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Magnetic field gradients and coherence-pathway elimination.

The amount of residual transverse magnetization after the application of a pulsed magnetic-field gradient (PFG) is calculated for a homogeneous volume of interest (VOI) with three orthogonal pairs of sides and for VOIs that deviate from this idealized case. Many of the results can be understood in terms of the Fourier-transform relationship between the VOI intensity profile as a function of position, I(x), and the residual signal as a function of net PFG strength, S(k). Dephasing of transverse magnetization is more effective with imperfect slice-selection profiles, a circular sample cross section, or decreased B1 intensity near the edges of a sample than in the idealized case. When two or more orthogonal PFGs are applied, the net amount of dephasing depends on the source of intensity variation (sample geometry or slice-selective radiofrequency pulse profiles) and the orientation of the PFGs. If a gradient is parallel to one side of a VOI with rectangular cross sections, dephasing is more effective if a second, orthogonal gradient of equal intensity is added than if the original intensity is doubled. In contrast, if a PFG is orthogonal to the axis of an NMR tube with a circular cross section, addition of a second gradient orthogonal to the tube axis provides only slightly greater dephasing and is less effective than doubling the original intensity.

Fourier Analysis↗

Urinary function and bother after radical prostatectomy or radiation for prostate cancer: a longitudinal, multivariate quality of life analysis from the Cancer of the Prostate Strategic Urologic Research Endeavor.

PURPOSE: We measure the effect of time on urinary function and bother during the first 2 years following treatment for early stage prostate cancer. MATERIALS AND METHODS: We studied urinary function and bother in 564 men recently diagnosed with early stage prostate cancer and treated with radiotherapy or radical prostatectomy with or without nerve sparing. Outcomes were assessed with the UCLA Prostate Cancer Index, which is a validated, health related quality of life instrument that includes these 2 domains. To minimize the influence of other factors we adjusted for age, co-morbidity, general health, pad use, anticholinergics or procedures for urethral stricture. All subjects were drawn from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), which is a national longitudinal database. RESULTS: Urinary function improved with time during the first year after surgery but remained fairly constant during year 2. Urinary function remained stable throughout the 2 years after radiation. Urinary bother was worse after radiation throughout the 2 years, although it improved markedly by the end of year 1. Age, ethnicity and co-morbidity did not impact urinary function or bother but being married did have an advantage. CONCLUSIONS: Patients undergoing surgery or radiation showed different longitudinal profiles of urinary function and bother during the first 2 years after treatment.

Aged↗

Beneficiary effect of dietary soy protein on lowering plasma levels of lipid and improving kidney function in type II diabetes with nephropathy.

OBJECTIVE: Heart and renal diseases are two major problems in diabetic patients. Hyperlipidemia is one of the main risk factors of cardiovascular complications in diabetes. The type of protein consumed also affects the changes in renal blood flow, glomerular resistance and renal function in these patients. Hence, this study was undertaken to show the effect of soy protein consumption on lipid profiles and kidney function of diabetic patients with nephropathy, who attended an educational university hospital as well as a private kidney disease clinic in Tehran. SUBJECTS AND METHODS: This crossover randomized clinical trial was conducted on 14 patients who were free of any uncontrolled condition or other renal diseases. The patients were asked to follow a usual nephropathy diet (0.8 g/kg protein, 70% animal and 30% vegetable protein) for 7 weeks. After a washout period of 4 weeks consuming the prestudy diet, subjects were readmitted to repeat the same cycle with a similar diet containing 35% soy protein and 30% vegetable protein. Paired t-test, carryover effect and period effect were used for statistical analysis. RESULT: : There were 10 men and four women whose mean (s.d.) of weight was 70.6 (10.3) kg. Significant reductions were seen in total cholesterol (P<0.01), triglyceride (P<0.002) and LDL-c (P<0.04), urinary urea nitrogen and proteinuria (P<0.001) after soy vs animal protein consumption. There were no significant changes in HDL-c, LDL-c/HDL-c levels. We also saw a favorable effect on renal function. CONCLUSION: Soy inclusion in the diet can modify the risk factors of heart disease and improve kidney function in these patients.

Cardiovascular Diseases↗

The cowpox virus SPI-3 and myxoma virus SERP1 serpins are not functionally interchangeable despite their similar proteinase inhibition profiles in vitro.

The myxoma virus (MYX) serpin SERP1 is a secreted glycoprotein with anti-inflammatory activity that is required for full MYX virulence in vivo. The cowpox virus (CPV) serpin SPI-3 (vaccinia virus ORF K2L) is a nonsecreted glycoprotein that blocks cell-cell fusion, independent of serpin activity, and is not required for virulence of vaccinia virus or CPV in mice. Although SPI-3 has only 29% overall identity to SERP1, both serpins have arginine at the P1 position in the reactive center loop, and SPI-3 has a proteinase inhibitory profile strikingly similar to that of SERP1 [Turner, P. C., Baquero, M. T., Yuan, S., Thoennes, S. R., and Moyer, R. W. (2000) Virology 272, 267-280]. To determine whether SPI-3 and SERP1 were functionally equivalent, a CPV variant was constructed where the SPI-3 gene was deleted and replaced with the SERP1 gene regulated by the SPI-3 promoter. Cells infected with CPVDeltaSPI-3::SERP1 secrete SERP1 and show extensive fusion, suggesting that SERP1 is unable to functionally substitute for SPI-3 in fusion inhibition. In the reciprocal experiment, both copies of SERP1 were deleted from MYX and replaced with SPI-3 under the control of the SERP1 promoter. Cells infected with the MYXDeltaSERP1::SPI-3 recombinant unexpectedly secreted SPI-3, suggesting either that the cellular secretory pathway is enhanced by MYX or that CPV encodes a protein that prevents SPI-3 secretion. MYXDeltaSERP1::SPI-3 was as attenuated in rabbits as MYXDeltaSERP1::lacZ, indicating that SPI-3 cannot substitute for SERP1 in MYX pathogenesis.

Animals↗

Effects of monensin and forage:concentrate ratio on feed intake, endocrine, and ovarian function in beef heifers.

The objective of this study was to determine the effects of monensin (M) and altered forage:concentrate ratio (F:C) on feed intake, hormonal profiles, and ovarian function in beef heifers. Four ruminally cannulated heifers were maintained in metabolism crates and fed twice daily. Diets contained 0 or 200mg per day M in diets of 70:30 (high forage, HF) or 30:70 (high concentrate, HC) F:C. Diets were limit fed to achieve isocaloric intake of calculated ME. Monensin supplementation had no effect on feed intake, but heifers fed HF had greater refusals compared with heifers fed HC (P<0.005). Serum insulin, progesterone, and estradiol concentrations did not differ between diets or treatments (P>0.10). Diet and/or treatment tended to alter the size or number of follicles on either or both ovaries. Monensin resulted in more waves of follicular development per estrous cycle with HF diets, but fewer with HC diets (P<0.07). The interovulatory interval, lifespan of the corpus luteum, and the size of the dominant follicle in the first two follicular waves were not different due to diet or treatment. However, the HC diet tended to produce a larger ovulatory follicle compared with the HF diet (HF=12.25, HC=13.5; P<0.08). We conclude that feeding monensin affects estradiol secretion and a higher proportion of concentrates alters ovarian dynamics, which could affect fertility in beef heifers.

Animals↗

Effects of alcohol and fluvastatin on lipid metabolism and hepatic function.

OBJECTIVE: To determine the effects of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, combined with moderate alcohol consumption on lipid profiles and hepatic function in patients with primary hypercholesterolemia. DESIGN: Randomized, placebo-controlled, crossover study. SETTING: Lipid clinic of a university hospital. PATIENTS: 31 patients with primary hypercholesterolemia (low-density lipoprotein cholesterol levels > or = 4.2 mmol/L) who had previously received a lipid-lowering diet. INTERVENTIONS: After a dietary baseline period, 26 patients were randomly assigned to receive 6 weeks of treatment with either 1) fluvastatin, 40 mg/d, added to 20 g of ethanol and diluted to 20% with orange juice or 2) fluvastatin added to orange juice alone. After a 6-week washout period, the two groups crossed over. MAIN OUTCOME MEASURES: Plasma fluvastatin levels, lipid levels, and clinical variables were determined at the end of each treatment period. RESULTS: Six patients left the study prematurely. The remaining patients (15 men, 5 women; mean age +/- SD 49.1 +/- 14.5 years; mean body mass index +/- SD 24.5 +/- 2.2 kg/m2) completed the study. Fluvastatin, alone and combined with alcohol, resulted in similar decreases in levels of total cholesterol (22% and 23%, respectively; P < 0.001 when compared with baseline), low-density lipoprotein cholesterol (28% and 29%, respectively; P < 0.001 compared with baseline), and apolipoprotein B (17% and 20%, respectively; P < 0.001 compared with baseline). High-density lipoprotein cholesterol and triglyceride levels were not changed. Fluvastatin with alcohol resulted in a significantly greater area under the plasma concentration curve (23.4 +/- 4.7 compared with 18.2 +/- 3.2 x 10(3) ng.min/mL) and in a greater time to maximum concentration (187.5 +/- 16.6 min compared with 130.9 +/- 7.0 min) than fluvastatin alone. Terminal half-life tended to increase. No important adverse clinical effects were observed. CONCLUSION: Six weeks of daily, moderate alcohol consumption influenced the metabolism of fluvastatin but did not interfere with its lipid-lowering efficacy and had no adverse effects.

Adult↗

The outcome of episodic versus persistent adolescent depression in young adulthood.

OBJECTIVE: Study of the impact of episodic and persistent depression on psychosocial and mental functioning of young adults. METHODS: In a longitudinal representative community sample, four groups of subjects were identified who were depressed either in pre-adolescence, late adolescence or young adulthood or persistently depressed across time, and compared among each other and with a young adult control group. The 90th percentile on one or two self-reported symptom scales (i.e., the Center for Epidemiological Depression Scale (CES-D) or the Anxious/Depressed subscale of either the Youth Self-Report (YSR) or the Young Adult Self-Report (YASR)) served as the cut-off for the depression groups. Outcome was studied with regard to various psychosocial variables including life events, coping, self-related cognitions, size and efficiency of the social network, perceived parental behaviour, family relations and mental functioning. RESULTS: For the large majority of psychosocial variables, the persistent depression group showed the most abnormal scores. The YASR profile of mental functioning at outcome of the persistent depression group was also clearly distinguishable by higher scores from all other groups on the majority of scales. On a few scales, the young adult episodic group was not significantly different from the persistent depression group. CONCLUSION: This study shows that persistent rather than episodic adolescent depression carries a risk for abnormal psychosocial and mental functioning in young adulthood. The study also reflects the burden of young adult depression.

Adaptation, Psychological↗

The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine.

RATIONALE: Clozapine is a unique antipsychotic, with efficacy against positive symptoms in treatment-resistant schizophrenic patients, and the ability to improve cognition and treat the negative symptoms characteristic of this disease. Despite its unique clinical actions, no specific molecular mechanism responsible for these actions has yet been described. OBJECTIVES AND METHODS: To comprehensively profile a large library of neuropsychiatric drugs, including most antipsychotics, at human monoamine receptors using R-SAT, an in vitro functional assay. RESULTS: Profiling revealed that N-desmethylclozapine (NDMC), the principal metabolite of clozapine, but not clozapine itself, is a potent and efficacious muscarinic receptor agonist, a molecular property not shared by any other antipsychotic. To further explore the role of NDMC muscarinic receptor agonist properties in mediating the physiological actions of clozapine, systemically administered NDMC was found to stimulate the phosphorylation of mitogen-activated protein kinase (MAP kinase) in mouse CA1 hippocampal neurons, an effect that was blocked by scopolamine, confirming central M1 muscarinic receptor agonist activity in vivo. Lastly, an analysis of clozapine and NDMC serum levels in schizophrenic patients indicated that high NDMC/clozapine ratios better predicted improvement in cognitive functioning and quality of life than the levels of either compound alone. CONCLUSIONS: The muscarinic receptor agonist activities of NDMC are unique among antipsychotics, and provide a possible molecular basis for the superior clinical effects of clozapine pharmacotherapy.

Animals↗

Uncovering functionally relevant signaling pathways using microarray-based expression profiling.

The introduction of microarray technology to the scientific and medical communities has fundamentally altered the way in which we now address basic biomedical questions. Microarrays technology facilitates a more complete and inclusive experimental approach where alterations in the transcript level of entire genomes can be simultaneously assayed in response to a variety of stimuli. Conceptually different approaches to the development of microarray technology have resulted in the generation of two different array formats: oligonucleotide arrays and cDNA arrays. The application of microarray and related technologies to identify specific targets of defined genes that have clearly been implicated in cancer progression requires a specific experimental approach. The objective of this approach is to define changes in transcriptional profile that occur in response to modulating the expression level of the gene to be studied. The resulting altered expression profile can then be viewed as a blueprint by which that gene effects its cellular function. We have used oligonucleotide array-based expression profiling in collaboration with Affymetrix to identify downstream transcriptional targets of the BRCA1 tumor-suppressor gene as a means of defining its function. BRCA1 has been implicated in at least three functional pathways, namely, mediating the cellular response to DNA damage, as a cell cycle checkpoint protein and in the regulation of transcription. The physiological significance of these properties and their implications for the function of BRCA1 as a tumor-suppressor gene remain to be defined.

DNA, Complementary↗

Transient hyperthyroidism of hyperemesis gravidarum.

OBJECTIVE: To characterise the clinical, biochemical and thyroid antibody profile in women with transient hyperthyroidism of hyperemesis gravidarum. DESIGN: Prospective observational study. SETTING: Hospital inpatient gynaecological ward. POPULATION: Women admitted with hyperemesis gravidarum and found to have hyperthyroidism. METHODS: Fifty-three women were admitted with hyperemesis gravidarum and were found to have hyperthyroidism. Each woman was examined for clinical signs of thyroid disease and underwent investigations including urea, creatinine, electrolytes, liver function test, thyroid antibody profile and serial thyroid function test until normalisation. MAIN OUTCOME MEASURES: Gestation at which thyroid function normalised, clinical and thyroid antibody profile and pregnancy outcome (birthweight, gestation at delivery and Apgar score at 5 minutes). RESULTS: Full data were available for 44 women. Free T4 levels normalised by 15 weeks of gestation in the 39 women with transient hyperthyroidism while TSH remained suppressed until 19 weeks of gestation. None of these women were clinically hyperthyroid. Thyroid antibodies were not found in most of them. Median birthweight in the infants of mothers who experienced weight loss of > 5% of their pre-pregnancy weight was lower compared with those of women who did not (P = 0.093). Five women were diagnosed with Graves' disease based on clinical features and thyroid antibody profile. CONCLUSIONS: In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalises by the middle of the second trimester without anti-thyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent. Apart from a non-significant trend towards lower birthweights in the infants of mothers who experienced significant weight loss, pregnancy outcome was generally good. Routine assessment of thyroid function is unnecessary for women with hyperemesis gravidarum in the absence of any clinical features of hyperthyroidism.

Adult↗

Splicing profile based protein categorization between human and mouse genomes by use of the DDBJ Web services.

In one scenario of gene evolution, exon shuffling plays a fundamental role in increasing gene diversity. This paper is an appraisal of the biological relevance of categorising proteins by their splicing profiles (exon-intron structures). The central question is whether protein function is more correlated with splicing profiles than sequence similarity, or not. To approach this question, a splicing profile similarity (SPS) index, which measures relative exon length discrepancy, was devised. Arbitrary human proteins were compared, in terms of SPS and amino acid sequence similarity, to their 1) mouse orthologues and 2) human paralogues, which epitomise functional equivalence and non-equivalence, respectively, to methodically elucidate the global relationship between a) biological function, b) splicing profile similarity, and c) sequence similarity. Protein function is more correlated with splicing profile similarity than sequence similarity as demonstrated by the fact that human-mouse orthologues (HMOs) display significantly higher splicing profile similarity than do human-human paralogues (HHPs), despite the mutual sequence similarity between these two categories. This finding indicates that splicing profile-based protein categorisation is biologically meaningful.

Alternative Splicing↗

Inferring functional linkages between proteins from evolutionary scenarios.

Identifying potential protein interactions is of great importance in understanding the topologies of cellular networks, which is much needed and valued in current systematic biological studies. The development of our computational methods to predict protein-protein interactions have been spurred on by the massive sequencing efforts of the genomic revolution. Among these methods is phylogenetic profiling, which assumes that proteins under similar evolutionary pressures with similar phylogenetic profiles might be functionally related. Here, we introduce a method for inferring functional linkages between proteins from their evolutionary scenarios. The term evolutionary scenario refers to a series of events that occurred in speciation over time, which can be reconstructed given a phylogenetic profile and a species tree. Common evolutionary pressures on two proteins can then be inferred by comparing their evolutionary scenarios, which is a direct indication of their functional linkage. This scenario method has proven to have better performance compared with the classical phylogenetic profile method, when applied to the same test set. In addition, predicted results of the two methods are found to be fairly different, suggesting the possibility of merging them in order to achieve a better performance. We analyzed the influence of the topology of the phylogenetic tree on the performance of this method, and found it to be robust to perturbations in the topology of the tree. However, if a completely random tree is incorporated, performance will decline significantly. The evolutionary scenario method was used for inferring functional linkages in 67 species, and 40,006 linkages were predicted. We examine our prediction for budding yeast and find that almost all predicted linkages are supported by further evidence.

Computational Biology↗

Sarcoplasmic reticulum K(+) channels from human and sheep atrial cells display a specific electro-pharmacological profile.

It has recently been proposed that the Ca(2+) uptake by the SR is inhibited by blocking Cl(-) and/or K(+) movements across this intracellular membrane. We have characterised the functional and pharmacological profile of the SR K(+) channel derived from human and sheep atrial cells. Mammalian atrial SR preparations were subjected to [(3)H]-ryanodine binding assays, SDS-PAGE analysis and channel protein reconstitution into planar lipid bilayers. Assessment of [(3)H]-ryanodine binding on the SR Ca(2+) release channel revealed that it was inhibited by both Ruthenium Red and Mg(2+) with IC(50) values of 4.11 microM and 9.12 m M, respectively. In crude populations as well as in all SR-enriched fractions, activity of K(+) selective channels was recorded. This channel displayed a high conductance value of 193 and 185 pS for human and sheep preparations respectively. Gating and conducting behaviours of this channel were unaffected by the addition of up to 5m M 4-Aminopyridine (4-AP), 100 n M Iberiotoxin (IbTX), 10 microM E-4031 and 30 microM amiodarone. However, 100n M Dendrotoxin (gamma-DTX) largely increase the occurrence of the SR K(+) channel subconducting states without an effect on the main unitary conductance. These results demonstrate that the SR K(+) channel, present in all mammalian atrial SR membranes tested (as assessed by [(3)H]-ryanodine binding and its typical inhibition by ruthenium red and the magnesium), displays different properties than those classically described for cardiac sarcolemmal K(+) channels. Despite the fact that the biophysical properties of the SR K(+) channel are well known, its molecular identity remains to be ascertained.

Animals↗

Diverse enzymatic specificities of digestive proteases, 'intestains', enable Colorado potato beetle larvae to counteract the potato defence mechanism.

In response to insect attack, high levels of proteinase inhibitors are synthesised in potato leaves. This can cause inefficient protein digestion in insects, leading to reduced growth, delayed development and lower fecundity. It has been suggested that Colorado potato beetle overcomes this defence mechanism by inducing the production of a set of cysteine proteases that are resistant to potato proteinase inhibitors. Experiments with gut extracts showed that these proteases have unusual inhibition profiles as they are not inhibited by most of the cystatins but are strongly inhibited by thyropins. In this study we have isolated three cysteine proteases from adapted guts of Colorado potato beetle larvae, named intestains 1, 2 and 3, the first cysteine proteases known to be involved in extracellular protein digestion. The N-terminal sequences suggest their classification into the papain family. Intestains differ in substrate specificities and inhibitory profiles. Their substrate specificities suggest that intestains 1 and 2 are general digestive enzymes, while intestain 3 has a more specific function. The inhibitory profile of intestain 1 is similar to that of proteases of the papain family. However, the Ki values for the interaction of intestain 2 with the same set of inhibitors are several hundred fold higher, which would enable the enzyme to circumvent the potato defence mechanism characterised by high concentrations of protease inhibitors in attacked potato leaves. A further, different strategy of the Colorado potato beetle to avoid potato defence is exhibited by intestain 3, which is able to cleave off the N-terminus of model cystatin and thus inactivate the inhibitor. These results suggest that the Colorado potato beetle combines different strategies to counteract plant defence mechanisms.

Amino Acid Sequence↗

Correlating function and gene expression of individual basal ganglia neurons.

Functional studies at the level of individual neurons have greatly contributed to our current understanding of basal ganglia function and dysfunction. However, identification of the expressed genes responsible for these distinct neuronal phenotypes is less advanced. Qualitative and quantitative single-cell gene-expression profiling, combined with electrophysiological analysis, allows phenotype-genotype correlations to be made for individual neurons. In this review, progress on gene-expression profiling of individual, functionally characterized basal ganglia neurons is discussed, focusing on ion channels and receptors. In addition, methodological issues are discussed and emerging novel techniques are introduced that will enable a genome-wide comparison of function and gene expression for individual neurons.

Animals↗

Accelerated mental aging in alcoholic patients.

Discriminant function and polynomial regression methods were used to define a mental age function from scale score profile patterns found in the WAIS manual. Values on the mental age function then were calculated from WAIS scale score profiles for 164 alcoholics in the age range 35 to 74. Validity of the mental age function was evident in clear discrimination between chronological age groups in the alcoholic sample. As compared with WAIS normative values for the mental age function, the mean mental age for patients in the alcoholic sample was advanced approximately 7 years over age-matched normals. Unweighted means ANOVA revealed the accelerated mental aging of alcoholic patients to be statistically significant. This finding is discussed in the context of other research that supports a premature aging hypothesis.

Adult↗

Diastolic heart failure in the community: clinical profile, natural history, therapy, and impact of proposed diagnostic criteria.

BACKGROUND: Diastolic heart failure (DHF) has been broadly defined as "signs and symptoms of congestive heart failure (CHF) with normal/near normal systolic function." The clinical profile and natural history of the syndrome remain controversial. Furthermore, the frequency with which patients with CHF and normal ejection fraction (EF) fulfill recently proposed standardized diagnostic criteria for DHF is unclear. Our objective was to determine the clinical profile, Doppler echocardiographic features, current management, prognosis, and predictors of outcome of all patients with new onset CHF who had normal EF in Olmsted County, Minnesota, during 1996-1997. The frequency with which patients met recently proposed standardized criteria for diagnosis of DHF was assessed. METHODS: Using the resources of the Rochester Epidemiology Project, all residents of Olmsted County, Minnesota, with a new diagnosis of CHF in 1996-1997, an ejection fraction >45%, and no valve disease (n = 83) were identified. RESULTS: Patients were elderly (79 +/- 13 yr), predominantly female (76%), and had hypertension and/or coronary artery disease (85%). New-onset atrial fibrillation, ischemia, and medical comorbidities were frequently present at diagnosis. Although most patients (81%) met criteria for "probable DHF" by recently proposed clinical criteria, only half of patients met European criteria in which evidence of abnormal function/filling is required. The 1-, 2-, and 3-year mortality rates were 29%, 39%, and 60%, respectively. Angiotensin-converting enzyme inhibition (P =.0008) and beta-blocker (P =.02) therapy were independently associated with improved survival. CONCLUSION: This population-based study provides a comprehensive clinical profile, current management, prognosis, and predictors of outcome of patients with new onset CHF who had normal ejection fraction.

Adult↗

A Monte Carlo investigation of fluence profiles collimated by an electron specific MLC during beam delivery for modulated electron radiation therapy.

Modulated electron radiation therapy (MERT) is able to deliver conformal dose to shallow tumors while significantly reducing dose to distal structures and surrounding tissues. An electron specific multileaf collimator (eMLC) has been proposed and constructed as an effective means of delivering electron beams for MERT. The aim of this work is to apply the Monte Carlo method to investigate the fluence profiles collimated by the eMLC in order to achieve accurate beam delivery for MERT. In this work, the EGS4/BEAM code was used to simulate the eMLC collimated electron beams of 6-20 MeV generated from a Varian Clinac 2100C linear accelerator. An attempt was made to describe the fluence profiles with an analytic Sigmoid function. The function parameters were determined by the fittings of the Monte Carlo simulated fluence profiles. How the function parameters depend on the eMLC aperture size, the off-axis location, and the electron beam energy has been investigated. It has been found that the eMLC collimated fluence profiles are dependent on beam energy, while almost independent of leaf location or dimension of MLC aperture. There is little difference in the fluence profiles collimated by the leaf side and the leaf end for the straight-edged leaves. It is possible that these energy-dependent Sigmoid functions can serve as operators to account for the energy dependence of the eMLC collimated fluence profiles. These operators can be incorporated into the inverse planning algorithm to derive desired dose distributions using a set of electron beams of variable energy and field size suitable for delivery by the eMLC.

Computer Simulation↗