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An online survey was conducted in the USA to obtain information about the knowledge and experiences of patients with painful diabetic peripheral neuropathy (pDPN). 506 adults with diabetes and pDPN affecting the feet for ≥6 months, for which pain medication had been prescribed for ≥6 months, completed an online survey questionnaire in March 2021. 79% of respondents had type 2 diabetes, 60% were male, 82% were Caucasian and 87% had comorbidities. Pain was significant to severe in 49% of respondents, and 66% had disability due to nerve pain. Anticonvulsants, over-the-counter pills and supplements were the most commonly used medications. Topical creams/patches were prescribed in 23% of respondents. 70% had tried multiple medications for their pain. 61% of respondents had to see ≥2 doctors before receiving a correct diagnosis of pDPN. 85% of respondents felt that the doctor understood their pain and its impact on their life. 70% had no difficulty finding the information they wanted. 34% felt insufficiently informed about their condition. A medical professional was the primary, and most trusted, source of information. Frustration, worry, anxiety and uncertainty were the most commonly reported emotions. Respondents were generally eager to find new medications for pain relief and desperate for a cure. Lifestyle changes because of nerve pain were most commonly associated with physical disabilities and sleep disturbance. Better treatments and freedom from pain were the overriding perspectives when considering the future. Patients with pDPN are generally well informed about their pain and trust their doctor but remain unsatisfied with their current treatment and struggle to find a lasting solution for their pain. Early identification and diagnosis of pain in diabetics, and education about treatments, is important to minimize the impact of pain on quality of life and emotional well-being.

Wine survey analysis has been utilized in previous research to assess a myriad of applications in the wine industry. These surveys typically evaluate the consumer bases within the wine industry and examine their perceptions, tendencies, and habits. This research aims to further supplement data in this context and surveyed consumers from across the world from a wide range of consumer types. By utilizing market segmentation, this vast consumer base can be separated into smaller groups which are more telling of how various segments differ from each other. This study evaluated consumer perceptions of red and white wine, wine closure type, wine label information, and wine serving temperature. Furthermore, an examination of how consumers treated their wine allowed us to identify differences in refrigeration preference, temperatures commonly used to store wine, how quickly the wine is consumed after opening, and how frequently the consumer drank wine. Chi-square analysis demonstrated numerous significant results across multiple segments. Firstly, the question of knowledge appeared to be one of the most enlightening questions, as this seemed to connect with underlying motivations for consumer’s habits and perceptions. Those that were more knowledgeable tended to be slightly older, more frequent consumers, were more interested in wine information, and more likely to own niche wine products such as wine refrigerators and wine preservation devices. Those that were not as knowledgeable about wine were the opposite, where they were less frequent consumers, less interested in wine information, and less likely to own niche wine products like wine refrigerators and wine preservation devices. Regionally there were not many differences observed. Most regions that were evaluated were fairly consistent with each other. However, some regions like South Africa and the U.S. appear to show a higher preference for red wine compared to other regions. When considering price, South Africa seems to pay a fairly low price for wine compared to other regions. Australia was also observed to pay a considerably higher price for red wine. European consumers also appeared to spend less on wine than those in the U.S. and also seemed to be less biased towards certain wine attributes than those in the U.S. Overall, this study successfully demonstrated many significant differences among wine consumers, and further demonstrated the need to fully understand these different segments. By knowing the differences in these habits, the wine industry can more aptly anticipate wine consumer demands and tendencies. This information can help inform these decisions and alleviate the complexity in this vast consumer market.

Social norms interventions are a common approach to addressing the problem of college student drinking. An increasingly popular but not yet well-validated social-norms-based intervention consists of providing normative feedback to students in small groups. Objective, Participants, and Methods: In this study, the authors used a randomized design to test an interactive form of small-group social norms correction with 502 first-year students during September and October 2001. Because the unit of random assignment was at the level of the classroom, the authors used hierarchical linear modeling to estimate variability. They investigated whether small-group interactive social norms correction could influence alcohol perceptions and behaviors above and beyond a noninteractive social norms education approach. Results: Results indicate that the approach has a fairly substantial influence on student perceptions; however, the findings do not support an influence of interactive small-group social norms correction on measures of alcohol use behaviors. Conclusions: Given these findings, the use of interactive small-group social norms approach to influence student misperceptions may be considered as a primer for population-level preventive interventions.

Single molecule fluorescence microscopy and single molecule spectroscopy provide tremendously powerful methods for studying the behavior of a wide variety of biological systems. In this way, single molecule techniques can be used to gain an increased understanding of molecular mechanisms underlying basic phenomena in biology, materials science, and soft matter. In general, these approaches allow for detailed molecular information to be obtained when compared to bulk level methods performed using macroscopic techniques. In the first part of this thesis, we use single molecule fluorescence microscopy (SMFM) to develop and characterize a new class of fluorescent probes. Using SMFM, target biomolecules are commonly labeled with single fluorescent dyes allowing for real-time observation of dynamics and transient events. However, single molecule fluorescence imaging critically relies on bright dyes for robust signal detection above a noisy cellular background. Additionally, photostable dyes are desired to allow for continuous imaging of long time scale biological processes. To address this challenge, we developed a new class of fluorescent probes for SMFM using a two primary strategies designed to increase brightness and photostability. First, we developed fluorescent dendrimer nanoconjugates (FDN) consisting of multiple individual Cy5 dye molecules conjugated to a polymer dendrimer scaffold, which allows for increases in the total brightness of the molecules. In addition, we designed a series of ‘self-healing’ dendrimers that have a photoprotective molecule, Trolox, covalently attached to the probes, thereby resulting in increased photostability. Specifically, we designed the ‘self-healing’ FDNs using two complementary synthetic strategies, termed ‘random addition’ and ‘controlled addition’ allowing for control over the average stoichiometric ratio between Trolox and Cy5, and exact conjugation of Trolox and Cy5 with a precise one-to-one ratio. In all FDNs synthesized with the ‘self-healing’ strategy, we observe increases in probe photostability. In the second part of this thesis, we use single molecule force spectroscopy (SMFS) to study the mechanical properties of polymer systems. Here, we specifically examine the effect of the photostabilizer Trolox on the physical properties of the biopolymer, DNA. Using this technique, we exert force on a single polymer and observe the response of the molecule (typically increased extension under a stretching force). Using this method, we are able to determine polymer physical properties such as persistence length and contour length. We use magnetic tweezers for SMFS, a commonly used technique where a paramagnetic bead is attached to a tethered polymer, allowing for an external magnetic field to pull on the polymer. By observing the bead position over time, we can extract information on the polymer physical properties. We compare how these properties change with the addition of commonly used solution additives, primarily Trolox, used in fluorescence studies in polymer physics to provide enhanced photostability. In particular, we show that the addition of Trolox into solution with DNA induces an increase in the total contour length, consistent with results from our lab on DNA stretching experiments with SMFM. In summary, my work applies a consistent theme of addressing dye photostability and the photophysical properties of fluorescent probes for single molecule techniques. We demonstrate the development of a new class of photostable probes for fluorescence microscopy, and we determine the effect of commonly used photostabilizer on the physical properties of a model polymer system, DNA. Overall, this work will help advance the techniques available in single molecule imaging by increasing our understanding of the photophysical mechanisms underlying multi-dye conjugates and the possible physical changes to a system that can occur when using photostabilizing agents.

MECP2 duplication syndrome (MDS) is a rare X-linked neurodevelopmental disorder caused by duplications of the dosage-sensitive methyl-CpG-binding protein 2 (MECP2) gene. Developing effective therapies for MDS is particularly challenging due to the variability in MECP2 expression among patients and the potential risk of inducing Rett syndrome through excessive pharmacological intervention. Reducing dosage to optimize silencing levels often compromises durability and necessitates increased dosing frequency. We present here a series of fully chemically modified small interfering RNAs (siRNAs) designed for both isoform-selective and total MECP2 silencing. Among these, we identify six lead siRNA candidates across two distinct chemical scaffolds, achieving targeted total MECP2 expression reductions ranging from 25% to 75%, sustained for at least four months following a single administration. The efficacy and safety of human ortholog silencing were evaluated using two mouse models with distinct levels of human MECP2 transgene expression. In the severe duplication model, a single dose of the total isoform-silencing siRNA fully rescued early mortality and behavioral impairments. Additionally, we show that the isoform-selective targeting strategy may be safer in mild cases of MDS where exaggerated pharmacology may lead to Rett Syndrome. Overall, this study introduces a series of preclinical candidates with the capacity to address the varying levels of MECP2 duplication encountered in clinical settings. Furthermore, it establishes a target selection strategy that may be applied to other dosage-sensitive gene imbalances.

Interference between independently generated photons is a key step towards distributing entanglement over long distances, but it requires synchronization between the distantly-located photon sources. Synchronizing the clocks of such photon sources using coexisting two-way classical optical communications over the same fiber that transport the quantum photonic signals is a promising approach for achieving photon-photon interference over long distances, enabling entanglement distribution for quantum networking using the deployed fiber infrastructure. Here, we demonstrate photon-photon interference by observing the Hong-Ou-Mandel dip between two distantly-located sources: a weak coherent state source obtained by attenuating the output of a laser and a heralded single-photon source. We achieve a maximum dip visibility of \\(0.58 \\pm 0.04\\) when the two sources are connected via \\(4.3\\) km of deployed fiber. Dip visibilities \\(>0.5\\) are nonclassical and a first step towards achieving teleportation over the deployed fiber infrastructure. In our experiment, the classical optical communication is achieved with \\(-21\\) dBm of optical signal launch power, which is used to synchronize the clocks in the two independent, distantly-located photon sources. The impact of spontaneous Raman scattering from the classical optical signals is mitigated by appropriate choice of the quantum and classical channel wavelengths. All equipment used in our experiment (the photon sources and the synchronization setup) is commercially available. Finally, our experiment represents a scalable approach to enabling practical quantum networking with commercial equipment and coexistence with classical communications in optical fiber.

This dissertation develops a general, scalable framework for controlling dynamical, networked systems based on mathematical optimization theory, with a strong focus on applications to freeway traffic management. The generality of the framework allows for controllers to consider high-level objectives applied to systems with complex, nonlinear dynamics.A continuous freeway traffic model and its discretization was developed specifically for onramp metering control. The application serves as the motivating example behind the theory developed subsequently. To apply effective control on such systems, a discrete-adjoint-based model-predictive-control (MPC) approach for controlling networked systems of conservation laws is presented, with explicit derivations for ramp metering applications. Linear scalability of the method with respect to network size and time horizon is derived for the discrete adjoint computations. To enable a more asynchronous control architecture, the dissertation presents a distributed optimization algorithm for dynamical, networked systems. The algorithm allows for a physical network to be partitioned into subnetworks that optimize locally and communicate only with adjacent subnetworks to achieve a globally optimal performance.Within the context of the Connected Corridors project associated with UC Berkeley PATH, the developed theory was implemented in a production-level traffic management and simulation environment. Numerical examples applied to the San Diego I15 freeway are presented alongside the theory to motivate the highly practical aspects of the work. Simulations demonstrate the superiority of the MPC approach over existing methods widely used in practice.The optimization tools are applied to an investigation of security and vulnerabilities of traffic control systems. The potential impact of a compromise of freeway traffic metering lights is analyzed using MPC and multi-objective optimization tools. Several realizable scenarios that exploit traffic system vulnerability locations are constructed and simulated to illustrate the severity of compromises.Investigations are made into optimal rerouting strategies while controlling only a subset of network flow. A novel behavioral model is developed to account for the interaction of controllable and uncontrollable agents sharing a single flow network, where latency is a function of total flow. Using static freeway traffic models and communication network models, a framework based on convex optimization techniques is presented for computing rerouting policies, with numerical examples given for both freeway and communication networks.

This thesis is an English translation and assessment of the Arabic Book of the Maccabees from the London Polyglot Bible of 1657. The text, which was dubbed “The Fifth Book of the Maccabees” in an earlier English translation, is an historical narrative of the Hasmonean and Herodian families from circa 170 B.C. to circa 6 B.C. Until the late nineteenth and early twentieth centuries this work was regarded as a genuinely ancient and independent historical source for the events it narrates, but has since been neglected. Analysis of the language of the text, especially proper names, indicates that the work is a medieval Arabic translation of a Hebrew text, which was largely derived from a Latin translation or epitome of Flavius Josephus' Antiquities and Jewish War. This text is therefore neither ancient, nor of independent worth for the events it narrates.

The 35-minute programme of contortions and breathing exercises will be led by Prime Minister Narendra Modi, a yoga devotee who persuaded the United Nations to allocate the day to the ancient discipline. Since taking office last year, the 64-yearold has set up a government \"yoga ministry\", ordered his civil servants to join him for morning stretches and tweets different postures to his 13 million followers each day.