Rebuttal to Hasty and Vijg: ‘Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity’

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72056/1/j.1474-9728.2004.00084.x.pd

Novel sol–gel preparation of (PO)–(CaO)–(NaO)–(TiO) bioresorbable glasses (X = 0.05, 0.1, and 0.15)

Quaternary phosphate-based glasses in the PO–CaO–NaO–TiO system with a fixed PO and CaO content of 40 and 25 mol% respectively have been successfully synthesised via sol–gel method and bulk, transparent samples were obtained. The structure, elemental proportion, and thermal properties of stabilised sol–gel glasses have been characterised using X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), P nuclear magnetic resonance (P NMR), titanium K-edge X-ray absorption near-edge structure (XANES), fourier transform infrared (FTIR) spectroscopy, and differential thermal analysis (DTA). The XRD results confirmed the amorphous nature for all stabilized sol–gel derived glasses. The EDX result shows the relatively low loss of phosphorus during the sol–gel process and Ti K-edge XANES confirmed titanium in the glass structure is in mainly six-fold coordination environment. The P NMR and FTIR results revealed that the glass structure consist of mainly Q and Q phosphate units and the Ti cation was acting as a cross-linking between phosphate units. In addition DTA results confirmed a decrease in the glass transition and crystallisation temperature with increasing NaO content. Ion release studies also demonstrated a decrease in degradation rates with increasing TiO content therefore supporting the use of these glasses for biomedical applications that require a degree of control over glass degradation. These sol–gel glasses also offer the potential to incorporate proactive molecules for drug delivery application due to the low synthesis temperature employed

Endoscopic laser-ablation for the treatment of orthotopic and ectopic ureteroceles in dogs: 13 cases (2008-2017).

BACKGROUND: Ureteroceles are a rare condition in dogs in which conventional treatments can result in substantial morbidity. Cystoscopic and fluoroscopic-guided laser ablation (CLA) of ureteroceles can successfully relieve obstruction. OBJECTIVES: To describe the technique and outcomes of attempting CLA for treatment of ureteroceles in dogs. ANIMALS: Thirteen client-owned dogs that underwent CLA for treatment of ureteroceles. METHODS: Retrospective multicentered study. Medical records were reviewed in all dogs that underwent CLA for ureterocele(s). A laser was used to extend the opening of the ureteral orifice (UO) unless surgical conversion was necessary. Data collected included signalment, clinicopathologic data, imaging, procedural findings, complications, and short- and long-term outcome. RESULTS: Thirteen dogs with 13 ureteroceles associated with 14 UOs resulting in ureteral obstruction were included. One ureterocele extended bilaterally. Treatment was initiated via retrograde cystoscopy (7 females), percutaneous perineal urethrocystoscopy (4 males), or percutaneous antegrade cystoscopy (2 males). Surgical conversion was necessary in 2 males. Ten of 14 (71%) UOs associated with the ureteroceles were ectopic. Thirteen of 14 had stenotic or imperforate UOs. No postoperative complications were noted. Preoperative incontinence or pollakiuria was present in 9 of 13 and 3 of 13 dogs and resolved in 8 of 9 and 3 of 3 dogs, respectively. Follow-up imaging showed resolution of all ureteroceles and improved ureteral/renal pelvic dilatation. Median follow-up time was 27 months (range, 3-96 months). CONCLUSIONS AND CLINICAL IMPORTANCE: Cystoscopic-guided laser ablation was effective for the treatment of ureteroceles(s) in 11 of 13 dogs

Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud \ud Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud \ud Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud \ud Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising

In vitro bioactivity of titanium-doped bioglass

Previous studies have suggested that incorporating relatively small quantities of titanium dioxide into bioactive glasses may result in an increase in bioactivity and hydroxyapatite formation. The present work therefore investigated the in vitro bioactivity of a titanium doped bioglass and compared the results with 45S5 bioglass. Apatite formation was evaluated for bioglass and Ti-bioglass in the presence and absence of foetal calf serum. Scanning electron microscopy (SEM) images were used to evaluate the surface development and energy dispersive X-ray measurements provided information on the elemental ratios. X-ray diffraction spectra confirmed the presence of apatite formation. Cell viability was assessed for bone marrow stromal cells under direct and indirect contact conditions and cell adhesion was assessed using SEM

Conditional Sampling for Max-Stable Processes with a Mixed Moving Maxima Representation

This paper deals with the question of conditional sampling and prediction for the class of stationary max-stable processes which allow for a mixed moving maxima representation. We develop an exact procedure for conditional sampling using the Poisson point process structure of such processes. For explicit calculations we restrict ourselves to the one-dimensional case and use a finite number of shape functions satisfying some regularity conditions. For more general shape functions approximation techniques are presented. Our algorithm is applied to the Smith process and the Brown-Resnick process. Finally, we compare our computational results to other approaches. Here, the algorithm for Gaussian processes with transformed marginals turns out to be surprisingly competitive.Comment: 35 pages; version accepted for publication in Extremes. The final publication is available at http://link.springer.co

Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels

The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive because its transduction channels open over a very narrow range of displacements. The synchronous gating of transduction channels also underlies the active hair-bundle motility that amplifies and tunes responsiveness. The extent to which the gating of independent transduction channels is coordinated depends on how tightly individual stereocilia are constrained to move as a unit. Using dual-beam interferometry in the bullfrog's sacculus, we found that thermal movements of stereocilia located as far apart as a bundle's opposite edges display high coherence and negligible phase lag. Because the mechanical degrees of freedom of stereocilia are strongly constrained, a force applied anywhere in the hair bundle deflects the structure as a unit. This feature assures the concerted gating of transduction channels that maximizes the sensitivity of mechanoelectrical transduction and enhances the hair bundle's capacity to amplify its inputs.Comment: 24 pages, including 6 figures, published in 200

X-Ray Measurement of Material Properties in Composites

Advanced materials for use in the aerospace industry are presently being developed and applied at an astonishing rate. This pace is driven by the need for materials that can withstand higher operating temperatures and loads, yet remain cost competitive. As the performance demands of aerospace materials push nearer and nearer the theoretical limit for strength, the allowed flaw size in traditional materials is driven smaller, making quality control more stringent. This demand for improved performance characteristics is also generating strong interest in other materials such as: exotic alloys, ceramics and reinforced composites. A need exists for characterizing these advanced materials for composition variations, flaw content, inclusions and porosity using nondestructive techniques at all stages of the materials life cycle. These stages include initial characterization of a new material, process control during the manufacturing of the material, quality control of incoming material, and the in service inspection of the final part