On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of homochiral and heterochiral peptides, a variety of computational methods were employed. 10 prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple previous meteorite, spark discharge, and hydrothermal vent studies. We focused on what had been reported as primary early Earth polypeptide analogs: 1ARK, 1PPT, 1ZFI, and 2LZE. Tripeptide composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in minimal folding energy of peptides, while the classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed 10 prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Prebiotic polypeptides were built up to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. Most interestingly, among 129 residues, mutation sensitivity profiles presented that the ratio of more stable to less stable to equally stable D-amino acids was about 1:1:1. In conclusion, some combinations of a mixture of L- and D-amino acids can act as essential building blocks of life. Peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets.

Explaining the evolution of a predominantly homochiral environment on the early Earth remains an outstanding challenge in chemistry. We explore here the mathematical features of a simple chemical model system that simulates chiral symmetry breaking and amplification towards homochirality. The model simulates the reaction of a prochiral molecule to yield enantiomers via interaction with an achiral surface. Kinetically, the reactions and rate constants are chosen so as to treat the two enantiomeric forms symmetrically. The system, however, incorporates a mechanism whereby a random event might trigger chiral symmetry breaking and the formation of a dominant enantiomer; the non-linear dynamics of the chemical system are such that small perturbations may be amplified to near homochirality. Mathematical analysis of the behavior of the chemical system is verified by both deterministic and stochastic numerical simulations. Kinetic description of the model system will facilitate exploration of experimental validation. Our model system also supports the notion that one dominant enantiomeric structure might be a template for other critical molecules.

We present computational models for the replication of double stranded RNA (dsRNA) or related macromolecules under thermal cycling conditions that would reflect prebiotic (i.e. non-enzymatic) environments. Two models of the replication of dsRNA are represented as multi-step chemical systems. The objective of this investigation was to better understand the kinetic features of such chemical systems. It is shown that thermal cycling in a chemical system is advantageous (relative to a fixed temperature) if there are two competing reactions, one favored at high temperature and one favored at low temperature. For the prebiotic replication of dsRNA, a high temperature favors formation of the two single stranded RNA (ssRNA) templates and a presumptive catalysis or catalytic surface is active at low temperature at which the ssRNA template is copied. Our models may facilitate understanding possible prebiotic conditions for the replication of dsRNA.

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Penney-Ante is a well known two-player (Player I and Player II) game based on an information paradox.  We present a new approach, using \emph{difference-equations}, to analyzing the outcome for each player. One strategy yields a winning outcome of 75\% for Player II, the player playing second. The approach also permits investigation of non-optimal strategies, and demonstrates how  mixing of such strategies can be used to tune the winning edge of either player. We generalize the analysis to accommodate the possibility of a biased coin.

Computational modeling of reaction systems can provide a strong foundation for experimental investigations. In this investigation, we first propose a unique theoretical system for breaking chiral symmetry that utilizes thermal cycling to amplify a small initial asymmetry. Unlike models in the literature, no autocatalytic reactions were needed for homochirality in this model to emerge. Following from the theoretical model, experiments were designed with thermal cycling of NaClO3 solutions in DMSO. NaClO3 is not optically active in solution, but crystallizes into two optically active forms; under typical crystallization conditions, both forms arise in roughly equal amounts. With thermal cycling, however, one of the two optically active forms predominates. We hope to extend this experimental model to biologically important reactions to learn if thermal cycling played a role in chiral symmetry breaking in pre-biotic chemistry Introduction: The emergence of chiral selectivity in biological molecules such as amino acids (L) and sugars (D) has long been a topic of interest in the scientific community (1). The fact that traditional synthesis of such compounds yields racemic mixtures (equal amounts of both forms) and not an excess of one enantiomer begs the question as to how such an enantiomeric excess (ee) could arisen to provide the foundation for life on the planet. The famous Frank model suggests that an asymmetric autocatalytic system, in which one species acts as a catalyst for itself and an inhibitor for formation of its enantiomer, would be sensitive enough for a small initial imbalance between the two enantiomers to drive the reaction system to chiral symmetry breaking (1). This model has gained a great deal of attention and has since been demonstrated experimentally via the Soai reaction (2). One of the goals of this project was to create a computational chemical model, which would amplify a small asymmetry (such as in the Frank model), but do so via thermal cycling. Thermal cycling has been shown in previous computational studies to yield counter-intuitive results that were not observed at any individual temperature (3,4). Here we investigate the effect of thermal cycling on reaction systems in order to drive chiral symmetry breaking. Also, we investigated the crystallization of NaClO3 as a possible process that might achieve chiral resolution via thermal cycling. Despite NaClO3 not being chiral itself, it solidifies into two different optically active crystal forms. NaClO3 also posses a quality referred to as chiral amnesia (5), meaning that when in solution, the NaClO3 molecules lose their distinct optical activity that they possessed in crystal form, thus providing a mechanism for rapid racemization. Experiments have shown that racemic mixtures of NaClO3 can break chiral symmetry via stirring, boiling, or aerosol solutions (6,7,8). Based on the results from our computational model, we employed thermal cycling conditions in an attempt to achieve similar results. Applications of such a mechanism could inspire new and creative approaches to prebiotic synthesis reactions to break chiral symmetry. Results: Computations Models Kintecus 3.96, a powerful Arrhenius-based program was used to develop possible reaction schemes and calculate concentrations of theoretical chemical components over time (9). A reaction scheme was designed in which a racemic mixture of R and S exist and have the potential to racemize (Fig 1a and 1b). Also a catalytic surface, C, can bind with an enantiomer (equally with R and S), and the resulting product catalyzes racemization to favor production of the bound enantiomer. At a high temperature however, the catalytic surface becomes inactivated and any bound enantiomers are released back into solution. The only asymmetry in this model is a small difference (less than 1.5%) in the rate of decomposition between the two different enantiomer-catalytic surface species. It is also interesting that this model does not possess an autocatalytic reaction, thus deviating from the Frank model (1). The reaction was simulated for 10,000 seconds at 300K and 400K (initial conditions listed in Table 1); no significant enantiomeric excess was achieved at either fixed temperature (Fig. 2b). However, by simply changing the parameters to cycle back and forth between either temperature (60 seconds at 300K and 15 seconds a 400K) chiral symmetry breaking is achieved (Fig 2). Due to the nature of the reaction, each cycle is able to ensure that more of the Cs complex remains (as compared to the Cr complex) after the high temperature beings to inactive the catalytic surface. Thus, the racemization at the low temperature increasingly shifts the production of S at the expense of R; however, this is still a very small change in ee after one cycle, but there is amplification with thermal cycling giving rise to an enantiomeric excess over time with multiple cycles. Results: Experimental Crystallizations with Sodium Chlorate Sufficient sodium chlorate (3 grams) (Fisher Scientific) was added to 5mL of dimethyl sulfoxide (DMSO) so that solid NaClO3 remained and was at equilibrium with NaClO3 in solution. The initial solutions used were basically racemic, and three reaction conditions were employed: 1. Constant room temperature with stirring 2. Thermal cycling between 70 C for 10 minutes and room temperature (28 o C) for 30 minutes 3. Thermal cycling (as above) and stirring Previous experiments conducted by Viedma et al. show that stirring solutions of NaClO3 was sufficient agitation to bring about just one type of the optically active crystal (6). DMSO was chosen as a solvent for these experiments because of future aspirations to use NaClO3 solutions to drive the pro-chiral organic reactions to breaking symmetry. To quantify the enantiomeric excess of the resulting crystal formations of NaClO3, a polarizing light microscope was employed. When the polarizer and analyzer are set to be about 87 degrees apart, then the two different NaClO3 crystals can be visualized as either dark or light. Thus it follows when the polarizer and analyzer are roughly 93 degrees apart, the previous dark crystals have now become the light crystals and vise verse (Fig 3 a,b) Various samples throughout the stirring and thermal cycling solutions were taken and the number of each optically active crystal recorded to determine percent enantiomeric excess (%ee). Our experiments agreed with the Viedma crystallizations (Fig 4a), in that simple stirring achieved an enantiomeric excess of one form of crystal over time. However, the thermal cycling solutions were able to achieve an ee much more quickly than just stirring (Fig 4b). Combining both thermal cycling and stirring proved to be even more efficient. Overall, a significant increase in ee was achieved by thermal cycling. Further experiments with NaClO3 crystals with more cycles (10 cycles of heating and cooling) and stirring showed Oswald ripening as a possible mechanism for chiral resolution (Fig 5). Discussion Computational models: Thermal cycling has been previously shown to yield counter-intuitive results of relatively simple reaction systems (3,4). Here, we were able to design a reaction system that was unable to produce an enantiomeric excess at any fixed temperature, but broke chiral symmetry if thermal cycling conditions were employed. It is conceivable that such thermal cycling conditions could have naturally existed on a prebiotic earth setting, such as a simple night and day cycle or even underwater thermal vents (11). Experimental Crystallizations: The theoretical model inspired the NaClO3 crystallization experiments so that thermal cycling could be experimentally established as a condition that can in fact be manipulated to produce an enantiomeric excess. Indeed, thermal cycling was found to be even more efficient in producing an enantiomeric excess than stirring, but a combination of both was even more efficient than any single condition. Oswald ripening was observed after 10 cycles, and therefore suggests a mechanism behind this chiral amplification. Thus, thermal cycling has been shown experimentally as a mechanism to produced chiral symmetry breaking. Future Plans: Having preliminary data that supports thermal cycling as a means of obtaining homochirality, more tests will be conducted to definitely conclude that thermal cycling can give rise to one form of NaClO3. Once established, a prochiral organic reaction will be performed in the presence of just one type of the NaClO3 crystal, in hope that it will provide a catalytic surface to select one of the enantiomers (12). If thermal cycling can break chiral symmetry during the syntheses of an asymmetric molecule, then such a mechanism might explain the synthesis of Lamino acids under prebiotic conditions. The role of thermal cycling may have theoretical and practical implications for achieving homochirality in chemical and biological

Optical activity using an iPad as a source of polarized light is demonstrated. A sample crystal or solution can be placed on the iPad running a white screen app. The sample is viewed through a polarized filter that can be rotated. This setup can be used in the laboratory or with a document camera to easily project in a large lecture hall.

Computational models of chemical systems provide clues to counterintuitive interactions and insights for new applications. We have been investigating models of chemical reaction systems under forced, thermal cycling conditions and have found that some hypothetical processes generate higher yields under thermal cycling than under single, fixed temperature conditions. A simple kinetic model of an actual process, the two-temperature polymerase chain reaction that replicates DNA, is used to simulate the important features of a chemical system operating under thermal cycling. This model provides insights into the design of other chemical systems that may have important applications in chemistry, biochemistry and chemical engineering.

Systems chemistry is a new discipline which investigates the interactions within a network of chemical reactions. We have studied several computational models of chemical systems inspired by mathematical paradoxes and have found that even simple systems may behave in a counterintuitive, non-linear manner depending upon various conditions. In the present study, we modeled a set of reactions inspired by one such paradox, Braess’ paradox, an interesting phenomenon whereby the introduction of additional capacity (e.g. pathways) in some simple network systems can lead to an unexpected reduction in the overall flow rate of “traffic” through the system. We devised several chemical systems that behaved in this counterintuitive manner; the overall rate of product formation was diminished when an additional pathway was introduced and, conversely, there was an enhancement of product formation when the same interconnecting pathway was removed. We found that, unlike a traffic model, the chemical model needed to include reversible pathways in order to mimic “congestion”—a condition necessary to produce Braess-like behavior. The model was investigated numerically, but a full analytical solution is also included. We propose that this intriguing situation may have interesting implications in chemistry, biochemistry and chemical engineering.

A mathematical concept known as Parrondo’s paradox motivated the development of several novel computational models of chemical systems, in which thermal cycling was explored. In these kinetics systems, we compared the rates of formation of products under temperature-cycling and steady-state conditions. We found model chemical systems that counter-intuitively predicted a greater concentration of product under oscillating temperature conditions than under fixed conditions. At a practical level, these computational models of thermal cycling suggest new applications in chemistry, biochemistry and chemical engineering. More fundamentally, these models contribute to a growing understanding that even simple chemical systems may behave paradoxically, and that forced oscillating conditions may induce such an outcome.

Parrondo's paradox is a mathematical concept describing two losing games played in an alternate fashion to give a winning outcome. Our objective was to devise computational models of chemical and biochemical systems that were analogous to the paradox. The model systems were created using Kintecus, a chemical kinetics simulation program based on the Arrhenius equation. Model I is a multi‐step system with a temperature sensitive catalyst. The predicted concentration of the target product after 15000 sec at 300K is 6.5x10−3 M and at 480K is 1.6x10−2M. Paradoxically, if the model is run with an oscillating temperature profile between 300K and 480K (23 cycles), then it predicts that considerably more product, 1.25x10−1M is made; this is more product than predicted at any fixed temperature between 300K and 480K. There are few examples of chemical reactions that are actually conducted under oscillating temperature conditions. Model II describes the thermal cycling conditions of PCR under a two‐temperature protocol (2T‐PCR). The computational model predicted that little double‐stranded DNA was synthesized at either 330K (57C) or 370K (97C) but that with thermal cycling (26 cycles in 23000sec), dsDNA is produced almost exponentially until substrates/primers are consumed. This model will allow prediction and optimization of 2T‐PCR reactions. These models suggest that thermal cycling should be explored further in chemical and biochemical systems. This research was supported by the University of New Haven.

Clinical diagnosis of pathological conditions is accomplished regularly via the recording and subsequent analysis of a physiological variable from a subject. Problems with current common practice centre around the obtrusive and rigid nature of this process. These include the length, timing and location of the diagnostic recording session, transfer of data to clinical staff, liaison between clinical staff and subjects and the integration of such diagnostic check-ups into the overall health care process. We have designed a modular diagnostic monitor that is centered around a wearable computer system which, when integrated into a suitable computer network and database architecture, is capable of addressing the above problems. The system is modular, allowing researchers and practitioners to utilise various sensor modules, reconfigure the unit in terms of its on-board storage and wireless telemetry capabilities, select the appropriate level of data preprocessing (before archiving data) and choose the appropriate level and nature of feedback to the subject. The system is GRID enabled, supporting e-clinical-trials. GRID clients can display live data, historical data, or perform data mining.

In this paper we show how we have used and adapted GT3 to support scalable and flexible remote medical monitoring applications on the Grid. We use two lightweight monitoring devices (a java phone and a wearable computer), which monitor blood glucose levels and ECG/SpO2 activity. We have connected those devices to the Grid by means of proxies, allowing those devices to be intermittently connected. The data from the devices is collected in a database on the Grid, and practitioners can obtain real time data or observe the patients historical data.