Targeted Expression of Cre Recombinase Provokes Placental-Specific DNA Recombination in Transgenic Mice

Background: Inadequate placental development is associated with a high incidence of early embryonic lethality and serious pregnancy disorders in both humans and mice. However, the lack of well-defined trophoblast-specific gene regulatory elements has hampered investigations regarding the role of specific genes in placental development and fetal growth. Principal Findings: By random assembly of placental enhancers from two previously characterized genes, trophoblast specific protein a (Tpbpa) and adenosine deaminase (Ada), we identified a chimeric Tpbpa/Ada enhancer that when combined with the basal Ada promoter provided the highest luciferase activity in cultured human trophoblast cells, in comparison with non-trophoblast cell lines. We used this chimeric enhancer arrangement to drive the expression of a Cre recombinase transgene in the placentas of transgenic mice. Cre transgene expression occurred throughout the placenta but not in maternal organs examined or in the fetus. Significance: In conclusion, we have provided both in vitro and in vivo evidence for a novel genetic system to achieve placental transgene expression by the use of a chimeric Tpbpa/Ada enhancer driven transgene. The availability of thi

An Application of the Concept of the Therapeutic Alliance To Sadomasochistic Pathology

This paper traces the history of the therapeutic alliance concept, examining how it has been used and misused, at times elevated to a central position and at others rejected altogether. The loss of this concept created a vacuum in classical psychoanalysis that has been filled by rival theories. The continuing usefulness of looking at the treatment process through the lens of the therapeutic alliance, particularly in relation to the manifold difficulties of working with sadomasochistic pathology, is suggested. To this end, revisions of the theory of the therapeutic alliance are suggested to address some of the difficulties that have arisen in conceptualizing this aspect of the therapeutic relationship, and to provide an integrated dynamic model for working with patients at each phase of treatment. This revised model acknowledges the complexity of the domain and encompasses the multiple tasks, functions, partners, and treatment phases involved. The utility of the revised theory is illustrated in application to understanding the sadomasochistic, omnipotent resistances of a female patient through the phases of her analysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66889/2/10.1177_00030651980460031301.pd

Dissecting the First Transcriptional Divergence During Human Embryonic Development

The trophoblast cell lineage is specified early at the blastocyst stage, leading to the emergence of the trophectoderm and the pluripotent cells of the inner cell mass. Using a double mRNA amplification technique and a comparison with transcriptome data on pluripotent stem cells, placenta, germinal and adult tissues, we report here some essential molecular features of the human mural trophectoderm. In addition to genes known for their role in placenta (CGA, PGF, ALPPL2 and ABCG2), human trophectoderm also strongly expressed Laminins, such as LAMA1, and the GAGE Cancer/Testis genes. The very high level of ABCG2 expression in trophectoderm, 7.9-fold higher than in placenta, suggests a major role of this gene in shielding the very early embryo from xenobiotics. Several genes, including CCKBR and DNMT3L, were specifically up-regulated only in trophectoderm, indicating that the trophoblast cell lineage shares with the germinal lineage a transient burst of DNMT3L expression. A trophectoderm core transcriptional regulatory circuitry formed by 13 tightly interconnected transcription factors (CEBPA, GATA2, GATA3, GCM1, KLF5, MAFK, MSX2, MXD1, PPARD, PPARG, PPP1R13L, TFAP2C and TP63), was found to be induced in trophectoderm and maintained in placenta. The induction of this network could be recapitulated in an in vitro trophoblast differentiation model

Trading energy yield for frequency regulation: Optimal control of kinetic energy in wind farms

The burden on conventional units to regulate the system frequency increases if they are replaced due to wind farms. This paper explores up to which time scales the rotating kinetic energy in wind turbines can smooth frequency variations and assist with the regulation task. To this end, a comparison is made between a standard wind turbine controller and optimal control of wind turbines, respectively derived from causal time-domain simulations and an optimization algorithm that allows predicting. The latter algorithm is used to give a benchmark for the smoothing potential, shown by plotting the Pareto efficiency of the normalized standard deviation of frequency variability versus a normalized measure of the energy yield. Results indicate that smoothing comes with an energy loss that is determined by the energy content of power imbalances. It is shown that a wind share of 20%, within the instantaneous generation mix, can absorb frequency variations on timescales up to 100 sec while the energy loss is limited to only 2%. A higher share of wind power aggravates frequency variability. Nevertheless, in such circumstances the potential of rotating kinetic energy in wind farms increases

In-situ Mechanical Neutron Diffraction Loading Characteristics of GRCop-84 Fabricated by SLM

GRCop-84 is a precipitation strengthened alloy composed of Cu-8Cr-4Nb at % with Cr2Nb precipitates that provide dispersion and precipitation strengthening characteristics and limited solubility in the Cu matrix. The particle role of Cr2Nb(C15Laves) is unusual only contributing 1/3 of strengthening at high temperatures while the matrix provides the remainder. The particles mechanically and thermally stabilize the matrix retaining purity and preventing coarsening and loss of strength. At high temperatures (50-85%TmCu), GRCop-84 provides the best thermal and mechanical properties of available alloys. GRCop-84 is currently in development for reusable launch vehicles including the Space Launch System (SLS) with a focus on fabrication with additive manufacturing (AM) techniques. GRCop-84 is an optimal material for consolidating with AM. The base material is costly, the production times are long, and more geometry control can considerably improve cooling efficiency. Development of AMGR Cop-84 with selective laser melting (SLM) has rapidly progressed due to ease of printing and limited operator adjustment between builds, but the necessary knowledge-base of thermal history and stress state during builds is still under development