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Stimulating Mindfulness-To-Meaning: Noninvasive Brain Stimulation Targeting the Upward Spiral of Mindful Positive Emotion Regulation
Get PDFObjectives: Worry is highly prevalent and associated with internalizing disorders, such as generalized anxiety disorder. Foremost treatments for worry include mindfulness-based interventions. Paradoxically, engagement in mindfulness practices may be especially difficult for individuals with negative repetitive thinking habits, like worry. Mindfulness training may be improved for chronic worriers by stimulating neural areas associated with a mindful state, such as the left dorsolateral prefrontal cortex (L-DLPFC). Beyond its association with mindful states, L-DLPFC activation is associated with the underlying cognitive processes of a leading theory explaining how mindfulness produces psychological benefits: mindfulness-to-meaning theory. Cognitive processes improved by mindfulness and associated with L-DLPFC activation include inhibition of automatic responses (inhibitory control) and reinterpretation of stressors in a positive light (positive reappraisal). Inhibitory control and positive reappraisal are particular areas of difficulty for chronic worriers. Improvements in these areas may facilitate chronic worriers' ability to disengage from worry and instead derive meaning from stressors, which can contribute to improved psychological functioning. Therefore, transcranial direct current stimulation (tDCS) targeting the L-DLPFC was hypothesized improve engagement in mindfulness practices, mindfulness-to-meaning processes (e.g., decentering), and psychological functioning (e.g., decreased generalized anxiety) in chronic worriers. Methods: Adult novice meditators ( N = 64) with clinically elevated worry were randomized to one of four groups using a 2 (mindfulness vs mind-wandering) x 2 (active vs sham tDCS) design. At an initial lab visit, participants listened to instructional recordings during stimulation, then completed three remote follow-ups over the course of one week. Follow-ups included additional shorter mindfulness and mind-wandering practices without stimulation. Results: No changes in decentering, inhibitory control, or positive reappraisal were observed. However, among participants who received mindfulness, active stimulation enhanced engagement, reductions in generalized anxiety, and increases in trait mindfulness. Additionally, although no potentiating effect was observed, mindfulness and active tDCS separately contributed to reducing catastrophizing tendencies. Contrary to hypotheses, however, mind-wandering also produced beneficial outcomes, including increases in trait mindfulness. Conclusions: Importantly, the current findings suggest that supplementing the first mindfulness session with L-DLPFC stimulation (vs sham) improved engagement and reduced generalized anxiety symptoms during a brief mindfulness intervention. Unexpectedly, mind wandering increased trait mindfulness. Therefore, rather than functioning as an inactive control condition as intended, deliberate mind wandering may instead imitate aspects of mindfulness interventions, particularly among chronic worriers. No improvements were observed in decentering, inhibitory control, and positive reappraisal, which are central mindfulness-to-meaning processes. However, reductions in generalized anxiety and catastrophizing are promising outcomes for chronic worriers. Future studies should explore whether increased dosage and/or extended follow-ups beyond the first week of practice may demonstrate improvements in the cognitive processes which are central to mindfulness-to-meaning theory
Leveraging the Reactivity of Photogenerated Quinone Methides From 2H-Chromenes for Target-Directed Synthesis: The Total Synthesis of Piperaduncin A and Alfileramine
No full textIn a recent study conducted by the Hitchcock Center of Chemical Ecology focused on analyzing phytochemical diversity of plant species within a specific area of Ecuador, a new 2 H -chromene, its prenylated benzoic acid precursor, and its dimer were found within methanolic extracts of the leaves of Piper kelleyi . Due to the structural similarities of the three compounds, it was apparent that a clear biosynthetic relationship was present between them, and research began on 2 H -chromenes and their synthetic relationship to complex natural products in cases where they are found concurrently. 2 H- chromene compounds represent a natural molecular motif found throughout many different families of plants that has been studied for many years due to their unique photoreactivity. Upon exposure to UV light, chromenes can ring open into the o-quinone methide and its tautomer, resulting in multiple different alkenes and exhibiting a diverse display of reactivity, thus allowing the chromene to act as a manifold in the biosynthesis of a diverse array of complex natural products. One of the most pivotal reactive pathways occurring in nature and stemming from chromene precursors involves Diels Alder type cycloadditions resulting from the generation of multiple alkene intermediates throughout the ring-opening pathway. It was through this mechanism that the existence of chromene dimers in nature were understood to exist, as demonstrated by Jeffrey group collaborators in the total synthesis of dimer 15 isolated from Piper kelleyi and marked by scheme 1.6. Additionally, however, there was found to be HRMS evidence that indicated the existence of another chromene dimer within the original isolate that was unfortunately never fully purified. This compound had remained a mystery and has since been synthetically targeted as a possible chromene dimer made in nature, given the possibility of cycloaddition occurring at different reaction sites about the o-quinone methide intermediates. Despite this apparent possibility, none of the dimers of other isomeric forms were ever successfully synthesized with the method utilized by Jeffrey group collaborators, and largely remained a missing piece of the chromene studies. The presence of these isomeric possibilities has been further evidenced by the findings of different kinds of chromene dimers in nature of different stereochemical makeup, found across several different families of plants and representing at least 4 different isomeric forms resulting from (seemingly) Diels Alder type cycloadditions. Of these cases, the Zanthoxylum alkaloid family discovered by Stermitz et al. will be discussed in detail later on. This thesis will present several different syntheses of 2 H -chromenes of varying functionality that would later be used to study the unique reactivity of the o-quinone methide. These model chromenes were then utilized in two major reactive pathways, that of the electrophilic aromatic substitution pathway that would lead to the total synthesis of piperaduncin A, as well as the novel [4+1] dimerization pathway that would lead to the total synthesis of alfileramine. The EAS pathway has been previously established, and involves the trapping of the o-quinone methide by substitution onto a reactive aryl group. The [4+1] pathway represents a new discovery that could uncover the methodology describing how certain chromene dimers are made in nature, featuring the usage of an oxidation catalyst that can generate radical cations upon reactive alkene species to generate highly reactive dienophiles in situ. Through this method, otherwise unfavored Diels Alder type cycloadditions can become thermodynamically favored, thus rapidly producing dimerization products that were previously a synthetic mystery. The specific class of dimers resulting from this pathway can be used to access alfileramine, one of the isomeric forms first discovered by Stermitz et al. Furthermore, the stereochemical findings and subsequent mechanistic analysis performed for this reactive pathway provide evidence for a non-Diels Alder type mechanism that leads to the natural dimers. While this finding is not yet fully understood and is still under investigation, these pieces of evidence will provide further insight into 2 H -chromene reactivity and perhaps unlock one of the biosynthetic blueprints that would lead to this specific class of chromene dimers found in nature
A Pilot Study: Self-Reported Anxiety and Depression in Regular Exercisers
No full textBackground: Current physical activity guidelines emphasize physical health outcomes and lack any mention of mental health outcomes. Physical activity guidelines need to be updated to reflect current research and include mental health outcomes. Unfortunately, the literature lacks discussion on the liminal period between the end of a physical activity intervention and the long-term follow up. Additionally, while low intensity (LI) physical activity and high intensity interval training are main topics of discussion in the literature, there is a lack of research on high intensity (HI) physical activity and its effect on mental health outcomes. Purpose: To examine the efficacy of HI physical activity as a management tool for self-reported anxiety and depression in college age students who engage in regular physical activity. Methods: A total of 27 participants (20 female, 7 male; mean age 20.59 ± 2.19; mean height 65.98 ± 3.65 inches; mean weight 143.44 ± 31.17 pounds) elected to partake in either LI or HI physical activity classes and completed 16 weeks of regular physical activity. The HI group consisted of 17 participants and the LI group consisted of 10 participants. Anxiety and depression scores were observed in the last 4 weeks of class using the PHQ-ADS questionnaire. A 2x4 factorial ANOVA was used to conduct within and between group comparisons. Results: Anxiety and depression levels remained consistent in the LI and HI groups across four weeks of observation. Conclusion: LI and HI physical activity can be considered effective at managing self-reported anxiety and depression in college-age students who engage in regular physical activity
A New Hybrid Model based on Non-Gaussian Autoregressive Process and Neural Network Model for Financial Market Prediction
Get PDFIn financial modeling, the assumption of Gaussian noise, has been a classical assumption. Models based on this assumption have been widely used in various fields due to their interpretability, e.g, Autoregression (AR), Moving Agerage models, (MA), Autoregressive Integrated Moving Average (ARIMA), etc. However, the Gaussian assumption is often violated in practice. Consequently, the use of time series models with non-Gaussian distributions, machine learning, and hybrid approaches has increased as alternatives. In order to improve the predictive accuracy of time series models, different approaches have been applied such as Autoregressive models assuming non-Gaussian innovations and hybrid models with traditional time series models and modern non-linear technique. Most of the hybrid models in the literature combine a classic ARIMA model and a machine learning method. This study aims to bridge non-Gaussian models and machine learning methods. Specifically, we proposes a hybrid combination model based on the Autoregressive process with Laplace innovations and neural network. Traditional autoregressive models have strong interpretability and simple architecture. The main strength of neural network is their wide range of uses and their flexibility. By combining their relative advantages, we can capture unpredictable behaviors of the data. Furthermore, since we use a Laplace distribution error as an alternative to the classic autoregressive model with Gaussian innovations, this makes the model more robust in the presence of outliers. In the first stage, AR model fitted, and linear predictions and residuals obtained. Next, perform NN on the residuals. Then, calculate the predicted residuals. The final predicted values are obtained by the summation of linear predictions and non-linearly predicted values. We also evaluate the performance in terms of RMSE and MAE of single models and hybrid models for comparison purposes. Our simulation generates synthetic data from three different classic non-linear time series models. The empirical application to the real datasets (Leading economic indicators), the results exhibit the proposed hybrid model shows better accuracy of forecasting compared to the other benchmark models. Although further investigation is still needed, the results demonstrate that a hybrid model incorporating a non-Gaussian component can serve as a practical tool for financial time series modeling. We also conduct a comprehensive analysis of the bond market to gain preliminary insights and explore the behavior of residuals taken from autoregressive models with leading economic indicators
"It's My Life": Music, Baseball, and Identity
Get PDFThis thesis investigates the relationship between music and baseball, focusing on how music serves as an indicator of personal, cultural, and/or racial identity. Baseball and music are joined together, and music's role has always been more than entertainment. For players and teams, it's become an outlet for expression of identity. I analyze music's usage throughout the gameday experience, demonstrating that by utilizing certain genres or artists, players and teams display cultural and racial identities. I analyze music's usage as a way players connect with their fandom. By selecting popular music, organizations create a sense of personal connection with fans, expanding their following. Using music aids in branding for players and teams. My analysis also shows, through music selection, music's use in baseball creates an inclusive space for players and fans. Music showcases diversity within the sport and shapes the perception of the game both on and off the field
EXPLORING TWISTED STRING ACTUATION FOR APPLICATION IN SOFT ROBOTICS
Get PDFTo make robots more ubiquitous, robotic structures that are compliant, lightweight, and low-cost are desired. Soft robots, which are fabricated using compliant materials and soft actuators, are ideal for such applications. However, producing high-performance soft robots is challenging due to the lack of systematic procedures and inherent limitations of the actuators which drive them. Despite many advances in the field of soft actuators and artificial muscles, the quest for an ideal soft actuator which exhibits sufficient contraction and force generation, while being compact is still an ongoing effort. In an attempt to explore novel actuation techniques for soft robotics, in this dissertation, the employment of twisted string actuation for soft robotic applications is investigated and potential limitations which arise as a consequence are addressed. Due to their tendon-based (muscle-like) linear actuation, high force generation, and high operational bandwidth, twisted string actuators (TSAs) are highly suitable to actuate soft robotic devices with advantages over other soft actuators. TSAs typically generate strains of 30--40% of their untwisted length, exhibit energy efficiency of 75--80%, and can exert more stress than skeletal muscles. Although TSAs have been widely adopted in multiple robotic applications, their inclusion in soft robots has been limited.In this dissertation, the application of TSAs in soft robotic manipulation is explored, in that a soft robotic manipulator is presented. The design of the robot is discussed. A physics-based model is developed to predict the manipulator's kinematic motion. An inverse model is derived to realize open-loop control. The proposed modeling and control approaches were experimentally verified to be effective. While the proposed soft robot exhibited promising performance, there were a few notable limitations due to the soft material and actuation mechanism: Firstly, the usage of soft material resulted in the nonlinear behavior called hysteresis. In addition, termed as lonely stroke, the first input-output cycle of the soft robots was inconsistent with subsequent cycles that were repeatable and exhibited hysteresis. The lonely stroke not only affected the behavior of the hysteretic system, but also presented coupling with the subsequent repeatable hysteresis cycles. As a part of this dissertation, a model to capture and compensate for the hysteresis with lonely stroke property is proposed. A modeling approach is developed through the expansion of the input range of the Preisach operator, a widely adopted hysteresis model, to physically infeasible region. The effectiveness of the proposed scheme was validated by simulation and experimental results.Secondly, most existing studies on control of TSAs assume that the external force applied to the TSA is measurable or predictable. Furthermore, existing studies also assume that all the TSA parameters such as the motor properties and string stiffnesses are accurately known. However, the system parameters could be difficult to measure, could change over time due to general wear and tear, and creep. The external forces applied to the TSA could be difficult to predict or measure. To address these issues, parameter estimation and control strategies were developed for TSAs, assuming {little or} no knowledge about the system parameters. A parameter estimation strategy which utilized the least squares algorithm and gradient algorithm is presented. An adaptive control strategy based on model reference control with feedback linearization is proposed. The developed estimation and control strategies were tested to be effective through simulation.Lastly, the limited strain exhibited by TSAs adversely affected the design and performance of the soft robot. Therefore, it is strongly desirable but challenging to enhance the TSAs' consistent strain generation while maintaining compliance. Existing studies predominantly considered coiling after the regular twisting stage to be undesirable�"non-uniform and unpredictable knots, entanglements, and coils formed to create an unstable and failure-prone structure. Coiling would work well for TSAs when uniform coils can be consistently formed. As a part of this dissertation, we realize uniform and consistent coil formation in coiled TSAs, which greatly increases their strain. Furthermore, we investigate methods for enabling uniform coil formation upon coiling the strings in a TSA and present a procedure to systematically “train” the strings. Coiling resulted in approximately 70% strain in stiff TSAs and approximately 60% strain in compliant TSAs. TSAs capable of operating in the coiling phase were termed as twisted and coiled string (TCS) actuators.To further establish the coiling mechanism as a reliable actuation mode for TCS actuators, the behavior of the TCS actuators in the coiling phase was experimentally characterized. The non-smooth behavior was investigated by using sequences of input motor turns with different frequencies. The hysteretic behavior and the properties of transitioning conditions were examined by applying input cycles with different bandwidths and under multiple loading conditions. Secondly, a physics-based kinematic modeling strategy which utilized the geometry of the coiled strings were developed to capture the behavior of the coiling-induced non-smooth behavior of the TCS actuators. Lastly, the kinematic model was inverted to realize open-loop control of TCS muscles through inverse compensation. The proposed modeling and control strategies were experimentally validated to be efficient
Multi-Tiered Systems of Support in Medical Education
Get PDFMedical school is challenging for all with some of the most intelligent individuals in the world who have hopes of being healers. For medical students with disabilities this path can be extra challenging. This exploratory qualitative case study looked at a piloted student support model modeled from the K-12 Multi-Tiered Systems of Support (MTSS) by reviewing the experiences of 10 medical students who described their experiences with the support model. These students are also students with disabilities. Overall, the students indicated that having a designated support person to support them during medical school was beneficial in their path throughout their four-year program. Other themes identified included stigma, difficulty with required testing, and lack of understanding of the support model
Post-synthetic Modification of Nanographenes using C-H Activation and Alkyne Benzannulation
No full text“Bottom-up” (BU) synthetic strategies have now given chemists the tools to further modify large polycyclic aromatic hydrocarbon (PAH) molecules in a relatively straightforward man-ner. A powerful BU technique is alkyne benzannulation as it allows for the reliable prepara-tion of pyrenacene (pyrene, peropyrene, teropyrene, etc.) molecules in high yield. Coupling this strategy with the postsynthetic modification of nanographene’s (NG) is a relatively new area of interest in the world of materials chemistry. Edge functionalization is the most pre-dominant method regarding postsynthetic modification as it allows the change of shape, electronics, and chirality of the NG to occur. In this work, we have developed new methods to successfully elongate the size of pyrenacene NGs with the use of iridium catalyzed C-H bond activation to make dissymmetric chiral peropyrenes, and the longest atomically precise oligomeric graphene nanoribbon (GNR) fragment. Additionally, the C-H activation of a complex pyrene molecule allowed us to prepare two dissymmetrical chiral peropyrenes that were separated by high-performance liquid chromatography (HPLC) and were both studied for their photophysical and electrochemical properties. Lastly, we were able to successfully brominate the starkly unresearched teropyrene in excellent yields using extant electrophilic aromatic substation (EAS) techniques that required no further purification upon completion. This tetra-brominated species was then further functionalized via Stille C-C coupling reac-tions resulting in the preparation of backbone functionalized teropyrene derivatives that led to near red-light absorbing NGs. Additionally, a single crystal was grown to unambiguously prove structure of one of the teropyrene derivatives
miR-10b-5p Rescues Type 1 Diabetes in Mice, Rats, and Dogs
Get PDFType 1 diabetes (T1D) is characterized by insulin deficiency and hyperglycemia via destruction of insulin-producing pancreatic β cells. Degeneration of pancreatic β cells arises from diverse elements like autoimmune systems, genetic problems, and infection of viruses. Therefore, the molecular mechanism of T1D onset remains poorly understood. Our previous study showed that anti-diabetic miRNAs, miR-10b-5p is a key factor of growth and survival of pancreatic β cells via targeting KLF11. The reduction of miR-10b-5p induced diabetes with the dysfunction of pancreatic β cells, but restoration of miR-10b-5p rescued diabetes with regeneration of pancreatic β cells. In the present study, we found that a global mir-10b knock-out (KO) mouse model had decreased insulin level with developing diabetes. Also, we found that miR-10b-5p was substantially reduced in pancreatic islet cells or pancreatic islet as well as blood in both the autoimmune non-obese T1D (NOD) mice and streptozotocin (STZ)-induced T1D mice with insulin deficiency and hyperglycemia. Surprisingly, we also identified that miR-10b-5p is prominently down-regulated in peripheral blood mononuclear cells (PBMC) and serum from T1D patients. Additionally, STZ-alloxan (ALX)-induced or spontaneously developing diabetic dogs had remarkedly an decrease in insulin levels with the reduction of miR-10b-5p. Furthermore, restoration of miR-10b-5p led to decreased blood glucose and increased insulin levels to healthy conditions in NOD and STZ-induced mice with recovery of degenerated pancreatic islets. Injection of the miR-10b-5p mimic rescued hyperglycemia with STZ-induced T1D rats as well as mice. STZ-ALX-induced or spontaneously developing diabetic dogs had a marked decrease in insulin expression with the reduction of miR-10b-5p. Taken together, the reduced miR-10b-5p leads to insulin-dependent diabetes. Moreover, the deficiency of insulin induced the reduction of miR-10b-5 inversely. Our previous study showed that Krüppel-like factor 11 (KLF11) was up-regulated in KIT+ cell specific-mir-10b KO mice. In addition, miR-10b-5p mimic reduced KLF11 expression in pancreatic β cells and showed the targeting effects of miR-10b-5p on KLF11 by regulating insulin expression directly. KLF11 is known as a major factor in promoting apoptosis and inhibiting cell growth. It also regulated the activity of insulin by binding its promoter in β cells. Finally, we also identified that miR-10b-5p is significantly down-regulated in peripheral blood mononuclear cells (PBMC) and serum from T1D patients. In summary, we uncovered that the lack of miR-10b-5p triggered T1D via the KLF11 pathway in pancreatic β cells. Moreover, restoration of miR-10b-5p reversed T1D phenotypes like hyperglycemia and insulin deficiency in T1D mice, rats, and dogs. Here, we report a new therapeutic nomination for T1D with novel insight into the destruction of pancreatic β cells by figuring out the role of miR-10b-5p in T1D
