SPARC deficiency leads to early-onset cataractogenesis

PURPOSE: To determine the role of SPARC (secreted protein, acidic, and rich in cysteine) in cataractogenesis by examining mice deficient in a matricellular protein SPARC. METHODS: Mice were rendered SPARC-deficient by a targeted disruption of the gene. Slit-lamp microscopy and histology were used to examine the eyes of SPARC-null and wild-type mice from birth to 14 months of age. RESULTS: SPARC-null mice developed opacities in the posterior cortex of the eye as early as 1.5 months after birth. The diffuse cataracts appeared to progress toward the anterior cortex and reached maturity in many animals by 3.5 months of age. Early stages of cataractogenesis in SPARC-null mice included inhibition of normal lens fiber cell differentiation, degeneration of fiber cells, vacuole formation at the equator, and liquefaction of the cortex. No cataracts were detected in wild-type mice up to the age of 8 months. CONCLUSIONS: The early onset of cataracts in SPARC-null mice establishes that the gene is essential to the maintenance of lens transparency.     

Deciphering the Effect of Lysine Acetylation on the Misfolding and Aggregation of Human Tau Fragment 171IPAKTPPAPK180 Using Molecular Dynamic Simulation and the Markov State Model

The formation of neurofibrillary tangles (NFT) with β-sheet-rich structure caused by abnormal aggregation of misfolded microtubule-associated protein Tau is a hallmark of tauopathies, including Alzheimer’s Disease. It has been reported that acetylation, especially K174 located in the proline-rich region, can largely promote Tau aggregation. So far, the mechanism of the abnormal acetylation of Tau that affects its misfolding and aggregation is still unclear. Therefore, revealing the effect of acetylation on Tau aggregation could help elucidate the pathogenic mechanism of tauopathies. In this study, molecular dynamics simulation combined with multiple computational analytical methods were performed to reveal the effect of K174 acetylation on the spontaneous aggregation of Tau peptide ¹⁷¹IPAKTPPAPK¹⁸⁰, and the dimerization mechanism as an early stage of the spontaneous aggregation was further specifically analyzed by Markov state model (MSM) analysis. The results showed that both the actual acetylation and the mutation mimicking the acetylated state at K174 induced the aggregation of the studied Tau fragment; however, the effect of actual acetylation on the aggregation was more pronounced. In addition, acetylated K174 plays a major contributing role in forming and stabilizing the antiparallel β-sheet dimer by forming several hydrogen bonds and side chain van der Waals interactions with residues I171, P172, A173 and T175 of the corresponding chain. In brief, this study uncovered the underlying mechanism of Tau peptide aggregation in response to the lysine K174 acetylation, which can deepen our understanding on the pathogenesis of tauopathies.     

Effect of sparse long‐chain branching on the step‐strain behavior of a series of well‐defined polyethylenes

The effect of sparse long chain branching, LCB, on the shear step‐strain relaxation modulus is analyzed using a series of eight high‐density polyethylene (HDPE) resins. Strains of 1 to 1250% are imposed on materials with LCB content ranging from zero to 3.33 LCB per 10,000 carbon atoms. All materials are observed to obey time–strain separation beyond some characteristic time, τ_k. The presence of LCB is observed to increase the value of τ_k relative to the linear resin. The behavior of the relaxation modulus at times shorter than τ_k is investigated by an analysis of the enhancement seen in the linear relaxation modulus, G⁰(t), as a function of strain and LCB content. This enhancement is seen to (1) increase with increasing strain in all resins, (2) be significantly larger in the sparsely branched HDPE resins relative to the linear HDPE resin, and (3) increase in magnitude with increasing LCB content. The shape and smoothness of the damping function is also investigated. The finite rise time to impose the desired strain is compared to the Rouse relaxation time of linear HDPE resins studied. Sparse LCB is found to increase the magnitude of the relaxation modulus at short times relative to the linear resin. POLYM. ENG. SCI., 2010. © 2010 Society of Plastics Engineers     

Comparison of Conventional and Cross-Layer Multimedia Transport Schemes for Wireless Networks

Three competing schemes have been proposed for multimedia transport over broadband wireless channels: (a) traditional UDP (Postel, The User Datagram Protocol, 1980 [1]), (b) semi-cross-layer UDP-Lite (The Lightweight User Datagram Protocol, 2004 [2]), and (c) cross-layer header estimation (Khayam et al., IEEE Transactions on Multimedia 9(2):377–385, 2007 [3]; Khayam and Radha, IEEE Transactions on Wireless Communications 6(11):3946–3954, 2007 [4]). In all these schemes, corrupted and lost packets are recovered using FEC at the application layer. In this paper, we analytically and experimentally compare the performances of these broadband wireless multimedia schemes. First, we derive lower bounds on the excepted FEC redundancy required by ideal cross-layer header estimation, UDP and UDP-Lite over an arbitrary-order Markov wireless channel. We show that under realistic wireless channel conditions, the cross-layer header estimation scheme always requires lesser redundancy than UDP and UDP-Lite. We then propose a practical minimum distance decoding (MDD) header estimation scheme, which is receiver-based, low complexity and highly accurate. Trace-driven multimedia experiments over wireless LANs demonstrate that MDD header estimation requires significantly lesser FEC redundancy and renders better video quality than existing schemes.     

A Functional Programming Framework for Latency Insensitive Protocol Validation

Latency insensitive protocols (LIPs) have been proposed as a viable means to connect synchronous IP blocks via long interconnects in a system-on-chip. The reason why one needs to implement LIPs on long interconnects stems from the fact that with increasing clock frequencies, the signal delay on some interconnects exceeds the clock period. Correctness of a system composed of synchronous blocks communicating via LIPs is established by showing latency equivalence between a completely synchronous composition of the blocks, and the LIP based composition. A design flow based on a synchronous composition specification, and stepwise refinement to LIP composition can be easily conceived, and a proof obligation to show latency equivalence between the synchronous specification and the refinement needs to be discharged. In this work, we propose a functional programming based framework for modeling and simulating LIP, and implement the semantics of various refinement steps in the programming model, so we can validate the LIP model against the original system within this functional programming framework. Such validation becomes easier due to the inherent denotational model of functional languages. We specifically use Standard ML to model the original system implementation as well as its latency insensitive version and compare the two by creating a model that contains both, giving them the same inputs and checking their outputs to be latency equivalent.     

A comprehensive design and performance evaluation study of counter flow wet cooling towers

Fouling of cooling tower fills is one of the most important factors affecting its thermal performance, which reduces cooling tower effectiveness and capability with time. In this paper, the fouling model presented in an earlier paper using the experimental data on fill fouling, is used to investigate the risk based thermal performance of the cooling tower. It is demonstrated that effectiveness of the cooling tower degrades significantly with time indicating that for a low risk level (p=0.01), there is about 6.0% decrease in effectiveness for the given fouling model. The sensitivity analysis of the cooling tower is investigated for both rating and design calculation for different values of mass flow rate ratios. The effect of atmospheric pressure on the thermal performance of the cooling tower is also demonstrated.