Organs from animals for man

In the following review some of the problems of xenotransplantation shall be discussed, based on the few experimental data available so far and on reports in the literature describing investigations which may be of importance for xenotransplantation. The impact of gravity on the upright posture of man versus almost all other mammals, the dysfunction between enzymes and hormones in different species and the lack of interactions between interleukins, cytokines and vasoactive substances will be taken into consideration. The question must be asked whether different levels of carrier molecules or serum proteins play a role in the physiological network. Even though the development of transgenic animals or other imaginative manipulations may lead to the acceptance of any type of xenografted organ, it has to be established for how long the products of the xenografts are able to act in the multifactorial orchestra. We are far from understanding xenogeneic molecular mechanisms involved in toxicity, necrosis and apoptosis or even reperfusion injury and ischemia in addition to the immediate mechanisms of the hyperacute xenogeneic rejection. Here, cell adhesion, blood clotting and vasomotion collide and bring micro-and macrocirculation to a standstill. All types of xenogeneic immunological mechanisms studied so far were found to have a more serious impact than those seen in allogeneic transplantation. In addition we are now only beginning to understand that so-called immunological parameters in allogeneic mechanisms act also in a true physiological manner in the xenogeneic situation. These molecular mechanisms occur behind the curtain of hyperacute, accelerated, acute or chronic xenograft rejection of which only some folds have been lifted to allow glimpses of part of the total scene. Other obstacles are likely to arise when long-term survival is achieved. These obstacles include retroviral infections, transfer of prions and severe side effects of the massive immunosuppression which will be needed. Moral, ethical and religious concerns are under debate and the species-specific production of proteins of the foreign donor species developed for clinical use suddenly appears to be a greater problem than anticipated

Enhancing engagement in evidence-based tobacco cessation treatment for smokers with mental illness: A pilot randomized trial.

ObjectiveTo evaluate the efficacy of a brief telephone-delivered Motivational Interviewing (MI)-based intervention to facilitate engagement in evidence-based cessation treatment for Veterans with mental illness referred to smoking cessation treatment.Methods86 military Veteran smokers with mental illness were recruited from a tobacco cessation consult clinic and randomized to receive either a MI-based treatment engagement intervention (TE; n = 48) or a non-MI assessment and information control (CON; n = 38) condition. Intervention was delivered during a single brief telephone contact. Primary engagement outcomes were 1) attending a treatment session within 30 days and 2) combination treatment (attending session plus using pharmacotherapy). Cessation outcomes included self-reported 24 h cessation attempts and 7 day point abstinence at 3 months post-intervention. Outcomes were assessed at 1 and 3 months post intervention.ResultsOutcome analyses included 85 participants (47 TE, 38 CON) using an intent-to-treat analytic approach. Participants were on average 49.5 (13.4) years old, 88% Male, 59% white, 18% African American and 14% Hispanic/Latino(a). Following intervention delivery TE and CON participants did not differ on likelihood of attending a treatment session during the subsequent 30 days (47% vs 45%, respectively). A significant difference was observed when classified as utilizing combination treatment, 40% of TE versus 18% of CON reported use of smoking cessation medication and behavioral counseling (p = 0.04). No statistical differences were observed for cessation outcomes, although more TE than CON participants reported 7 day point abstinence at 3 months post-intervention (30% vs 18%).ConclusionsThe present pilot study provides initial evidence for the feasibility, acceptability and efficacy of a telephone delivered TE intervention for enhancing engagement in combinationevidence evidence-based treatment in a sample of Veteran smokers with mental illness referred to smoking cessation treatment. Smokers with mental illness typically have greater difficulty stopping smoking than those without mental illness. Increased engagement in combination treatment thus has the potential to increase quit rates and ultimately reduce the burden of tobacco use for this population

Optimizing Stimulation and Analysis Protocols for Neonatal fMRI

The development of brain function in young infants is poorly understood. The core challenge is that infants have a limited behavioral repertoire through which brain function can be expressed. Neuroimaging with fMRI has great potential as a way of characterizing typical development, and detecting abnormal development early. But, a number of methodological challenges must first be tackled to improve the robustness and sensitivity of neonatal fMRI. A critical one of these, addressed here, is that the hemodynamic response function (HRF) in pre-term and term neonates differs from that in adults, which has a number of implications for fMRI. We created a realistic model of noise in fMRI data, using resting-state fMRI data from infants and adults, and then conducted simulations to assess the effect of HRF of the power of different stimulation protocols and analysis assumptions (HRF modeling). We found that neonatal fMRI is most powerful if block-durations are kept at the lower range of those typically used in adults (full on/off cycle duration 25-30s). Furthermore, we show that it is important to use the age-appropriate HRF during analysis, as mismatches can lead to reduced power or even inverted signal. Where the appropriate HRF is not known (for example due to potential developmental delay), a flexible basis set performs well, and allows accurate post-hoc estimation of the HRF

Diffusion Enhancement in a Periodic Potential under High-Frequency Space-Dependent Forcing

We study the long-time behavior of underdamped Brownian particle moving through a viscous medium and in a systematic potential, when it is subjected to a space-dependent high-frequency periodic force. When the frequency is very large, much larger than all other relevant system-frequencies, there is a Kapitsa time-window wherein the effect of frequency dependent forcing can be replaced by a static effective potential. Our new analysis includes the case when the forcing, in addition to being frequency-dependent, is space-dependent as well. The results of the Kapitsa analysis then lead to additional contributions to the effective potential. These are applied to the numerical calculation of the diffusion coefficient (D) for a Brownian particle moving in a periodic potential. Presented are numerical results, which are in excellent agreement with theoretical predictions and which indicate a significant enhancement of D due to the space-dependent forcing terms. In addition we study the transport property (current) of underdamped Brownian particles in a ratchet potential.Comment: RevTex 6 pages, 5 figure

Symmetry of two terminal, non-linear electric conduction

The well-established symmetry relations for linear transport phenomena can not, in general, be applied in the non-linear regime. Here we propose a set of symmetry relations with respect to bias voltage and magnetic field for the non-linear conductance of two-terminal electric conductors. We experimentally confirm these relations using phase-coherent, semiconductor quantum dots.Comment: 4 pages, 4 figure

Enhanced Zeeman splitting in Ga0.25In0.75As quantum point contacts

The strength of the Zeeman splitting induced by an applied magnetic field is an important factor for the realization of spin-resolved transport in mesoscopic devices. We measure the Zeeman splitting for a quantum point contact etched into a Ga0.25In0.75As quantum well, with the field oriented parallel to the transport direction. We observe an enhancement of the Lande g-factor from |g*|=3.8 +/- 0.2 for the third subband to |g*|=5.8 +/- 0.6 for the first subband, six times larger than in GaAs. We report subband spacings in excess of 10 meV, which facilitates quantum transport at higher temperatures.Comment: [Version 2] Revtex4, 11 pages, 3 figures, accepted for publication in Applied Physics Letter

Probing the Sensitivity of Electron Wave Interference to Disorder-Induced Scattering in Solid-State Devices

The study of electron motion in semiconductor billiards has elucidated our understanding of quantum interference and quantum chaos. The central assumption is that ionized donors generate only minor perturbations to the electron trajectories, which are determined by scattering from billiard walls. We use magnetoconductance fluctuations as a probe of the quantum interference and show that these fluctuations change radically when the scattering landscape is modified by thermally-induced charge displacement between donor sites. Our results challenge the accepted understanding of quantum interference effects in nanostructures.Comment: 8 pages, 5 figures, Submitted to Physical Review