A method for preparing chelate-cytokine conjugates with retention of protein structure, biological activity, and pharmacokinetic properties

The chelating agent diethylenetriaminepentaacetic acid (DTPA) has been conjugated site-specifically to the N-terminus of recombinant human interleukin-2 (rhIL-2) by reaction with DTPA dianhydride at an initial pH of 6.0, thus demonstrating broader application of the conjugation method previously described for the structurally related cytokine rhG-CSF (Ralph et al., 1995). Purity of the DTPA-rhIL-2 conjugate, isolated by cation-exchange FPLC, and chelation of 111In were revealed by cation-exchange HPLC. Purity of the conjugate as well as chelation of radiometal were also demonstrated by SDS-PAGE and TLC, respectively. The stoichiometric molar ratio of DTPA to protein for the conjugate was approximately 1:1 as determined by TLC and mass spectrometry. Localization of the DTPA moiety was resolved by a peptide mapping procedure. The protein retained > 95% secondary structure (alpha helicity) following the conjugation. Addition of metal induced an approximate 22% loss of secondary structure for the conjugate. The in vitro biological activity of the protein was unaffected by the conjugated DTPA, even with chelated metal. Pharmacokinetic analysis of DTPA-conjugated cytokines, following chelated 111In, showed clearance and pharmacokinetic parameter values comparable to those of the corresponding unmodified cytokine. DTPA-conjugated cytokines may prove useful in cytokine research, and furthermore may represent a novel class of molecules for imaging, diagnosing, and/or treatment of malignancies where the cytokine receptor is overexpressed.     

School-based prevention of depressive symptoms: A randomized controlled study of the effectiveness and specificity of the penn resiliency program.

The authors investigated the effectiveness and specificity of the Penn Resiliency Program (PRP; J. E. Gillham, L. H. Jaycox, K. J. Reivich, M. E. P. Seligman, & T. Silver, 1990), a cognitive-behavioral depression prevention program. Children (N = 697) from 3 middle schools were randomly assigned to PRP, Control (CON), or the Penn Enhancement Program (PEP; K. J. Reivich, 1996; A. J. Shatté, 1997), an alternate intervention that controls for nonspecific intervention ingredients. Children's depressive symptoms were assessed through 3 years of follow-up. There was no intervention effect on average levels of depressive symptoms in the full sample. Findings varied by school. In 2 schools, PRP significantly reduced depressive symptoms across the follow-up relative to both CON and PEP. In the 3rd school, PRP did not prevent depressive symptoms. The authors discuss the findings in relation to previous research on PRP and the dissemination of prevention programs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning Conceptual Knowledge in the Engineering Sciences: Overview and Future Research Directions

Learning conceptual knowledge in engineering science is a critical element in the development of competence and expertise in engineering. To date, however, research on conceptual learning in engineering science has been limited. Therefore, this article draws heavily on fundamental research by cognitive psychologists and applied research by science educators to provide a background on fundamental issues in the field and methods for assessing conceptual knowledge. Some of the most common conceptual difficulties from three domains: mechanics, thermal science and direct current electricity, are discussed to provide concrete examples of what students find difficult to learn. The article concludes with a discussion of possible sources of these difficulties, implications for instruction, and suggestions for future research.     

School-based prevention of depression and anxiety symptoms in early adolescence: A pilot of a parent intervention component.

Previous studies suggest that school-based cognitive-behavioral interventions can reduce and prevent depressive symptoms in youth. This pilot study investigated the effectiveness of a cognitive-behavioral depression prevention program, the Penn Resiliency Program for Children and Adolescents (the PRP-CA), when combined with a parent intervention component. Forty-four middle school students and their parents were randomly assigned to the enhanced PRP (the PRP-CA plus parent program) or control conditions. Students completed measures of depression and anxiety symptoms at baseline and 2 weeks, 6 months, and 1 year after the intervention ended. The combined version of the PRP significantly reduced symptoms of depression and anxiety during the follow-up period. Children assigned to the intervention condition were less likely than controls to report clinical levels of anxiety symptoms. Findings suggest that school-based cognitive-behavioral interventions that include parents may prevent depression and anxiety symptoms in early adolescence. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Experimental and computational studies of oxidizer and fuel side addition of ethanol to opposed flow air/ethylene flames

Results of computations based on a detailed chemical kinetic combustion mechanism and results of experiments are compared to understand the influence of ethanol vapor addition upon soot formation and OH radical concentration in opposed flow ethylene/air diffusion flames. For this work, ethanol vapor was added to either the fuel or the oxidizer gases. Experiment and calculations are in qualitative agreement, and both show differing concentrations of soot, soot precursors, and OH depending on whether the ethanol is added to the fuel or oxidizer gases. An explanation for the observed differences for oxidizer or fuel side ethanol addition to opposed flow ethylene/air diffusion flames is proposed, based on an analysis of the chemical kinetic mechanism used in the computations.     

Reduction of PAH and soot in premixed ethylene-air flames by addition of ethanol

Results are presented from a combined experimental and modeling study undertaken to understand the pathways by which the addition of ethanol to fuel-rich ethylene flames causes reductions in PAH and soot. The experimental work was conducted in a flat-flame burner at equivalence ratios of 2.34 and 2.64. Ethanol was added to the ethylene at two levels corresponding to 5 and 10% oxygen by weight in the fuel. Soot was measured by laser-induced incandescence calibrated with light extinction, and aromatic species were measured using laser-induced fluorescence. Modeling was based on a 1-D premixed flame model and kinetic mechanisms available in the literature. The modeling work captures the trends in aromatic species with changes in equivalence ratio and oxygen concentration in the fuel. However, the soot predictions do not match the increases observed at the higher equivalence ratio. Analysis of the modeling results for the lower equivalence ratio shows that the addition of ethanol to the ethylene reduces the aromatic species mainly by reducing the amount of carbon that is available to form precursor species.     

Integrating Energy-Optimizing Scheduling of Moldable Streaming Tasks with Design Space Exploration for Multiple Core Types on Configurable Platforms

Design space exploration of a configurable, heterogeneous system for a given application with required throughput searches for a combination of cores or softcores with different architectures that can be accommodated within the given ASIC or FPGA area and that achieves the required throughput and optimizes power consumption. For a soft real-time streaming application, modeled as a task graph with internally parallelizable streaming tasks, this requires assigning a core type and quantity and DVFS frequency level to each task, which implies task runtime and energy consumption, and mapping and scheduling the tasks, such that the throughput requirement is met. We tightly integrate such static scheduling for stream processing applications with design space exploration of the best heterogeneous core combination, and solve the resulting combined optimization problem by an integer linear program (ILP). We evaluate our solution for different numbers of core types on synthetic and application-based task graphs, and demonstrate improvements of up to 34.8% for ARM big and LITTLE cores, and 70.5% for 3 different core types.

     

The Effects of a First‐Year Engineering Design Course on Student Intellectual Development as Measured by the Perry Scheme

In response to the demand for enhanced design, problem‐solving, and team skills in engineering graduates, Penn State has instituted a number ofteam‐based, project‐learning courses, including one taken by nearly every first‐year engineering student. To determine the impact of these experiences on our students we have begun a cross‐sectional and longitudinal study of their intellectual development based upon the Perry model. In this paper, we describe the research methodology and results for the initial group of first‐year students interviewed. The results of the study include the effects on intellectual development of the first‐year design course, gender, honors status, and the students' academic ability as indicated by SAT scores and grade point average. Design experience was positively related to enhanced intellectual development. Honors status, gender, and academic ability were not significantly related to Perry rating. We discuss the implications of these findings for instruction and curricular reform.