Top-down proteomic analysis by MALDI-TOF profiling: Concentration-independent biomarkers

Although numerous protein biomarkers have been correlated with advanced disease states, no new clinical assays have been developed. Goals often anticipate disease-specific protein changes that exceed values among healthy individuals, a property common to acute phase reactants. This review considers somewhat different approaches. It focuses on intact protein isoform ratios that present a biomarker without change in the total concentration of the protein. These will seldom be detected by peptide level analysis or by most antibody-based assays. For example, application of an inexpensive method to large sample groups resulted in observation of several polymorphisms, including the first structural polymorphism of apolipoprotein C1. Isoform distribution of this protein was altered and was eventually linked to increased obesity. Numerous other protein isoforms included C- and N-terminal proteolysis, changes of glycoisoform ratios and certain types of sulfhydryl oxidation. While many of these gave excellent statistical correlation with advanced disease, clinical utility was not apparent. More important may be that protein isoform ratios were very stable in each individual. Diagnosis by longitudinal analysis of the same individual might increase sensitivity of protein biomarkers by 20-fold or more. Protein changes that exceed the range of values found among healthy individuals may be uncommon.     

Roll manufacturing of flexible microfluidic devices in thin PMMA and COC foils by embossing and lamination

Microfluidics on foil is gaining momentum due to a number of advantages of employing thin films combined with the capability of cost-effective high-volume manufacturing of devices. In this work, ultra-thin, flexible Y-microreactors with microchannels of 100 μm width and 30 μm depth were fabricated in thermoplastic polymer foils. The fluidic pattern was hot roll embossed in 125 μm thick poly-methyl-methacrylate (PMMA) and 130 μm thick cyclic-olefin-copolymer (COC) films using a dry-etched microstructured silicon wafer as a flat embossing tool in a laminator. The sealing of the channels was performed with two different techniques, one based on lamination of SU8 dry film resist (DFR) and the other one based on spin-coated poly-dimethylsiloxane (PDMS). Testing of the interconnected microreactor was carried out using two dye colorant solutions to demonstrate mixing.     

An educational strategy for occupational therapy community service

In response to the increasing trend toward community health care, a model of training that prepares students for community practice was incorporated into the occupational therapy curriculum at the University of Southern California. During academic training students are placed in a part-time community assignment where no occupational therapy services are offered. Training students for the role of community health specialist produces a dilemma for curriculum design. A balance must be achieved between providing traditional clinical content and providing the knowledge and expertise necessary for community practice. However, this training is considered necessary for maintaining the viability of the profession in a changing health system. Significantly, during the four-year period using this model, many graduates have sought employment in "nontraditional" community roles.     

Somatosensory Processing and Schizophrenia Liability: Proprioception, Exteroceptive Sensitivity, and Graphesthesia Performance in the Biological Relatives of Schizophrenia Patients.

In the present study, the authors examined somatosensory processing in 30 biological relatives of persons with schizophrenia (hereafter called "schizophrenia relatives"), 30 biological relatives of persons with bipolar affective disorder (psychiatric family control subjects), and 30 healthy control subjects with no family history of psychopathology. All 3 groups completed a weight discrimination task, a 2-point discrimination task, and a complex cognitive somatosensory task (i.e., graphesthesia). The schizophrenia relatives performed significantly worse on all 3 somatosensory tasks compared with both the healthy control subjects and the bipolar relatives. The healthy control subjects and psychiatric family control subjects showed no significant differences on any of the somatosensory tasks. Within the weight discrimination and 2-point discrimination tasks, schizophrenia relatives showed group differences on the d' index, the measure of sensitivity, whereas all 3 groups did not differ on lnβ, the measure of response bias, suggesting a genuine difference in weight and touch sensitivity. The d' value of the weight discrimination task was significantly associated with both the cognitive-perceptual factor and negative symptom factor of the clinical questionnaire (e.g., Schizotypal Personality Questionnaire; SPQ), whereas the 2-point discrimination d' value and graphesthesia scores were significantly associated only with the cognitive-perceptual factor of the SPQ. Implications for the possible relation between somatosensory task performance and schizophrenia liability are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Management of imprecision and uncertainty for production activity control

The operational levels of production management, often called production activity control (PAC) or manufacturing process control, require increasing reaction capabilities in order to adapt the workshop management to the changes of its environment. It often implies giving more responsibilities to the low decision levels. However, the management of the corresponding degrees of freedom is generally unusual. In such a situation, decision support systems (DSSs) provide a way to reconcile the satisfaction of mid-level objectives and the reaction requirements. A conceptual model is described that provides a design framework for a PAC DSS. Since the available knowledge lies mainly in expertise, a DSS has been implemented using a knowledge-based system. The uncertainty and imprecision of the managed information led to the use of fuzzy logic as a modeling tool. Moreover, various inference semantics have been implemented in the expert rules because different kinds of reasoning have been identified. Two versions of the DSS are described and several examples of implemented reasoning processes are developed.     

Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells

Vascular endothelial growth factor (VEGF) is the pivotal angiogenic growth factor activating endothelial cells to migrate, proliferate, and form capillary tubes. For an ordered endothelial cell migration, tissue invasion, and degradation of the extracellular matrix, proteolytic machinery is indispensable. Such machinery, suitable for localized proteolysis, is provided by the prourokinase-urokinase-plasmin system. Prourokinase (pro-uPA), the initial component of this system, is, however, synthesized in its inactive precursor form and as such bound to its cellular receptor uPAR. Here we identify a mechanism via which VEGF(165) interacting with its receptor VEGFR-2 rapidly induces prourokinase activation that is dependent on a change in integrin affinity, activation of matrix metalloproteinase 2 (MMP-2), and pro-uPA being bound to its surface receptor uPAR. This VEGF-induced pro-uPA activation on endothelial cells is responsible for VEGF-dependent local fibrinolytic activity and might be one of the initial steps in the angiogenic process.     

Physical association of starch biosynthetic enzymes with starch granules of maize endosperm. Granule-associated forms of starch synthase I and starch branching enzyme II

Antibodies were used to probe the degree of association of starch biosynthetic enzymes with starch granules isolated from maize (Zea mays) endosperm. Graded washings of the starch granule, followed by release of polypeptides by gelatinization in 2% sodium dodecyl sulfate, enables distinction between strongly and loosely adherent proteins. Mild aqueous washing of granules resulted in near-complete solubilization of ADP-glucose pyrophosphorylase, indicating that little, if any, ADP-glucose pyrophosphorylase is granule associated. In contrast, all of the waxy protein plus significant levels of starch synthase I and starch branching enzyme II (BEII) remained granule associated. Stringent washings using protease and detergent demonstrated that the waxy protein, more than 85% total endosperm starch synthase I protein, and more than 45% of BEII protein were strongly associated with starch granules. Rates of polypeptide accumulation within starch granules remained constant during endosperm development. Soluble and granule-derived forms of BEII yielded identical peptide maps and overlapping tryptic fragments closely aligned with deduced amino acid sequences from BEII cDNA clones. These observations provide direct evidence that BEII exits as both soluble and granule-associated entities. We conclude that each of the known starch biosynthetic enzymes in maize endosperm exhibits a differential propensity to associate with, or to become irreversibly entrapped within, the starch granule.     

An integer goal programming model for determining capital expenditures for correctional facilities

The selection of capital expenditure projects for the construction of state correctional facilities is often complicated by the existence of multiple and conflicting objectives on the part of the various interest groups involved in the decision-making process. While some groups view the limited availability of state funds to construct such facilities as the paramount consideration, others might consider having adequate capacity to house prisoners in a satisfactory manner, and the effect of prison overcrowding on prisoner sentencing as the primary factors in the decision to construct new facilities. As such. it is imperative that the limited funds available for constructing correctional facilities be allocated in the most efficient and satisfactory manner possible. In this paper, integer goal programming is demonstrated via a case example as a means for allocating funds for capital expenditures for new and renovated correctional facilities. Sensitivity analysis is performed using the model in order to demonstrate its capability for testing various planning scenarios including alternative priority structures, goal constraints and goal levels.