Asymmetric syntheses of analogs of kainic acid

Kainic acid has been used for nearly 50 years as a tool in neuroscience due to its pronounced neuroexcitatory properties. However, the significant price increase of kainic acid resulting from the disruption in the supply from its natural source, the alga Digenea Simplex, as well as inefficient synthesis of kainic acid, call for the exploration of functional mimics of kainic acid that can be synthesized in a simpler way. Aza kainoids analog could be one of them. The unsubstituted aza analog of kainoids has demonstrates its ability as an ionotropic glutamate receptor agonist and showed affinity in the chloride dependent glutamate (GluCl) binding site. This opened a question of the importance of the presence of one nitrogen or both nitrogens in the aza kainoid analogs for binding to glutamate receptors. Therefore, two different pyrrolidine analogs of kainic acid, trans -4-(carboxymethyl)pyrrolidine-3-carboxylic acid and trans -2-carboxy-3-pyrrolidineacetic acid, were synthesized through multi-step sequences. The lack of the affinity of both pyrrolidine analogs in GluCl binding site indicated that both nitrogens in aza kainoid analogs are involved in hydrogen bonding with receptors, significantly enhancing their affinity in GluCl binding site. Another potential functional mimic of kainic acid is isoxazolidine analogs of kainoids whose skeleton can be constituted directly via a 1, 3 dipolar cycloaddition as the key step. The difficulty in synthesizing N-unsubstituted isoxazolidines when applying such common protecting groups as alkyl, phenyl and benzyl groups, and the requirement of a desired enantioselectivity due to the three chiral ceneters in kainic acid, pose great challenges. Hence, several different protected nitrones were studied to establish that diphenylmethine nitrone may be a good candidate as the dipole in that the generated isoxazolidines can be deprotected in mild conditions with high yields. Our investigations also indicated that the exo/endo selectivity of the 1, 3 dipolar cycloaddition can be controlled by Lewis acids, and that the application of a directing group in dipolarophiles can accomplish a satisfied enantioselectivity. Those results demonstrated the synthesis of isoxazoldines analogs of kainic acid is very promising.

Capacity planning methodology for concurrent engineer -to -order operations

This research focuses on developing a capacity planning methodology for the emerging concurrent engineer-to-order (ETO) operations. The primary focus is placed on the capacity planning at sales stage. This study examines the characteristics of capacity planning in a concurrent ETO operation environment, models the problem analytically, and proposes a practical capacity planning methodology for concurrent ETO operations in the industry. A computer program that mimics a concurrent ETO operation environment was written to validate the proposed methodology and test a set of rules that affect the performance of a concurrent ETO operation. ^ This study takes a systems engineering approach to the problem and employs systems engineering concepts and tools for the modeling and analysis of the problem, as well as for developing a practical solution to this problem. This study depicts a concurrent ETO environment in which capacity is planned. The capacity planning problem is modeled into a mixed integer program and then solved for smaller-sized applications to evaluate its validity and solution complexity. The objective is to select the best set of available jobs to maximize the profit, while having sufficient capacity to meet each due date expectation. ^ The nature of capacity planning for concurrent ETO operations is different from other operation modes. The search for an effective solution to this problem has been an emerging research field. This study characterizes the problem of capacity planning and proposes a solution approach to the problem. This mathematical model relates work requirements to capacity over the planning horizon. The methodology is proposed for solving industry-scale problems. Along with the capacity planning methodology, a set of heuristic rules was evaluated for improving concurrent ETO planning. ^

The Creation and Evaluation of Novel Canine Training Aids for Cocaine Using Molecularly Encapsulated Sol-Gel Polymers and an Investigation of Canine Field Accuracy

Biological detectors, such as canines, are valuable tools used for the rapid identification of illicit materials. However, recent increased scrutiny over the reliability, field accuracy, and the capabilities of each detection canine is currently being evaluated in the legal system. For example, the Supreme Court case, State of Florida v. Harris, discussed the need for continuous monitoring of canine abilities, thresholds, and search capabilities. As a result, the fallibility of canines for detection was brought to light, as well as a need for further research and understanding of canine detection. This study is two-fold, as it looks to not only create new training aids for canines that can be manipulated for dissipation control, but also investigates canine field accuracy to objects with similar odors to illicit materials. It was the goal of this research to improve upon current canine training aid mimics. Sol-gel polymer training aids, imprinted with the active odor of cocaine, were developed. This novel training aid improved upon the longevity of currently existing training aids, while also provided a way to manipulate the polymer network to alter the dissipation rate of the imprinted active odors. The manipulation of the polymer network could allow handlers to control the abundance of odors presented to their canines, familiarizing themselves to their canine’s capabilities and thresholds, thereby increasing the canines’ strength in court. The field accuracy of detection canines was recently called into question during the Supreme Court case, State of Florida v. Jardines, where it was argued that if cocaine’s active odor, methyl benzoate, was found to be produced by the popular landscaping flower, snapdragons, canines will false alert to said flowers. Therefore, snapdragon flowers were grown and tested both in the laboratory and in the field to determine the odors produced by snapdragon flowers; the persistence of these odors once flowers have been cut; and whether detection canines will alert to both growing and cut flowers during a blind search scenario. Results revealed that although methyl benzoate is produced by snapdragon flowers, certified narcotics detection canines can distinguish cocaine’s odor profile from that of snapdragon flowers and will not alert.

Compilation of 220 sediment core d13C data from the glacial Atlantic Ocean

We compare a compilation of 220 sediment core d13C data from the glacial Atlantic Ocean with three-dimensional ocean circulation simulations including a marine carbon cycle model. The carbon cycle model employs circulation fields which were derived from previous climate simulations. All sediment data have been thoroughly quality controlled, focusing on epibenthic foraminiferal species (such as Cibicidoides wuellerstorfi or Planulina ariminensis) to improve the comparability of model and sediment core carbon isotopes. The model captures the general d13C pattern indicated by present-day water column data and Late Holocene sediment cores but underestimates intermediate and deep water values in the South Atlantic. The best agreement with glacial reconstructions is obtained for a model scenario with an altered freshwater balance in the Southern Ocean that mimics enhanced northward sea ice export and melting away from the zone of sea ice production. This results in a shoaled and weakened North Atlantic Deep Water flow and intensified Antarctic Bottom Water export, hence confirming previous reconstructions from paleoproxy records. Moreover, the modeled abyssal ocean is very cold and very saline, which is in line with other proxy data evidence.

(Table 1) Core top Globorotalia truncatulinoides d18O ratios of Atlantic Ocean samples

We investigate whether the oxygen isotope ratio in the test of Globorotalia truncatulinoides can serve as a proxy for intermediate depth (200-500 m) density. Since intermediate depth horizontal density gradients are associated with the vertical shear of upper ocean flows, this proxy could provide a tool for reconstructing past ocean circulation. The spatial pattern of core top Gr. truncatulinoides d18O in the Atlantic Ocean mimics the upper ocean density gradients associated with the major ocean currents. To better constrain the controls on the calcification depth(s) of Gr. truncatulinoides, we attempt to simulate the surface sediment data set using water column temperature and salinity conditions above the core sites. We predicted foraminiferal d18O for each core site assuming (1) the calcification occurs at a single depth and (2) the initial calcification is at the surface and the subsequent calcification is at 800 m water depth. The predicted d18O best resembles measured d18O of Gr. truncatulinoides when using (1) a single depth calcification at 350 m or (2) a two-depth approximation with 30% surface and 70% 800-m calcification. This result gives us confidence in the ability of d18O in Gr. truncatulinoides to proxy lateral density gradients at the intermediate depths associated with upper ocean flow.

Toy model to describe the effect of positional blocklike disorder in metamaterials composites

We study theoretically the effect of a new type of blocklike positional disorder on the effective electromagnetic properties of one-dimensional chains of resonant, high-permittivity dielectric particles, where particles are arranged into perfectly well-ordered blocks whose relative position is a random variable. This creates a finite order correlation length that mimics the situation encountered in metamaterials fabricated through self-assembled techniques, whose structures often display short-range order between near neighbors but long-range disorder, due to stacking defects. Using a spectral theory approach combined with a principal component statistical analysis, we study, in the long-wavelength regime, the evolution of the electromagnetic response when the composite filling fraction and the block size are changed. Modifications in key features of the resonant response (amplitude, width, etc.) are investigated, showing a regime transition for a filling fraction around 50%.

On the dual-cone nature of the conical refraction phenomenon

In conical refraction (CR), a focused Gaussian input beam passing through a biaxial crystal and parallel to one of the optic axes is transformed into a pair of concentric bright rings split by a dark (Poggendorff) ring at the focal plane. Here, we show the generation of a CR transverse pattern that does not present the Poggendorff fine splitting at the focal plane, i.e., it forms a single light ring. This light ring is generated from a nonhomogeneously polarized input light beam obtained by using a spatially inhomogeneous polarizer that mimics the characteristic CR polarization distribution. This polarizer allows modulating the relative intensity between the two CR light cones in accordance with the recently proposed dual-cone model of the CR phenomenon. We show that the absence of interfering rings at the focal plane is caused by the selection of one of the two CR cones. (C) 2015 Optical Society of America

Functional educational characterisation of the utility of embalming fluids for anatomical education and research

Human cadavers have long been used to teach human anatomy and are increasingly used in other disciplines. Different embalming techniques have been reported in the literature; however there is no clear consensus on the opinion of anatomists on the utility of embalmed cadavers for the teaching of anatomy. To this end, we aimed to survey British and Irish anatomy teachers to report their opinions on different preservation methods for the teaching of anatomy. In this project eight human cadavers were embalmed using formalin, Genelyn, Thiel and Imperial College London- Soft Preserving (ICL-SP) techniques to compare different characteristics of these four techniques. The results of this thesis show that anatomy teachers consider hard-fixed cadavers not to be the most accurate teaching model in comparison to the human body, although it still serves as a useful teaching method (Chapter 2). In addition, our findings confirm that joints of cadavers embalmed using ICL-SP solution faithfully mimics joints of an unembalmed cadaver compared to the other techniques (Chapter 3). Embalming a human body prevents the deterioration in the quality of images and our findings highlight that the influence of the embalming solutions varied with the radiological modality used (Chapter 4). The method developed as part of this thesis enables anatomists and forensic scientists to quantify the decomposition rate of an embalmed human cadaver (Chapter 5). Formalin embalming solution showed the strongest antimicrobial abilities followed by Thiel, Genelyn and finally by ICL-SP (Chapter 6). The overarching viewpoint of this set of studies show that it is inaccurate to state that one embalming technique is ultimately the best. The value of each technique differs based on the requirement of the particular education or research area. Hence we highlight how different embalming techniques may be better suited to certain fields of study.

On the Threshold of Paradise and Present: Memory in Contemporary Cuban – American Literature

The exile leaving his or her homeland for new and unknown territory travels with much more than just luggage and the clothes on his or her back. He or she carries a weighty collection of memories. Available for the exile in times when the harmony of the past is far removed from the difficult circumstances present during the process of cultural assimilation, these memories present an opportunity for the exile to fashion for him or herself an identity that mimics the realities of life in the home left behind. In this creative endeavor, I seek to examine the powerful potential of memory as it is exercised by a collection of Cubans and Cuban-Americans in different corners of the United States. Analyzing Achy Obejas’ Memory Mambo, Cristina García’s Dreaming in Cuban, Ana Menéndez’s In Cuba I Was a German Shepherd, and Elías Miguel Muñoz’s Brand New Memory, I aim to trace the suggestive potential of memory as it is used by each of the characters in these works in an effort to reconcile their Cuban identities with the ones that are in the process of creation in the U.S. I will borrow from a collection of literature dealing with identity and exile, relevant graduate-level theses on Cuban-American literature, as well as theoretical perspectives on memory formation and nostalgia in order to trace the various ways in which memory is relied on in the process of cultural assimilation and emotional coping. Being presented in Miami, which hosts the largest concentration of Cuban immigrants, this thesis aims to present itself as a reflective tool for Cubans and Cuban-Americans who may find value in seeing their personal sentiments portrayed in literature, thus allowing for a potential reevaluation of identity. If the existing literature on my topic of analysis reveals anything, it is that the scope of my project is one that has not been inspected previously, thus making my analytical contribution a new one that will add a new interpretive set of lens through which readers of contemporary Cuban-American literature can examine the works.

On the Threshold of Paradise and Present: Memory in Contemporary Cuban‐American Literature

The exile leaving his or her homeland for new and unknown territory travels with much more than just luggage and the clothes on his or her back. He or she carries a weighty collection of memories. Available for the exile in times when the harmony of the past is far removed from the difficult circumstances present during the process of cultural assimilation, these memories present an opportunity for the exile to fashion for him or herself an identity that mimics the realities of life in the home left behind. In this creative endeavor, I seek to examine the powerful potential of memory as it is exercised by a collection of Cubans and Cuban-Americans in different corners of the United States. Analyzing Achy Obejas’ Memory Mambo, Cristina García’s Dreaming in Cuban, Ana Menéndez’s In Cuba I Was a German Shepherd, and Elías Miguel Muñoz’s Brand New Memory, I aim to trace the suggestive potential of memory as it is used by each of the characters in these works in an effort to reconcile their Cuban identities with the ones that are in the process of creation in the U.S. I will borrow from a collection of literature dealing with identity and exile, relevant graduate-level theses on Cuban-American literature, as well as theoretical perspectives on memory formation and nostalgia in order to trace the various ways in which memory is relied on in the process of cultural assimilation and emotional coping. Being presented in Miami, which hosts the largest concentration of Cuban immigrants, this thesis aims to present itself as a reflective tool for Cubans and Cuban-Americans who may find value in seeing their personal sentiments portrayed in literature, thus allowing for a potential reevaluation of identity. If the existing literature on my topic of analysis reveals anything, it is that the scope of my project is one that has not been inspected previously, thus making my analytical contribution a new one that will add a new interpretive set of lens through which readers of contemporary Cuban-American literature can examine the works.

Test sizes of planktic foraminifera from the South Atlantic

Geographical size distribution within entire Holocene foraminiferal assemblages is related to global environmental gradients such as temperature, primary productivity, and environmental variability. This study demonstrates that these correlations are also recognizable in late Quaternary assemblages from three locations in the South Atlantic on temporal and latitudinal scales. The size response to temporal paleoenvironmental changes during glacial-interglacial cycles mimics the geographic Holocene size variability. The amplitude of size variability is directly related to the amplitude of the climatic fluctuations as shown by the stable size-temperature relationship over time. The documented changes in the assemblage size are caused by species replacement and intraspecific size variability. The relative importance of these processes depends on the environmental setting. Species have been shown to reach their maximum size and abundance under certain optimum conditions and decrease in size if environmental conditions differ from these optima. We confirm that late Quaternary species sizes were largest at paleotemperatures identical to Holocene ones.

Mechanical properties and cellular response of novel electrospun nanofibers for ligament tissue engineering: Effects of orientation and geometry

Electrospun nanofibers are a promising material for ligamentous tissue engineering, however weak mechanical properties of fibers to date have limited their clinical usage. The goal of this work was to modify electrospun nanofibers to create a robust structure that mimics the complex hierarchy of native tendons and ligaments. The scaffolds that were fabricated in this study consisted of either random or aligned nanofibers in flat sheets or rolled nanofiber bundles that mimic the size scale of fascicle units in primarily tensile load bearing soft musculoskeletal tissues. Altering nanofiber orientation and geometry significantly affected mechanical properties; most notably aligned nanofiber sheets had the greatest modulus; 125% higher than that of random nanofiber sheets; and 45% higher than aligned nanofiber bundles. Modifying aligned nanofiber sheets to form aligned nanofiber bundles also resulted in approximately 107% higher yield stresses and 140% higher yield strains. The mechanical properties of aligned nanofiber bundles were in the range of the mechanical properties of the native ACL: modulus=158±32MPa, yield stress=57±23MPa and yield strain=0.38±0.08. Adipose derived stem cells cultured on all surfaces remained viable and proliferated extensively over a 7 day culture period and cells elongated on nanofiber bundles. The results of the study suggest that aligned nanofiber bundles may be useful for ligament and tendon tissue engineering based on their mechanical properties and ability to support cell adhesion, proliferation, and elongation.

The comparative utility of fluorescence in situ hybridization and reverse transcription-polymerase chain reaction in the diagnosis of alveolar rhabdomyosarcoma.

Fluorescence in situ hybridization (FISH) for FOXO1 gene rearrangement and reverse transcription-polymerase chain reaction (PCR) for PAX3/7-FOXO1 fusion transcripts have become routine ancillary tools for the diagnosis of alveolar rhabdomyosarcomas (ARMS). Here we summarize our experience of these adjunct diagnostic modalities at a tertiary center, presenting the largest comparative series of FISH and PCR for suspected or possible ARMS to date. All suspected or possible ARMS tested by FISH or PCR for FOXO1 rearrangement or PAX3/7-FOXO1 fusion transcripts over a 7-year period were included. FISH and PCR results were correlated with clinical and histologic findings. One hundred samples from 95 patients had FISH and/or PCR performed. FISH had higher rates of technical success (96.8 %) compared with PCR (88 %). Where both tests were utilized successfully, there was high concordance rate between them (94.9 %). In 24 histologic ARMS tested for FISH or PCR, 83.3 % were translocation-positive (all for PAX3-FOXO1 by PCR) and included 3 histologic solid variants. In 76 cases where ARMS was excluded, there were 3 potential false-positive cases with FISH but none with PCR. PCR had similar sensitivity (85.7 %) and better specificity (100 %) in aiding the diagnosis of ARMS, compared with FISH (85 and 95.8 %, respectively). All solid variant ARMS harbored FOXO1 gene rearrangements and PAX3-FOXO1 ARMS were detected to the exclusion of PAX7-FOXO1. In comparative analysis, both FISH and PCR are useful in aiding the diagnosis of ARMS and excluding its sarcomatous mimics. FISH is more reliable technically but has less specificity than PCR. In cases where ARMS is in the differential diagnosis, it is optimal to perform both PCR and FISH: both have similar sensitivities for detecting ARMS, but FISH may confirm or exclude cases that are technically unsuccessful with PCR, while PCR can detect specific fusion transcripts that may be useful prognostically.

Neural networks would 'vote' according to Borda's Rule

Can neural networks learn to select an alternative based on a systematic aggregation of convicting individual preferences (i.e. a 'voting rule')? And if so, which voting rule best describes their behavior? We show that a prominent neural network can be trained to respect two fundamental principles of voting theory, the unanimity principle and the Pareto property. Building on this positive result, we train the neural network on profiles of ballots possessing a Condorcet winner, a unique Borda winner, and a unique plurality winner, respectively. We investigate which social outcome the trained neural network chooses, and find that among a number of popular voting rules its behavior mimics most closely the Borda rule. Indeed, the neural network chooses the Borda winner most often, no matter on which voting rule it was trained. Neural networks thus seem to give a surprisingly clear-cut answer to one of the most fundamental and controversial problems in voting theory: the determination of the most salient election method.

Panoramic Sea Happening (After Kantor): Video Installation

Panoramic Sea Happening (After Kantor) is a 7 minute durational film that reimagines part of Tadeusz Kantor's original sea happenings from 1967 in a landscape in which the sea has retreated. The conductor of Kantor’s original performance is replaced with a sound object cast adrift on a beach in Dungeness (UK). The object plays back the sound of the sea into the landscape, which was performed live and then filmed from three distinct angles. The first angle mimics the position of the conductor in Kantor’s original happening, facing outwards into the horizon of the beach and recalls the image in Kantor’s work of a human figure undertaking the absurd task of orchestrating the sound of a gigantic expanse of water. The second angle exposes the machine itself and the large cone that amplifies the sound, reinforcing the isolation of the object. The third angle reveals a decommissioned nuclear power station and sound objects used as a warning system for the power plant. Dungeness is a location where the sea has been retreating from the land, leaving traces of human activity through the disused boat winches, abandoned cabins and the decommissioned nuclear buildings. It is a place in which the footprint of the anthropocene is keenly felt. The sound object is intended to act as an anthropomorphic figure, ghosting the original conductor and offering the sound of the sea back into the landscape through a wide mouthpiece, echoing Kantor’s own load hailer in the original sequence of sea happenings. It speculates on Kantor's theory of the bio-object, which proposed a symbiotic relationship between the human and the nonhuman object in performance, as a possible instrument to access a form of geologic imagination. In this configuration, the human itself is absent, but is evoked through the objects left behind. The sound object, helpless in a red dingy, might be thought of as a co-conspirator with the viewer, enabling a looking back to the past in a landscape of an inevitable future. The work was originally commissioned by the University of Kent in collaboration with the Polish Cultural Institute for the Symposium Kantorbury Kantorbury in Canterbury (UK) to mark the 100 years since Tadeusz Kantor’s birth (15 - 19 September 2015). It should be projected and requires stereo speakers.