1952, July 25 - Correspondence - Jack R. Wells

Correspondence from Jack R. Wells, mayor of Athens, GA, to Edna Webb Darwin referencing an honor paid by the Young Women\u27s Christian Association in her name.https://digitalcommons.gardner-webb.edu/fay-webb-gardner-edna-webb-darwin-family/1002/thumbnail.jp

Layered rare-earth hydroxides as multi-modal medical imaging probes: particle size optimisation and compositional exploration

Recently, layered rare-earth hydroxides (LRHs) have received growing attention in the field of theranostics. We have previously reported the hydrothermal synthesis of layered terbium hydroxide (LTbH), which exhibited high biocompatibility, reversible uptake of a range of model drugs, and release-sensitive phosphorescence. Despite these favourable properties, LTbH particles produced by the reported method suffered from poor size-uniformity (670 ± 564 nm), and are thus not suitable for therapeutic applications. To ameliorate this issue, we first derive an optimised hydrothermal synthesis method to generate LTbH particles with a high degree of homogeneity and reproducibility, within a size range appropriate for in vivo applications (152 ± 59 nm, n = 6). Subsequently, we apply this optimised method to synthesise a selected range of LRH materials (R = Pr, Nd, Gd, Dy, Er, Yb), four of which produced particles with an average size under 200 nm (Pr, Nd, Gd, and Dy) without the need for further optimisation. Finally, we incorporate Gd and Tb into LRHs in varying molar ratios (1 : 3, 1 : 1, and 3 : 1) and assess the combined magnetic relaxivity and phosphorescence properties of the resultant LRH materials. The lead formulation, LGd1.41Tb0.59H, was demonstrated to significantly shorten the T2 relaxation time of water (r2 = 52.06 mM−1 s−1), in addition to exhibiting a strong phosphorescence signal (over twice that of the other LRH formulations, including previously reported LTbH), therefore holding great promise as a potential multi-modal medical imaging probe

Layered rare-earth hydroxides as multi-modal medical imaging probes: particle size optimisation and compositional exploration

Recently, layered rare-earth hydroxides (LRHs) have received growing attention in the field of theranostics. We have previously reported the hydrothermal synthesis of layered terbium hydroxide (LTbH), which exhibited high biocompatibility, reversible uptake of a range of model drugs, and release-sensitive phosphorescence. Despite these favourable properties, LTbH particles produced by the reported method suffered from poor size-uniformity (670 ± 564 nm), and are thus not suitable for therapeutic applications. To ameliorate this issue, we first derive an optimised hydrothermal synthesis method to generate LTbH particles with a high degree of homogeneity and reproducibility, within a size range appropriate for in vivo applications (152 ± 59 nm, n = 6). Subsequently, we apply this optimised method to synthesise a selected range of LRH materials (R = Pr, Nd, Gd, Dy, Er, Yb), four of which produced particles with an average size under 200 nm (Pr, Nd, Gd, and Dy) without the need for further optimisation. Finally, we incorporate Gd and Tb into LRHs in varying molar ratios (1 : 3, 1 : 1, and 3 : 1) and assess the combined magnetic relaxivity and phosphorescence properties of the resultant LRH materials. The lead formulation, LGd1.41Tb0.59H, was demonstrated to significantly shorten the T2 relaxation time of water (r2 = 52.06 mM−1 s−1), in addition to exhibiting a strong phosphorescence signal (over twice that of the other LRH formulations, including previously reported LTbH), therefore holding great promise as a potential multi-modal medical imaging probe

Abelian D-terms and the superpartner spectrum of anomaly-mediated supersymmetry breaking

We address the tachyonic slepton problem of anomaly mediated supersymmetry breaking using abelian D-terms. We demonstrate that the most general extra U(1) symmetry that does not disrupt gauge coupling unification has a large set of possible charges that solves the problem. It is shown that previous studies in this direction that added both an extra hypercharge D-term and another D-term induced by B-L symmetry (or similar) can be mapped into a single D-term of the general ancillary U(1)_a. The U(1)_a formalism enables identifying the sign of squark mass corrections which leads to an upper bound of the entire superpartner spectrum given knowledge of just one superpartner mass.Comment: 10 pages, 2 figures, [v2] reference added, [v3] Eq. (9) corrected, results unaffected, [v4] version to be published in Phys. Rev. D, expanded parameter space for figures to match tex

Data for 'Something in the way she moves': the functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI)

Protein disulfide isomerase (PDI) has diverse functions in the endoplasmic reticulum as catalyst of redox transfer, disulfide isomerization and oxidative protein folding, as molecular chaperone and in multi-subunit complexes. It interacts with an extraordinarily wide range of substrate and partner proteins, but there is only limited structural information on these interactions. Extensive evidence on the flexibility of PDI in solution is not matched by any detailed picture of the scope of its motion. A new rapid method for simulating the motion of large proteins provides detailed molecular trajectories for PDI demonstrating extensive changes in the relative orientation of its four domains, great variation in the distances between key sites and internal motion within the core ligand-binding domain. The review shows that these simulations are consistent with experimental evidence and provide insight into the functional capabilities conferred by the extensive flexible motion of PDI

Sticky DNA, a Long GAA·GAA·TTC Triplex That Is Formed Intramolecularly, in the Sequence of Intron 1 of the Frataxin Gene

Friedreich's ataxia is caused by the massive expansion of GAA.TTC repeats in intron 1 of the frataxin (X25) gene. Our prior investigations showed that long GAA.TTC repeats formed very stable triplex structures which caused two repeat tracts to adhere to each other (sticky DNA). This process was dependent on negative supercoiling and the presence of divalent metal ions. Herein, we have investigated the formation of sticky DNA from plasmid monomers and dimers; sticky DNA is formed only when two tracts of sufficiently long (GAA.TTC)(n) (n = 59-270) are present in a single plasmid DNA and are in the direct repeat orientation. If the inserts are in the indirect (inverted) repeat orientation, no sticky DNA was observed. Furthermore, kinetic studies support the intramolecular nature of sticky DNA formation. Electron microscopy investigations also provide strong data for sticky DNA as a single long triplex. Hence, these results give new insights into our understanding of the capacity of sticky DNA to inhibit transcription and thereby reduce the level of frataxin protein as related to the etiology of Friedreich's ataxia

Higgs boson mass limits in perturbative unification theories

Motivated in part by recent demonstrations that electroweak unification into a simple group may occur at a low scale, we detail the requirements on the Higgs mass if the unification is to be perturbative. We do this for the Standard Model effective theory, minimal supersymmetry, and next-to-minimal supersymmetry with an additional singlet field. Within the Standard Model framework, we find that perturbative unification with sin2(thetaW)=1/4 occurs at Lambda=3.8 TeV and requires mh<460 GeV, whereas perturbative unification with sin2(thetaW)=3/8 requires mh<200 GeV. In supersymmetry, the presentation of the Higgs mass predictions can be significantly simplified, yet remain meaningful, by using a single supersymmetry breaking parameter Delta_S. We present Higgs mass limits in terms of Delta_S for the minimal supersymmetric model and the next-to-minimal supersymmetric model. We show that in next-to-minimal supersymmetry, the Higgs mass upper limit can be as large as 500 GeV even for moderate supersymmetry masses if the perturbative unification scale is low (e.g., Lambda=10 TeV).Comment: 20 pages, latex, 6 figures, references adde

Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia

During hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. Here, we describe a mechanism of brain oxygen sensing that mediates the dilation of intraparenchymal cerebral blood vessels in response to reductions in oxygen supply. In vitro and in vivo experiments conducted in rodent models show that during hypoxia, cortical astrocytes produce the potent vasodilator nitric oxide (NO) via nitrite reduction in mitochondria. Inhibition of mitochondrial respiration mimics, but also occludes, the effect of hypoxia on NO production in astrocytes. Astrocytes display high expression of the molybdenum-cofactor-containing mitochondrial enzyme sulfite oxidase, which can catalyze nitrite reduction in hypoxia. Replacement of molybdenum with tungsten or knockdown of sulfite oxidase expression in astrocytes blocks hypoxia-induced NO production by these glial cells and reduces the cerebrovascular response to hypoxia. These data identify astrocyte mitochondria as brain oxygen sensors that regulate cerebral blood flow during hypoxia via release of nitric oxide

ASCR/HEP Exascale Requirements Review Report

This draft report summarizes and details the findings, results, and recommendations derived from the ASCR/HEP Exascale Requirements Review meeting held in June, 2015. The main conclusions are as follows. 1) Larger, more capable computing and data facilities are needed to support HEP science goals in all three frontiers: Energy, Intensity, and Cosmic. The expected scale of the demand at the 2025 timescale is at least two orders of magnitude -- and in some cases greater -- than that available currently. 2) The growth rate of data produced by simulations is overwhelming the current ability, of both facilities and researchers, to store and analyze it. Additional resources and new techniques for data analysis are urgently needed. 3) Data rates and volumes from HEP experimental facilities are also straining the ability to store and analyze large and complex data volumes. Appropriately configured leadership-class facilities can play a transformational role in enabling scientific discovery from these datasets. 4) A close integration of HPC simulation and data analysis will aid greatly in interpreting results from HEP experiments. Such an integration will minimize data movement and facilitate interdependent workflows. 5) Long-range planning between HEP and ASCR will be required to meet HEP's research needs. To best use ASCR HPC resources the experimental HEP program needs a) an established long-term plan for access to ASCR computational and data resources, b) an ability to map workflows onto HPC resources, c) the ability for ASCR facilities to accommodate workflows run by collaborations that can have thousands of individual members, d) to transition codes to the next-generation HPC platforms that will be available at ASCR facilities, e) to build up and train a workforce capable of developing and using simulations and analysis to support HEP scientific research on next-generation systems.Comment: 77 pages, 13 Figures; draft report, subject to further revisio

Signatures of the Light Down-Squark Scenario at the Upgraded Tevatron

In scenarios with relatively light down squarks, motivated, e.g., by SO(10) D terms, jets + missing $E_T$ signals can be observed at the luminosity upgraded Tevatron even if the squarks are much heavier than the gluinos and the common gaugino mass ($M_{{1/2}}$) at $M_G$ lies above the LEP allowed lower bound. In the conventional mSUGRA model with heavy squarks practically no signal is expected in this channel. The possiblity of distinguishing between various SUGRA motivated scenarios by exploiting the missing $E_T$ and jet $p_T$ distributions, opposite sign dileptons + jets + missing $E_T$ events and clean trilepton signals have been discussed.Comment: 14 pages, 3 ps figure