Operating policies in a model with terminal scrapping

We draw on three strands of literature dealing with utilization, maintenance, and scrapping in order to analyze the properties of the respective policies and their interac-tions. We do so by focusing on the last period of the received multi-period service life model and extending it in three directions: first, by associating the physical deteriora-tion of equipment to the intensity of its utilization and maintenance; second, by ex-panding on the range of explainable operating policies to allow for idling, mothballing, capacity depleting, capacity preserving, full capacity, upgrading, and downgrading; and, third, by linking the operating policies to the capital policy of scrapping. Owing to these enhancements, the analysis leads to several important findings. One among them is that optimal operating policies behave usually in opposite directions, proceed-ing in time from harder to softer or vice versa, depending on the net revenue earning capability of the equipment under consideration. Another is that profit (loss) making equipment is scrappable iff on the average the operating capital deteriorates faster (slower), or equivalently improves slower (faster), than the scrapping capital. And still an-other result is that operating policies are determined jointly with scrapping policy capi-tal policies, thus suggesting that empirical investigations of their determinants should allow for this simultaneity.Utilization, maintenance, idling, mothballing, capacity depleting, capacity pre-serving, upgrading, downgrading, scrapping.

The Transmission Property of the Discrete Heisenberg Ferromagnetic Spin Chain

We present a mechanism for displaying the transmission property of the discrete Heisenberg ferromagnetic spin chain (DHF) via a geometric approach. By the aid of a discrete nonlinear Schr\"odinger-like equation which is the discrete gauge equivalent to the DHF, we show that the determination of transmitting coefficients in the transmission problem is always bistable. Thus a definite algorithm and general stochastic algorithms are presented. A new invariant periodic phenomenon of the non-transmitting behavior for the DHF, with a large probability, is revealed by an adoption of various stochastic algorithms.Comment: 16 pages, 7 figure

From Single-Cell to Whole-Body: Developing a Molecular Neuroscience Toolkit

Throughout my Ph.D. I have worked on technology development, at first to answer basic scientific questions and eventually for therapeutic applications. This technology development applied to a variety of fields, from neuroscience to development to gene therapy, and acted upon biological systems in a wide range of scale, from the single-cell monitoring to organism-wide gene-transfer. My graduate research began with the engineering of microbial rhodopsin spectral properties and fluorescence. By making use of their ability to absorb light and emit fluorescence in a voltage-dependent manner, I aimed to interrogate neuronal activity during behavior at the single-cell level. That line of research ended with publication of the voltage-sensor Archer, which I used to track activity of a single cell in vivo in awake, behaving worms. I then shifted from tracking activity at the single cell level, to visualizing entire organisms, by developing clearing techniques that enable a high-resolution, three-dimensional analysis of a diverse range of tissues. I began by optimizing tissue-clearing parameters for various tissue types and a wide variety of experimental needs. I then took that knowledge and applied it to visualizing and tracking the developing neural crest in cleared, whole-mount chicken embryos, discovering some unexpected derivates. Finally, I became interested not only in visualizing entire organisms, but in developing technologies to facilitate gene transfer throughout the body. The rapidly growing field of gene therapy is in constant need of new tools that target specific tissues, avoiding off-target effects. The end of my Ph.D. has been spent engineering viruses that can be delivered body-wide, but target only specific areas of therapeutic interest, like the brain and lungs.</p

On the Optimal Lifetime of Real Assets

We show that the “abandonment” model emphasized by researchers in capital budgeting and the “steady state” replacement model emphasized by economic theorists constitute sub-cases of a more general class of transitory replacement models in which the horizon of reinvestments is determined endogenously along with the other decision variables. Moreover, comparisons between our model and that of steady state replacement revealed that there are considerable differences. In particular, we found that: i) the two models lead to different estimates concerning the profit horizon, the duration of replacements, the timing of abandonment or scrapping, and the impact of productive capacity and market structure on service lives, as these are determined by various parameters, ii) even though the steady state replacement policy may result in higher total profit, it does so at great expense in flexibility for the planner, because the replacements are built into the model from the beginning, and iii) the transitory replacement policy seems more realistic in that the replacements are undertaken only if forced on the planner by decreasing profits

Broad gene expression throughout the mouse and marmoset brain after intravenous delivery of engineered AAV capsids

Genetic intervention is increasingly explored as a therapeutic option for debilitating disorders of the central nervous system. The safety and efficacy of gene therapies relies upon expressing a transgene in affected cells while minimizing off-target expression. To achieve organ/cell-type specific targeting after intravenous delivery of viral vectors, we employed a Cre-transgenic-based screening platform for fast and efficient capsid selection, paired with sequential engineering of multiple surface-exposed loops. We identified capsid variants that are enriched in the brain and detargeted from the liver in mice. The improved enrichment in the brain extends to non-human primates, enabling robust, non-invasive gene delivery to the marmoset brain following IV administration. Importantly, the capsids identified display non-overlapping cell-type tropisms within the brain, with one exhibiting high specificity to neurons. The ability to cross the blood–brain barrier with cell-type specificity in rodents and non-human primates enables new avenues for basic research and potential therapeutic interventions unattainable with naturally occurring serotypes

Broad gene expression throughout the mouse and marmoset brain after intravenous delivery of engineered AAV capsids

Genetic intervention is increasingly explored as a therapeutic option for debilitating disorders of the central nervous system. The safety and efficacy of gene therapies relies upon expressing a transgene in affected cells while minimizing off-target expression. To achieve organ/cell-type specific targeting after intravenous delivery of viral vectors, we employed a Cre-transgenic-based screening platform for fast and efficient capsid selection, paired with sequential engineering of multiple surface-exposed loops. We identified capsid variants that are enriched in the brain and detargeted from the liver in mice. The improved enrichment in the brain extends to non-human primates, enabling robust, non-invasive gene delivery to the marmoset brain following IV administration. Importantly, the capsids identified display non-overlapping cell-type tropisms within the brain, with one exhibiting high specificity to neurons. The ability to cross the blood–brain barrier with cell-type specificity in rodents and non-human primates enables new avenues for basic research and potential therapeutic interventions unattainable with naturally occurring serotypes

Transition from ballistic to drift motion in high-field transport in GaAs

With strong THz pulses, we measure ultrafast transport of electrons, holes, and an electron-hole plasma in GaAs. The transition from ballistic to drift-like transport is strongly influenced by electron-hole scattering

Nonequilibrium Electron Interactions in Metal Films

Ultrafast relaxation dynamics of an athermal electron distribution is investigated in silver films using a femtosecond pump-probe technique with 18 fs pulses in off-resonant conditions. The results yield evidence for an increase with time of the electron-gas energy loss rate to the lattice and of the free electron damping during the early stages of the electron-gas thermalization. These effects are attributed to transient alterations of the electron average scattering processes due to the athermal nature of the electron gas, in agreement with numerical simulations

Directed Evolution of Gloeobacter violaceus Rhodopsin Spectral Properties

Proton-pumping rhodopsins (PPRs) are photoactive retinal-binding proteins that transport ions across biological membranes in response to light. These proteins are interesting for light-harvesting applications in bioenergy production, in optogenetics applications in neuroscience, and as fluorescent sensors of membrane potential. Little is known, however, about how the protein sequence determines the considerable variation in spectral properties of PPRs from different biological niches or how to engineer these properties in a given PPR. Here we report a comprehensive study of amino acid substitutions in the retinal binding pocket of Gloeobacter violacaeus rhodopsin (GR) that tune its spectral properties. Directed evolution generated 70 GR variants with absorption maxima shifted by up to +/- 80 nm, extending the protein’s light absorption significantly beyond the range of known natural PPRs. While proton pumping activity was disrupted in many of the spectrally shifted variants, we identified single tuning mutations that incurrred blue and red shifts of 42 nm and 22 nm, respectively, that did not disrupt proton pumping. Blue-shifting mutations were distributed evenly along the retinal molecule while red-shifting mutations were clustered near the residue K257, which forms a covalent bond with retinal through a Schiff base linkage. Thirty-four of the identified tuning mutations are not found in known microbial rhodopsins. We discovered a subset of red-shifted GRs that exhibit high levels of fluorescence relative to the wild-type protein

Lineage-specific Gene Expression in the Sea Urchin Embryo

Within a few days of fertilization, the sea urchin embryo develops into a small differentiated organism consisting of about 1800 cells and capable of feeding, swimming, and the further ontogenic transformations required in the succeeding weeks of larval growth. A number of distinct cell lineages that are clearly specialized at the morphological and functional levels can be discerned in the advanced embryo, and many of these can be traced back to particular sets of early blastomeres. Classical cell lineage and experimental studies (Hörstadius 1939; for review, see Angerer and Davidson 1984) have shown that certain of these lineages appear to be specified, at least in part, in consequence of the maternal components inherited in those regions of egg cytoplasm occupied by their progenitor cells. Specification of others among the early cell lineages clearly depends on inductive interactions that occur between blastomeres during cleavage. For the molecular biologist, as for his predecessors, this rapidly developing and simply constructed embryo offers the advantages of experimental accessibility. Thus, in respect to direct molecular-level analyses of gene activity in the embryo, for both specific genes and overall transcript populations and their protein products, the sea urchin is at present the best known embryonic system (e.g., reviews of Hentschel and Birnstiel 1981; Davidson et al. 1982; Angerer and Davidson 1984)