Resource estimation in high performance medical image computing.

Medical imaging analysis processes often involve the concatenation of many steps (e.g., multi-stage scripts) to integrate and realize advancements from image acquisition, image processing, and computational analysis. With the dramatic increase in data size for medical imaging studies (e.g., improved resolution, higher throughput acquisition, shared databases), interesting study designs are becoming intractable or impractical on individual workstations and servers. Modern pipeline environments provide control structures to distribute computational load in high performance computing (HPC) environments. However, high performance computing environments are often shared resources, and scheduling computation across these resources necessitates higher level modeling of resource utilization. Submission of 'jobs' requires an estimate of the CPU runtime and memory usage. The resource requirements for medical image processing algorithms are difficult to predict since the requirements can vary greatly between different machines, different execution instances, and different data inputs. Poor resource estimates can lead to wasted resources in high performance environments due to incomplete executions and extended queue wait times. Hence, resource estimation is becoming a major hurdle for medical image processing algorithms to efficiently leverage high performance computing environments. Herein, we present our implementation of a resource estimation system to overcome these difficulties and ultimately provide users with the ability to more efficiently utilize high performance computing resources.

Analysis of vocal tract characteristics for near-term suicidal risk assessment.

OBJECTIVES: Among the many clinical decisions that psychiatrists must make, assessment of a patient's risk of committing suicide is definitely among the most important, complex and demanding. One of the authors reviewing his clinical experience observed that successful predictions of suicidality were often based on the patient's voice independent of content. The voices of suicidal patients exhibited unique qualities, which distinguished them from non-suicidal patients. In this study we investigated the discriminating power of lower order mel-cepstral coefficients among suicidal, major depressed, and non-suicidal patients. METHODS: Our sample consisted of 10 near-term suicidal patients, 10 major depressed patients, and 10 non-depressed control subjects. Gaussian mixtures were employed to model the class distributions of the extracted features. RESULTS AND CONCLUSIONS: As a result of two-sample ML classification analyses, first four mel-cepstral coefficients yielded exceptional classification performance with correct classification scores of 80% between near-term suicidal patients and non-depressed controls, 75% between depressed patients and non-depressed controls, and 80% between near-term suicidal patients and depressed patients.

Multiwavelet prefilters--part II: optimal orthogonal prefilters.

Prefiltering a given discrete signal has been shown to be an essential and necessary step in applications using unbalanced multiwavelets. In this paper, we develop two methods to obtain optimal second-order approximation preserving prefilters for a given orthogonal multiwavelet basis. These procedures use the prefilter construction introduced in part I of this paper. The first prefilter optimization scheme exploits the Taylor series expansion of the prefilter combined with the multiwavelet. The second one is achieved by minimizing the energy compaction ratio (ECR) of the wavelet coefficients for an experimentally determined average input spectrum. We use both methods to find prefilters for the cases of the DGHM and Chui-Lian (CL) multiwavelets. We then compare experimental results using these filters in an image compression scheme. Additionally, using the DGHM multiwavelet with the optimal prefilters from the first scheme, we find that quadratic input signals are annihilated by the high-pass portion of the filter bank at the first level of decomposition.

Acoustical properties of speech as indicators of depression and suicidal risk.

Acoustic properties of speech have previously been identified as possible cues to depression, and there is evidence that certain vocal parameters may be used further to objectively discriminate between depressed and suicidal speech. Studies were performed to analyze and compare the speech acoustics of separate male and female samples comprised of normal individuals and individuals carrying diagnoses of depression and high-risk, near-term suicidality. The female sample consisted of ten control subjects, 17 dysthymic patients, and 21 major depressed patients. The male sample contained 24 control subjects, 21 major depressed patients, and 22 high-risk suicidal patients. Acoustic analyses of voice fundamental frequency (Fo), amplitude modulation (AM), formants, and power distribution were performed on speech samples extracted from audio recordings collected from the sample members. Multivariate feature and discriminant analyses were performed on feature vectors representing the members of the control and disordered classes. Features derived from the formant and power spectral density measurements were found to be the best discriminators of class membership in both the male and female studies. AM features emerged as strong class discriminators of the male classes. Features describing Fo were generally ineffective discriminators in both studies. The results support theories that identify psychomotor disturbances as central elements in depression and suicidality.

Expression and purification of the first nucleotide-binding domain and linker region of human multidrug resistance gene product: comparison of fusions to glutathione S-transferase, thioredoxin and maltose-binding protein.

Many membrane proteins that belong to the ATP-binding cassette (ABC) superfamily are clinically important, including the cystic fibrosis transmembrane conductance regulator, the sulphonylurea receptor and P-glycoprotein (multidrug resistance gene product; MDR1). These proteins contain two multispanning transmembrane domains, each followed by one nucleotide-binding domain (NBD) and a linker region distal to the first NBD. ATP hydrolysis by the NBDs is critical for ABC protein function; the linker region seems to have a regulatory role. Previous attempts to express soluble NBDs and/or linker regions without detergent solubilization, or to purify NBDs at high yields as soluble fusion proteins, have been unsuccessful. Here we present a system for the expression in Escherichia coli of the first NBD of MDR1 followed by its linker region (NBD1MLD). A comparison of the expressions of NBD1MLD fused to glutathione S-transferase, thioredoxin and maltose-binding protein (MBP) shows that a high level of expression in the soluble fraction (approx. 8% of total E. coli protein) can be achieved only for MBP-NBD1MLD. The addition of a proteolytic thrombin site just proximal to the N-terminal end of NBD1MLD allows the cleavage of NBD1MLD from MBP, which can be easily purified with retention of its ATPase activity. In summary, success was obtained only when using an MBP fusion protein vector containing a thrombin proteolytic site between MBP and NBD1MLD. The approach described here could be generally applicable to solving the problems of expression and purification of NBDs/linker regions of ABC proteins.

Comparison of the immune response to recombinant gp120 in humans and chimpanzees.

OBJECTIVE: To assess similarities and differences in antibody responses to recombinant (r) HIV-1IIIB gp120 in chimpanzees, previously protected from HIV-1 infection, and human volunteers immunized in connection with a Phase I clinical trial. METHODS: Frozen sera from humans immunized with rgp120 from HIV-1IIIB and chimpanzees immunized with the same antigen or recombinant soluble gp160 were compared in a variety of serologic assays. RESULTS: The magnitude of the antibody response to gp120 was similar in both species; however, the half-life of the antibody response to rgp120 was approximately 4.5 times longer in humans (9 weeks) than in chimpanzees (2 weeks). Antibodies to gp120 in both species were broadly cross-reactive with gp120 from diverse isolates of HIV-1 and were effective in blocking the binding of gp120 to CD4. Antibody binding to native gp120 was greater than to denatured gp120 in both species. Antibody responses to the principal neutralizing determinant (V3 domain) and virus neutralization titers were approximately 10-fold lower in humans than chimpanzees. The relative avidity of antibody binding to gp120 was higher in the sera from the immunized chimpanzees than in the immunized humans. CONCLUSIONS: While the antibody responses to rgp120 elicited in man and chimpanzees were in many ways similar, significant differences did occur. Predictions made on the basis of chimpanzee immunogenicity studies over-estimated the potency of the virus neutralizing titers and under-estimated the duration of the antibody response achieved in humans.

Strain specificity and binding affinity requirements of neutralizing monoclonal antibodies to the C4 domain of gp120 from human immunodeficiency virus type 1.

The binding properties of seven CD4-blocking monoclonal antibodies raised against recombinant gp120 of human immunodeficiency virus type 1 strain MN (HIV-1MN) and two CD4-blocking monoclonal antibodies to recombinant envelope glycoproteins gp120 and gp160 of substrain IIIB of HIVLAI were analyzed. With a panel of recombinant gp120s from seven diverse HIV-1 isolates, eight of the nine antibodies were found to be strain specific and one was broadly cross-reactive. Epitope mapping revealed that all nine antibodies bound to epitopes located in the fourth conserved domain (C4) of gp120. Within this region, three distinct epitopes could be identified: two were polymorphic between HIV-1 strains, and one was highly conserved. Studies with synthetic peptides demonstrated that the conserved epitope, recognized by antibody 13H8, was located between residues 431 and 439. Site-directed mutagenesis of gp120 demonstrated that residue 429 and/or 432 was critical for the binding of the seven antibodies to gp120 from HIV-1MN. Similarly, residues 423 and 429 were essential for the binding of monoclonal antibody 5C2 raised against gp120 from HIV-1IIIB. The amino acids located at positions 423 and 429 were found to vary between strains of HIV-1 as well as between molecular clones derived from the MN and LAI isolates of HIV-1. Polymorphism at these positions prevented the binding of virus-neutralizing monoclonal antibodies and raised the possibility that HIV-1 neutralization serotypes may be defined on the basis of C4 domain sequences. Analysis of the binding characteristics of the CD4-blocking antibodies demonstrated that their virus-neutralizing activity was directly proportional to their gp120-binding affinity. These studies account for the strain specificity of antibodies to the C4 domain of gp120 and demonstrate for the first time that antibodies to this region can be as effective as those directed to the principal neutralizing determinant (V3 domain) in neutralizing HIV-1 infectivity.