Mechanisms for the maintenance and eventual degradation of neurofilament proteins in the distal segments of severed goldfish Mauthner axons

Cellular mechanisms that might affect the degradation of neurofilament proteins (NFPs) were examined in the distal segments of severed goldfish Mauthner axons (M-axons), which do not degenerate for more than 2 months after severance. Calpain levels, as determined by reactivity to a polyclonal antibody, remained constant for 80 d postseverance in distal segments of M-axons and then declined from 80 to 85 d postseverance. Calpain activity in rat brain, as determined by a spectrophotometric assay, was much higher than calpain activity in control and severed goldfish brain, spinal cord, muscle, or M-axons. Calpain activity was extremely low in M-axons compared with that in all other tissues and remained low for up to 80 d postseverance in distal segments of M-axons. Phosphorylated NFPs, as determined by Stains-All treatment of SDS gels, were maintained for up to 72 d postseverance and then decreased noticeably at 75 d postseverance when NFP breakdown products appeared on silver-stained gels. By 85 d postseverance, phosphorylated NFPs no longer were detected, and NFP breakdown products were the most prominent bands on silver-stained gels. These results suggest that the distal segments of M-axons survive for months after severance, because NFPs are maintained in a phosphorylated state that stabilizes and protects NFPs from degradation by low levels of calpain activity in the M-axon; the distal segments of severed M-axons degenerate eventually when NFPs no longer are maintained in a phosphorylated state and become susceptible to degradation, possibly by low levels of calpain activity in the M-axon.This work was supported by an Advanced Technology Project Grant to G.D.B.Neuroscienc

Rapid hepatic clearance of full length CCN-2/CTGF: a putative role for LRP1-mediated endocytosis

CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min). Immunosorbent assay and immunostaining showed that CCN-2 distributed mainly to the liver and was taken up by hepatocytes. Steady state clearance in rats, determined by continuous infusion of CCN-2, was fast (45 mL/kg/min). Renal CCN-2 clearance, determined by arterial and renal vein sampling, accounted for only 12 % of total clearance. Co-infusion of CCN-2 with receptor-associated protein (RAP), an antagonist of LDL-receptor family proteins, showed that RAP prolonged CCN-2 half-life and completely prevented CCN-2 internalization by hepatocytes. This suggests that hepatic uptake of CCN-2 is mediated by a RAP-sensitive mechanism most likely involving LRP1, a member of the LDL-receptor family involved in hepatic clearance of various plasma proteins. Surface plasmon resonance binding studies confirmed that CCN-2 is an LRP1 ligand. Co-infusion of CCN-2 with an excess of the heparan sulphate-binding protamine lowered the large initial distribution volume of CCN-2 by 88 % and reduced interstitial staining of CCN-2, suggesting binding of CCN-2 to heparan sulphate proteoglycans (HSPGs). Protamine did not affect clearance rate, indicating that RAP-sensitive clearance of CCN-2 is HSPG independent. In conclusion, unlike its amino-terminal fragment which is cleared by the kidney, fu

Proceedings of the ANDROID Doctoral School

The Doctoral School initiative which was set up by the ANDROID network is a core element of the overall project that aims to strengthen the link between research and teaching in the area of disaster resilience. The mixed teaching space that we have developed as part of this ongoing project has attempted to encourage and promote the work of doctoral students in this field. The ANDROID disaster resilience network doctoral school consists of two programmes: 1. Online Doctoral School (ODS) and 2. Residential Doctoral School (RDS) The interlinked programmes work together to deliver on a varied number of teaching and research driven objectives. The online doctoral school which was conducted in Spring 2013 provided an innovative platform to transfer and develop the knowledge base of doctoral candidates. This was achieved through the conduct of a series of domain expert presentations along with thematic sessions aimed at engaging the doctoral researchers in knowledge discovery through detailed discussion. The online doctoral school will be rolled out again in Spring 2014

Robust estimation, regression and ranking with applications in portfolio optimization

Thesis (Ph. D.)--Massachusetts Institute of Technology, Sloan School of Management, Operations Research Center, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (p. 108-112).Classical methods of maximum likelihood and least squares rely a great deal on the correctness of the model assumptions. Since these assumptions are only approximations of reality, many robust statistical methods have been developed to produce estimators that are robust against the deviation from the model assumptions. Unfortunately, these techniques have very high computational complexity that prevents their application to large scale problems. We present computationally efficient methods for robust mean-covariance estimation and robust linear regression using special mathematical programming models and semi-definite programming (SDP). In the robust covariance estimation problem, we design an optimization model with a loss function on the weighted Mahalanobis distances and show that the problem is equivalent to a system of equations and can be solved using the Newton-Raphson method. The problem can also be transformed into an SDP problem from which we can flexibly incorporate prior beliefs into the estimators without much increase in the computational complexity. The robust regression problem is often formulated as the least trimmed squares (LTS) regression problem where we want to nd the best subset of observations with the smallest sum of squared residuals. We show the LTS problem is equivalent to a concave minimization problem, which is very hard to solve. We resolve this difficulty by introducing the maximum trimmed squares" problem that finds the worst subset of observations. This problem can be transformed into an SDP problem that can be solved efficiently while still guaranteeing that we can identify outliers.(cont.) In addition, we model the robust ranking problem as a mixed integer minimax problem where the ranking is in a discrete uncertainty set. We use mixed integer programming methods, specifically column generation and network flows, to solve the robust ranking problem. To illustrate the power of these robust methods, we apply them to the mean-variance portfolio optimization problem in order to incorporate estimation errors into the model.by Tri-Dung Nguyen.Ph.D

Developing a Model of Aged Decellularized Muscle Matrix with Advanced Glycation Cross-linking

Volumetric muscle loss (VML) has been found to overwhelm muscle regeneration, resulting in loss of long-term muscle functionality. Decellularized muscle matrices (DMMs) provide an effective environment for muscle regeneration; however, the age of their source has not been adequately explored for clinical translation. Advanced glycation end-products (AGEs) are chemical cross-links that contribute to the aging process by accumulating on collagen fibers, resulting in a stiffening of the collagenous matrix and an increase in inflammation via the receptor for advanced glycation end-products (RAGE). In previous experiments, we found increased levels of AGE-specific cross-links within DMMs in old mice compared to young as proven by ALT-711 treatment. In this study, we developed a model of aged rat DMMs using AGE cross-links and hypothesized that our AGE-DMM model will contain a higher number of collagen cross-links compared to the control. This AGE-DMM model aims to elucidate the effect of AGEs on muscle regeneration when used in vitro or implanted in a volumetric muscle loss model.https://scholarscompass.vcu.edu/uresposters/1424/thumbnail.jp

Towards Robust Policy: Enhancing Offline Reinforcement Learning with Adversarial Attacks and Defenses

Offline reinforcement learning (RL) addresses the challenge of expensive and high-risk data exploration inherent in RL by pre-training policies on vast amounts of offline data, enabling direct deployment or fine-tuning in real-world environments. However, this training paradigm can compromise policy robustness, leading to degraded performance in practical conditions due to observation perturbations or intentional attacks. While adversarial attacks and defenses have been extensively studied in deep learning, their application in offline RL is limited. This paper proposes a framework to enhance the robustness of offline RL models by leveraging advanced adversarial attacks and defenses. The framework attacks the actor and critic components by perturbing observations during training and using adversarial defenses as regularization to enhance the learned policy. Four attacks and two defenses are introduced and evaluated on the D4RL benchmark. The results show the vulnerability of both the actor and critic to attacks and the effectiveness of the defenses in improving policy robustness. This framework holds promise for enhancing the reliability of offline RL models in practical scenarios

Three new “caecate” earthworm species from Sulawesi, Indonesia (Oligochaeta, Megascolecidae)

Three new earthworm species are described from Sulawesi, Indonesia. Two belong to the genus Pithemera Sims & Easton, 1972, namely P. suwastikai Fahri, Amaliah & Atmowidi, sp. n. and P. tadulako Fahri, Amaliah & Atmowidi, sp. n. The new species, P. suwastikai sp. n. is distinguished by a medium size (135–165 mm long, 4.5–6.5 mm diameter), four pairs of spermathecal pores in 5/6/7/8/9, 7–12 setae between male pores, no genital markings, holandry, and simple intestinal caeca. Pithemera tadulako sp. n. is recognized by a large size (217–340 mm long, 13–15 mm diameter), two pairs of spermathecal pores in 7/8/9, no setae between male pores, no genital markings, holandry, and simple intestinal caeca. Another new species, Metaphire rusydii Fahri, Amaliah & Nguyen, sp. n., is diagnosed by its large size (250–280 mm long,12–16 mm diameter), two pairs of spermathecal pores in 7/8/9, no setae between male porophores, presence of genital markings in the male region, holandry, and complex intestinal caeca. Additionally, an identification key to “caecate” species is provided to the Sulawesi’s fauna

SOME REMARKS ON THE LOGARITHMIC SIGNATURES OF FINITE ABELIAN GROUPS

In the paper about the cryptosystem MST3, Svaba and Trung pro- posed a way to build a cryptosystem based on the concept of logarithmic signa- tures, and they choose Suzuki\u27s group, which is not abelian for implementing. Recently, to reason why these methods cannot be applied to abelian groups; Sv- aba, Trung and Wolf developed some algorithms to factorize the fused transver- sal logarithmic signatures (FTLS). Their attacks can be avoided by some mod- ications, which is the aim of this paper, where we will use the weakness of the discrete logarithm problem (DLP) to propose two cryptosystems. The rst one is based on the new concept about quasi-logarithmic signature of nite solvable groups, which is the generalization of logarithmic signatures. The second is built on the logarithmic signatures of nite cyclic 2-groups, which include two interesting examples on Pell\u27s curves and elliptic curves over nite elds

Child stunting is associated with child, maternal, and environmental factors in Vietnam

Child stunting in Vietnam has reduced substantially since the turn of the century but has remained relatively high for several years. We analysed data on children 6–59 months (n = 85,932) from the Vietnam Nutritional Surveillance System, a nationally representative cross‐sectional survey. Multivariable Poisson regression models were used to estimate relative risk (RR) of stunting, stratified by child age and ecological region. Covariates at the child, maternal, household, and environmental levels were included based on available data and the World Health Organization conceptual framework on child stunting. Among children 6–23 months, the strongest associations with child stunting were child age in years (RR: 2.49; 95% CI [2.26, 2.73]), maternal height < 145 cm compared with ≥150 cm (RR: 2.04; 95% CI [1.85, 2.26]), living in the Northeast compared with the Southeast (RR: 2.01; 95% CI [1.69, 2.39]), no maternal education compared with a graduate education (RR: 1.77; 95% CI, [1.44, 2.16]), and birthweight < 2,500 g (RR: 1.75; 95% CI [1.55, 1.98]). For children 24–59 months, the strongest associations with child stunting were no maternal education compared with a graduate education (RR: 2.07; 95% CI [1.79, 2.40]), living in the Northeast compared with the Southeast (RR: 1.94; 95% CI [1.74, 2.16]), and maternal height < 145 cm compared with ≥150 cm (RR: 1.81; 95% CI [1.69, 1.94]). Targeted approaches that address the strongest stunting determinants among vulnerable populations are needed and discussed. Multifaceted approaches outside the health sector are also needed to reduce inequalities in socioeconomic status.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151838/1/mcn12826.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151838/2/mcn12826_am.pd