Antagonists of myostatin, a blood-borne negative regulator of muscle growth produced in muscle cells, have shown considerable promise for enhancing muscle mass and strength in rodent studies and could serve as potential therapeutic agents for human muscle diseases. One of the most potent of these agents, follistatin, is both safe and effective in mice, but similar tests have not been performed in nonhuman primates. To assess this important criterion for clinical translation, we tested an alternatively spliced form of human follistatin that affects skeletal muscle but that has only minimal effects on nonmuscle cells. When injected into the quadriceps of cynomolgus macaque monkeys, a follistatin isoform expressed from an adeno-associated virus serotype 1 vector, AAV1-FS344, induced pronounced and durable increases in muscle size and strength. Long-term expression of the transgene did not produce any abnormal changes in the morphology or function of key organs, indicating the safety of gene delivery by intramuscular injection of an AAV1 vector. Our results, together with the findings in mice, suggest that therapy with AAV1-FS344 may improve muscle mass and function in patients with certain degenerative muscle disorders.

Purpose The purpose of this paper is to identify the development of planned organisational change models (POCMs) since Lewin’s three-step model and to highlight key linkages between them. Design/methodology/approach A total of 13 commonly used POCMs were identified and connections with Lewin’s three-step framework and associated process attributes were made, reflecting the connections between these models and Lewin. Findings The findings show that first Lewin’s three-step model represents a framework for planned change; however, these steps could not be viewed in isolation of other interrelated processes, including action research, group dynamics, and force field analysis. These process steps underpin the iterative aspects of his model. Second, all 13 POCMs have clearly identified linkages to Lewin, suggesting that the ongoing development of POCMs is more of an exercise in developing ongoing procedural steps to support change within the existing framework of the three-step model. Research limitations/implications The authors recognise that the inclusion of additional POCMs would help strengthen linkages to Lewin. The findings from this paper refocus attention on the three-step model, suggesting its ongoing centrality in planned organisational change rather than it being dismissed as an historical approach from which more recently developed models have become more relevant. Practical implications This paper presents opportunities for organisational change management researchers to challenge their thinking with regard to the ongoing search for model refinement, and for practitioners in the design and structure of POCM. Originality/value An analysis of the ongoing relevance of Lewin and his linkage with modern POCMs assist in rationalising the broadening, and often confusing literature on change. This paper therefore not only contributes to filtering such literature, but also helps clarify the myriad of POCMs and their use.

Although this evaluation instrument for measuring clinic attending performance must be considered preliminary, this study suggests that relatively few attending evaluations are required to reliably profile an individual attending's performance, that attending identity is associated with a large amount of the scale score variation, and that special issues of attending performance more relevant to the outpatient setting than the inpatient setting (availability in clinic and sensitivity to time efficiency) should be considered when evaluating clinic attending performance.

We consider the group isomorphism problem: given two finite groups G and H specified by their multiplication tables, decide if G ∼ = H. The n log n barrier for group isomorphism has withstood all attacks -even for the special cases of p-groups and solvable groups -ever since the n log n+O(1) generator-enumeration algorithm. Following a framework due to Wagner, we present the first significant improvement over n log n by reducing group isomorphism to composition-series isomorphism which is then reduced to low-degree graph isomorphism. We show that group isomorphism is n (1/2) log p n+O(1) Turing reducible to composition-series isomorphism where p is the smallest prime dividing the order of the group. Combining our reduction with an n O(p) algorithm for p-group composition-series isomorphism, we obtain an n (1/2) log n+O(1) algorithm for p-group isomorphism. We then generalize our techniques from p-groups using Sylow bases to derive an n (1/2) log n+O(log n/ log log n) algorithm for solvable-group isomorphism. Finally, we relate group isomorphism to the collision problem which allows us replace the 1/2 in the exponents with 1/4 using randomized algorithms and 1/6 using quantum algorithms. arXiv:1205.0642v6 [cs.DS] 11 Dec 2013 Theorem 1.2. Group isomorphism is n (1/2) log p n+O(1) time deterministic Turing reducible to compositionseries isomorphism where p is the smallest prime dividing the order of the group.A composition series S is a tower of subgroups G 0 = 1 · · · G m = G such that no additional subgroups can be inserted. The factor groups G i+1 /G i are called the composition factors of S. We say that two composition seriesIn the composition-series isomorphism problem, we are given composition series S and S where the subgroups are specified by their corresponding subsets and must decide whether S ∼ = S .Wagner [39] showed a Karp reduction from composition-series isomorphism to low-degree graph isomorphism [26,6,5]. Using this reduction, he gave an n O(p) algorithm for p-group composition series isomorphism using an n O(d) algorithm 1 for isomorphism of graphs of degree at most d. Wagner's reduction also applies to general groups, but produces graphs of large degree when there are large composition factors. Wagner reduced the degrees by using a modification of the generatorenumeration algorithm to guess the action of the isomorphism on large composition factors; the graphs are then modified to enforce this mapping. This would have yielded an n O(log n/ log log n) algorithm for isomorphism of composition series for arbitrary groups. Unfortunately, the resulting graphs depend on which coset representatives are chosen so the algorithm is flawed. Wagner attempted to fix this error in two subsequent revisions [40,41]; unfortunately, these contain a more subtle manifestation of the same flaw. Wagner retracted his attempted fix in the latest revision of his paper [42] following further discussions with the author (see Appendix E.) However, we will show that Wagner's generator-fixing trick can still be salvaged in a s...

Extended superposed quantum-state initialization using disjoint prime implicants is an algorithm for generating quantum arrays for the purpose of initializing a desired quantum superposition. The quantum arrays generated by this algorithm almost always use fewer gates than other algorithms and in the worst case use the same number of gates. These improvements are achieved by allowing certain parts of the quantum superposition that cannot be initialized directly by the algorithm to be initialized using special circuits. This allows more terms in the quantum superposition to be initialized at the same time which decreases the number of gates required by the generated quantum array.