gebhart/patrepeval huggingface dataset:
Intermediate Partitioning Kinetic Isotope Effects for the NIH Shift of 4-Hydroxyphenylpyruvate Dioxygenase and the Hydroxylation Reaction of Hydroxymandelate Synthase Reveal Mechanistic Complexity (2013)

4-Hydroxyphenylpyruvate dioxygenase (HPPD) and hydroxymandelate synthase (HMS) are similar enzymes that catalyze complex dioxygenation reactions using the substrates 4-hydroxyphenylpyruvate (HPP) and dioxygen. Both enzymes decarboxylate HPP and then hydroxylate the resulting hydroxyphenylacetate (HPA). The hydroxylation reaction catalyzed by HPPD displaces the aceto substituent of HPA in a 1,2-shift to form 2,5-dihydroxyphenylacetate (homogentisate, HG), whereas the hydroxylation reaction of HMS places a hydroxyl on the benzylic carbon forming 3'-hydroxyphenylacetate (S-hydroxymandelate, HMA) without ensuing chemistry. The wild-type form of HPPD and variants of both enzymes uncouple to form both native and non-native products. We have used intermediate partitioning to probe bifurcating steps that form these products by substituting deuteriums for protiums at the benzylic position of the HPP substrate. These substitutions result in altered ratios of products that can be used to calculate kinetic isotope effects (KIE) for the formation of a specific product. For HPPD, secondary normal KIEs indicate that cleavage of the bond in the displacement reaction prior to the shift occurs by a homolytic mechanism. NMR analysis of HG derived from HPPD reacting with enantiomerically pure R-3'-deutero-HPP indicates that no rotation about the bond to the radical occurs, suggesting that collapse of the biradical intermediate is rapid. The production of HMA was observed in HMS and HPPD variant reactions. HMS hydroxylates to form exclusively S-hydroxymandelate. When HMS is reacted with R-3'-deutero-HPP, the observed kinetic isotope effect represents geometry changes in the initial transition state for the nonabstracted proton. These data show evidence of sp(3) hybridization in a HPPD variant and sp(2) hybridization in HMS variants, suggesting that HMS stabilizes a more advanced transition state in order to catalyze H-atom abstraction.
Human PrimPol activity is enhanced by RPA (2017)

Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.
Racism, structural racism, and the American Association for Anatomy: Initial report from a task force (2022)

In 2021, the American Association for Anatomy (AAA) Board of Directors appointed a Task Force on Structural Racism to understand how the laws, rules, and practices in which the Association formed, developed and continues to exist affect membership and participation. This commentary is the first public report from the Task Force. We focus on African Americans with some comments on Jews and women, noting that all marginalized groups deserve study. Through much of its 130 year history, some members were an essential part of perpetuating racist ideas, the Association largely ignored racism and had some practices that prevented participation. The Task Force concluded that individual and structural racism within the AAA, combined with the broader social context in which the Association developed, contributed to the current underrepresentation of African Americans who constitute 4.1% of the membership even though 13.4% of the U.S. population is Black. Intentional efforts within the AAA to reckon with racism and other forms of bias have only begun in the last 10-20 years. These actions have led to more diverse leadership within the Association, and it is hoped that these changes will positively affect the recruitment and retention of marginalized people to science in general and anatomy in particular. The Task Force recommends that the AAA Board issue a statement of responsibility to acknowledge its history. Furthermore, the Task Force advocates that the Board commit to (a) sustaining ongoing projects to improve diversity, equity, and inclusion and (b) dedicating additional resources to facilitate novel initiatives.
MicroRNA-34a induces endothelial progenitor cell senescence and impedes its angiogenesis via suppressing silent information regulator 1 (2010)

Endothelial progenitor cells (EPCs) play an important role in angiogenesis, which is essential for numerous physiological processes as well as tumor growth. Several microRNAs (miRNAs) have been reported to be involved in angiogenesis. MiR-34a, recently reported as a tumor suppressor, has been found to target silent information regulator 1 (Sirt1), leading to cell cycle arrest or apoptosis. However, the role of miR-34a in EPC-mediated angiogenesis was unknown. The present study tested the hypothesis that miR-34a inhibits EPC-mediated angiogenesis by inducing senescence via suppressing Sirt1. Bone marrow-derived EPCs from adult male Sprague-Dawley rats were used. Results of flow cytometry showed that EPCs after 7 days of culture expressed both stem cell markers CD34 and CD133 and endothelial cell markers VEGFR-2 (flk-1) and VE-cadherin. MiR-34a was expressed in normal EPCs, and overexpression of miR-34a via its mimic transfection significantly increased its expression and impaired in vitro EPC angiogenesis. MiR-34a overexpression led to a significantly increased EPC senescence, paralleled with an approximately 40% Sirt1 reduction. Furthermore, knockdown of Sirt1 by its siRNA resulted in diminished EPC angiogenesis and increased senescence. Finally, overexpression of miR-34a increased the level of Sirt1 effector-acetylated forkhead box O transcription factors 1 (FoxO1), an effect mimicked in EPCs following Sirt1 knockdown. In conclusion, miR-34a impairs EPC-mediated angiogenesis by induction of senescence via inhibiting Sirt1.
Applications of Smartphone-Based Sensors in Agriculture: A Systematic Review of Research (2015)

Smartphones have become a useful tool in agriculture because their mobility matches the nature of farming, the cost of the device is highly accessible, and their computing power allows a variety of practical applications to be created. Moreover, smartphones are nowadays equipped with various types of physical sensors which make them a promising tool to assist diverse farming tasks. This paper systematically reviews smartphone applications mentioned in research literature that utilize smartphone built-in sensors to provide agricultural solutions. The initial 1,500 articles identified through database search were screened based on exclusion criteria and then reviewed thoroughly in full text, resulting in 22 articles included in this review. The applications are categorized according to their agricultural functions. Those articles reviewed describe 12 farming applications, 6 farm management applications, 3 information system applications, and 4 extension service applications. GPS and cameras are the most popular sensors used in the reviewed papers. This shows an opportunity for future applications to utilize other sensors such as accelerometer to provide advanced agricultural solutions.
Sarcopenia: characteristics, mechanisms and functional significance (2010)

Sarcopenia reflects a progressive withdrawal of anabolism and an increased catabolism, along with a reduced muscle regeneration capacity. Muscle force and power decline more than muscle dimensions: older muscle is intrinsically weak. Sarcopenic obesity (SO) among the elderly corroborates to the loss of muscle mass increasing the risk of metabolic syndrome development. Recent studies on the musculoskeletal adaptations with ageing and key papers on the mechanisms of muscle wasting, its functional repercussions and on SO are included. Neuropathic, hormonal, immunological, nutritional and physical activity factors contribute to sarcopenia. Selective fast fibre atrophy, loss of motor units and an increase in hybrid fibres are typical findings of ageing. Satellite cell number decreases reducing muscle regeneration capacity. SO promotes further muscle wasting and increases risk of metabolic syndrome development. The proportion of fast to slow fibres seems maintained in old age. In elderly humans, nuclear domain is maintained constant. Basal protein synthesis and breakdown show little changes in old age. Instead, blunting of the anabolic response to feeding and exercise and of the antiproteolytic effect of insulin is observed. Further understanding of the mechanisms of sarcopenia requires disentangling of the effects of ageing alone from those of disuse and disease. The causes of the greater anabolic resistance to feeding and exercise of elderly women need elucidating. The enhancement of muscle regeneration via satellite cell activation via the MAPK/notch molecular pathways seems particularly promising.
Vibration control of a coupled nonlinear string system in transverse and longitudinal directions (2011)

In this paper, vibration control is considered in both transverse and longitudinal directions for a coupled nonlinear flexible string system. The vibrating string is nonlinear due to the consideration of the coupling between transverse and longitudinal displacements. By using Hamilton's principle, the dynamics of the nonlinear string are presented by two partial differential equations (PDEs) and four ordinary differential equations (ODEs). Based on Lyapunov's direct method, boundary control is constructed to regulate the string's vibration and stabilize the system. Numerical simulations are provided to demonstrate the effectiveness of the proposed control.
Design of recursive group-delay filters by autoregressive modeling (1982)

A new method of design of recursive group-delay filters is presented in this paper. The method uses autoregressive modeling to derive parameters of the filter. The design is based on the following line of argument. The desired group-delay characteristics are to be realized through a stable all-pass filter. The transfer function of an all-pass filter is completely determined by the coefficients of either the numerator or the denominator polynomial. For a stable all-pass filter, the denominator polynomial must be a minimum phase polynomial. For a minimum phase polynomial, the magnitude function and the group-delay function are related through cepstral coefficients. Therefore, from the given group-delay specification, the cepstral coefficients corresponding to the pole part (inverse of the denominator polynomial) of the desired filter are first determined. The magnitude spectrum corresponding to these cepstral coefficients is approximated using autoregressive modeling. A wide variety of group-delay filters can be realized by the proposed method, depending on the nature of approximation used and the accuracy desired. The design procedure is illustrated through examples.
Development of a Translator from LLVM to ACL2 (2014)

In our current work a library of formally verified software components is to be created, and assembled, using the Low-Level Virtual Machine (LLVM) intermediate form, into subsystems whose top-level assurance relies on the assurance of the individual components. We have thus undertaken a project to build a translator from LLVM to the applicative subset of Common Lisp accepted by the ACL2 theorem prover. Our translator produces executable ACL2 formal models, allowing us to both prove theorems about the translated models as well as validate those models by testing. The resulting models can be translated and certified without user intervention, even for code with loops, thanks to the use of the def::ung macro which allows us to defer the question of termination. Initial measurements of concrete execution for translated LLVM functions indicate that performance is nearly 2.4 million LLVM instructions per second on a typical laptop computer. In this paper we overview the translation process and illustrate the translator's capabilities by way of a concrete example, including both a functional correctness theorem as well as a validation test for that example.
Conducting Non-adaptive Experiments in a Live Setting: A Bayesian Approach to Determining Optimal Sample Size (2019)

Abstract This research studies the use of predetermined experimental plans in a live setting with a finite implementation horizon. In this context, we seek to determine the optimal experimental budget in different environments using a Bayesian framework. We derive theoretical results on the optimal allocation of resources to treatments with the objective of minimizing cumulative regret, a metric commonly used in online statistical learning. Our base case studies a setting with two treatments assuming Gaussian priors for the treatment means and noise distributions. We extend our study through analytical and semi-analytical techniques which explore worst-case bounds, the presence of unequal prior distributions, and the generalization to k treatments. We determine theoretical limits for the experimental budget across all possible scenarios. The optimal level of experimentation that is recommended by this study varies extensively and depends on the experimental environment as well as the number of available units. This highlights the importance of such an approach which incorporates these factors to determine the budget.
Sleep Deprivation by Exposure to Novel Objects Increases Synapse Density and Axon–Spine Interface in the Hippocampal CA1 Region of Adolescent Mice (2019)

Sleep has been hypothesized to rebalance overall synaptic strength after ongoing learning during waking leads to net synaptic potentiation. If so, because synaptic strength and size are correlated, synapses on average should be larger after wake and smaller after sleep. This prediction was recently confirmed in mouse cerebral cortex using serial block-face electron microscopy (SBEM). However, whether these findings extend to other brain regions is unknown. Moreover, sleep deprivation by gentle handling was reported to produce hippocampal spine loss, raising the question of whether synapse size and number are differentially affected by sleep and waking. Here we applied SBEM to measure axon-spine interface (ASI), the contact area between pre-synapse and post-synapse, and synapse density in CA1 stratum radiatum. Adolescent YFP-H mice were studied after 6-8 h of sleep (S = 6), spontaneous wake at night (W = 4) or wake enforced during the day by novelty exposure (EW = 4; males/females balanced). In each animal ≥425 ASIs were measured and synaptic vesicles were counted in ~100 synapses/mouse. Reconstructed dendrites included many small, nonperforated synapses and fewer large, perforated synapses. Relative to S, ASI sizes in perforated synapses shifted toward higher values after W and more so after EW. ASI sizes in nonperforated synapses grew after EW relative to S and W, and so did their density. ASI size correlated with presynaptic vesicle number but the proportion of readily available vesicles decreased after EW, suggesting presynaptic fatigue. Thus, CA1 synapses undergo changes consistent with sleep-dependent synaptic renormalization and their number increases after extended wake.<b>SIGNIFICANCE STATEMENT</b> Sleep benefits learning, memory consolidation, and the integration of new with old memories, but the underlying mechanisms remain highly debated. One hypothesis suggests that sleep's cognitive benefits stem from its ability to renormalize total synaptic strength, after ongoing learning during wake leads to net synaptic potentiation. Supporting evidence for this hypothesis mainly comes from the cerebral cortex, including the observation that cortical synapses are larger after wake and smaller after sleep. Using serial electron microscopy, we find here that sleep/wake synaptic changes consistent with sleep-dependent synaptic renormalization also occur in the CA1 region. Thus, the role of sleep in maintaining synaptic homeostasis may extend to the hippocampus, a key area for learning and synaptic plasticity.
Re: Sim1 Neurons are Sufficient for MC4R-Mediated Sexual Function in Male Mice (2018)

No AccessJournal of UrologyUrological Survey1 Nov 2018Re: Sim1 Neurons are Sufficient for MC4R-Mediated Sexual Function in Male Mice Anthony AtalaMD Anthony AtalaAnthony Atala More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.07.076AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Sim1 Neurons are Sufficient for MC4R-Mediated Sexual Function in Male Mice." The Journal of Urology, 200(5), p. 948 © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 200Issue 5November 2018Page: 948 Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anthony Atala More articles by this author Expand All Advertisement PDF downloadLoading ...
Intragastric balloon for obesity (2007)

Evidence from this review is limited for decision making, since there was large heterogeneity in IGB trials, regarding both methodological and clinical aspects. However, a co-adjuvant factor described by some authors in the loss and maintenance of weight has been the motivation and the encouragement to changing eating habits following a well-organized diet and a program of behavioural modification. The IGB alone and the technique of positioning appear to be safe. Despite the evidence for little additional benefit of the intragastric balloon in the loss of weight, its cost should be considered against a program of eating and behavioural modification.
C1-Ten Is a Protein Tyrosine Phosphatase of Insulin Receptor Substrate 1 (IRS-1), Regulating IRS-1 Stability and Muscle Atrophy (2013)

Muscle atrophy occurs under various catabolic conditions, including insulin deficiency, insulin resistance, or increased levels of glucocorticoids. This results from reduced levels of insulin receptor substrate 1 (IRS-1), leading to decreased phosphatidylinositol 3-kinase activity and thereby activation of FoxO transcription factors. However, the precise mechanism of reduced IRS-1 under a catabolic condition is unknown. Here, we report that C1-Ten is a novel protein tyrosine phosphatase (PTPase) of IRS-1 that acts as a mediator to reduce IRS-1 under a catabolic condition, resulting in muscle atrophy. C1-Ten preferentially dephosphorylated Y612 of IRS-1, which accelerated IRS-1 degradation. These findings suggest a novel type of IRS-1 degradation mechanism which is dependent on C1-Ten and extends our understanding of the molecular mechanism of muscle atrophy under catabolic conditions. C1-Ten expression is increased by catabolic glucocorticoid and decreased by anabolic insulin. Reflecting these hormonal regulations, the muscle C1-Ten is upregulated in atrophy but downregulated in hypertrophy. This reveals a previously unidentified role of C1-Ten as a relevant PTPase contributing to skeletal muscle atrophy.
A Novel Radio-Over-Fiber System Based on Carrier Suppressed Frequency Eightfold Millimeter Wave Generation (2017)

We propose a novel and simple scheme for photonic frequency eightfold millimeter wave (mm-wave) generation with optical carrier suppression based on only one single-drive Mach–Zehnder modulator (MZM). According to our theoretical analysis and experimental demonstration, by adopting designed direct current bias voltage of MZM and the amplitude voltage of the radio frequency (RF) drive signal, two fourth-order optical subcarriers are generated via a single-drive MZM. Furthermore, the corresponding optical central carrier and undesired sidebands are suppressed simultaneously. Based on our proposed scheme, the generation of 72-GHz optical mm-wave by an RF signal of 9 GHz without any optical filtering is experimentally demonstrated. The radio-over-fiber system with 3.5-Gb/s OOK downstream link based on this generated 72-GHz mm-wave is also experimentally demonstrated. As we know, it is the first time to realize frequency eightfold mm-wave signal generation with simultaneous carrier suppression by using only one single-drive MZM in experiment.
Thermal and Chemical Expansion of Sr-Doped Lanthanum Cobalt Oxide (La1-xSrxCoO3-δ) (2005)

The equilibrium thermal expansivity (βT) and oxygen-vacancy chemical expansivity (βC) of polycrystalline La1-xSrxCoO3-δ (LSC; x = 0.2, 0.4, and 0.7) have been measured at 600 °C < T < 900 °C and 10-4 atm < PO2 < 0.21 atm using controlled-atmosphere dilatometry. These measurements show only a moderate dependence of βT on temperature, suggesting that increases often observed in the coefficient of thermal expansion when measured at constant PO2 are primarily thermally induced chemical expansion associated with changes in oxygen stoichiometry. The dependences of βT and βC on the temperature, oxygen-vacancy concentration, and Sr content (x) were characterized and found to follow a consistent nonlinear trend, which may result from the relaxation of lattice strain with increasing defect concentration. A slowly relaxing secondary expansion effect (and/or expansion hysteresis) was also discovered. Possible causes of this behavior, including phase transition/segregation at high vacancy concentration, are discussed.
Planning for a reverberation field experiment (2012)

A basic research reverberation experiment, supported by the US Office of Naval Research, is planned for 2013. Measurement issues that arise when planning such an experiment are discussed. The fundamental requirement for this basic research experiment is that the environment is characterized in sufficient detail to allow accurate numerical modeling of the acoustical results based on the environmental description. The main goal is to measure mid-frequency shallow water reverberation with full companion environmental measurements so that model/data can be compared without ambiguity. Included in the goal is to make statistical estimates of the uncertainties associated with all the environmental conditions. The frequency range of interest is 1-10 kHz with emphasis at 3 kHz. A pilot field experiment was conducted off the coast of Panama City, Florida. Data from the pilot experiment will be discussed in light of the forthcoming main experiment, including simulations on both propagation/forward-scatter and reverberation for given noise background on both vertical and horizontal arrays which will be deployed in the main experiment.