couplings have employed nucleophiles wherein the nucleophilic site is part of a π system (N: carbazole, indole, and imidazole; S: aryl thiol; O: phenol; C: cyanide). On the other hand, our initial efforts to utilize nucleophiles that lack this feature were unsuccessful. For example, under conditions in which carbazole6a and cyclohexanecarboxamide6b undergo alkylation by an unactivated secondary halide in good yield, the corresponding alkylation of a primary aliphatic amine does not proceed (eq 2 and eq 3). Having the nucleophilic site incorporated within a π system might be important for any of a variety of reasons, including determining the viability of the initial photoexcitation (A → B in Figure 1)12 and/or of electron transfer from that excited state to the electrophile to generate a copper(II) complex (B → C).13

While examining the functional-group compatibility of a method that we had developed for photoinduced, copper-catalyzed arylations of phenols,9d we discovered that the presence of 1.0 equiv of an aliphatic amine additive unexpectedly leads to predominant N-arylation of the aliphatic amine, rather than O-arylation of the phenol (eq 4; in the absence of n-BuNH2: 80% yield of PhO–Ar).

One of the possible pathways by which phenol might enable the photoinduced, copper-catalyzed cross-coupling of an aliphatic amine is depicted in Figure 2. Thus, photoexcitation of a copper(I)–phenoxide complex (E → F) and then electron transfer to an electrophile (R–X) affords a copper(II)–phenoxide (G) and an organic radical (R•). Ligand exchange of the copper(II)–phenoxide with an amine (NH2R) leads to a copper(II)–amido (H)14 that engages in C–N bond formation with the organic radical to furnish the cross-coupling product (R–NHR) and a copper(I) complex (I).15 Ligand substitution then regenerates a copper(I)–phenoxide complex (E).

Given the paucity of systematic studies of metal-catalyzed substitution reactions of unactivated alkyl halides by aliphatic amines, we attempted to exploit our initial observation (eq 4) to devise a photoinduced, copper-catalyzed process that would address this deficiency. Indeed, building on this lead result, we have been able to develop a method that achieves the selective mono-alkylation of a primary aliphatic amine by an unactivated secondary alkyl halide under mild conditions (−10 °C) in good yield (92%).

Control reactions establish that essentially none of the coupling product is generated in the absence of CuI, rac-BINOL, light, or BTPP (Table 1, entries 2–6). A variety of copper(I) and copper(II) sources furnish a good yield of the desired secondary amine, whereas copper nanopowder does not (entries 7–11). N-Alkylation proceeds less efficiently in the presence of less BINOL (entries 12 and 13) and when BINOL is replaced with related ligands (entries 14 and 15). The use of other Brønsted bases (entries 16 and 17), a smaller excess of electrophile or BTPP (entries 18 and 19), or a lower catalyst loading (entry 20; no further reaction after 24 h) also leads to significantly lower yields. Under our standard conditions, other cyclohexyl electrophiles (bromide, chloride, and tosylate) do not serve as suitable coupling partners (entries 21–23). Cross-coupling does occur in the presence of a small amount of air or water, although less effectively (entries 24 and 25).

An array of unactivated secondary alkyl iodides, both cyclic and acyclic, serve as suitable electrophiles in this photoinduced, copper-catalyzed mono-alkylation of aliphatic amines (Table 2).16 The efficiency of the coupling is sensitive to steric effects, with more hindered electrophiles furnishing more modest yields (entries 6 and 7). Saturated oxygen and sulfur heterocycles are compatible with the reaction conditions (entries 8 and 9), and C–N bond formation can be achieved with excellent diastereoselectivity (entries 11 and 12; >20:1). In a gram-scale reaction, the alkylation illustrated in entry 1 proceeds in good yield with 10% CuI/20% BINOL (1.32 g, 81%).

Although many unactivated primary alkyl halides can serve as useful electrophiles in SN2 reactions, neopentyl halides typically are rather poor substrates.17 Nevertheless, the combination of a CuI/BINOL catalyst and blue-LED irradiation enables the alkylation of an aliphatic amine by neopentyl iodide in good yield at −10 °C (eq 5). In contrast, a simple SN2 reaction proceeds very slowly even at 100 °C, and the addition of CuI/BINOL is not beneficial (eq 5).

We have also examined the scope of this photoinduced, copper-catalyzed N-alkylation with respect to the nucleophile (Table 3). Thus, the efficiency of C–N bond formation does not appear to be highly sensitive to the steric demand of the aliphatic amine (entries 1 and 2). The method is compatible with a variety of functional groups, including an ether, an acetal, an aryl chloride, an aryl bromide, a furan, and a thiophene (entries 3–10).

Through an additive study, we have further assessed the functional-group compatibility of this method. For the coupling illustrated in entry 1 of Table 2, the addition of 1.0 equiv of an alcohol (5-nonanol), an alkyne (5-decyne), an ester (methyl octanoate), a ketone (2-nonanone), a cis olefin (cis-5-decene), and a trans olefin (trans-5-decene) has little impact on N-alkylation (>75% yield), and the additive is virtually unaffected (>90% recovery). On the other hand, the addition of a nitroalkane (nitrocyclopentane) or an aldehyde (cyclohexanecarboxaldehyde) impede coupling (<5% and 51% yield, respectively).

If desired, N-protection of the secondary amine can be effected in situ in good yield. For example, upon completion of the alkylation illustrated in entry 1 of Table 2, direct trifluoroacetylation followed by purification provides the TFA-protected amine in 86% yield. Similarly, a 73% yield of the purified carbamate can be obtained after in situ protection with Boc2O.

Although reaction development is the primary focus of this investigation, we have also carried out preliminary mechanistic studies; as mentioned earlier, one of the possible pathways for this process is outlined in Figure 2. With regard to the identity of the primary photoreductant, ESI–MS of a reaction mixture after partial conversion reveals the presence of copper(I)–binaphtholate complex E'; alternatively, deprotonated BINOL itself could also fill this role.18,19 The illustrated mechanism includes d9 copper(II) complexes as intermediates, and we have indeed detected such species via EPR spectroscopy by sampling a catalyzed coupling at partial conversion; at least two copper(II) species are evident (hyperfine coupling to copper), which together account for ~60% of the total copper that is present in the reaction mixture.

According to the pathway depicted in Figure 2, C–N bond formation occurs through out-of-cage coupling of an organic radical (R•) with a copper(II)–amido complex.15 Consistent with this hypothesis, the addition of TEMPO (1.5 equiv) to a reaction mixture leads to the formation of a TEMPO adduct (eq 6).

In summary, we have determined that the combination of visible light and a copper catalyst provides the first general method for the transition-metal-catalyzed alkylation of aliphatic amines by unactivated secondary alkyl halides. This process addresses some of the deficiencies of the classic SN2 approach, including its need for reactive electrophiles and its propensity for over-alkylation. With respect to our efforts to expand photoinduced, copper-catalyzed coupling reactions, this represents our first success with nucleophiles wherein the nucleophilic site is not part of a π system. With our optimized method, C–N bond formation proceeds without significant over-alkylation (<1%) under mild conditions (−10 °C) in the presence of a variety of functional groups, upon irradiation by blue-LED lamps of a catalyst derived from commercially available components. A preliminary mechanistic study is consistent with the formation of an alkyl radical that engages in out-of-cage C–N bond formation. Our future work will focus on expanding photoinduced, copper-catalyzed couplings to other classes of non-conjugated nucleophiles, as well as on elucidating the mechanisms of these processes.

Answer: Although the alkylation of an amine by an alkyl halide serves as a \xe2\x80\x9ctextbook example\xe2\x80\x9d of a nucleophilic substitution reaction, the selective mono-alkylation of aliphatic amines by unactivated, hindered halides persists as a largely unsolved challenge in organic synthesis. We report herein that primary aliphatic amines can be cleanly mono-alkylated by unactivated secondary alkyl iodides in the presence of visible light and a copper catalyst. The method operates under mild conditions (\xe2\x88\x9210 \xc2\xb0C), displays good functional-group compatibility, and employs commercially available catalyst components. A trapping experiment with TEMPO is consistent with C\xe2\x80\x93N bond formation via an alkyl radical in an out-of-cage process.


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:
since 1965 when brnemark et al.1 introduced and established the osseointegration concept , dental implant has achieved enormous development and progress . defined as direct connection between bone and implant surface ,
osseointegration is formed by the process of bone formation between bone and implant surface . because the success and failure of implant is determined by osseointegration , it is a precondition for prosthetic repair through implant .
the primary stability is obtained by mechanical fixation of the implant with bone , and this is one of the basic conditions for osseointegration.2 primary stability is related with implant surface area , geometry , length , contact area between implant and bone .
other factors include ratio of spongy bone vs. cortical bone , and implant technique.3 the secondary stability is generated secondarily by bone formation and bone remodeling in the process of osseointegration due to biological fixation in the interface between bone and implant.4 therefore , we can evaluate the degree of osseointegration through the measurement of changes in the implant stability.5 meredith et al .
reported on the use of the resonance frequency analyzer to evaluate the stability of implant , and demonstrated the ability of the device to evaluate the changes in stiffness of the interface in the early in vitro experiment.6,7 recently , histomorphologic studies suggested that the resonance frequency value has a high correlation with the level of contact between bone and implant.8 - 11 this discovery supports the use of resonance frequency analysis to evaluate the changes in the process of osseointegration and bone healing after placement of implant .
the resonance frequency analyzer can measure clinically and noninvasively the stability of implant and estimate the degree of osseointegration . in this study , we used a recently developed magnetic resonance frequency analyzer to measure the stability of implant . for measurement unit , implant stability quotient ( isq ) is used which is recorded as a number between 1 and 100 with 100 representing the highest stability.12 this study intends to measure and analyze the changes in implant stability without load during an early healing period of six months after placement of three different types of implants by one stage implant . in this way , this study will provide useful information for prosthetic treatment planning through immediate and early loading after placement of implant as well as the evaluation of long - term prognosis for it .
a total of 28 patients ( 25 males and 3 females , mean age : 58.6  9.23 ) were selected among the patients who visited between march and september 2004 with the main purpose of implant placement .
inclusion criteria were as follows
 adults aged 18 or olderpatients who understand and agree to this studyadequate oral hygiene ( 1 or lower mean modified sulcus bleeding index , 1 or lower mean modified plaque index)sufficient bone volume to place the planned implantone or more edentulous mandible parts which are six months or longer after dental extraction ( however , adjacent teeth must be healthy and properly repaired)fertile women who received pregnancy test no later than one week before surgery and have been confirmed to be negative
  adults aged 18 or older patients who understand and agree to this study adequate oral hygiene ( 1 or lower mean modified sulcus bleeding index , 1 or lower mean modified plaque index ) sufficient bone volume to place the planned implant one or more edentulous mandible parts which are six months or longer after dental extraction ( however , adjacent teeth must be healthy and properly repaired ) fertile women who received pregnancy test no later than one week before surgery and have been confirmed to be negative exclusion criteria were as follows
 smokers over 10 cigarettes / daya history of alcoholism or drug addition during the past 5 yearssevere teeth clenching or bruxismrisk of subacute bacterial endocarditisuncontrolled hypertension or diabetespatients with malignant tumor
  smokers over 10 cigarettes / day a history of alcoholism or drug addition during the past 5 years severe teeth clenching or bruxism risk of subacute bacterial endocarditis uncontrolled hypertension or diabetes patients with malignant tumor the three types of 45 implants were divided into 3 groups including osseospeed ( group a , astra tech , sweden ) , camlog ( group c , biotechnologies ag , switzerland ) , and replace ( group r , nobelbiocare , sweden ) in this study .
one assigned operator placed implants by one stage technique in accordance with the surgical protocol suggested by the manufacturer .
bone quality classification followed the criteria proposed by lekholm & zarb , and type 1 , 2 , 3 or 4 was determined on the basis of the sense of resistance during bone drilling .
after placement , isq was measured , a healing abutment was connected , and sutured . for magnetic resonance frequency analyzer , this study used osstell ( gteborg , sweden ) .
a special smart peg was connected to the implant body at 4 - 5 n / cm torque , and measurements were made at 2 - 3 mm away so that the probe tip of the analyzer would point to the small magnet above the smart peg ( fig .
if the probe measures two values simultaneously and the difference between these two values is 3 isq or higher , the values must be indicated simultaneously .
isq was measured immediately after placement , after 3 weeks , 6 weeks , 8 weeks , 10 weeks , 12 weeks and 24 weeks .
in addition , we examined the existence of discomfort at the time of healing abutment removal and the smart peg connection .
the data were analyzed by implant type , bone type , healing time , and location .
the data were recorded as implant isq over time , and were analyzed by implant type , bone type , healing time , and location . for the analysis by bone type , interaction between time and type with two - factor effect mixed model was used . here , the comparison between the time points used contrast comparison in the two - factor effect mixed model . for comparison of bone types at different time points , the multi - comparisons of anova and tukey were used ( p = .05 ) .
the analysis by mandible location used the time effect with two - factor effect mixed model and the location effect with two - factor effect mixed model .
the data were recorded as implant isq over time , and were analyzed by implant type , bone type , healing time , and location . for the analysis by bone type , interaction between time and type with two - factor effect mixed model was used . here , the comparison between the time points used contrast comparison in the two - factor effect mixed model . for comparison of bone types at different time points , the multi - comparisons of anova and tukey were used ( p = .05 ) .
the analysis by mandible location used the time effect with two - factor effect mixed model and the location effect with two - factor effect mixed model .
the surgeries produced no complications in all the patients and the isq numbers were obtained without causing inconvenience to the patients .
bone types 2 and 3 were grouped together , because recent papers demonstrated that it was difficult to reliably differentiate the drilling resistance in intermediate bone .
the two - factor mixed model anova was used to determine the existence of interaction between bone type and time in groups a , c and r ( p = .0022 , p = .017 , p = .0018 ) .
in other words , the change patterns of isq by time were different by bone type ( fig . 2 - 4 ) .
furthermore , the isq values of bone types were compared through multi - comparisons of anova and tukey . in the groups a , c and r , the measurements immediately after placement showed statistical differences in bone types 1 , bone types 2 & 3 , and bone type 4 ( p < .05 ) .
the mean isq of implants immediately after placement was over 70 in the bone type 1 , between 65 and 70 in the bone type 2 & 3 , and between 48 and 50 in the bone type 4 ( fig .
a , between week 0 and 6 , isq increased 4.78% in bone type 1 , 8.73% in bone type 2 & 3 , and 56.47% in bone type 4 .
the bone type 1 did not show significant change ( p = .052 ) , while bone types 2 , 3 and 4 showed significant changes ( p = .044 , p = .0326 ) . in group c , between week 0 and 6
, isq increased 0.52% in bone type 1 , 6.38% in bone type 2 & 3 , and 49.11% in bone type 4 .
the bone type 1 , 2 & 3 showed slow increase between six weeks and six months .
the bone types 1 , 2 & 3 showed significant changes ( p = .0356 , p < .0001 ) , but type 4 did not show significant changes ( p = .3715 ) . in group r , between week 0 and 6 , isq increased 7.37% in bone type 1 , 11.87% in bone type 2 & 3 , and 47.81% in bone type 4 .
the bone types 1 did not show significant changes ( p = .6411 ) , but type 4 showed significant changes ( p = .0005 , p = .0462 ) . according to the two - factor mixed model , groups a and c did not show significant differences in stability changes by healing time according to the anatomical location between maxilla and mandible .
in group r , the change of stability by healing time showed significant difference between maxilla and mandible ( p = .0238 ) .
however , the comparison between maxilla and mandible by the two - sample t - test did not find significant difference among 3 groups ( fig . 9 - 12 ) .
according to the two - factor mixed model , groups a and c did not show significant differences in stability changes by healing time according to the anatomical location between maxilla and mandible .
in group r , the change of stability by healing time showed significant difference between maxilla and mandible ( p = .0238 ) .
however , the comparison between maxilla and mandible by the two - sample t - test did not find significant difference among 3 groups ( fig .
the need for clinical diagnosis tools with high accuracy to recognize the stability of implant and early healing changes is increasing along with the immediate and early load concept .
the resonance frequency device invented by meredith4 has been used for clinical reference of the stability of implant placed in various bone types .
there are several reports about implant stability influenced by healing time.8,10,11 this study also found through an analysis with the interaction between time and type with two - factor effect mixed model that the interaction of time and bone quality had significant influence on the isq values .
the result of implant stability immediately after placement was bone type 4 < type 2 & 3 < type 1 in all implant groups . the implant stability measured immediately after placement is primary stability resulting from the mechanical press - fitting of implant with a greater diameter than the hole in the bone , and is influenced by the stiffness of adjacent bones.3,4 in other words , the higher the stiffness of adjacent bones , the higher the primary stability .
therefore , the stability immediately after placement of bone type i that has a high volume of cortical bone and a small volume of spongy bone is higher . on the other hand , bone types 2 & 3 and type 4 have a less volume of cortical bone and a more volume of spongy bone , which decreases the stiffness of bones and lowers the stability immediately after placement of implant.13 the three bone types experienced great changes in stability between week 0 and week 6 . in an experiment with rabbits
, robert14 reasoned that human bone quality would undergo significant changes between week 0 and week 6 by the formation of woven bone and the deposition of lamellar bone .
furthermore , the size of changes between week 0 and week 6 varied by bone type . the ascending order of the size of changes was bone type 1 > type 2 & 3 < type 4 .
however , the cancellous healing showed was fast because in addition to trabecular remodeling , the bone is close to bone marrow that has a rich vascular system and mesenchymal progenitor cells which can be differentiated into osteoblasts .
therefore , it seems that the closer to bone type 4 , the higher implant stability by the fast regeneration of woven bones.15 the slow increase of implant stability between week 6 and six months ( plateau effect ) has been reported by cochran et al.16 this phenomenon has a correlation with the strengthened bone formation concept around the implant .
robert14 believed that the later stage of the deposition of the lamellar bone into the grids in human woven bones and the interface remodeling begins at week 6 and continues until week 18 , and the deposition of lamellar bone gives sufficient strength to withstand load .
the changes of stability by healing time according to the mandible location were not significantly different between the upper and lower mandible groups .
there are many existing studies that found that the lower mandible shows higher stability.17,18 the result of this study was different , which seems to be due to the small number of samples ( there were five cases of bone type 4 in the 13 maxilla cases )
. the implant length may be an important factor that influences isq value.19 however , this study could not analyze the differences due to the insufficient number of samples by length .
within the limitation of this study , we found that the time / bone quality interaction had significant influence on isq values through an analysis among implant groups a , c , and r. in other words , in all the implant groups a , c and r , the change patterns of isq over time differed by bone type .
implant stability increased greatly between week 0 and week 6 ( order of increase : type 1 < type 2 & 3 < type 4 ) , and showed slow increase between week six and six months ( plateau effect ) .
however , no significant difference in stability changes by healing time according to locations was found in all the implant groups .
more studies are required about the mechanotransduction effect during the early implant loading in various implant systems , and the effect of this on the magnetic resonance frequency analyzer during the early healing period .

Answer:
purposeto determine the change in stability of single - stage , three different design of implant systems in humans utilizing resonance frequency analysis for early healing period ( 24 weeks ) , without loading.material and methodstwenty - five patients were included into this study . a total of 45 implants , three different design of implant systems ( group a , c , r ) were placed in the posterior maxilla or mandible .
 the specific transducer for each implant system was used .
 isq ( implant stability quotient ) reading were obtained for each implant at the time of surgery , 3 , 6 , 8 , 10 , 12 , 24 weeks postoperatively .
 data were analyzed for different implant type , bone type , healing time , anatomical locations.resultsfor each implant system , a two - factor mixed - model anova demonstrated that a significant effect on isq values ( group a = 0.0022 , c = 0.017 , r = 0.0018 ) .
 for each implant system , in a two - factor mixed model anova , and two - sample t - test , the main effect of jaw position ( p > .005 ) on isq values were not significant.conclusionsall the implant groups a , c and r , the change patterns of isq over time differed by bone type .
 implant stability increased greatly between week 0 and week six and showed slow increase between week six and six months ( plateau effect ) .


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:
a 50-year - old , 168 cm , 68 kg man without significant past medical history , was admitted to emergency room following a slip - down accident . on admission ,
neurologic examination confirmed a glasgow coma scale ( gcs ) of 15 , and the pupils were symmetrical and reactive . emergent skull x - ray series , facial computerized tomography ( ct ) and forearm x - ray revealed fracture of the frontal sinus , skull base , and right distal radius fracture . computed tomography ( ct ) of the brain showed multiple small subdural pneumocephalus ( fig .
emergent lumbar drainage was performed to manage csf rhinorrhea and empirical prophylactic antibiotic treatment was given .
the patient 's post - traumatic symptoms improved gradually in the surgical intensive care unit . at post - trauma 8 days , following trauma , the patient underwent orthopedic surgery for distal radius fracture under general anesthesia .
anesthesia was induced with intravenous thiopental 300 mg and 0.5 g / kg / min remifentanil infusion .
endotracheal intubation was performed after administering 50 mg rocuronium injection with 100% oxygen mask ventilation for 3 min without any difficulties .
anesthesia was maintained with oxygen ( 2 l / min)-air ( 2 l / min)-sevoflurane ( 1 - 1.5 vol% ) , continuous infusion of 0.125 - 0.5 g / kg / min remifentanil and 10 - 15 mg / h of rocuronium .
tidal volume and respiratory rate were adjusted to maintain end - tidal carbon dioxide tension at 30 - 35 mmhg .
following surgery , the patient was extubated in the operation room after gaining consciousness and spontaneous ventilation .
he was then transferred to the post - anesthesia care unit where he recovered fully without complications .
ten hours later , the patient complained of severe , increasing , headache and exhibited abrupt deterioration in mental state . in view of his clinical aggravation ,
neurologic examination demonstrated a gcs 11 and emergent brain ct showed large quantity of both frontal and right occipital pneumocephalus ( fig .
high flow ( 8 l / min ) oxygen via a partial non - rebreathing mask was administered in conjunction with supportive care for 2 days .
no infectious neuromeningeal complications occurred during hospitalization , and the patient was discharged at post - trauma day 32 .
it develops mostly from acute and subacute complications of head trauma , or as late complications during the recovery phase of head injury .
subarachnoid or subdural air accumulation is the most common form of pneumocephalus , and intracerebral pneumocephalus can occur albeit rarely .
intracranial air is accumulated as a result of communications between paranasal sinuses , mastoid air cells and the cranial fossa , associated with dural tear .
the other mechanism of air penetration is a ball - valve effect like sudden increase of nasopharyngeal pressure , such as during coughing and sneezing , forcing air into the cranial cavity which subsequently remained trapped .
injuries of the paranasal sinuses , which are closely contiguous to bony structures , the dura mater and the brain frequently accompany head traumas .
75 - 90% of pneumocephalus are posttraumatic and the incidence of pneumocephalus secondary to head injury range from 0.5% to 13.2% .
other causes include facial tumors that eroded through the skull , gas - forming bacterial infections , paranasal sinusitis and neurosurgical and facial procedures .
pneumocephalus is mostly asymptomatic and self - limiting , because gas is not irritating to the surrounding brain .
intracerebral pneumocephalus have usually become sizable when it is confirmed by simple skull x - ray or brain ct .
tension pneumocephalus caused by large amounts air can evoke sudden or insidious mass effects capable of shifting midline structures , causing major neurological deficits .
representable iatrogenic pneumocephalus are related to positive pressure ventilation in the upper airway , such as nasal continuous positive airway pressure , face mask ventilation and even nasal oxygen cannulae .
it is well known that positive airway pressure can result in pneumothorax , pneumomediastinum and subcutaneous emphysema .
it is difficult to predict which head trauma patients who do not initially develop pneumocephalus will experience iatrogenic pnemocephalus during positive pressure oxygen therapies .
the mechanism of air delivered via manually operated mask tracking into the cranial cavities appears to be identical to that in traumatic pneumocephalus . because csf leakage is usually a result of osteomeningeal fistula , csf rhinorrhea is commonly associated with pneumocephaus , as demonstrated in this patient .
his initial primary pneumocephalus accompanied by rhinorrhea was completely subsided following lumbar drainage and general supportive care , but post - anesthetic secondary pneumocephalus probably developed during anesthesia induction using ppmv .
therefore , avoidance of excessive positive pressure during mask ventilation is recommended to prevent pneumocephalus . because most mild pneumocephalus usually recover spontaneously within one week
, its management includes strict bed rest in the semi - fowler position , analgesia and antibiotics .
prevention of intracranial pressure elevation by avoiding the valsalva maneuvers , coughing , sneezing , nose blowing , and excessive physical activities is important to avoid pneumocephalus aggravation . because severe headache , personality change , disorientation , and mass effect associated with midline structure shift are the symptoms and signs of tension pneumocephalus , emergent surgical procedures , such as subdural drainage to decrease intracranial pressure , should be considered immediately after confirming the diagnosis with x - rays or brain ct .
when the patient experienced severe headache and became rapidly lethargic , analgesia , antibiotic and high flow , high fio2 oxygen via a partial non - rebreathing reservoired mask were administered under a presumed diagnosis of impending tension pneumocephalus .
the management principle is as follows : high fio2 oxygen reduces blood and brain tissue nitrogen concentration , thereby increases the nitrogen concentration gradient that promotes pneumocephalus gas absorption . to avoid tension pneumocephalus in head trauma patients , lma or tracheostomy tube intubation
in addition , anesthesiologists should be aware of potential complications caused by low intracranial pressure during anesthesia in head trauma patients . in theory ,
hypotension , hypovolemia , excessive hypercapnia and head - up position during anesthesia can reduce intracranial pressure that facilitates air influx through open osteomeningeal fistulae secondary to head trauma , causing pneumocephalus . in conclusion
, anesthesiologists and surgeons should be aware of pneumocephalus as a potential complication during positive pressure mask ventilation for facial trauma , secondary to air invasion through osteomeningeal fistulae .
close monitoring for pneumocephalus development should be mandatory following general anesthesia or during respiratory care with continuous positive airway pressure in head trauma patients .

Answer:
pneumocephalus is a condition which usually results from head trauma .
 it has been known that iatrogenic pneumocephalus can occur as a complication of positive pressure mask ventilation during induction of anesthesia or ventilatory care for head trauma patients .
 we report a case of mask ventilation during anesthesia induction in a 50-year - old male patient with head trauma .
 initial pneumocephalus associated with cerebrospinal fluid leakage was diagnosed immediate following head injury involving facial sinuses .
 he was managed with emergent lumbar drainage and supportive care .
 pneumocephalus recurred following positive pressure mask ventilation ( ppmv ) during anesthesia induction for surgery on the right arm .
 recurred pneumocephalus was managed with high flow oxygen and supportive care .
 anesthesiologists should be aware of pneumocephalus as a potential complication of ppmv in head trauma patients , even after resolution of previous pneumocephalus .


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:
oculogyric crisis ( ogc ) , classified as eyeball dystonia , was first described in patients suffering from encephalitis lethargica.1 nowadays , this symptom is more frequently observed as a side effect of treatment with dopamine receptor - blocking drugs ( drbds).2 it manifests as spasmodic deviations of the eyeballs , mainly upward but also in other directions , lasting from a few minutes to several hours.3 it occurs during the first hours or days after the introduction of drbds .
tetrabenazine is mainly used in patients with hyperkinetic movement disorders , such as tics , chorea , tardive dyskinesia , and dystonia .
its mechanism of action involves the reversible inhibition of vesicular monoamine transporter type 2 , thus preventing the uptake of serotonin , norepinephrine , and dopamine by presynaptic neurons .
jankovic and beach found that acute dystonic reactions occurred in nine ( 2.3% ) patients and two ( 0.5% ) additional patients had acute oculogyric crises attributed to tetrabenazine.4 we present a case report of a patient suffering from gilles de la tourette syndrome ( gts ) who developed ogc during treatment with tetrabenazine .
an 18-year - old male patient with gts began to experience head shaking followed by coughing at the age of 11 years . during the next several years , he developed numerous motor and vocal tics ( nose twitching , jaw tightening , biting his cheek , clenching his fingers into a fist , throwing his head back , rolling his eyes to one side , tensing his buttocks , twisting movements of the hands and feet , resulting in abnormal posture , bending his body to one side giving the sustained position of his body , and exhaling loudly ) .
his tic - reducing therapy included haloperidol , perphenazine , quetiapine , sulpiride , and clonazepam without success , and thus he was referred to piotr janik ( the first author of this paper ) at age 17 years .
he had a positive family history of tics ( his brother ) and obsessive  compulsive behaviors on his paternal side ( his brother , uncle , and grandfather ) .
we found his tics to be associated with lower educational achievements and negative impacts on his family and social life . during the next year
, he was put one by one on risperidone , aripiprazole , and topiramate without success . during another visit at age 18 years , he presented with jaw snaps , head jerks , quickly flexing and extending arms , popping knuckles , tensing of the abdomen , nose picking , rubbing one foot against the other , bending up of the nose using a finger combined with frowning , and rapid jerking of the body .
his vocal tics included screeching ; throat clearing ; and sniffing , humming , and squeaking noises .
he also displayed self - injurious behavior  he had to use a mouthguard to protect his teeth from damage caused by clenching his jaw . to assess the severity of his tics
comorbid conditions included depression at age 16 treated with escitalopram and paroxetine . at the time of examination ,
no comorbid mental disorders were diagnosed . due to the lack of effectiveness of previous treatments , tetrabenazine in gradually increasing dose
was introduced . however , after 8 days of therapy , at a dose of 62.5 mg of tetrabenazine daily , the patient developed involuntary movements of the eyeballs characterized by spasmodic deviations of the eyes upward and to one side that lasted for around an hour , with a frequency of a few times per day .
in addition to ogc , the patient experienced severe , brief episodes of throwing back his head and twisting movements of his hands and feet that resembled retrocollis and limb dystonia , respectively .
excessive salivation , slurred speech , and food dropping from the mouth were also reported by the patient .
all symptoms resolved a week after tapering the tetrabenazine dose to 37.5 mg daily . at this dose , tics remained poorly controlled and tetrabenazine was totally stopped . despite further treatment with other drbds , among them
permission from an ethics committee was not necessary in the presented case , as tetrabenazine is a widely approved treatment for gts .
the drug has previously been used as a last - resort treatment for patients with severe tics ; therefore , no novel medical treatments were performed on our patient .
acute ogc seems to be a rare complication in the treatment of gts patients because , nowadays , mostly second - generation drbds are used to alleviate tics .
there are only a few case reports in the literature of this complication arising with the use of second - generation drbds .
two papers report the development of acute ogc shortly after administration of aripiprazole and one paper reports similar symptoms after treatment with risperidone.57 we also observed two young adults with gts who developed ogc after treatment with risperidone 4 mg daily and sulpiride 300 mg daily .
the only two reports of tetrabenazine - induced acute dystonia were those of jankovic and beach4 and burke et al.8 the four patients described by burke et al varied in terms of drug dose ( from 25 to 300 mg ) , underlying condition ( gts in one case , dystonia in three others ) , patients age ( from 20 to 30 years ) , and sex ( two females , two males).8 unfortunately , the characteristics of patients who developed acute dystonia with tetrabenazine treatment were not included in the second paper.4 both authors reported that acute dystonia was dose - related and improved spontaneously when the dosage was reduced , as was the case with our patient . in contrast to burke s patient with gts who developed ogc and retrocollis while being treated with tetrabenazine 300 mg , we observed such a complication on a low dose of tetrabenazine .
the fact that tetrabenazine - induced ogc is rarely seen and may occur with different doses suggests that this complication will develop in vulnerable young adults in particular .
in addition , our patient had some dystonic tics as part of his tic repertoire since early adolescence .
interestingly , these tics as well as some facial and cervical motor tics worsened during treatment with tetrabenazine .
the severity of all these tics abated after tetrabenazine treatment was reduced and then stopped . since dystonic tics often resemble acute dystonic reaction , it is not always easy to differentiate these movement disorders . compared to dystonia , tics are shorter lasting movements , typically not painful , are preceded by premonitory sensations , and do not cause persistent postures .
based on these clues , we classified these movements as worsened tics rather than drug - induced acute dystonic reaction .
it is believed that to cause acute dystonic reactions , the drug must be able to block dopamine receptors .
however , tetrabenazine , a monoamine - depleting medication , and alpha - methyl - para - tyrosine , a catecholamine - depleting agent , may induce acute dystonic reactions.8,9 our case report is not in line with the hypothesis that tetrabenazine causes this side effect by dopamine blockade rather than monoamine depletion because it is also able to block dopamine receptors in rat brain.10,11 our patient had been exposed to numerous drbds before and after he developed ogc , which never caused symptoms of acute dystonia .
the resolution of ogc after a reduction in the dosage of tetrabenazine , which probably resulted in enhanced dopaminergic transmission , is compatible with the theory that the decrease of dopamine transmission induced by tetrabenazine could also be involved in the pathogenesis of acute dystonia .

Answer:
tetrabenazine is used in the treatment of chorea , tardive dyskinesia , tics , and dystonia .
 it rarely causes acute eyeball dystonia and the description of this complication in gilles de la tourette syndrome is limited .
 we provide a description of an acute oculogyric crisis caused by tetrabenazine in a patient with severe tics .
 the patient had never developed acute dystonic reactions , although he was previously exposed to numerous dopamine receptor - blocking agents .
 after 8 days of therapy with tetrabenazine at a dose of 62.5 mg daily , the patient developed involuntary movement of the eyeballs .
 withdrawal of tetrabenazine caused resolution of all symptoms after a week .
 the purpose of this description is to draw attention to the potential of tetrabenazine to induce acute oculogyric crisis as well as the difficulty of differentiating drug - induced dystonia from dystonic tics in patients with gilles de la tourette syndrome .


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:
pursuing the goal of improved health literacy requires more alliances between health and education sectors to improve literacy levels in the population .
it is important for health educators to know about knowledge transfer to meet their needs in transferring their knowledge to public
. knowledge transfer , which means the synthesis , exchange and ethically application of knowledge within a complex system of relationship among researchers and users , has become one of the recent priorities in research centers . the word
the method of knowledge transfer , apart from its characteristics , requires active interactions between researchers and users .
caplan proposes the two- communities theory indicating a gap between researchers and policymakers , whereas these days another gap has been formed between researchers and other users .
in addition to illiteracy in developing countries that hampers effective health education , there are multitudes of non - medical specialists who do not have enough information about daily health affairs , and this lack is more remarkable in countries that welcome immigrants .
immigrants often have significant language and health literacy difficulties , which are further exacerbated by cultural barriers .
alongside with sophisticated methods like computer and internet , using simple methods help us bring to achieve our health goals[68 ] . also , the lack of health literacy needs more attention when it is manifested in caregivers .
it is believed that some of the undesirable health outcomes in children are because of inadequate health knowledge among caregivers . in the usa ,
therefore researchers have considered different methods to come up with this deficiency by having children to cooperate in their health programs .
a research group in india endeavored to transfer knowledge on leprosy in cooperation with children and informed their parents through them .
jacob et al ( 1994 ) started conducting a similar research that yields promising results .
rimal and flora ( 1998 ) express that parental dietary behavior is partially affected by children .
the findings from studies in this field have encouraged other experts to apply similar methods to conduct their research projects , allahverdipour and bashirian , onyango - ouma and mwangagain from the influence of children in order to teach different parts of their society[1316 ] . despite the researcher 's trends in using novel methods in this field ,
none of them have used childish poem as a medium for knowledge transferring . in this study
, we try to raise families health knowledge about infectious diseases by a method that uses children as health agents .
infectious diseases are still the leading cause of mortality in children less than 60 months in developing countries .
juvenile age is accompanied by learning childish poems , which can be sung contnuously at home and potentially become as part of both children 's and parents memories .
we decided to transfer health knowledge to families through altering this information to childish poems and teaching children at kindergartens . in this method
the outcome of transferring health knowledge through childish poems has been assessed in this study .
in this study , we use the method of interventional pre and post series to conduct our research .
the proposal of this non - invasive project was approved by the research committee of hamadan medical university in january 2009 .
it was also accepted by hamadan welfare organization , which is the responsible organization of kindergartens in hamadan .
our methodology is briefly explained as follows . at first , a sub specialist in pediatric infectious diseases provides seven short texts about health and common pediatric infectious diseases prevention .
then , a poet transfers these conceptions to childish poems for the first time ( appendix 1&2 ) . in the process of preparing an accurate questionnaire , at first 30 questions with three choices of
,  false  and  do not know  were made , but 24 items of those are confirmed as valid questions by two experts of health education and infectious diseases . to assess
the reliability of the questionnaire a pilot study on a 40 participant sample was performed and cronbach 's alpha of the questionnaire was determined as 83 percent .
in addition , we defined knowledge mark ( km ) as a parent mark in both the pre - test and/or post - tests . among 35 kindergartens in hamadan , we selected 7 kindergartens by simple random method .
the parents ( either father or mother , the one who is responsible to take her / his child ) of all five to six year old children of the selected kindergartens are asked to participate in the survey and a verbal consent is obtained from those who accepted .
we excluded the following children from our sample : those whose parents are physicians , nurses , health - care workers , and those children whose parents work at the kindergarten ( exclusion criteria ) .
we asked the parents of the sample survey to participate in a pretest by answering to a questionnaire when they are in the kindergartens .
also , they were asked to come to the kindergartens personally one more time when it is required ( to answer to the post test ) . then , we asked our kindergarten tutors to teach children seven musical poems about hydatid cyst , antibiotic misuse , botulinum toxin in home - canned foods , dysentery , the importance of sixth tooth , brucellosis and tetanus . in this step , children were not allowed to take home these texts , but they were asked to sing the poems at home and want their parents to re - write the poems on a paper and give them the papers to take to the kindergarten .
the teaching stage took between three to four months . during the next stage , parents took a post - test survey with the same 24 questions .
parents of 115 kids participated in the pre - test and 103 of them completed the post - test .
statistical analysis is done on 103 who completed both tests by paired t - test .
the sample data consists of 103 parents who provided solutions to both the pre- and post - test question survey . of the participants 77 were female and 26 male . from the level of education point of view
, 19 were below high school diploma , 45 had high school diploma , 8 had associate degree , 27 had ba , 3 had ma , and 1 had phd .
the results of the survey show a significant difference between the correct answers in both pre - test and post - test stages ( fig .
1 ) . the frequency of correct answers to the tests
 table 1 shows the mean of the correct answers in the pre - test stage is 59.22 while the same figure for the post - test step is 81 ( p < 0.001 ) .
in addition , we define knowledge mark ( km ) as a parent mark in both the pre - test and/or post - test stages . the mean km shows a significant increase ( 5.01 ) from 13.62 in the pre - test to 18.63 in the post - test ( table 2 ) .

mean percent of correct answers to pre - test and post - test categories
  analyzed by paired t - test sd : standard deviation mean of knowledge mark in pre - test and post test analysed by paired t - test the difference of km promotion among females and males was not significant ( 21.6120.17 in males and 20.331.61 in females , p=0.8 ) . the km was increased to 19.9325.06 among parents who at most had high school diploma and 23.4720.84 among parents with upper educational levels ( p=0.5 ) .
health has been the concern of poets such as fiona sampson for years , however , these poems never had educational purposes . the results of this study
confirm our hypothesis about the role of children in raising family 's knowledge on health .
the results show that neither gender nor the grade of knowledge degree ( below and upper high school diploma or below and upper ba ) affect answers .
therefore , people with different educational status have received the information similarly implying that this method can be extended to general cases in a straightforward manner .

1 shows that the percentage of correct answers has increased in 23 out of 24 questions .
the percent - age of correct answer to post - test has decreased only in one item ( item 11 ) which compares the risk of brucellosis transmission via unpasteurized milk and yogurt . although the term yogurt has not been mentioned directly in the related poem , but there is a hint about boiling mechanism and we expect that the audience discover the answer by logical thinking about the necessitation of boiling milk for preparing yogurt .
the decrease in answering is 2 percent which is not significant ; however , it shows that it would be better to mention the conceptions directly in these types of poems in order to avoid any misconceptions .
moreover , the percentage of correct answers to the questions of selected topics in pre - test and post - test has been compared ( table 1 ) and shows that parents have done better in post - test about all topics except one .
the difference of correct answers to the questions about brucellosis does not show a significant increase in post - test .
this finding is probably due to higher basic knowledge about brucellosis among parents . in other words , parents have had acceptable information about brucellosis even without our educational program , so we observe lower contrast between pre - test and post - test about brucellosis
. it should be taken into consideration that brucellosis is an endemic disease in hamadan and people have been educated in different ways about this disease in recent years . although the lowest contrast between pre - test and post - test correct answers belongs to a question about botulism , the overall assessment shows that parent 's knowledge about this topic has been promoted significantly ( p<0.001 , table 1 ) . the significant difference between the pre - test and post - test km , based on the results of table 2 , is the sign of successful knowledge transfer through childish poems .
the researcher 's method is impressively successful ; however , the fact that he mentions that some mothers can not distinguish the semantic difference between information and advice , needs serious attention .
in addition , since daughters may misunderstand the information , it would be probable to transfer the misconceived information to their mothers and this fact threats the successfulness of study in applying . while , in our study ; firstly , childish poems do not imply sententious , secondly , if the poem is sung wrong , the disturbance in rhythm will be appeared , so the information which is transferred through poems is not at risk of alteration . in evans research ,
parents get familiar with educated topics with the help of their children in homework assignments designed for asthma management , and are taught about asthma indirectly .
the advantage of our study in comparison with evans is that in evans method knowledge transfer brings to bear via homework assignment , while in our study there is no obligation for doing home works , and parents are educated while enjoying their child 's singing . on account of the fact that making communication with younger children is not as difficult as with adolescents for parents , we are sure that knowledge transfers within a family through a continuous and friendly communication will work .
christensen expressed the importance of children 's role in promoting the family health status . in his article , he emphasized on the activities that children can perform to enhance their health and promote their family health situation via the health efforts for themselves .
we showed that children , additionally to what christensen mentioned , are able to affect their family 's health status directly . they can improve their family 's health as little teachers in health .
it should be taken into consideration that the limitations of this study was the impact of other media on participant 's knowledge , which was not preventable .
one of the acceptable results of this survey was publishing the poems as a book for children which was republished and welcomed by public .
this study 's results suggest that health knowledge transfer to families through childish poems is an applicable method that has many advantages . by applying this joyful , cost - effective and easy - to - use method
however , it should be taken into consideration that this method is applicable for families with trainable children , for teaching in larger scales more general ways should be added to this method .
moreover , the simplicity of poems and expressing the topics in a less elaborative form are the key factors that affect the successfulness of this way .

Answer:
objectivethe purpose of this study is to propose an innovative method of knowledge transfer that aims to improve health literacy about pediatric infectious diseases prevention in families .
 children have an appreciable role in this scheme.methodsthis study is a before and after trial that has been conducted in hamedan in 2009 . after changing seven infectious disease topics into childish poems , we selected five kindergartens randomly and taught these poetries to the children . teaching process held after a pretest containing 24 questions that examined 103 of parents about mentioned topics .
 the same post - test was given after 4 months of teaching process.findingsthe mean of correct answers to the pretest was 59.22% comparable with 81.00% for post - test ( p<0.00 ) .
 gender and knowledge degree could not change the results significantly .
 assuming one 's correct answers to the questions as his / her knowledge mark , the mean of this variable increased to 5.32 by this method.conclusionthis cost - effective and joyful method had successful results in promoting health knowledge .
 children are able to play an active role in family 's health situation .
 learning within family atmosphere without any obligations makes our scheme a solution for paving the knowledge transferring way .


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 class i elements include the long terminal repeat ( ltr ) retrotransposons , the non - ltr retrotransposons and the short interspersed nucleotide elements ( sines ) 1 , 2 .
the class ii elements have terminal inverted repeats with transposase - binding sites , and include the p elements found in drosophila .
the best - known sines are the alu elements of primates , which are thought to have a common origin with the b1 elements of rodents 1 , 3 , 4 .
alu elements are the most abundant transposable elements in the human genome , being present in about 500,000 copies .
these retroposons consist of two related monomers in tandem and , as the name implies , contain a restriction site for the enzyme alui .
they have no open reading frames , and the factors necessary for their amplification are thought to come from long interspersed elements ( lines ) which code for functional reverse transcriptases with an endonuclease domain 2 , 4 .
the present work describes the first sine detected in the genome of the cephalochordate amphioxus .
previous studies of transposable elements in amphioxus are limited to a class i non - ltr retrotransposon ( bfcr1 ) 5 and a class ii , non autonomous transposable element ( ate-1 ) 6 .
amphioxus ( branchiostoma ) is an aquatic invertebrate with a much simpler body plan than vertebrates ( e.g. no paired eyes , ears or limbs ) .
moreover , the amphioxus genome appears to have a similar organization as that of vertebrates but lacks the extensive gene duplications that occurred in the vertebrate lineage 7 .
however , recent analyses done with large gene sets have placed amphioxus basal in the chordates with the rapidly evolving tunicates as the sister group of vertebrates 8 , 9 .
amphioxus is , therefore , the most appropriate organism for comparison with vertebrates to understand how the vertebrates evolved from invertebrate chordate ancestors .
the surprising finding of the present work is not that amphioxus has transposable elements or that this element is a sine , which are common in eukaryotic genomes , but that it contains three alui sites , two of which are in tandem .
thus , the finding of an alu element in amphioxus raises the question whether amphioxus and primates are an example of convergent evolution or whether they both arose from an alu element in the ancestral chordate .
the transposable element was located by blastn searches of the amphioxus ( branchiostoma floridae ) genome sequences in the trace archives of genbank with portions of the upstream regulatory region of the foxd gene ( af512537 ) , which we had sequenced from cosmid mpmgc117o0129 available from the rzpd ( http://www.rzpd.de ) .
sequences that were present in this cosmid , but absent from at least one of the foxd alleles in the trace archives , were suspected transposable elements . additional copies of this transposable element were located by blastn searches of amphioxus bac clones deposited in genbank .
we have previously identified a notochord - specific enhancer in the foxd gene in amphioxus ( branchiostoma floridae ) 10 .
this enhancer encompassed 4.7 kb upstream of the atg start codon and has several binding sites for the notochord marker brachyury as well as for fox d itself , suggesting autoregulation .
subsequently , we determined that the 5 ' portion of this enhancer , which includes these binding sites , is essential for directing expression to the notochord [ j - k .
] however , just downstream of the foxd binding sites are two sites for foxa2 ( hnf3 ) , which , like brachyury , is expressed in the notochord ( figure 1a ) .
therefore , it seemed likely that this region with the foxa2 sites is also involved in directing notochordal expression .
surprisingly , blast searches of the amphioxus genome sequences in the trace archives of genbank , which represent the two alleles of a single individual , revealed that both alleles lacked the region with the foxa2 binding sites that corresponds to 1168 to 1543 upstream of the foxd atg start codon in the clone we previously sequenced , which was from a different individual ( figure 2 ) .
moreover , we found this 375 bp region in numerous traces with flanking regions that did not correspond to the foxd gene .
an estimate would be 50 - 100 copies in the genome of the individual sequenced .
figure 1b compares this sine with eight representative homologous sines found in the trace archives and in cosmid sequences , all of which are from the two alleles of the same individual .
the first two of these eight sines are located in cosmids containing respectively , the tbx15/18/21 gene and the pax1/9 gene . in the former ,
the sine is 4200 bp upstream of the atg start codon of tbx15/18/21 and in the latter it is 40 kb upstream of the 5 ' end of pax 1/9 and located within an intron of a hypothetical gene coding for a cyclic nucleotide - gated cation channel .
the remaining sines in figure 1 were contained in relatively short bac end sequences and genomic traces , and therefore , their location relative to particular genes can not be determined until the full genome sequence is available .
the amphioxus sine has several characteristic features of sines in general and of primate alu elements in particular , and i , therefore , term it the amphi - alu element .
sines generally are about 300 bp long with a polya tail of varying length and have similar , but not identical , left and right halves 11 - 13 .
sines typically have a region derived from trna that contains a consensus rna polymerase promoter 14 .
the amphioxus element is 375 bp long , the polya tail ranges from 1 - 13 bases ( figure 1b ) , and the right and left halves are 52% identical ( clustal w alignment ) .
most of the copies of this element have from one to three alui sites , although they can be mutated ( figure 1b ) .
moreover , alignments with trna sequences from sea urchin available at http://lowelab.ucsc.edu/gtrnadb/ reveal a high percentage of identities with a sea urchin trna for glutamine with an imperfect match for the rna polymerase promoter  a  site and a nearly perfect one for the  b  site ( figure 3 ) . as is typical for sines , deletions of portions of either the left arm or the right arm are common .
show that these repeats are within the alu element and not in the flanking region .
such repeats are lacking at the 3 ' end of the alu element and in the adjacent 3 ' flanking sequence .
figure 2 shows the insertion site in the foxd gene for an allele lacking amphi - alu .
the potential insertion site in is between 2  t  residues and is flanked by direct repeats of ctttgtt . in the clones containing the amphi - alu element , there are direct repeats in the flanking regions of some clones ( e.g. gttttattg / gtttcttg for foxd ) .
however , direct repeats are not always present on either side of amphi - alu , raising the possibility , which can be tested when the full genome assembly is available , that some amphi - alu sines may be longer than the one in the amphifoxd allele shown in figure 1 10 .
one unusual feature of amphi - alu is that the region with the highest identity to a trna is from base 199 to base 183 , rather than at the 5 ' end 13 as is typical for sines .
although it is possible that figure 1 depicts amphi - alu in the reverse orientation , this is not likely since a varying number of  a  residues were present in all clones at the end designated as the 3 ' end in figure1b .
moreover , comparisons of the reverse strand of amphi - alu with trnas from a range of species , including sea urchin , had few matches .
this raises the possibility that the amphi - alu sine is a chimeric element , but it is puzzling that in either orientation , the putative rna polymerase iii sites are not near the ends of the element .
alu elements have previously been described only in primates 15 , raising the question of whether amphi - alu and primate alu elements are descended from a common ancestral alu , or whether the presence of alu sites in these two sines from primates and amphioxus represent convergent evolution .
it has been argued that the fla ( free left arm ) alu family arose at the origin of mammals about 112 mya 15 .
however , alignments of human alu elements and amphi - alu do not reveal a high level of identity ; in general , amphi - alu is not as gc rich as human alu elements , and the most at - rich region is not central as in human alu elements but starts at base 290 .
morover , human alus and the related b1 elements of rodents have a 7sl rna - related region 3 , 13 , 16 , while amphi - alu is related to a trna for asparagine .
thus , since amphioxus and vertebrate lineages are estimated to have split about 520 mya , it seems more likely that the alu sites in the amphioxus and mammalian alu elements have arisen through convergent evolution . however , there are few descriptions transposable elements in basal vertebrates such as agnathans 17 or in tunicates 18 , which recent phylogenetic analyses place as the sister group to vertebrates , amphioxus being basal in the chordates 8 , 9
. alignments of a tunicate sine ( cics-1 ) , which lacks alui sites , with amphi - alu reveal only a few short regions of identity 18 .
a thorough study of transposable elements in amphioxus and these animals is critical for understanding the evolutionary history of alu elements . in the three instances where complete cosmid or bac sequences were available ,
the amphi - alu elements were located in likely regulatory dna either upstream of the atg start codon ( foxd and clone ch302 63l21 ) or within an intron ( ch302 119j21 ) .
human alu elements within introns have been implicated in alternative splicing and exonization whereby part of the sine is not spliced out of the mrna and can cause frame shifts and gene inactivation 2 , 19 .
moreover , whether in the upstream regulatory region or in an intron , sines may provide binding sites for transcription factors and thus influence gene regulation .
the amphi - alu element has probable binding sites for foxa2 , which is normally expressed in the endoderm and notochord of amphioxus 20 .
its location in the foxd gene just downstream of an important enhancer ( figure 1a ) , suggests that it might be contributing to regulation of the foxd gene in the individuals that have it in the foxd regulatory region .
alu elements have been implicated in regulation of many genes 21 , 22 . to what extent
such transposable elements might mediate evolution of cis - regulation in animals in nature is not known .
however , it is certainly a possible mechanism for effecting large changes in cis - regulation . in summary ,
the finding of an alu element in the amphioxus genome that is present in the regulatory dna of some , but not all , alleles of the foxd gene and in the regulatory regions of other genes raises questions both about the evolution of sines in chordates and suggests that the insertion of such sines into regulatory dna could mediate evolution of cis - regulatory regions .
there is some evidence for positive selection for such transposon - mediate changes in regulatory dna 21 , 22 , and it may become evident with the sequencing of the genomes of more organisms like amphioxus with relatively short life cycles are sequenced to what extent such changes in regulatory dna mediate large evolutionary changes .
the amphi - alu sine from the foxd gene in an individual of branchiostoma floridae .
a. schematic diagram of the upstream regulatory region showing the foxd repeat region in cosmid mpmgc117o0129 , which we have shown is essential for directing expression of foxd to the notochord just upstream of the amphi - alu element , which is inserted into the foxd gene at base 1168 upstream of the atg start codon .
this element contains two binding sites for foxa2 which is also expressed in the notochord , but as it is not present in two other foxd alleles , it can not be essential for notochord expression .
b. representative sequence variations of the amphi - alu sine from the foxd gene in cosmid mpmgc117o0129 and from six bac clones and two genomic traces from the trace archive database ( http://www.ncbi.nlm.nih.gov/traces/trace.cgi ? ) .
the amphi - alu sine in bac ch302 63l21 is located in the presumed upstream regulatory region of the tbx15/18/21 gene and that from ch302 119j21 within an intron of a hypothetical gene coding for a cyclic nucleotide gated cation channel .
since the other sequences are either from bac end sequencing or shot - gun sequencing , it is not possible as yet to determine if they are within regulatory regions of genes .
the amphi - alu sequence is shown in the reverse orientation of its insertion into the foxd locus to orient the polya stretches as polya tails ( double - underlining ) .
the 5 ' end of the alu element is shown as 1 , the alu sites are shaded in grey , two regions corresponding to the binding sites for rna polymerase on the trna - like region are underlined and the binding sites for foxa2 are shown by thick lines over the sequence the amphifoxd genomic region lacking the amphi - alu sine from a sequence in the trace archives of genbank ( gnl|ti|545126576 name : afsa504495.g2 ) .
the site corresponding to the insertion site of the amphi - alu sine in the foxd gene in cosmid mpmgc117o0129 is shown by the arrowhead .
alignment of the sea urchin ( strongylocentrotus purpuratus ) trna for asparagine and the corresponding region of the amphi - alu element .
the regions with high identity to the a and b binding sites for rna polymerase iii are boxed .

Answer:
transposable elements of about 300 bp , termed
  short interspersed nucleotide elements or sines are common in eukaryotes .
 however , alu elements , sines containing restriction sites for the alui enzyme , have been known only from primates . here
 i report the first sine found in the genome of the cephalochordate , amphioxus .
 it is an alu element of 375 bp that does not share substantial identity with any genomic sequences in vertebrates .
 it was identified because it was located in the foxd regulatory region in a cosmid derived from one individual , but absent from the two foxd alleles of bacs from a second individual .
 however , searches of sequences of bacs and genomic traces from this second individual gave an estimate of 50 - 100 copies in the amphioxus genome .
 the finding of an alu element in amphioxus raises the question of whether alu elements in amphioxus and primates arose by convergent evolution or by inheritance from a common ancestor .
 genome - wide analyses of transposable elements in amphioxus and other chordates such as tunicates , agnathans and cartilaginous fishes could well provide the answer .