Controlling Transition Metal-Catalyzed Alkyne Annulations Utilizing Polarized Ynol Ethers

Transition metal-catalyzed alkyne annulations have developed into incredibly powerful synthetic tools over there the past quarter century. These reactions provide rapid access to important organic scaffolds such as indole, quinoline, isoquinoline, indene, and isocoumarin scaffolds. Transition metal mediated alkyne annulations have proven invaluable in synthetic fields, such as natural product total synthesis, by offering efficient pathways to otherwise synthetically difficult to access substrates. Foundational works performed by chemist such as Larock, Ackermann, Satoh, and Miura have been established through relying upon the usage of symmetrical alkynes. When unsymmetrical alkynes are used in annulation processes mixtures of regioisomers are often isolated. While methodologies have been developed which regioselectively deliver annulation products, the regioselective nature of these reactions is often empirically determined and obtained with little synthetic design to impact the alkyne migratory insertion step of the catalytic cycle. In recent years few examples of polarized, unsymmetrical alkynes have been sparingly used in transition metal alkyne annulations. Still, these limited examples provide the roadmap for how to regioselectively control alkyne annulations. Researchers have displayed that one class of polarized alkynes, ynol ethers, exhibit the ability to react regioselectively in transition metal-catalyzed migratory insertion processes. There has been little research focused on expanding this regioselective nature of ynol ethers into transition metal-catalyzed alkyne annulations. This dissertation provides the work we have accomplished in efforts to bridge this gap. We have established the use of ynol ethers as compatible annulations partners in transition metal-catalyzed alkyne annulations. They have been utilized in the regioselective synthesis of diverse 4-oxy-substituted isoquinolinones. These substrates can be further functionalized into prolyl-4-hydroxylase domain inhibitor analogues. Ynol ethers were also employed to regioselectively facilitate the palladium catalyzed synthesis of complex indenol ethers. Through inhibiting the terminal step in this indene synthesis, -hydride elimination and intercepting the in-situ generated palladium intermediate, the isolation of an enantiomeric mixture of isomers was observed. To date we have partially optimized a regioselective, enantioselective, intermolecular Heck–Suzuki–Miyaura cascade reaction. Further investigation is necessary to fully understand regioselective transition metal-catalyzed ynol ether annulations, but the groundwork has been laid for this work to continue

Colorimetric and Longitudinal Analysis of Leukocoria in Recreational Photographs of Children with Retinoblastoma

Retinoblastoma is the most common primary intraocular tumor in children. The first sign that is often reported by parents is the appearance of recurrent leukocoria (i.e., “white eye”) in recreational photographs. A quantitative definition or scale of leukocoria – as it appears during recreational photography – has not been established, and the amount of clinical information contained in a leukocoric image (collected by a parent) remains unknown. Moreover, the hypothesis that photographic leukocoria can be a sign of early stage retinoblastoma has not been tested for even a single patient. This study used commercially available software (Adobe Photoshop®) and standard color space conversion algorithms (operable in Microsoft Excel®) to quantify leukocoria in actual “baby pictures” of 9 children with retinoblastoma (that were collected by parents during recreational activities i.e., in nonclinical settings). One particular patient with bilateral retinoblastoma (“Patient Zero”) was photographed >7, 000 times by his parents (who are authors of this study) over three years: from birth, through diagnosis, treatment, and remission. This large set of photographs allowed us to determine the longitudinal and lateral frequency of leukocoria throughout the patient's life. This study establishes: (i) that leukocoria can emerge at a low frequency in early-stage retinoblastoma and increase in frequency during disease progression, but decrease upon disease regression, (ii) that Hue, Saturation and Value (i.e., HSV color space) are suitable metrics for quantifying the intensity of retinoblastoma-linked leukocoria; (iii) that different sets of intraocular retinoblastoma tumors can produce distinct leukocoric reflections; and (iv) the Saturation-Value plane of HSV color space represents a convenient scale for quantifying and classifying pupillary reflections as they appear during recreational photography

Connection between the Accretion Disk and Jet in the Radio Galaxy 3C 111

We present the results of extensive multi-frequency monitoring of the radio galaxy 3C 111 between 2004 and 2010 at X-ray (2.4--10 keV), optical (R band), and radio (14.5, 37, and 230 GHz) wave bands, as well as multi-epoch imaging with the Very Long Baseline Array (VLBA) at 43 GHz. Over the six years of observation, significant dips in the X-ray light curve are followed by ejections of bright superluminal knots in the VLBA images. This shows a clear connection between the radiative state near the black hole, where the X-rays are produced, and events in the jet. The X-ray continuum flux and Fe line intensity are strongly correlated, with a time lag shorter than 90 days and consistent with zero. This implies that the Fe line is generated within 90 light-days of the source of the X-ray continuum. The power spectral density function of X-ray variations contains a break, with steeper slope at shorter timescales. The break timescale of 13 (+12,-6) days is commensurate with scaling according to the mass of the central black hole based on observations of Seyfert galaxies and black hole X-ray binaries (BHXRBs). The data are consistent with the standard paradigm, in which the X-rays are predominantly produced by inverse Compton scattering of thermal optical/UV seed photons from the accretion disk by a distribution of hot electrons --- the corona --- situated near the disk. Most of the optical emission is generated in the accretion disk due to reprocessing of the X-ray emission. The relationships that we have uncovered between the accretion disk and the jet in 3C 111, as well as in the FR I radio galaxy 3C 120 in a previous paper, support the paradigm that active galactic nuclei and Galactic BHXRBs are fundamentally similar, with characteristic time and size scales proportional to the mass of the central black holeComment: Accepted for publication in ApJ. 18 pages, 17 figures, 11 tables (full machine readable data-tables online in ApJ website

Tamm Review: Management of mixed-severity fire regime forests in Oregon, Washington, and Northern California

Increasingly, objectives for forests with moderate- or mixed-severity fire regimes are to restore successionally diverse landscapes that are resistant and resilient to current and future stressors. Maintaining native species and characteristic processes requires this successional diversity, but methods to achieve it are poorly explained in the literature. In the Inland Pacific US, large, old, early seral trees were a key historical feature of many young and old forest successional patches, especially where fires frequently occurred. Large, old trees are naturally fire-tolerant, but today are often threatened by dense understory cohorts that create fuel ladders that alter likely post-fire successional pathways. Reducing these understories can contribute to resistance by creating conditions where canopy trees will survive disturbances and climatic stressors; these survivors are important seed sources, soil protectors, and critical habitat elements. Historical timber harvesting has skewed tree size and age class distributions, created hard edges, and altered native patch sizes. Manipulating these altered forests to promote development of larger patches of older, larger, and more widely-spaced trees with diverse understories will increase landscape resistance to severe fires, and enhance wildlife habitat for underrepresented conditions. Closed-canopy, multi-layered patches that develop in hot, dry summer environments are vulnerable to droughts, and they increase landscape vulnerability to insect outbreaks and severe wildfires. These same patches provide habitat for species such as the northern spotted owl, which has benefited from increased habitat area. Regional and local planning will be critical for gauging risks, evaluating trade-offs, and restoring dynamics that can support these and other species. The goal will be to manage for heterogeneous landscapes that include variably-sized patches of (1) young, middle-aged, and old, closed canopy forests growing in upper montane, northerly aspect, and valley bottom settings, (2) a similar diversity of open-canopy, fire-tolerant patches growing on ridgetops, southerly aspects, and lower montane settings, and (3) significant montane chaparral and grassland areas. Tools to achieve this goal include managed wildfire, prescribed burning, and variable density thinning at small to large scales. Specifics on ‘‘how much and where?” will vary according to physiographic, topographic and historical templates, and regulatory requirements, and be determined by means of a socio-ecological process

Tamm Review: Management of mixed-severity fire regime forests in Oregon, Washington, and Northern California

Increasingly, objectives for forests with moderate- or mixed-severity fire regimes are to restore successionally diverse landscapes that are resistant and resilient to current and future stressors. Maintaining native species and characteristic processes requires this successional diversity, but methods to achieve it are poorly explained in the literature. In the Inland Pacific US, large, old, early seral trees were a key historical feature of many young and old forest successional patches, especially where fires frequently occurred. Large, old trees are naturally fire-tolerant, but today are often threatened by dense understory cohorts that create fuel ladders that alter likely post-fire successional pathways. Reducing these understories can contribute to resistance by creating conditions where canopy trees will survive disturbances and climatic stressors; these survivors are important seed sources, soil protectors, and critical habitat elements. Historical timber harvesting has skewed tree size and age class distributions, created hard edges, and altered native patch sizes. Manipulating these altered forests to promote development of larger patches of older, larger, and more widely-spaced trees with diverse understories will increase landscape resistance to severe fires, and enhance wildlife habitat for underrepresented conditions. Closed-canopy, multi-layered patches that develop in hot, dry summer environments are vulnerable to droughts, and they increase landscape vulnerability to insect outbreaks and severe wildfires. These same patches provide habitat for species such as the northern spotted owl, which has benefited from increased habitat area. Regional and local planning will be critical for gauging risks, evaluating trade-offs, and restoring dynamics that can support these and other species. The goal will be to manage for heterogeneous landscapes that include variably-sized patches of (1) young, middle-aged, and old, closed canopy forests growing in upper montane, northerly aspect, and valley bottom settings, (2) a similar diversity of open-canopy, fire-tolerant patches growing on ridgetops, southerly aspects, and lower montane settings, and (3) significant montane chaparral and grassland areas. Tools to achieve this goal include managed wildfire, prescribed burning, and variable density thinning at small to large scales. Specifics on ‘‘how much and where?” will vary according to physiographic, topographic and historical templates, and regulatory requirements, and be determined by means of a socio-ecological process

SOUL at LBT: commissioning results, science and future

The SOUL systems at the Large Bincoular Telescope can be seen such as precursor for the ELT SCAO systems, combining together key technologies such as EMCCD, Pyramid WFS and adaptive telescopes. After the first light of the first upgraded system on September 2018, going through COVID and technical stops, we now have all the 4 systems working on-sky. Here, we report about some key control improvements and the system performance characterized during the commissioning. The upgrade allows us to correct more modes (500) in the bright end and increases the sky coverage providing SR(K)>20% with reference stars G$_{RP}$<17, opening to extragalcatic targets with NGS systems. Finally, we review the first astrophysical results, looking forward to the next generation instruments (SHARK-NIR, SHARK-Vis and iLocater), to be fed by the SOUL AO correction.Comment: 13 pages, 10 figures, Adaptive Optics for Extremely Large Telescopes 7th Edition, 25-30 Jun 2023 Avignon (France

Developing a Series of AI Challenges for the United States Department of the Air Force

Through a series of federal initiatives and orders, the U.S. Government has been making a concerted effort to ensure American leadership in AI. These broad strategy documents have influenced organizations such as the United States Department of the Air Force (DAF). The DAF-MIT AI Accelerator is an initiative between the DAF and MIT to bridge the gap between AI researchers and DAF mission requirements. Several projects supported by the DAF-MIT AI Accelerator are developing public challenge problems that address numerous Federal AI research priorities. These challenges target priorities by making large, AI-ready datasets publicly available, incentivizing open-source solutions, and creating a demand signal for dual use technologies that can stimulate further research. In this article, we describe these public challenges being developed and how their application contributes to scientific advances

Cardiorespiratory and Biomechanical Changes with Hippotherapy in Children with and without Cerebral Palsy

Hippotherapy utilizes the rhythmic movement of the horse to improve functional abilities and quality of life of individuals with neurological impairments. Little is known regarding the changes in body segment kinematics and cardiovascular responses of the rider due to the therapy. A change in the magnitude of pelvic displacement (PD) may allow those who use the therapy to more easily perform activities of daily living. Also, reduced cardiovascular stress to similar physical activities may be an important, but overlooked, therapeutic benefit of hippotherapy. The purpose of this study was to characterize PD and cardiorespiratory (CR) responses to simulated horseback riding (SHR) and walking in children with minimal-to-moderate spastic cerebral palsy (CP) before and after eight weeks of hippotherapy. These results were compared to healthy children undergoing the same protocol. Our hypothesis was that eight weeks of hippotherapy would elicit an increase in PD and reduced CR response during SHR and treadmill walking in children with CP. Eight children with CP (1 female, 7 males; 10 + 4 years of age; height 54 + 10 in; weight 70.2 + 34.3 lb) and eight healthy children (5 females, 3 males; 11 + 2 years of age; height 59 + 6 in; weight 104.6 + 33.4 lb) underwent similar hippotherapy training. Before and after the intervention, both groups completed simulated horseback riding (SHR) at an intensity approximating a fast walk (0.65 Hz) and walked on a treadmill (1 mph, 0% grade). PD along the anterior-posterior, superior-inferior and medial-lateral axes and HR, VO2, VE, SBP, and DBP were measured at steady-state exercise. Mean arterial pressure and rate pressure product were calculated. Prior to hippotherapy, PD was increased in healthy children (p = 0.032) but CR responses were similar in both groups during SHR (p \u3e 0.05 for all). Treadmill walking elicited greater PD and CR responses compared to SHR in both groups and significantly greater responses in CP compared to healthy children (p \u3c 0.05 for all). Eight weeks of hippotherapy did not alter acute responses. Our findings demonstrate treadmill walking at 1 mph elicits greater PD and CR responses than SHR. The walking responses are more pronounced in children with CP compared to healthy children. Observable cardiovascular adaptations or kinematic changes in children with CP are unaffected by short-term hippotherapy training