Caveolin and Ras function

Experimental protocols that allow confident assignment of signaling proteins to specific subdomains of the plasma membrane are essential for a full understanding of the complexities of signal transduction. This is especially relevant for Ras proteins, where the different membrane anchors of the Ras isoforms target them to functionally distinct microdomains that in turn allow quantitatively different signal outputs from otherwise highly homologous proteins. The methods outlined in this chapter, in addition to being invaluable in addressing Ras function, should also have wide utility in the study of many mammalian signal transduction pathways.

Impact of malocclusion and orthognathic reconstruction surgery on resonance and articulatory function: an examination of variability in five cases

Articulatory patterns and nasal resonance were assessed before and 6 months after orthognathic reconstruction surgery in five patients with dentofacial deformities. Perceptual and physiological assessments showed disorders of nasality and articulatory function preoperatively, two patients being hyponasal, and one hypernasal. Four patients had mild articulatory deficits, and four had reduced maximal lip or tongue pressures. Operation resulted in different patterns of change. Nasality deteriorated in three patients and articulatory precision and intelligibility improved in only one patient and showed no change in the other four. Operation improved interlabial pressures in three patients, while its impact on tongue pressures varied, being improved in one case, deteriorating in one, and remaining unchanged in the other three. The variability in the results highlights the need for routine assessment of speech and resonance before and after orthognathic reconstruction. (C) 2002 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Science Ltd. All rights reserved.

Morphology, ultrastructure, and implied function of ciliated sensory structures on the developmental stages of Merizocotyle icopae (Monogenea : Monocotylidae)

Experimental infections were used to track the fate of the dorsal sensilla of Merizocotyle icopae (Monogenea: Monocotylidae) from nasal tissue of the shovelnose ray, Rhinobatos typus (Rhinobatidae). Scanning and transmission electron microscopy revealed that 3 types of uniciliate dorsal sensilla exist at different times in the development of the monogenean. Type 1 sensilla have little or no invagination where the cilium exits the distal end of the dendrite and possess a ring of epidermis surrounding the cilium distal to the invagination. Type 2 sensilla have a deep invagination where the cilium exits the dendrite. Type 3 sensilla can be distinguished from the other types by the shape of the dendrite. The larvae have predominantly Type I dorsal sensilla, most of which are lost approximately 24 h after infection and a few Type 2 sensilla, which are retained. Additional Type 2 sensilla (termed Adult Type 2 sensilla), which are slightly different morphologically from the Type 2 sensilla of the larvae, form in later stages of development. Numerous Type 3 sensilla are unique to the dorsal surface of adults. Loss of all Type I sensilla upon attachment to the host, R. typus, suggests that these may be chemo- or mechanoreceptors responsible for host location by the swimming infective larvae. Type 2 sensilla appear to be important in the larvae, juveniles, and adults whereas the modality mediated by Type 3 is specific to adults. (C) 2003 Wiley-Liss, Inc.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE: To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and Symptom status in patients with symptomatic coronary artery disease. METHODS: Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a, more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function.(brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION: Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden. Am J Med. 2003;114:445-453. (C) 2003 by Excerpta Medica Inc.

Usefulness of B-type natriuretic peptide in hypertensive patients with exertional dyspnea and normal left ventricular ejection fraction and correlation with new echocardiographic indexes of systolic and diastolic function

B-type natriuretic peptide (BNP) levels increase in systolic heart failure (HF). However, the value of BNP in hypertensive patients with suspected diastolic HF (symptoms suggestive of HF but normal ejection fraction) and its relation to myocardial function in these patients is unclear. We prospectively studied 72 ambulatory hypertensive subjects (40 women, mean age 58 +/- 8 years) with exertional dyspnea and ejection fraction greater than or equal to50%. Diastolic function was evaluated with transmitral and pulmonary venous Doppler, mitral annular velocities (pulsed-wave tissue Doppler), and flow propagation velocity (color M-mode). Systolic function was assessed with strain and strain rate derived from color tissue Doppler imaging. BNP was related to myocardial function and the presence or absence of global diastolic dysfunction. By conventional Doppler criteria, 34 patients had normal left ventricular diastolic function and 38 had isolated diastolic dysfunction. BNP values were higher in patients with diastolic dysfunction (46 +/- 48 vs 20 +/- 20 pg/ml, p = 0.004) and were related independently to blood pressure, systolic strain rate, left atrial function (p < 0.01 for all), and age (p = 0.015). Patients with diastolic dysfunction and pseudonormal filling had higher BNP levels compared with impaired relaxation (89 +/- 47 vs 35 +/- 42 pg/ml, p = 0.001). However, 79% of patients with diastolic dysfunction had BNP levels within the normal range. We conclude that in ambulatory hypertensive patients with symptoms suggestive of mild HF and normal ejection fraction, BNP is related to atrial and ventricular systolic parameters, blood pressure, and age. Although elevated in the presence of diastolic dysfunction, the BNP level mostly is in the normal range and, therefore, has limited diagnostic value in stable patients with suspected diastolic HF. (C) 2003 by Excerpta Medica, Inc.

Cortex, cognition and the cell: New insights into the pyramidal neuron and prefrontal function

Arguably the most complex conical functions are seated in human cognition, the how and why of which have been debated for centuries by theologians, philosophers and scientists alike. In his best-selling book, An Astonishing Hypothesis: A Scientific Search for the Soul, Francis Crick refined the view that these qualities are determined solely by cortical cells and circuitry. Put simply, cognition is nothing more, or less, than a biological function. Accepting this to be the case, it should be possible to identify the mechanisms that subserve cognitive processing. Since the pioneering studies of Lorent de No and Hebb, and the more recent studies of Fuster, Miller and Goldman-Rakic, to mention but a few, much attention has been focused on the role of persistent neural activity in cognitive processes. Application of modern technologies and modelling techniques has led to new hypotheses about the mechanisms of persistent activity. Here I focus on how regional variations in the pyramidal cell phenotype may determine the complexity of cortical circuitry and, in turn, influence neural activity. Data obtained from thousands of individually injected pyramidal cells in sensory, motor, association and executive cortex reveal marked differences in the numbers of putative excitatory inputs received by these cells. Pyramidal cells in prefrontal cortex have, on average, up to 23 times more dendritic spines than those in the primary visual area. I propose that without these specializations in the structure of pyramidal cells, and the circuits they form, human cognitive processing would not have evolved to its present state. I also present data from both New World and Old World monkeys that show varying degrees of complexity in the pyramidal cell phenotype in their prefrontal cortices, suggesting that cortical circuitry and, thus, cognitive styles are evolving independently in different species.

Contribution towards a reflection about methodological strategies in design education and the function of drawing in design

This work presents a reflection on Design education and specifically on the role of Drawing in this area. As a subject, Design has expanded its field of action expanding into new areas such as Experience Design or Service Design. It became necessary for the designer to have more than an education based on technological knowledge or know-how. Many authors like Meredith Davis, Don Norman or Jamie Hobson point out the urgency to review the curricula of Design courses because nowadays “… design is more than appearance, design is about interaction, about strategy and about services. Designers change social behavior” (Norman 2011). When shifting from a product-centered design to a person-centered design (in a structure, a service or in a relationship) what should the function of drawing in a design course be? What should its curriculum be? Our work methodology will be to confront today’s perspectives on design theory and practice in an attempt to add to the discussion on the methodological strategies in design teaching in the contemporary context.

Contribution towards a reflection about methodological strategies in Design Education and the function of Drawing in Design

This work presents a reflection on Design education and specifically on the role of Drawing in this area. As a subject, Design has expanded its field of action expanding into new areas such as Experience Design or Service Design. It became necessary for the designer to have more than an education based on technological knowledge or know-how. Many authors like Meredith Davis, Don Norman or Jamie Hobson point out the urgency to review the curricula of Design courses because nowadays “ … design is more than appearance, design is about interaction, about strategy and about services. Designers change social behavior” (Norman, 2011) When shifting from a product-centered design to a person-centered design (in a structure, a service or in a relationship) what should the function of drawing in a design course be? What should its curriculum be? Our work methodology will be to confront today’s perspectives on design theory and practice in an attempt to add to the discussion on the methodological strategies in design teaching in the contemporary context.

Effects of the length and timing of nighttime naps on task performance and physiological function

OBJECTIVE: To examine the effects of the length and timing of nighttime naps on performance and physiological functions, an experimental study was carried out under simulated night shift schedules. METHODS: Six students were recruited for this study that was composed of 5 experiments. Each experiment involved 3 consecutive days with one night shift (22:00-8:00) followed by daytime sleep and night sleep. The experiments had 5 conditions in which the length and timing of naps were manipulated: 0:00-1:00 (E60), 0:00-2:00 (E120), 4:00-5:00 (L60), 4:00-6:00 (L120), and no nap (No-nap). During the night shifts, participants underwent performance tests. A questionnaire on subjective fatigue and a critical flicker fusion frequency test were administered after the performance tests. Heart rate variability and rectal temperature were recorded continuously during the experiments. Polysomnography was also recorded during the nap. RESULTS: Sleep latency was shorter and sleep efficiency was higher in the nap in L60 and L120 than that in E60 and E120. Slow wave sleep in the naps in E120 and L120 was longer than that in E60 and L60. The mean reaction time in L60 became longer after the nap, and faster in E60 and E120. Earlier naps serve to counteract the decrement in performance and physiological functions during night shifts. Performance was somewhat improved by taking a 2-hour nap later in the shift, but deteriorated after a one-hour nap. CONCLUSIONS: Naps in the latter half of the night shift were superior to earlier naps in terms of sleep quality. However performance declined after a 1-hour nap taken later in the night shift due to sleep inertia. This study suggests that appropriate timing of a short nap must be carefully considered, such as a 60-min nap during the night shift.

Lymphocyte subpopulations and neutrophil function in chronic human Chagas' disease

The absolute numbers of total leukocytes, lymphocytes, T cells, helper/inducer, suppressor/cytotoxic and B cells were decreased in the peripheral blood of patients with chronic Chagas' disease. Since antilymphocyte antibodies were present only in a minority of patients they probably cannot account for the abnormalities in lymphocyte subsets. Patient neutrophils stimulated with endotoxin-treated autologous plasma showed depressed chemotactic activity and this seems to be an intrinsic cellular defect rather than plasma inhibition. Random migration of neutrophils was normal. Reduction of nitroblue tetrazolium by endotoxin- stimulated neutrophils was also decreased. These findings further document the presence of immunosuppression in human Chagas' disease. They may be relevant to autoimmunity, defense against microorganisms and against tumor cells at least in a subset of patients with more severe abnormalities.

Adaptive Penalty and Barrier function based on Fuzzy Logic

Optimization methods have been used in many areas of knowledge, such as Engineering, Statistics, Chemistry, among others, to solve optimization problems. In many cases it is not possible to use derivative methods, due to the characteristics of the problem to be solved and/or its constraints, for example if the involved functions are non-smooth and/or their derivatives are not know. To solve this type of problems a Java based API has been implemented, which includes only derivative-free optimization methods, and that can be used to solve both constrained and unconstrained problems. For solving constrained problems, the classic Penalty and Barrier functions were included in the API. In this paper a new approach to Penalty and Barrier functions, based on Fuzzy Logic, is proposed. Two penalty functions, that impose a progressive penalization to solutions that violate the constraints, are discussed. The implemented functions impose a low penalization when the violation of the constraints is low and a heavy penalty when the violation is high. Numerical results, obtained using twenty-eight test problems, comparing the proposed Fuzzy Logic based functions to six of the classic Penalty and Barrier functions are presented. Considering the achieved results, it can be concluded that the proposed penalty functions besides being very robust also have a very good performance.

Degree of disability, pain levels, muscle strength, and electromyographic function in patients with Hansen's disease with common peroneal nerve damage

INTRODUCTION: This study evaluated the degree of disability, pain levels, muscle strength, and electromyographic function (RMS) in individuals with leprosy. METHODS: We assessed 29 individuals with leprosy showing common peroneal nerve damage and grade 1 or 2 disability who were referred for physiotherapeutic treatment, as well as a control group of 19 healthy participants without leprosy. All subjects underwent analyses of degree of disability, electromyographic tests, voluntary muscle force, and the Visual Analog Pain Scale. RESULTS: McNemar's test found higher levels of grade 2 of disability (Δ = 75.9%; p = 0.0001) among individuals with leprosy. The Mann-Whitney test showed greater pain levels (Δ = 5.0; p = 0.0001) in patients with leprosy who had less extension strength in the right and left extensor hallucis longus muscles (Δ = 1.28, p = 0.0001; Δ = 1.55, p = 0.0001, respectively) and dorsiflexion of the right and left feet (Δ = 1.24, p = 0.0001; Δ = 1.45, p = 0.0001, respectively) than control subjects. The Kruskal-Wallis test showed that the RMS score for dorsiflexion of the right (Δ = 181.66 m·s-2, p = 0.001) and left (Δ = 102.57m·s-2, p = 0.002) feet was lower in patients with leprosy than in control subjects, but intragroup comparisons showed no difference. CONCLUSIONS: Leprosy had a negative influence on all of the study variables, indicating the need for immediate physiotherapeutic intervention in individuals with leprosy. This investigation opens perspectives for future studies that analyze leprosy treatment with physical therapeutic intervention.

Contribution of Doppler echocardiography to the evaluation of systolic and diastolic function of obese women versus a control group

OBJECTIVE: To study by doppler echocardiography the cardiac systolic and diastolic functions of health, uncomplicated obese subjects. METHODS: Fifty-nine obese women with an average body mass index (BMI) of 35 kg/m² were evaluated and compared with 19 subjects with an average BMI of 23 kg/m² (control group). RESULTS: In the obese group, a clear tendency was observed toward higher systolic pressure, increased wall thickness and, consequently, myocardial mass, elevation on the circumference stress of the left ventricular wall, and an indisputable presence of diastolic abnormalities. Filling abnormalities were observed with impaired relaxation, with prolonged isovolumic relaxation time (IVRT) and augmented atrium contribution representing early indexes of cardiac dysfunction when systolic performance is still normal. CONCLUSION: Obesity is generally a chronic condition, and doppler echocardiography can be used as a noninvasive instrument for early evaluation of left ventricular diastolic indexes.