Muscle unloading induces slow to fast transitions in myofibrillar but not mitochondrial properties. Relevance to skeletal muscle abnormalities in heart failure

Muscle deconditioning is a common observation in patients with congestive heart failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or prolonged bed rest. To gain further insight into metabolic and mechanical properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal muscles, we induced experimental muscle deconditioning by hindlimb suspension (HS) in rats for 3 weeks. Cardiac muscle was also studied. Besides profound muscle atrophy, increased proportion of fast type II fibers as well as fast myosin isoenzymes, we found decreased calcium sensitivity of Triton X-100 skinned fiber bundles of soleus muscle directed towards the fast muscle phenotype. Glycolytic enzymes such as hexokinase and pyruvate kinase were increased, and the LDH isoenzyme pattern was clearly shifted from an oxidative to an anaerobic profile. Creatine kinase (CK) and myokinase activities were increased in HS soleus towards EDL values. Moreover, the M-CK mRNA level was greatly increased in soleus, with no change in EDL. However, oxygen consumption rate assessed in situ in saponin skinned fibers (12.5 +/- 0.8 in C and 15.1 +/- 0.9 micromol O2/min/g dw in HS soleus compared to 7.3 +/- 1.3 micromol O2/min/g dw in control EDL), as well as mitochondrial CK (mi-CK) and citrate synthase activities, were preserved in HS soleus. Following deconditioning no change in Km for ADP of mitochondrial respiration, either in the absence (511 +/- 92 in C and 511 +/- 111 microM in HS soleus compared to 9 +/- 4 microM in control EDL) or presence of creatine (88 +/- 10 in C and 95 +/- 16 microM in HS soleus compared to 32 +/- 9 microM in control EDL), was found. The results show that muscle deconditioning induces a biochemical and functional slow to fast phenotype transition in myofibrillar and cytosolic compartments of postural muscle, but not in the mitochondrial compartment, suggesting that these compartments are differently regulated under conditions of decreased activity.     

Cost models for future software life cycle processes: COCOMO 2.0

Current software cost estimation models, such as the 1981 Constructive Cost Model (COCOMO) for software cost estimation and its 1987 Ada COCOMO update, have been experiencing increasing difficulties in estimating the costs of software developed to new life cycle processes and capabilities. These include non-sequential and rapid-development process models; reuse-driven approaches involving commercial off-the-shelf (COTS) packages, re-engineering, applications composition, and applications generation capabilities; object-oriented approaches supported by distributed middleware; and software process maturity initiatives. This paper summarizes research in deriving a baseline COCOMO 2.0 model tailored to these new forms of software development, including rationale for the model decisions. The major new modeling capabilities of COCOMO 2.0 are a tailorable family of software sizing models, involving Object Points, Function Points, and Source Lines of Code; nonlinear models for software reuse and re-engineering; an exponentdriver approach for modeling relative software diseconomies of scale; and several additions, deletions and updates to previous COCOMO effort-multiplier cost drivers. This model is serving as a framework for an extensive current data collection and analysis effort to further refine and calibrate the model's estimation capabilities.     

Prototyping Versus Specifying: A Multiproject Experiment

In this experiment, seven software teams developed versions of the same small-size (2000-4000 source instruction) application software product. Four teams used the Specifying approach. Three teams used the Prototyping approach. The main results of the experiment were the following. 1) Prototyping yielded products with roughly equivalent performance, but with about 40 percent less code and 45 percent less effort. 2) The prototyped products rated somewhat lower on functionality and robustness, but higher on ease of use and ease of learning. 3) Specifying produced more coherent designs and software that was easier to integrate. The paper presents the experimental data supporting these and a number of additional conclusions.     

Maximum performance of solar heat engines

Thermodynamic principles are considered to see if these concepts may indicate possibilities for improvements in solar thermal power plants. Aspects related to rate limitations and temperature effects in heat-engine cycles, thermodynamic availability of solar radiation and sink temperature considerations are noted. Considerably higher instantaneous plant efficiencies are possible by raising the maximum temperature and lowering the minimum temperature of the cycles. Some cycles that indicate desirable characteristics for efficiency improvement are discussed.     

Garbage collection in an uncooperative environment

We describe a technique for storage allocation and garbage collection in the absence of significant co-operation from the code using the allocator. This limits garbage collection overhead to the time actually required for garbage collection. In particular, application programs that rarely or never make use of the collector no longer encounter a substantial performance penalty. This approach greatly simplifies the implementation of languages supporting garbage collection. It further allows conventional compilers to be used with a garbage collector, either as the primary means of storage reclamation, or as a debugging tool. Our approach has two potential disadvantages. First, some garbage may fail to be reclaimed. Secondly, we use a ‘stop and collect’ approach, thus making the strategy unsuitable for applications with severe real-time constraints. We argue that the first problem is, to some extent, inherent in any garbage collection system. Furthermore, based on our experience, it is usually not significant in practice. In spite of the second problem, we have had favourable experiences with interactive applications, including some that use a heap of several megabytes.     

Identifying quality-requirement conflicts

Without a well-defined set of quality-attribute requirements, software projects are vulnerable to failure. The authors have developed QARCC, a knowledge-based tool that helps users, developers, and customers analyze requirements and identify conflicts among them     

Systemic lupus erythematosus is associated with increased auto-antibody titers against calreticulin and grp94, but calreticulin is not the Ro/SS-A antigen

Auto-antibodies against purified human calreticulin were determined by an ELISA in sera from patients with systemic lupus erythematosus (SLE) and from healthy persons or patients without an autoimmune disease. More than 80% of patients with SLE had titers exceeding the highest value obtained in the group without SLE. Almost 30% of the patients had also elevated auto-antibody titers against purified rat grp94, another resident ER-protein of the KDEL-protein family, but not against rat ERp72 (CaBP2), an ER-resident protein of the proteindisulfide isomerase family. It could, however, be excluded that calreticulin is the Ro/SS-A antigen on the basis of the following observations: 1) Calreticulin purified from rat, bovine or human liver contained far less than 1 mol of phosphate per mol of calreticulin, showed an E280/E260-absorption ratio of about 2.0, and did not contain extractable RNA; 2) Sera from patients with SLE did not react with or precipitate endogenous calreticulin from Hep G2 cells; they did, however, precipitate hY-RNA from these cells; 3) Sera from SLE-patients, but not anti-calreticulin antisera precipitated [32P]-hY-RNA from [32P]-labelled Hep G2 cells.