Development of explosive welding techniques for fabrication of regeneratively cooled thrust chambers for large rocket engine requirements Final report, 28 Jun. 1967 - 15 Sep. 1970

Explosive welding techniques in fabricating regeneratively cooled thrust chambers for large rocket engine requirements including ultrasonic inspection, metallography, and burst testin

On the Complexity of Searching in Trees: Average-case Minimization

We focus on the average-case analysis: A function w : V -> Z+ is given which defines the likelihood for a node to be the one marked, and we want the strategy that minimizes the expected number of queries. Prior to this paper, very little was known about this natural question and the complexity of the problem had remained so far an open question. We close this question and prove that the above tree search problem is NP-complete even for the class of trees with diameter at most 4. This results in a complete characterization of the complexity of the problem with respect to the diameter size. In fact, for diameter not larger than 3 the problem can be shown to be polynomially solvable using a dynamic programming approach. In addition we prove that the problem is NP-complete even for the class of trees of maximum degree at most 16. To the best of our knowledge, the only known result in this direction is that the tree search problem is solvable in O(|V| log|V|) time for trees with degree at most 2 (paths). We match the above complexity results with a tight algorithmic analysis. We first show that a natural greedy algorithm attains a 2-approximation. Furthermore, for the bounded degree instances, we show that any optimal strategy (i.e., one that minimizes the expected number of queries) performs at most O(\Delta(T) (log |V| + log w(T))) queries in the worst case, where w(T) is the sum of the likelihoods of the nodes of T and \Delta(T) is the maximum degree of T. We combine this result with a non-trivial exponential time algorithm to provide an FPTAS for trees with bounded degree

Deterministic and Probabilistic Binary Search in Graphs

We consider the following natural generalization of Binary Search: in a given undirected, positively weighted graph, one vertex is a target. The algorithm's task is to identify the target by adaptively querying vertices. In response to querying a node $q$, the algorithm learns either that $q$ is the target, or is given an edge out of $q$ that lies on a shortest path from $q$ to the target. We study this problem in a general noisy model in which each query independently receives a correct answer with probability $p > \frac{1}{2}$ (a known constant), and an (adversarial) incorrect one with probability $1-p$. Our main positive result is that when $p = 1$ (i.e., all answers are correct), $\log_2 n$ queries are always sufficient. For general $p$, we give an (almost information-theoretically optimal) algorithm that uses, in expectation, no more than $(1 - \delta)\frac{\log_2 n}{1 - H(p)} + o(\log n) + O(\log^2 (1/\delta))$ queries, and identifies the target correctly with probability at leas $1-\delta$. Here, $H(p) = -(p \log p + (1-p) \log(1-p))$ denotes the entropy. The first bound is achieved by the algorithm that iteratively queries a 1-median of the nodes not ruled out yet; the second bound by careful repeated invocations of a multiplicative weights algorithm. Even for $p = 1$, we show several hardness results for the problem of determining whether a target can be found using $K$ queries. Our upper bound of $\log_2 n$ implies a quasipolynomial-time algorithm for undirected connected graphs; we show that this is best-possible under the Strong Exponential Time Hypothesis (SETH). Furthermore, for directed graphs, or for undirected graphs with non-uniform node querying costs, the problem is PSPACE-complete. For a semi-adaptive version, in which one may query $r$ nodes each in $k$ rounds, we show membership in $\Sigma_{2k-1}$ in the polynomial hierarchy, and hardness for $\Sigma_{2k-5}$

Dynamic treatment regimes: Technical challenges and applications

Dynamic treatment regimes are of growing interest across the clinical sciences because these regimes provide one way to operationalize and thus inform sequential personalized clinical decision making. Formally, a dynamic treatment regime is a sequence of decision rules, one per stage of clinical intervention. Each decision rule maps up-to-date patient information to a recommended treatment. We briefly review a variety of approaches for using data to construct the decision rules. We then review a critical inferential challenge that results from nonregularity, which often arises in this area. In particular, nonregularity arises in inference for parameters in the optimal dynamic treatment regime; the asymptotic, limiting, distribution of estimators are sensitive to local perturbations. We propose and evaluate a locally consistent Adaptive Confidence Interval (ACI) for the parameters of the optimal dynamic treatment regime. We use data from the Adaptive Pharmacological and Behavioral Treatments for Children with ADHD Trial as an illustrative example. We conclude by highlighting and discussing emerging theoretical problems in this area

Doubly robust learning for estimating individualized treatment with censored data

Individualized treatment rules recommend treatments based on individual patient characteristics in order to maximize clinical benefit. When the clinical outcome of interest is survival time, estimation is often complicated by censoring. We develop nonparametric methods for estimating an optimal individualized treatment rule in the presence of censored data. To adjust for censoring, we propose a doubly robust estimator which requires correct specification of either the censoring model or survival model, but not both; the method is shown to be Fisher consistent when either model is correct. Furthermore, we establish the convergence rate of the expected survival under the estimated optimal individualized treatment rule to the expected survival under the optimal individualized treatment rule. We illustrate the proposed methods using simulation study and data from a Phase III clinical trial on non-small cell lung cancer

Crystal, Solution and In silico Structural Studies of Dihydrodipicolinate Synthase from the Common Grapevine

Dihydrodipicolinate synthase (DHDPS) catalyzes the rate limiting step in lysine biosynthesis in bacteria and plants. The structure of DHDPS has been determined from several bacterial species and shown in most cases to form a homotetramer or dimer of dimers. However, only one plant DHDPS structure has been determined to date from the wild tobacco species, Nicotiana sylvestris (Blickling et al. (1997) J. Mol. Biol. 274, 608–621). Whilst N. sylvestris DHDPS also forms a homotetramer, the plant enzyme adopts a ‘back-to-back’ dimer of dimers compared to the ‘head-to-head’ architecture observed for bacterial DHDPS tetramers. This raises the question of whether the alternative quaternary architecture observed for N. sylvestris DHDPS is common to all plant DHDPS enzymes. Here, we describe the structure of DHDPS from the grapevine plant, Vitis vinifera, and show using analytical ultracentrifugation, small-angle X-ray scattering and X-ray crystallography that V. vinifera DHDPS forms a ‘back-to-back’ homotetramer, consistent with N. sylvestris DHDPS. This study is the first to demonstrate using both crystal and solution state measurements that DHDPS from the grapevine plant adopts an alternative tetrameric architecture to the bacterial form, which is important for optimizing protein dynamics as suggested by molecular dynamics simulations reported in this study