MRI fuzzy segmentation of brain tissue using neighborhood attraction with neural-network optimization.

Image segmentation is an indispensable process in the visualization of human tissues, particularly during clinical analysis of magnetic resonance (MR) images. Unfortunately, MR images always contain a significant amount of noise caused by operator performance, equipment, and the environment, which can lead to serious inaccuracies with segmentation. A robust segmentation technique based on an extension to the traditional fuzzy c-means (FCM) clustering algorithm is proposed in this paper. A neighborhood attraction, which is dependent on the relative location and features of neighboring pixels, is shown to improve the segmentation performance dramatically. The degree of attraction is optimized by a neural-network model. Simulated and real brain MR images with different noise levels are segmented to demonstrate the superiority of the proposed technique compared to other FCM-based methods. This segmentation method is a key component of an MR image-based classification system for brain tumors, currently being developed. Index Terms-Improved fuzzy c-means clustering (IFCM), magnetic resonance imaging (MRI), neighborhood attraction, segmentation.     

Modeling language acquisition in atypical phenotypes.

An increasing number of connectionist models have been proposed to explain behavioral deficits in developmental disorders. These simulations motivate serious consideration of the theoretical implications of the claim that a developmental disorder fits within the parameter space of a particular computational model of normal development. The authors examine these issues in depth with respect to a series of new simulations investigating past-tense formation in Williams syndrome. This syndrome and the past-tense domain are highly relevant because both have been used to make strong theoretical claims about the processes underlying normal language acquisition. The authors conclude that computational models have great potential to advance psychologists' understanding of developmental deficits because they focus on the developmental process itself as a pivotal causal factor in producing atypical phenotypic outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chemokine receptors: structure, function and role in microbial pathogenesis

The chemokine superfamily is composed of at least 20 different leukocyte chemoattractants that act by binding to a family of G protein-coupled receptors. Leukocyte subtypes respond preferentially to unique but overlapping subsets of chemokines as determined by the receptor distribution, yet the receptors appear to signal through a common Gi-type G protein. Since chemokines appear to play major roles in inflammatory pathology, their receptors may be good targets for developing leukocyte selective anti-inflammatory drugs. Two chemokine receptors, CC CKRS and ONCC, function pathologically as cell entry factors respectively for human immunodeficiency virus 1, the cause of AIDS, and Plasmodium vivax, the major cause of malaria.     

Disulfide bond assignment in human interleukin-7 by matrix-assisted laser desorption/ionization mass spectroscopy and site-directed cysteine to serine mutational analysis

Interleukin-7 (IL-7) is a proteinaceous biological response modifier that has a bioactive tertiary structure dependent on disulfide bond formation. Disulfide bond assignments in human (h)IL-7 are based upon the results of matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy and Cys to Ser mutational analyses. A gene encoding the hIL-7 was synthesized incorporating Escherichia coli codon usage bias and was used to express biologically active protein as determined by stimulation of precursor B-cell proliferation. MALDI mass spectroscopic analysis of trypsin-digested hIL-7 was performed and compared with the anticipated results of a simulated tryptic digestion. Many of the anticipated hIL-7 tryptic fragments were detected including one with a molecular mass equivalent to the sum of two polypeptides linked through a disulfide bond formed from Cys residues (Cys3 and Cys142). Subsequently, Cys to Ser substitution mutational analyses were performed. A hIL-7 variant with all six Cys substituted with Ser was found to be biologically inactive (EC50 > 1 x 10(-7) M). In contrast, a family of single disulfide bond-forming variants of hIL-7 were constructed by reintroducing Cys pairs (Cys3-Cys142, Cys35-Cys130, and Cys48-Cys93), and each could stimulate cell proliferation with an EC50 of 4 x 10(-9), 2 x 10(-8), and 2 x 10(-9) M, respectively. In single disulfide bond-forming mutants of hIL-7, the ability to stimulate cell proliferation was abolished in the presence of 2 mM dithiothreitol. The results presented strongly suggest that only a single disulfide bond is required for hIL-7 to form a tertiary structure capable of stimulating precursor B-cell proliferation.     

A T42A Ran mutation: differential interactions with effectors and regulators, and defect in nuclear protein import

Ran, the small, predominantly nuclear GTPase, has been implicated in the regulation of a variety of cellular processes including cell cycle progression, nuclear-cytoplasmic trafficking of RNA and protein, nuclear structure, and DNA synthesis. It is not known whether Ran functions directly in each process or whether many of its roles may be secondary to a direct role in only one, for example, nuclear protein import. To identify biochemical links between Ran and its functional target(s), we have generated and examined the properties of a putative Ran effector mutation, T42A-Ran. T42A-Ran binds guanine nucleotides as well as wild-type Ran and responds as well as wild-type Ran to GTP or GDP exchange stimulated by the Ran-specific guanine nucleotide exchange factor, RCC1. T42A-Ran.GDP also retains the ability to bind p10/NTF2, a component of the nuclear import pathway. In contrast to wild-type Ran, T42A-Ran.GTP binds very weakly or not detectably to three proposed Ran effectors, Ran-binding protein 1 (RanBP1), Ran-binding protein 2 (RanBP2, a nucleoporin), and karyopherin beta (a component of the nuclear protein import pathway), and is not stimulated to hydrolyze bound GTP by Ran GTPase-activating protein, RanGAP1. Also in contrast to wild-type Ran, T42A-Ran does not stimulate nuclear protein import in a digitonin permeabilized cell assay and also inhibits wild-type Ran function in this system. However, the T42A mutation does not block the docking of karyophilic substrates at the nuclear pore. These properties of T42A-Ran are consistent with its classification as an effector mutant and define the exposed region of Ran containing the mutation as a probable effector loop.     

Psychological interventions to prevent HIV infection are urgently needed: New priorities for behavioral research in the second decade of AIDS.

Behavior change remains the only means for primary prevention of HIV disease. Psychology should take a leading role in efforts to curtail the epidemic, but has not contributed to HIV prevention at a level proportionate to the urgency of the crisis. The authors propose an updated agenda for behavioral research on AIDS-HIV prevention implementing accelerated community trials of promising behavior change models, conducting trials of community-level interventions on a large scale and focused on populations most vulnerable to HIV infections, establishing partnerships between HIV research and community service organizations, integrating efforts from across psychology disciplines to advance and refine HIV prevention interventions, and mobilizing interdisciplinary HIV prevention resources and communication mechanisms to rapidly translate research findings to community and public policy arenas. (PsycINFO Database Record (c) 2010 APA, all rights reserved)