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At least 145 records · Page 8

The Role of Hydrophobic Nodes in the Dynamics of Class A β-Lactamases

Class A β-lactamases are known for being able to rapidly gain broad spectrum catalytic efficiency against most β-lactamase inhibitor combinations as a result of elusively minor point mutations. The evolution in class A β-lactamases occurs through optimisation of their dynamic phenotypes at different timescales. At long-timescales, certain conformations are more catalytically permissive than others while at the short timescales, fine-grained optimisation of free energy barriers can improve efficiency in ligand processing by the active site. Free energy barriers, which define all coordinated movements, depend on the flexibility of the secondary structural elements. The most highly conserved residues in class A β-lactamases are hydrophobic nodes that stabilize the core. To assess how the stable hydrophobic core is linked to the structural dynamics of the active site, we carried out adaptively sampled molecular dynamics (MD) simulations in four representative class A β-lactamases (KPC-2, SME-1, TEM-1, and SHV-1). Using Markov State Models (MSM) and unsupervised deep learning, we show that the dynamics of the hydrophobic nodes is used as a metastable relay of kinetic information within the core and is coupled with the catalytically permissive conformation of the active site environment. Finally, our results collectively demonstrate that the class A enzymes described here, share several important dynamic similarities and the hydrophobic nodes comprise of an informative set of dynamic variables in representative class A β-lactamases.

59 BASIC BIOLOGICAL SCIENCES↗

The Physical Parameters of Clumps Associated with Class I Methanol Masers

We present a study of the association between class I methanol masers and cold dust clumps from the APEX Telescope Large Area Survey of the Galaxy (ATLASGAL) survey. It was found that almost 100% of class I methanol masers are associated with objects listed in the ATLASGAL compact source catalog. We find a statistically significant difference in the flux density, luminosity, number and column density, and temperature distributions of ATLASGAL sources associated with 95/44 GHz methanol masers compared with those ATLASGAL sources devoid of 95 GHz methanol masers. The masers tend to arise in clumps with higher densities, luminosities, and temperatures compared with both the full sample of ATLASGAL clumps, as well as the sample of ATLASGAL sources that were cross-matched with positions previously searched for methanol masers but with no detections. Comparison between the peak position of ATLASGAL clumps and the interferometric positions of the associated class I and II methanol masers reveals that class I masers are generally located at larger physical distances from the peak submillimeter emission than class II masers. We conclude that the tight association between ATLASGAL sources and class I methanol masers may be used as a link toward understanding the conditions of the pumping of these masers and evolutionary stages at which they appear.

79 ASTRONOMY AND ASTROPHYSICS↗

Two Year Cosmology Large Angular Scale Surveyor (CLASS) Observations: Long Timescale Stability Achieved with a Front-end Variable-delay Polarization Modulator at 40 GHz

The Cosmology Large Angular Scale Surveyor (CLASS) is a four-telescope array observing the largest angular scales (2≲ ℓ ≲ 200) of the cosmic microwave background (CMB) polarization. These scales encode information about reionization and inflation during the early universe. The instrument stability necessary to observe these angular scales from the ground is achieved through the use of a variable-delay polarization modulator as the first optical element in each of the CLASS telescopes. Here, we develop a demodulation scheme used to extract the polarization timestreams from the CLASS data and apply this method to selected data from the first 2 yr of observations by the 40 GHz CLASS telescope. These timestreams are used to measure the 1/f noise and temperature-to-polarization (T → P) leakage present in the CLASS data. We find a median knee frequency for the pair-differenced demodulated linear polarization of 15.12 mHz and a T → P leakage of <3.8 × 10 -4 (95% confidence) across the focal plane. We examine the sources of 1/f noise present in the data and find the component of 1/f due to atmospheric precipitable water vapor (PWV) has an amplitude of 203 ± 12 µK RJ $\sqrt{{s}}$ for 1 mm of PWV when evaluated at 10 mHz; accounting for ~17% of the 1/f noise in the central pixels of the focal plane. In conclusion, the low levels of T → P leakage and 1/f noise achieved through the use of a front-end polarization modulator are requirements for observing of the largest angular scales of the CMB polarization by the CLASS telescopes.

79 ASTRONOMY AND ASTROPHYSICS↗

Definition of spectrally separable classes for soil survey research

A procedure is outlined for defining spectral classes such that the differences between classes can be quantified. It also facilitates determination of a number of classes such that the classes are spectrally discriminable. This is accomplished by partitioning the data into many classes and then combining similar spectral classes on the basis of appropriate criteria. Multispectral data were collected over a 12-mile flightline in White County, Indiana, in connection with the 1971 Corn Blight Watch Experiment. Data were collected in May by the University of Michigan airborne scanning spectrometer at an altitude of 5000 feet. Spectral maps resulting from the analysis were compared to existing soil surveys of the National Cooperative Soil Survey. The method should help determine the extent to which spectral properties of soil surfaces can be associated with morphologic and topographic differences of interest to soil surveyors engaged in operational soil mapping.

Cipra, J. E.↗

Use of multi-frequency, multi-polarization, multi-angle airborne radars for class discrimination in a southern temperature forest

The utility of radar scatterometers for discrimination and characterization of natural vegetation was investigated. Backscatter measurements were acquired with airborne multi-frequency, multi-polarization, multi-angle radar scatterometers over a test site in a southern temperate forest. Separability between ground cover classes was studied using a two-class separability measure. Very good separability is achieved between most classes. Longer wavelength is useful in separating trees from non-tree classes, while shorter wavelength and cross polarization are helpful for discrimination among tree classes. Using the maximum likelihood classifier, 50% overall classification accuracy is achieved using a single, short-wavelength scatterometer channel. Addition of multiple incidence angles and another radar band improves classification accuracy by 20% and 50%, respectively, over the single channel accuracy. Incorporation of a third radar band seems redundant for vegetation classification. Vertical transmit polarization is critically important for all classes.

Mehta, N. C.↗

A class Hierarchical, object-oriented approach to virtual memory management

The Choices family of operating systems exploits class hierarchies and object-oriented programming to facilitate the construction of customized operating systems for shared memory and networked multiprocessors. The software is being used in the Tapestry laboratory to study the performance of algorithms, mechanisms, and policies for parallel systems. Described here are the architectural design and class hierarchy of the Choices virtual memory management system. The software and hardware mechanisms and policies of a virtual memory system implement a memory hierarchy that exploits the trade-off between response times and storage capacities. In Choices, the notion of a memory hierarchy is captured by abstract classes. Concrete subclasses of those abstractions implement a virtual address space, segmentation, paging, physical memory management, secondary storage, and remote (that is, networked) storage. Captured in the notion of a memory hierarchy are classes that represent memory objects. These classes provide a storage mechanism that contains encapsulated data and have methods to read or write the memory object. Each of these classes provides specializations to represent the memory hierarchy.

Russo, Vincent F.↗

CLASS: The Cosmology Large Angular Scale Surveyor

The Cosmology Large Angular Scale Surveyor (CLASS) is an experiment to measure the signature of a gravitational wave background from inflation in the polarization of the cosmic microwave background (CMB). CLASS is a multi-frequency array of four telescopes operating from a high-altitude site in the Atacama Desert in Chile. CLASS will survey 70% of the sky in four frequency bands centered at 38, 93, 148, and 217 GHz, which are chosen to straddle the Galactic-foreground minimum while avoiding strong atmospheric emission lines. This broad frequency coverage ensures that CLASS can distinguish Galactic emission from the CMB. The sky fraction of the CLASS survey will allow the full shape of the primordial B-mode power spectrum to be characterized, including the signal from reionization at low-length. Its unique combination of large sky coverage, control of systematic errors, and high sensitivity will allow CLASS to measure or place upper limits on the tensor-to-scalar ratio at a level of r = 0:01 and make a cosmic-variance-limited measurement of the optical depth to the surface of last scattering, tau. (c) (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

propagation↗

FAUST I. The hot corino at the heart of the prototypical Class I protostar L1551 IRS5

The study of hot corinos in solar-like protostars has been so far mostly limited to the Class 0 phase, hampering our understanding of their origin and evolution. In addition, recent evidence suggests that planet formation starts already during Class I phase, which therefore represents a crucial step in the future planetary system chemical composition. Hence, the study of hot corinos in Class I protostars has become of paramount importance. Here, we report the discovery of a hot corino towards the prototypical Class I protostar L1551 IRS5, obtained within the ALMA (Atacama Large Millimeter/submillimeter Array) Large Program FAUST (Fifty AU STudy of the chemistry in the disc/envelope system of solar-like protostars). We detected several lines from methanol and its isotopologues (13CH3OH and CH2DOH), methyl formate, and ethanol. Lines are bright towards the north component of the IRS5 binary system, and a possible second hot corino may be associated with the south component. The methanol lines' non-LTE analysis constrains the gas temperature (∼100 K), density (≥1.5 × 10^8 per cu.cm), and emitting size (∼10 au in radius). All CH3OH and 13CH3OH lines are optically thick, preventing a reliable measure of the deuteration. The methyl formate and ethanol relative abundances are compatible with those measured in Class 0 hot corinos. Thus, based on this work, little chemical evolution from Class 0 to I hot corinos occurs.

astrochemistry, stars: formation, ISM: molecules↗

Diagnostic classification of flash drought events reveals distinct classes of forcings and impacts

Recent years have seen growing appreciation that rapidly intensifying flash droughts are significant climate hazards with major economic and ecological impacts. This has motivated efforts to inventory, monitor, and forecast flash drought events. Here we consider the question of whether the term “flash drought” comprises multiple distinct classes of event, which would imply that understanding and forecasting flash droughts might require more than one framework. To do this, we first extend and evaluate a soil moisture volatility–based flash drought definition that we introduced in previous work and use it to inventory the onset dates and severity of flash droughts across the contiguous United States (CONUS) for the period 1979–2018. Using this inventory, we examine meteorological and land surface conditions associated with flash drought onset and recovery. These same meteorological and land surface conditions are then used to classify the flash droughts based on precursor conditions that may represent predictable drivers of the event. We find that distinct classes of flash drought can be diagnosed in the event inventory. Specifically, we describe three classes of flash drought: “dry and demanding” events for which antecedent evaporative demand is high and soil moisture is low, “evaporative” events with more modest antecedent evaporative demand and soil moisture anomalies, but positive antecedent evaporative anomalies, and “stealth” flash droughts, which are different from the other two classes in that precursor meteorological anomalies are modest relative to the other classes. The three classes exhibit somewhat different geographic and seasonal distributions. We conclude that soil moisture flash droughts are indeed a composite of distinct types of rapidly intensifying droughts, and that flash drought analyses and forecasts would benefit from approaches that recognize the existence of multiple phenomenological pathways.

Mahmoud Osman↗

New Mastcam Multispectral Rock Classes in Sulfate-Bearing Strata, Gale Crater, Mars

Orbital data of Gale Crater, Mars has identified a transition in the stratigraphy of Mt. Sharp indicating an environmental change from a wetter one that accommodated clay mineral formation to a drier environment that led to the precipitation of sulfates. Mt. Sharp is not the only location on Mars for which this transition has been observed which suggests a global environmental change around the Noachian-Hesperian transition. Also visible from orbit is a dark-toned marker band that lies within the sulfate-bearing strata hypothesized to be a volcanic ash deposit. The Mars Science Laboratory (MSL) Curiosity rover is currently exploring this region of Mt. Sharp. In-situ analyses by the rover show changes in morphology and chemistry between the sulfate-bearing layers below and above the marker band and the marker band itself. The MSL instrument payload includes the Mast Camera (Mastcam), which collects multispectral images to provide context for other instruments and broad mineralogic interpretations. In addition to mafic Fe-bearing minerals, Mastcam is sensitive to oxides and some hydrated minerals, important indicators of alteration. In our previous work, we compiled a database of Mastcam spectra through Curiosity’s exploration of Vera Rubin ridge (sols 0-2302), from which 9 spectral classes of rocks were identified (Fig. 1D). Each class has diagnostic spectral features that reflect a common mineralogic interpretation. More recently, as Curiosity traversed through the clay-rich region, Glen Torridon (GT), there was some variation in the rock spectral classes potentially due to nontronite and other phyllosilicates, but not enough to warrant new spectral classes (Fig. 1B). We hypothesize that new classes will appear in accordance with sulfate-bearing strata and the marker band, specifically appearing as a ‘downturn’ in the last two wavelength filters that is inherent, but not unique, to polyhydrated Mg-sulfates. Here, we expand upon our analysis of Mastcam multispectral observations through Curiosity’s second encounter with the marker band (up to sol 3672), comparing the spectral diversity within the sulfate-bearing unit and the marker band to the spectral classes encountered previously in the traverse. These analyses will provide a basis for comparison and aid in selecting targets for in-situ investigations as Curiosity continues its ascent of Mt. Sharp.

A M Eng↗

In-situ sensor monitoring of multi-class gas porosity formation in laser powder bed fusion using convolutional neural network

In-situ monitoring of defect formation remains a significant challenge in the laser powder bed fusion (LPBF) process. Recent advances have enabled real-time defect detection with machine learning and in-situ sensing technologies; however, most studies focus on binary classification of keyhole pores, limiting nuanced multi-class pore differentiation and formation mechanisms. This work introduces a multi-class pore detection framework (no pore, small pores < 15 µm, and large pores > 15 µm) by leveraging photodiode sensor data alongside high-fidelity synchrotron X-ray imaging. The 15 µm threshold is selected to distinguish between two fundamentally different defect mechanisms, following the physical size-mechanism boundary established by prior high-resolution synchrotron X-ray characterization of Al6061 LPBF. Distinguishing these classes is critical because large keyhole pores are structurally detrimental, whereas small gas pores are often benign, requiring different process control strategies. Thermal emission monitoring data collected simultaneously with high-speed X-ray imaging at the Stanford Synchrotron Radiation Lightsource (SSRL), are correlated with subsurface melt pool dynamics to establish ground truth. Continuous Wavelet Transform (CWT) with optimized parameters converts the photodiode time-series signals into time–frequency images, facilitating feature extraction. Convolutional Neural Networks (CNN) are then applied for real-time multi-class pore classification in an average inference time of 1 ms per signal window. It achieves 79% accuracy and an Area Under the Receiver Operating Characteristic curve (AUC ROC) score of 0.89 with five-fold cross-validation. The results demonstrate that coupling CWT-based feature engineering with CNN architecture enables reliable multi-class pore detection in Al6061 builds using affordable in-situ sensors. This approach advances scalable and affordable quality assurance in additive manufacturing by moving beyond binary defect detection toward more nuanced classification of porosity mechanisms with in-situ sensors and machine learning.

Laser powder bed fusion, Multi-class pores, In-sit↗

‘Flux+Mutability’: a conditional generative approach to one-class classification and anomaly detection

Abstract Anomaly Detection is becoming increasingly popular within the experimental physics community. At experiments such as the Large Hadron Collider, anomaly detection is growing in interest for finding new physics beyond the Standard Model. This paper details the implementation of a novel Machine Learning architecture, called Flux+Mutability, which combines cutting-edge conditional generative models with clustering algorithms. In the ‘flux’ stage we learn the distribution of a reference class. The ‘mutability’ stage at inference addresses if data significantly deviates from the reference class. We demonstrate the validity of our approach and its connection to multiple problems spanning from one-class classification to anomaly detection. In particular, we apply our method to the isolation of neutral showers in an electromagnetic calorimeter and show its performance in detecting anomalous dijets events from standard QCD background. This approach limits assumptions on the reference sample and remains agnostic to the complementary class of objects of a given problem. We describe the possibility of dynamically generating a reference population and defining selection criteria via quantile cuts. Remarkably this flexible architecture can be deployed for a wide range of problems, and applications like multi-class classification or data quality control are left for further exploration.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Evolution of carbapenemase activity in the class C β-lactamase ADC-1

Antibiotic resistance in bacteria poses a significant threat to public health. Among dozens of available antimicrobial agents, carbapenems are used as drugs of choice for the treatment of serious infections caused by pathogens resistant to other antibiotics. However, their usefulness has been severely compromised due to the emergence and wide spread of carbapenem-resistant clinical isolates worldwide. High-level resistance to carbapenems in bacteria is mediated by the production of β-lactamases from three molecular classes, A, B, and D, but not by class C enzymes. In this study, we selected a triple mutant of the intrinsic class C Acinetobacter-derived cephalosporinase ADC-1 (ADC-1 TM ) that confers high-level resistance to the carbapenems meropenem, ertapenem, and doripenem. Kinetic experiments demonstrated that the apparent binding affinity, along with the acylation and deacylation rates, were all improved for the mutant enzyme. X-ray crystallography, molecular docking, and molecular dynamics simulations revealed that the amino acid substitutions in ADC-1 TM produce significant changes in the enzyme active site architecture and binding mode of the carbapenem ertapenem. These changes allow for better positioning of a deacylating water for nucleophilic attack, thus explaining the significantly improved rate of ertapenem deacylation by ADC-1 TM . In this study, we showed for the first time that a class C β-lactamase can produce high-level resistance to carbapenem antibiotics, which underlines the potential for enzymes of this class to evolve such resistance and could further exacerbate the problem of antibiotic resistance in bacteria.

59 BASIC BIOLOGICAL SCIENCES↗

The Cosmology Large Angular Scale Surveyor (CLASS)

The Cosmology Large Angular Scale Surveyor (CLASS) is a four telescope array designed to characterize relic primordial gravitational waves from in ation and the optical depth to reionization through a measurement of the polarized cosmic microwave background (CMB) on the largest angular scales. The frequencies of the four CLASS telescopes, one at 38 GHz, two at 93 GHz, and one dichroic system at 145/217 GHz, are chosen to avoid spectral regions of high atmospheric emission and span the minimum of the polarized Galactic foregrounds: synchrotron emission at lower frequencies and dust emission at higher frequencies. Low-noise transition edge sensor detectors and a rapid front-end polarization modulator provide a unique combination of high sensitivity, stability, and control of systematics. The CLASS site, at 5200 m in the Chilean Atacama desert, allows for daily mapping of up to 70% of the sky and enables the characterization of CMB polarization at the largest angular scales. Using this combination of a broad frequency range, large sky coverage, control over systematics, and high sensitivity, CLASS will observe the reionization and recombination peaks of the CMB E- and B-mode power spectra. CLASS will make a cosmic variance limited measurement of the optical depth to reionization and will measure or place upper limits on the tensor-to-scalar ratio, r, down to a level of 0.01 (95% C.L.).

The Cosmology Large Angular Scale Surveyor (CLASS)↗

Estimation of soil classes and their relationship to grapevine vigor in a Bordeaux vineyard: advancing the practical joint use of electromagnetic induction (EMI) and NDVI datasets for precision viticulture

Working within a vineyard in the Pessac Léognan Appellation of Bordeaux, France, this study documents the potential of using simple statistical methods with spatially-resolved and increasingly available electromagnetic induction (EMI) geophysical and normalized difference vegetation index (NDVI) datasets to accurately estimate Bordeaux vineyard soil classes and to quantitatively explore the relationship between vineyard soil types and grapevine vigor. First, co-located electrical tomographic tomography (ERT) and EMI datasets were compared to gain confidence about how the EMI method averaged soil properties over the grapevine rooting depth. Then, EMI data were used with core soil texture and soil-pit based interpretations of Bordeaux soil types (Brunisol, Redoxisol, Colluviosol and Calcosol) to estimate the spatial distribution of geophysically-identified Bordeaux soil classes. A strong relationship (r = 0.75, p < 0.01) was revealed between the geophysically-identified Bordeaux soil classes and NDVI (both 2 m resolution), showing that the highest grapevine vigor was associated with the Bordeaux soil classes having the largest clay fraction. The results suggest that within-block variability of grapevine vigor was largely controlled by variability in soil classes, and that carefully collected EMI and NDVI datasets can be exceedingly helpful for providing quantitative estimates of vineyard soil and vigor variability, as well as their covariation. The method is expected to be transferable to other viticultural regions, providing an approach to use easy-to-acquire, high resolution datasets to guide viticultural practices, including routine management and replanting.

54 ENVIRONMENTAL SCIENCES↗

The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s

Highlights: • The crystal structure of CYP116B45 (P450-TT) from T. thermophilus has been solved. • P450-TT crystal structure is the first example of a class VII P450 structure. • P450-TT adopts the typical P450-fold. • Structural deviation of regions involved in substrate recognition is observed. • Analysis of 96 class VII sequences revealed conservation of active site residues. The first crystal structure of a class VII P450, CYP116B46 from Tepidiphilus thermophilus, has been solved at 1.9 Å resolution. The structure reveals overall conservation of the P450-fold and a water conduit around the I-helix. Active site residues have been identified and sequence comparisons have been made with other class VII enzymes. A structure similarity search demonstrated that the P450-TT structure is similar to enzymes capable of oxy-functionalization of fatty acids, terpenes, macrolides, steroids and statins. The insight gained from solving this structure will provide a guideline for future engineering and modelling studies on this catalytically promiscuous class of enzymes.

60 APPLIED LIFE SCIENCES↗

Uncovering the underlying physical mechanism for cancer-immunity of MHC class I diversity

The cancer cells are heterogeneous populated, which can be classified as MHC class I positive and MHC I class negative. They influence the immune system differently. In this work, we build a core cancer-immune circuit of MHC class I diversity including MHC class I positive cancer type, MHC I class I negative cancer type and 4 immune cell types to uncover the underlying mechanism of the cancer immunity based on the underlying landscape topography. We quantify four steady state attractors, normal state, two low cancer states and a high cancer state. The landscape topography changes upon changes in cancer self-activation and the related killing rate of the killer cells are illustrated. It demonstrates that the competition between the two cancer cell types. We simulate the tumorigenesis and development of cancer according to its biological process and classify these into 7 stages. This landscape framework provides a quantitative way to understand characteristics of these two cancer cell types under immune microenvironment and the underlying physical mechanisms of cancer cell evolution along cancer development.

60 APPLIED LIFE SCIENCES↗

Generalizable Class Solutions for Treatment Planning of Spinal Stereotactic Body Radiation Therapy

Purpose: Spinal stereotactic body radiation therapy (SBRT) continues to emerge as an effective therapeutic approach to spinal metastases; however, treatment planning and delivery remain resource intensive at many centers, which may hamper efficient implementation in clinical practice. We sought to develop a generalizable class solution approach for spinal SBRT treatment planning that would allow confidence that a given plan provides optimal target coverage, reduce integral dose, and maximize planning efficiency. Methods and Materials: We examined 91 patients treated with spinal SBRT at our institution. Treatment plans were categorized by lesion location, clinical target volume (CTV) configuration, and dose fractionation scheme, and then analyzed to determine the technically achievable dose gradient. A radial cord expansion was subtracted from the CTV to yield a planning CTV (pCTV) construct for plan evaluation. We reviewed the treatment plans with respect to target coverage, dose gradient, integral dose, conformality, and maximum cord dose to select the best plans and develop a set of class solutions. Results: The class solution technique generated plans that maintained target coverage and improved conformality (1.2-fold increase in the 95% van't Riet Conformation Number describing the conformality of a reference dose to the target) while reducing normal tissue integral dose (1.3-fold decrease in the volume receiving 4 Gy (V{sub 4Gy}) and machine output (19% monitor unit (MU) reduction). In trials of planning efficiency, the class solution technique reduced treatment planning time by 30% to 60% and MUs required by {approx}20%: an effect independent of prior planning experience. Conclusions: We have developed a set of class solutions for spinal SBRT that incorporate a pCTV metric for plan evaluation while yielding dosimetrically superior treatment plans with increased planning efficiency. Our technique thus allows for efficient, reproducible, and high-quality spinal SBRT treatment planning.

62 RADIOLOGY AND NUCLEAR MEDICINE↗