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Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

This paper presents results from an experiment using electroencephalography to measure neurophysiological activations of mechanical engineers and industrial designers when designing and problem-solving. In this study, we adopted and then extended the tasks described in a previous functional magnetic resonance imaging study reported in the literature. The block experiment consists of a sequence of three tasks: problem-solving, basic design and open design using a physical interface. The block is preceded by a familiarizing pre-task and then extended to a fourth open design task using free-hand sketching. This paper presents the neurophysiological results from 36 experimental sessions of mechanical engineers and industrial designers. Results indicate significant differences in activations between the problem-solving and the open design tasks. The paper focuses on the two prototypical tasks of problem-solving layout and open design sketching and presents results for both aggregate and temporal activations across participants within each domain and across domains.

New tools from neuroscience allow design researchers to explore design neurocognition. By taking the advantage of EEG's temporal resolution we give up spatial resolution to focus on the performance of time-related design tasks. This paper presents results from an experiment using EEG to measure brain activation to study mechanical engineers and architects to compare their design neurocognition. In this study, we adopted and extended the tasks described in a previous fMRI study of design neurocognition reported in the literature. The block experiment consists of a sequence of 3 tasks: problem solving, basic design and open design using a physical interface. The block is preceded by a familiarizing pre-task using the physical interface and then extended to a fourth task using free-hand sketching. Brainwaves were collected from both mechanical engineers and architects. Results comparing 36 mechanical engineers and architects while designing were produced. These results indicate design cognition differences between the two domains in task-related power between the problem-solving task and the design tasks, in temporal resolution and transformed power.

Expression of BCR/ABL, a constitutively active tyrosine kinase, is a primary event in the pathogenesis of chronic myeloid leukemia (CML) and Ph-positive acute lymphoblastic leukemia (Ph+ALL). Inhibition of the BCR/ABL kinase activity in the BV173 CML cell line with STI571 resulted in a significant overexpression of a 10-kb novel mRNA, found to be the human ortholog of the murine Bach2, a B-cell-specific transcription factor. The human BACH2 cDNA is >9,120 bp long and includes an open reading frame of 2,526 bp encoding a protein with a basic leucine zipper (bZip) and a BTB/POZ domain, mediating DNA-binding and heterodimerization. BACH2 was consistently upregulated (2-10-fold) in all 10 Ph+ lymphoid lines tested following BCR/ABL inhibition. In CML myeloid cell lines (n = 8) and BCR/ABL-negative lines (n = 6), BACH2 was either undetectable by Northern blotting or did not change in response to STI571, suggesting that BACH2 repression by BCR/ABL may be specifically relevant to lymphoid transformation. Quantitative RT/PCR revealed a significantly lower level of BACH2 expression in leukocytes from patients with CML (n = 24) as compared to normal individuals (n = 23) (P < 0.0005). Moreover, CD34+ cells treated in vitro with STI571 exhibited a consistent upregulation of BACH2 in 8 of 10 CMLs but in none of the 9 normal individuals tested. Transcription regulation of BACH2 in BCR/ABL-positive cells was exerted via the MEK pathways, as shown by their responses to the U0126-specific inhibitor. Radiation hybrid mapping and FISH revealed that BACH2 is located on chromosome 6, band q15, a region frequently associated with deletions in ALL and non-Hodgkin's lymphoma, suggesting its possible role as a tumor suppressor gene. However, no rearrangement or loss of signal was observed by Southern blotting in 34 lymphomas, 10 B-cell ALLs, or seven reactive lymph nodes. The pattern of BACH2 expression in BCR/ABL-positive cells suggests that transcriptional repression by this regulator is impaired in CML and may contribute to the emergence of lymphoid blast crisis.

Key pointsr The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype r Chronic intermittent workload induced features of adaptive hypertrophy r This was paralleled by protection against acute pressure overload insult r The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. AbstractThe present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg -1 , S.C.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week -1 for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca Abbreviations Akt/mTOR, protein kinase B/mammalian target of rapamycin; BN, blue native; BW, body weight; CO, cardiac output; dP/dt max , peak rate of pressure rise; dP/dt min , peak rate of pressure fall; ESP, end-systolic pressure; EDP, end-diastolic pressure; ESV, end-systolic volume; EDV, end-diastolic volume; E a , arterial elastance; EF, ejection fraction; ESPVR, end-systolic pressure volume relation; E max , maximal elastance; EDPVR, end-diastolic pressure volume relation; Gast/BW, gastrocnemius weight/body weight; Gast, gastrocnemius weight; HR, heart rate; HW, heart weight; HW/BW, heart weight/body weight; LV, left ventricle; LV+S, left ventricle+septum; LV+S/BW, left ventricle+septum/body weight; LVP max , left ventricular peak systolic pressure; MHC, myosin heavy chain; PRSW, preload-recrutable stroke work; P max , peak systolic pressure; SERCA2a, sarcoplasmic reticulum Ca 2+

This paper presents results from an experiment to determine brain activation differences between problem-solving and designing of mechanical engineers. The study is part of a research project whose goal is to correlate design cognition with brain behavior across design domains. The study adopted and extended the tasks described in a fMRI study of design cognition and measured brain activation using EEG. By taking the advantage of EEG’s temporal resolution we focus on time-related neural responses during problem-solving compared to design tasks. Statistical analyses indicate increased activation when designing compared to problem-solving. Results of time-related neural responses connected to Brodmann areas cognitive functions, contribute to a better understanding of mechanical engineers’ cognition in open design tasks.

Using structured methods for managing business innovation can be an effective way to improve the ideation process. Teaching structured methods is a potent way to enhance the innovative capabilities of companies and to develop creative products for the marketplace. In this paper, structured models of innovation and product development are reviewed and an approach to them is presented, based on several MSc student projects. The implications for managers, such as the need to train employees in structured methods, and the implications for those who teach innovation management are discussed in detail.