Perspectives on Design and Innovation

A series of studies of top European and other firms has revealed patterns of design management associated with commercial success. Firms that invest resources and professional expertise in product and industrial design in traditional and new industries have been commercially more successful than firms that pay less attention to these aspects of design. As an industry matures there is a shift in emphasis from design associated with technological innovation, to designs supporting technical improvements, and then to supporting user needs, fashion and product variants. These issues are illustrated through the history of the evolution of the bicycle.     

Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Airway stents. Present and future

Tracheobronchial stent insertion is a relatively new technique used to palliate or cure central airways obstruction. When performed by experienced thoracic endoscopists, this procedure is both safe and effective, even if complications of indwelling stents may require repeat endoscopic intervention. Although proven clinically beneficial to many patients, airway prostheses have not yet been the subject of large comparative case studies or randomized controlled investigations. Reports are often experiential and anecdotal. Further research is needed to determine the effects of stenting on survival in patients with malignant airway disease and its degree of success in patients with benign airway strictures. Only then will airway stents truly deserve their place alongside other therapies for tracheobronchial obstruction.     

Knowledge, data, and models

The object-oriented approach to integrating knowledge data, and models is examined. Under the object-oriented paradigm, everything is an object, which is itself an encapsulation of data and methods to manipulate and access the data within the object. Thus knowledge, data, and models can be defined as special kinds of objects. Active knowledge/data language (KDL), a functional object-oriented database system is considered, covering the active-KDL-type system and functions, and query-driven simulation     

Paroxysmal atrial fibrillation

Paroxysmal atrial fibrillation is the most frequent of cardiac arrhythmias and its frequency increases with age. Its diagnosis is difficult since the symptoms are often absent or misleading. It is based on electrocardiogram performed during the attack, and this has been made easier by the Holter technique or by sequential recordings triggered by the patient himself. It is only in special cases, when percritical recordings could not be made that intracavitary electrophysiological study is used to obtain indirect arguments in favour of the diagnosis. All heart diseases can be attended by this cardiac rhythm disorder which usually marks an unfavourable turn in the course of the disease, with an increased risk of sudden death in the end. But in most cases the only disorder found is a common arterial hypertension. Atrial fibrillation carries a risk of peripheral, and in particular cerebral, embolism evaluated at 5% per annum. This risk is high in patients with cardiopathy, but it also exists even with a normal heart. The value of anticoagulants has been demonstrated by large controlled studies, but it is important to know that a very strong anticoagulant treatment is unnecessary to reduce the risk of embolism. Only antiarrhythmic agents can maintain the patients in sinus rhythm for as long as possible before the passage to permanent fibrillation. Although no beneficial effect on mortality has been proved, these drugs are indicated for patients who have very marked symptoms or a major cardiopathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related changes in cognitive ERPs of attenuation

The purpose of this article is to deliberate the moral and legal dilemma entailed in the weapon of the labour strike as a pressure tactic on the Israeli Finance Ministry regarding job slots, budgets and, in effect, violating the collective agreement signed by the nurses and impairing patients' treatment, as opposed to refraining from striking and suffering the heavy burden of work, the lack of trained personnel, low wages, and the inability to give patients proper, high quality treatment.     

Early use of inhaled steroids in children with asthma. Concluding comments

OBJECTIVE: To describe a rare case of right renal agenesia and left pelvic ectopy. To our knowledge, only 10 such cases have been reported in the world literature. METHODS: A 76-year-old male patient who consulted for irritative prostatic syndrome is described. Patient evaluation included IVP and CT. RESULTS: IVP revealed the absence of the right kidney in addition to an anomalous position of the left kidney. The foregoing findings were confirmed by CT. CONCLUSION: This uncommon congenital anomaly is essentially asymptomatic and is generally diagnosed in infants through its complications. In the case described herein, however, this anomaly had been incidentally detected during IVP and CT assessment of a 76-year-old patient who had consulted for irritative prostatic syndrome.     

RNA-diethylstilbestrol interaction studied by Fourier transform infrared difference spectroscopy

Diethylstilbestrol (DES), a synthetic estrogen, is known to be a carcinogen in human and in animals. This study was designed to examine the interaction of DES with yeast RNA in aqueous solution at physiological pH with drug/RNA-phosphate (P) molar ratios of 1/80, 1/40, 1/20, 1/10, 1/4, and 1/2. Fourier transform infrared (FTIR) difference spectroscopy was used to determine the drug binding mode, the binding constant, the sequence selectivity, and RNA secondary structure in the RNA.DES complexes. Spectroscopic evidence showed that at low drug concentration (1/80 and 1/40), DES is intercalating through both Gua-Cyt and Ade-Urd base pairs with minor interaction with the backbone PO2 group (external binding). The calculated binding constant of K approximately 8.5 x 10(4) M-1 at a drug concentration of 3.12 x 10(-4) M shows that DES is a weaker intercalator than those of the methylene blue, acridine orange, and ethidium bromide. At high drug content (r > 1/40, where r represents the DES/RNA-phosphate molar ratio), a partial helix destabilization occurs with no alteration of RNA conformation upon drug complexation. However, a comparison with DNA.DES complexes showed that drug intercalation causes major reduction of the B-DNA structure in favor of A-DNA with no participation of the backbone PO2 group in the DES. DNA complexation.