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Apoptosis is induced in cancer cells and tumor xenografts by the thyroid hormone analogue tetraiodothyroacetic acid (tetrac) or chemically modified forms of tetrac. The effect is initiated at a hormone receptor on the extracellular domain of plasma membrane integrin αvβ3. The tumor response to tetrac includes 80% reduction in size of glioblastoma xenograft in two weeks of treatment, with absence of residual apoptotic cancer cell debris; this is consistent with efferocytosis. The molecular basis for efferocytosis linked to tetrac is incompletely understood, but several factors are proposed to play roles. Tetrac-based anticancer agents are pro-apoptotic by multiple intrinsic and extrinsic pathways and differential effects on specific gene expression, e.g., downregulation of the X-linked inhibitor of apoptosis (XIAP) gene and upregulation of pro-apoptotic chemokine gene, CXCL10. Tetrac also enhances transcription of chemokine CXCR4, which is relevant to macrophage function. Tetrac may locally control the conformation of phagocyte plasma membrane integrin αvβ3; this is a cell surface recognition system for apoptotic debris that contains phagocytosis signals. How tetrac may facilitate the catabolism of the engulfed apoptotic cell debris requires additional investigation. [ABSTRACT FROM AUTHOR]

Copyright of Retos: Nuevas Perspectivas de Educación Física, Deporte y Recreación is the property of Federacion Espanola de Asociaciones de Docentes de Educacion Fisica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

DNA is a re-configurable, biological information-storage unit, and much remains to be learned about its heterogeneous structural dynamics. For example, while it is known that molecular dyes templated onto DNA exhibit increased photostability, the mechanism by which the structural dynamics of DNA affect the dye photophysics remains unknown. Here, we use femtosecond, two-dimensional electronic spectroscopy measurements of a cyanine dye, Cy5, to probe local conformations in samples of single-stranded DNA (ssDNA–Cy5), double-stranded DNA (dsDNA–Cy5), and Holliday junction DNA (HJ–DNA–Cy5). A line shape analysis of the 2D spectra reveals a strong excitation–emission correlation present in only the dsDNA–Cy5 complex, which is a signature of inhomogeneous broadening. Molecular dynamics simulations support the conclusion that this inhomogeneous broadening arises from a nearly degenerate conformer found only in the dsDNA–Cy5 complex. These insights will support future studies on DNA's structural heterogeneity. [ABSTRACT FROM AUTHOR]

Objective: There are few methods that focus on therapists' experiences of supervision. To facilitate the development of psychologist students, a supervisee‐centred supervision, based on deliberate practice, feedback informed treatment and self‐compassion, was introduced. Methods: This study examines six supervisees' experiences of a supervisee‐centred supervision. A semi‐ structured interview was used for the collection of the data, which identified two main themes: Learning and Development and five associated sub‐themes: structure and purposesfulness, prerequisites, experience‐based learning, therapeutic skills and personal development. Conclusion: The experience‐ and feedback‐based approach was perceived as efficient, structured and goal oriented. This created high‐focused activity and participation, a strong group dynamic and a good alliance with the supervisors, providing a good climate for learning and development. Focusing on performance and feedback was perceived as a potential obstacle that could create stress and anxiety. [ABSTRACT FROM AUTHOR]

Several cardiovascular disease (CVD) risk factors (e.g., hypertension, poor glycemic control) can affect and be affected by autonomic nervous system (ANS) activity. Since excess adiposity can influence CVD development through its effect on hypertension and diabetes mellitus, it is important to determine how adiposity and altered ANS activity are related. The present study employed structural equation modeling to investigate the relation between adiposity and ANS activity both directly and indirectly through biological variables typically associated with glycemic impairment and cardiac stress in older adults. Utilizing the Atherosclerosis Risk in Communities (ARIC) dataset, 1,145 non-smoking adults (74±4.8 yrs, 62.8% female) free from known CVD, hypertension, and diabetes and not currently taking beta-blockers were evaluated for fasting blood glucose (FBG), insulin, and HbA1c concentrations, waist circumference (WC), blood pressure (BP), and markers of ANS activity. WC was recorded just above the iliac crest and was used to reflect central adiposity. Resting 2-minute electrocardiograph recordings, pulse wave velocity, and ankle-brachial index data were used to assess the root mean square of successive differences in RR intervals (RMSSD) and the pre-ejection period (PEP), markers of parasympathetic and sympathetic activity, respectively. FBG, insulin, and HbA1c inferred a latent variable termed glycemic impairment (GI), whereas heart rate and diastolic BP inferred a latent variable termed cardiac stress (CS). The structural equation model fit was acceptable [root mean square error of approximation = 0.050 (90% CI =.036,.066), comparative fit index =.970, Tucker Lewis Index = 0.929], with adiposity having both significant direct (β = 0.208, p = 0.018) and indirect (β = -.217, p =.041) effects on PEP through GI. Adiposity displayed no significant direct effect on RMSSD. CS displayed a significant pathway (β = -0.524, p = 0.035) on RMSSD, but the indirect effect of WC on RMSSD through CS did not reach statistical significance (β = -0.094, p = 0.137). These results suggest that adiposity's relation to ANS activity is multifaceted, as increased central adiposity had opposing direct and indirect effects on markers of sympathetic activity in this population of older adults. [ABSTRACT FROM AUTHOR]

The process of SARS-CoV-2 infection, responsible for the COVID-19 pandemic, is carried out through different steps, with the interaction between ACE2 and Spike protein (S) being crucial. Besides of that, the acidic environment of endosomes seems to play a relevant role in the virus uptake into cells and its intracellular replication. Patients affected by two rare genetic tubulopathies, Gitelman's and Bartter's Syndromes, and a rare genetic metabolic disease, Fabry Disease, have shown intrinsic protection from SARS-CoV-2 infection and COVID-19 on account of specific intrinsic features that interfere with the virus uptake into cells and its intracellular replication, which will be reported and discussed in this paper, providing interesting insights for present and future research. [ABSTRACT FROM AUTHOR]

A noncollinear optical parametric amplifier (NOPA) can produce few-cycle femtosecond laser pulses that are ideally suited for time-resolved optical spectroscopy measurements. However, the nonlinear-optical process giving rise to ultrabroadband pulses is susceptible to spatiotemporal dispersion problems. Here, we detail refinements, including chirped-pulse amplification (CPA) and pulse-front matching (PFM), that minimize spatiotemporal dispersion and thereby improve the properties of ultrabroadband pulses produced by a NOPA. The description includes a rationale behind the choices of optical and optomechanical components, as well as assessment protocols. We demonstrate these techniques using a 1 kHz, second-harmonic Ti:sapphire pump configuration, which produces ∼5-fs duration pulses that span from about 500 to 800 nm with a bandwidth of about 200 THz. To demonstrate the utility of the CPA-PFM-NOPA, we measure vibrational quantum beats in the transient–absorption spectrum of methylene blue, a dye molecule that serves as a reference standard. [ABSTRACT FROM AUTHOR]

Evidence suggests affective responses to exercise can influence exercise adherence. However, there is a limited understanding of how and when to measure core affect in resistance training. As such, the objective of this systematic review was to analyze how the Feeling Scale and/or the Felt Arousal Scale have been used in resistance training to assess core affect. Focus was given to the contextual feasibility, timing, and frequency of assessment. A search in PubMed, SPORTDiscus, and PsycINFO databases was conducted (last search date July, 2022) with the purpose of including experimental and non-experimental studies, utilizing the Feeling Scale and/or the Felt Arousal Scale in resistance training, and focused on apparently healthy individuals of any age. Twenty-seven studies (N = 718 participants) published between 2009–2022 were qualitatively analyzed. Both scales appeared to be able to detect core affect within a wide array of intensities, ages, and equipment. As for the timing and frequency of measurement, no apparent standardization was evident. The use of the Feeling Scale, the Felt Arousal Scale, or both, to measure core affect appears to be feasible in resistance training practices. However, a lack of methodological background raises concerns regarding the quality of previous studies' assessments and comparisons of results across studies. [ABSTRACT FROM AUTHOR]

The metabolic network of a living cell is highly intricate and involves complex interactions between various pathways. In this study, we propose a computational model that integrates glycolysis, the pentose phosphate pathway (PPP), the fatty acids beta-oxidation, and the tricarboxylic acid cycle (TCA cycle) using queueing theory. The model utilizes literature data on metabolite concentrations and enzyme kinetic constants to calculate the probabilities of individual reactions occurring on a microscopic scale, which can be viewed as the reaction rates on a macroscopic scale. However, it should be noted that the model has some limitations, including not accounting for all the reactions in which the metabolites are involved. Therefore, a genetic algorithm (GA) was used to estimate the impact of these external processes. Despite these limitations, our model achieved high accuracy and stability, providing real-time observation of changes in metabolite concentrations. This type of model can help in better understanding the mechanisms of biochemical reactions in cells, which can ultimately contribute to the prevention and treatment of aging, cancer, metabolic diseases, and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

The metabolic network of a living cell is highly intricate and involves complex interactions between various pathways. In this study, we propose a computational model that integrates glycolysis, the pentose phosphate pathway (PPP), the fatty acids beta-oxidation, and the tricarboxylic acid cycle (TCA cycle) using queueing theory. The model utilizes literature data on metabolite concentrations and enzyme kinetic constants to calculate the probabilities of individual reactions occurring on a microscopic scale, which can be viewed as the reaction rates on a macroscopic scale. However, it should be noted that the model has some limitations, including not accounting for all the reactions in which the metabolites are involved. Therefore, a genetic algorithm (GA) was used to estimate the impact of these external processes. Despite these limitations, our model achieved high accuracy and stability, providing real-time observation of changes in metabolite concentrations. This type of model can help in better understanding the mechanisms of biochemical reactions in cells, which can ultimately contribute to the prevention and treatment of aging, cancer, metabolic diseases, and neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

It has sometimes been suggested that Addison never in fact outgrew Dryden's influence, not even in the "Pleasures of the Imagination" papers; that the imaginative and "psychological" emphases of those papers were already present in Dryden's criticism, in his most Longinian essays such as "Of Heroique Playes" (1672) and "The Author's Apology for Heroic Poetry; and Poetique Licence" (1677).[55] According to Clarence De Witt Thorpe, "Dryden ... contributed so much in the way of lively forward-looking discussion of basic critical problems ... that there was little in Addison's theory that had not been at least intimated in his great essays."[56] C. H. Salter was more trenchant: "it was Dryden, and not Addison, who broke with the canons of neo-classical criticism [and] laid the foundations of Romantic aesthetics": Addison's apparent innovations as a critic are the result of "his concealment of his sources and attempts to disagree with them, if necessary by misrepresenting them." The notes contain few dateable references: Addison's determination to present himself as a poetry-lover rather than scholar entailed a refusal to flaunt authorities in the manner of Dennis and the nit-picking "Dutch commentator(s)" Dryden had taught Addison to deride.[14] But those texts Addison does mention by name, or which can be identified from circumstantial details in his allusions to them, all date from between 1689 and 1692. I explain how it was that Addison effectively invented eighteenth-century aesthetics not in I The Spectator i but fifteen years earlier - and in an essay on Virgil's I Georgics i , the most Augustan poet's most Augustan poem. i. notes on ovid Two dates for the composition of Addison's "Notes on Ovid" are current in modern scholarship: 1697 and 1704. [Extracted from the article]

Background: Contrast-induced encephalopathy (CIE) is an infrequent but serious neurological condition that occurs shortly after the administration of contrast during endovascular and angiography procedures. Patients suffering from chronic kidney disease (CKD) or end-stage kidney disease (ESKD) are considered to be at a higher risk of contrast medium neurotoxicity, due to the delayed elimination of the contrast medium. However, the occurrence and characteristics of CIE in CKD/ESKD patients have not been extensively investigated. Methods: We conducted a comprehensive literature search, utilizing databases such as MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, up to September 2022. The purpose was to identify documented cases of CIE among patients with CKD or ESKD. Employing a random-effects model, we calculated the pooled incidence and odds ratio (OR) of CIE in CKD/ESKD patients. Results: Our search yielded a total of eleven articles, comprising nine case reports and two observational studies. Among these studies, 2 CKD patients and 12 ESKD patients with CIE were identified. The majority of the CKD/ESKD patients with CIE (93%) had undergone intra-arterial contrast media and/or endovascular procedures to diagnose acute cerebrovascular disease, coronary artery disease, and peripheral artery disease. The male-to-female ratio was 64%, and the median age was 63 years (with an interquartile range of 55 to 68 years). In the two observational studies, the incidence of CIE was found to be 6.8% in CKD patients and 37.5% in ESKD patients, resulting in a pooled incidence of 16.4% (95% CI, 2.4%–60.7%) among the CKD/ESKD patients. Notably, CKD and ESKD were significantly associated with an increased risk of CIE, with ORs of 5.77 (95% CI, 1.37–24.3) and 223.5 (95% CI, 30.44–1641.01), respectively. The overall pooled OR for CIE in CKD/ESKD patients was 32.9 (95% CI, 0.89–1226.44). Although dialysis prior to contrast exposure did not prevent CIE, approximately 92% of CIE cases experienced recovery after undergoing dialysis following contrast exposure. However, the effectiveness of dialysis on CIE recovery remained uncertain, as there was no control group for comparison. Conclusions: In summary, our study indicates an association between CIE and CKD/ESKD. While patients with CIE showed signs of recovery after dialysis, further investigations are necessary, especially considering the lack of a control group, which made the effects of dialysis on CIE recovery uncertain. [ABSTRACT FROM AUTHOR]

Background: Contrast-induced encephalopathy (CIE) is an infrequent but serious neurological condition that occurs shortly after the administration of contrast during endovascular and angiography procedures. Patients suffering from chronic kidney disease (CKD) or end-stage kidney disease (ESKD) are considered to be at a higher risk of contrast medium neurotoxicity, due to the delayed elimination of the contrast medium. However, the occurrence and characteristics of CIE in CKD/ESKD patients have not been extensively investigated. Methods: We conducted a comprehensive literature search, utilizing databases such as MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, up to September 2022. The purpose was to identify documented cases of CIE among patients with CKD or ESKD. Employing a random-effects model, we calculated the pooled incidence and odds ratio (OR) of CIE in CKD/ESKD patients. Results: Our search yielded a total of eleven articles, comprising nine case reports and two observational studies. Among these studies, 2 CKD patients and 12 ESKD patients with CIE were identified. The majority of the CKD/ESKD patients with CIE (93%) had undergone intra-arterial contrast media and/or endovascular procedures to diagnose acute cerebrovascular disease, coronary artery disease, and peripheral artery disease. The male-to-female ratio was 64%, and the median age was 63 years (with an interquartile range of 55 to 68 years). In the two observational studies, the incidence of CIE was found to be 6.8% in CKD patients and 37.5% in ESKD patients, resulting in a pooled incidence of 16.4% (95% CI, 2.4%–60.7%) among the CKD/ESKD patients. Notably, CKD and ESKD were significantly associated with an increased risk of CIE, with ORs of 5.77 (95% CI, 1.37–24.3) and 223.5 (95% CI, 30.44–1641.01), respectively. The overall pooled OR for CIE in CKD/ESKD patients was 32.9 (95% CI, 0.89–1226.44). Although dialysis prior to contrast exposure did not prevent CIE, approximately 92% of CIE cases experienced recovery after undergoing dialysis following contrast exposure. However, the effectiveness of dialysis on CIE recovery remained uncertain, as there was no control group for comparison. Conclusions: In summary, our study indicates an association between CIE and CKD/ESKD. While patients with CIE showed signs of recovery after dialysis, further investigations are necessary, especially considering the lack of a control group, which made the effects of dialysis on CIE recovery uncertain. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archaeology in Oceania is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Known almost exclusively now as the author of The Spectator and Cato , Joseph Addison was also highly regarded throughout the eighteenth and nineteenth centuries as a Latin poet. This article presents a new addition to the canon of Addison's Latin verse: a 57-line hexameter poem entitled Arcus Triumphalis which survives in a unique manuscript copy recently acquired by Addison's alma mater Magdalen College, Oxford. The article begins by describing the manuscript (scans of the leaves containing Addison's poem are included), detailing its likely genesis and confirming its attribution of the poem to Addison. Then it reconstructs the contexts of the poem, which describes a firework display put on in St James's Square on the evening of 2 December 1697 to celebrate William III's triumphal return to London after concluding the Peace of Ryswick. A third section provides a critical reading of the poem, concentrating on its surprising presentation of William III and its bold use of ekphrasis. The article concludes by assessing the place of Arcus Triumphalis in Addison's career, in relation to the early development of his Whiggism and as a forerunner of several of his definitive concerns in The Spectator : privacy and the public sphere, urban spectacle, and the aesthetics of looking. An edited text of the poem and an English translation are provided in an appendix. [ABSTRACT FROM AUTHOR]

We present the first observations of seismic waves propagating through the core of Mars. These observations, made using seismic data collected by the InSight geophysical mission, have allowed us to construct the first seismically constrained models for the elastic properties of Mars' core. We observe core-transiting seismic phase SKS from two farside seismic events detected on Mars and measure the travel times of SKS relative to mantle traversing body waves. SKS travels through the core as a compressional wave, providing information about bulk modulus and density. We perform probabilistic inversions using the core-sensitive relative travel times together with gross geophysical data and travel times from other, more proximal, seismic events to seek the equation of state parameters that best describe the liquid iron-alloy core. Our inversions provide constraints on the velocities in Mars' core and are used to develop the first seismically based estimates of its composition. We show that models informed by our SKS data favor a somewhat smaller (median core radius = 1,780 to 1,810 km) and denser (core density = 6.2 to 6.3 g/cm3) core compared to previous estimates, with a P-wave velocity of 4.9 to 5.0 km/s at the core-mantle boundary, with the composition and structure of the mantle as a dominant source of uncertainty. We infer from our models that Mars' core contains a median of 20 to 22 wt% light alloying elements when we consider sulfur, oxygen, carbon, and hydrogen. These data can be used to inform models of planetary accretion, composition, and evolution. [ABSTRACT FROM AUTHOR]

Two human genetic tubulopathies, Bartter's (BS) and Gitelman's (GS) syndromes, have normo/hypotension and absent cardiac remodeling despite their apparent angiotensin system (RAS) activation. This seeming contradiction has led to an extensive investigation of BSGS patients, the result of which is that BSGS represents a mirror image of hypertension. BSGS's unique set of properties has then permitted their use as a human model to probe and characterize RAS system pathways and oxidative stress in cardiovascular and renal remodeling and pathophysiology. This review details the results using GSBS patients that provide a deeper understanding of Ang II signaling and its associated oxidants/oxidative stress in humans. By providing a more complete and complex picture of cardiovascular and renal remodeling pathways and processes, studies of GSBS can inform the identification and selection of new targets and therapies to treat these and other oxidant-related disorders. [ABSTRACT FROM AUTHOR]

COVID-19, Brexit, war, and some other similar cases will leave/have left us with a lesson that has had an impact on the supply chains of almost all product types. Countries have now recognized that some products cannot be sustained in a situation of uncertainty. This research covers the gap in understanding and identifying the successful factors affecting the criticality level of supply required of intermediate and final products (IFP) at the national level. It investigates the relationship between two factors: the casual factor supply risk (independent factor); and the impacted (dependent factors) political, economic, sociocultural, and technological (PEST) factors in terms of identifying critical products using the principle of Resource Dependency Theory (RDT). A literature review was conducted, followed by a mixed-method approach. Semi-structured interviews with 23 Saudi experts were carried out initially; then, a questionnaire was shared with 152 Saudi experts in different sectors. The qualitative study identified 30 key measurement variables for both factors, in which 19 variables were confirmed using the factor analysis (FA) technique. [ABSTRACT FROM AUTHOR]

NASA's InSight has detected a large magnitude seismic event, labeled S1222a. The event has a moment magnitude of MWMa ${\mathrm{M}}_{\mathrm{W}}^{\text{Ma}}$4.7, with five times more seismic moment compared to the second largest event. The event is so large that features are clearly observed that were not seen in any previously detected events. In addition to body phases and Rayleigh waves, we also see Love waves, minor arc surface wave overtones, and multi‐orbit surface waves. At long periods, the coda event exceeds 10 hr. The event locates close to the North‐South dichotomy and outside the tectonically active Cerberus Fossae region. S1222a does not show any evident geological or tectonic features. The event is extremely rich in frequency content, extending from below 1/30 Hz up to 35 Hz. The event was classified as a broadband type event; we also observe coda decay and polarization similar to that of very high frequency type events. Plain Language Summary: After 3 years of seismic monitoring of Mars by InSight Seismic Experiment for Interior Structure instrument, we detected a marsquake largest ever observed during the mission. The event is larger by factor of 5 in seismic moment compared to previously detected events. With such an energetic event, we discovered various seismic features that was never observed before. For the first time, we were able to detect body waves and surface waves with their overtones. The large variety of detected seismic phases will enable us to probe the internal structure of Mars. Second, the event was located outside a well‐known seismically active region of Cerberus Fossae. This might indicate that event do not come from the same fault system with other major marsquakes. Finally, this event shows simultaneously features of marsquakes that were previously classified into different types. S1222a is classified as a broadband event with a wide frequency range of seismic energy. At the same time, the coda shape and decay at high frequency resembles that of very high frequency type events. It was an open question how different types of marsquakes are excited of what makes such differences and such event will be a key to uncover such mystery of marsquakes. Key Points: InSight detected on 4 May 2022 a MWMa ${\mathrm{M}}_{\mathrm{W}}^{\text{Ma}}$4.7 marsquake, S1222a, which is the largest seismic event detected so farThe exceptional signal‐to‐noise allows multiple phases to be identified, with a rich collection of surface wavesS1222a was located 37° southeast of the InSight landing site and close to the Martian dichotomy boundary [ABSTRACT FROM AUTHOR]

The shallowest intracrustal layer (extending to 8 ± 2 km depth) beneath the Mars InSight Lander site exhibits low seismic wave velocity, which is likely related to a combination of high porosity and other lithological factors. The SsPp phase, an SV‐ to P‐wave reflection on the receiver side, is naturally suited for constraining the seismic structure of this top crustal layer since its prominent signal makes it observable with a single station without the need for stacking. We have analyzed six broadband and low‐frequency seismic events recorded on Mars and made the first coherent detection of the SsPp phase on the red planet. The timing and amplitude of SsPp confirm the existence of the ∼8 km interface in the crust and the large wave speed (or impedance) contrast across it. With our new constraints from the SsPp phase, we determined that the average P‐wave speed in the top crustal layer is between 2.5 and 3.2 km/s, which is a more precise and robust estimate than the previous range of 2.0–3.5 km/s obtained by receiver function analysis. The low velocity of Layer 1 likely results from the presence of relatively low‐density lithified sedimentary rocks and/or aqueously altered igneous rocks that also have a significant amount of porosity, possibly as much as 22%–30% by volume (assuming an aspect ratio of 0.1 for the pore space). These porosities and average P‐wave speeds are compatible with our current understanding of the upper crustal stratigraphy beneath the InSight Lander site. Plain Language Summary: The NASA InSight mission sent a seismometer to Mars in 2018. One of the science goals of the mission is to better understand how rocky planets form and evolve by investigating the interior structure of Mars. Previous seismological studies with InSight data have revealed a shallow crustal layer (i.e., Layer 1, extending to 8 ± 2 km depth) with low seismic wave speed under the instrument. In this study, we have identified a new seismic signal on the seismograms recorded on Mars. The existence of this seismic phase confirmed the low speed of compressional (P) waves in Layer 1 and provided additional constraints on the average P‐wave speed, that is, between 2.5 and 3.2 km/s. Based on these low speeds, we found that the seismic properties of Layer 1 likely result primarily from the presence of sedimentary rocks and/or aqueously altered igneous rocks that also have a significant amount of porosity, possibly as much as ∼30% by volume. These porosities and average P‐wave speeds are compatible with our current understanding of the upper crustal stratigraphy beneath the InSight Lander site. Key Points: We analyzed marsquakes and made the first coherent detection of the SsPp phase (an SV‐ to P‐wave reflection on the receiver side)We determined that the average P‐wave speed in the top crustal layer (Layer 1, above 8 km) is between 2.5 and 3.2 km/sThe average P‐wave speed in Layer 1 is consistent with the current understanding of the upper crustal stratigraphy beneath InSight [ABSTRACT FROM AUTHOR]

The principal hormonal product of the thyroid gland, L-thyroxine (T4), is a prohormone for 3,3’,5-triiodo-L-thyronine, T3, the major ligand of nuclear thyroid hormone receptors (TRs). At a cell surface thyroid hormone analogue receptor on cancer cell and endothelial cell plasma membrane integrin avb3, however, T4 at physiological concentrations is biologically active and is the major ligand. At this site in solid tumor cells, T4 nongenomically initiates cell proliferation, is anti-apoptotic by multiple mechanisms, supports radioresistance and enhances cancer-related angiogenesis. In contrast, hypothyroidism has been reported clinically to slow tumor growth. At physiological levels, T3 is not biologically active at the integrin and maintenance of euthyroidism with T3 in cancer patients may be associated with slowed tumor proliferation. Against this background, we raise the possibility that host serum T4 levels that are spontaneously in the upper tertile or quartile of the normal range in cancer patients may be a factor that contributes to aggressive tumor behavior. Recent observations on tumor metastasis and tumor-associated propensity for thrombosis due to T4 also justify clinical statistical analysis for a relationship to upper tertile hormone levels. That reverse T3 (rT3) may stimulate tumor growth has recently been reported and thus the utility of adding this measurement to thyroid function testing in cancer patients requires assessment. In summary, T4 at physiological concentrations promotes tumor cell division and aggressiveness and euthyroid hypothyroxinemia arrests clinically advanced solid tumors. These findings support the clinical possibility that T4 levels in the upper tertile of the normal range require examination as a tumor supporting factor. [ABSTRACT FROM AUTHOR]

This paper discusses challenges for M&S if it is to be increasingly important to decision aiding and policy analysis. It suggests an approach that—from the outset of a policy analysis project—incorporates M&S of a varied resolution with the intent that (1) the results of analysis will be communicated with a relatively simple model and corresponding narrative that scans the system problem in breadth, having been informed by richer modeling, and (2) the broad view is supplemented by the selective detail (zooms) and selected change of the perspective as needed. This is not just a matter of "dumbing down" communication, but a matter of thinking about both forests and trees from the outset and about designing analytic tools accordingly. It will also enable exploratory analysis amidst uncertainty and disagreement, which is central to modern policy analysis and decision-aiding. All of this poses significant challenges for those who design and build M&S. [ABSTRACT FROM AUTHOR]

When behaviours or character traits match sociocultural expectation, heteronomy is a natural suspicion. A further natural suspicion is that the behaviours or character traits are unhealthy for the agent or for objectives of social justice and liberation. Second Wave feminism therefore includes a robust narrative of unease about female self-sexualisation. Third Wave feminism has more upbeat narratives of the latter, in terms of confidence and empowerment. The preceding tension is refracted through cases such as Ronda Rousey and 'derby girls', as well as those of many less ostentatious women. It is argued that such self-sexualisation can be autonomous as opposed to heteronomous. It is argued, furthermore, that it is not a priori unhealthy for the agent and that autonomous female self-sexualisation admits of degrees of self-consciousness and articulacy. At the same time, such self-sexualisation takes place within gendered social structures, with consequences that legitimate the reinvocation of Second Wave motifs such as the commodification of female sexuality and the privileging of precise images of female sexuality. [ABSTRACT FROM AUTHOR]

We have observed both minor‐arc (R1) and major‐arc (R2) Rayleigh waves for the largest marsquake (magnitude of 4.7 ± 0.2) ever recorded. Along the R1 path (in the lowlands), inversion results show that a simple, two‐layer model with an interface located at 21–29 km and an upper crustal shear‐wave velocity of 3.05–3.17 km/s can fit the group velocity measurements. Along the R2 path, observations can be explained by upper crustal thickness models constrained from gravity data and upper crustal shear‐wave velocities of 2.61–3.27 and 3.28–3.52 km/s in the lowlands and highlands, respectively. The shear‐wave velocity being faster in the highlands than in the lowlands indicates the possible existence of sedimentary rocks, and relatively higher porosity in the lowlands. Plain Language Summary: The largest marsquake ever recorded occurred recently and waves propagating at the surface, called surface waves, have been observed. Owing to the relatively large magnitude (i.e., 4.7 ± 0.2) of this event, surface wave energy is still clearly visible after one orbit around the red planet. The shortest path taken by the wave propagating between the source and the receiver is located in the northern lowlands, near the boundary with the southern highlands (called dichotomy). The surface wave traveling in the opposite direction, following the longer distance between the quake and the seismic station, mostly passes through the highlands. Analyses of these two paths reveal that the average shear‐wave velocity is faster in the highlands than in the lowlands near the dichotomy boundary. This lower velocity in the lowlands may be due to the presence of thick accumulations of sedimentary rocks and relatively higher porosity. Key Points: Analyses of the minor‐arc and major‐arc Rayleigh waves reveal different Martian crustal structures across the dichotomy boundaryThe average shear‐wave velocity is faster in the highlands than in the lowlands near the dichotomy boundaryThe lower shear‐wave velocity in the lowlands may be due to the presence of sedimentary rocks and relatively higher porosity [ABSTRACT FROM AUTHOR]

Thyroid hormone as L-thyroxine (T4) acts nongenomically at physiological concentrations at its cancer cell surface receptor on integrin ανβ3 ('thyrointegrin') to cause cancer cell proliferation. In the case of estrogen receptor (ERα)-positive breast cancer cells, T4 via the integrin promotes ERa-dependent cancer growth in the absence of estrogen. Thus, tumor growth in the post-menopausal patient with ERα-positive cancer may again be ER-dependent because of T4. Additional mechanisms by which T4 may contribute uniquely to aggressive breast cancer behavior--independently of ER --are stimulation of immune checkpoint inhibitor gene expression and of several anti-apoptosis mechanisms. These observations may call for consideration of elimination of host T4 production in breast cancer patients whose response is suboptimal to standard chemotherapy regimens. Euthyroidism in such a setting may be maintained with exogenous 3,3',5-triiodo-L-thyronine (T3). [ABSTRACT FROM AUTHOR]

The article focuses on the historical significance of the Scanlon Plan and the Scanlon Leadership Network in shaping collaborative workplaces. Topics include the origins of the Scanlon organization; its decline in 2013; the importance of Joe Scanlon's vision in humanizing the workplace; and the relevance of Scanlon principles to servant-leadership and the interconnected dreams of Joe Scanlon, Carl Frost and Robert K. Greenleaf in creating innovative and collaborative organizational cultures.

During the COVID-19 pandemic, a low rate of SARS-CoV-2 infection, with mild disease manifestations were reported in FD patients [[6]]. Dear Editor, Angiotensin-converting enzyme 2 (ACE2) has attracted widespread research attention given its role as a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic [Supplementary ref. 1]. We also found a low rate of SARS-CoV-2 infection upon surveying our cohort of 40 ERT-treated FD patients, where only one patient tested positive for COVID-19 with only minor symptoms [[7]]. [Extracted from the article]

A queueing theory based model of mTOR complexes impact on Akt-mediated cell response to insulin is presented in this paper. The model includes several aspects including the effect of insulin on the transport of glucose from the blood into the adipocytes with the participation of GLUT4, and the role of the GAPDH enzyme as a regulator of mTORC1 activity. A genetic algorithm was used to optimize the model parameters. It can be observed that mTORC1 activity is related to the amount of GLUT4 involved in glucose transport. The results show the relationship between the amount of GAPDH in the cell and mTORC1 activity. Moreover, obtained results suggest that mTORC1 inhibitors may be an effective agent in the fight against type 2 diabetes. However, these results are based on theoretical knowledge and appropriate experimental tests should be performed before making firm conclusions. [ABSTRACT FROM AUTHOR]

Wastewater-based epidemiology (WBE) has emerged as a valuable epidemiologic tool to detect the presence of pathogens and track disease trends within a community. WBE overcomes some limitations of traditional clinical disease surveillance as it uses pooled samples from the entire community, irrespective of health-seeking behaviors and symptomatic status of infected individuals. WBE has the potential to estimate the number of infections within a community by using a mass balance equation, however, it has yet to be assessed for accuracy. We hypothesized that the mass balance equation-based approach using measured SARS-CoV-2 wastewater concentrations can generate accurate prevalence estimates of COVID-19 within a community. This study encompassed wastewater sampling over a 53-week period during the COVID-19 pandemic in Gainesville, Florida, to assess the ability of the mass balance equation to generate accurate COVID-19 prevalence estimates. The SARS-CoV-2 wastewater concentration showed a significant linear association (Parameter estimate = 39.43, P value < 0.0001) with clinically reported COVID-19 cases. Overall, the mass balance equation produced accurate COVID-19 prevalence estimates with a median absolute error of 1.28%, as compared to the clinical reference group. Therefore, the mass balance equation applied to WBE is an effective tool for generating accurate community-level prevalence estimates of COVID-19 to improve community surveillance. [ABSTRACT FROM AUTHOR]

The article presents the views of late U. S. senator John McCain in contrast to other American politicians, regarding Vladimir Putin's personality and foreign policy. Topics include Putin was a lieutenant colonel in the KGB and served in Communist East Germany during the Cold War; Putin had used GRU (military intelligence) kill and critically injure Russian critics.; and Putin's demonstration of authoritarianism is a threat to the free nations and it should stand firm in defense of democracy.

Molecular aggregates are of interest to a broad range of fields including light harvesting, organic optoelectronics, and nanoscale computing. In molecular aggregates, nonradiative decay pathways may emerge that were not present in the constituent molecules. Such nonradiative decay pathways may include singlet fission, excimer relaxation, and symmetry-breaking charge transfer. Singlet fission, sometimes referred to as excitation multiplication, is of great interest to the fields of energy conversion and quantum information. For example, endothermic singlet fission, which avoids energy loss, has been observed in covalently bound, linear perylene trimers and tetramers. In this work, the electronic structure and excited-state dynamics of dimers of a perylene derivative templated using DNA were investigated. Specifically, DNA Holliday junctions were used to template the aggregation of two perylene molecules covalently linked to a modified uracil nucleobase through an ethynyl group. The perylenes were templated in the form of monomer, transverse dimer, and adjacent dimer configurations. The electronic structure of the perylene monomers and dimers were characterized via steady-state absorption and fluorescence spectroscopy. Initial insights into their excited-state dynamics were gleaned from relative fluorescence intensity measurements, which indicated that a new nonradiative decay pathway emerges in the dimers. Femtosecond visible transient absorption spectroscopy was subsequently used to elucidate the excited-state dynamics. A new excited-state absorption feature grows in on the tens of picosecond timescale in the dimers, which is attributed to the formation of perylene anions and cations resulting from symmetry-breaking charge transfer. Given the close proximity required for symmetry-breaking charge transfer, the results shed promising light on the prospect of singlet fission in DNA-templated molecular aggregates. [ABSTRACT FROM AUTHOR]

Perceptions of teammates and training load have been shown to influence athletes’ physical and psychological health; however, limited research has investigated these factors in relation to burnout. Athletes (N = 140) from a variety of competitive team sports, ranging in level from regional to professional, completed questionnaires measuring individual burnout, perceptions of teammates’ burnout, and training hours per week on two occasions separated by three months. After controlling for burnout at time one, training hours were associated with athletes’ burnout and perceptions of teammates’ burnout at time two. Multilevel modeling indicated actual team burnout (i.e., the average burnout score of the individual athletes in a team) and perceived team burnout were associated with individual’s own burnout. The findings highlight that burnout is dynamic and relates to physiological stressors associated with training and psychological perceptions of teammates’ burnout. Future research directions exploring potential social influences on athlete burnout are presented. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the influence of flotation REST upon skilled and less skilled golfers’ anxiety in terms of physiological indicators of stress, self-rated anxiety scores, muscle tension, and the effect on golf putting. Prior to performing the putting task participants underwent a treatment of flotation REST or a period of resting in an armchair. Participants completed both treatments in a randomized order with a two-week interval. The results showed that both flotation REST and the armchair treatment reduced systolic blood pressure and heart rate, with no differences between treatments or athlete skill levels. No significant differences between treatments were revealed regarding self-ratings, level of muscle tension or putting precision. The results indicate that flotation REST may be useful for reducing negative symptoms related to stress and anxiety in general; however, no support for direct positive effects on golf performance were found. [ABSTRACT FROM AUTHOR]

The magnetomechanical behavior of ferromagnetic shape memory alloys such as Ni-Mn-Ga, and hence the relationship between structure and nanoscale magnetomechanical properties, is of interest for their potential applications in actuators. Furthermore, due to its crystal structure, the behavior of Ni-Mn-Ga is anisotropic. Accordingly, nanoindentation and magnetic force microscopy were used to probe the nanoscale mechanical and magnetic properties of electropolished single crystalline 10M martensitic Ni-Mn-Ga as a function of the crystallographic c-axis (easy magnetization) direction relative to the indentation surface (i.e., c-axis in-plane versus out-of-plane). Load-displacement curves from 5–10 mN indentations on in-plane regions exhibited pop-in during loading, whereas this phenomenon was absent in out-of-plane regions. Additionally, the reduced elastic modulus measured for the c-axis out-of-plane orientation was ∼50% greater than for in-plane. Although heating above the transition temperature to the austenitic phase followed by cooling to the room temperature martensitic phase led to partial recovery of the indentation deformation, the magnitude and direction of recovery depended on the original relative orientation of the crystallographic c-axis: positive recovery for the in-plane orientation versus negative recovery (i.e., increased indent depth) for out-of-plane. Moreover, the c-axis orientation for out-of-plane regions switched to in-plane upon thermal cycling, whereas the number of twins in the in-plane regions increased. We hypothesize that dislocation plasticity contributes to the permanent deformation, while pseudoelastic twinning causes pop-in during loading and large recovery during unloading in the c-axis in-plane case. Minimization of indent strain energy accounts for the observed changes in twin orientation and number following thermal cycling. [ABSTRACT FROM AUTHOR]

The present study examines cricketers’ perceptions of emotional interactions between competitors. Semistructured interviews with 12 male professional cricketers explored experiences (i.e., emotions, cognitions, behaviors) relating to incidents during competition where they or an opponent attempted to evoke an emotional reaction (e.g., sledging). Cricketers described their use of sledging as aggressive actions and verbal interactions with the aim of disrupting concentration and altering the emotional states of opponents. They described experiencing a variety of emotions (e.g., anxiety, anger) in response to opponents’ attempts at interpersonal emotion regulation; linguistic analyses indicated that both positive than negative emotions were experienced. A range of strategies in response to competitors’ deliberate attempts at interpersonal emotion regulation were outlined. The present study extends previous research investigating interpersonal emotion regulation within teams by indicating that professional cricketers are aware of the impact of cognitions and emotions on performance and attempt to negatively influence these factors in competitors. [ABSTRACT FROM AUTHOR]

Lipoarabinomannan (LAM), a component of the Mycobacterium tuberculosis (MTB) cell wall, is detectable in the urine of MTB infected patients with active tuberculosis (TB). LAM-specific antibodies (Igs) have been developed by a variety of traditional and recombinant methods for potential use in a rapid diagnostic test (RDT). We evaluated the analytical performance of the TB LAM Igs to identify pairs that offer superior performance over existing urine LAM tests. We assessed 25 new and 4 existing Igs in a matrixed format using a multiplex electrochemiluminescence-based liquid immunoassay. A total of 841 paired Ig combinations were challenged with in vitro cultured LAM (cLAM) derived from MTB strains representing diverse phylogenetic lineages, alongside urinary LAM (uLAM) from the urine of adults with active pulmonary TB. Analytical sensitivity of down-selected Ig pairs was determined using MTB Aoyama-B cLAM, while diagnostic accuracy was determined using clinical samples. When testing cLAM, the reactivity of Ig pairs was similar across MTB lineages 1–4 but lineage 5:6 had significantly more reactivity among Ig pairs. Overall, 41 Ig pairs had a strong binding affinity to cLAM, as compared to the reference pair of S4-20/A194-01, and 28 Ig pairs therein exhibited a strong affinity for both cLAM and uLAM. Retrospective testing on clinical urine specimens demonstrated varying sensitivities (12–80%) and specificities (14–100%). The five top pairs had a similar analytical limit of detection to the reference pair but in four instances, the sensitivity and specificity with clinical uLAM samples was poor. Overall, epitopes presented by uLAM are different from cLAM, which may affect antibody performance when testing uLAM in patient samples. Several new Ig pairs had similar ranges of high sensitivity to cLAM but overall, there were no new candidate Ig pairs identified in this round of screening with increased performance with uLAM as compared to an existing optimal pair. [ABSTRACT FROM AUTHOR]

Thyroid hormones, T3 (triiodothyronine) and T4 (thyroxine), induce a variety of long-term effects on important physiological functions, ranging from development and growth to metabolism regulation, by interacting with specific nuclear or cytosolic receptors. Extranuclear or nongenomic effects of thyroid hormones are mediated by plasma membrane or cytoplasmic receptors, mainly by αvβ3 integrin, and are independent of protein synthesis. A wide variety of nongenomic effects have now been recognized to be elicited through the binding of thyroid hormones to this receptor, which is mainly involved in angiogenesis, as well as in cell cancer proliferation. Several signal transduction pathways are modulated by thyroid hormone binding to αvβ3 integrin: protein kinase C, protein kinase A, Src, or mitogen-activated kinases. Thyroid hormone-activated nongenomic effects are also involved in the regulation of Na+-dependent transport systems, such as glucose uptake, Na+/K+-ATPase, Na+/H+ exchanger, and amino acid transport System A. Of note, the modulation of these transport systems is cell-type and developmental stage-dependent. In particular, dysregulation of Na+/K+-ATPase activity is involved in several pathological situations, from viral infection to cancer. Therefore, this transport system represents a promising pharmacological tool in these pathologies. [ABSTRACT FROM AUTHOR]

Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvβ3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy. [ABSTRACT FROM AUTHOR]

When molecules are aggregated such that their excited states form delocalized excitons, their spatial arrangement, or packing, can be coarsely controlled by templating and finely controlled by chemical substitution; however, challenges remain in controlling their packing on intermediate length scales. Here, we use an approach based on mechanically interlocked molecules to promote an elusive oblique packing arrangement in a series of three squaraine rotaxane dimers. We template the squaraine rotaxane dimers using DNA and observe two excitonically split bands of near‐equal intensity in their absorption spectra – a distinct signature of oblique packing, validated by theoretical modeling of the experimental results. Additional fine control of packing is demonstrated by fluorinating the macrocycle of the rotaxane, which promotes denser packing and stronger excitonic interactions. [ABSTRACT FROM AUTHOR]

The radial forearm free flap (RFFF) is one option of many free-tissue flaps that is frequently selected to reconstruct defects of the head and neck. It is popular due to its relatively thin and pliable associated soft tissue, reliable supplying vasculature, and appropriate diameter and length of the supplying vessels to perform microvascular anastomosis. This case report describes the use of the RFFF to reconstruct an oral cavity defect following tumor resection in a patient who required adjustment of the typical RFFF design. This patient has a significant psychiatric history leading to self-induced forearm lacerations that resulted in substantial scarring of her bilateral forearms in the anatomical area typically included in the RFFF. Since the RFFF was the optimal reconstructive option for this patient, the design of the RFFF was able to be moved proximally up her forearm to avoid inclusion of the scars in the flap. Adequate blood flow of the ulnar artery was confirmed with an Allen0s test preoperatively to ensure the radial artery could be taken as part of the RFFF without causing ischemia of the hand. Following surgical resection of the patient0s tumor, the RFFF was harvested and inset to reconstruct the resulting oral cavity defect. The patient has had no complications following her resection and reconstruction to date. This report highlights the adaptability of the RFFF, allowing adjustments to typical flap design to optimize outcomes for each individualized patient. [ABSTRACT FROM AUTHOR]

Lacking in the philosophy of sport is discussion of the gendered numbers of sets played in Grand Slam tennis. We argue that the practice is indefensible. It can be upheld only through false beliefs about women or repressive femininity ideals. It treats male tennis players unfairly in forcing them to play more sets because of their sex. Its ideological consequences are pernicious, since it reinforces the respective identifications of the female and male with physical limitation and heroism. Both sexes have compelling reason to reject the practice. [ABSTRACT FROM AUTHOR]

Heteronemin (Haimian jing) is a sesterterpenoid-type natural marine product that is isolated from sponges and has anticancer properties. It inhibits cancer cell proliferation via different mechanisms, such as reactive oxygen species (ROS) production, cell cycle arrest, apoptosis as well as proliferative gene changes in various types of cancers. Recently, the novel structure and bioactivity evaluation of heteronemin has received extensive attention. Hormones control physiological activities regularly, however, they may also affect several abnormalities such as cancer. L-Thyroxine (T4), steroid hormones, and epidermal growth factor (EGF) up-regulate the accumulation of checkpoint programmed death-ligand 1 (PD-L1) and promote inflammation in cancer cells. Heteronemin suppresses PD-L1 expression and reduces the PD-L1-induced proliferative effect. In the current review, we evaluated research and evidence regarding the antitumor effects of heteronemin and the antagonizing effects of non-peptide hormones and growth factors on heteronemin-induced anti-cancer properties and utilized computational molecular modeling to explain how these ligands interacted with the integrin αvβ3 receptors. On the other hand, thyroid hormone deaminated analogue, tetraiodothyroacetic acid (tetrac), modulates signal pathways and inhibits cancer growth and metastasis. The combination of heteronemin and tetrac derivatives has been demonstrated to compensate for anti-proliferation in cancer cells under different circumstances. Overall, this review outlines the potential of heteronemin in managing different types of cancers that may lead to its clinical development as an anticancer agent. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones (TH), T4 and T3, mediate pro-mitogenic effects in cancer cells through binding the membrane receptor αvβ3 integrin. The deaminated analogue tetrac effectively blocks TH binding to this receptor and prevents their action. While computational data on TH binding to the αvβ3 integrin was published, a comprehensive analysis of additional TH metabolites is lacking. Methods: In-silico docking of 26 TH metabolites, including the biologically active thyroid hormones (T3 and T4) and an array of sulfated, deiodinated, deaminated or decarboxylated metabolites, to the αvβ3 receptor binding pocket was performed using DOCK6, based on the three-dimensional representation of the crystallographic structure of the integrin. As the TH binding site upon the integrin is at close proximity to the well-defined RGD binding site, linear and cyclic RGD were included as a reference. Binding energy was calculated for each receptor-ligand complex using Grid score and Amber score with distance movable region protocol. Results: All TH molecules demonstrated negative free energy, suggesting affinity to the αvβ3 integrin. Notably, based on both Grid and Amber scores sulfated forms of 3,3' T2 (3,3' T2S) and T4 (T4S) demonstrated the highest binding affinity to the integrin, compared to both cyclic RGD and an array of examined TH metabolites. The major thyroid hormones, T3 and T4, showed high affinity to the integrin, which was superior to that of linear RGD. For all hormone metabolites, decarboxylation led to decreased affinity. This corresponds with the observation that the carboxylic group mediates binding to the integrin pocket via divalent cations at the metal-ion-dependent adhesion (MIDAS) motif site. A similar reduced affinity was documented for deaminated forms of T3 (triac) and T4 (tetrac). Lastly, the reverse forms of T3, T3S, and T3AM showed higher Amber scores relative to their native form, indicating that iodination at position 5 is associated with increased binding affinity compared to position 5'. Summary: Three-dimensional docking of various TH metabolites uncovered a structural basis for a differential computational free energy to the αvβ3 integrin. These findings may suggest that naturally occurring endogenous TH metabolites may impact integrin-mediate intracellular pathways in physiology and cancer. [ABSTRACT FROM AUTHOR]