Ed Boas — Selected publications

Research overviews »

Radiology
Molecular modeling and design

 


24 papers, cited 1194 times.
★ indicates especially notable or interesting publications.

Papers

16. Boas FE, Kadivar F, Kelly PD, Drebin JA, Vollmer CM, Shlansky-Goldberg RD. (2015) "Targeted transgastric drainage of isolated pancreatic duct segments to cure persistent pancreaticocutaneous fistulas from pancreatitis." J Vasc Interv Radiol. 26(2): 247-51. More »
Chronic pancreaticocutaneous fistulas can be difficult to treat. This paper presents a snare-target technique for draining a non-dilated pancreatic duct into the stomach, thus diverting pancreatic fluid away from the pancreaticocutaneous fistula to allow it to heal. Internal or internal/external transgastric pancreatic duct or fistula drains were placed in 6 patients. After an average of 4 months of drainage, all 6 patients had resolution of the cutaneous fistula. 2 patients developed a pseudocyst but no recurrent fistula after drain removal, and the other 4 had no pseudocyst or fistula after an average of 27 months follow up (range 6-74 months).
★ 15. Boas FE, Do B, Louie JD, Kothary N, Hwang GL, Kuo WT, Hovsepian DM, Kantrowitz M, Sze DY. (2015) "Optimal imaging surveillance schedules after liver-directed therapy for hepatocellular carcinoma." J Vasc Interv Radiol. 26(1): 69-73. More »
Purpose: To optimize surveillance schedules for detecting recurrent hepatocellular carcinoma (HCC) after liver-directed therapy.

Materials and Methods: New methods have emerged that allow quantitative analysis and optimization of surveillance schedules for diseases with substantial rates of recurrence such as HCC. We applied these methods to 1766 consecutive chemoembolization (TACE), radioembolization (RE), and radiofrequency ablation (RFA) procedures performed on 910 patients between 2006 and 2011. The CT or MRI obtained just prior to repeat therapy was set as the time of recurrence. "Recurrence" included residual and locally recurrent tumor, as well as new liver tumors. Time-to-recurrence distribution was estimated using Kaplan-Meier. Average diagnostic delay (time between recurrence and detection) was calculated for each proposed surveillance schedule, using the time-to-recurrence distribution. An optimized surveillance schedule could then be derived to minimize the average diagnostic delay.

Results: Recurrence is 6.5 times more likely in the first year after treatment, compared to the second. Therefore, screening should be much more frequent in the first year. For 8 time points in the first 2 years of follow-up, the optimal schedule is 2, 4, 6, 8, 11, 14, 18, and 24 months. This schedule reduces diagnostic delay compared to published schedules, and is cost effective.

Conclusion: The calculated optimal surveillance schedules include shorter interval follow-up when there is a higher probability of recurrence, and longer interval follow-up when there is a lower probability. Cost can be optimized for a specified acceptable diagnostic delay, or diagnostic delay can be optimized within a specified acceptable cost.
★ 14. Boas FE, Kamaya A, Do B, Desser TS, Beaulieu CF, Vasanawala SS, Hwang GL, Sze DY. (2015) "Classification of hypervascular liver lesions based on hepatic artery and portal vein blood supply coefficients calculated from triphasic CT scans." Journal of Digital Imaging. 28: 213-23. More »
Perfusion CT of the liver typically involves scanning the liver at least 20 times, resulting in a large radiation dose. We developed and validated a simplified model of tumor blood supply that can be applied to standard triphasic scans, and evaluated whether this can be used to distinguish benign and malignant liver lesions. Triphasic CTs of 46 malignant and 32 benign liver lesions were analyzed. For each phase, regions of interest were drawn in the arterially enhancing portion of each lesion, as well as the background liver, aorta, and portal vein. Hepatic artery and portal vein blood supply coefficients for each lesion were then calculated by expressing the enhancement curve of the lesion as a linear combination of the enhancement curves of the aorta and portal vein. Hepatocellular carcinoma (HCC) and hypervascular metastases on average both had increased hepatic artery coefficients compared to the background liver. Compared to HCC, benign lesions on average had either a greater hepatic artery coefficient (hemangioma), or greater portal vein coefficient (focal nodular hyperplasia, or transient hepatic attenuation difference). Hypervascularity with washout is a key diagnostic criterion for HCC, but it had a sensitivity of 72% and specificity of 81% for diagnosing malignancy in our diverse set of liver lesions. The sensitivity for malignancy was increased to 89% by including enhancing lesions that were hypodense on all phases. The specificity for malignancy was increased to 97% (p=0.039) by also examining hepatic artery and portal vein blood supply coefficients, while maintaining a sensitivity of 76%.
13. Olcott EW, Shin LK, Sommer G, Chan I, Rosenberg J, Molvin FL, Boas FE, Fleischmann D. (2014) "Model-based Iterative Reconstruction Compared to Adaptive Statistical Iterative Reconstruction and Filtered Back-projection in CT of the Kidneys and the Adjacent Retroperitoneum." Academic radiology. 21(6): 774-84.

★ 12. Boas FE and Fleischmann D (2012). "CT artifacts: Causes and reduction techniques." Imaging in Medicine. 4(2): 229-40. More »
Artifacts are commonly encountered in clinical computed tomography (CT), and may obscure or simulate pathology. There are many different types of CT artifacts, including noise, beam hardening, scatter, pseudoenhancement, motion, cone beam, helical, ring, and metal artifacts. We review the cause and appearance of each type of artifact, correct some popular misconceptions, and describe modern techniques for artifact reduction. Noise can be reduced using iterative reconstruction or by combining data from multiple scans. This enables lower radiation dose and higher resolution scans. Metal artifacts can also be reduced using iterative reconstruction, resulting in more accurate diagnosis. Dual and multi-energy (photon counting) CT can reduce beam hardening and provide better tissue contrast. Methods for reducing noise and out-of-field artifacts may enable ultra-high resolution limited-field-of-view imaging of tumors and other structures.
11. Abelson JA, Murphy JD, Wiegner EA, Abelson D, Sandman DN, Boas FE, Hristov D, Fleischmann D, Daly ME, Chang DT, Loo BW, Hara W, Le QT. (2011) "Evaluation of a metal artifact reduction technique in tonsillar cancer delineation." Practical Radiation Oncology. 2(1): 27-34. More »

★ 10. Boas FE and Fleischmann D. (2011) "Evaluation of two iterative techniques for reducing metal artifacts in computed tomography." Radiology. 259(3): 894-902. More »
Purpose: To evaluate two methods for reducing metal artifacts in computed tomography (CT)—the metal deletion technique (MDT) and the selective algebraic reconstruction technique (SART)—and compare these methods with filtered back projection (FBP) and linear interpolation (LI).

Materials and Methods: The institutional review board approved this retrospective HIPAA-compliant study; informed patient consent was waived. Simulated projection data were calculated for a phantom that contained water, soft tissue, bone, and iron. Clinical projection data were obtained retrospectively from 11 consecutively identified CT scans with metal streak artifacts, with a total of 178 sections containing metal. Each scan was reconstructed using FBP, LI, SART, and MDT. The simulated scans were evaluated quantitatively by calculating the average error in Hounsfield units for each pixel compared with the original phantom. Two radiologists who were blinded to the reconstruction algorithms used qualitatively evaluated the clinical scans, ranking the overall severity of artifacts for each algorithm. P values for comparisons of the image quality ranks were calculated from the binomial distribution.

Results: The simulations showed that MDT reduces artifacts due to photon starvation, beam hardening, and motion and does not introduce new streaks between metal and bone. MDT had the lowest average error (76% less than FBP, 42% less than LI, 17% less than SART). Blinded comparison of the clinical scans revealed that MDT had the best image quality 100% of the time (95% confidence interval: 72%, 100%). LI had the second best image quality, and SART and FBP had the worst image quality. On images from two CT scans, as compared with images generated by the scanner, MDT revealed information of potential clinical importance.

Conclusion: For a wide range of scans, MDT yields reduced metal streak artifacts and better-quality images than does FBP, LI, or SART.
9. Fleischmann D and Boas FE. (2011) "Computed tomography: Old ideas and new technology." European Radiology. 21: 510-17. More »
Several recently introduced 'new' techniques in computed tomography—iterative reconstruction, gated cardiac CT, multiple-source, and dual-energy CT—actually date back to the early days of CT. We review the historic origins and evolution of these techniques, which may provide some insight into the latest innovations in commercial CT systems.
★ 8. Boas FE, Harbury PB. (2008) "Design of protein-ligand binding based on the molecular-mechanics energy model." Journal of Molecular Biology. 380: 415-24. More »
While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual labs. Here we show that a standard molecular-mechanics potential energy function without any modifications can be used to engineer protein-ligand binding. A molecular-mechanics potential is used to reconstruct the coordinates of various binding sites with an average root mean square error of 0.61 Å, and to reproduce known ligand-induced side-chain conformational shifts. Within a series of 34 mutants, the calculation can always distinguish weak (Kd > 1 mM) and tight (Kd < 10 μM) binding sequences. Starting from partial coordinates of the ribose binding protein lacking the ligand and the ten primary contact residues, the molecular-mechanics potential is used to redesign a ribose binding site. Out of a search space of 2×1012 sequences, the calculation selects a point mutant of the native protein as the top solution (experimental Kd = 17 μM), and the native protein as the second best solution (experimental Kd = 210 nM). The quality of the predictions depends on the accuracy of the generalized Born electrostatics model, treatment of protonation equilibria, high resolution rotamer sampling, a final local energy minimization step, and explicit modeling of the bound, unbound, and unfolded states. The application of unmodified molecular-mechanics potentials to protein design links two fields in a mutually beneficial way. Design provides a new avenue to test molecular-mechanics energy functions, and future improvements in these energy functions will presumably lead to more accurate design results.
Key words: protein design, generalized Born, force field, dissociation constant, structure prediction.
7. Boas FE and Harbury PB. (2007) "Potential energy functions for protein design." Current Opinion in Structural Biology. 17: 199-204. More »
Different potential energy functions have predominated in protein dynamics simulations, protein design calculations, and protein structure prediction. Clearly, the same physics applies in all three cases. The differences in potential energy functions reflect differences in how the calculations are performed. With improvements in computer power and algorithms, the same potential energy function should be applicable to all three problems. In this review, we examine energy functions currently used for protein design, and look to the molecular mechanics field for advances that could be used in the next generation of design algorithms. In particular, we focus on improved models of the hydrophobic effect, polarization and hydrogen bonding.
6. Bass JL, Bhatia A, Boas FE, Sansary J, Rauch D. (2006) "Validation of a body mass index nomogram for children as an obesity screening tool in young children." Clinical Pediatrics. 45(8): 718-24. More »

5. Arava Y, Boas FE, Brown PO, Herschlag D. (2005) "Dissecting eukaryotic translation and its control by ribosome density mapping." Nucleic Acids Research. 33(8):2421-32. More »
Translation of an mRNA is generally divided into three stages: initiation, elongation and termination. The relative rates of these steps determine both the number and position of ribosomes along the mRNA, but traditional velocity sedimentation assays for the translational status of mRNA determine only the number of bound ribosomes. We developed a procedure, termed Ribosome Density Mapping (RDM), that uses site-specific cleavage of polysomal mRNA followed by separation on a sucrose gradient and northern analysis, to determine the number of ribosomes associated with specified portions of a particular mRNA. This procedure allows us to test models for translation and its control, and to examine properties of individual steps of translation in vivo. We tested specific predictions from the current model for translational control of GCN4 expression in yeast and found that ribosomes were differentially associated with the uORFs elements and coding region under different growth conditions, consistent with this model. We also mapped ribosome density along the ORF of several mRNAs, to probe basic kinetic properties of translational steps in yeast. We found no detectable decline in ribosome density between the 5' and 3' ends of the ORFs, suggesting that the average processivity of elongation is very high. Conversely, there was no queue of ribosomes at the termination site, suggesting that termination is not very slow relative to elongation and initiation. Finally, the RDM results suggest that less frequent initiation of translation on mRNAs with longer ORFs is responsible for the inverse correlation between ORF length and ribosomal density that we observed in a global analysis of translation. These results provide new insights into eukaryotic translation in vivo.
★ 4. Boas FE. (2000) "Linkage to Gaucher mutations in the Ashkenazi population: Effect of drift on decay of linkage disequilibrium and evidence for heterozygote selection." Blood Cells, Molecules, and Diseases. 26(4): 348-59. More »
The two most common Gaucher disease mutations in the Ashkenazi population, 1226A→G and 84G→GG in the glucocerebrosidase gene, are tightly linked to a marker in the nearby pyruvate kinase gene. This paper develops a simulation of the Ashkenazi population that considers the effects of selection and drift on the mutant allele frequency and the recombinant haplotype frequency over time. Although the fraction of mutants that are linked to the original marker decays exponentially on average, this expected value is not very likely to occur. Instead, due to random loss of the recombinant haplotype, a mutation has a significant probability of retaining complete linkage disequilibrium long after its origin, so there may be large errors in estimating the age of a mutation based on linkage data. The simulations show that the 1226G mutation probably originated between 40 and 1000 generations ago (1000 to 25,000 years ago), and the 84GG mutation probably originated between 50 and 4800 generations ago (1300 to 120,000 years ago). The recent origin of the 1226G mutation and its high current allele frequency provide strong evidence for heterozygote selection. New techniques and results developed in this paper have general applicability towards analyzing linkage disequilibrium near other mutations. For example, they potentially explain the unexpected pattern of linkage disequilibrium seen around the ΔF508 mutation of the cystic fibrosis transmembrane conductance regulator gene.
Key words: Gaucher disease, linkage disequilibrium, heterozygote advantage, genetic drift, Ashkenazi, computer simulation
3. Demina A, Boas E, and Beutler E. (1998) "Structure and linkage relationships of the region containing the human L-type pyruvate kinase (PKLR) and glucocerebrosidase (GBA) genes." Hematopathol. Mol. Hematol. 11(2): 63-71.
Both the L-type pyruvate kinase gene (PKLR) and glucocerebrosidase (GBA) gene are on band q21 of chromosome 1 in humans. Two overlapping P1 bacteriophage clones containing PKLR and GBA were identified and mapped, defining the locations of these two genes as well as those of the GBA pseudogene (ΨGBA), metaxin (MTX), the MTX pseudogene (ΨMTX), and thrombospondin 3 (THBS3). The distance between 5' ends of GBA and PKLR was determined to be 71 kb. The direction of transcription of the PKLR gene was convergent to that of the GBA gene. All 195 Gaucher disease patients homozygous for the 1226G mutation, representing 390 chromosomes with the 1226G mutation, had a PvuII −/− GBA haplotype and a C/C at nt 1705 of the PKLR gene (−/− haplotype). All 56 Gaucher disease patients who were 1226G/84GG compound heterozygotes manifested a −/+ GBA haplotype and 55 of 56 patients were −/+ at PKLR nt 1705. Only 1 patient with 1226G/84GG genotype showed a crossover with the PKLR polymorphism, with a −/− haplotype at nt 1705. Similarly, 9 patients deficient in pyruvate kinase with the PKLR 1529A/1529A genotype were all found to have the same −/− GBA haplotype.
Key words: Gaucher disease, anemia, hemolytic, mapping, polymorphism, linkage.
★ 2. Boas FE, Forman L, and Beutler E. (1998) "Phosphatidylserine exposure and red cell viability in red cell aging and in hemolytic anemia." Proc. Natl. Acad. Sci., USA. 95: 3077-3081. More »
Phosphatidylserine (PS) normally localizes to the inner leaflet of cell membranes but becomes exposed in abnormal or apoptotic cells, signaling macrophages to ingest them. Along similar lines, it seemed possible that the removal of red cells from circulation because of normal aging or in hemolytic anemias might be triggered by PS exposure. To investigate the role of PS exposure in normal red cell aging, we used N-hydroxysuccinimide-biotin to tag rabbit red cells in vivo, then used phycoerythrin-streptavidin to label the biotinylated cells, and annexin V-fluorescein isothiocyanate (FITC) to detect the exposed PS. Flow cytometric analysis of these cells drawn at 10-day intervals up to 70 days after biotinylation indicated that older, biotinylated cells expose more PS. Furthermore, our data match a simple model of red cell senescence that assumes both an age-dependent destruction of senescent red cells preceded by several hours of PS exposure and a random destruction of red cells without PS exposure. By using this model, we demonstrated that the exposure of PS parallels the rate at which biotinylated red cells are removed from circulation. On the other hand, using an annexin V-FITC label and f low cytometry demonstrates that exposed PS does not cause the reduced red cell life span of patients with hemolytic anemia, with the possible exception of those with unstable hemoglobins or sickle cell anemia. Thus, in some cases PS exposure on the cell surface may signal the removal of red cells from circulation, but in other cases some other signal must trigger the sequestration of cells.
1. Ahn CS, Boas E, and Rahn B. (1997) "The geometry and the game theory of chases." The UMAP Journal. 18.3: 225-242. More »
(We investigate the hunting and fleeing strategies of a fast predator and its agile prey in a chase of finite time.)


Talks and abstracts

14. Boas FE, Kelly P, and Shlansky-Goldberg R. (2014) "Targeted transgastric drainage of persistent pancreaticocutaneous fistulas." JVIR 25(3): S41. Presented at SIR, San Diego, 2014-03-23. More »

13. Do BH, Boas FE, Muelly M, Massaband PM, Biswal S. (2013) "Simplying the understanding of shoulder labral tears using a multimedia reporting enabled PACS." Presented at RSNA, Chicago, 2013.

12. Boas F, Kamaya A, Do B, Beaulieu C, Desser T, Vasanawala S, Hwang G, Sze D. (2013) "Hepatic artery and portal vein blood volumes in hypervascular liver lesions: Estimation from triphasic CT scans." Presented at ARRS, Washington, DC, 2013-04-15. More »

11. Blake T, Dao C, Boas FE, Fearon W, Miller D, Fleischmann D. (2012) "CT-based instantaneous calculation of viewing angles for device deployment in patients undergoing transcatheter aortic valve replacement (TAVR)." Presented at RSNA, Chicago, 2012-11-27. More »

10. Boas FE, Bammer R, Fleischmann D. (2012) "Optimized CT metal artifact reduction using the Metal Deletion Technique (MDT)." Presented at RSNA, Chicago, 2012-11-26. More »

9. Boas FE. (2012) "CT metal artifact reduction and other image post-processing applications." Stanford Radiology grand rounds, Stanford, CA, 2012-04-03. More »

8. Fleischmann D, Dao C, Blake T, Boas FE, Liang D, Yeung, A, Fearon W, Fischbein M, Miller DC. (2012) "Computed tomography based prediction of angiographic deployment angles may reduce procedure time and contrast medium volume for transcatheter aortic valve replacement." J Am Coll Cardiol. 59(13s1):E1199-E1199. More »

7. Fleischmann D, Boas FE, Tye GA, Sheahan D, Molvin LZ. (2011) "Effect of low radiation dose on image noise and subjective image quality for analytic vs iterative image reconstruction in abdominal CT." Presented at RSNA, Chicago, 2011-12-01.

6. Boas FE. (2011) "Iterative techniques for metal artifact reduction." Presented at the International Society for Computed Tomography meeting, San Francisco, 2011-06-13. More »

★ 5. Boas FE, Desser TS, and Kamaya A. (2011) "Does separating the resistive index into pre- and postglomerular resistance and vascular compliance improve upon the diagnostic accuracy of renal transplant doppler sonography?" AJR 196(5): A31-35. Presented at ARRS, Chicago, 2011-05-03. More »
Objective: Doppler ultrasound resistive index (RI) is a widely used parameter in the assessment of renal transplant function, but current work suggests that its sensitivity and specificity for acute rejection is low. Although RI (which is a measure of pulsatile flow) does increase with postglomerular vascular resistance, it also increases with increased vascular compliance, decreased preglomerular vascular resistance, increased pulse pressure, and increased heart rate. We postulated that separating out these potentially confounding factors and directly calculating vascular resistance and compliance would allow for more accurate assessment of kidney transplants.

Materials and Methods: Forty-seven kidney transplant ultrasound studies were analyzed. RI was measured at the segmental renal arteries. We modeled the transplanted kidney vasculature as a tube with a preglomerular and postglomerular vascular resistance, and a vascular compliance (three-element Windkessel model). This model accurately describes in vivo blood flow in rat kidneys. The parameters were adjusted to fit the experimental mid renal artery velocity waveforms, given the patient's vital signs.

Results: Normal transplant kidneys have an average RI of 0.71 ± 0.11, and kidneys in acute rejection have an RI of 0.77 ± 0.11. Using a cutoff of 0.8 results in a sensitivity of 38% and specificity of 63% for acute rejection. An RI greater than 1 was only seen in renal vein thrombosis (two cases). Waveforms for acute rejection, chronic rejection, hydronephrosis, and delayed graft function had a large amount of overlap with normal waveforms. Using the three-element Windkessel model, we showed that these four diagnoses are associated with vascular resistances and compliances within 1 SD of normal, and none of the differences were statistically significant. On the other hand, renal vein thrombosis is associated with a nonsignificant increase in postglomerular resistance and significant decreases in preglomerular resistance (p = 0.01) and vascular compliance (p = 0.0003).

Conclusion: Doppler ultrasound of kidney transplants has limited value in diagnosing acute rejection. We examined RI, preglomerular resistance, postglomerular resistance, vascular compliance, and the shape of the mid renal artery velocity waveform. None of these variables could reliably predict acute rejection, chronic rejection, hydronephrosis, or delayed graft function. However, RI greater than 1 was associated with renal vein thrombosis in two out of two cases.
4. Golden C, Mazin SR, Boas FE, Tye G, Ghanouni P, Gold G, Sofilos M, Pelc NJ. (2011) "A comparison of four algorithms for metal artifact reduction in CT imaging." Proc. SPIE. 7961: 79612Y. More »
Streak artifacts caused by the presence of metal have been a significant problem in CT imaging since its inception in 1972. With the fast evolving industry of medical devices, the level of metal objects implanted in patients is increasing annually. This correlates directly with an increased likelihood of encountering metal in a patient CT scan, thus necessitating the need for an effective and reproducible metal artifact reduction (MAR) algorithm. Comparisons between MAR algorithms have been limited by the range of metal implants evaluated and the scope of anatomical regions from which patient data was taken. Although, the results of many methods are promising [1-4], the reproducibility of these results is key to providing more tangible evidence of their effectiveness. This study presents a direct comparison between the performances of four MAR algorithms: 3 non-iterative and one iterative method, all applied and compared to the original clinical DICOM images. The results of the evaluation indicated a negative mean score in almost all uses for two of the non-iterative methods, signifying an overall decrease in the diagnostic quality of the images, generally due to perceived loss of detail. One non-iterative algorithm showed a slight improvement. The iterative algorithm was superior in all studies by producing a considerable improvement in all uses.
3. Boas FE and Fleischmann D. (2010) "Evaluation of the metal deletion technique (MDT): A new method for reducing metal streak artifacts in computed tomography scans." Presented at RSNA, Chicago, 2010-11-29. More »
Purpose. Current techniques for reducing metal streak artifacts in CT images have not achieved widespread clinical use, and they introduce new artifacts. We present a a simple new method, called the Metal Deletion Technique (MDT), and compare it to existing methods.

Materials and Methods. Simulated projection data was calculated for a phantom containing water, soft tissue, bone, and iron. Experimental projection data was obtained for 11 consecutively identified patients with metal streak artifact scanned at our Siemens Sensation 64 CT scanner. Each scan was reconstructed using filtered backprojection (FBP), linear interpolation (LI), selective algebraic reconstruction technique (SART), and MDT. The MDT algorithm works as follows. First, an adaptive filter is applied to the experimental projection data that effectively expands the detectors in regions with low photon counts. Next, the initial image is constructed using a combination of FBP and LI. Finally, metal pixels are erased, and filtered backprojection is iterated 4 times. On each iteration, rays that pass through metal are replaced with forward projected values from the previous iteration.

Results. The simulations showed that MDT reduces artifacts due to photon counting noise, beam hardening, and motion, while avoiding new artifacts. MDT had the lowest root-mean-square error: 76% less than FBP, 42% less than LI, and 17% less than SART. For the experimental scans, a blinded comparison showed that MDT had the best image quality 100% of the time (95% confidence interval: 78 to 100%). No manual steps or adjustment of parameters was necessary. In two of the scans, MDT changed the radiologic diagnosis. In one case, peri-rectal lymphadenopathy obscured by hip replacement artifacts were identified in a patient with a history of rectal cancer. In the second case, a pacemaker lead that appeared to perforate through the right ventricle was seen to be non-perforated.

Conclusion. MDT reduces metal streak artifacts and produces better quality images than FBP, LI, or SART, for a wide range of scans.

Clinical relevance. MDT is a promising new technique for reducing metal streak artifacts in CT scans. It is the first metal artifact reduction technique that has been shown to change the radiologic diagnosis.
2. Boas FE, Forman L, and Beutler E. (1997) "Phosphatidylserine exposure and red cell viability in red cell ageing, storage, and in hemolytic anemia." Blood. 90.10 (Supplement 1, Part 1): 272a.

1. Boas FE, Forman L, and Beutler E. (1997) "Phosphatidylserine exposure in red cell aging." The Scripps Research Institute Scientific Report 1996-97. pp. 258-60.


Other publications

4. Boas FE. (2012) "Iterative reduction of artifacts in computed tomography images using forward projection and an edge-preserving blur filter." U.S. Patent 8233586. More »

★ 3. Boas FE. (2008) Physics-Based Design of Protein-Ligand Binding. PhD dissertation, Department of Biochemistry, Stanford University. More »
Different potential energy functions have been used in protein dynamics simulations, protein design calculations, and protein structure prediction. Clearly, the same physics applies in all three cases, so the variation in potential energy functions reflects differences in how the calculations are performed. With improvements in computer power and algorithms, the same potential energy function should be applicable to all three problems.

Here we show that a standard molecular-mechanics potential energy function without any modifications can be used to engineer protein-ligand binding. A molecular-mechanics potential is used to reconstruct the coordinates of various binding sites with an average root mean square error of 0.61 Å, and to reproduce known ligand-induced side-chain conformational shifts. Within a series of 34 mutants, the calculation can always distinguish weak (Kd > 1 mM) and tight (Kd < 10 μM) binding sequences. Starting from partial coordinates of the ribose binding protein lacking the ligand and the ten primary contact residues, the molecular-mechanics potential is used to redesign a ribose binding site. Out of a search space of 2×1012 sequences, the calculation selects a point mutant of the native protein as the top solution (experimental Kd = 17 μM), and the native protein as the second best solution (experimental Kd = 210 nM). The quality of the predictions depends on the accuracy of the generalized Born electrostatics model, treatment of protonation equilibria, high resolution rotamer sampling, a final local energy minimization step, and explicit modeling of the bound, unbound, and unfolded states.

After this initial proof of principle experiment, we next used a standard molecular mechanics potential energy function to redesign ribose binding protein to bind a series of ligands: L-arabinose, D-xylose, indole-3-acetic acid, and estradiol. The resulting proteins have 5 - 10 mutations from the native, are stable, the predicted structures have good hydrogen bonds and shape complementarity, and they use motifs similar to natural binding proteins. All of the designed proteins bind to their target ligands with measurable but weak affinity. The affinity was improved by random mutagenesis and screening.

The application of unmodified molecular-mechanics potentials to protein design links two fields in a mutually beneficial way. Design provides a new avenue to test molecular-mechanics energy functions, and future improvements in these energy functions will presumably lead to more accurate design results.

This is the first time a single model has been used to predict structures, binding constants, and to design new small-molecule binding sites. Using a standard model should improve the generality of protein design, which could enable the creation of custom proteins for a wide variety of applications, including sensors, enzymes, and protein therapeutics.
2. Boas FE. (2008) "Methods and apparatus for reducing artifacts in computed tomography images." U.S. Patent Application 2008/0273651 (abandoned). More »
We present an iterative method for reducing artifacts in computed tomography (CT) images. In each iteration, constraints such as non-negativity are applied, then the image is blurred to guide convergence to a smoother image. Next, the image is modified using an algebraic reconstruction algorithm to try to match the projection data to within the experimental error. A mask is calculated which specifies which parts of the image to update during each iteration. The mask allows us to first solve regions of the image that are determined by rays with low photon counts (and thus high error). Then, regions of the image determined by rays with higher photon counts (and thus lower error), are solved using those ray sums. Reducing CT scan artifacts results in clearer and higher resolution images, faster scan times, and less radiation use.
★ 1. Boas FE. (1999) "Polyvalent inhibitors of Pseudomonas aeruginosa adhesion." Senior honors thesis, Harvard University. More »
We synthesized polymers displaying multiple copies of a peptide from the cystic fibrosis transmembrane conductance regulator (residues 108-117). This peptide is the minimal sequence needed for binding of Pseudomonas aeruginosa. Using an in vitro bacterial internalization assay, our preliminary results indicate that such a polyvalent ligand can prevent P. aeruginosa from attaching to (and being internalized by) epithelial cells. The most effective polymer we synthesized was a polyacrylamide with CFTR peptide covalently attached to 0.5% of its acrylamide subunits. This polymer has an IC50 value of 700 pM, 40,000 times lower than monovalent CFTR peptide. Polyacrylamide at the same concentration does not inhibit internalization.

We also developed a simulation to qualitatively describe how a polyvalent ligand binds to a surface. This simulation demonstrates that the polymer binds to the surface cooperatively. Binding can be enhanced by a larger degree of polymerization, a larger fraction of polymer subunits that can attach to the surface, and greater diffusibility of binding sites on the surface.

Unpublished research

Does catheter cavography before IVC filter retrieval lower procedural supply costs? (2015)
Calculating the probability of malignancy of thyroid nodules using adjusted naïve Bayes (2011)
Virtual angiography (2007)
High dynamic range images in radiology (2007)
Proposal for intelligent drug delivery by engineered encapsulated cells (2004)
Predicting protein binding sites (2000)
Gallery of coiled coils (2001)


Last updated: 2015-11-23
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