1,088 research outputs found
Mechanistic Investigations into the Palladium-Catalyzed Decarboxylative Allylic Alkylation of Ketone Enolates Using the PHOX Ligand Architecture
No full textPalladium-catalyzed asymmetric allylic alkylation has become a large and important field for chemical synthesis. Many methodologies in this field offer mild conditions under which challenging and important molecular features can be reliably synthesized, including chiral all-carbon quaternary stereocenters. As a result, palladium- catalyzed asymmetric allylic alkylation has found significant use in total synthesis, and growing use in industry. While the general process of palladium-catalyzed asymmetric allylic alkylation has been studied for decades, there have been a number of recent modifications and developments, such as asymmetric versions of decarboxylative allylic alkylation procedures that are not yet well understood. The development of future implementations and improvements to palladium-catalyzed asymmetric allylic alkylation and related methodologies is expected to be facilitated by a better understanding of these more recent developments, and thus further mechanistic investigation is warranted.
Reported herein is a set of investigations into the palladium-catalyzed decarboxylative asymmetric allylic alkylation of ketone enolates using the PHOX ligand architecture. By monitoring the reaction via 31P NMR, a series of previously unidentified key intermediates is discovered. Two representatives of these key intermediates are isolated and characterized. The solution behavior of these species under reaction-like conditions is studied along with a few novel and related complexes. The role of these intermediates and their impact on the behavior of the reaction and product formation is discussed. Previously confounding experimentally observed behavior for this methodology is rationalized via the properties elucidated for these discovered intermediates.</p
Hydrogen sulfide supplementation as a potential treatment for primary mitochondrial diseases
No full textPrimary mitochondrial diseases (PMD) are amongst the most common inborn errors of metabolism causing fatal outcomes within the first decade of life. With marked heterogeneity in both inheritance patterns and physiological manifestations, these conditions present distinct challenges for targeted drug therapy, where effective therapeutic countermeasures remain elusive within the clinic. Hydrogen sulfide (H2S)-based therapeutics may offer a new option for patient treatment, having been proposed as a conserved mitochondrial substrate and post-translational regulator across species, displaying therapeutic effects in age-related mitochondrial dysfunction and neurodegenerative models of mitochondrial disease. H2S can stimulate mitochondrial respiration at sites downstream of common PMD-defective subunits, augmenting energy production, mitochondrial function and reducing cell death. Here, we highlight the primary signalling mechanisms of H2S in mitochondria relevant for PMD and outline key cytoprotective proteins/pathways amenable to post-translational restoration via H2S-mediated persulfidation. The mechanisms proposed here, combined with the advent of potent mitochondria-targeted sulfide delivery molecules, could provide a framework for H2S as a countermeasure for PMD disease progression.</p
Nathaniel Faulkhead
No full textThe author discusses the life of Nathaniel Faulkhead, who was Treasurer of the Echo Publishing House in Australia and a high ranking member of the Masonic Lodge
The great stone face /
No full textPublication date supplied by cataloger.Title from cover.Mode of access: Internet.OSU's copy 3: Bound with: The snow image / by Nathaniel Hawthorne -- The miraculous pitcher / by Nathaniel Hawthorne -- Circe's palace -- The three golden apples / by Nathaniel Hawthorne -- Selected poems -- The vision of Sir Launfal / by James Russell Lowell -- Prose selections -- The deserted village / by Oliver Goldsmith -- Cotter's Saturday night and other poems / by Robert Burns -- The rime of the ancient mariner / by Samuel Taylor Coleridge -- Brewer's collection of favorite songs -- Brewer{u2019}s collection of popular songs.OSU's copy 3 lacking portrait
Nathaniel Hawthorne as a Revolutionary Author. Feminism in The Scarlet Letter
No full textThe protagonist of The Scarlet Letter works as a predecessor for fictional feminist heroines. Much like modern times, Hester Prynne is born into a society that favors men and the main character suffers from the unfair treatment that is brought upon her due to her femininity. Nathaniel Hawthorne invents a universe to show female oppression and how harmful it can be for individuals to be regarded as less important because of one’s gender. The purpose of this study is to investigate how Nathaniel Hawthorne was able to create one of the first strong female protagonists by using elements from feminist movements that occurred even after his death. The concept of the second and third waves of feminism was not yet invented before the author passed, but it is still possible to find traces of these feminist waves in The Scarlet Letter. At the time of its publication, The Scarlet Letter revolutionized female-centred narratives; the main character of The Scarlet Letter is unique since her behavior and mindset differ from other female characters of the 19th century. By using feminist theory it is clear that Nathaniel Hawthorne’s innovative way of thinking sets the foundation for him to create the feminist character of Hester Prynne. The author shows, through his novel, that he is aware of how unfair women are treated and reflects that into The Scarlet Letter. Even though women today are not facing the same problems that Hester Prynne encounters, there are still social changes that need to be made for women to be equal to men. By considering issues from real life and by being inspired by feminists from the 19th century, Nathaniel Hawthorne has created a feminist that is still relevant to this day
Nathaniel Hawthorne's Shadow in The Scarlet Letter
No full textScholars of American literature have produced innumerable interpretations on Nathaniel Hawthorne's masterpiece The Scarlet Letter. Notably, each different approach to the work has revealed a different viewpoint hidden within the story. Here, the story is to be analyzed in relation to the lifelong inner angst of author Nathaniel Hawthorne. This new approach shows the main characters to be individuals into whom the depth of Nathaniel Hawthorne's psychological mindset has been projected. Arthur Dimmesdale, a young minister, reflects the author's internal struggle over his ancestor's past involvement in the judgement of witches, including at the Salem witch trial in 1692. Chillingworth, a diabolical man, represents Nathaniel Hawthorne's sense of guilt, and shows his commitment as an artist to observing people's inner souls. Hester's freethinking manner and way of life can be seen as Nathaniel Hawthorne's strong determination to become an independent artist, and one who is never to fall victim to the stains of the past and society. Nathaniel Hawthorne's longing for British culture is reflected in Pearl. The particular end that each character meets can also be interpreted as carrying its own unique message. Nathaniel Hawthorne is very negative about Chillingworth; the author shows no sympathy for his own inevitably sinful fate of peeping into people's inner souls. The implications of Dimmesdale's death after his final confession on the scaffold are somewhat ambiguous. It is uncertain whether he was saved or severely judged. More likely, there is a mixture of both elements, and his death clearly shows us that the sinful lifestyle of Nathaniel Hawthorne's ancestors must end. Hester ultimately returns of her own free will to the puritan society of Boston, after having lived for a while in the Old World with her daughter Pearl. Hester's return tells us that Nathaniel Hawthorne's desire for freedom includes the possibility of serving the puritan society. Pearl is the only character alive at the end of the novel, happily married, and possibly in England. Nathaniel Hawthorne's decision to live as an artist includes aspirations of British heritage. Dimmesdale's inherited strong animal nature is the root of the persecuting spirit in the history of the author's' ancestors. Therefore, the scarlet letter A in the story can be interpreted as the initial letter of the word 'animal.'7KJ00002449582論文Articledepartmental bulletin pape
Adaptability to eccentric exercise training is diminished with age in female mice
No full textThe ability of skeletal muscle to adapt to eccentric contractions has been suggested to be blunted in older muscle. If eccentric exercise is to be a safe and efficient training mode for older adults, preclinical studies need to establish if older muscle can effectively adapt and if not, determine the molecular signatures that are causing this impairment. The purpose of this study was to quantify the extent age impacts functional adaptations of muscle and identify genetic signatures associated with adaptation (or lack thereof). The anterior crural muscles of young (4 mo) and older (28 mo) female mice performed repeated bouts of eccentric contractions in vivo (50 contractions/wk for 5 wk) and isometric torque was measured across the initial and final bouts. Transcriptomics was completed by RNA-sequencing 1 wk following the 5th bout to identify common and differentially regulated genes. Young muscle exhibited a robust ability to adapt, increasing isometric torque 20-36%, while isometric torque of older muscle decreased up to 18%; adaptive potential was less in older muscle compared to young muscle (p≤0.047). Using differential gene expression, young and older muscles shared some common transcriptional changes in response to eccentric exercise training, whereas other transcripts appeared to be age dependent. That is, the ability to express particular genes after repeated bouts of eccentric contractions was not the same between ages. These molecular signatures may reveal, in part, why older muscles do not appear to be as adaptive to exercise training as young muscles.</p
Characterization of the protective tryptophan clusters and key sensitizing residues
No full textThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2013.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis. In title on title page [g̳a̳m̳m̳a̳] appear as lower case Greek letters.Includes bibliographical references (pages. 162-178).by Nathaniel Schafheimer.Ph.D
Experimental methods in permutation patterns and bijective proof
No full textExperimental mathematics is the technique of developing conjectures and proving theorems through the use of experimentation; that is, exploring finitely many cases and detecting patterns that can then be rigorously proved. This thesis applies the techniques of experimental mathematics to several problems.
First, we generalize the translation method of Wood and Zeilberger [49] to algebraic proofs, and as an example, produce (by computer) the first bijective proof of Franel’s recurrence for an(3)=Σnk=0(nk)3.
Next, we apply the method of enumeration schemes to several problems in the fieldof patterns on permutations and words. Given a word w on the alphabet [n] and σ ∈ Sk, we say that w contains the pattern σ if some subsequence of the letters of w is orderisomorphic to σ. First, we find an enumeration scheme that allows us to count the words containing r copies of each letter that avoid the pattern 123. Then we look at the case where w is in fact a permutation in Sn. A repeating permutation is one that is the direct sum of several copies of a smaller permutation. We produce an enumeration scheme to count permutations avoiding repeating patterns of low codimension, and show that for each repeating pattern, the problem belongs to the eventually polynomial ansatz.Ph.D.Includes bibliographical referencesby Nathaniel Sha
Musculoskeletal responses to spaceflight: mechanisms, countermeasures, and key gaps
No full textSpaceflight and partial-gravity environments impose profound challenges to the human musculoskeletal system, driving rapid muscle atrophy, progressive bone loss, and tendon maladaptation. At the molecular level, unloading suppresses anabolic signaling, enhances proteolysis, and induces mitochondrial stress, while bone and tendon exhibit reduced extracellular matrix turnover and impaired mechanotransduction. Recent space-omics and cross-species studies, including rodent and C. elegans models, reveal that these catabolic responses are evolutionarily conserved and involve systemic pathways mediated by myokines, osteokines, and tendon-derived signals. Current countermeasure strategies primarily consist of structured exercise regimens with limited pharmacologic support. While these strategies mitigate some loss, they fail to fully preserve musculoskeletal integrity, particularly tendon properties and microarchitectural bone quality. Key gaps remain in the development of tendon-specific interventions, integrated pharmacologic and exercise regimens, nutrition and dietary protocols, and methods for partial-gravity adaptation and safe re-entry. Leveraging real-time monitoring, individualized exercise programs, and systemic biomarker discovery through space omics presents major opportunities for next-generation, personalized countermeasures. This mini-review synthesizes current knowledge of musculoskeletal responses with a particular focus on tendon maladaptation and inter-organ cross talk to spaceflight and partial gravity, highlights countermeasure efficacy and limitations, and identifies critical gaps that must be addressed to ensure astronaut health and performance during future missions. Insights from these studies also provide translational relevance for disuse atrophy, osteoporosis, and tendon injuries on Earth. </p
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