Charge transport in GaAs nanowires: interplay between conductivity through the interior and surface conductivity.

The charge transport through GaAs nanowires, partially p-doped and partially intrinsic, is analyzed by four-point resistance profiling along freestanding nanowires using a multip-STM. The charge transport channel in the undoped segment is assigned to the surface conductivity, while the interior of the nanowire is the conductance channel in the p-doped segment. The convoluted interplay between conduction through the interior of the nanowire and surface state conduction is studied in detail. Measurements of the I-V curves along the nanowires provide the experimental basis for the proposed charge transport model for the transition of the conduction from the interior to the surface of the nanowire. A voltage drop along the surface state conduction channel leads to an upward shift of the band edges at the surface. This results, for higher applied voltages, in the removal of the depletion layer and an opening of a conductance channel between the interior of the nanowire and the surface states.

Invited Review Article: Multi-tip scanning tunneling microscopy: Experimental techniques and data analysis.

In scanning tunneling microscopy, we witness in recent years a paradigm shift from "just imaging" to detailed spectroscopic measurements at the nanoscale and multi-tip scanning tunneling microscope (STM) is a technique following this trend. It is capable of performing nanoscale charge transport measurements like a "multimeter at the nanoscale." Distance-dependent four-point measurements, the acquisition of nanoscale potential maps at current carrying nanostructures and surfaces, as well as the acquisition of I - V curves of nanoelectronic devices are examples of the capabilities of the multi-tip STM technique. In this review, we focus on two aspects: How to perform the multi-tip STM measurements and how to analyze the acquired data in order to gain insight into nanoscale charge transport processes for a variety of samples. We further discuss specifics of the electronics for multi-tip STM and the properties of tips for multi-tip STM, and present methods for a tip approach to nanostructures on insulating substrates. We introduce methods on how to extract the conductivity/resistivity for mixed 2D/3D systems from four-point measurements, how to measure the conductivity of 2D sheets, and how to introduce scanning tunneling potentiometry measurements with a multi-tip setup. For the example of multi-tip measurements at freestanding vapor liquid solid grown nanowires, we discuss contact resistances as well as the influence of the presence of the probing tips on the four point measurements.

Four-point probe measurements using current probes with voltage feedback to measure electric potentials.

We present a four-point probe resistance measurement technique which uses four equivalent current measuring units, resulting in minimal hardware requirements and corresponding sources of noise. Local sample potentials are measured by a software feedback loop which adjusts the corresponding tip voltage such that no current flows to the sample. The resulting tip voltage is then equivalent to the sample potential at the tip position. We implement this measurement method into a multi-tip scanning tunneling microscope setup such that potentials can also be measured in tunneling contact, allowing in principle truly non-invasive four-probe measurements. The resulting measurement capabilities are demonstrated for [Formula: see text] and [Formula: see text] samples.

Surface and Step Conductivities on Si(111) Surfaces.

Four-point measurements using a multitip scanning tunneling microscope are carried out in order to determine surface and step conductivities on Si(111) surfaces. In a first step, distance-dependent four-point measurements in the linear configuration are used in combination with an analytical three-layer model for charge transport to disentangle the 2D surface conductivity from nonsurface contributions. A termination of the Si(111) surface with either Bi or H results in the two limiting cases of a pure 2D or 3D conductance, respectively. In order to further disentangle the surface conductivity of the step-free surface from the contribution due to atomic steps, a square four-probe configuration is applied as a function of the rotation angle. In total, this combined approach leads to an atomic step conductivity of σ(step)=(29±9) Ω(-1) m(-1) and to a step-free surface conductivity of σ(surf)=(9±2)×10(-6) Ω(-1)/□ for the Si(111)-(7×7) surface.

Combined frequency modulated atomic force microscopy and scanning tunneling microscopy detection for multi-tip scanning probe microscopy applications.

A method which allows scanning tunneling microscopy (STM) tip biasing independent of the sample bias during frequency modulated atomic force microscopy (AFM) operation is presented. The AFM sensor is supplied by an electronic circuit combining both a frequency shift signal and a tunneling current signal by means of an inductive coupling. This solution enables a control of the tip potential independent of the sample potential. Individual tip biasing is specifically important in order to implement multi-tip STM/AFM applications. An extensional quartz sensor (needle sensor) with a conductive tip is applied to record simultaneously topography and conductivity of the sample. The high resonance frequency of the needle sensor (1 MHz) allows scanning of a large area of the surface being investigated in a reasonably short time. A recipe for the amplitude calibration which is based only on the frequency shift signal and does not require the tip being in contact is presented. Additionally, we show spectral measurements of the mechanical vibration noise of the scanning system used in the investigations.

Selective adsorption of C60 on Ge/Si nanostructures.

Selective adsorption of C60 on nanoscale Ge areas can be achieved, while neighboring Si(111) areas remain uncovered, if the whole surface is initially terminated by Bi. Fullerene chemisorption is found at Bi vacancies which form due to partial thermal desorption of the Bi surfactant. The growth rate and temperature dependence of the C60 adsorption were measured using scanning tunneling microscopy and are described consistently by a rate equation model. The selectivity of the C60 adsorption can be traced back to an easier vacancy formation in the Bi layer on top of the Ge areas compared to the Si areas. Furthermore, it is also possible to desorb C60 from Ge areas, allowing the use of C60 as a resist on the nanoscale.

Ultra compact multitip scanning tunneling microscope with a diameter of 50 mm.

We present a multitip scanning tunneling microscope (STM) where four independent STM units are integrated on a diameter of 50 mm. The coarse positioning of the tips is done under the control of an optical microscope or scanning electron microscopy in vacuum. The heart of this STM is a new type of piezoelectric coarse approach called KoalaDrive. The compactness of the KoalaDrive allows building a four-tip STM as small as a single-tip STM with a drift of less than 0.2 nm/min at room temperature and lowest resonance frequencies of 2.5 kHz (xy) and 5.5 kHz (z). We present as examples of the performance of the multitip STM four point measurements of silicide nanowires and graphene.

Adaptive servoventilation improves cardiac function and respiratory stability.

Cheyne-Stokes respiration (CSR) in patients with chronic heart failure (CHF) is of major prognostic impact and expresses respiratory instability. Other parameters are daytime pCO2, VE/VCO2-slope during exercise, exertional oscillatory ventilation (EOV), and increased sensitivity of central CO2 receptors. Adaptive servoventilation (ASV) was introduced to specifically treat CSR in CHF. Aim of this study was to investigate ASV effects on CSR, cardiac function, and respiratory stability. A total of 105 patients with CHF (NYHA ≥ II, left ventricular ejection fraction (EF) ≤ 40%) and CSR (apnoea-hypopnoea index ≥ 15/h) met inclusion criteria. According to adherence to ASV treatment (follow-up of 6.7 ± 3.2 months) this group was divided into controls (rejection of ASV treatment or usage <50% of nights possible and/or <4 h/night; n = 59) and ASV (n = 56) adhered patients. In the ASV group, ventilator therapy was able to effectively treat CSR. In contrast to controls, NYHA class, EF, oxygen uptake, 6-min walking distance, and NT-proBNP improved significantly. Moreover, exclusively in these patients pCO2, VE/VCO2-slope during exercise, EOV, and central CO2 receptor sensitivity improved. In CHF patients with CSR, ASV might be able to improve parameters of SDB, cardiac function, and respiratory stability.

Role of copper and manganese in prion disease progression.

The cellular prion protein (PrP(C)), a copper binding protein has a primary role in the pathogenesis of in prion diseases. In these diseases alterations in the levels of copper and manganese have been described but how these alterations are involved in the pathogenesis is still unknown. Here we analysed synaptosomes of scrapie infected mice and observed a significant reduction in the amount of copper and an increase of the manganese content at day 100 after infection. Moreover a reduction of the copper content in mouse brains induced by application of copper poor diets was found to reduce the survival time of scrapie infected mice significantly, whereas enhanced administration of copper induced a significant delay in prion disease onset. Interestingly a significant higher amount of PrP(C) full length and misfolded PK-resistant PrP was observed in mice that were treated with an enhanced copper diet compared to controls. Moreover we could demonstrate that in healthy mock infected mice, a Cu(2+) rich/Mn(2+) poor diet induced a significantly decreased cleavage capability of PrP(C) compared to control mice. These new findings suggest that the copper content in mouse brains exerts an influence on the amount of PrP(C) and its cleavage properties and may affect the PrP conversion by depleted availability of functional PrP full length.

Afferentation of a caudal forebrain area activated during courtship behavior: a tracing study in the zebra finch (Taeniopygia guttata).

A caudal forebrain area of zebra finches that comprises a part of the caudal nidopallium and a part of the intermediate arcopallium is highly activated during courtship. This activation is thought to reflect the processing of information that is necessary for the choice of an appropriate mate. In addition to the information on the potential mate, control of courtship behavior includes motivational aspects. Being involved in the integration of external input and previously stored information, as well as in adding motivational factors, the caudal nidopallium and intermediate arcopallium should be integrative areas receiving input from many other regions of the brain. Our results indeed show that the caudal nidopallium receives input from a variety of telencephalic regions including the secondary visual and auditory areas. The intermediate arcopallium is recipient of input from intermediate and caudal nidopallium, mesopallium and densocellular hyperpallium. Regions closely associated with the song control nuclei also innervate both regions. There are also specific visual and auditory thalamic inputs, while specific motivating catecholaminergic mesencephalic afferents include the ventral tegmental area, the substantia nigra and the locus coeruleus. In addition, non-specific activation reaches these areas from the mesencephalic reticular formation. Bilateral innervation by ventral intermediate arcopallium indicates links with sensori-motor pathways, while the projection from the caudal nidopallium to intermediate arcopallium suggests monosynaptic and disynaptic input to downstream motor pathways. These findings support the idea of an involvement of the caudal nidopallium and the intermediate arcopallium in the control of courtship behavior.

Pyrexia, anorexia, adipsia, and depressed motor activity in rats during systemic inflammation induced by the Toll-like receptors-2 and -6 agonists MALP-2 and FSL-1.

Macrophage-activating lipopeptide-2 (MALP-2) from Mycoplasma fermentans has been identified as a pathogen-associated molecular pattern of Mycoplasmas that causes activation of the innate immune system through the activation of the heterodimeric Toll-like receptors (TLRs)-2 and -6. The aim of this study was to characterize the ability of MALP-2 and a synthetic analog fibroblast-stimulating lipopeptide-1 (FSL-1; represents the NH2-terminal sequence of a lipoprotein from M. salivarium) to act as exogenous pyrogens, to induce formation of cytokines (endogenous pyrogens), and to cause sickness behavior, such as depressed motor activity, anorexia, and adipsia. For this purpose, body temperature, activity, food intake, and water intake were recorded for 3 days by use of telemetry devices in several groups of rats treated with MALP-2/FSL-1 or the respective control solutions. Intraperitoneal injections of FSL-1 caused fever at doses of 10 or 100 microg/kg, which was preceded by a pronounced phase of hypothermia in response to a dose of 1,000 microg/kg. The maximal fever (a peak of 1.5 degrees C above baseline) was caused by the 100 microg/kg dose with almost identical responses to both MALP-2 and FSL-1. Fever was accompanied by pronounced rises of the proinflammatory cytokines TNF and IL-6 in plasma. Treatment with the TLR-2 and -6 agonists further induced a dose-dependent manifestation of anorexia and adipsia, as well as a reduction of motor activity. We could thus demonstrate that activation of TLR-2 and -6 can induce systemic inflammation in rats accompanied by the classical signs of brain-controlled illness responses.

Nuclear STAT3 translocation in guinea pig and rat brain endothelium during systemic challenge with lipopolysaccharide and interleukin-6.

During systemic inflammation, cytokines are released by immune-competent cells into the circulation, which in turn signal the brain to mediate brain-controlled signs of illness. Cytokine-responsive brain cells can be mapped by histological analysis of cytokine-induced transcription factors or transcription factor-associated molecules revealing different cell phenotypes that respond to activation of the immune system. Critical sites mediating cytokine-dependent immuneffector functions can be divided into two groups, one group of responding cells situated along a tight blood-brain barrier (BBB), and a second cell group in structures with an open BBB, e.g., the sensory circumventricular organs (CVOs). Previous reports from our group suggest that activation of the signal transducer and activator of transcription factor 3 (STAT3) during lipopolysaccharide (LPS)-induced systemic inflammation is mediated by interleukin-6 (IL-6) and occurs in astrocytes of the rat CVOs. Here we show in the guinea pig a time-dependent marked LPS-induced STAT3 activation within astrocytes and endothelial cells of the CVOs, within astrocytes located in brain structures with a functional BBB and within the brain endothelium of the entire brain. In addition, systemic treatment of rats with either rat recombinant IL-6 or LPS induced STAT3 activation in brain endothelial cells in a similar way as observed in the guinea pig brain, stressing the involvement of IL-6 in this phenomenon in a more generalized way. The STAT3-activated brain cells are located in critical target structures mediating cytokine action during LPS-induced inflammation. STAT3-controlled transcriptional activation with yet unknown cell-specific functional consequences seems to be involved in this process.

Localized vs. systemic inflammation in guinea pigs: a role for prostaglandins at distinct points of the fever induction pathways?

In guinea pigs, dose-dependent febrile responses were induced by injection of a high (100 microg/kg) or a low (10 microg/kg) dose of bacterial lipopolysaccharide (LPS) into artificial subcutaneously implanted Teflon chambers. Both LPS doses further induced a pronounced formation of prostaglandin E(2) (PGE(2)) at the site of localized subcutaneous inflammation. Administration of diclofenac, a nonselective cyclooxygenase (COX) inhibitor, at different doses (5, 50, 500, or 5,000 microg/kg) attenuated or abrogated LPS-induced fever and inhibited LPS-induced local PGE(2) formation (5 or 500 microg/kg diclofenac). Even the lowest dose of diclofenac (5 microg/kg) attenuated fever in response to 10 microg/kg LPS, but only when administered directly into the subcutaneous chamber, and not into the site contralateral to the chamber. This observation indicated that a localized formation of PGE(2) at the site of inflammation mediated a portion of the febrile response, which was induced by injection of 10 microg/kg LPS into the subcutaneous chamber. Further support for this hypothesis derived from the observation that we failed to detect elevated amounts of COX-2 mRNA in the brain of guinea pigs injected subcutaneously with 10 microg/kg LPS, whereas subcutaneous injections of 100 microg/kg LPS, as well as systemic injections of LPS (intra-arterial or intraperitoneal routes), readily caused expression of the COX-2 gene in the guinea pig brain, as demonstrated by in situ hybridization. Therefore, fever in response to subcutaneous injection of 10 microg/kg LPS may, in part, have been evoked by a neural, rather than a humoral, pathway from the local site of inflammation to the brain.

Modulation of L-type voltage-gated calcium channels by recombinant prion protein.

The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies. Here we analysed in detail the effect of recombinant PrPC and N- and C-terminal fragments of PrPC on the whole-cell current amplitude through voltage-gated calcium channels (VGCCs) of cultured wild-type cerebellar granule cells. With the application of full-length recombinant PrPC (50-500 nm), a highly significant reduction of the whole-cell current amplitude was observed in a dose-dependent manner. Amplitude reduction was abolished when cells were pre-incubated with nifedipine, a specific blocker of voltage-gated L-type calcium channels. N-terminal PrP fragments also led to a dose-dependent reduction of the maximal current amplitude, whereas a C-terminal fragment did not affect the current amplitude. These data demonstrate that nanomolar concentrations of PrPC modulate L-type VGCCs in mouse cerebellar granule cells, an effect that is dependent upon the copper-binding amino-terminal domain of PrPC.

Methods for studying synaptosomal copper release.

Cu is thought to play an important role in the pathogenesis of several neurodegenerative diseases, such as Wilson's, Alzheimer's, and probably in prion protein diseases like Creutzfeld-Jakob's disease. Until now, no method existed to determine the concentration of this cation in vivo. Here, we present two possible approaches combined with a critical comparison of the results. The successful use of fluorescent ligands for the determination of Ca2+-concentrations in recent years encouraged us to seek a fluorophore which specifically reacts to Cu2+ and to characterize it for our purposes. We found that the emission of TSPP (tetrakis-(4-sulfophenyl)porphine) at an emission wavelength of 645 nm is in vitro highly specific to Cu2+ (apparent dissociation constant Kd=0.43 +/- 0.07 microM at pH 7.4). It does not react with the most common divalent cations in the brain, Ca2+ and Mg2+, unlike most of the other dyes examined. In addition, Zn2+ quenches TSPP fluorescence at a different emission wavelength (605 nm) with a Kd of 50 +/- 2.5 microM (pH 7.0). With these findings, we applied the measurement of Cu with TSPP to a biological system, showing for the first time in vivo that there is release of copper by synaptosomes upon depolarisation. Our findings were validated with a completely independent analytical approach based on ICP-MS (inductively-coupled-plasma mass-spectrometry).