Story and tradition in the narrative of 2 Samuel 2-4, 9-20 and 1 Kings 1-2

PhD Thesi

Unbound Universe

Astronom

Gap Junctions in Stem Cells Provide an Essential Conduit for Cell-Cell Communication

Introduction: Myocardial infarction (MI) results from the death of cardiomyocytes (CM) following obstruction of blood flow and diminished oxygen supply to the tissue (hypoxia). Human adipose tissue-derived stem cells (hADSCs) used in pre-clinical models can replace damaged CM, however, this has not been replicated in human clinical trials due to early loss of hADSCs. We hypothesize that coupling of hADSCs to dying CMs may account for part of this loss. Furthermore, cell culturing is essential aspect of any in-vitro experiment. Through multiple trials we sought to maximize the efficiency of our culturing procedures in order to best facilitate the work in our lab. Methods: Four aliquots of hADSCs were cultured and the effects of various reagents and culturing practices were investigated. To examine cell coupling, hADSCs will be cultured for different lengths of time with fluorescent dyes that are either permeable or impermeable to the cell membrane. We will assess the time course of coupling between hADSCs under both normoxic and hypoxic conditions by using fluorescent-activated cell sorting (FACS). Results: Our previous studies demonstrate that adult mesenchymal stem cells possess membrane proteins (connexins) that contribute to cell-cell coupling. The proposed studies will address the functional significance of connexins related to hADSC coupling. The results of our hADSC culturing trials found we can optimize our cultures to facilitate these experiments through several procedural and reagent modifications. Key modifications to culturing protocols include, 1. decreased time spent in culture, 2. utilization of pure, established cell lots, 3. using smaller flasks

Unpublished Opinions Shall Not Be Cited as Authority: The Emerging Contours of Texas Rule of Appellate Procedure 90(I).

In Texas, worries of judicial overproduction have persisted throughout the twentieth century. Although the Texas Supreme Court began to use per curiam opinions more frequently around 1925, the flood continues. Texas now has more courts and judges than ever before, and history offers no reason to expect retrenchment. The present scheme in Texas creates two classes of judicial opinions, published and unpublished. Unpublished opinions are not supposed to count for purposes of stare decisis, while published opinions do. Texas Appellate Rule 90 regulates the issuance of opinions from the courts of appeals. Part (a) requires intermediate courts to issue written opinions in conjunction with the decision of each case, yet there is no such requirement for the Texas Supreme Court. Consequently, publication rates vary widely among the fourteen courts of appeals. A nonpublication rule necessarily entails some disadvantages. Complaints are common whenever opinions are subject to a “do not publish” order. One frequently finds concern that courts are deliberately burying their work product and suppressing precedent. Although one can easily see how a published opinion may affect the jurisprudence of the state, how can an unpublished opinion ever do so, since Rule 90(i) forbids its citation as authority? Rule 90 strikes a balance between two competing interests. First, it limits the production of precedent by allowing for unpublished opinions. In so doing, it slows the growth of law libraries and reduces the availability of those decisions. Second, it bans reliance on unpublished opinions. This prohibition levels the playing field which would otherwise tilt in favor of the well-financed. Technology may provide a “solution” by making even unpublished opinions readily accessible to all. But because an adversary system generates pressure to final all relevant authorities, the “cure” could be worse than the disease

Woolf et als GWAS by subtraction is not useful for cross-generational Mendelian randomization studies

Mendelian randomization (MR) is an epidemiological method that can be used to strengthen causal inference regarding the relationship between a modifiable environmental exposure and a medically relevant trait and to estimate the magnitude of this relationship1. Recently, there has been considerable interest in using MR to examine potential causal relationships between parental phenotypes and outcomes amongst their offspring. In a recent issue of BMC Research Notes, Woolf et al (2023) present a new method, GWAS by subtraction, to derive genome-wide summary statistics for paternal smoking and other paternal phenotypes with the goal that these estimates can then be used in downstream (including two sample) MR studies. Whilst a potentially useful goal, Woolf et al. (2023) focus on the wrong parameter of interest for useful genome-wide association studies (GWAS) and downstream cross-generational MR studies, and the estimator that they derive is neither efficient nor appropriate for such use.Comment: 8 pages, 0 figure

Cosmic homogeneity demonstrated with luminous red galaxies

We test the homogeneity of the Universe at $z\sim 0.3$ with the Luminous Red Galaxy (LRG) spectroscopic sample of the Sloan Digital Sky Survey. First, the mean number $N(R)$ of LRGs within completely surveyed LRG-centered spheres of comoving radius $R$ is shown to be proportional to $R^3$ at radii greater than $R\sim 70 h^{-1} \mathrm{Mpc}$. The test has the virtue that it does not rely on the assumption that the LRG sample has a finite mean density; its results show, however, that there \emph{is} such a mean density. Secondly, the survey sky area is divided into 10 disjoint solid angular regions and the fractional rms density variations of the LRG sample in the redshift range $0.2<z<0.35$ among these ($\sim 2\times10^7 h^{-3} \mathrm{Mpc^3}$) regions is found to be 7 percent of the mean density. This variance is consistent with typical biased \lcdm models and puts very strong constraints on the quality of SDSS photometric calibration.Comment: submitted to Ap

Asymmetric preference formation in willingness to pay estimates in discrete choice models

Individuals when faced with choices amongst a number of alternatives often adopt a variety of processing rules, ranging from simple linear to complex non-linear treatment of each attribute defining the offer of each alternative. In this paper we investigate the presence of asymmetry in preferences to test for reference effects and differential willingness to pay according to whether we are valuing gains or losses. The findings offer clear evidence of an asymmetrical response to increases and decreases in attributes when compared to the corresponding values for a reference alternative, where the degree of asymmetry varies across attributes and population segments

Selection and photometric properties of K+A galaxies

Two different simple measurements of galaxy star formation rate with different timescales are compared empirically on $156,395$ fiber spectra of galaxies with $r<17.77$ mag taken from the Sloan Digital Sky Survey in the redshift range $0.05<z<0.20$: a ratio \Aamp / \Kamp found by fitting a linear sum of an average old stellar poplulation spectrum (\Kamp) and average A-star spectrum (\Aamp) to the galaxy spectrum, and the equivalent width (EW) of the \Halpha emission line. The two measures are strongly correlated, but there is a small clearly separated population of outliers from the median correlation that display excess \Aamp /\Kamp relative to \Halpha EW. These ``K+A'' (or ``E+A'') galaxies must have dramatically decreased their star-formation rates over the last $\sim 1$ Gyr. The K+A luminosity distribution is very similar to that of the total galaxy population. The K+A population appears to be bulge-dominated, but bluer and higher surface-brightness than normal bulge-dominated galaxies; it appears that K+A galaxies will fade with time into normal bulge-dominated galaxies. The inferred rate density for K+A galaxy formation is $\sim 10^{-4} h^3 Mpc^{-3} Gyr^{-1}$ at redshift $z\sim 0.1$. These events are taking place in the field; K+A galaxies don't primarily lie in the high-density environments or clusters typical of bulge-dominated populations.Comment: submitted to Ap

Age-related mitochondrial DNA depletion and the impact on pancreatic beta cell function

Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes