Bootstrapping spectral statistics in high dimensions

Statistics derived from the eigenvalues of sample covariance matrices are called spectral statistics, and they play a central role in multivariate testing. Although bootstrap methods are an established approach to approximating the laws of spectral statistics in low-dimensional problems, these methods are relatively unexplored in the high-dimensional setting. The aim of this paper is to focus on linear spectral statistics as a class of prototypes for developing a new bootstrap in high-dimensions --- and we refer to this method as the Spectral Bootstrap. In essence, the method originates from the parametric bootstrap, and is motivated by the notion that, in high dimensions, it is difficult to obtain a non-parametric approximation to the full data-generating distribution. From a practical standpoint, the method is easy to use, and allows the user to circumvent the difficulties of complex asymptotic formulas for linear spectral statistics. In addition to proving the consistency of the proposed method, we provide encouraging empirical results in a variety of settings. Lastly, and perhaps most interestingly, we show through simulations that the method can be applied successfully to statistics outside the class of linear spectral statistics, such as the largest sample eigenvalue and others.Comment: 42 page

Mesenchymal stromal cell therapy for feline chronic gingivostomatitis: Long term experience

IntroductionMesenchymal stromal cells (MSC) therapy has emerged as a potential treatment option for refractory FCGS. However, there is a lack of long-term data on the use of MSC therapy in cats. This study aimed to evaluate the long-term safety and efficacy of MSC therapy for FCGS and investigate potential factors associated with treatment outcomes.MethodsThis study was a retrospective evaluation of 38 client-owned cats with refractory FCGS who received MSC therapy. Medical records, histopathology, and the Stomatitis Activity Disease Index (SDAI) were reviewed. Correlations of the long-term follow-up success rates with SDAI and cell line type used were conducted. A client survey was also performed to assess side effect occurrence, quality-of-life following treatment, and overall treatment satisfaction.ResultsLong-term follow-up ranged from 2 to 9 years post-MSC treatment. The overall positive response rate to MSC treatment was 65.5%, with 58.6% of cats exhibiting permanent improvement or cure. Adverse effects occurring during or immediately after treatment were noted in 34.2% of cases, the majority being transient, self-resolving transfusion-like reactions. No long-term adverse events were noted. No significant correlation in outcome was detected between allogeneic and autologous MSC treatment (p = 0.871) or the severity of the SDAI at entry (p = 0.848) or exit (p = 0.166), or the delta SDAI between entry and exit (p = 0.178). The status 6 months (none to partial improvement vs. substantial improvement to resolution) post-therapy was a predictor of long-term response (value of p < 0.041). Most clients were satisfied with the treatment and outcomes, with 90.6% willing to pursue treatment again, given a similar situation.DiscussionThe results of this study support the use of both autologous and allogeneic MSC as an efficacious and safe therapeutic option for refractory FCGS

Some Bootstrap Methods for Regression and Time Series

In the first part of the dissertation, we discuss a residual bootstrap method for high-dimensional ridge regression. If the dimension and sample size are of the same order asymptotically, and the singular values of the design matrix follow a power law decay, we show that the method is able to consistently approximate the distribution of certain linear contrasts of the estimated regression coefficients. An automatic procedure for selecting tuning parameters is proposed and is shown to perform well in numerical experiments. In the last part of the dissertation, we propose a moment-adjusted autoregressive sieve bootstrap procedure for univariate time series. The new bootstrap procedure is shown to be consistent for various statistics and models where the original autoregressive sieve fails. The method is demonstrated to be effective through simulations. Furthermore, the moment-adjusted autoregressive sieve bootstrap procedure shows improved power for the detection of non-linear time series compared to the original autoregressive sieve

Mesenchymal stromal cell therapy for feline chronic gingivostomatitis: Long term experience

IntroductionMesenchymal stromal cells (MSC) therapy has emerged as a potential treatment option for refractory FCGS. However, there is a lack of long-term data on the use of MSC therapy in cats. This study aimed to evaluate the long-term safety and efficacy of MSC therapy for FCGS and investigate potential factors associated with treatment outcomes.MethodsThis study was a retrospective evaluation of 38 client-owned cats with refractory FCGS who received MSC therapy. Medical records, histopathology, and the Stomatitis Activity Disease Index (SDAI) were reviewed. Correlations of the long-term follow-up success rates with SDAI and cell line type used were conducted. A client survey was also performed to assess side effect occurrence, quality-of-life following treatment, and overall treatment satisfaction.ResultsLong-term follow-up ranged from 2 to 9 years post-MSC treatment. The overall positive response rate to MSC treatment was 65.5%, with 58.6% of cats exhibiting permanent improvement or cure. Adverse effects occurring during or immediately after treatment were noted in 34.2% of cases, the majority being transient, self-resolving transfusion-like reactions. No long-term adverse events were noted. No significant correlation in outcome was detected between allogeneic and autologous MSC treatment (p = 0.871) or the severity of the SDAI at entry (p = 0.848) or exit (p = 0.166), or the delta SDAI between entry and exit (p = 0.178). The status 6 months (none to partial improvement vs. substantial improvement to resolution) post-therapy was a predictor of long-term response (value of p < 0.041). Most clients were satisfied with the treatment and outcomes, with 90.6% willing to pursue treatment again, given a similar situation.DiscussionThe results of this study support the use of both autologous and allogeneic MSC as an efficacious and safe therapeutic option for refractory FCGS

Multiple optical receive system for a single optical terminal: preliminary design

Current satellite optical communications systems, e.g. EDRS, include a single optical terminal for point-to-point links. In case of a hand-over to a next available location, the optical terminal must actively repoint and reacquire the signal. We investigate a novel satellite telescope design covering multiple optical ground stations within its field-of-view. Additionally, orbital perturbations, mainly the ones due to inclination, distort the received optical field over the period of one day and must be compensated for each link individually. We present preliminary design of the space telescope and focal-plane-array and plan of the following breadboarding activity

GRHR agonist MR-409 protects β-cells from streptozotocin-induced diabetes

Patients with type 1 diabetes (T1D) suffer from insufficient functional β-cell mass, which results from infiltration of inflammatory cells and cytokine-mediated β-cell death. Previous studies demonstrated the beneficial effects of agonists of growth hormone-releasing hormone receptor (GHRH-R), such as MR-409 on preconditioning of islets in a transplantation model. However, the therapeutic potential and protective mechanisms of GHRH-R agonists on models of T1D diabetes have not been explored. Using in vitro and in vivo models of T1D, we assessed the protective propertie of the GHRH agonist, MR409 on β-cells. The treatment of insulinoma cell lines and rodent and human islets with MR-409 induces Akt signaling by induction of insulin receptor substrate 2 (IRS2), a master regulator of survival and growth in β-cells, in a PKA-dependent manner. The increase in cAMP/PKA/CREB/IRS2 axis by MR409 was associated with decrease in β-cell death and improved insulin secretory function in mouse and human islets exposed to proinflammatory cytokines. The assessment of the effects of GHRH agonist MR-409 in a model of T1D induced by low-dose streptozotocin showed that mice treated with MR-409 exhibited better glucose homeostasis, higher insulin levels, and preservation of β-cell mass. Increased IRS2 expression in β-cells in the group treated with MR-409 corroborated the in vitro data and provided evidence for the underlying mechanism responsible for beneficial effects of MR-409 in vivo. Collectively, our data show that MR-409 is a novel therapeutic agent for the prevention and treatment of β-cells death in T1D

Soil-Water Partitioning Behavior of Oxyfluorfen Under California Rice Field Conditions

The herbicide oxyfluorfen [OXY; 2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene] has recently surged in interest among rice farmers with the development of OXY-tolerant rice and its demonstrated effectiveness against problematic rice weeds in California. Not currently registered for use with rice, its fate in rice fields is poorly understood. Using a batch equilibrium method, we characterize the soil-water partitioning behavior of OXY under simulated California rice field conditions. Sorption data imply strong, primarily concentration-independent binding correlated with soil organic carbon (log[Koc] 4.79−5.19; N 0.87−1.08) across all soil, temperature, and salinity treatments. Temperature significantly enhanced binding affinity for sorption and desorption processes (P < 0.01). Bound OXY was poorly desorbed (9.3 to 27.0% desorption) from rice soils and exhibited significant sorption hysteresis (HI > 0) in all treatments. These results indicate that OXY will predominantly remain in soil and will be resistant to release into water in California rice fields

Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis

Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase ( AMPK ) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase ( ACC ). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin ( < 1.0 mM ); effects not observed in prostate ( PNT1A ) and lung ( MRC-5 ) epithelial cell lines. Salicylate concentrations of 1 mM increased the phosphorylation of ACC and suppressed de novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin ( 100 μM ) and eliminated in mouse embryonic fibroblasts ( MEFs ) deficient in AMPK β1. Supplementation of media with fatty acids and/or cholesterol reverses the suppressive effects of salicylate and metformin on cell survival indicating the inhibition of de novo lipogenesis is probably important. Pre-clinical studies evaluating the use of salicylate based drugs alone and in combination with metformin to inhibit de novo lipogenesis and the survival of prostate and lung cancers are warranted

Normal Corneal Thickness and Endothelial Cell Density in Rhesus Macaques (Macaca mulatta)

PurposeTo define the normal range of central corneal thickness (CCT) and corneal endothelial cell density (ECD) in rhesus macaques (Macaca mulatta) and the effects of age, body weight, sex, and intraocular pressure (IOP) on these parameters.MethodsOphthalmic examinations were performed on 144 rhesus macaques without anterior segment pathology. The CCT was measured via ultrasound pachymetry (USP) and specular microscopy, and the ECD was semiautomatically and manually counted using specular microscopy. Rebound tonometry was used to measure IOP. Linear regression and mixed-effects linear regression models were used to evaluate the effects of age, body weight, sex, and IOP on CCT and ECD.ResultsWe included 98 females and 46 males with an age range of 0.2 to 29.4 years. The mean CCT by USP and specular microscopy were 483 ± 39 and 463 ± 33 µm, respectively, and were statistically different (P &lt; 0.001). The ECDs were 2717 ± 423 and 2747 ± 438 cells/mm2 by semiautomated and manual analysis, respectively. Corneal endothelial degeneration was identified in one aged rhesus macaque.ConclusionsThe mean USP and specular microscopy CCT values differed significantly, whereas the semiautomatic and manual ECD did not. The CCT was associated with the IOP and sex, whereas the ECD was associated with body weight and age (P &lt; 0.05). As in humans, corneal disease in rhesus macaques is uncommon.Translational relevanceEstablishing reference values is fundamental to use rhesus macaques as a model for corneal disease or to identify toxicity in studies of ocular drugs or devices