High-level Language Support for User-defined Reductions

The optimized handling of reductions on parallel supercomputers or clusters of workstations is critical to high performance because reductions are common in scientific codes and a potential source of bottlenecks. Yet in many high-level languages, a mechanism for writing efficient reductions remains surprisingly absent. Further, when such mechanisms do exist, they often do not provide the flexibility a programmer needs to achieve a desirable level of performance. In this paper, we present a new language construct for arbitrary reductions that lets a programmer achieve a level of performance equal to that achievable with the highly flexible, but low-level combination of Fortran and MPI. We have implemented this construct in the ZPL language and evaluate it in the context of the initialization of the NAS MG benchmark. We show a 45 times speedup over the same code written in ZPL without this construct. In addition, performance on a large number of processors surpasses that achieved in the NAS implementation showing that our mechanism provides programmers with the needed flexibility.     

Science, common sense, and the determination of mental capacity.

In 1993, when the Supreme Court decided Daubert and created the modern standard for the admissibility of scientific evidence, it almost certainly did not consider its possible effect on evidentiary hearings in probate courts even though such courts routinely admit expert testimony in will contests and guardianship hearings. Probate courts also admit testimony of lay witnesses who express their opinion as to the mental capacity of the individual in question. Yet both expert and lay witnesses are only "fact bringers" and not "fact interpreters" because the ultimate question of capacity is legal, not factual. Because the determination of legal capacity is made by the judge or jury, the role of experts in capacity trials is not fundamentally different than that of lay persons. The limited role of the expert suggests that probate courts should allow great latitude in the admission of expert testimony because the fact finders must ultimately rely on their own amorphous sense of "legal capacity." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Limited hydrolysis of soy proteins with endo- and exoproteases

Changes in the native state and functional properties of soy protein achieved by limited proteolysis of soy flour were investigated. Different enzyme-to-substrate ratios (E/S) were used to obtain low (3–5%) and medium (5–10%) degrees of hydrolysis (DH). Six protease preparations (three with predominately exopeptidase activities and three with predominately endopeptidase activities) were evaluated, and their effects on solubility, emulsification capacity, SDS-PAGE profiles, and denaturation enthalpies were characterized. Endoproteases (Multifect^® Neutral, Protex^? 6L, and Multifect^® P-3000) and exoproteases (Fungal Protease Concentrate, Experimental Fungal Protease #1, and Experimental Fungal Protease #2) yielded similar increases in soy protein solubility. The modifications to the soy peptide profile were similar for the three exoprotease mixtures at a 1% E/S ratio, whereas the extent of hydrolysis with Protex^? 6L was more pronounced than with the two other endoproteases (Multifect^® Neutral and Multifect^® P-3000). The emulsification capacity of protease-modified soy flour declined regardless of DH and enzyme type (exo- or endoprotease). After hydrolysis to >4% DH, denaturation enthalpies of glycinin and β-conglycinin decreased significantly, whereas hydrolysis to lower DH did not affect these values.     

Stereochemistry of Host Plant Monoterpenes as Mate Location Cues for the Gall Wasp Antistrophus rufus

In spring, adult males of the gall wasp Antistrophus rufus L. emerge from inconspicuous galls in stems of their host plant Silphium laciniatum L. and search for sites on stems where females will later emerge. The behavior of males suggests that they use olfaction rather than visual or tactile cues in searching for mates. In an earlier publication, we reported that galls of A. rufus were associated with changes in enantiomeric ratios of alpha- and beta-pinene emitted by plant stems, and hypothesized that monoterpene stereochemistry served as a mate location cue for adult males. Here, we support this hypothesis with bioassays that demonstrate that males can discriminate between galled and ungalled stems, as well as between blends of synthetic monoterpenes with ratios of enantiomers representative of galled and ungalled stems.     

Covalent disulfide-linked anti-CEA diabody allows site-specific conjugation and radiolabeling for tumor targeting applications

An engineered anti-carcinoembryonic antigen (CEA) diabody (scFv dimer, 55 kDa) was previously constructed from the murine anti-CEA T84.66 antibody. Tumor targeting, imaging and biodistribution studies in nude mice bearing LS174T xenografts with radiolabeled anti-CEA diabody demonstrated rapid tumor uptake and fast blood clearance, which are favorable properties for an imaging agent. Current radiolabeling approaches result in random modification of the protein surface, which may impair immunoreactivity especially for smaller antibody fragments. Site-specific conjugation approaches can direct modifications to reactive groups located away from the binding site. Here, cysteine residues were introduced into the anti-CEA diabody at three different locations, to provide specific thiol groups for chemical modification. One version (with a C-terminal Gly-Gly-Cys) existed exclusively as a disulfide-bonded dimer. This cysteine-modified diabody (Cys-diabody) retained high binding to CEA and demonstrated tumor targeting and biodistribution properties identical to the non-covalent diabody. Furthermore, following reduction of the disulfide bond, the Cys-diabody could be chemically modified using a thiol-specific bifunctional chelating agent, for radiometal labeling. Thus, the Cys-diabody provides a covalently linked alternative to conventional diabodies, which can be reduced and modified site-specifically. This format will provide a versatile platform for targeting a variety of agents to CEA-positive tumors.     

Humanization of the anti-CEA T84.66 antibody based on crystal structure data

Chimeric T84.66 (cT84.66) is a monoclonal antibody (mAb) of high specificity and affinity for the tumor-associated carcinoembryonic antigen (CEA). Radiolabeled cT84.66 has demonstrated utility in the clinic as a reagent for the radioimmunoscintigraphy and radioimmunotherapy of CEA-positive colorectal and breast malignancies. To extend the therapeutic efficacy of T84.66, humanization by complementary determining region (CDR) grafting was employed. CDR grafting is a well-established technique, though often a series of framework back-mutations is required to restore high affinity. Recently, the crystal structure of the T84.66 diabody (scFv dimer) derived from the murine T84.66 mAb was determined, facilitating the humanization process by the availability of crystal structure data for both the graft donor and graft acceptor. A search of the Protein Data Bank revealed close structural similarity (r.m.s.d. of 1.07 A) between the Fv of T84.66 and the Fv of 4D5v8, a humanized anti-p185HER2 antibody marketed as Herceptin (Trastuzumab). This resulted in two humanized versions of the T84.66 M5A and M5B mAbs that differed only in the number of murine residues present in the C-terminal half of CDR-H2. Biochemical analysis and animal biodistribution studies were conducted to evaluate the humanized mAbs. The M5A, M5B and cT84.66 mAbs showed sub-nanomolar affinity for CEA and as radiolabeled mAbs exhibited specific tumor localization in tumor bearing mice. The T84.66 M5A mAb was selected for clinical development due to a slightly higher tumor uptake and a larger content of human residues, and was renamed hT84.66. A limited-scale production and animal imaging study have demonstrated hT84.66's ability to support clinical trials. Planned clinical trials will determine the effective utilization of this structure-based approach in the development of a promising new therapeutic.     

An inverse design of an open,head/neck RF coil for MRI

Radio-frequency (RF) coils are a necessary component of magnetic resonance imaging (MRI) systems. When used in transmit operation, they act to generate a homogeneous RF magnetic field within a volume of interest and when in receive operation, they act to receive the nuclear magnetic resonance signal from the RF-excited specimen. This paper outlines a procedure for the design of open RF coils using the time-harmonic inverse method. This method entails the calculation of an ideal current density on a multipaned planar surface that would generate a specified magnetic field within the volume of interest. Because of the averaging effect of the regularization technique in the matrix solution, the specified magnetic field is shaped within an iterative procedure until the generated magnetic field matches the desired magnetic field. The stream-function technique is used to ascertain conductor positions and a method of moments package is then used to finalize the design. An open head/neck coil was designed to operate in a clinical 2T MRI system and the presented results prove the efficacy of this design methodology.     

Structural features of bovine caseinomacropeptide A and B by 1H nuclear magnetic resonance spectroscopy

Samples of bovine caseinomacropeptide (CMP) were isolated from kappa-casein A and kappa-casein B and fractionated to give aglycosylated CMP A and CMP B and monoglycosylated CMP A. The secondary structures of these three peptides were compared under neutral and acidic (pH 4.2) conditions, using two-dimensional (2D) 1H nuclear magnetic resonance (NMR) spectroscopy. The differences between the spectra at pH 4.2 and 7.0 and the spectra of the aglycosylated and glycosylated CMP A were subtle, indicating little change in backbone conformation with these changes. These results Suggest that differences in the coagulation properties of milks containing either kappa-casein A or kappa-casein B are more likely to be related to factors, such as micelle size or charge, than to structural differences arising from altered backbone conformation of the macropeptide segments of the kappa-caseins.