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Hyperspectral Imaging (HSI) for fluorescence-guided brain tumor resection enables visualization of differences between tissues that are not distinguishable to humans. This augmentation can maximize brain tumor resection, improving patient outcomes. However, much of the processing in HSI uses simplified linear methods that are unable to capture the non-linear, wavelength-dependent phenomena that must be modeled for accurate recovery of fluorophore abundances. We therefore propose two deep learning models for correction and unmixing, which can account for the nonlinear effects and produce more accurate estimates of abundances. Both models use an autoencoder-like architecture to process the captured spectra. One is trained with protoporphyrin IX (PpIX) concentration labels. The other undergoes semi-supervised training, first learning hyperspectral unmixing self-supervised and then learning to correct fluorescence emission spectra for heterogeneous optical and geometric properties using a reference white-light reflectance spectrum in a few-shot manner. The models were evaluated against phantom and pig brain data with known PpIX concentration; the supervised model achieved Pearson correlation coefficients (R values) between the known and computed PpIX concentrations of 0.997 and 0.990, respectively, whereas the classical approach achieved only 0.93 and 0.82. The semi-supervised approach's R values were 0.98 and 0.91, respectively. On human data, the semi-supervised model gives qualitatively more realistic results than the classical method, better removing bright spots of specular reflectance and reducing the variance in PpIX abundance over biopsies that should be relatively homogeneous. These results show promise for using deep learning to improve HSI in fluorescence-guided neurosurgery., Comment: 20 pages, 8 figures, 3 tables - Under Review

A majority of the 34 million people who currently smoke cigarettes report wanting to quit smoking yet most attempts to quit end in relapse. A mindfulness based intervention (MBI) is an intervention package used to reinforce an individual's practice of mindfulness meditation in daily life. MBIs delivered by phone app offer daily prompts to guide bouts of mindfulness meditation, that is, sustained attention to moment-by-moment experience without behavior reactivity. Daily bouts of mindfulness meditation offer individuals a replacement behavior for smoking during a quit attempt, and MBI app instruction aims to increase an individual's skill in non-reactivity when they experience cravings. Our study objective is to test the effect of an app-based MBI on abstinence during a scheduled quit attempt among people who currently smoke and who are willing to make a voluntary quit attempt on a selected near-term date. Our delivery of a smartphone app-based MBI occurs daily for the two weeks preceding a planned quit date. Study participants are randomized to an app-based MBI or psychoeducation control group and asked to self-administer their intervention two times a day in 10-min segments for 14 sequential days for a total of 280 min. This preparatory period capitalizes on time to help participants orient toward a near-term goal to quit smoking, practice mindfulness meditation, and increase the skill of non-reactivity during states of craving to smoke. We recruit people who smoke cigarettes from all 58 counties in California. We test the hypothesis that an app-based MBI will outperform a time-matched psychoeducation control on increasing smoking abstinence. Findings contribute knowledge to the addictions treatment field about whether MBIs delivered by app can increase smoking cessation in a geographically-diverse sample.

BACKGROUND: The rise of depression, anxiety, and suicide rates has led to increased demand for telemedicine-based mental health screening and remote patient monitoring (RPM) solutions to alleviate the burden on, and enhance the efficiency of, mental health practitioners. Multimodal dialog systems (MDS) that conduct on-demand, structured interviews offer a scalable and cost-effective solution to address this need. OBJECTIVE: This study evaluates the feasibility of a cloud based MDS agent, Tina, for mental state characterization in participants with depression, anxiety, and suicide risk. METHOD: Sixty-eight participants were recruited through an online health registry and completed 73 sessions, with 15 (20.6%), 21 (28.8%), and 26 (35.6%) sessions screening positive for depression, anxiety, and suicide risk, respectively using conventional screening instruments. Participants then interacted with Tina as they completed a structured interview designed to elicit calibrated, open-ended responses regarding the participants feelings and emotional state. Simultaneously, the platform streamed their speech and video recordings in real-time to a HIPAA-compliant cloud server, to compute speech, language, and facial movement-based biomarkers. After their sessions, participants completed user experience surveys. Machine learning models were developed using extracted features and evaluated with the area under the receiver operating characteristic curve (AUC). RESULTS: For both depression and suicide risk, affected individuals tended to have a higher percent pause time, while those positive for anxiety showed reduced lip movement relative to healthy controls. In terms of single-modality classification models, speech features performed best for depression (AUC = 0.64; 95% CI = 0.51-0.78), facial features for anxiety (AUC = 0.57; 95% CI = 0.43-0.71), and text features for suicide risk (AUC = 0.65; 95% CI = 0.52-0.78). Best overall performance was achieved by decision fusion of all mode

Complete resection of malignant gliomas is hampered by the difficulty in distinguishing tumor cells at the infiltration zone. Fluorescence guidance with 5-ALA assists in reaching this goal. Using hyperspectral imaging, previous work characterized five fluorophores' emission spectra in most human brain tumors. In this paper, the effectiveness of these five spectra was explored for different tumor and tissue classification tasks in 184 patients (891 hyperspectral measurements) harboring low- (n=30) and high-grade gliomas (n=115), non-glial primary brain tumors (n=19), radiation necrosis (n=2), miscellaneous (n=10) and metastases (n=8). Four machine learning models were trained to classify tumor type, grade, glioma margins and IDH mutation. Using random forests and multi-layer perceptrons, the classifiers achieved average test accuracies of 84-87%, 96%, 86%, and 93% respectively. All five fluorophore abundances varied between tumor margin types and tumor grades (p < 0.01). For tissue type, at least four of the five fluorophore abundances were found to be significantly different (p < 0.01) between all classes. These results demonstrate the fluorophores' differing abundances in different tissue classes, as well as the value of the five fluorophores as potential optical biomarkers, opening new opportunities for intraoperative classification systems in fluorescence-guided neurosurgery., Comment: 22 pages, 8 figures

Likens the situation in today's public health to war, recommending a military-style strategic plan that focuses on three concepts (ends, ways, and means), and suggesting that until these three are in balance, the best way for the United States to win a public health war is to focus on the enemy's center of gravity, prioritize ends, and apply efficacious instruments of power graduated according to means. (SM)

This chapter focuses on the interaction of metal ions mainly with RNA. It is an update of the previous Chapter 3.21 in the 2nd Edition of Comprehensive Inorganic Chemistry II (2013) but focusing solely on RNA. Metal ions are key to folding, structure, and function of any nucleic acid. These interactions are generally of a weak and highly dynamic nature as they concern mostly K+ and Mg2+ in living organisms. Aside from the large excess of loosely bound ions for charge compensation, a network of inner-sphere and outer-sphere interactions holds more specifically bound ions in place. Hence, metal ion binding to larger RNAs is rather complicated and has many facets. After a few general considerations on the basic properties of metal ions and the potential coordination sites on the RNA, the thermodynamics of metal ion binding to RNA and known metal ion binding motifs in RNA are described. This is followed by today's knowledge on the role of metal ions in folding, dynamics, sensing, and/or catalysis of riboswitches and ribozymes, respectively, is summarized.

Combination of matrix isolation techniques with theoretical methods for identification and characterization of some dithiiranes and oxathiiranes is presented. In general, both dithiiranes and oxathiiranes were generated via flask vacuum pyrolysis of suitable sulfur-containing precursors such as 1,2,4-trithiolanes, 1,3-dithietane 1,3-dioxide or thiocarbonyl S-oxides (sulfines). Novel applications of dimethyldioxirane (DMDO) and (trifluoromethyl)methyl dioxirane (TFMDO) as versatile oxidizing reagents published in the period 2008–2018 are summarized. Methods applied for manufacturing of new polymeric materials functionalized with dioxirane moieties and reported in patents are presented. Mechanisms involving Criegee intermediates in reactions of carbonyl compounds with dioxiranes using experimental and theoretical methods are discussed in the light of recent results.

chapter. The properties, reactivity, ring synthesis and formation of various derivatives of 1,2,3-oxadiazole are reviewed. For a comprehensive view of the field, it is recommended that this chapter is read in conjunction with the earlier chapters published in CHEC (1984), CHEC-II (1996) and CHEC-III (2008).

The research relating to oxatriazoles, published since 2007, is covered in this Chapter. The properties, reactivity, ring synthesis and formation of various derivatives of oxadiazoles are reviewed. For a comprehensive view of the field, it is recommended that this Chapter is read in conjunction with the earlier chapters published in CHEC (1984), CHEC-II (1996) and CHEC-III (2008).

The United States Army Futures Command (AFC) is comparing multiple modernization levels of various programs in order to prepare for military operations in 2035 and beyond. This thesis supports that effort by analyzing a data set of three modernization level possibilities for 68 programs. There are 2.78 nonillion possible combinations in this data set, and the current methodology requires an analyst to select a single combination, and then calculate the overall benefit score. The time to complete this calculation is over 1 second, so by using the current methodology it would require 8.8 X 10^22 centuries to compute. Therefore, this thesis started with two objectives: (1) develop a faster method for calculating the benefit score for a singular combination of programs, and (2) develop a methodology for comparing multiple scores to each other at once. While in pursuit of the first two objectives, the programming Julia proved to be exponentially faster for singular calculations, resulting in the ability to view nearly 9,000 scores within one second, all while using CPU encoding. These faster calculations led to the development of a third objective: compare the speed and accuracy of a machine learning (ML) algorithm. The third objective resulted in speeds 40 times faster than the CPU model, but with a relative error of 1.3%., The Research and Analysis Center, Major, United States Army, Approved for public release. Distribution is unlimited.

Mindfulness-based interventions (MBIs) may offer a means for Latinx families to ameliorate stress, enhance emotion regulation, and foster social support. We assessed pilot data from Latinx parents in Eastside Los Angeles (n = 27) matched with their children aged 10-16 (n = 32) to determine whether participation in a community-derived MBI was associated with greater improvements in dispositional mindfulness, perceived stress, emotion regulation, and family social support compared to a control condition. Compared to the control group, parents in the MBI group showed greater reductions in perceived stress scale (PSS) scores (B = - 2.94, 95% CI [- 5.58, - 0.39], p = 0.029), while their children reported greater increases in perceived social support from family (B = 2.32, 95% CI [0.26, 4.38], p = 0.027). Findings show a community-derived MBI may improve stress in Latinx parents and social support for their children.

Bacterial infection is a major problem world-wide that not only threatens public health but also causes heavy economic burdens. This problem is made worse by the rise in antimicrobial resistance in consequence of over-prescription and improper use of antimicrobial agents. Thus, development of alternative antimicrobials and their formulation has become an urgent need. Hydrogels are biomaterials that can be endowed with antimicrobial function by incorporating another active agent or through their self-assembled component. However, current hydrogels have some limitations such as lack of chemical diversity, toxicity, and undesired burst-release of bioactive agents. This work explores the synthesis of glyoxylamide- and anthranilamide-based short peptides as self-assembled gels and their antibacterial potency. The glyoxylamide- and anthranilamide-based short peptides were synthesised via ring-opening reactions of N-acylisatins and isatoic anhydride, respectively, with L-phenylalanyl-L-phenylalanine in solution phase. These short peptides successfully formed hydrogels at relatively low concentrations (0.08 - 0.20% w/v) and their properties were characterised using various spectroscopy and microscopy techniques.Hydrogels made from glyoxylamide-based short peptide exhibited high loading capacity (40% w/w), a sustained release profile, and capability to retain the antibacterial efficacy of ciprofloxacin (an antibacterial) against Gram positive and Gram negative bacteria. On the other hand, hydrogels developed from anthranilamide-based short peptides exhibited inherent antibacterial activity by showing significant bacterial reductions against S. aureus. Importantly, the majority of glyoxylamide- and anthranilamide-based hydrogels demonstrated low toxicity against mammalian cells.The current study also investigated the potential of anthranilamide-based short peptides for nitric oxide (NO) delivery. The hydrogel formed from anthranilamide-based hydrogel bearing NO donor, as the

Exoplanets are abundant in our galaxy and yet characterizing them remains a technical challenge. Solar System planets provide an opportunity to test the practical limitations of exoplanet observations with high signal-to-noise data that we cannot access for exoplanets. However, data on Solar System planets differ from exoplanets in that Solar System planets are spatially resolved while exoplanets are unresolved point-sources. We present a novel instrument designed to observe Solar System planets as though they are exoplanets, the Planet as Exoplanet Analog Spectrograph (PEAS). PEAS consists of a dedicated 0.5-m telescope and off-the-shelf optics, located at Lick Observatory. PEAS uses an integrating sphere to disk-integrate light from the Solar System planets, producing spatially mixed light more similar to the spectra we can obtain from exoplanets. This paper describes the general system design and early results of the PEAS instrument.

Exoplanets are abundant in our galaxy and yet characterizing them remains a technical challenge. Solar System planets provide an opportunity to test the practical limitations of exoplanet observations with high signal-to-noise data that we cannot access for exoplanets. However, data on Solar System planets differ from exoplanets in that Solar System planets are spatially resolved while exoplanets are unresolved point-sources. We present a novel instrument designed to observe Solar System planets as though they are exoplanets, the Planet as Exoplanet Analog Spectrograph (PEAS). PEAS consists of a dedicated 0.5-m telescope and off-the-shelf optics, located at Lick Observatory. PEAS uses an integrating sphere to disk-integrate light from the Solar System planets, producing spatially mixed light more similar to the spectra we can obtain from exoplanets. This paper describes the general system design and early results of the PEAS instrument., Comment: SPIE Astronomical Telescopes & Instrumentation 2020 Proceedings (11447-153), 9 pages, 9 figures

Antimicrobial resistance is a major worldwide threat to public health and there is an urgent need for the development of novel antibacterial agents. This research project focused on the development of short cationic peptidomimetics that employ 3'-amino-[1, 1 '-biphenyl)-3-carboxylic acid and anthranilic acidbackbones segregated by hydrophobic and cationic groups. The biphenyl peptidomimetic compounds showed that simple diaminoethanes and their respective guanidine cationic groups were sufficient to mimic lysine and arginine amino acids of natural antimicrobial peptides. The biphenyl backbone was important for antibacterial activity and tryptophan was important for bacterial cell membrane permeability. The most active compound showed good minimum inhibitory concentrations (MIC) against S. aureus (15.6 μM) and E.coli (7.8 μM) but was inactive against P. aeruginosa strain PA01. Based on these results, anthranilamide derivatives with tryptophan and simple amine cationic groups were developed. The anthranilamide peptidomimetic compounds showed that the guanidine group was important for good antibacterial activity against S. aureus (3.9 μM), E.coli (15.6 μM), and these compounds had low cytotoxicity (>100 μM). Active compounds disrupted 75% of established S. aureus biofilms. Biphenyl could be used as an alternative to naphthoyl groups to give hydrophobic groups to the mimetics. Increasing the net charge by adding lysine decreased antibacterial activity compared to compounds containing simple amine groups but improved the compound's cytotoxicity.Various alkyl-substituted guanidine compounds were investigated. Increasing the lipophilicity (adding alkyl groups) at the guanidine residues decreased antibacterial activity. Increasing the cationicity increased antibacterial activity against P. aeruginosa. The most active compound showed broad-spectrumantibacterial activity of against S. aureus (2.0 μM), E.coli (7.8 μM), and P. aeruginosa (32.0 μM). The active compounds at 4.0-8.

During stereotactic brain tumor biopsies, the detection of protoporphyrin IX (PpIX) fluorescence and microvascular perfusion using laser Doppler flowmetry (LDF) with a handheld fiber optic probe allows the identification of tumor tissue while decreasing the risk of intracranial hemorrhage. Neurosurgeons performing this procedure usually view the measurement values on a screen. When their visual focus is directed at the surgical site, they require an assistant to verbally relay the values. An auditory and visual user interface (UI), which displays measurement values accurately and allows fast and intuitive signal recognition, can improve this procedure. This paper experimentally evaluates an auditory and visual UI for providing real-time measurement feedback during stereotactic brain tumor biopsies. In a user study (n = 15), the accuracy of auditory and visual response was determined using function response tests, and user acceptance was evaluated. The auditory signals proved to be intuitive and easy to recognize and remember. The visual display of measurement values was easy to understand and facilitated the user’s decision-making process. Moreover, the UI exhibited high user acceptance., Funding agencies: LiU-cancer; Swedish Childhood Cancer Foundation [2013-0043]; ALF Grants Region Ostergotland [LIO-599651]

A Samaritan State Revisited brings together a refreshing group of emerging and leading scholars to reflect on the history of Canada's overseas development aid. Addressing the broad ideological and institutional origins of Canada's official development assistance in the 1950s and specific themes in its evolution and professionalization after 1960, this collection is the first to explore Canada's history with foreign aid with this level of interrogative detail. Extending from the 1950s to the present and covering Canadian aid to all regions of the Global South, from South and Southeast Asia to Latin America and Africa, these essays embrace a variety of approaches and methodologies ranging from traditional, archival-based research to textual and image analysis, oral history, and administrative studies. A Samaritan State Revisited weaves together a unique synthesis of governmental and non-governmental perspectives, providing a clear and readily accessible explanation of the forces that have shaped Canadian foreign aid policy.

A Samaritan State Revisited brings together a refreshing group of emerging and leading scholars to reflect on the history of Canada's overseas development aid. Addressing the broad ideological and institutional origins of Canada's official development assistance in the 1950s and specific themes in its evolution and professionalization after 1960, this collection is the first to explore Canada's history with foreign aid with this level of interrogative detail. Extending from the 1950s to the present and covering Canadian aid to all regions of the Global South, from South and Southeast Asia to Latin America and Africa, these essays embrace a variety of approaches and methodologies ranging from traditional, archival-based research to textual and image analysis, oral history, and administrative studies. A Samaritan State Revisited weaves together a unique synthesis of governmental and non-governmental perspectives, providing a clear and readily accessible explanation of the forces that have shaped Canadian foreign aid policy.

Since hyperactivity of the protein kinase DYRK1A is linked to several neurodegenerative disorders, DYRK1A inhibitors have been suggested as potential therapeutics for Down syndrome and Alzheimer’s disease. Most published inhibitors to date suffer from low selectivity against related kinases or from unfavorable physicochemical properties. In order to identify DYRK1A inhibitors with improved properties, a series of new chemicals based on [b]-annulated halogenated indoles were designed, synthesized, and evaluated for biological activity. Analysis of crystal structures revealed a typical type-I binding mode of the new inhibitor 4-chlorocyclohepta[b]indol-10(5H)-one in DYRK1A, exploiting mainly shape complementarity for tight binding. Conversion of the DYRK1A inhibitor 8-chloro-1,2,3,9-tetrahydro-4H-carbazol-4-one into a corresponding Mannich base hydrochloride improved the aqueous solubility but abrogated kinase inhibitory activity.

In cattle breeding, the development of genomic selection strategies based on single nucleotide polymorphism (SNP) interrogation has led to improved rates of genetic gain. Additionally, the application of genomic selection to in-vitro produced (IVP) embryos is expected to bring further benefits thanks to the ability to test a greater number of individuals before establishing a pregnancy and to ensure only carriers of desirable traits are born. However, aneuploidy, a leading cause of developmental arrest, is known to be common in IVP embryos. Karyomapping is a comprehensive screening test based on SNP typing that can be used for simultaneous genomic selection and aneuploidy detection, offering the potential to maximize pregnancy rates. Moreover, Karyomapping can be used to characterize the frequency and parental origin of aneuploidy in bovine IVP embryos, which have remained underexplored to date. Here, we report the use of Karyomapping to characterize the frequency and parental origin of aneuploidy in IVP bovine embryos in order to establish an estimate of total aneuploidy rates in each parental germline. We report an estimate of genome wide recombination rate in cattle and demonstrate, for the first time, a proof of principle for the application of Karyomapping to cattle breeding, with the birth of five calves after screening. This combined genomic selection and aneuploidy screening approach was highly reliable, with calves showing 98% concordance with their respective embryo biopsies for SNP typing and 100% concordance with their respective biopsies for aneuploidy screening. This approach has the potential to simultaneously improve pregnancy rates following embryo transfer and the rate of genetic gain in cattle breeding, and is applicable to basic research to investigate meiosis and aneuploidy.

Canada’s engagement with post-independence Africa presents a puzzle. Although Canada is recognized for its activism where Africa is concerned, critics have long noted the contradictions that underlie Canadian involvement. Focusing on the period following 2000, and by juxtaposing Jean Chrétien’s G8 activism with the Harper government’s retreat from continental engagement, David R. Black’s Canada and Africa in the New Millennium illustrates a history of consistent inconsistency in Canada’s relationship with Africa. Black combines three interpretive frames to account for this record: the tradition of “good international citizenship”; Canada’s role as a benign face of Western hegemonic interests in Africa; and Africa’s role as the basis for a longstanding narrative concerning Canada’s ethical mission in the world. To examine Africa’s place in Canada’s foreign policy—and Canada’s place in Africa—Black focuses on G8 diplomacy, foreign aid, security assistance through peace operations and training, and the increasingly controversial impact of Canadian extractive companies. Offering an integrated account of Canada’s role in sub-Saharan Africa, Black provides a way of understanding the nature and resilience of recent shifts in Canadian policy. He underscores how Africa—though marginal to Canadian interests as traditionally conceived—has served as an important marker of Canada’s international role.

PURPOSE: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon. METHODS: The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training. RESULTS: The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate. CONCLUSION: The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displ, Funding agencies: Swedish Childhood Cancer foundation [MT 2013-0043]; Cancer network at Linkoping University (LiU-cancer); National Institutes of Health [P41 EB015902, P41 EB015898, R01EB014955, U24CA180918], OTP

This project aimed to synthesize fused-ring systems derived from flavanones and isoflavanones by utilizing the chemistry of the highly reactive ortho-quinone methide (o-QM) intermediate. The synthesis of cis-4-arylisoflavan and isoflavene derivatives was also explored by employing different metal catalysts.The fused-ring systems were synthesized via inverse electron-demand Diels Alder (iEDDA) reaction between dienophiles and o-QM intermediate, which was generated in situ by thermolysis of the corresponding Mannich base. The reaction proceeded in a highly regioselective way, which can be explained by the charge distribution of the reacting partners. However, in the case of 7-hydroxyflavanone, the cycloadduct mixture contained both ring-closed flavanone product and ring-opened chalcone product. The iEDDA reactions were found to give cycloadducts in high yields when electron-rich alkenes were used. In contrast, electron-poor dienophiles remained unreactive in this reaction.The chemistry of o-QM was further studied using dihydrodaidzein, an isoflavanone-type compound as a scaffold. The ability of o-QM to undergo both [4+2] cycloaddition reaction with dienophiles and Michael addition with nucleophiles was explored. However, under certain conditions, the isoflavanone core underwent ring-opening, a process which was proposed to involve the formation of a propenone intermediate. Electron-rich arenes such as 3,5-dimethoxyphenol and 3,5-dimethoxyaniline participated in a Michael addition reaction to furnish the biarylmethane analogues, possessing a methylene bridge which connected the C8 of dihydrodaidzein with the arene moiety. Interestingly, with sulfur-containing arenes, the resulting products possessed a thioether linkage. A rationale for this observation has been proposed.4-Arylisoflavans and isoflavenes were reported to exhibit promising anticancer activities. The synthesis of these derivatives was explored by utilizing metal catalysts. cis-4-Arylisoflavans were prepare

Sleep problems are prevalent among older adults, often persist untreated, and are predictive of health detriments. Given the limitations of conventional treatments, non-pharmacological treatments such as mindfulness-based interventions (MBIs) are gaining popularity for sleep ailments. However, nothing is yet known about the impact of MBIs on sleep in older adults with prodromal sleep disturbances. This article details the design and methodology of a 6-week parallel-group RCT calibrated to test the treatment effect of the Mindful Awareness Practices (MAPs) program versus sleep hygiene education for improving sleep quality, as the main outcome, in older adults with prodromal sleep disturbances. Older adults with current sleep disturbances will be recruited from the urban Los Angeles community. Participants will be randomized into two standardized treatment conditions, MAPs and sleep hygiene education. Each condition will consist of weekly 2-hour group-based classes over the course of the 6-week intervention. The primary objective of this study is to determine if mindfulness meditation practice as engaged through the MAPs program leads to improved sleep quality relative to sleep hygiene education in older adults with prodromal sleep disturbances.

The primary aim of this project is to develop novel anti-tumor agents based on the scaffolds of two natural flavonoids phenoxodiol and (+)-catechin, and evaluate their biological properties and mechanism of action in cancer cells.The phenoxodiol scaffold was structurally modified through molecular hybridization and addition of fused-ring systems. Phenoxodiol was combined with 1-amino-2-propanol and thiosemicarbazone moieties to generate novel phenoxodiol-hybrids. The 1-amino-2-propanol and thiosemicarbazone moieties were linked with phenoxodiol through nucleophilic ring-opening of an epoxide intermediate, and through Schiff base condensation with an aldehyde or ketone intermediate. Synthesis of fused hybrid systems was carried out via an inverse electron demand Diels-Alder reaction between electron-rich dienophiles and ortho-quinone methide intermediate of phenoxodiol.In order to overcome the poor bioavailability of flavonoids, which limits their clinical use, different drug delivery vehicles for phenoxodiol and (+)-catechin were explored. Carbohydrates, β-cyclodextrin and dextran, were selected for their aqueous solubility and biocompatibility. Phenoxodiol was encapsulated into β-cyclodextrin via a modified co-evaporation method, and was alternatively conjugated onto dextran using an enzymatic method. (+)-Catechin was conjugated onto β-cyclodextrin via a cycloaddition strategy.In vitro anti-proliferative activities of the newly synthesized compounds were evaluated against various cancer cell types. In general, most of the compounds exhibited strong anti-proliferative activities across all the tested cancer cell lines. Importantly, many of them also showed an overall increase in specificity as compared to the parent molecule.As angiogenesis plays an important role in cancer progression, the anti-angiogenic mechanism for dextran-catechin conjugate was investigated and demonstrated that it inhibited angiogenesis by disrupting copper metabolism within the endothelial c

Bacterial biofilms on life-saving implanted medical devices are a serious problem in long-term. At present, no effective strategies are available and the emergence of multi-drug resistance has highlighted the need to develop novel antibacterial coatings to combat device-related infections. One approach is to block the bacterial communication pathway or quorum sensing (QS), which is responsible for biofilm formation, by incorporating QS inhibitors (QSIs) such as dihydropyrrolones (DHPs) and furanones (FUs) on biomaterial surfaces and polymers. The endogenous biological signalling molecule nitric oxide (NO) is also a potential candidate for prevention of biomedical infections due to its antibiofilm activity.In this study, DHPs and brominated FUs were immobilized on surfaces via a non-specific nitrene-insertion method. The successful covalent attachment of compounds was confirmed by X-ray photoelectron spectroscopy. The coated surfaces showed excellent in vitro activity against Staphylococcus aureus and Pseudomonas aeruginosa. Interestingly, DHP surfaces at low concentrations (0.17–0.35 % halogen) were found to display similar levels of activity as FUs with higher surface attachment (0.41–0.74 % Br), which was possibly due to change in orientation of DHP during attachment.The influence of DHP orientation and absence of an exocyclic double bond on the biological activity was then examined by specific covalent attachment using EDC/NHS coupling. The orientation of DHP with free lactam ring exposed to bacterial medium showed higher activity compared to DHPs attached from the nitrogen of the lactam ring. In addition, DHPs lacking the exocyclic double bond were also able to reduce bacterial adhesion without killing both strains of bacteria, indicating DHPs retained their activity even in absence of the exocyclic bond.This project also focused on developing dual-action surfaces and polymers that were functionalized by DHPs via Michael-addition reaction and diazeniumdiolates (

The project investigated two aspects of novel structures containing indoles, benzimidazoles, and benzothiazoles. One focus was the synthesis of compounds with improved antimicrobial properties. The other focus was on the synthesis of new biheterocyclic structures and their potential conversion into novel porphyrin-like macrocycles.Novel indole-based inhibitors of bacterial RNA holoenzyme formation were investigated. The Knoevenagel condensation was found to be a convenient method for the synthesis of novel inhibitors which incorporate 2-phenyl benzimidazole, 2-phenylbenzothiazole, or 4,6-dimethoxyindole-2-carboxylate scaffolds with rhodanine analogues. The synthesised compounds have been tested for their ability to inhibit RNA polymerase – σA interactions using an enzyme-linked immunosorbent assay. Furthermore, antibacterial activities against Escherichia coli and Bacillus subtilis were also investigated. The structure-activity relationship studies of synthesised compounds revealed that biological activities were affected by the C2 modifications of the indole. The 2-thiobarbituric acid moiety was found to be necessary for the antibacterial activity and several of these novel inhibitors showed significant antibacterial activities against Bacillus subtilis at micromolar concentration. One indole-2-carboxylate -2-thiobarbituric acid hybrid was recognized as a lead compound for further investigation.IVFour different 2,7’-indolylheteroaromatic systems were investigated, including 2,7’-indolylbenzimidazole, 2,7’-indolylbenzothiazole, 2,7’-indolylbenzoxazole and 2,7’-indolylbenzofuran. Specially activated examples of 2,7’-indolylbenzimidazoles and 2,7’-indolylbenzofurans were prepared from 4,6-dimethoxyindoles, and their reactivity was investigated. The 2,7’-indolylbenzimidazoles were shown to form 2:1 complexes with zinc, copper, and nickel. The ML2 structures were confirmed by NMR and high resolution mass spectrometry data.Numerous attempts were made to convert the bihet

New technologies are rapidly changing our concepts of space and time. Through the theoretical framework of Canadian scholar Harold Innis’ “bias of communication,” this study uses content analysis to investigate how current distance education literature (as represented by five peer-reviewed journals over 15 years of publication) reflects evidence of a space-bias in distance education technology. An understanding of Innis’ notion of time and space can inform distance education practice by proposing the use of more synchronicity and orality in the design of distance education learning materials., 2017 - June

Solving the atomic structure of metallic clusters is fundamental to understanding their optical, electronic, and chemical properties. Herein we present the structure of the largest aqueous gold cluster, Au146(p-MBA)57 (p-MBA: para-mercaptobenzoic acid), solved by electron micro-diffraction (MicroED) to subatomic resolution (0.85 Å) and by X-ray diffraction at atomic resolution (1.3 Å). The 146 gold atoms may be decomposed into two constituent sets consisting of 119 core and 27 peripheral atoms. The core atoms are organized in a twinned FCC structure, whereas the surface gold atoms follow a C2 rotational symmetry about an axis bisecting the twinning plane. The protective layer of 57 p-MBAs fully encloses the cluster and comprises bridging, monomeric, and dimeric staple motifs. Au146(p-MBA)57 is the largest cluster observed exhibiting a bulk-like FCC structure as well as the smallest gold particle exhibiting a stacking fault.

There was much controversy in Western Australian politics during the period in which the world was shaken by the 11 September terrorist attacks in the United States. Major electoral law changes, together with legislation intended to remove discrimination against the gay and lesbian community, provoked much public controversy and long and bitter parliamentary debates. The Gallop Labor government, which began the period under review with a minor Cabinet reshuffle, also delivered its first budget. As former National Party leader Hendy Cowan had resigned his Merredin in seat in a quest for a Senate berth in the 10 November federal election, this necessitated a keenly fought by-election with the National Party requiring victory to retain its status as an official party.

Paul D Williams, Commonwealth of Australia David Clune, New South Wales Nick Economou, Victoria John Wanna, Queensland David Black and Harry C.J. Phillips, Western Australia Haydon Manning, South Australia Richard Herr, Tasmania David Carment, Northern Territory Gwyneth Singleton, Australian Capital Territory

Experimental and theoretical evidence reveals the resilience and stability of the larger aqueous gold clusters protected with p-mercaptobenzoic acid ligands (pMBA) of composition Aun(pMBA)p or (n, p). The Au144(pMBA)60, (144, 60), or gold-144 aqueous gold cluster is considered special because of its high symmetry, abundance, and icosahedral structure as well as its many potential uses in material and biological sciences. Yet, to this date, direct confirmation of its precise composition and total structure remains elusive. Results presented here from characterization via high-resolution electrospray ionization mass spectrometry on an Orbitrap instrument confirm Au102(pMBA)44 at isotopic resolution. Further, what usually appears as a single band for (144, 60) in electrophoresis (PAGE) is shown to also contain the (130, 50), recently determined to have a truncated-decahedral structure, and a (137, 56) component in addition to the dominant (144, 60) compound of chiral-icosahedral structure. This finding is significant in that it reveals the existence of structures never before observed in all-aromatic water-soluble species while pointing out the path toward elucidation of the thermodynamic control of protected gold nanocrystal formation.

Western Australian politics returned to its traditional mode when Coalition Premier Richard Court reverted to the early February time slot for the State election rather than opting for a pre-Christmas poll as was the case in 1996. He did break new ground, however, by announcing the election in the regional city of Bunbury where the neighbouring marginal seats of Bunbury and Mitchell were two of the eleven seats the Australian Labor Party (ALP) needed to win to gain a majority in its own right in the 57 member Legislative Assembly. Gains of such a magnitude had not been achieved by an Opposition in Western Australia since Labor's first big victory in 1911. After an election-free year in Australia in 2000, the Western Australian election was also to hold more than usual interest as the first "cab off the rank" in the aftermath of the CST and the petrol pricing controversies.

During the second half of 2000 there was much speculation as to the likely date of the next election. Eventually Premier Court ruled out a pre-Christmas poll after the so-called Finance Brokers' Scandal continued to draw adverse publicity. Difficulties in the major portfolio areas of health, education and transport also bedevilled the government while several ministers came under fire for actions that were alleged to have breached expected standards of ministerial conduct.

The undertaken research has been realized in two fundamental areas: indoles as novel antibacterial agents and versatile precursors of complex heterocyclic structures. Several classes of structurally related hydrazine-linked bis-indoles were synthesized and evaluated towards inhibition of bacterial transcription initiation complex formation. The compounds were found to efficiently inhibit the β'-σ70/σA interaction essential for RNA polymerase holoenzyme formation as well as the growth of both Gram-positive and Gram-negative bacteria. Structure-activity relationship (SAR) studies were carried out in order to identify the structural features of the synthesized inhibitors potentially required for biological activity. Structurally related scaffolds were explored as well. Synthesis and evaluation of antibacterial activity of a variety of mono-indole-, mono-benzofuran-, bis-indolylmethane- and tetra-indole-based carbox- and glyoxyloylamides, and carbo- and glyoxyloylhydrazides demonstrated that significant reduction in molecule size resulted in not only solubility enhancement, but also in retention of biological activity both at the level of inhibition of the β′-σ70/σA interaction and bacterial growth in culture. Chemistry of 2,7'-bi-indolyls has been developed in two main directions. Functionalization of the position 7 of the 2,7'-bi-indolyl scaffold resulted in the synthesis of carbohydrazides and glyoxyloylamides. Vilsmeier-Haack-type reactions taking place at position 7 were investigated as well. Stability of 2,7'-bi-indolyls in the presence of strong bases was explored and the unusual ring opening reaction observed. Efficient and regioselective procedures for bromination of 2,7'-bi-indolyls and quinazolin-7-ones using bromine and N-bromosuccinimide were developed to afford a wide range of novel mono-, di-, tri- and tetrabrominated derivatives. New method for the synthesis of macrocyclic tetra-indolyls via acid-catalyzed coupling of the 2'-bromo-2,7'-bi-indolyl was rep

The work presented in this thesis aims to highlight the versatile reactions of N-acylisatins as precursors for the synthesis of novel peptide mimics and heterocycles. N-arylisatins were prepared via Chan-Lam coupling of various electron-deficient arylboronic acids with isatin. Attempts to ring-open these N-arylisatins with primary alcohols were unsuccessful. However, when subjected to tert-butylamine in refluxing conditions, the corresponding N-glyoxylacid salts were obtained along with the N-glyoxylamides as minor products. A novel series of first generation amphiphilic peptide mimics were prepared from the ring-opening reactions of hydrophobic N-acylisatins by various amines. Further modification allowed for the introduction of cationic moieties such as those mimicking positively charged amino acids as well as tertiary ammonium groups. An extension of this chemistry was used to prepare a series of second generation peptide mimics from terephthaloyl chloride. By altering the core structure of these compounds the balance of charge and hydrophobicity could be controlled.The N-acylisatin ring-opening strategy was applied to the synthesis of benzene-1,3,5-tricarboxamides (BTA) allowing access to both novel BTA-N-glyoxylesters and amides with peripheral alkyl chains. Furthermore BTA-N-glyoxylamides with peripheral amino acid esters were prepared in a similar fashion demonstrating the ease with which BTAs can be functionalized using this strategy.Various N-protected amino acids were coupled to isatin forming N-amino acyl isatins. These novel N-acylisatins participate in ring-opening reaction with either alcohols or amines to give the corresponding N-glyoxylesters or amides. Upon deprotection these precursors cyclize to form1,4-benzodiazepin-2-ones bearing C5 pendant amide or ester groups. This is a novel synthetic strategy that provides access to these biologically relevant molecules from cheap and readily accessible starting materials.A number of strategies were investi

Infrared (IR) excesses around K-type red giants (RGs) have previously been discovered using IRAS data, and past studies have suggested a link between RGs with overabundant Li and IR excesses, implying the ejection of circumstellar shells or disks. We revisit the question of IR excesses around RGs using higher spatial resolution IR data, primarily from WISE. Our goal was to elucidate the link between three unusual RG properties: fast rotation, enriched Li, and IR excess. We have 316 targets thought to be K giants, about 40% of which we take to be Li-rich. In 24 cases with previous detections of IR excess at low spatial resolution, we believe that source confusion is playing a role, in that either (a) the source that is bright in the optical is not responsible for the IR flux, or (b) there is more than one source responsible for the IR flux as measured in IRAS. We looked for IR excesses in the remaining sources, identifying 28 that have significant IR excesses by ~20 um (with possible excesses for 2 additional sources). There appears to be an intriguing correlation in that the largest IR excesses are all in Li-rich K giants, though very few Li-rich K giants have IR excesses (large or small). These largest IR excesses also tend to be found in the fastest rotators. There is no correlation of IR excess with the carbon isotopic ratio, 12C/13C. IR excesses by 20 um, though relatively rare, are at least twice as common among our sample of Li-rich K giants. If dust shell production is a common by-product of Li enrichment mechanisms, these observations suggest that the IR excess stage is very short-lived, which is supported by theoretical calculations. Conversely, the Li-enrichment mechanism may only occasionally produce dust, and an additional parameter (e.g., rotation) may control whether or not a shell is ejected., Comment: 73 pages, 21 figures (some of which substantially degraded to meet arXiv file size requirements), accepted to AJ. Full table 1 (and full-res figures) available upon request to the author

This thesis describes a detailed examination of parameters that control formation of substituted benzalhydantoins in a multistep process from aldehydes and 3-un/substituted hydantoins following modifications of the Wheeler and Hoffman process. The purpose of the study was to develop optimal reaction conditions for a planned, automated parallel synthesis of indoles, with the benzalhydantoins as intermediates. An initial comparative study, based on preparative yields, of the synthesis of benzalhydantoins from the condensation of substituted aldehydes and unsubstituted and 3-substituted hydantoins under the established Wheeler and Hoffman procedure was found imprecise. Consequently, an LC-MS analytical method was developed for reaction monitoring. Investigation of the roles of temperature, reaction time, and aldehyde and hydantoin substituents showed dependence on the latter two features and revealed formation of benzylhydantoin alcohols. The process of 3-allylation of benzalhydantoins was investigated as a model for the final step in an alternative preparation of 3-alkylbenzalhydantoins. Overall, an excess of reagent allyl chloride played an important role in optimizing yields, however yields were limited. A microwave-irradiation method gave more rapid conversions and allowed better comparison of reaction rates. A parallel investigation of the scope of tandem allylation-condensation reactions, which indicated that the alkylation of hydantoin and the condensation of aldehydes with hydantoin occurred simultaneously, was described. 3-Unsubstituted benzalhydantoins were obtained as major products, even after prolonged reaction times, suggesting that condensation of aldehydes with 3-substituted hydantoins was slower than with hydantoin itself. A systematic study of the effect of microwave acceleration on the initial condensation was described, and the revealed benzylhydantoin alcohols were found as major products, rather than benzalhydantoins. The alcohols were studied in

Retinoids play a crucial role in the treatment of multiple human cancers, particularly neuroblastoma and leukaemia. However, their utility is often hampered by the inherent toxicities associated with the concentrations necessary for therapeutic benefit, as well as innate or acquired resistance to treatment. This thesis focuses on the discovery and development of novel scaffolds that possess cytotoxic activity mediated through the retinoid pathways.A protocol for docking scaffolds into the binding site of the retinoic acid receptor β (RARβ) was developed. These docking methodologies were used to identify novel scaffolds as potential RARβ ligands, as well as probe the mechanisms behind the observed structure activity relationships (SAR) of the prepared compounds.A wide range of novel indole-benzothiazole acetamides were synthesized via PyBOP amide coupling of 3-indoleacetic acids and 2-aminobenzothiazoles. These scaffolds were investigated for their cytotoxic activity against neuroblastoma cells. Several analogues were found to have low micromolar IC50 values, demonstrated selectivity towards cells with high RARβ expression and also were selective for cancerous cells over normal cells. Furthermore, the ability of these compounds to modulate RAR protein expression was demonstrated.Indole and quinoline-oxadiazoles were synthesized by the dehydrocyclization of bis-hydrazides by 4-toluenesulfonyl chloride. The cytotoxic activity of these scaffolds was investigated with their selectivity towards cells overexpressing different RAR subtypes (α, β, γ) also investigated.Benzothiazole-thieno[2,3-c]pyrazole amides were also synthesized by the one-pot, single step alkylation-aldol condensation of methyl thioglycolate and formyl-halopyrazoles. The cytotoxicity and SAR of these scaffolds was also explored.

Approximately half of the world's population lives in the tropics, and future changes in the hydrological cycle will impact not just the freshwater supplies but also energy production in areas dependent upon hydroelectric power. It is vital that we understand the mechanisms/processes that affect tropical precipitation and the eventual surface hydrological response to better assess projected future regional precipitation trends and variability. Paleo-climate proxies are well suited for this purpose as they provide long time series that pre-date and complement the present, often short instrumental observations. Here we present paleo-precipitation data from a speleothem located in Mesoamerica that reveal large multi-decadal declines in regional precipitation, whose onset coincides with clusters of large volcanic eruptions during the nineteenth and twentieth centuries. This reconstruction provides new independent evidence of long-lasting volcanic effects on climate and elucidates key aspects of the causal chain of physical processes determining the tropical climate response to global radiative forcing.

Summary: The purpose of this dissertation was to add to the literature on the school choice debate and educational voucher programs through an analysis of Florida’s John M. McKay Scholarship Program for Students with Disabilities. This dissertation looked at the major aspects of school choice theory, parental satisfaction, and reasoning for choice. A theoretical framework for analyzing school choice programs was put forth in this dissertation through an analysis of the over-arching dynamical elements that have shaped the administrative and political arguments for and against these programs. A comprehensive review of the literature on school choice comprised a substantial part of this study due to the need for citizens to better comprehend the origins and evolution of school choice planning and programming., 2015, Includes bibliography., Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2015, Collection: FAU Electronic Theses and Dissertations Collection