Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

The thermoelastic behaviour of semicrystalline and of glassy poly(ether-ether-ketone)

A thermoelastic evaluation, based on simultaneous measurements of the mechanical work and of the concomitant heat of deformation by a stretching micro calorimeter, was performed on semicrystalline and glassy PEEK. The objective of this study was to utilize the sensitive technique to detect differences that would account for observed effects of micro structure on mechanical performance. A clear difference was detected beyond a 0.6% strain, where the behaviour of glassy PEEK began to exhibit inelastic features such as yielding and plastic deformation. This difference between the glassy and the semicrystalline polymers was considered the reason for the superior mechanical fatigue and fracture properties produced by the latter micro structure.     

Locally random reductions: Improvements and applications

A (t, n)-locally random reduction maps a problem instancex into a set of problem instancesy ₁,...,y _n in such a way that it is easy to construct the answer tox from the answers toy ₁,...,y _n, and yet the distribution ont-element subsets ofy ₁,...,y _n depends only on |x|. In this paper we formalize such reductions and give improved methods for achieving them. Then we give a cryptographic application, showing a new way to prove in perfect zero knowledge that committed bitsx ₁,...,x _m satisfy some predicateQ. Unlike previous techniques for such perfect zero-knowledge proofs, ours uses an amount of communication that is bounded by a fixed polynomial inm, regardless of the computational complexity ofQ. These results were presented in preliminary form at the 10th Annual Crypto Conference, Santa Barbara, CA, August 1990. The work of D. Beaver was done at Harvard University, supported in part by NSF Grant CCR-870-4513. The work of J. Kilian was done at MIT and Harvard University, supported by an NSF postdoctoral fellowship.     

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.     

Bioenergy,food security and poverty reduction: trade-offs and synergies along the water–energy–food security nexus

This article provides a review of trade-offs and synergies of bioenergy within the water–energy–food security nexus, with emphasis on developing countries. It explores the links of bioenergy with food security, poverty reduction, environmental sustainability, health, and gender equity. It concludes that applying the nexus perspective to analyses of bioenergy widens the scope for achieving multiple-win outcomes along the above aspects.