Computational complexity of impact size estimation forspreading processes on networks

Spreading processes on networks are often analyzed to understand how the outcome of the process (e.g. the number of affected nodes) depends on structural properties of the underlying network. Most available results are ensemble averages over certain interesting graph classes such as random graphs or graphs with a particular degree distributions. In this paper, we focus instead on determining the expected spreading size and the probability of large spreadings for a single (but arbitrary) given network and study the computational complexity of these problems using reductions from well-known network reliability problems. We show that computing both quantities exactly is intractable, but that the expected spreading size can be efficiently approximated with Monte Carlo sampling. When nodes are weighted to reflect their importance, the problem becomes as hard as the s-t reliability problem, which is not known to yield an efficient randomized approximation scheme up to now. Finally, we give a formal complexity-theoretic argument why there is most likely no randomized constant-factor approximation for the probability of large spreadings, even for the unweighted case. A hybrid Monte Carlo sampling algorithm is proposed that resorts to specialized s-t reliability algorithms for accurately estimating the infection probability of those nodes that are rarely affected by the spreading proces

Do not attempt resuscitation : the importance of consensual decisions

Aims: To describe the involvement and input of physicians and nurses in cardiopulmonary resuscitation (cpr / do not attempt resuscitation (dnar) decisions; to analyse decision patterns; and understand the practical implications. Design: A qualitative grounded theory study using one-time open-ended interviews with 40 volunteer physicians and 52 nurses drawn from acute care wards with mixes of heterogeneous cases in seven different hospitals in German-speaking Switzerland. Results: Establishing dnar orders in the best interests of patients was described as a challenging task requiring the leadership of senior physicians and nurses. Implicit decisions in favour of cpr predominated at the beginning of hospitalisation; depending on the context, they were relieved/superseded by explicit dnar decisions. Explicit decisions were the result of hierarchical medical expertise, of multilateral interdisciplinary expertise, of patient autonomy and/or of negotiated patient autonomy. Each type of decision, implicit or explicit, potentially represented a team consensus. Non-consensual decisions were prone to precipitate personal or team conflicts, and, occasionally, led to non-compliance. Conclusion: Establishing dnar orders is a demanding task. Reaching a consensus is of crucial importance in guaranteeing teamwork and good patient care. Communication and negotiation skills, professional and personal life experience and empathy for patients and colleagues are pivotal. Therefore, leadership by experienced senior physicians and nurses is needed and great efforts should be made with regard to multidisciplinary education

I. Application of Chiral α,β-Unsaturated Acylammonium Salts for Efficient Catalytic Transformations II. Studies toward the Total Synthesis of Rameswaralide

The developments of novel catalytic transformations are just as important as the discoveries of new reactions. In the most common way, catalysts provide more efficient and economical alternatives to known reactions. Arguably, sometimes, catalysts enable new and amazing transformations. Described herein are methodologies that expand the field of chiral tertiary amine catalysis. In the past few decades, chiral tertiary amine-catalyzed reactions have become one of the most versatile and useful methodologies in organic transformations. Among several modes of activation by chiral tertiary amines, the α,β-unsaturated acylammonium salts is the most underexplored despite its potential to reveal three reactive sites. Two projects focusing on novel transformations of α,β-unsaturated acylammonium salts are described. The first development showed the potential of a conjugated acylammonium species in a multicomponent process, namely a Michael Michael aldol β-lactonization cascade. Three achiral (52-72% yield) and ten enantioselective (19-61% yield) examples have been demonstrated with this methodology, with excellent dr (>19:1) in the optically active examples. In parallel, an expansion of a nucleophile-catalyzed Michael proton-transfer lactamization is described with a focus on the syntheses of chiral piperidi-2-ones and a dihydropiperidinone. The NMR study of the intermediate α,β-unsaturated acylammonium salts gave us an insight into decreased 1,2-reactivity which promoted addition at the β-carbon of these reactive intermediates. Natural products continue to be an inspiration for drug discovery and development. Due to its potent biological activity in a variety of inflammatory assays, the synthesis of rameswaralide is highly desirable, as it would enable sufficient quantities of the natural product that could be used to elucidate its mechanism of action along with a full structure activity relationship investigation. In the second part, an approach to access the core structure of rameswralide is proposed, where the complexity is increased with each synthesized fragment. The bicyclic AD core of rameswaralide was obtained via a 6-step process from inexpensive commercially available starting materials. The tricyclic ABD and the tetracyclic core are being constructed involving either ring closing metathesis or organometallic coupling as a key step

New approaches to multi-objective optimization

A natural way to deal with multiple, partially conflicting objectives is turning all the objectives but one into budget constraints. Many classical optimization problems, such as maximum spanning tree and forest, shortest path, maximum weight (perfect) matching, maximum weight independent set (basis) in a matroid or in the intersection of two matroids, become NP-hard even with one budget constraint. Still, for most of these problems efficient deterministic and randomized approximation schemes are known. Not much is known however about the case of two or more budgets: filling this gap, at least partially, is the main goal of this paper. In more detail, we obtain the following main results: Using iterative rounding for the first time in multi-objective optimization, we obtain multi-criteria PTASs (which slightly violate the budget constraints) for spanning tree, matroid basis, and bipartite matching with $$k=O(1)$$ k = O ( 1 ) budget constraints. We present a simple mechanism to transform multi-criteria approximation schemes into pure approximation schemes for problems whose feasible solutions define an independence system. This gives improved algorithms for several problems. In particular, this mechanism can be applied to the above bipartite matching algorithm, hence obtaining a pure PTAS. We show that points in low-dimensional faces of any matroid polytope are almost integral, an interesting result on its own. This gives a deterministic approximation scheme for $$k$$ k -budgeted matroid independent set. We present a deterministic approximation scheme for $$k$$ k -budgeted matching (in general graphs), where $$k=O(1)$$ k = O ( 1 ) . Interestingly, to show that our procedure works, we rely on a non-constructive result by Stromquist and Woodall, which is based on the Ham Sandwich Theorem

Basic Amino Acid Mutations in the Nuclear Localization Signal of Hibiscus Chlorotic Ringspot Virus p23 Inhibit Virus Long Distance Movement

10.1371/journal.pone.0074000PLoS ONE89-POLN

Telomerase activity in human leukemic cells with or without monosomy 7 or 7q-

BACKGROUND: In bone marrow material from patients with various leukemias we noted that samples with either a deletion on the long arm of one chromosome 7 (7q-) or a monosomy 7 had a higher telomerase activity. Considering that introduction of a chromosome 7 into a cancer cell line had been reported to eliminate telomerase activity, that 7q- is a common negative prognostic finding in cancers, and that the deleted segment (band 7q31) contains an unidentified tumor suppressor gene, we wondered if this gene might be a telomerase inhibitor. RESULTS: We found no significant difference in telomerase activity between the three groups of patient samples. In contrast to reports on tumor cell lines we observed no amplification of the telomerase genes. METHODS: We analyzed telomerase activity and copy number of the telomerase genes hTERT and hTR in frozen archival bone marrow samples from leukemia patients with a referral diagnosis of AML, and either a monosomy for chromosome 7, a deletion on the long arm of chromosome 7 (7q-), or none of these aberrations. Telomerase activity was measured with a commercially available kit, and the copy number of the telomerase genes was tested by FISH. CONCLUSIONS: We found no evidence of a telomerase inhibitor in band 7q31. The lack of telomerase gene amplification found in cell lines from solid tumors could reflect that this amplification is a property of solid tumors, not of hematological cancers