Evolution of Ada technology in the flight dynamics area: Implementation/testing phase analysis

An analysis is presented of the software engineering issues related to the use of Ada for the implementation and system testing phases of four Ada projects developed in the flight dynamics area. These projects reflect an evolving understanding of more effective use of Ada features. In addition, the testing methodology used on these projects has changed substantially from that used on previous FORTRAN projects

Thermodynamic and Kinetic Investigation of Depsipeptide Oligomerization and Degradation Under Prebiotic Earth Conditions

The formation of polypeptides on the early Earth has been a long-standing problem in the field of prebiotic chemistry. Although it is generally accepted that amino acids were present on the prebiotic Earth based on the Miller-Urey experiment, the plausible mechanism to form long chain polypeptides is still unclear. This mechanism of polypeptide formation is known to be slow unless high temperatures or metal catalysts are used because of the high activation energies and the formation of side-products such as diketopiperazine (DKP). This thesis describes a simple system containing hydroxy acids and amino acids that combine to form depsipeptides, which are hypothesized to be precursors to polypeptides. Hydroxy acids form metastable oligoesters in an oscillating (hot dry/cool wet) environment and transform into mixed copolymers via the ester-amide exchange reaction. This pathway enables the amide bond formation in lower temperature and leads to a library of oligomers with random sequences containing catalytic functions crucial for sustaining life. The main theme of this thesis is thermodynamic and kinetic modeling of depsipeptide degradation, esterification, and exchange of prebiotic molecules such as lactic acid (a), glycolic acid (g), and glycine (G). The goal is to be able to explain the chemical driving forces of depsipeptide oligomerization and degradation under mild conditions using classi cal thermodynamics and kinetics. The specific aims are as follows: 1) determine whether models can be used to visualize how Gibbs free energy of lactic acid esterification and ester-amide exchange changes as a function of pH and temperature; 2) assess what type of behavior is anticipated from oligoester degradation, and finally 3) use the models to extract important parameters from experimental data such as the pH range that favors depsipeptide oligomerization. The answers to all these questions can be found in the five chapters of this thesis. Chapter 1 introduces the thesis. It discusses the background information of esterifica xx tion and the ester-amide exchange reaction and provides a thorough literature review of the reaction mechanisms and existing theories including the gaps. After reading the introduc tion, the reader will understand the motivation and objectives behind my research. Chapter 2 identifies and investigates the relevant kinetic mechanisms of depsipeptide degradation. Population balance kinetic models are created to form concentration profiles that yield valuable kinetic information such as half-lives and Arrhenius behavior. Depsipeptides are copolymers of hydroxy acids and amino acids. The study focuses on ester bonds since the amide bonds are more stable under plausible prebiotic conditions. This type of research is important for two reasons. The first reason is that once these mechanisms of depsipeptides are identified, we can predict behavior of similar peptides used to create biopolymers for pharmaceutical purposes such as drug delivery and tissue engineering. The second reason is that depsipeptides are much easier to form than traditional polypeptides. To investigate the kinetic mechanisms of ester reactions in depsipeptides, high performance liquid chromatography (HPLC) data of two test molecules are collected and quantified at different pH values and temperatures: multiple oligomers of an HO-dipeptide called gly colic acid alanine (gA) and a methylated molecule of the gA dimer called propionic acid alanine glycolic acid alanine ((PA)AgA). Chapter 3 provides a cohesive framework that explains the thermodynamic driving force of oligomerizations involving ester bond linkages under plausibly prebiotic condi tions. The framework predicts thermodynamics of oligomerizations of dimers and trimers as well as cyclic esters as function of pH and temperature for any hypothetical solution. Density functional theory (DFT) is used to compute thermochemical data and a benchmark compound is used to fix a critical parameter, pKa of the homodimer of lactic acid. Chapter 4 demonstrates a first-principles thermodynamic model that inputs key param eters such as pKa and allows visualization of a free energy map that shows the spontaneity of the exchange reaction gg + G ↔ gG + g as a function of temperature and pH. This model also shows the thermodynamic driving forces of the exchange reaction. A key result is that the reaction seems insensitive, and thus robust, over a range of dimer pKa’s. A grid search of the unknown pKa values of gG show what the possible pKa values could be for each dimer at 25°C, to favor the reaction. Chapter 5 concludes the thesis, summarizes its key points, and discusses potential future work. It is hoped that the reader gains a great appreciation for fundamental chemical modeling of a longstanding puzzle of the Earth: the origin of life. A secondary motivation of this dissertation is the pharmaceutical application of tissue engineering, hydrogels, and drug delivery. The models provide a computational and chemical engineering view of the problem. As the famous statistician George Box has stated, “All models are wrong, some are useful.” I believe that after seeing the models presented in this dissertation, they will be useful in the origins of life field.Ph.D

Time Waits for No One! Analysis and Challenges of Temporal Misalignment

When an NLP model is trained on text data from one time period and tested or deployed on data from another, the resulting temporal misalignment can degrade end-task performance. In this work, we establish a suite of eight diverse tasks across different domains (social media, science papers, news, and reviews) and periods of time (spanning five years or more) to quantify the effects of temporal misalignment. Our study is focused on the ubiquitous setting where a pretrained model is optionally adapted through continued domain-specific pretraining, followed by task-specific finetuning. We establish a suite of tasks across multiple domains to study temporal misalignment in modern NLP systems. We find stronger effects of temporal misalignment on task performance than have been previously reported. We also find that, while temporal adaptation through continued pretraining can help, these gains are small compared to task-specific finetuning on data from the target time period. Our findings motivate continued research to improve temporal robustness of NLP models.Comment: 9 pages, 6 figures, 3 table

Does acupuncture improve the outcome of in vitro fertilisation? Guidance for future trials

Abstract Introduction The comprehensive review was to appraise the current evidence from both randomized and non-randomized trials by using both Chinese and western databases and to highlight the issues which could guide future trial design. Many infertile couples have chosen acupuncture as an adjunct when they undergo in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. More than forty trials have emerged since the first clinical research published in 1999 explored the effects of acupuncture on the outcomes of IVF. However, the current evidence makes it difficult for clinical practitioners and patients to make a decision on whether to choose acupuncture as an adjunct when undergoing IVF or ICSI treatment. Methodology A total of thirty-three randomized and 5 non-randomized controlled trials were included in the review. Results Based on this comprehensive review and analysis of all the relevant trials, the authors identify the factors which have contributed to these inconsistencies, and which should be considered in the design of future studies. Discussion/conclusions These items included in the review could provide useful recommendations and guidelines, which will in turn promote better trial design and improve the evidence base for the use of acupuncture for IVF

Lifespan Development: a chronological approach [3rd Australasian edition]

Lifespan Development: a chronological approach [3rd Australasian edition] explores human physical, cognitive and social development within an Australian and New Zealand context. Building on the successful first and second editions, the resource's comprehensive theory coverage includes the latest local and international research in this ever-evolving field, and is perfectly complemented by numerous physical and mental health applications within local psychological, allied health and educational settings. This edition includes enhanced coverage of developmental theories, and increased integrated coverage of cross-cultural and Indigenous issues unique to the multicultural societies of Australia and New Zealand. It is an ideal resource offering for undergraduate students in both countries in order to enhance understanding of human development — from conception through to the end of life