Physicochemical properties and isoenzyme composition of hexokinase from normal and malignant human tissues.

The activity of hexokinase was studied in several normal and malignant human tissues. The enzyme activity in tumors was significantly higher. Isoenzyme studies on normal gastric mucosa and stomach cancer extracts showed that malignancy is accompanied by a "simplification" of the hexokinase isoenzyme pattern due to "deletion" of the slowest isoenzyme. Preparative polyacrylamide gel electrophoreis was used to isolate hexokinase isoenzymes from normal and malignant tissues. Tumor hexokinase isoenzymes displayed an increased affinity to glucose when compared to the corresponding normal prototypes (Km/glucose, 10(-6) M and 10(-5) M, respectively; Km = Michaelis constant). The molecular weights, subunit composition, and peptide patterns were identical for corresponding isoenzyme pairs from normal and tumor tissues.     

Spatial regulation of BMP signaling by patterned receptor expression

Local delivery of TGF-beta/BMP ligands is commonly used as a tissue engineering strategy for the spatial regulation of cell growth and differentiation. While the location and the dose of ligand are the only parameters that influence the spatial distribution and biological effects of the ligand in vitro, in vivo genetic studies of development reveal that spatial control of TGF-beta/BMP signaling can be accomplished at multiple levels, from ligand release to signal interpretation. Here we focus on spatial control of BMP signaling by patterned receptor expression. Motivated by our recent experimental analysis of the two-dimensional BMP signaling patterns in the developing Drosophila egg, we formulate one- and two-dimensional models of ligand diffusion and internalization in the presence of patterned receptor expression. Our analysis of these models shows that they can capture the quantitative features of the experimentally observed pattern of phosphorylated SMAD in Drosophila oogenesis and shows that patterned receptor expression provides versatile control of BMP signaling in developing tissues. Quantitative understanding of the mechanisms of spatiotemporal control of signaling pathways in development is essential for successful harnessing of these pathways in tissue engineering.     

Comparison of the clinical behavior of newly diagnosed stages II-IV low-grade serous carcinoma of the ovary with that of serous ovarian tumors of low malignant potential that recur as low-grade serous carcinoma

BACKGROUND: Serous ovarian tumors of low malignant potential (STLMP) frequently coexist with low-grade serous carcinoma of the ovary (LGSC) and, when they recur, frequently do so as LGSC. The purpose of this study was to compare the outcomes of patients with these two tumor types. METHODS: All patients with stages II-IV LGSC (group 1) or with STLMP that recurred as LGSC (group 2) seen at our institution from 1973 to 2003 were identified, and demographic data were obtained. For group 1, progression-free and overall survival times were calculated from the date of primary diagnosis to the date of disease progression/recurrence or the date of last contact/death, respectively. For group 2, progression-free and overall survival times were calculated from the date of first relapse as a LGSC to the date of progression or the date of last contact/death, respectively. The method of Kaplan and Meier was used to estimate survival, and the log-rank test was used to compare differences between survival curves. RESULTS: We identified 112 patients in group 1 and 41 in group 2. There were no statistically significant differences between the two groups in median age (42.7 vs. 45.4 years [at relapse]; P=0.37), progression-free survival time (19.5 vs. 25 months; P=0.92), or overall survival time (81.8 vs. 82.8 months; P=0.84). CONCLUSIONS: The age at diagnosis, progression-free survival time, and overall survival time associated with newly diagnosed stages II-IV LGSC of the ovary are similar to those of STLMP that recur as LGSC, providing further evidence of an association between these two tumor types.     

The Adaptive Nature of Eye Movements in Linguistic Tasks: How Payoff and Architecture Shape Speed‐Accuracy Trade‐Offs

We explore the idea that eye‐movement strategies in reading are precisely adapted to the joint constraints of task structure, task payoff, and processing architecture. We present a model of saccadic control that separates a parametric control policy space from a parametric machine architecture, the latter based on a small set of assumptions derived from research on eye movements in reading (Engbert, Nuthmann, Richter, & Kliegl, 2005; Reichle, Warren, & McConnell, 2009). The eye‐control model is embedded in a decision architecture (a machine and policy space) that is capable of performing a simple linguistic task integrating information across saccades. Model predictions are derived by jointly optimizing the control of eye movements and task decisions under payoffs that quantitatively express different desired speed‐accuracy trade‐offs. The model yields distinct eye‐movement predictions for the same task under different payoffs, including single‐fixation durations, frequency effects, accuracy effects, and list position effects, and their modulation by task payoff. The predictions are compared to—and found to accord with—eye‐movement data obtained from human participants performing the same task under the same payoffs, but they are found not to accord as well when the assumptions concerning payoff optimization and processing architecture are varied. These results extend work on rational analysis of oculomotor control and adaptation of reading strategy (Bicknell & Levy, 2010b ; McConkie, Rayner, & Wilson, 1973; Norris, 2009; Wotschack, 2009) by providing evidence for adaptation at low levels of saccadic control that is shaped by quantitatively varying task demands and the dynamics of processing architecture.