556 research outputs found
Catalytic promiscuity of a proline-based tautomerase: Aldolase activities and enzyme redesign
No full textNumerous enzymes have been found to catalyze additional and completely different types of reactions relative to the natural activity they evolved for. This interesting phenomenon, called catalytic promiscuity, has proven to be a fruitful guide for the development of novel biocatalysts for organic synthesis purposes. A remarkable example of an enzyme with catalytic promiscuity is 4-oxalocrotonate tautomerase (4-OT). This enzyme naturally catalyzes an enol-keto tautomerization step as part of a catabolic pathway for aromatic hydrocarbons, but can also promiscuously catalyze carbon-carbon bond-forming aldol and Michael-type addition reactions. Mehran Rahimi investigated the mechanism by which 4-OT catalyzes these unnatural reactions. Hydrogen-deuterium exchange and crystallographic studies of the enzyme in the presence of acetaldehyde provided strong evidence that the characteristic active site proline residue (Pro-1) of 4-OT reacts with acetaldehyde to give a covalent enamine species. A reaction between this nucleophilic intermediate and an electrophilic substrate, such as benzaldehyde or trans-β-nitrostyrene, results in carbon-carbon bond formation. Mehran Rahimi also discovered that 4-OT can promiscuously catalyze various inter- and intramolecular aldol reactions. By using a highly informative systematic mutagenesis strategy, ‘hotspot’ positions in 4-OT at which single mutations give a marked improvement in aldolase activity were identified. Activity screening of focused libraries in which only a few ‘hotspot’ positions were varied led to the discovery of 4-OT variants with strongly enhanced aldolase activities. Taken together, the results presented in Mehran Rahimi’s thesis demonstrate that a catalytically promiscuous tautomerase is a good starting point to develop novel biocatalysts for synthetically useful aldol reactions
Catalytic promiscuity of a proline-based tautomerase:Aldolase activities and enzyme redesign
No full textNumerous enzymes have been found to catalyze additional and completely different types of reactions relative to the natural activity they evolved for. This interesting phenomenon, called catalytic promiscuity, has proven to be a fruitful guide for the development of novel biocatalysts for organic synthesis purposes.A remarkable example of an enzyme with catalytic promiscuity is 4-oxalocrotonate tautomerase (4-OT). This enzyme naturally catalyzes an enol-keto tautomerization step as part of a catabolic pathway for aromatic hydrocarbons, but can also promiscuously catalyze carbon-carbon bond-forming aldol and Michael-type addition reactions.Mehran Rahimi investigated the mechanism by which 4-OT catalyzes these unnatural reactions. Hydrogen-deuterium exchange and crystallographic studies of the enzyme in the presence of acetaldehyde provided strong evidence that the characteristic active site proline residue (Pro-1) of 4-OT reacts with acetaldehyde to give a covalent enamine species. A reaction between this nucleophilic intermediate and an electrophilic substrate, such as benzaldehyde or trans-β-nitrostyrene, results in carbon-carbon bond formation.Mehran Rahimi also discovered that 4-OT can promiscuously catalyze various inter- and intramolecular aldol reactions. By using a highly informative systematic mutagenesis strategy, ‘hotspot’ positions in 4-OT at which single mutations give a marked improvement in aldolase activity were identified. Activity screening of focused libraries in which only a few ‘hotspot’ positions were varied led to the discovery of 4-OT variants with strongly enhanced aldolase activities.Taken together, the results presented in Mehran Rahimi’s thesis demonstrate that a catalytically promiscuous tautomerase is a good starting point to develop novel biocatalysts for synthetically useful aldol reactions
Catalytic promiscuity of a proline-based tautomerase:Aldolase activities and enzyme redesign
No full textNumerous enzymes have been found to catalyze additional and completely different types of reactions relative to the natural activity they evolved for. This interesting phenomenon, called catalytic promiscuity, has proven to be a fruitful guide for the development of novel biocatalysts for organic synthesis purposes.A remarkable example of an enzyme with catalytic promiscuity is 4-oxalocrotonate tautomerase (4-OT). This enzyme naturally catalyzes an enol-keto tautomerization step as part of a catabolic pathway for aromatic hydrocarbons, but can also promiscuously catalyze carbon-carbon bond-forming aldol and Michael-type addition reactions.Mehran Rahimi investigated the mechanism by which 4-OT catalyzes these unnatural reactions. Hydrogen-deuterium exchange and crystallographic studies of the enzyme in the presence of acetaldehyde provided strong evidence that the characteristic active site proline residue (Pro-1) of 4-OT reacts with acetaldehyde to give a covalent enamine species. A reaction between this nucleophilic intermediate and an electrophilic substrate, such as benzaldehyde or trans-β-nitrostyrene, results in carbon-carbon bond formation.Mehran Rahimi also discovered that 4-OT can promiscuously catalyze various inter- and intramolecular aldol reactions. By using a highly informative systematic mutagenesis strategy, ‘hotspot’ positions in 4-OT at which single mutations give a marked improvement in aldolase activity were identified. Activity screening of focused libraries in which only a few ‘hotspot’ positions were varied led to the discovery of 4-OT variants with strongly enhanced aldolase activities.Taken together, the results presented in Mehran Rahimi’s thesis demonstrate that a catalytically promiscuous tautomerase is a good starting point to develop novel biocatalysts for synthetically useful aldol reactions
Ecriture au feminin par procuration : Pierre de patience d'Atiq Rahimi
No full textThe author proposes a feminist interpretation of Pierre de patience, a novel by the afghan francophone writer Atiq Rahimi. He sees it as a francophone text come from elsewhere, as world literature, but also as a message and hope for our time and for gender equality
THE LURE OF THE IMAGE KEBOHONGAN PADA NARASI PEREMPUAN DALAM SYNGUE SABOUR PIERRE DE PATIENCE KARYA ATIQ RAHIMI
No full textThis study aims to determine the position of the author in women narration. With Rahimi’s background as a feminist, he said that with his novel he voiced the voices of Afghan women. Rahimi offered a strong female figure in the middle of the patriarchal shackles who is able to fight the system. The problem of this study is Rahimi’s ambiguity in narrating women. To determine the position of the author, the research uses the concept of the lure of the image belongs to Lidia Curti. The lure of the image is an offer provided by the author to give positions to women that are in fact not provided by them. Based on the research conducted, the results show that Rahimi keeps women as objects in a patriarchal world. In this case he is not able to pull the women out of the patriarchal zone. The space given to women by Rahimi reinforces male power. What Rahimi written in this novel is the lure of the image according to Curti’s concept which explains it as an image of women given by author or known as female gaze
Machine Learning in Feedback Systems: Provable Methods for Safe and Robust Autonomy
No full textThesis (Ph.D.)--University of Washington, 2024This dissertation explores the integration of machine learning into feedback control systems, addressing key challenges in the realm of control theory with a focus on autonomous navigation. Modern advances in sensing technologies and computational methods have enabled remarkable advancements in data-guided control. However, the reliability of machine learning, particularly deep learning, in safety-critical applications remains limited due to its inadequate handling of uncertainty. Furthermore, traditional methods in control theory impose limitations when the system is operating in complex environments with unknown uncertainties. This research seeks to bridge this gap by combining robust and optimal control techniques with machine learning to ensure reliable automated system behavior. \textbf{Part I} of the dissertation establishes a theoretical framework for the data-driven design of optimal controllers inspired by autonomous physical systems. It investigates the online regulation of both linear and nonlinear systems that are possibly unstable and partially unknown. A significant contribution of this part is the introduction of the concept of ``regularizability," which characterizes the extent by which a system can be regulated in finite time, offering a new perspective on system behavior compared to traditional stabilizability and controllability. This theoretical exploration challenges conventional understandings and provides novel insights into finite time regulation versus asymptotic behavior. \textbf{Part II} addresses the practical application of deep learning algorithms in processing high-dimensional data and generating a spectrum of outputs in automatic feedback control. The inherent challenge in this context is modeling uncertainties in the output, especially when these trained neural networks are employed as perception modules within control loops for autonomous navigation. To mitigate this, the dissertation introduces a novel approach utilizing a perception map as an approximate inverse. This perception-control loop demonstrates commendable attributes, provided that the controller is robustly designed to accommodate for the perception errors. The novelty of this part lies in developing methods to ensure robustness against state-dependent perception errors, thus contributing to more reliable machine learning applications in feedback control systems
Smith Professor Hillel Y. Levin offers his thoughts on the U.S. Supreme Court’s decision on U.S. v. Rahimi
No full textSmith Professor Hillel Y. Levin offers his thoughts on the U.S. Supreme Court’s decision on U.S. v. Rahimi:
What did the Supreme Court do in Rahimi?
As expected, the Court reversed the Fifth Circuit and held that when an individual has been found by a court to pose a credible threat to the physical safety of another, that individual may be temporarily disarmed consistent with the Second Amendment. The decision was 8-1, with only Justice Thomas dissenting.
On what basis did the Supreme Court decide the case?
The Court held that when looking for historical analogues of modern-day restrictions on firearms, it is not necessary to find a perfectly equivalent regulation from the Founding or post-Civil War eras. In the words of Chief Justice Roberts, the author of the majority opinion, the Second Amendment permits more than just those regulations identical to ones that could be found in 1791. It is sufficient that there be sufficient historical analogues that impose similar burdens or restrictions on the right to bear arms for similar reasons. Here, the Court concluded that the country has a tradition of disarming individuals who pose a clear threat of physical violence to another, even if not quite in the same manner as the law that was applied to Rahimi.
Does this clarify Bruen? How will it impact other cases?
This was a fairly narrow opinion. The Court kept the Bruen regime intact and gave little guidance to lower courts in applying it to other kinds of regulations. At most, the Court clarified that historical analogues need not be perfect in order to justify a modern restriction. However, lower courts will continue to struggle to determine just how similar a modern restriction must be to the historical analogue.
University of Georgia School of Law Smith Professor Hillel Y. Levin is available for further commentary at [email protected]
Smith Professor Hillel Y. Levin offers his thoughts on the U.S. Supreme Court’s decision on U.S. v. Rahimi
No full textSmith Professor Hillel Y. Levin offers his thoughts on the U.S. Supreme Court’s decision on U.S. v. Rahimi:
What did the Supreme Court do in Rahimi?
As expected, the Court reversed the Fifth Circuit and held that when an individual has been found by a court to pose a credible threat to the physical safety of another, that individual may be temporarily disarmed consistent with the Second Amendment. The decision was 8-1, with only Justice Thomas dissenting.
On what basis did the Supreme Court decide the case?
The Court held that when looking for historical analogues of modern-day restrictions on firearms, it is not necessary to find a perfectly equivalent regulation from the Founding or post-Civil War eras. In the words of Chief Justice Roberts, the author of the majority opinion, the Second Amendment permits more than just those regulations identical to ones that could be found in 1791. It is sufficient that there be sufficient historical analogues that impose similar burdens or restrictions on the right to bear arms for similar reasons. Here, the Court concluded that the country has a tradition of disarming individuals who pose a clear threat of physical violence to another, even if not quite in the same manner as the law that was applied to Rahimi.
Does this clarify Bruen? How will it impact other cases?
This was a fairly narrow opinion. The Court kept the Bruen regime intact and gave little guidance to lower courts in applying it to other kinds of regulations. At most, the Court clarified that historical analogues need not be perfect in order to justify a modern restriction. However, lower courts will continue to struggle to determine just how similar a modern restriction must be to the historical analogue.
University of Georgia School of Law Smith Professor Hillel Y. Levin is available for further commentary at [email protected]
Domestic violence against women in Atiq Rahimi\u27s The Patience Stone
No full textDomestic violence against women is a common social ill that destroys thousands of women?s lives worldwide (Khan, 2000). However, the growth of this concern, particularly in developing countries such as Afghanistan, requires more scholarly attention not only because the lives of many Afghan women are affected by it, but also because it remains overlooked due to socio-cultural norms that consider discussions about it as taboo. Of late, however, there is a rising trend among members of the Afghan Diaspora in portraying domestic violence against their womenfolk back home through such artistic mediums as fiction (Parveen, 2015). Therefore, in this paper, we shall examine the manifestations of domestic violence against women in the Afghan context through a textual analysis of The Patience Stone by Atiq Rahimi, an author belonging to the Afghan Diaspora. Originally written in French, this breakthrough novella highlights the harsh reality of the misery suffered by many Afghan women on a regular basis, notably the various forms of domestic violence that they have to endure in the poverty-stricken, war-torn and staunchly patriarchal environment of their homeland. Through a feminist reading of The Patience Stone (2011), we shall examine Rahimi?s depictions of domestic violence against women in the novella as a highly engendered phenomenon resulting from gender inequality and a sexist hierarchy of power prevalent in Afghan society. Furthermore, this paper is outlined based on three main forms of domestic violence, namely physical, sexual and emotional abuse, which are depicted in The Patience Stone through the novella?s female characters, notably the main protagonist
Characterization of the passive layer on ferrite and austenite phases of super duplex stainless steel
No full textIn this study, we report on a combined microscopic, analytical and electrochemical characterization of the nanoscopic passive layer on a tungsten‑molybdenum-containing super duplex stainless steel. We used scanning transmission electron microscopy/energy dispersive X-ray spectroscopy, scanning Kelvin probe force microscopy, scanning tunneling spectroscopy, and Mott–Schottky electrochemical impedance spectroscopy analysis to correlate the local chemical composition and electronic properties of passive layers on austenite and ferrite phases. The passive layer on the ferrite phase contains a higher amount of Mo, W, and Cr, which accommodates a higher nobility of ferrite and a higher local energy of the band gap compared to those on the austenite. The two aforementioned phases exhibit a different composition and semi-conductive properties of their passive layers leading to dissimilar local corrosion susceptibility. These findings are of pivotal importance in further studies of austenite and ferrite phase resolved corrosion resistance of duplex stainless steel demanding a dedicated alloying strategy.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.(OLD) MSE-6QN/Zandbergen La
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