bluuebunny/crossref_metadata_2025 huggingface dataset:
Cysteine oxidation as a regulatory mechanism of Arabidopsis plastidial NAD‐dependent malate dehydrogenase
Authors: Cosse Maike , Rehders Tanja , Eirich Jürgen , Finkemeier Iris , Selinski Jennifer
Published: May 2024

Malate dehydrogenases (MDHs) catalyze a reversible NAD(P)‐dependent‐oxidoreductase reaction that plays an important role in central metabolism and redox homeostasis of plant cells. Recent studies suggest a moonlighting function of plastidial NAD‐dependent MDH (plNAD‐MDH; EC 1.1.1.37) in plastid biogenesis, independent of its enzyme activity. In this study, redox effects on activity and conformation of recombinant plNAD‐MDH from Arabidopsis thaliana were investigated. We show that reduced plNAD‐MDH is active while it is inhibited upon oxidation. Interestingly, the presence of its cofactors NAD+ and NADH could prevent oxidative inhibition of plNAD‐MDH. In addition, a conformational change upon oxidation could be observed via non‐reducing SDS‐PAGE. Both effects, its inhibition and conformational change, were reversible by re‐reduction. Further investigation of single cysteine substitutions and mass spectrometry revealed that oxidation of plNAD‐MDH leads to oxidation of all four cysteine residues. However, cysteine oxidation of C129 leads to inhibition of plNAD‐MDH activity and oxidation of C147 induces its conformational change. In contrast, oxidation of C190 and C333 does not affect plNAD‐MDH activity or structure. Our results demonstrate that plNAD‐MDH activity can be reversibly inhibited, but not inactivated, by cysteine oxidation and might be co‐regulated by the availability of its cofactors in vivo.
It is, uh, very likely? The impact of prosodic uncertainty cues on the perception and interpretation of spoken verbal probability phrases
Authors: Vromans Ruben D. , van de Ven Charlot C. M. , Willems Sanne J. W. , Krahmer Emiel J. , Swerts Marc G. J.
Published: May 2024

People typically use verbal probability phrases when discussing risks (“It is likely that this treatment will work”), both in written and spoken communication. When speakers are uncertain about risks, they can nonverbally signal this uncertainty by using prosodic cues, such as a rising, question‐like intonation or a filled pause (“uh”). We experimentally studied the effects of these two prosodic cues on the listener's perceived speaker certainty and numerical interpretation of spoken verbal probability phrases. Participants (N = 115) listened to various verbal probability phrases that were uttered with a rising or falling global intonation and with or without a filled pause before the probability phrase. For each phrase, they gave a point estimate of their numerical interpretation in percentages and indicated how certain they thought the speaker was about the correctness of the probability phrase. Speakers were perceived as least certain when the verbal probability phrases were spoken with both prosodic uncertainty cues. Interpretation of verbal probability phrases varied widely across participants, especially when rising intonation was produced by the speaker. Overall, high probability phrases (e.g., “very likely”) were estimated as lower (and low probability phrases, such as “unlikely,” as higher) when they were uttered with a rising intonation. The effects of filled pauses were less pronounced, as were the uncertainty effects for medium probability phrases (e.g., “probable”). These results stress the importance of nonverbal communication when verbally communicating risks and probabilities to people, for example, in the context of doctor–patient communication.
Toward a middle‐range theory of environmental morality
Authors: Hannigan John
Published: May 2024

Nearly three decades ago, Gramling and Freudenburg (1996) urged that greater attention be given to middle‐range efforts in environmental sociology. In this article, I will argue that since Gramling and Freudenburg offered their advice, there has been a critical mass of work in environmental sociology undertaken from the perspective of middle‐range theory, but this has been undervalued in our never‐ending odyssey in search for grand theory. To illustrate this, I review sociological enquiry into risk and risk communication. To make a case of my own for a middle‐range sociology appropriate to the second quartile of the 21st century, I advocate the development of a “sociology of environmental morality” (see Farrell, 2015; Hannigan forthcoming, 2024; Stock, 2020) to be pursued via a middle‐range perspective. I conclude by outlining two strategies for pursuing a middle‐range sociology of environmental morality.
A call for a sociology of adaptation
Authors: Falzon Danielle , Sen Raka
Published: May 2024

Interest in examining climate change adaptation has arisen in many disciplines in the past two decades; however to date, sociologists have given only sparse attention to the issue. This is both a missed opportunity for sociologists and a detriment to the study of adaptation. In this paper, we set out the following research agenda: bringing core concerns of sociology into the critically important conversation of how society will respond to climate change. We identify five broad themes in which sociologists can begin their work on adaptation: (1) structures and resource access, (2) social cohesion and future planning, (3) constraints of social stratifications, (4) power and agency in decision‐making, and (5) justice in process and outcomes. After summarizing existing sociological work on adaptation and detailing our research agenda, we draw examples from our own work in Bangladesh to illustrate how this agenda might be taken up. In doing so, we point to several places where sociological insights come into play in questions related to development, organizations, expertise, migration, gender, and labor. We believe a robust sociological analysis can produce a clarified, reparative, and just conceptualization of adaptation that will contribute to the growing global discourse on the topic.
Molecular mechanisms underlying low temperature inhibition of grain filling in maize (Zea mays L.): coordination of growth and cold responses
Authors: Xu Chenchen , Wang Xin , Wu Yi , Gao Jia , Zhang Ping , Zhao Yating , Liu Xiaoli , Wang Pu , Huang Shoubing
Published: May 2024

Low temperature (LT) greatly restricts grain filling in maize (Zea mays L.), but the relevant molecular mechanisms are not fully understood. To better understand the effect of LT on grain development, 17 hybrids were subjected to LT stress in field trials over 3 years, and two hybrids of them with contrasting LT responses were exposed to 30/20°C and 20/10°C for 7 days during grain filling in a greenhouse. At LT, thousand‐kernel weight declined, especially in LT‐sensitive hybrid FM985, while grain‐filling rate was on average about 48% higher in LT‐tolerant hybrid DK159 than FM985. LT reduced starch synthesis in kernel mainly by suppression of transcript levels and enzyme activities for sucrose synthase and hexokinase. Brassinolide (BR) was abundant in DK159 kernel, and genes involved in BR and cytokinin signals were inducible by stress. LT downregulated the genes in light‐harvesting complex and photosystem I/II subunits, accompanied by reduced photosynthetic rate and Fv/Fm in ear leaf. The LT‐tolerant hybrid could maintain a high soluble sugar content and fast interconversion between sucrose and hexose in the stem internode and cob, improving assimilate allocation to kernel at LT stress and paving the way for simultaneous growth and LT stress responses.
Mitochondrial respiration is lower in the intrauterine growth‐restricted fetal sheep heart
Authors: Chang Eileen I. , Stremming Jane , Knaub Leslie A. , Wesolowski Stephanie R. , Rozance Paul J. , Sucharov Carmen C. , Reusch Jane E. B. , Brown Laura D.
Published: May 2024

Fetuses affected by intrauterine growth restriction have an increased risk of developing heart disease and failure in adulthood. Compared with controls, late gestation intrauterine growth‐restricted (IUGR) fetal sheep have fewer binucleated cardiomyocytes, reflecting a more immature heart, which may reduce mitochondrial capacity to oxidize substrates. We hypothesized that the late gestation IUGR fetal heart has a lower capacity for mitochondrial oxidative phosphorylation. Left (LV) and right (RV) ventricles from IUGR and control (CON) fetal sheep at 90% gestation were harvested. Mitochondrial respiration (states 1–3, LeakOmy, and maximal respiration) in response to carbohydrates and lipids, citrate synthase (CS) activity, protein expression levels of mitochondrial oxidative phosphorylation complexes (CI–CV), and mRNA expression levels of mitochondrial biosynthesis regulators were measured. The carbohydrate and lipid state 3 respiration rates were lower in IUGR than CON, and CS activity was lower in IUGR LV than CON LV. However, relative CII and CV protein levels were higher in IUGR than CON; CV expression level was higher in IUGR than CON. Genes involved in lipid metabolism had lower expression in IUGR than CON. In addition, the LV and RV demonstrated distinct differences in oxygen flux and gene expression levels, which were independent from CON and IUGR status. Low mitochondrial respiration and CS activity in the IUGR heart compared with CON are consistent with delayed cardiomyocyte maturation, and CII and CV protein expression levels may be upregulated to support ATP production. These insights will provide a better understanding of fetal heart development in an adverse in utero environment.

image

Key points

Growth‐restricted fetuses have a higher risk of developing and dying from cardiovascular diseases in adulthood.

Mitochondria are the main supplier of energy for the heart. As the heart matures, the substrate preference of the mitochondria switches from carbohydrates to lipids.

We used a sheep model of intrauterine growth restriction to study the capacity of the mitochondria in the heart to produce energy using either carbohydrate or lipid substrates by measuring how much oxygen was consumed.

Our data show that the mitochondria respiration levels in the growth‐restricted fetal heart were lower than in the normally growing fetuses, and the expression levels of genes involved in lipid metabolism were also lower. Differences between the right and left ventricles that are independent of the fetal growth restriction condition were identified.

These results indicate an impaired metabolic maturation of the growth‐restricted fetal heart associated with a decreased capacity to oxidize lipids postnatally.
Influence of soundboard modelling approaches on piano string vibration
Authors: Miranda Valiente Pablo , Squicciarini Giacomo , Thompson David J.
Published: May 2024

This work explores the influence of the dynamics of the piano soundboard on string vibration and on the force acting between the vibrating string and the bridge. Four different soundboard representations of different complexities are considered: (i) a finite element model that considers the complete dynamic behavior of the soundboard at the connection point with the string within the frequency range of interest, (ii) a reduced modal model containing only five modes, (iii) a Kelvin–Voigt system characterized by an equivalent stiffness and damping, and (iv) a rigid soundboard represented by a simply supported boundary condition. The connection between the string and the soundboard is modelled by coupling a simply supported stiff string model with the different representations of the soundboard through a contact stiffness. As well as directly accounting for the string-soundboard coupling, this approach also includes the duplex scaling segment. The latter can be left to vibrate freely or muted with a continuous distribution of dampers. Although the simplest soundboard representation is not dissimilar from the other more complex models, the dynamics of the soundboard affect the decay time of the note, the force transmitted to it, and the vibration of the radiating surface of the soundboard.
Frequency-dependent temporary threshold shifts in the Eastern painted turtle (Chrysemys picta picta)
Authors: Salas Andria K. , Capuano Alyssa M. , Harms Craig A. , Piniak Wendy E. D. , Mooney T. Aran
Published: May 2024

Testudines are a highly threatened group facing an array of stressors, including alteration of their sensory environment. Underwater noise pollution has the potential to induce hearing loss and disrupt detection of biologically important acoustic cues and signals. To examine the conditions that induce temporary threshold shifts (TTS) in hearing in the freshwater Eastern painted turtle (Chrysemys picta picta), three individuals were exposed to band limited continuous white noise (50–1000 Hz) of varying durations and amplitudes (sound exposure levels ranged from 151 to 171 dB re 1 μPa2 s). Control and post-exposure auditory thresholds were measured and compared at 400 and 600 Hz using auditory evoked potential methods. TTS occurred in all individuals at both test frequencies, with shifts of 6.1–41.4 dB. While the numbers of TTS occurrences were equal between frequencies, greater shifts were observed at 600 Hz, a frequency of higher auditory sensitivity, compared to 400 Hz. The onset of TTS occurred at 154 dB re 1 μPa2 s for 600 Hz, compared to 158 dB re 1 μPa2 s at 400 Hz. The 400-Hz onset and patterns of TTS growth and recovery were similar to those observed in previously studied Trachemys scripta elegans, suggesting TTS may be comparable across Emydidae species.
Arg1 from
Cryptococcus neoformans
lacks PI3 kinase activity and conveys virulence roles via its IP
3-4
kinase activity
Authors: Desmarini Desmarini , Liu Guizhen , Jessen Henning , Bowring Bethany , Connolly Angela , Crossett Ben , Djordjevic Julianne Teresa
Published: May 2024

Inositol tris/tetrakis phosphate kinases (IP
3-4
K) in the human fungal priority pathogens,
Cryptococcus neoformans
(
Cn
Arg1) and
Candida albicans
(
Ca
Ipk2), convey numerous virulence functions, yet it is not known whether the IP
3-4
K catalytic activity or a scaffolding role is responsible. We therefore generated a
C. neoformans
strain with a non-functional kinase, referred to as the dead-kinase (dk)
Cn
Arg1 strain (dkArg1). We verified that, although dk
ARG1
cDNA cloned from this strain produced a protein with the expected molecular weight, dkArg1 was catalytically inactive with no IP
3-4
K activity. Using recombinant
Cn
Arg1 and
Ca
Ipk2
,
we confirmed that, unlike the IP
3-4
K homologs in humans and
Saccharomyces cerevisiae
,
Cn
Arg1 and
Ca
Ipk2 do not phosphorylate the lipid-based substrate, phosphatidylinositol 4,5-bisphosphate, and therefore do not function as class I PI3Ks. Inositol polyphosphate profiling using capillary electrophoresis-electrospray ionization-mass spectrometry revealed that IP
3
conversion is blocked in the dkArg1 and
ARG1
deletion (
Cnarg1
Δ) strains and that 1-IP
7
and a recently discovered isomer (4/6-IP
7
) are made by wild-type
C. neoformans
. Importantly, the dkArg1 and
Cnarg1
Δ strains had similar virulence defects, including suppressed growth at 37°C, melanization, capsule production, and phosphate starvation response, and were avirulent in an insect model, confirming that virulence is dependent on IP
3-4
K catalytic activity. Our data also implicate the dkArg1 scaffold in transcriptional regulation of arginine metabolism but via a different mechanism to
S. cerevisiae
since
Cn
Arg1 is dispensable for growth on different nitrogen sources. IP
3-4
K catalytic activity therefore plays a dominant role in fungal virulence, and IPK pathway function has diverged in fungal pathogens.

IMPORTANCE

The World Health Organization has emphasized the urgent need for global action in tackling the high morbidity and mortality rates stemming from invasive fungal infections, which are exacerbated by the limited variety and compromised effectiveness of available drug classes. Fungal IP
3-4
K is a promising target for new therapy, as it is critical for promoting virulence of the human fungal priority pathogens,
Cryptococcus neoformans
and
Candida albicans
, and impacts numerous functions, including cell wall integrity. This contrasts to current therapies, which only target a single function. IP
3-4
K enzymes exert their effect through their inositol polyphosphate products or via the protein scaffold. Here, we confirm that the IP
3-4
K catalytic activity of
Cn
Arg1 promotes all virulence traits in
C. neoformans
that are attenuated by
ARG1
deletion
,
reinforcing our ongoing efforts to find inositol polyphosphate effector proteins and to create inhibitors targeting the IP
3-4
K catalytic site, as a new antifungal drug class.
Aspartyl peptidase May1 induces host inflammatory response by altering cell wall composition in the fungal pathogen
Cryptococcus neoformans
Authors: Li Yeqi , Chadwick Benjamin , Pham Tuyetnhu , Xie Xiaofeng , Lin Xiaorong
Published: May 2024

Cryptococcus neoformans
causes cryptococcal meningoencephalitis, a disease that kills more than 180,000 people annually. Contributing to its success as a fungal pathogen is its cell wall surrounded by a capsule. When the cryptococcal cell wall is compromised, exposed pathogen-associated molecular pattern molecules (PAMPs) could trigger host recognition and initiate attack against this fungus. Thus, cell wall composition and structure are tightly regulated. The cryptococcal cell wall is unusual in that chitosan, the acetylated form of chitin, is predominant over chitin and is essential for virulence. Recently, it was shown that acidic pH weakens the cell wall and increases exposure of PAMPs partly due to decreased chitosan levels. However, the molecular mechanism responsible for the cell wall remodeling in acidic pH is unknown. In this study, by screening for genes involved in cryptococcal tolerance to high levels of CO
2
, we serendipitously discovered that the aspartyl peptidase May1 contributes to cryptococcal sensitivity to high levels of CO
2
due to acidification of unbuffered media. Overexpression of
MAY1
increases the cryptococcal cell size and elevates PAMP exposure, causing a hyper-inflammatory response in the host while
MAY1
deletion does the opposite. We discovered that May1 weakens the cell wall and reduces the chitosan level, partly due to its involvement in the degradation of Chs3, the sole chitin synthase that supplies chitin to be converted to chitosan. Consistently, overexpression of
CHS3
largely rescues the phenotype of
MAY1
oe
in acidic media. Collectively, we demonstrate that May1 remodels the cryptococcal cell wall in acidic pH by reducing chitosan levels through its influence on Chs3.

IMPORTANCE

The fungal cell wall is a dynamic structure, monitoring and responding to internal and external stimuli. It provides a formidable armor to the fungus. However, in a weakened state, the cell wall also triggers host immune attack when PAMPs, including glucan, chitin, and mannoproteins, are exposed. In this work, we found that the aspartyl peptidase May1 impairs the cell wall of
Cryptococcus neoformans
and increases the exposure of PAMPs in the acidic environment by reducing the chitosan level. Under acidic conditions, May1 is involved in the degradation of the chitin synthase Chs3, which supplies chitin to be deacetylated to chitosan. Consistently, the severe deficiency of chitosan in acidic pH can be rescued by overexpressing
CHS3
. These findings improve our understanding of cell wall remodeling and reveal a potential target to compromise the cell wall integrity in this important fungal pathogen.
Oligocene and Miocene blowtorch volcanism within the California Borderland and its influence on the plate-boundary transition
Authors: Balbas Andrea , Konrad Kevin , Onderdonk Nathan , Castillo Paterno R. , Behl Richard
Published: May 2024

The California Borderland is a uniquely broad and complex region of the North American–Pacific transform margin. Oligocene to Miocene structural reorganization, including large-magnitude extension and vertical-axis rotation of crustal blocks, formed a network of submerged fault-bounded basins, ridges, and islands offshore of southern California during its evolution from a convergent to transform boundary. Here, we report new 40Ar/39Ar incremental heating age determinations and geochemical analyses of volcanic rocks in the California Borderland, as well as a reconciled regional tectonic model. The California Borderland volcanic rocks are calc-alkaline in composition and mostly silica-oversaturated and represent relatively large-degree partial melts of the asthenosphere that incorporated hydrated forearc lithospheric components. A temporal reconciliation of these records shows that subduction of an active spreading center starting in the Oligocene and again in the Miocene was the critical control on the observed volcanism at ca. 31–30 Ma and 19–13 Ma. We posit that prolonged trench-ridge interaction generated a blowtorch effect, which resulted in widespread forearc volcanism and weakening of the crust to facilitate the unique deformation styles documented in the borderland that did not occur elsewhere along the North American–Pacific plate boundary.
Conformational Diversity of Lipids
Authors: Boldyrev I. A.
Published: May 2024

The conformational diversity of hydrophobic lipid chains has been studied. The number of possible conformations of a lipid chain, as well as the number of these conformations that can be realized in a real system, has been determined. A set theory approach to the analysis of conformations of lipid molecules has been proposed, and a relation of the sets of conformations realized in a lipid structure to the energy of the system has been introduced. Using the set theory, it has been considered which conformations of hydrophobic lipid chains can be realized in the real system. The notion of the key conformation has been formulated to estimate the correlation between the structural characteristics of lipids and the energy characteristics of membranes.
On the Saturation of the Instability of Induced Ordinary Microwave Scattering in the Edge Transport Barrier of a Tokamak during Electron Cyclotron Resonance Heating of a Plasma
Authors: Gusakov E. Z. , Popov A. Yu.
Published: May 2024

The saturation of the low-threshold parametric decay instability of an ordinary wave during electron cyclotron resonance heating in the edge transport barrier of a tokamak due to the stochastic damping of a daughter two-dimensionally localized oblique Langmuir wave has been considered. It has been found that the saturation of instability in modern devices occurs at a relatively low level and does not affect the energy balance during plasma heating. It has been shown that the efficiency of nonlinear pump under expected conditions of microwave power injection in the International Thermonuclear Experimental Reactor will exceed the maximum efficiency of stochastic damping, which will result in the breaking of amplitude-dependent saturation and can significantly modify the power deposition profile.
Socioeconomic gradients in 24-hour movement patterns across weekends and weekdays in a working-age sample: evidence from the 1970 British Cohort Study
Authors: Blodgett Joanna M , Bann David , Chastin Sebastien F M , Ahmadi Matthew , Stamatakis Emmanuel , Cooper Rachel , Hamer Mark
Published: May 2024

Background

Socioeconomic differences in movement behaviours may contribute to health inequalities. The aim of this descriptive study was to investigate socioeconomic patterns in device-measured 24-hour movement and assess whether patterns differ between weekdays and weekends.

Methods

4894 individuals aged 46 years from the 1970 British Cohort Study were included. Participants wore thigh-worn accelerometers for 7 days. Movement behaviours were classified in two 24-hour compositions based on intensity and posture, respectively: (1) sleep, sedentary behaviour, light-intensity activity and moderate-vigorous activity; and (2) sleep, lying, sitting, standing, light movement, walking and combined exercise-like activity. Four socioeconomic measures were explored: education, occupation, income and deprivation index. Movement behaviours were considered compositional means on a 24-hour scale; isometric log ratios expressed per cent differences in daily time in each activity compared with the sample mean.

Results

Associations were consistent across all socioeconomic measures. For example, those with a degree spent more time in exercise-like activities across weekdays (10.8%, 95% CI 7.3 to 14.7; ref: sample mean) and weekends (21.9%, 95% CI 17.2 to 26.9). Other patterns differed markedly by the day of the week. Those with no formal qualifications spent more time standing (5.1%, 95% CI 2.3 to 7.1), moving (10.8%, 95% CI 8.6 to 13.1) and walking(4.0%, 95% CI 2.2 to 6.1) during weekdays, with no differences on weekends. Conversely, those with no formal qualifications spent less time sitting during weekdays (−6.6%, 95% CI −7.8 to –4.8), yet more time lying on both weekends (8.8%, 95% CI 4.9 to 12.2) and weekdays (7.5%, 95% CI 4.0 to 11.5).

Conclusions

There were strong socioeconomic gradients in 24-hour movement behaviours, with notable differences between weekdays/weekends and behaviour type/posture. These findings emphasise the need to consider socioeconomic position, behaviour type/posture and the day of the week when researching or designing interventions targeting working-age adults.
Smokers' beliefs about “Light” and “Ultra Light” cigarettes
Authors: Shiffman Saul , Pillitteri Janine L , Burton Steven L , Rohay Jeffrey M , Gitchell Joe G
Published: May 2024

OBJECTIVE

To assess beliefs about the tar and nicotine delivery characteristics and health benefits of Light and Ultra Light cigarettes among cigarette smokers.

DESIGN

Random digit dialed telephone survey conducted in September 1999.

SUBJECTS

Daily smokers (n = 2120) of Regular (46%), Light (39%), and Ultra Light (15%) cigarettes in the USA. The sample was weighted to match the US smoker population on age, sex, and ethnicity.

MAIN OUTCOME MEASURES

Beliefs about Light and Ultra Light cigarettes were summarised on three dimensions: Safety (reduced health risk), Delivery (lowered tar and nicotine delivery), and Sensation (less harsh).

RESULTS

Most smokers believed Lights and Ultra Lights were less harsh and delivered less tar and nicotine. On average, smokers believed that Lights afforded a 25% reduction in risk, and Ultra Lights a 33% reduction in risk. Light and Ultra Light cigarette smokers evaluated the risks of their own cigarette types more favourably. Light smokers had greater interest in quitting than Ultra Light smokers. Quitting intention was modestly related to beliefs about these cigarettes. Believing that Lights and Ultra Lights delivered less tar and nicotine and that they were less harsh each independently contributed to the belief that these cigarettes were safer.

CONCLUSIONS

Many Light and Ultra Light smokers believe that smoking these cigarettes impart a substantial health benefit, due in part to their experience that these cigarettes are less harsh and the belief that these cigarettes deliver less tar.
Design stability charts for construction procedure of basement walls using staged bermed excavation: a parametric study
Authors: Cano Miguel , Pastor José Luis , Riquelme Adrián , Tomás Roberto
Published: May 2024

The construction of basement walls using discontinuous staged berms is based on excavating the central zone of a lot and leaving a lateral berm—which is then removed in phases with unexcavated sections (buttresses) remaining until a concrete wall is completed in the excavated areas. It is a commonly used technique in many nations, but its use is unsupported by regulations or scientific studies. This paper addresses the need for a analysis of this technique and makes a study of the geotechnical parameters of the subsoils where it is applied, as well as the commonly used practices. The research involved over 4000 finite element method calculations integrating geotechnical parameters with construction geometry. The results have enabled the preparation of four stability design charts based on linear polynomial surface adjustment for two project scenarios: with and without surcharge load. This paper proposes the use of these stability design charts for staged bermed excavations in a broad spectrum of soil types and the incorporation of a designer-defined safety level to ensure temporary stability. Additional charts are provided to assess the safety factor of projects once the geometries and geotechnical parameters of the subsoil are known.
Synthesis, mechanism of action, and SAR studies on the cyclic lipopeptide antibiotic daptomycin
Authors: Taylor Scott D.
Published: May 2024

Daptomycin is a calcium-dependent cyclic lipopeptide antibiotic. It is one of only two new structural classes of antibiotics that have been approved for clinical use over the last 40 years. It is used to treat serious infections caused by Gram-positive bacteria. Although daptomycin has been used in the clinic since 2003, clinical resistance to daptomycin is not yet widespread. However, reports of clinical isolates that are resistant to daptomycin have been increasing in recent years, which is a cause for concern since daptomycin is often used to treat serious infections that are resistant to other antibiotics. Structural variation of antibiotics is a strategy that has often been used to overcome bacterial resistance. To pursue such a strategy with daptomycin, knowledge of its mechanism of action and methods for preparing daptomycin analogues, and the development of daptomycin structure–activity relationships (SARs) are necessary. This article, which is based on the 2023 Bernard Belleau Award Lecture, provides an overview of some of the key investigations that were undertaken by the Taylor group on daptomycin, including mechanism of action studies, the total synthesis of daptomycin, daptomycin SARs, and characterization of the interaction of daptomycin with phosphatidylglycerol, its primary target.
Gravity-induced entanglement between two massive microscopic particles in curved spacetime: II. Friedmann–Lemaître–Robertson–Walker universe
Authors: Zhang Chi , Shu Fu-Wen
Published: May 2024

In our previous work (Zhang and Shu in Eur Phys J. C 84(3):256, 2024), we have explored quantum gravity induced entanglement of masses (QGEM) in curved spacetime, observing entanglement formation between particles moving along geodesics in a Schwarzschild spacetime background. We find that long interaction time induces entanglement, even for particles with microscopic mass, addressing decoherence concerns. In this work, we build upon our previous work (Zhang and Shu 2024) by extending our investigation to a time-dependent spacetime. Specifically, we explore the entanglement induced by the mutual gravitation of massive particles in the Friedmann–Lemaître–Robertson–Walker (FLRW) universe. With the help of the phase shift and the QGEM spectrum, our proposed scheme offers a potential method for observing the formation of entanglement caused by the quantum gravity of massive particles as they propagate in the FLRW universe. Consequently, it provides insights into the field of entanglement in cosmology.
Plug-and-Play Algorithms for Dynamic Non-line-of-sight Imaging
Authors: Ye Juntian , Hong Yu , Su Xiongfei , Yuan Xin , Xu Feihu
Published: May 2024

Non-line-of-sight (NLOS) imaging has the ability to recover 3D images of scenes outside the direct line of sight, which is of growing interest for diverse applications. Despite the remarkable progress, NLOS imaging of dynamic objects is still challenging. It requires a large amount of multibounce photons for the reconstruction of single-frame data. To overcome this obstacle, we develop a computational framework for dynamic time-of-flight NLOS imaging based on plug-and-play (PnP) algorithms. By combining imaging forward model with the deep denoising network from the computer vision community, we show a 4 frames-per-second (fps) 3D NLOS video recovery (128 × 128 × 512) in post-processing. Our method leverages the temporal similarity among adjacent frames and incorporates sparse priors and frequency filtering. This enables higher-quality reconstructions for complex scenes. Extensive experiments are conducted to verify the superior performance of our proposed algorithm both through simulations and real data.
Technical Perspective on 'Better Differentially Private Approximate Histograms and Heavy Hitters using the Misra-Gries Sketch'
Authors: Cormode Graham
Published: May 2024

The topics of private data analysis and streaming data management have both been separately the focus of much study within the data management community for many years. However, more recently there have been studies which bring these two previously isolated topics together.
Technical Perspective: Allocating Isolation Levels to Transactions in a Multiversion Setting
Authors: Fekete Alan D.
Published: May 2024

Among the ways a database management system adds value, is the transaction abstraction, where the application coder can group together multiple data accesses that collectively perform one meaningful real-world activity. The platform will provide the "ACID"properties (atomic, consistent, isolated and durable) so the whole transaction happens like a single event. The mechanisms that allow this appearance include crash recovery and rollback (usually based on log entries) and concurrency control (typically involving locks).
Efficient and Reusable Lazy Sampling
Authors: Sanca Viktor , Chrysogelos Periklis , Ailamaki Anastasia
Published: May 2024

Modern analytical engines rely on Approximate Query Processing (AQP) to provide faster response times than the hardware allows for exact query answering. However, existing AQP methods impose steep performance penalties as workload unpredictability increases. While offline AQP relies on predictable workloads to a priori create samples that match the queries, as soon as workload predictability diminishes, returning to existing online AQP methods that create query-specific samples with little reuse across queries results in significantly smaller gains in response times. As a result, existing approaches cannot fully exploit the benefits of sampling under increased unpredictability.

We propose LAQy, a framework for building, expanding, and merging samples to adapt to the changes in workload predicates. We propose lazy sampling to overcome the unpredictability issues that cause fast-but-specialized samples to be query-specific and design it for a scale-up analytical engine to show the adaptivity and practicality of our framework in a modern system. LAQy speeds up online sampling processing as a function of data access and computation reuse, making sampler placement after expensive operators more practical.
Auto-Tables: Relationalize Tables without Using Examples
Authors: Li Peng , He Yeye , Yan Cong , Wang Yue , Chaudhuri Surajit
Published: May 2024

Relational tables, where each row corresponds to an entity and each column corresponds to an attribute, have been the standard for tables in relational databases. However, such a standard cannot be taken for granted when dealing with tables "in the wild". Our survey of real spreadsheettables and web-tables shows that over 30% of such tables do not conform to the relational standard, for which complex table-restructuring transformations are needed before these tables can be queried easily using SQL-based tools. Unfortunately, the required transformations are non-trivial to program, which has become a substantial pain point for technical and non-technical users alike, as evidenced by large numbers of forum questions in places like StackOverflow and Excel/Tableau forums.
Technical Perspective: A Fresh Look at Stream Computation through DSP Glasses
Authors: Olteanu Dan
Published: May 2024

DBSP (Data Base Stream Processing) is a simple yet expressive language for stream computation that draws inspiration from DSP (Digital Signal Processing). In DBSP, stream computation is expressed using circuits of stream operators whose input and output are (possibly infinite) sequences of database updates.
Testing and Evaluation of Hard Sandstone Aggregate in Hot Mix Asphalt
Authors: PeiRong Liu , LiMing Yang , Jun Huang , ChaoYang Li , DaTian Yang
Published: May 2024

To address the shortage of the aggregate used in a hot mix asphalt (HMA) pavement in Guangxi, properties such as the aggregate crushing, polished stone, and Los Angeles abrasion values of a type of hard sandstone aggregate used in HMA were tested after various conditioning treatments. The hard sandstone aggregate met the technical requirements for aggregate in HMA. In addition, the influence of the Marshall compaction on the hard sandstone aggregate-combined grading was tested. The combined grading curve changed a little, and the aggregate satisfied the corresponding technical requirements. Therefore, according to the abovementioned results, the hard sandstone aggregate can be used as a coarse aggregate in HMA.
Level of Heavy Metals and Potential Ecological Risks in Irrigated Horticultural Farms in the Vicinity of Lake Ziway, Central Ethiopian Rift Valley Region
Authors: Yimer GirmaTilahun
Published: May 2024

Research on heavy metal pollution in horticultural farms located around lakes in the Central Ethiopian Rift Valley Region has focused on measuring the levels of heavy metals and their health implications. However, the ecological risks of horticultural farms contaminated with heavy metals in this region have not been studied. The current study addresses this gap by providing information on the degree of heavy metal contamination and the ecological risk associated with horticultural farms around Lake Ziway, using various pollution indices. An inductively coupled plasma optical emission spectrometer (ICP-OES) was used to measure the concentrations of nine heavy metals (As, Cd, Co, Cu, Cr, Ni, Pb, Hg, and Zn) in a total of 30 composite soil and irrigation water samples, each consisting of a mix of six subsamples. The results indicated that the mean concentrations of Hg, Cd, Pb, and Zn in soils collected from all the sampling sites exceeded the FAO/WHO maximum permissible limit (MPL). The values of both the contamination factor (CF) and contamination degree (Cd) of the heavy metals ranged from 0.04 to 2.66 and 2.81 to 6.14, respectively, indicating a low to medium level of contamination for both indices. The pollution load index (PLI) values of 0.451, 0.449, and 0.157 for sites 2, 1, and 3, respectively, indicate “unpolluted” to “moderately polluted” levels of heavy metal pollution. However, the ecological risk indices (ERIs) at sites 2 and 1 (158.92 and 141, respectively) showed a potentially high ecological risk due to soil pollution. Therefore, close monitoring and early intervention mechanisms must be in place to control pollution in the study area.
Prevalence of Malaria and Associated Factors during the Minor Malaria Season among Febrile Under-Five Children Attending Mohammed Akile Memorial General Hospital
Authors: File Temesgen , Jemal Feysal
Published: May 2024

Malaria is one of the major public health problems in sub-Saharan Africa, including Ethiopia. Children under the age of five are immunologically naive to plasmodium parasites, making them the most vulnerable group to clinical manifestations of malaria infection. Despite the severity of the disease in children under five years of age, most studies on malaria focus on the adult population. In the present study, a cross-sectional study design based on health facilities was used during the minor malaria season from February 18 to May 28, 2023, at Mohammed Akile Memorial General Hospital, in Afar Regional State, district of Amibara located in the town of Berta. The finding revealed that 19.8% prevalence among symptomatic children with 61.04% and 38.96% of P. falciparum and P. vivax, respectively. In the present study area, malaria infection in children under five years of age is significantly associated with the presence of stagnant water in the residential area, inappropriate or no use of insecticide-treated net, and indoor residual spraying (IRS). The prevalence of malaria among symptomatic children under five years of age is higher compared to the national prevalence of malaria among the general population. Therefore, community mobilization through health promotion, aiming to interrupt the transmission of malaria at the community level, is paramount.
Preparation and Characterization of Protein-Based Hydrogel: Cottonseed Protein Grafted with 2-Acrylamido-2-Methylpropanesulfonic Acid (AMPS)
Authors: Tassw Dehenenet Flatie , Tesfaye Tamrat , Babu K. Murugesh
Published: May 2024

Using synthetic polymers in the production of superabsorbent polymers offers significant advantages such as low cost, extended service life, and a high water absorption rate. However, concerns about the environmental impact and potential adverse effects on plant growth arise from the degradation products of these polymers after disposal. In addition, handling these polymers can cause rashes, irritations, and even toxic shock syndrome. To overcome these issues, researchers are exploring the synthesis of superabsorbent polymers from natural sources. Cottonseed protein is identified as a potential natural polymer for the synthesis of natural superabsorbent polymers. Notably, there is no existing research on hydrogel synthesis using cottonseed protein and 2-acrylamido-2-methylpropanesulfonic acid (AMPS). This study addresses this gap by focusing on modifying cottonseed protein (CSP) through graft copolymerization, utilizing the partially neutralized form of 2-acrylamido-2-methylpropanesulfonic acid (AMPS) in a water-based solution. N,N-methylene bisacrylamide serves as the crosslinking agent, while potassium persulfate (PPS) and sodium bisulfite (SBS) function as redox initiators. The optimization of hydrogel synthesis conditions was achieved using Design Expert-11 software, adjusting the AMPS to CSP ratio. The research reveals that the hydrogel reaches its maximum swelling capacity (195.7 g/g) with 0.03 g of MBA, 0.01 g of PPS, 0.01 g of SBS, and a 1wt% AMPS to CSP ratio. Swelling properties were assessed under diverse pH conditions, and the study delved into swelling kinetics (both pseudo-first-order model and pseudo-second-order model) and performance under different loads. Grafting evidence was validated through FTIR analysis. The maximum water uptake was obtained when there was no load, and the pH value was around neutral (7). In conclusion, the results indicate that the developed hydrogel holds a promise for applications in water retention, reducing water loss, and serving as an environment-friendly, biocompatible superabsorbent polymer so we can use such hydrogel in biomedical applications.
New Nanosized V(III), Fe(III), and Ni(II) Complexes Comprising Schiff Base and 2-Amino-4-Methyl Pyrimidine: Synthesis, Properties, and Biological Activity
Authors: Al-Fakeh Maged S. , Alsikhan Maha A. , Alnawmasi Jawza S. H. , Alluhayb Abdullah H. , Al-Wahibi Mona S.
Published: May 2024

A new synthesis of mixed ligand complexes vanadium(III), iron(III), and nickel(II), [M : L1 : L2], where L1 = Schiff base 2-((E)-((4-(((E)-benzylidene)amino)phenyl)imino)methyl)-naphthalene-1-ol (C24H18N2O) as for L2 = AMPY 2-amino-4-methyl pyrimidine (C5H7N3) were prepared in powder and investigated. Element analysis, molar conductivity, FT-IR, UV-vis, and magnetic susceptibility values have been acquired to describe the generated complexes. The values of vanadium(III), iron(III), and nickel(II) compounds are, respectively, 2.88 BM, 5.96 BM, and 2.92 BM, demonstrating that all compounds conform to the recommended octahedral geometry. Thermal gravimetric analysis (TGA) is used to further assess the complexes and establish the temperature stability and degradation of the metal complexes. The calculations abstracted from XRD patterns propose nanosized complexes (average size 29–50 nm). The microstructures of the samples have also been investigated by scanning electron microscopy (SEM). The disc diffusion method was used to assess and analyze the inhibition of the growth of compounds against harmful bacterial and fungal strains. The prepared complexes were tested against three strains of bacteria, one gram-positive strain (Bacillus subtilis), two gram-negative strains (Escherichia coli and Pseudomonas aeruginosa), and one fungus (Aspergillus fumigatus). The complexes inferred antimicrobial activity against the studied organisms. Specifically, vanadium(III) and nickel(II) are more effective than iron(III), making them promising drugs.
Anti–4-1BB×PDL1 Bispecific Antibody Reinvigorates Tumor-Specific Exhausted CD8+ T Cells and Enhances the Efficacy of Anti-PD1 Blockade
Authors: Jeon Seung Hyuck , You Gihoon , Park Junsik , Chung Youseung , Park Kyungjin , Kim Hyunjoo , Jeon Jaehyoung , Kim Youngkwang , Son Woo-Chan , Jeong Da Som , Shin Eui-Cheol , Lee Jung-Yun , Han Dai Hoon , Jung Jaeho , Park Su-Hyung
Published: May 2024

Purpose:

To overcome the limited efficacy of immune checkpoint blockade, there is a need to find novel cancer immunotherapeutic strategies for the optimal treatment of cancer. The novel anti–4-1BB×PDL1 bispecific antibody—ABL503 (also known as TJ-L14B)—was designed to simultaneously target PDL1 and 4-1BB and demonstrated strong antitumor T-cell responses without considerable toxicity. In this study, we investigated the mechanisms by which the combination of ABL503 and anti-PD1 blockade affected the reinvigoration of exhausted tumor-infiltrating CD8+ T cells (CD8+ TIL) and antitumor efficacy.

Experimental Design:

Single-cell suspensions of hepatocellular carcinoma and ovarian cancer tissues from treatment-naïve patients were used for immunophenotyping of CD8+ TILs and in vitro functional assays. Humanized hPD1/hPDL1/h4-1BB triple–knock-in mice were used to evaluate the effects of ABL503 and anti-PD1 blockade in vivo.

Results:

We observed that ABL503 successfully restored the functions of 4-1BB+ exhausted CD8+ TILs, which were enriched for tumor-specific T cells but unresponsive to anti-PD1 blockade. Importantly, compared with anti-PD1 blockade alone, the combination of ABL503 and anti-PD1 blockade further enhanced the functional restoration of human CD8+ TILs in vitro. Consistently, the combination of ABL503 with anti-PD1 in vivo significantly alleviated tumor growth and induced enhanced infiltration and activation of CD8+ TILs.

Conclusions:

ABL503, a PDL1 and 4-1BB dual-targeting bispecific antibody, elicits pronounced additive tumor growth inhibition, with increased infiltration and functionality of exhausted CD8+ T cells, which in turn enhances the anticancer effects of anti-PD1 blockade. These promising findings suggest that ABL503 (TJ-L14B) in combination with PD1 inhibitors will likely further enhance therapeutic benefit in clinical trials.

See related commentary by Molero-Glez et al., p. 3971
Project Optimus Elicits the “Holistic” Benefits of PK/PD Modeling of Immunotherapy
Authors: Gopalakrishnan Mathangi , Amaria Rodabe N.
Published: May 2024

Leveraging a heterogeneous dataset, a recent article demonstrated the application of pharmacometric modeling to inform the dosing of nivolumab–relatlimab fixed-dose combination in special populations, including adolescents lacking clinical data. The use of model-informed approaches during clinical drug development can be cost-effective, which ensures fast access to drugs and enhances patient outcomes.

See related article by Zhao et al., p. 3050
Figure S5 from Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas
Authors: Nakashoji Ayako , Haratake Naoki , Bhattacharya Atrayee , Mao Weipu , Xu Kangjie , Wang Keyi , Daimon Tatsuaki , Ozawa Hiroki , Shigeta Keisuke , Fushimi Atsushi , Yamashita Nami , Morimoto Yoshihiro , Shimokawa Mototsugu , Saito Shin , Egloff Ann Marie , Uppaluri Ravindra , Long Mark D. , Kufe Donald
Published: May 2024

Regulation of SOX2 expression in HSC3 cells.
Figure S4 from Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas
Authors: Nakashoji Ayako , Haratake Naoki , Bhattacharya Atrayee , Mao Weipu , Xu Kangjie , Wang Keyi , Daimon Tatsuaki , Ozawa Hiroki , Shigeta Keisuke , Fushimi Atsushi , Yamashita Nami , Morimoto Yoshihiro , Shimokawa Mototsugu , Saito Shin , Egloff Ann Marie , Uppaluri Ravindra , Long Mark D. , Kufe Donald
Published: May 2024

Regulation of ∆Np63 expression in HSC3 cells.