bluuebunny/crossref_metadata_2025 huggingface dataset:
MmpL3, Wag31, and PlrA are involved in coordinating polar growth with peptidoglycan metabolism and nutrient availability
Authors: Arejan Neda Habibi , Czapski Desiree R. , Buonomo Joseph A. , Boutte Cara C.
Published: September 2024

Cell growth in mycobacteria involves cell wall expansion that is restricted to the cell poles. The DivIVA homolog Wag31 is required for this process, but the molecular mechanism and protein partners of Wag31 have not been described. In this study of
Mycobacterium smegmatis
, we identify a connection between
wag31
and trehalose monomycolate (TMM) transporter
mmpl3
in a suppressor screen and show that Wag31 and polar regulator PlrA are required for MmpL3’s polar localization. In addition, the localization of PlrA and MmpL3 is responsive to nutrient and energy deprivation and inhibition of peptidoglycan metabolism. We show that inhibition of MmpL3 causes delocalized cell wall metabolism but does not delocalize MmpL3 itself. We found that cells with an MmpL3 C-terminal truncation, which is defective for localization, have only minor defects in polar growth but are impaired in their ability to downregulate cell wall metabolism under stress. Our work suggests that, in addition to its established function in TMM transport, MmpL3 has a second function in regulating global cell wall metabolism in response to stress. Our data are consistent with a model in which the presence of TMMs in the periplasm stimulates polar elongation and in which the connection between Wag31, PlrA, and the C-terminus of MmpL3 is involved in detecting and responding to stress in order to coordinate the synthesis of the different layers of the mycobacterial cell wall in changing conditions.

IMPORTANCE

This study is performed in
Mycobacterium smegmatis
, which is used as a model to understand the basic physiology of pathogenic mycobacteria such as
Mycobacterium tuberculosis
. In this work, we examine the function and regulation of three proteins involved in regulating cell wall elongation in mycobacterial cells, which occurs at the cell tips or poles. We find that Wag31, a regulator of polar elongation, works partly through the regulation of MmpL3, a transporter of cell wall constituents and an important drug target. Our work suggests that, beyond its transport function, MmpL3 has another function in controlling cell wall synthesis broadly in response to stress.
Isolation of a
bla
NDM-1
-positive strain in Israel predating the earliest observations from India
Authors: Grenier Frédéric , Baby Vincent , Allard Sarah , Lévesque Simon , Papale François , Sullivan Richard , Landecker Hannah L. , Higgins Paul G. , Rodrigue Sébastien , Haraoui Louis-Patrick
Published: September 2024

bla
NDM
, the most prevalent carbapenemase among carbapenem-resistant Enterobacteriaceae, is thought to have emerged in India, as its initial detection in 2008 was linked to this country, and subsequent retrospective surveys had so far established the earliest
bla
NDM
-positive strains to be isolated in India in 2005. Molecular dating and analyses suggest
bla
NDM
emerged within
Acinetobacter
species decades prior to 2005 on a Tn
125
transposon. Despite early reports of elevated rates of carbapenem-resistant
Acinetobacter
species in Israel starting in the 1990s, limited molecular data are available from this location. We searched for
bla
NDM
among
Acinetobacter
species isolated in Israel between 2001 and 2006. One
A. junii
strain, Ajun-H1-3, isolated in January 2004, carried
bla
NDM-1
within a Tn
125
-like transposon on a 49-kb plasmid, pNDM-Ajun-H1-3, making Ajun-H1-3 the earliest NDM-positive isolate observed to date. The pNDM-Ajun-H1-3 plasmid matched numerous BJ01-like NDM-positive plasmids identified from 2005 onward in
Acinetobacter
species as well as Enterobacterales. These results indicate the need for further retrospective work on global strain archives to shed light on the conditions favoring the emergence as well as subsequent evolution and spread of
bla
NDM
.

IMPORTANCE

This study presents the earliest observation of
bla
NDM-1
, isolated in a geographical region distant from where it is believed to have originated. In doing so, this study provides novel insights into the emergence and spread of
bla
NDM
, the most prevalent carbapenemase among carbapenem-resistant Enterobacteriaceae, and its associated mobile genetic elements. It also sheds light on the conditions that foster the evolution of antimicrobial resistance, one of the greatest public health challenges we face.
Re-updating the taxonomy of
Kluyvera
genus for a better understanding of CTX-M β-lactamase origin
Authors: Rodriguez Maria Margarita , Gutkind Gabriel
Published: September 2024

The taxonomic definitions within the
Kluyvera
genus are still unclear, as several deposits might belong to misidentified species or genus or genome assemblies comprehend large indeterminate nucleotide zones. In this study, we performed a comparative phylogenomic analysis of
Kluyvera
chromosomes and other selected
Enterobacterales
. We also included the genomic analysis of chromosomal
bla
CTX-M/KLU
from
Kluyvera
isolates and assigned the plasmid-encoded
bla
CTX/M
genes. The study allowed us to propose a new
Kluyvera
genomospecies and to better define
Kluyvera
genomosp. 5. Two new CTX-M sub-groups could also be suggested. Even if no chromosomal
bla
CTX-M/KLU
gene can be found in
K. intermedia
and
Kluyvera
genomosp. 6, accurate identification can be achieved by using these gene sequences in the remaining strains.

IMPORTANCE

The use of whole-genome sequencing (WGS) accelerated the identification of new
Kluyvera
species proposals, but a rigorous analysis of these sequences is needed for a better definition, including preexisting, and even established species.
Kluyvera
genomosp. 5 could be more clearly defined, and, among isolates that do not produce a chromosome-encoded CTX-M enzyme, true
K. intermedia
should be kept within the genus as well as a new genomospecies (
Kluyvera
genomosp. 6) different from
K. intermedia
. We could clean up true
Kluyvera
from those that deserved transfer to other genera, and some deposits as
K. ascorbata
,
K. cryocrescens
,
K. georgiana
, and several
Kluyvera
sp. to the real species. Two new sub-groups of CTX-M enzymes could be proposed. The accurate identification of the chromosome-encoded
bla
CTX-M/KLU
gene in
Kluyvera
isolates could be a useful taxonomic tool to guide the species classification.
Contributions to forearm desaturation during transient ischemia in healthy adult males and females across the lifespan
Authors: Perlet Michael R. , Traylor Miranda K. , Ransom Kyndall V. , Batman Genevieve B. , Hill Ethan C. , Weir Joseph P. , Keller Joshua L.
Published: September 2024

This study investigated skeletal muscle tissue oxygenation (StO2) desaturation in males and females across the adult lifespan. One hundred-two individuals (51 females) of 41 young, 34 midlife, and 27 older adults completed a vascular occlusion test with near-infrared spectroscopy (NIRS + VOT). This included five minutes of arterial occlusion, inducing transient ischemia in the forearm flexor muscle group while recording StO2. The magnitude of desaturation (StO2mag) was quantified as the difference between baseline StO2 and the minimum StO2 value observed during ischemia. The rate of desaturation was also examined. Forearm adipose tissue thickness (ATT), forearm lean mass, and handgrip muscular strength were measured. A p ≤ 0.05 was considered significant. Two-way between factor Analysis of variance (ANOVAs) indicated that males exhibited significantly ( p < 0.001) less ATT than females (collapsed across age) and that forearm lean mass ( p < 0.001) and muscular strength ( p < 0.001) decreased across the lifespan independent of sex. Bivariate analyses revealed significant ( p < 0.05) associations for sex, age, ATT, forearm lean mass, and muscular strength with the desaturation metrics. The ATT values demonstrated the strongest relations with StO2mag and desaturation rate ( r = −0.620 and 0.618). Using a model comparison approach, ATT plus age offered the best predictive power for StO2mag and desaturation rate ( R2 = 0.456 and 0.438) such that the inclusion of sex did not improve the models. These findings suggested differences in desaturation were primarily explained by variations in ATT and, to a lesser extent, age, but biological sex had no meaningful effect. Future studies must determine what other factors influence desaturation during ischemia.
Quantum isomorphism of 2-graphs
Authors: Joardar Soumalya , Rahaman Atibur , Sharma Jitender
Published: September 2024

We formulate a notion of the quantum automorphism group of a [Formula: see text]-graph. After some preliminary computations, we define quantum isomorphism between a pair of [Formula: see text]-graphs. We produce a “nontrivial” example of a pair of [Formula: see text]-graphs that are not quantum isomorphic to each other.
Thermal Annealing-Induced Recovery of the VT of Irradiated Commercial MOS Transistors
Authors: Mitrović Nikola , Guirado Damián , Danković Danijel , Palma Alberto J. , Ristić Goran , Carvajal Miguel A.
Published: September 2024

This paper describes and compares the recovery of the threshold voltage shift of lateral and vertical p-channel double diffused MOS field effect transistors caused by irradiation. The internal structure of both p-VDMOS and p-LDMOS devices is analyzed, alongside a thermal compensation technique that takes advantage of the analyzed structures. Thermal characterization and irradiation are performed on two different series of commercial devices: the CD4007, which contains p-channel lateral DMOSFET, and the commercial p-channel power vertical DMOSFETs IRF9520 and IRF9530. After irradiation, thermal annealing was carried out, in order to measure threshold voltage recovery and to compare and assess both groups of devices as dosimeters. The measuring setup and conditions for all experiment phases are described in detail. The results are discussed, and the usage of these devices as dosimeters in some commercial applications is considered.
Commutativity of Cascaded Connected Fractional Order Linear Time-Varying Systems
Authors: Ibrahim Salisu , Isah Abdulnasir , Iqbal Mujahid , Chang Phang , Baleanu Dumitru
Published: September 2024

In this work, we present a comprehensive study of the commutativity of fractional-order linear time-varying systems (LTVSs). Commutativity is a fundamental property in the analysis and control of dynamic systems and is often used to simplify the design of controllers. Fractional-order systems, which are characterized by a noninteger-order derivative, have been widely studied in recent years due to their ability to model a wide range of phenomena. However, the commutativity of fractional-order LTVSs has not been widely explored. In this work, we present a comprehensive study of the commutativity of fractional-order LTVSs. We first provide a mathematical definition of commutativity for these systems and demonstrate that it is equivalent to the commutativity of their transfer functions. We then propose a method for verifying the general condition for commutativity of fractional-order LTVSs under zero initial conditions (ICs) and prove it mathematically. Based on our findings, we realized that the commutative requirements, properties, theories, and conditions are general for fractional-order LTVSs, please observed that some fractional-order LTVSs are commutative, some are not commutative, while some are commutative under certain conditions. Based on this fact, we can say that not all fractional-order LTVSs are commutative.

We apply explicit commutative results to several examples of fractional-order LTVSs. Our theoretical and simulation results show a good agreement and prove that our fractional-order LTVSs are commutative under certain conditions, moreover, the commutativity property holds for certain conditions and classes of fractional-order LTVSs, but not for others. Because of the application of fraction commutativity in various fields of science and engineering, we find it necessary to come up with explicit results for the first time.
A FinFET-Based Low Leakage 10T Static Random Access Memory Cell
Authors: Srivastav Anandita , Tiwari Usha , Mandal Sushanta K. , Sachdeva Ashish
Published: September 2024

In this work, a transmission gate-based low-power ten FinFET (TGLP10T) single-ended read/write SRAM cell is proposed. The proposed cell achieves low leakage operation along with improved write-ability. The performance metric results obtained from TGLP10T are compared with five previously published bit-cell designs, i.e., conventional 6T (Con6T), robust transmission gate-based 10T SRAM (RTG10T), transmission gate-based variation resistant 9T SRAM (TGVR9T), PNN (PMOS-NMOS-NMOS) inverter-based 10T (PNN10T) and PPN (PMOS-PMOS-NMOS) inverter-based read decoupled 10T (PPNRD10T. The leakage power in proposed design is reduced by [Formula: see text] compared to Con6T/RTG10T/TGVR9T/PNN10T/PPNRD10T cells. The write power and WSNM are improved by [Formula: see text] and [Formula: see text], respectively, compared to Con6T/RTG10T/TGVR9T/PNN10T/PPNRD10T cells. The read delay and write delay are improved by [Formula: see text] and 1.68 [Formula: see text], respectively, compared to Con6T/RTG10T/TGVR9T/PNN10T/PPNRD10T cells. The proposed design shows the least data retention voltage compared to other SRAM bit-cells.
Deep Neural Network-Based Backhaul Algorithm in Emergency Communication Base Stations Under Large-Scale MIMO Ad hoc Network Scenarios
Authors: Chen Xiaoqing , Feng Ziliang
Published: September 2024

Emergency communication is a key link to ensure the stable operation of communication networks. And large-scale multiple-input multiple-output (MIMO) technology can significantly improve coverage of communication systems. This work aims to optimize the backhaul process through deep neural network to improve the response speed and data transmission efficiency of base stations. Specifically, the proposed method uses deep neural network to represent the backhaul process of base stations, and explores data transmission under high efficiency and low delay. Simulation experiments are designed to verify performance advantages of the proposed method in large-scale MIMO wireless ad hoc networking scenarios, by using three comparison metrics. The experimental results show that the proposed method has a significant performance improvement in data transmission rate, system stability and resource utilization compared with traditional methods. Besides, the feasibility and effectiveness of the algorithm in practical application are verified by simulation and actual environment test. To sum up, the proposed algorithm can provide a new direction for the technical research in the field of emergency communication.
INVESTIGATION OF STRAIN TRANSFER MECHANISM OF FIBER GRATING SENSOR SUBJECT TO TEMPERATURE AND FATIGUE LOADING
Authors: ZHANG XUEBING , CAO JUN , CHEN ZHIZHAN , ZHENG ZHIZHOU , WANG HUAPING , XIANG PING
Published: September 2024

Due to the error between the strain measured by the fiber grating sensor pasted on the surface of the substrate and the real strain of the substrate, the analysis of the relationship between the strain measured by the fiber and the actual strain of the substrate is the focus of this research. Since structures are subjected to various harsh conditions in actual service, such as temperature changes, fatigue, corrosion, aging, cracks and other external factors, when using surface-adhesive fiber Bragg grating (FBG) sensors for structural health monitoring, all external factors may affect the measurement accuracy of the sensors and cause measurement errors, so it is necessary to consider some specific factors in a comprehensive manner. In this paper, we theoretically study the average strain transfer rate of the three-layer strain transfer model of a surface-adhesive fiber grating sensor under the effects of temperature change and fatigue load, derive the formula for the average dynamic strain transfer rate under the combined effects of two external factors using the shear-lag method and analyze the parameters of the fiber-optic sensor to correct the error and optimize the measurement accuracy of the sensor in order to better monitor the structure under temperature change and fatigue load. The shear hysteresis method is also used to analyze the parameters of the fiber-optic sensor to correct the errors and optimize the measurement accuracy of the sensor in order to better monitor the real dynamic strain of the substrate under temperature and fatigue loads and provide theoretical guidance for its measurement.
Existence of traversable wormholes in the minimally coupled gravity model
Authors: Naseer Tayyab , Sharif M. , Faiza Mona
Published: September 2024

The objective of this study is to examine the possible existence of traversable wormhole geometries within the context of [Formula: see text] gravity. To meet this objective, we employ the Karmarkar condition to construct the shape function that aids in identifying the wormhole configurations. This developed function is found to satisfy the essential conditions and provides a link between two asymptotically flat spacetime regions. We then assume the Morris–Thorne line element that expresses the wormhole configuration and formulate the anisotropic gravitational equations for a particular minimal matter-spacetime coupled model of the modified theory. Afterward, we develop three solutions and determine their viability by analyzing whether they violate the null energy conditions. Different stability methods are applied to the resulting geometries to explore the acceptance of the considered modified model. We conclude that the developed wormhole structures potentially fulfill the required criteria and thus exist in this modified gravity under all choices of the matter Lagrangian density.
Vicarious nucleophilic substitution of hydrogen and synthesis of nickel-, copper-, and cobalt-porphyrinates – double functionalized at the β-positions of the same pyrrole unit
Authors: Mikus Agnieszka , Ostrowski Stanisław
Published: September 2024

2-Nitro-5,10,15,20-tetraphenylporphyrin–nickel(II), –copper(II), and –cobalt(II) complexes reacted with carbanions of halomethyl aryl sulphones andpara-chlorophenoxyacetonitrile according to the vicarious nucleophilic substitution scheme. This leads to the substitution of hydrogen products, in the position ortho- to the NO2 group, thus giving β,β-disubstituted derivatives on the same pyrrole ring. The yields were satisfactory, up to 95%. These types of products, being practically unavailable by alternative methods, are attractive starting materials for the synthesis of more complex porphyrinoid moieties.
Permanence and extinction of the delay tumor-immune system with the stochastic environment
Authors: Wang Zhen , Jin Mengmeng
Published: September 2024

In this paper, we consider dynamical behaviors of the delay tumor-immune system perturbed by the environmental noise. For the stochastic delay tumor-immune system, we prove the existence and uniqueness of the globally positive solution and the boundedness of the solution. Using the stochastic Lyapunov analysis, comparison theorem and strong ergodic theorem, we establish sufficient conditions for the extinction, permanence and existence of the stationary distribution by considering the dynamics on the boundary. Moreover, we study the dynamical behaviors of the solution to the stochastic delay system around the equilibria of the deterministic model. In addition, numerical simulations and discussions are given to illustrate our analysis results. The numerical simulations show that for any delay [Formula: see text], [Formula: see text] is the threshold, which can characterize the stochastic permanence ([Formula: see text]) and extinction ([Formula: see text]) for the stochastic tumor-immune system.
Bounded acyclicity and relative simplicial volume
Authors: Li Kevin , Löh Clara , Moraschini Marco
Published: September 2024

In this paper, we provide new vanishing and glueing results for relative simplicial volume, following up on two current themes in bounded cohomology: The passage from amenable groups to boundedly acyclic groups and the use of equivariant topology. More precisely, we consider equivariant nerve pairs and relative classifying spaces for families of subgroups. Typically, we apply this to uniformly boundedly acyclic families of subgroups. Our methods also lead to vanishing results for [Formula: see text]-Betti numbers of aspherical CW-pairs with small relative amenable category and to a relative version of a result by Dranishnikov and Rudyak concerning mapping degrees and the inheritance of freeness of fundamental groups.
Rapid and controllable microwave synthesis of nickel cobalt sulfide electrodes for high-performance asymmetric supercapacitors
Authors: Zhao Guanghong , Liu Chao , Wei Yuan , Gao Yuhui , Liu Yubing , Liu Ronghui , Jiang Yanyan , Zhang Yulan , Shi Gaofeng , Wang Guoying
Published: September 2024

The efficient and controllable synthesis method of high-performance energy storage electrode materials is crucial for advancing the development of energy storage technologies. Herein, by leveraging microwave heating technology in the sulfidation of nickel cobalt MOF, we effectively enhanced the efficiency of the synthesis process. Notably, sulfidation time emerged as a pivotal factor in tuning the crystalline phase structure and conductive properties of the material, leading to the successful development of NCS2 electrode material with a unique structure through optimized sulfidation conditions. Electrochemical performance tests of the NCS2 material revealed exceptional results; it exhibited a specific capacity of 1311 Fg[Formula: see text] at a current density of 1 Ag[Formula: see text] and retained 73.4% of its initial capacity when the current density increased to 10 Ag[Formula: see text], demonstrating outstanding rate performance. The composite NCS2//AC supercapacitor exhibits an energy density of 24.2 Whkg[Formula: see text] at power density of 800 Wkg[Formula: see text], even though after 1000 consecutive charge-discharge cycles, the capacity retention rate remained high at 77.1%, validating the exceptional stability and reliability of the NCS2 material during cycling. This work employs microwave sulfidation for the rapid and controlled synthesis of nickel cobalt sulfides, providing a green and efficient synthetic strategy for metal sulfide active materials.
On Artinian rings whose ideal graph is a star
Authors: Jinnah M. I. , Mathew Shine C.
Published: September 2024

For each commutative ring [Formula: see text] we associate a simple graph [Formula: see text]. We investigate the properties of an Artinian ring [Formula: see text] when [Formula: see text] is a star.
Acoustic Radiation from Double Composite cylindrical Shells with Cyclic Rectangular Rib-Plates: Creeping Waves and Asymptotic Analyses
Authors: Cao Xiongtao
Published: September 2024

Acoustic radiation from double composite laminated cylindrical shells with cyclic rectangular rib-plates is analytically investigated by using the Sommerfeld-Watson transform. High-frequency acoustic model of double composite cylindrical shells with rectangular rib-plates is established in terms of creeping waves, geometrical acoustic waves and sound pressure asymptotic integrals. One kind of bending wave boundary layers for the shear deformable rectangular rib-plate is shown. Each set of creeping wave poles for the composite cylindrical shells with rectangular rib-plates is uniformly distributed by the cyclic period. This characteristic still holds for the cyclic structures with the smallest period. Creeping wave poles of the stiffened composite cylindrical shells appear in the entire complex circumferential wavenumber plane. The asymptotic integrals with Airy function are proposed to fast calculate acoustic pressure in the shadow and penumbra regions without making use of creeping wave poles.
Short Takeoff and Vertical Landing Aircraft Deceleration Transition Control Based on L1 Adaptive Control
Authors: Li Yifan , Zou Yuchun , Ding Jian , Liu Senlin , Zhen Ziyang
Published: September 2024

Addressing the issues of nonlinearity, control redundancy and coupling, and system uncertainties in the deceleration transition process from level flight to hover in short takeoff and vertical landing (STOVL) aircraft, this paper establishes a six-degree-of-freedom nonlinear mathematical model for the STOVL deceleration transition process. An augmented control method based on [Formula: see text] adaptive control is proposed for the deceleration transition process: dynamic inversion (DI) method is used to design the fundamental control laws for the inner and the outer loops, while an [Formula: see text] adaptive controller is employed as the augmented controller to enhance performance and robustness under system uncertainties. Simulation results validate that this method effectively suppresses system uncertainties and improves the transition control performance.
Mechanistic Analysis of Lithium-Air Battery with Organic Redox Mediator-Coated Air-Electrode
Authors: Azuma Shota , Moro Itsuki , Sano Mitsuki , Ozawa Fumisato , Saito Morihiro , Nomura Akihiro
Published: September 2024

Redox mediators (RMs) suppress the charging overpotential to enhance the cycle performance of lithium-air batteries (LABs), but inappropriate RM incorporation can adversely shorten cycle life. In this study, three typical organic RMs; tetrathiafulvalene (TTF), 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), and 10-methylphenothiazine (MPT), were incorporated into the air-electrode (AE) of the LAB (RM-on-AE), rather than dissolving them in the electrolyte (RM-in-EL), to maximize the RM effect throughout the cycle life. The discharge/charge cycle test confirmed that the cells with RM-on-AE prevented the reductive decomposition of RM with the lithium anode, deriving the RM effect for a longer cycle life than the cells with RM-in-EL. The measurement of AE deposits revealed that the TTF- and TEMPO-on-AE cells failed to generate a quantitative amount of Li2O2 discharge product. In contrast, the MPT-on-AE provided a 96% yield of Li2O2 after the first discharge because of the reductive tolerance of the MPT as organic RM. The quantitative analysis also revealed an accumulation of Li2CO3 on the AEs, along with the generation of carboxylate, as the side products of irrelevant battery reactions. This study provides a practical methodology for selecting RMs and their incorporation for developing long-life LABs.
Analysis of the therapeutic effect of pestle needle and EEG biofeedback and methylphenidate in the treatment of attention-deficit/hyperactivity disorder
Authors: Wang Ying , Liu Qifen , Liu Min , Wang Wei , Ye Shumeng , Liu Xiaobo , Liang Huan , Xue Xiaobao , Gao Haoyue
Published: September 2024

The pestle needle combined with EEG biofeedback and methylphenidate in ADHD children can elevate the IVA-CPT score. The pestle needle combined with EEG biofeedback and methylphenidate in ADHD children can improve EEG waves. The pestle needle combined with EEG biofeedback and methylphenidate in ADHD children can improve sleep quality. The pestle needle combined with EEG biofeedback and methylphenidate in ADHD children can regulate serum indicators.
Buoyancy Regulation in Insects
Authors: Matthews Philip G. D.
Published: September 2024

Multiple insect lineages have successfully reinvaded the aquatic environment, evolving to complete either part or all of their life cycle submerged in water. Although these insects vary in their reliance on atmospheric oxygen, with many having the ability to extract dissolved oxygen directly from the water, all retain an internal air-filled respiratory system, their tracheal system, due to their terrestrial origins. However, carrying air within their tracheal system, and even augmenting this volume with additional air bubbles carried on their body, dramatically increases their buoyancy, which can make it challenging to remain submerged. But by manipulating this air volume a few aquatic insects can deliberately alter or regulate their position in the water column. Unlike cephalopods and teleost fish that control the volume of gas within their hydrostatic organs by either using osmosis to pull liquid from a rigid chamber or secreting oxygen at high pressure to inflate a flexible chamber, insects have evolved hydrostatic control mechanisms that rely either on the temporary stabilization of a compressible air bubble volume with O2 unloaded from hemoglobin or on the mechanical expansion and contraction of a gas-filled volume with rigid, gas-permeable walls. The ability to increase their buoyancy while submerged separates aquatic insects from the buoyancy compensation achieved by other air-breathing aquatic animals that also use air within their respiratory systems to offset their submerged weight. The mechanisms they have evolved to achieve this are unique and provide new insights into the function and evolution of mechanochemical systems.
Modeling of Long‐Term Load Forecast in Jordan Based on Statistical Techniques
Authors: Momani Mohammad Awad , Tashtush Sajedah A. , Shahrour Rahaf J. , AlSatari Abeer M.
Published: September 2024

The paper proposes a mathematical model for long‐term load forecast (LTLF) based on parametric and time series statistical techniques. The flowchart of the proposed algorithm was also presented. The multiple linear regression (MLR) as well as the autoregressive integrated moving average (ARIMA) model with different model orders are employed in load forecasting. Historical data from 1990 to 2022 were utilized in the model implementation and validation. The input data imply gross domestic product (GDP), oil prices, population, and the energy from renewable energy projects as independent variables, and the annual peak load is the dependent variable. The results obtained by MLR show that population and GDP have a positive impact on electricity demand, whereas the oil price and the penetration of the renewable energy have a negative impact on electricity demand. In ARIMA, the load forecast is estimated based on error (residual) estimation that is determined based on the time lag operator and autoregressive and moving average coefficients. The ARIMA (p, d, and q) model with six different model orders is investigated. The Bayesian information criteria (BIC) and Akaike information criteria (AIC) indices are used as a measure in the selection of the appropriate model for prediction. The comparison between the six model’s scenarios shows that ARIMA (1, 1, 1) is the best model that fits the time series with minimum error and with the lowest BIC and AIC. The RMSE, MAPE, MSE, and MAE provided by ARIMA (1, 1, 1) are 3.57%, 2.55%, 0.13%, and 54.36, respectively, whereas the AIC and BIC are 386.8 and 394.0, respectively. A comparison between ARIMA and MLR shows that ARIMA is better than MLR in terms of time series fitting and error level. The LTLF forecast period covering the period 2024–2035 considers three scenarios of future development in the country: the normal (medium forecast), the optimistic (high forecast), and the pessimistic (low forecast). The forecast is made in the three directions (i.e., medium, high, and low) to avoid the ambiguity and uncertainty that may occur in the data input used in forecasting the electricity demand. A comparison between the MLR and ARIMA in the last year 2035 shows a small deviation between the two methods with the forecasted values in the range between 5480 MW and 5520 MW, respectively.
Supplementary Figure 2 from Therapeutic Efficacy of IL7/CCL19-Expressing CAR-T Cells in Intractable Solid Tumor Models of Glioblastoma and Pancreatic Cancer
Authors: Ohta Keisuke , Sakoda Yukimi , Adachi Keishi , Shinozaki Taro , Nakajima Masao , Yasuda Hiroyuki , Nagano Hiroaki , Tamada Koji
Published: September 2024

Supplementary Figure 2. Therapeutic effects of lower number of 7×19 CAR-T in pre-established solid tumor model of human glioblastoma.
Figure 4 from Therapeutic Efficacy of IL7/CCL19-Expressing CAR-T Cells in Intractable Solid Tumor Models of Glioblastoma and Pancreatic Cancer
Authors: Ohta Keisuke , Sakoda Yukimi , Adachi Keishi , Shinozaki Taro , Nakajima Masao , Yasuda Hiroyuki , Nagano Hiroaki , Tamada Koji
Published: September 2024

The diversity of TCR repertoire in T cells before and after the injection of 7 × 19 CAR-T. 7 × 19 CAR-T cells generated from PBMC were sorted into CAR-positive or -negative T cells and analyzed for repertoire of TCRα and TCRβ chains (before injection). Spleen cells were harvested from the mice which rejected U87MG EGFRvIII by the injection of anti-EGFRvIII 7 × 19 CAR, 42 days after tumor inoculation. Spleen cells were sorted into CAR-positive or -negative T cells for analysis of TCRα- and TCRβ-chain repertoire (after injection). TCR repertoire was analyzed using the next-generation sequencer, and the frequencies of V and J region usage were displayed as 3D graphs. The numbers in the graphs represent the diversity index calculated as Shannon–Weaver index H (a lower number indicates a less diversity). Representative data from three samples per group are shown.
Intraoperative Guidance of Pancreatic Cancer Resection Using a Toll-like Receptor 2–Targeted Fluorescence Molecular Imaging Agent
Authors: Huynh Amanda S. , Cohen Allison S. , Doligalski Michael , Casagni Todd J. , Moberg Valerie E. , Huang Xuan , Morse Jennifer , Abrahams Dominique , Lloyd Mark C. , Centeno Barbara A. , Baldwin Margaret K. , McLaughlin Mark L. , Vagner Josef , Morse David L.
Published: September 2024

To increase the achievement of negative R0 surgical margins and increase the low survival rates of pancreatic cancer, improvements in assessing tumor margins during surgical resections are needed. This can be accomplished by using pancreatic cancer–targeted fluorescence molecular imaging agents to intraoperatively detect tumor margins in real time. Because Toll-like receptor 2 (TLR2) is broadly expressed among many cancer types including pancreatic adenocarcinomas, a high-affinity TLR2-targeted fluorescence molecular imaging agent (TLR2L-800) was developed. We investigate the potential for increased survival by employing real-time intraoperative tumor detection in a preclinical orthotopic human pancreatic xenograft tumor model using TLR2L-800. Three cohorts of nude mice bearing orthotopic human pancreatic xenograft tumors were intravenously injected with TLR2L-800. At 24 hours postinjection, one cohort underwent in vivo fluorescence-guided surgical removal of tumors using a real-time fluorescence imaging platform, a second cohort underwent visible light surgery (VLS), and a third cohort did not undergo surgery. A fourth, nontumor-bearing cohort was administered TLR2L-800 with no surgery. At 41 days postsurgery, the survival rates were 53% for the fluorescence-guided surgery (FGS) group and 0% for both the VLS and the tumor-bearing no-surgery group. The overall 200-day survival rate of 35% for the FGS group was significant compared with 0% for the VLS group (P value = 0.0018). This study demonstrates the potential of increasing disease-free survival for patients with pancreatic cancer by increasing the attainment of R0 margins using a novel tumor-targeted lipopeptide ligand-based fluorescence molecular imaging agent, TLR2L-800, during real-time FGS.

Significance:

Human TLR2 is broadly expressed among pancreatic adenocarcinomas, and the highly specific TLR2L-800 fluorescence molecular imaging agent has potential for use in fluorescence-guided surgery to increase R0 margins and improve patient survival.
A Precision Engineered Interleukin-2 for Bolstering CD8+ T- and NK-cell Activity without Eosinophilia and Vascular Leak Syndrome in Nonhuman Primates
Authors: Ma Lina , Acuff Nicole V. , Joseph Ingrid B. , Ptacin Jerod L. , Caffaro Carolina E. , San Jose Kristine M. , Aerni Hans R. , Carrio Roberto , Byers Anthony M. , Herman Rob W. , Pavlova Yelena , Pena Michael J. , Chen David B. , Buetz Christen , Ismaili Taylor K. , Pham Helene V. , Cucchetti Margot , Sassoon Ingrid , Koriazova Lilia K. , Leveque Joseph A. , Shawver Laura K. , Mooney Jill M. , Milla Marcos E.
Published: September 2024

We have created a precisely pegylated IL-2 [SAR-444245 (SAR’245) or pegenzileukin, previously THOR-707] designed for proliferation of target CD8+ T and NK cells for anticancer activity, with minimal expansion of anti-target regulatory CD4+ T cells (Treg) that counter their action, or eosinophils that trigger vascular leak syndrome (VLS). We performed in vivo studies in nonhuman primates (NHP) to monitor the safety of SAR’245, pharmacokinetic profile, and pharmacodynamic parameters including expansion of peripheral CD8+ T and NK cells, and effects on Tregs and eosinophils. Studies included multiple ascending dosing and repeat dosing with different regimens (QW, Q2W, Q3W and Q4W). We also conducted ex vivo studies using human primary cells to further evaluate SAR’245 stimulation of target cells alone and in combination with programmed cell-death 1 (PD-1) checkpoint inhibitors. The pharmacokinetic profile of SAR’245 in NHP demonstrated dose-proportional exposure that was comparable with redosing. It elicited expansion of peripheral CD8+ T and NK cells that was comparable with each dose and with multiple dosing regimens. Once-weekly dosing showed no significant adverse effects, including no hallmark signs of VLS at dosing levels up to 1 mg/kg. Ex vivo, SAR’245 enhanced T-cell receptor responses alone and in combination with PD-1 inhibitors without inducing cytokines associated with cytokine release syndrome or VLS. Results support the clinical development of SAR’245 as a drug candidate for the treatment of solid tumors, alone or in combination with PD-1 inhibitory agents.

Significance:

SAR-444245 (SAR’245, pegenzileukin) is an extended half-life IL-2 that targets effector CD8+ T and NK cells, with little effect on regulatory T cells. We show that in the nonhuman primate model that closely approximates human immune function and response to IL-2, SAR’245 selectively activates CD8+ T and NK effectors without significant serious side effects (vascular leak syndrome or cytokine release syndrome), suggesting its potential for the treatment of solid tumors in humans.
Peripheral Blood IFN Responses to Toll-Like Receptor 1/2 Signaling Associate with Longer Survival in Men with Metastatic Prostate Cancer Treated with Sipuleucel-T
Authors: Brown Michael C. , D’Anniballe Vincent M. , Boczkowski David , Kandadi Harini , Sheikh Nadeem , Kornahrens William , Heath Elisabeth I. , Thakur Archana , Chen Wei , Lum Lawrence , Cackowski Frank C. , Boerner Julie , Gunn Michael D. , Armstrong Andrew J. , Nair Smita K.
Published: September 2024

Mounting evidence links systemic innate immunity with cancer immune surveillance. In advanced metastatic castration-resistant prostate cancer (mCRPC), Black patients have been found to have increased inflammatory markers and longer survival after sipuleucel-T (sip-T) therapy, an FDA-approved, autologous cell therapy. We hypothesized these differences may be explained by previously reported ancestral differences in pattern recognition receptor signaling, which broadly governs innate inflammation to control adaptive immune cell activation, chemotaxis, and functionality. We discovered that peripheral blood mononuclear cell IFN-β responses to Toll-like receptor 1/2 (TLR1/2), a sensor of bacterial and gut microbiome constituents, associated with significantly longer survival after sip-T therapy in two separate cohorts of men with mCRPC (discovery cohort: n = 106, HR = 0.12; P = 0.019; validation cohort: n = 28, HR < 0.01; P = 0.047). Higher IFN-β induction after TLR1/2 stimulation was associated with lower HRs than biomarkers of vaccine potency and other prognostic factors in mCRPC. TLR1/2-dependent cytokine induction was stronger in Black individuals (1.2-fold higher for IFN-β; P = 0.04) but was associated with survival independently of race or numbers of vaccine-induced tumor antigen–specific T cells. IFN-β responses to TLR1/2 signaling correlated with increased numbers of IFN-γ producing T cells after broad, tumor antigen–independent stimulation. Thus, peripheral innate immunity differs by race, may predict survival after sip-T, and associates with peripheral T-cell functionality in men with mCRPC.

Significance:

The identification of factors that determine successful cancer immunotherapy, particularly in refractory tumor types like mCRPC, is urgently needed: both to identify patients that may benefit from such therapies and to uncover routes to sensitize patients with cancer to immunotherapy. Our work links functional peripheral immune responses with race and survival after cellular immunotherapy in men with mCRPC.
External Validation of a Vision Prognostication Tool for Vision Loss after Plaque Brachytherapy
Authors: Guillot Florian H. , Miller Audra K. , Kosydar Misty , Kaya Erin , Merz Brandon , Binder Christina , Kahn Jenna M. , Johnson Alicia J. , Skalet Alison H.
Published: September 2024

Introduction: Vision loss remains a significant concern for patients undergoing radiation treatment for uveal melanoma. Herein, we identify predictors of vision loss after plaque brachytherapy at our academic medical center and, using this independent data set, evaluate a published vision prognostication tool. Methods: A retrospective chart review identified 252 posterior uveal melanoma patients treated with iodine-125 plaque brachytherapy from 2013 to 2018. Interval-censored nonparametric survival analysis estimated risk for moderate (<20/50) and severe (<20/200) vision loss at 3 and 5 years post-brachytherapy. Factors affecting vision loss were evaluated using interval-censored proportional hazards regression models. The prognostication tool was evaluated using a receiver operating curve and comparing predicted risk to observed risk. Results: Increased age, tumor height, and radiation dose to optic disc were associated with vision loss for patients with baseline VA ≥20/50. For those with baseline VA ≥20/200, risk factors included dose to optic disc, female sex, and baseline vision worse than 20/50. The vision prognostication tool demonstrated a moderate ability to differentiate patients with 3-year vision <20/200, with an area under the curve of 0.75. Conclusion: The vision prognostication tool was predictive for vision loss but generally overestimated risk, possibly reflecting evolving practice patterns including anti-VEGF use for radiation retinopathy.
ENaCγ in Urinary Extracellular Vesicles as an Indicator of MR Signaling in Primary Aldosteronism
Authors: Hayama Yuto , Kuribayashi-Okuma Emiko , Fujii Norihiko , Ochiai-Homma Fumika , Yamazaki Osamu , Tsurutani Yuya , Nishikawa Tetsuo , Shibata Shigeru
Published: September 2024

BACKGROUND:

Aldosterone and the MR (mineralocorticoid receptor) are important therapeutic targets for hypertension and cardiovascular diseases. However, biomarkers of tissue MR signaling are not fully established. Extracellular vesicles released from eukaryotic cells can provide information on tissue signaling. Using samples from patients with primary aldosteronism (PA), we explored the potential of urinary extracellular vesicles (uEVs) as a noninvasive indicator of MR signaling to guide treatment.

METHODS:

We analyzed proteins contained in PA uEVs by liquid chromatography tandem mass spectrometry. We narrowed down candidate biomarkers by referring to an existing database of urinary exosomes. The results were validated through Western blot analysis involving 63 patients with PA and 11 healthy volunteers.

RESULTS:

We identified a total of 1940 proteins in PA uEVs. Comparative analysis with the existing database narrowed down the pathways enriched in PA uEVs, which were related to diabetic complications, Rac1 signaling, and aldosterone-regulated sodium reabsorption. A closer look at the identified proteins revealed ENaCγ (epithelial Na
+
channel γ) peptides near the proteolytic cleavage sites, and Western blot analysis confirmed the predominant presence of cleaved ENaCγ, a marker of aldosterone signaling in renal tubules. In PA uEVs, cleaved ENaCγ showed a 4.8-fold increase compared with healthy volunteers and was significantly correlated with the aldosterone-to-renin ratio, aldosterone levels, and fractional excretion of K
+
. Targeted treatment in PA reduced the abundance of cleaved ENaCγ, suggesting a causal role for MR in its induction.

CONCLUSIONS:

This study provides a list of proteins contained in PA uEVs and suggests that ENaCγ in uEVs is a promising biomarker for renal MR signaling.
Characteristics of Young Women Presenting With Acute Myocardial Infarction: The Prospective, Multicenter, Observational Young Women Presenting Acute Myocardial Infarction in France Study
Authors: Manzo‐Silberman Stéphane , Couturaud Francis , Bellemain‐Appaix Anne , Vautrin Estelle , Gompel Anne , Drouet Ludovic , Marliere Stephanie , Sollier Claire Bal Dit , Uhry Sabrina , Eltchaninoff Hélène , Bergot Tessa , Motreff Pascal , Lahlou Najiba , Cottin Yves , Mounier‐Vehier Claire , Gilard Martine , Montalescot Gilles ,   for the WAMIF Investigators
Published: September 2024

Background

The percentage of women <50 years of age hospitalized with myocardial infarction is increasing. We describe the clinical, morphological, and biological characteristics, as well as the clinical outcomes of this population.

Methods and Results

This prospective, observational study included consecutive women <50 years of age admitted for myocardial infarction at 30 centers in France (May 2017–June 2019). The primary outcome was the composite of net adverse clinical events: all‐cause death, cardiovascular death, recurrent myocardial infarction, stent thrombosis, any stroke, or major bleeding occurring during hospitalization with a 12‐month follow up. Three hundred fourteen women were included. The mean age was 43.0 (±5.7) years, 60.8% presented with ST‐segment–elevation myocardial infarction, 75.5% were current smokers, 31.2% had a history of complicated pregnancy, and 55.1% reported recent emotional stress. Most (91.6%) women presented with typical chest pain. Of patients on an estrogen‐containing contraceptive, 86.0% had at least 1 contraindication. Of patients with ST‐segment–elevation myocardial infarction, 17.8% had myocardial infarction with nonobstructive coronary arteries and 14.6% had spontaneous coronary artery dissection, whereas 29.3% presented with multivessel vessel disease. During hospitalization, 11 net adverse clinical events occurred in 9 (2.8%) women, but no deaths or stent thromboses occurred. By 12 months, 14 net adverse clinical events occurred in 10 (3.2%) women; 2 (0.6%) died (from progressive cancer) and 25 (7.9%) had an ischemia‐driven repeat percutaneous coronary intervention.

Conclusions

Most young women with myocardial infarction reported typical chest pain and had modifiable cardiovascular risk factors. History of adverse pregnancy outcomes and prescription of combined oral contraceptive despite a contraindication were prevalent, emphasizing the need for comprehensive cardiological and gynecological evaluation and follow‐up.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03073447.