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.     

Associative retuning in the thalamic source of input to the amygdala and auditory cortex: Receptive field plasticity in the medial division of the medial geniculate body.

The medial division of the medial geniculate body (MGm) projects to the lateral amygdala and the upper layer of the auditory cortex and develops physiological plasticity rapidly during classical conditioning. The effects of learning on frequency receptive fields (RFs) in the MGm of the guinea pig have been determined. Classical conditioning (tone–footshock), as indexed by rapid development of conditioned bradycardia, produced conditioned stimulus (CS)–frequency specific RF plasticity: increased response at the CS frequency with decreased responses at other frequencies, both immediately and after a 1-hr retention period. Sensitization training produced only general changes in RFs. These findings are considered with reference to both the elicitation of amygdala-mediated, fear-conditioned responses and the mechanism of retrieval of information stored in the auditory cortex during acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Ultra-dense planar metallic nanowire arrays with extremely large anisotropic optical and magnetic properties

A nanofabrication method for the production of ultra-dense planar metallic nanowire arrays scalable to wafer-size is presented. The method is based on an efficient template deposition process to grow diverse metallic nanowire arrays with extreme regularity in only two steps. First, III–V semiconductor substrates are irradiated by a low-energy ion beam at an elevated temperature, forming a highly ordered nanogroove pattern by a “reverse epitaxy” process due to self-assembly of surface vacancies. Second, diverse metallic nanowire arrays (Au, Fe, Ni, Co, FeAl alloy) are fabricated on these III–V templates by deposition at a glancing incidence angle. This method allows for the fabrication of metallic nanowire arrays with periodicities down to 45 nm scaled up to wafer-size fabrication. As typical noble and magnetic metals, the Au and Fe nanowire arrays produced here exhibited large anisotropic optical and magnetic properties, respectively. The excitation of localized surface plasmon resonances (LSPRs) of the Au nanowire arrays resulted in a high electric field enhancement, which was used to detect phthalocyanine (CoPc) in surface-enhanced Raman scattering (SERS). Furthermore, the Fe nanowire arrays showed a very high in-plane magnetic anisotropy of approximately 412 mT, which may be the largest in-plane magnetic anisotropy field yet reported that is solely induced via shape anisotropy within the plane of a thin film.

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