Studies of Na-segregation at Ni/α-quartz interfaces

Ni/α-quartz bilayers were irradiated at 77 K with 200 keV Na⁺ ions at a fluence of 5 × 10¹⁶ ions/cm² and annealed in hydrogen up to 883 K. The Na-migration at the Ni/α-quartz interface and towards the Ni-surface, the hydrogen storage in the irradiated region, and the Ni/α-quartz interface broadening due to Na implantation and decoration were investigated via Rutherford Backscattering Spectrometry (RBS) and Resonant Nuclear Reaction Analysis (RNRA). We demonstrate that after a one hour-annealing at 833 K a large fraction of the implanted Na has been trapped at the Ni/α-quartz interface from where it is released at 883 K. The results are discussed and compared with our findings in Na-irradiated metals and silicon compounds.     

Peptide Bioconjugates of Electron‐Poor Metallocenes: Synthesis,Characterization, and Anti‐Proliferative Activity

We report the synthesis of metallocene compounds Cp₂M with two different electron‐withdrawing substituents on both cyclopentadienyl rings (hexafluoroacetone (HFA) and chlorobenzoyl ( 1 – 5 ); HFA and COOH ( 6 and 7 ), M=Fe or Ru). The COOH‐containing derivatives were used to synthesize peptide bioconjugates with enkephalin ( 8 and 9 ) and neurotensin ( 10 and 11 ) as well as fluorescein‐labeled neurotensin ( 12 ). All the molecules were fully characterized, including X‐ray structures for 6 and 7 . The physicochemical properties (lipophilicity and electrochemistry) and cytotoxicity on MCF‐7, HT‐29, and PT‐45 cancer cells were evaluated for selected compounds. Electrochemical investigation by cyclic voltammetry revealed that all bis‐substituted metallocenes are up to 300 mV harder to oxidize compared to the monosubstituted 2‐ferrocenylhexafluoropropan‐2‐ol (FcHFA: Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =214 mV; disubstituted derivatives: up to Δ${E{{{\rm f}\hfill \atop 0\hfill}}}$ =512 mV; both vs. FcH^0/+). For the bis‐substituted compounds, log P determinations by RP‐HPLC showed increased lipophilicity in comparison to the monosubstituted FcHFA and RcHFA. Cellular uptake was investigated by fluorescence microcopy, and this revealed endosomal entrapment for 12 .     

In-situ monitoring of pharmaceutical and specialty chemicals crystallization processes using endoscopy–stroboscopy and multivariate image analysis

This contribution presents the proof of concept of endoscopy–stroboscopy based in situ low-cost imaging of crystallization processes. This low-cost sensor currently is widely spread in the field of medical diagnosis of human vocal chords and this work presents its application in the context of pharmaceutical and chemical crystallization process monitoring. The model compounds used in this study are the active pharmaceutical ingredient (API) flufenamic acid and citric acid.     

Interleukin-6-associated inflammatory processes in Alzheimer's disease: new therapeutic options

The cytokine interleukin-6 is consistently detected in the brains of Alzheimer's disease patients but not in the brains of nondemented elderly persons. Until recently it was unclear whether an interleukin-6-associated inflammatory mechanism is an early or late event in the pathological cascade of Alzheimer's disease. We investigated whether interleukin-6 could be detected in plaques of Alzheimer's disease patients prior to the onset of neuritic degeneration. We found interleukin-6 mostly in plaques where neuritic pathology has not yet developed. This indicates that the appearance of interleukin-6 may precede neuritic changes and is not just a consequence of neuritic degeneration. Therefore, one may hypothesize that activation of inflammatory mechanisms may cause neuritic degeneration in plaques. A suppression of interleukin-6 synthesis could, therefore, be of therapeutic value. Upon screening a number of substances, we found that a small number of nonsteroidal antiinflammatory drugs, including tenidap, were able to inhibit interleukin-6 synthesis in cultured human astrocytoma cells. These substances may be therapeutically useful in Alzheimer's disease and should be evaluated in clinical studies.     

RBS analyses of xenon-irradiated Ti and TiN films

TiN films of 30–300 nm thickness, deposited onto stainless steel via magnetron sputtering, and 10 μm thick Ti foils were irradiated with 80–360 keV Xe⁺ ions at influences of φ = 10¹⁵–10¹⁷ ions/cm². The Xe content was depth-profiled by means of 900 keV He⁺⁺ Rutherford backscattering. Irradiations of films with a thickness exceeding the ion range (at 80 and 250 keV) led to saturation effects due to sputtering and outdiffusion from the near-surface region. The sputtering yields deduced at low Xe fluences were compared to calculations for mono-elemental and compound sputtering. Surface blistering was observed after 250 keV saturation implantation into Ti. For TiN layers with a thickness comparable to the ion range, precipitation of the mixing gas at the interface was observed which finally led to the destruction of the layers. The dependence of the Xe fraction accumulated in the interface is discussed in terms of thermal-spike calculations.     

‘Baltimore does not condone profiteering in squalor’: the Baltimore Plan and the problem of housing-code enforcement in an American city

In 1941, the Baltimore City Council passed a law, the Ordinance on the Hygiene of Housing, declaring that all property in the city should be ‘maintained in good repair by the owner or agent, and fit for human habitation’. The campaign of housing-code enforcement that followed, known as the Baltimore Plan, made the city famous. When historians write about American housing-reform efforts during the mid-20th century, they tend to focus on big-ticket federal policies; by contrast, the Baltimore Plan seems too small to be significant. But it is more than a curiosity. First in Baltimore and then across the country, the neat cause-and-effect it posited between good stewardship and good housing crowded out more challenging ways of thinking about the problem. Eventually, the Baltimore Plan turned into a policy tool that reinforced the interests of the real estate industry at the expense of poor people. In that regard, the Baltimore Plan laid the foundations for federal disinvestment in the provision of decent housing and the midcentury tragedy of urban renewal.     

Effects of temperature and volatile anesthetics on GABA(A) receptors

BACKGROUND: Potentiation of the activity of the gamma-aminobutyric acid type A (GABA(A)) receptor channel by volatile anesthetic agents is usually studied in vitro at room temperature. Systematic variation of temperature can be used to assess the relevance of this receptor to general anesthesia and to characterize the modulation of its behavior by volatile agents at normal body temperature. METHODS: Potentiation of the GABA(A) receptor by halothane, sevoflurane, isoflurane, and methoxyflurane was studied at six temperatures in the range 10-37 degrees C using the whole-cell patch-clamp technique and mouse fibroblast cells stably transfected with defined GABA(A) receptor subunits. RESULTS: Control GABA concentration-response plots showed small and physically reasonable changes in the GABA concentration required for a half-maximal effect, the Hill coefficient, and maximal response over the range 10-30 degrees C. Potentiations of GABA (1 microM) responses by aqueous minimum alveolar concentrations of the volatile anesthetic agents decreased with increasing temperature from 10-37 degrees C in an agent-specific manner (methoxyflurane > isoflurane > sevoflurane > halothane) but tended to equalize at normal body temperature (37 degrees C). These findings are in line with published results on the temperature dependence of anesthetic potencies in animals. CONCLUSIONS: These results are consistent with direct binding of volatile anesthetic agents to the GABA(A) receptor channel playing an important role in general anesthesia. The finding that the degree of anesthetic potentiation was agent-specific at low temperatures but not at 37 degrees C emphasizes the importance of doing in vitro experiments at normal body temperature.     

The effects of temperature on the interactions between volatile general anaesthetics and a neuronal nicotinic acetylcholine receptor

1. Completely isolated identified neurones from the right parietal ganglion of the pond snail Lymnaea stagnalis were investigated under two-electrode voltage clamp. Neuronal nicotinic acetylcholine receptor (AChR) currents were studied at low acetylcholine concentrations (< or = 200 nM). 2. Inhibition of the ACh-induced currents by three volatile general anaesthetics (halothane, isoflurane and methoxyflurane) and the specific inhibitor (+)-tubocurarine was studied as a function of temperature (over the range 4-25 degrees C). 3. The inhibition by the volatile anaesthetics increased (inhibition constants decreased) with decreasing temperature while the inhibition by (+)-tubocurarine did not change significantly near room temperature, but decreased at lower temperatures. The (+)-tubocurarine inhibition appeared to be competitive in nature and showed no significant voltage-dependence. 4. The van't Hoff plots (logarithms of the dissociation constants against reciprocal absolute temperature) were linear for the anaesthetics, but markedly non-linear for (+)-tubocurarine. From these plots, values for the changes in the standard Gibbs free energy delta G degrees water-->AChR, enthalpy delta H degree water-->AChR, entropy delta S degree water-->AChR and heat capacity delta Cp degree water-->AChR were determined. Tubocurarine was found to bind very much tighter to the receptor than the volatile anaesthetics due, entirely, to a favourable increase in entropy on binding. 5. A comparison between the temperature-dependence of the anaesthetic inhibition of the ACh receptor and that of general anaesthetic potencies in animals indicates that the temperature-dependence of animal potencies might be simply accounted for in terms of changes in anaesthetic/receptor binding.