Preventing nanoscale wear of atomic force microscopy tips through the use of monolithic ultrananocrystalline diamond probes.

Nanoscale wear is a key limitation of conventional atomic force microscopy (AFM) probes that results in decreased resolution, accuracy, and reproducibility in probe-based imaging, writing, measurement, and nanomanufacturing applications. Diamond is potentially an ideal probe material due to its unrivaled hardness and stiffness, its low friction and wear, and its chemical inertness. However, the manufacture of monolithic diamond probes with consistently shaped small-radius tips has not been previously achieved. The first wafer-level fabrication of monolithic ultrananocrystalline diamond (UNCD) probes with <5-nm grain sizes and smooth tips with radii of 30-40 nm is reported, which are obtained through a combination of microfabrication and hot-filament chemical vapor deposition. Their nanoscale wear resistance under contact-mode scanning conditions is compared with that of conventional silicon nitride (SiN(x)) probes of similar geometry at two different relative humidity levels (approximately 15 and approximately 70%). While SiN(x) probes exhibit significant wear that further increases with humidity, UNCD probes show little measurable wear. The only significant degradation of the UNCD probes observed in one case is associated with removal of the initial seed layer of the UNCD film. The results show the potential of a new material for AFM probes and demonstrate a systematic approach to studying wear at the nanoscale.

NMR and quenched molecular dynamics studies of superpotent linear and cyclic alpha-melanotropins.

Conformational searching, computer simulations, synthesis and NMR are used on a variety of alpha melanocyte-stimulating hormone (alpha-MSH) analogues to understand the physical characteristics required for biological potency. Peptides I (Ac-[Nle4,Asp5,D-Phe7,Lys10]alpha-MSH(4-10)-NH2), II (Ac-c[Nle4,Asp5,D-Phe7,Lys10]alpha-MSH(4-10)-NH2) and III (Ac-[Nle4,Asp5,D-Phe7,Dap10]alpha-MSH(4-10)-NH2 all show very similar conformational properties (backbone and side-chain torsional angles), and all display high biological potencies. The modeling results for these compounds are supported by the NMR data. Peptide IV (Ac-c[Nle4,Asp5,D-Phe7,Dap10]alpha-MSH(4-10)-NH2) appears to have a markedly different conformation and has decreased biological potency.

Atomic force microscopy of human hair cuticles: a microscopic study of environmental effects on hair morphology.

We have used an atomic force microscope to provide quantitative real-time analysis of human hair morphologic changes under ambient conditions. This form of microscopy combines the lateral resolution of an electron microscope and the flexibility of a light microscope. Three experiments were performed: a study of hair morphology in air versus water, a kinetic study of hair hydration, and a determination of how pH changes affect hair morphology. The overlapping keratinized cells that form the hair cuticle spread out between 50 and 150% when hydrated, compared to a total shaft diameter change of 10%. This hydration reaches a saturation point within the first few minutes after immersion. Also, hair swells much more at higher pH.

Quenched molecular dynamics simulations of tuftsin and proposed cyclic analogues.

We have used high-temperature quenched molecular dynamics calculations to investigate the conformational properties of tuftsin (Thr-Lys-Pro-Arg) in solution. Conformers obtained after quenching of the dynamical structures were sorted into families depending on their relative energies and backbone conformations. By examination of these families, several cyclic analogues of tuftsin were proposed and examined theoretically by further quenched dynamics simulations. Two of the four proposed analogues were found to adopt essentially identical conformations to that of linear tuftsin. It is suggested that these two derivatives (cyclo[Thr-Lys-Pro-Arg-Gly] and cyclo[Thr-Lys-Pro-Arg-Asp]) may be biologically active, and that the introduction of cyclic conformational constraints should help to reduce the entropic penalty to peptide binding.

Chronic Ro 15-1788 treatment increases REM sleep in rats.

Administration of Ro 15-1788, a benzodiazepine antagonist (3.6 mg/kg/day in drinking water for 14 days), increased total sleep and rapid eye movement (REM) sleep in rats. Standard six-hour EEG recording periods were obtained on day 0, 1, 3, 7, 10, 14, as well as 24 and 72 hours following withdrawal. Enhanced REM sleep reached significance on day 7 of continuous drug treatment and remained significantly increased on day 10 and 14, as well as at 24 and 72 hours following drug withdrawal. The present data show that chronic administration of Ro 15-1788 increases total sleep time due to increases in REM sleep. The actions of Ro 15-1788 presumably occur through either adenosinergic or cholinergic mechanisms.

The effect of soluflazine on sleep in rats.

Soluflazine, a specific adenosine transport inhibitor, was intracerebroventricularly administered to rats in a dose range of 10, 25, and 50 nmoles. At a dose of 50 nmoles, soluflazine decreased waking and increased sleep during the first hour of EEG recording. Our previous work has shown that chronic intracerebroventricular administration of soluflazine to rats decreased radioligand binding to adenosine A1 and A2 receptors in specific brain regions. The present data show that administration of an adenosine transport inhibitor to rats produces a transient hypnotic effect presumably through increases in synaptic adenosine levels.

The effect of soluflazine on adenosine receptors in the rat brain.

Soluflazine, a potent adenosine transport inhibitor, was intracerebroventricularly administered to rats via ALZET mini osmotic pumps (4nmole, 0.5 L/hr) for 14 days and the effect on adenosine receptors was determined in specific brain areas. Soluflazine decreased adenosine A1 radioligand binding in the hippocampus as measured by [3H]R-PIA, and lowered adenosine A2 binding sites in the striatum, as estimated by the "NECA minus R-PIA" assay. Previous work from our lab has shown the ability of diazepam and triazolam to decrease adenosine binding in the same brain areas. The data show that a specific adenosine transport inhibitor produces the same effect on adenosine receptors as benzodiazepines, and suggest a role for adenosine in the CNS effects of benzodiazepines.