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The upper tropospheric ozone (O3) strongly influences the atmosphere's radiative budget. Using the Aerosol and Chemistry Model Intercomparison Project simulations, we study the influence of present‐day and future anthropogenic nitrogen oxides (NOx) emissions on the upper tropospheric O3 concentrations over India during the Asian summer monsoon (ASM). We observe that the upper tropospheric O3 concentrations increased 1.5 times over the ASM anticyclone region during the ASM due to higher NOx emissions in 2014 compared to 1850, and their transport due to convection. These NOx‐induced O3 changes exert a regional positive radiative forcing of 0.6 Wm−2 at the top of the atmosphere. The upper tropospheric O3 increases in the future with increasing NOx emissions. However, air quality policies to reduce surface NOx emissions also reduce the upper tropospheric O3 over India during the ASM. Plain Language Summary This study estimates the change in the upper tropospheric ozone concentration, during the Asian Summer Monsoon (ASM) over India, due to the changes in atmospheric nitrogen oxides (NOx) emissions. NOx emissions have increased globally over the last 150 years due to human activities such as fuel combustion. During the ASM, some of the surface NOx and ozone from India are transported to the upper troposphere due to the vertical winds. In the upper troposphere, this transported NOx chemically reacts with other atmospheric species to form more ozone there. The upper tropospheric ozone efficiently traps atmospheric heat and thus warms the planet. Using output from community atmospheric transport simulations of NOx and ozone, we estimate that the NOx‐induced changes in the upper tropospheric ozone concentration have increased the atmospheric heat considerably in the last 150 years over India during monsoon. The upper tropospheric ozone is projected to increase in the future if all countries continue emitting more NOx from combustion activities. However, cleaner air policies aimed at reducing surface NOx emissions also reduce the upper tropospheric ozone because of reduced near‐surface NOx and ozone available for vertical transport. Key Points Higher NOx in 2014 compared to 1850 increased the upper tropospheric O3 by 1.5 times over India during the Asian summer monsoon (ASM) NOx‐induced O3 changes exert a radiative forcing of 0.6 Wm−2 at the top of the atmosphere over the ASM anticyclone region during the ASM Projected increase in future NOx emissions leads to an increase in the upper tropospheric O3 over India during the ASM

Macromolecular modeling and design are increasingly useful in basic research, biotechnology, and teaching. However, the absence of a user-friendly modeling framework that provides access to a wide range of modeling capabilities is hampering the wider adoption of computational methods by non-experts. RosettaScripts is an XML-like language for specifying modeling tasks in the Rosetta framework. RosettaScripts provides access to protocol-level functionalities, such as rigid-body docking and sequence redesign, and allows fast testing and deployment of complex protocols without need for modifying or recompiling the underlying C++ code. We illustrate these capabilities with RosettaScripts protocols for the stabilization of proteins, the generation of computationally constrained libraries for experimental selection of higher-affinity binding proteins, loop remodeling, small-molecule ligand docking, design of ligand-binding proteins, and specificity redesign in DNA-binding proteins.

The Rosetta de novo enzyme design protocol has been used to design enzyme catalysts for a variety of chemical reactions, and in principle can be applied to any arbitrary chemical reaction of interest. The process has four stages: 1) choice of a catalytic mechanism and corresponding minimal model active site, 2) identification of sites in a set of scaffold proteins where this minimal active site can be realized, 3) optimization of the identities of the surrounding residues for stabilizing interactions with the transition state and primary catalytic residues, and 4) evaluation and ranking the resulting designed sequences. Stages two through four of this process can be carried out with the Rosetta package, while stage one needs to be done externally. Here, we demonstrate how to carry out the Rosetta enzyme design protocol from start to end in detail using for illustration the triosephosphate isomerase reaction.

The rapid growth of mobile payment platforms has enhanced transactional convenience but also introduced critical security challenges, notably shoulder spoofing. This attack occurs when unauthorized individuals or surveillance devices visually intercept sensitive information, such as Mobile Personal Identification Numbers (MPINs), during payment processes. Existing security mechanisms—including PIN masking and screen dimming—fail to detect environmental threats or provide adaptive responses, leaving users vulnerable in public spaces. To address this gap, propose a novel solution titled Gaze-Aware Threat Detection with Contextual Scene Analysis (GATCSA). GATCSA leverages the front-facing camera and on-device computer vision algorithms to monitor the surroundings during mobile transactions. The system identifies suspicious behavior such as gaze fixation by nearby individuals or the presence of surveillance equipment targeting the mobile screen. A risk evaluation module considers proximity, gaze direction, and focus duration to classify threat levels in real time. Upon detection, the system provides users with contextual alerts and actionable suggestions—such as changing the device angle, enabling a privacy screen, or halting the transaction—to safeguard against unauthorized visual access. Unlike traditional methods, GATCSA processes all data locally to ensure user privacy and operates efficiently on resource-constrained mobile devices. Preliminary testing in varied real-world conditions—differing in lighting, crowd density, and device orientation—demonstrates high accuracy in threat identification and user responsiveness. By integrating gaze tracking with environmental awareness, GATCSA represents a significant advancement in mobile payment security, enhancing user trust and privacy during digital transactions.

A novel architectural design is proposed to mitigate uneven thermal distribution, peak temperature, and heat spot generation, which are common issues that are observed in conventional battery packs. This approach features a multi-terminal configuration, incorporating a modified battery pack structure along with a multi-terminal switching algorithm that identifies the optimal terminal for current flow to the load. In the proposed design, the first and second terminals are placed at the first and fourth series string while the battery pack is divided into four regions, each corresponding to one series string. Additionally, terminal points represent the four thermal zones at the pack level. Experiments were conducted to evaluate the performance of the dual-terminal switching mechanism in three configurations—1S, 2S, and 3S. The 1S setup outperformed the single-terminal design, achieving a 6.23% improvement in reducing the zone temperature difference (ΔPz). The 2S configuration demonstrated an 11.11% improvement, while the 3S setup achieved an improvement in peak region difference (ΔPr) of >50%, without a cooling system. Finally, while forced air cooling effectively lowers peak temperature, it is insufficient in addressing thermal distribution and heat spot formation. However, integrating the proposed multi-terminal approach enables the effective control and management of all three critical thermal parameters—peak temperature, thermal distribution, and heat spot generation.

Patients with metastatic triple-negative breast cancer were treated with standard chemotherapy or the anti–Trop-2 antibody–drug conjugate sacituzumab govitecan. Patients receiving the drug conjugate had significantly longer progression-free and overall survival as well as more frequent myelotoxic effects and diarrhea.

Biophysical interactions between proteins and peptides are key determinants of molecular recognition specificity landscapes. However, an understanding of how molecular structure and residue-level energetics at protein–peptide interfaces shape these landscapes remains elusive. We combine information from yeast-based library screening, next-generation sequencing, and structure-based modeling in a supervised machine learning approach to report the comprehensive sequence–energetics–function mapping of the specificity landscape of the hepatitis C virus (HCV) NS3/4A protease, whose function—site-specific cleavages of the viral polyprotein—is a key determinant of viral fitness. We screened a library of substrates in which five residue positions were randomized and measured cleavability of ∼30,000 substrates (∼1% of the library) using yeast display and fluorescence-activated cell sorting followed by deep sequencing. Structure-based models of a subset of experimentally derived sequences were used in a supervised learning procedure to train a support vector machine to predict the cleavability of 3.2 million substrate variants by the HCV protease. The resulting landscape allows identification of previously unidentified HCV protease substrates, and graph-theoretic analyses reveal extensive clustering of cleavable and uncleavable motifs in sequence space. Specificity landscapes of known drug-resistant variants are similarly clustered. The described approach should enable the elucidation and redesign of specificity landscapes of a wide variety of proteases, including human-origin enzymes. Our results also suggest a possible role for residue-level energetics in shaping plateau-like functional landscapes predicted from viral quasispecies theory.

Posttranslational modification of ribosomally synthesized peptides provides an elegant means for the production of biologically active molecules known as RiPPs (ribosomally synthesized and posttranslationally modified peptides). Although the leader sequence of the precursor peptide is often required for turnover, the exact mode of recognition by the modifying enzymes remains unclear for many members of this class of natural products. Here, we have used X-ray crystallography and computational modeling to examine the role of the leader peptide in the biosynthesis of a homolog of streptide, a recently identified peptide natural product with an intramolecular lysine–tryptophan cross-link, which is installed by the radical S-adenosylmethionine (SAM) enzyme, StrB. We present crystal structures of SuiB, a close ortholog of StrB, in various forms, including apo SuiB, SAM-bound SuiB, and a complex of SuiB with SAM and its peptide substrate, SuiA. Although the N-terminal domain of SuiB adopts a typical RRE (RiPP recognition element) motif, which has been implicated in precursor peptide recognition, we observe binding of the leader peptide in the catalytic barrel rather than the N-terminal domain. Computational simulations support a mechanism in which the leader peptide guides posttranslational modification by positioning the cross-linking residues of the precursor peptide within the active site. Together the results shed light onto binding of the precursor peptide and the associated conformational changes needed for the formation of the unique carbon–carbon cross-link in the streptide family of natural products.