A reliable and manufacturable method to induce a stress of >1 GPa on a P-channel MOSFET in high volume manufacturing

This letter discusses a reliable and manufacturable integration technique to induce greater than 1 GPa of stress into a p-channel MOSFET, which will be required to increase the drive current beyond 1 mA//spl mu/m at the sub-90-nm process generation. Uniaxial compressive stress is introduced into the p-channel by both a selective deposition of SiGe in the source/drain and an engineered 2.5-GPa compressively stressed nitride. The highest to date compressively stressed SiN film is obtained by heavy ion bombardment during the deposition of the film.     

Synthesis and applications of heterobifunctional poly(ethylene oxide) oligomers

Poly(ethylene oxide) (PEO) oligomers are employed extensively in pharmaceutical and biomedical arenas mainly due to their excellent physical and biological properties, including solubility in water and organic solvents, lack of toxicity, and absence of immunogenicity. PEO can be chemically modified and reacted with, or adsorbed onto, other molecules and surfaces. Sophisticated applications for PEO have increased the demand for PEO oligomers with tailored functionalities, and heterobifunctional PEOs are often needed. This review discusses the synthesis and applications of heterobifunctional PEO oligomers possessing amine, carboxylate, thiol, and maleimide functional groups.     

Controlling insulin-like growth factor activity and the modulation of insulin-like growth factor binding protein and receptor binding

The insulin-like growth factors (IGF) and insulin perform seemingly unique roles by causing the same metabolic effect: cellular hypertrophy. Although overlapping, there are different consequences to cellular hypertrophy induced by IGF and that induced by insulin. The IGF enhance the cell hypertrophy that is requisite for cell survival, hyperplasia, and differentiation, and insulin enhances cell hypertrophy primarily as a means to increase nutrient stores. The effects of IGF and insulin are controlled by the segregation of their receptors between different cell types. A model is discussed that describes the need for three hormones (IGF-I, IGF-II, and insulin) to control nutrient partitioning. Insulin receptor localization, as well as an episodic mode of secretion, evolved to perform the short-term action of clearing excess nutrients from the circulation. In contrast, a complex and interactive set of factors ensure that maximal IGF activity occurs only when conditions are optimal for growth. A relatively invariant rate of secretion and the IGF binding proteins serve to maintain a large mutable pool of IGF. This pool exists to ensure a constant supply of IGF to maintain the basal metabolic rate and to ensure that, once a cell begins to proliferate or differentiate, adequate exposure is available to complete the process even after severe short-term physiological insults. The IGF concentrations only change in response to prolonged differences in protein and energy availabilities, environmental and body temperatures, and external stress. Also, evidence is now emerging that describes a discrete role for trace nutrients in the regulation of IGF activity. In this latter regard, zinc has the notable role of targeting IGF binding proteins to the cell surface. New data are presented showing that zinc also changes the affinity of the type 1 IGF receptor and cell-associated IGF binding proteins to optimize IGF activity.     

Factors affecting contrasting results between self-reported and performance-based levels of physical limitation

Molecular electrostatic potential (MEP) maps of certain 3-methoxy flavone derivatives having different anti-picornavirus activities have been studied. Geometries of the molecules were optimised and charge distributions computed using the AM1 molecular orbital method. Hybridization displacement charges (HDC) were combined with the L?wdin charge distributions to compute the MEP maps. Reliability of the method of computing MEP maps was tested by studying certain other molecules for which ab initio MEP results are available. The anti-picornavirus activities of the flavones have been shown to be related with negative MEP values in two regions, one near the 3-methoxy group and another in a diagonally opposite region near the substituent attached to the C7 atom of the molecules.     

A methodology for investigating effects of cell size on operational flexibility in flexible manufacturing systems

There are two aspects to cell formation in flexible manufacturing systems, cell sizing or deciding on the optimum number of machines to be allocated to each cell, and then allocation of specific machines to each cell. Although the latter problem has been investigated extensively there is a paucity of published work on the former. This paper discusses the effects of cell sizing on operational flexibility.Operational flexibility is that aspect of flexibility that enables manufacturing systems to respond with speed and efficiency to changes in the manufacturing environment while maintaining an effective level of control.     

Genetic fusions of subunit c in the F0 sector of H+-transporting ATP synthase. Functional dimers and trimers and determination of stoichiometry by cross-linking analysis

The multicopy c subunit of the H+-transporting ATP synthase of Escherichia coli folds through the transmembrane F0 sector as a hairpin of two hydrophobic alpha-helices with the proton-translocating aspartyl-61 side chain centered in the second transmembrane helix. The number of subunits c in the F0 complex, which is thought to determine the H+-pumping/ATP stoichiometry, was previously not determined with exactness but thought to range from 9-12. The studies described here indicate that the exact number is 12. Based upon the precedent of the subunit c in vacuolar-type ATPases, which are composed of four transmembrane helices and seem to have evolved by gene duplication of an F0-type progenitor gene, we constructed genetically fused dimers and trimers of E. coli subunit c. Both the dimeric and trimeric forms proved to be functional. These results indicate that the total number of subunit c in F0 should be a multiple of 2 and 3. Based upon a previous study in which the oligomeric organization of c subunits in F0 was determined by cross-linking of Cys-substituted subunits (Jones, P. C. , Jiang, W., and Fillingame, R. H. (1998) J. Biol. Chem. 273, 17178-17185), we introduced Cys into the first and last transmembrane helices of subunit c monomers, dimers, and trimers and attempted to generate cross-linked products by oxidation with Cu(II)-(1,10-phenanthroline)2. Double Cys substitutions at two sets of positions gave rise to extensive cross-linked multimers. Multimers of the monomer that extended up to the position of c12 were correlated and calibrated with distinct cross-linked species of the appropriate doubly Cys-substituted dimers (i.e. c2, c4, . c12) and doubly Cys-substituted trimers (i.e. c3, c6, c9, c12). The results show that there are 12 copies of subunit c per F0 in E. coli, the exact number having both mechanistic and structural significance.     

Responsiveness of self-reported and objective measures of disease severity in carpal tunnel syndrome

Responsiveness, the ability to detect meaningful clinical change, is a critical attribute of instruments used to evaluate outcomes of treatments. The authors hypothesized that self-administered symptom severity and functional status questionnaires are more responsive to clinical improvement after carpal tunnel release than traditional physical examination measures of strength and sensibility. Data were obtained from a randomized clinical trial of endoscopic versus open carpal tunnel release conducted in four university medical centers. Patients were evaluated before surgery and 3 months after surgery. Seventy-four patients indicating that they were more than 80% satisfied with the results of surgery were assumed to have clinically meaningful improvement and were the focus of the analysis. Evaluations included questionnaires assessing symptom severity, functional status, and activities of daily living as well as measurement of grip, pinch, and abductor pollicus brevis strength, and 2-point discrimination and Semmes-Weinstein pressure sensibility. Responsiveness was calculated with the standardized response mean (mean change/standard deviation of change) as well as the effect size (mean change/standard deviation of baseline values). The symptom severity scale was four times as responsive, and the functional status and activities of daily living scales were twice as responsive, as the measures of strength and sensibility. Self-administered symptom severity and functional status scales are much more responsive to clinical improvement than measures of neuromuscular impairment and should severe as primary outcomes in clinical studies of therapy for carpal tunnel syndrome.