Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs

We explore the possibility of characterizing sperm cells without the need to stain them using spectral and fluorescence lifetime analyses after multi-photon excitation in an insect model. The autofluorescence emission spectrum of sperm of the common bedbug, Cimex lectularius, was consistent with the presence of flavins and NAD(P)H. The mean fluorescence lifetimes showed smaller variation in sperm extracted from the male (tau m, τ_m = 1.54–1.84 ns) than in that extracted from the female sperm storage organ (tau m, τ_m = 1.26–2.00 ns). The fluorescence lifetime histograms revealed four peaks. These peaks (0.18, 0.92, 2.50 and 3.80 ns) suggest the presence of NAD(P)H and flavins and show that sperm metabolism can be characterized using fluorescence lifetime imaging. The difference in fluorescence lifetime variation between the sexes is consistent with the notion that female animals alter the metabolism of sperm cells during storage. It is not consistent, however, with the idea that sperm metabolism represents a sexually selected character that provides females with information about the male genotype.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Flammenpyrolytische Silikatbeschichtung bei Normaldruck als Alternative zu Vakuumverfahren. Combustion CVD of silica as an alternative method to vakuum treatment

In advancement of Pyrosil®‐technology a new kind of precursor delivery was developed, build and tested on real substrates. A Lab‐demonstrator was build to demonstrate the resources of the technology.     

E-Government-Initiative BundOnline 2005 — Gesellschaftlicher Mehrwert oder unwirtschaftliche Geldverschwendung?

Ohne Zusammenfassung     

Kommunikationsoberfläche Membran‐ Vorbild für moderne Nanoanalytik

A central event in the life of a cellular system is the interaction between the exterior and the interior compartments. Biochemical signals arrive at the cellular surface, bind to their membrane bound receptor followed by a conformational change triggering the release of an internal chemical or electrical signal.This basic principle is followed by all our perceptive abilities like sense of smell or taste, but also by different signal transduction pathways involved in nerve conductivity, vision, sense of touch or hearing. To follow and mimic this principle of parallel registration is one of the aims of modern nanobiotechnology. If we are able to specifically biofunctionalize small arrays of a solid surface, which could be an electrode or a semiconductor, this approach will enable us to build up devices called “biochips” or “biosensors” that allow the determination of bioactive molecules with high specificity at lowest concentrations. Potential pharmacological active substrates might be screened as well as new receptors may be determined. Applications in genomics as well as proteomics are realistic. The major prerequisite for such a broad spectrum of applications is the fabrication of receptive surfaces. Biomolecules have to be surface‐adsorbed in a highly reproducible, oriented and well organised fashion, a task which in biology is taken by the cellular membranes as external or internal receptive surfaces. The physical principles like hydrogen bonds, electrostatic or hydrophobic interactions that lead to such an organized surface are well known. To synthesize molecular building blocks and to position them onto an otherwise unspecific surface is one of the challenges of nanobiotechnology combining biological knowledge and chemical skills with biophysical techniques that allow to handle or analyze even single molecules.     

Synchronous Full-Scan for Asynchronous Handshake Circuits

Handshake circuits form a special class of asynchronous circuits that has enabled the industrial exploitation of the asynchronous potential such as low power, low electromagnetic emission, and increased cryptographic security. In this paper we present a test solution for handshake circuits that brings synchronous test-quality to asynchronous circuits. We add a synchronous mode of operation to handshake circuits that allows full controllability and observability during test. This technique is demonstrated on some industrial examples and gives over 99% stuck-at fault coverage, using test-pattern generators developed for synchronous circuits. The paper describes how such a full-scan mode can be achieved, including an approach to minimize the number of dummy latches in case latches are used in the data path of the handshake circuit.     

Regression of severe atherosclerotic plaque in patients with mild elevation of LDL cholesterol

BACKGROUND: Intensive risk factor reduction in patients with dyslipidemias and coronary atherosclerosis has been shown to result in alterations in coronary artery morphology and reduced clinical events. However, the impact of such interventions in populations with relatively normal levels of low-density lipoproteins (LDL) is unclear. METHODS: To test the hypothesis that intensive risk factor reduction results in angiographic regression in patients with only mildly elevated levels of LDL, 14 patients with angiographically proven coronary atherosclerosis were entered into the University of California Davis Coronary Artery Disease Regression Program and intensively treated with pharmacologic and nonpharmacologic interventions for 2 years. Quantitative angiography was performed prior to and after 2 years of therapy to determine changes in coronary artery diameter. RESULTS: As a result of this program, dietary fat intake was reduced by 58% and LDL fell from 120 +/- 7 mg/dL to 104 +/- 6 mg/dL (p = 0.05). The average diameter of the measured arterial locations (including all 53 stenoses and 292 nondiscrete regions) on study entry was 2.74 +/- 0.05 mm. After 24 months, there was a net increase in arterial diameter (regression) of +0.05 +/- 0.04 mm to 2.81 +/- 0.05 mm (p = 0.01). While there was no significant change in the average diameter of discrete stenoses, all 8 lesions > or = 50% initial diameter narrowing regressed, with a mean diameter change of + 0.2 mm. Conversely, only 1 of 8 mild lesions < or = 20% regressed, while 4 progressed. Intermediate lesions (20% to 50%, n = 37) had balanced progression and regression. CONCLUSIONS: When examined as a continuous variable, there was a significant linear correlation between initial lesion severity (% stenosis) and the extent of regression (mm). Therefore, risk factor reduction (dietary therapy, exercise, psycho-social counseling, and lipid lowering therapy) in patients with only mild dyslipidemia results in angiographic regression of more severe lesions (> 50% initial stenosis), but does not prevent progression of mild lesions (< 20%). These findings demonstrate that intensive risk factor reduction in patients with only mild elevation of lipids beneficially influences the morphology of the most severe lesions.