Synthetic Approach to Realkyation of Aged Acetylcholinesterase Using Quinone Methide Precursors

Mathematical and Physical SciencesOrganophosphorus (OP) nerve agents are a class of toxic compounds that inhibit acetylcholinesterase (AChE), an enzyme that catalyzes the conversion of acetylcholine to choline at neurosynaptic junctions. OP inhibits AChE by binding to the active site and this undergoes a subsequent irreversible process called aging, where the OP-AChE adduct is dealkylated. This results in the accumulation of excess acetylcholine in the central nervous system that causes significant nerve damage. Current oxime-based pharmaceutical agents, such as 2-PAM, used to treat inhibited AChE are ineffective on aged AChE. Previous studies have shown that quinone methides (QM) are alkylating agents and these could potentially reverse the aging process through a kinetically favored realkylation mechanism. In the past, we have designed and synthesized a library of QM precursors. Our research focuses on the analysis of these alkylating compounds and investigating their ability to realkylate model phosphonate.National Institute of Health (NIH) Grant 1U01–NS087983Academic Major: Chemistr

A new approach to modeling aviation accidents

General Aviation (GA) is a catchall term for all aircraft operations in the US that are not categorized as commercial operations or military flights. GA aircraft account for almost 97% of the US civil aviation fleet. Unfortunately, GA flights have a much higher fatal accident rate than commercial operations. Recent estimates by the Federal Aviation Administration (FAA) showed that the GA fatal accident rate has remained relatively unchanged between 2010 and 2015, with 1566 fatal accidents accounting for 2650 fatalities. Several research efforts have been directed towards betters understanding the causes of GA accidents. Many of these efforts use National Transportation Safety Board (NTSB) accident reports and data. Unfortunately, while these studies easily identify the top types of accidents (e.g., inflight loss of control (LOC)), they usually cannot identify why these accidents are happening. Most NTSB narrative reports for GA accidents are very short (many are only one paragraph long), and do not contain much information on the causes (likely because the causes were not fully identified). NTSB investigators also code each accident using an event-based coding system, which should facilitate identification of patterns and trends in causation, given the high number of GA accidents each year. However, this system is susceptible to investigator interpretation and error, meaning that two investigators may code the same accident differently, or omit applicable codes. To facilitate a potentially better understanding of GA accident causation, this research develops a state-based approach to check for logical gaps or omissions in NTSB accident records, and potentially fills-in the omissions. The state-based approach offers more flexibility as it moves away from the conventional event-based representation of accidents, which classifies events in accidents into several categories such as causes, contributing factors, findings, occurrences, and phase of flight. The method views aviation accidents as a set of hazardous states of a system (pilot and aircraft), and triggers that cause the system to move between hazardous states. I used the NTSB’s accident coding manual (that contains nearly 4000 different codes) to develop a “dictionary” of hazardous states, triggers, and information codes. Then, I created the “grammar”, or a set of rules, that: (1) orders the hazardous states in each accident; and, (2) links the hazardous states using the appropriate triggers. This approach: (1) provides a more correct count of the causes for accidents in the NTSB database; and, (2) checks for gaps or omissions in NTSB accident data, and fills in some of these gaps using logic-based rules. These rules also help identify and count causes for accidents that were not discernable from previous analyses of historical accident data. I apply the model to 6200 helicopter accidents that occurred in the US between 1982 and 2015. First, I identify the states and triggers that are most likely to be associated with fatal and non-fatal accidents. The results suggest that non-fatal accidents, which account for approximately 84% of the accidents, provide valuable opportunities to learn about the causes for accidents. Next, I investigate the causes of inflight loss of control using both a conventional approach and using the state-based approach. The conventional analysis provides little insight into the causal mechanism for LOC. For instance, the top cause of LOC is “aircraft control/directional control not maintained”, which does not provide any insight. In contrast, the state-based analysis showed that pilots’ tendency to clip objects frequently triggered LOC (16.7% of LOC accidents)—this finding was not directly discernable from conventional analyses. Finally, I investigate the causes for improper autorotations using both a conventional approach and the state-based approach. The conventional approach uses modifiers (e.g., “improper”, “misjudged”) associated with “24520: Autorotation” to identify improper autorotations in the pre-2008 system. In the psot-2008 system, the NTSB represents autorotation as a phase of flight, which has no modifier—making it impossible to determine if the autorotation was unsuccessful. In contrast, the state-based analysis identified 632 improper autorotation accidents, compared to 174 with a conventional analysis. Results from the state-based analysis show that not maintaining rotor RPM and improper flare were among the top reasons for improper autorotations. The presence of the “not possible” trigger in 11.6% of improper autorotations, suggests that it was impossible to make an autorotative landing. Improper use of collective is the sixth most frequent trigger for improper autorotation. Correct use of collective pitch control is crucial to maintain rotor RPM during an autorotation (considering that engines are generally not operational during autorotations)

Determinants of range of motion in cruciate retaining total knee arthroplasty: a prospective study

Background: Total knee replacement (TKR) is to provide a stable painless knee with adequate range of motion (ROM) for daily activities. The aim of the study is to evaluate various factors that influence ROM in cruciate retaining TKR postoperatively.Methods: Fourty four patients with osteoarthritis knee treated in our institute with TKR using cruciate retaining prosthesis are included in study and analysed prospectively. Mean follow up was 6 months. Patients are analyzed for following factors–age, gender, BMI, preoperative ROM, changes in posterior femoral condylar offset, posterior tibial slope after surgery. Statistical analysis of effect of all factors on knee ROM was done. Assessment was done preoperatively and 3 and 6 months postoperatively.Results: Gender did not affect the final ROM. Mean age of patients is 65. Age has negative correlation with ROM (p=-0.45). The mean knee range improved from 92˚ to 101˚. Factors that negatively affect ROM include, BMI (p=-0.04) and Preoperative flexion deformity (p=-0.03). Factors that positively affect ROM include, knee scores and good preoperative flexion (p=0.001). Males have good amount of flexion preoperatively and post operatively when compared to females.Conclusions: Preoperative ROM, flexion contracture and BMI are the important factors affecting the range of motion in total knee arthroplasty. Proper counselling of patient preoperatively regarding these various factors and appropriate selection of patient is of utmost important for satisfactory functional outcome

A Novel estimation and Correction of Channel errors in LTE SYSTEMS

The increase in the number of RF devices and the requirement for large data rates places major role in increasing demand on bandwidth. This necessitates the need for RF communication systems with increased throughput and capacity. MIMO-OFDM is one way to meet this basic requirement. OFDM is used in many (WCD) wireless communication devices and offers high spectral efficiency and resilience to multipath channel effects. Though OFDM is very sensitive to synchronization errors, it makes the task of channel equalization simple. MIMO utilize the multiple antennas to increase throughput without increasing transmitter power or bandwidth. This project presents an introduction to the (MPC) multipath fading channel and describes an appropriate channel model. Many modulation schemes are presented (i.e. BPSK, QPSK, QAM) that are often used in Conjunction with OFDM. Mathematical modeling and analysis of OFDM are given along with a discrete implementation common to modern RF communication systems. Synchronization errors are modeled mathematically and simulated, as well as techniques to estimate and correct those errors at the receiver accurately

Bayesian Joint Chance Constrained Optimization: Approximations and Statistical Consistency

This paper considers data-driven chance-constrained stochastic optimization problems in a Bayesian framework. Bayesian posteriors afford a principled mechanism to incorporate data and prior knowledge into stochastic optimization problems. However, the computation of Bayesian posteriors is typically an intractable problem, and has spawned a large literature on approximate Bayesian computation. Here, in the context of chance-constrained optimization, we focus on the question of statistical consistency (in an appropriate sense) of the optimal value, computed using an approximate posterior distribution. To this end, we rigorously prove a frequentist consistency result demonstrating the convergence of the optimal value to the optimal value of a fixed, parameterized constrained optimization problem. We augment this by also establishing a probabilistic rate of convergence of the optimal value. We also prove the convex feasibility of the approximate Bayesian stochastic optimization problem. Finally, we demonstrate the utility of our approach on an optimal staffing problem for an M/M/c queueing model

A minimax approach for the joint design of acoustic crosstalk cancellation filters

Journal ArticleAbstract-This paper presents a method for jointly designing immersive audio rendering filters for a single listener using loudspeakers. The filters for crosstalk cancellation are assumed to have finite impulse responses and are designed using the minimax criterion. In addition to the traditional Atal-Schroeder crosstalk canceler structure, this paper explores an alternate topology that requires the approximation of a single filter. In general, the minimax approach provides improved low-frequency performance leading to a better overall separation of the direct-path and cross-path transfer functions than least-squares designs. The performance of the single-filter structure is better than that of the traditional crosstalk cancellation structure