Organopalladium approaches to prostaglandins

Organopalladium chemistry has found considerable synthetic utility in organic chemistry. Advances in this chemistry led us to develop several efficient new synthetic routes to prostaglandins, hormones which have a host of regulatory functions in the human body. In this dissertation, several prostaglandins were synthesized utilizing organopalladium chemistry in the key step. In addition, a new synthetic approach to allylic aryl ethers was developed during our studies on prostaglandin synthesis;The first chapter of this thesis discusses the formal synthesis of prostaglandin F[subscript]2[alpha] and the total synthesis of 12-epi-PGF[subscript]2[alpha]. An extremely efficient three-component coupling was accomplished with optically active cis-4-t-butyldimethylsilyloxy-2-cyclopenten-1-ol, ethyl vinyl ether and 1-octen-3-one in the presence of Pd(OAc)[subscript]2;The second chapter discusses an efficient synthesis of the PGI[subscript]2 analogue (+)-5,6,7-trinor-4,8-m-phenylene PGI[subscript]2, which is known to have potent inhibitory activity for platelet aggregation. The strategy involves the intramolecular addition of an aryl radical to an olefin bond, followed by trapping of the resulting radical with a tri-n-butylstannyl allylic alcohol in a one-step procedure. The epimer, 12-epi-5,6,7-trinor-4,8-inter-m-phenylene PGI[subscript]2, was also synthesized by a sequence involving a one-step Pd(0)-mediated cyclization and subsequent enone coupling;The third chapter discusses the synthesis of a novel PGI[subscript]2 analogue, 12-epi-carbacyclin. A silyl enol ether prepared through organopalladium chemistry was treated with 1-octen-3-one in the presence of Pd(OAc)[subscript]2 to give an important intermediate in a single step;The last chapter discusses an efficient two-step synthesis of allylic aryl ethers from the corresponding allylic alcohols utilizing a [pi]-allylpalladium intermediate generated from allylic aryl carbonates. Allylic aryl carbonates were prepared either by using phenyl chloroformate or by using triphosgene and functionalized phenols

Effect of Compressive Load on Shrinkage of Larch Blocks During Radio-Frequency Vacuum Heating

This study was carried out to investigate the effect of a compressive load of 0.092 MPa on the shrinkage of the larch blocks with sides of 40 mm each, when subjected to vacuum combined with radio-frequency heating.The shrinkages in the loading direction were significantly increased; for example, the tangential shrinkages of the blocks loaded compressively on their radial surfaces (loaded-RS), and the radial shrinkages of the blocks loaded compressively on their tangential surfaces (loaded-TS) were approximately one and one-half times as much as those for the load-free blocks.The shrinkages perpendicular to the loading direction were restrained, for example, the radial shrinkage for the loaded-RS, and the tangential shrinkage for the loaded-TS

Non-Smooth, H\"older-Smooth, and Robust Submodular Maximization

We study the problem of maximizing a continuous DR-submodular function that is not necessarily smooth. We prove that the continuous greedy algorithm achieves an [(1-1/e)\OPT-\epsilon] guarantee when the function is monotone and H\"older-smooth, meaning that it admits a H\"older-continuous gradient. For functions that are non-differentiable or non-smooth, we propose a variant of the mirror-prox algorithm that attains an [(1/2)\OPT-\epsilon] guarantee. We apply our algorithmic frameworks to robust submodular maximization and distributionally robust submodular maximization under Wasserstein ambiguity. In particular, the mirror-prox method applies to robust submodular maximization to obtain a single feasible solution whose value is at least (1/2)\OPT-\epsilon. For distributionally robust maximization under Wasserstein ambiguity, we deduce and work over a submodular-convex maximin reformulation whose objective function is H\"older-smooth, for which we may apply both the continuous greedy and the mirror-prox algorithms

Projection-Free Online Convex Optimization with Stochastic Constraints

This paper develops projection-free algorithms for online convex optimization with stochastic constraints. We design an online primal-dual projection-free framework that can take any projection-free algorithms developed for online convex optimization with no long-term constraint. With this general template, we deduce sublinear regret and constraint violation bounds for various settings. Moreover, for the case where the loss and constraint functions are smooth, we develop a primal-dual conditional gradient method that achieves $O(\sqrt{T})$ regret and $O(T^{3/4})$ constraint violations. Furthermore, for the setting where the loss and constraint functions are stochastic and strong duality holds for the associated offline stochastic optimization problem, we prove that the constraint violation can be reduced to have the same asymptotic growth as the regret

RHOA in Gastric Cancer: Functional Roles and Therapeutic Potential

The well-known signal mediator and small GTPase family member, RHOA, has now been associated with the progression of specific malignancies. In this review, we appraise the biomedical literature regarding the role of this enzyme in gastric cancer (GC) signaling, suggesting potential clinical significance. To that end, we examined RHOA activity, with regard to second-generation hallmarks of cancer, finding particular association with the hallmark “activation of invasion and metastasis.” Moreover, an abundance of studies show RHOA association with Lauren classification diffuse subtype, in addition to poorly differentiated GC. With regard to therapeutic value, we found RHOA signaling to influence the activity of specific widely used chemotherapeutics, and its possible antagonism by various dietary constituents. We also review currently available targeted therapies for GC. The latter, however, showed a paucity of such agents, underscoring the urgent need for further investigation into treatments for this highly lethal malignancy