bluuebunny/crossref_metadata_2025 huggingface dataset:
Electron attachment dynamics following UV excitation of iodide-2-thiouracil complexes
Authors: Koga Masafumi , Asplund Megan , Neumark Daniel M.
Published: June 2022

The dynamics of low energy electron attachment to the thio-substituted uracil analog 2-thiouracil are investigated using time-resolved photoelectron spectroscopy (TRPES) of iodide-2-thiouracil (I−·2TU) binary clusters. In these experiments, the anions are excited at pump energies of 4.16 and 4.73 eV, and the ensuing dynamics are probed by photodetachment at 1.59 and 3.18 eV. Upon excitation near the vertical detachment energy (4.16 eV), dipole bound (DB) and valence bound (VB) anion signals appear almost instantaneously, and the DB state of the 2TU anion undergoes an ultrafast decay (∼50 fs). At 4.73 eV, there is no evidence for a DB state, but features attributed to two VB states are seen. The transient negative ions formed by photoexcitation decay by autodetachment and I− fragmentation. The I− dissociation rates and their dependence on excitation energy agree reasonably well with the Rice–Ramsperger–Kassel–Marcus calculations. Notable differences with respect to TRPES of the related iodide–uracil anion are observed and discussed.
Soot particle size distribution reconstruction in a turbulent sooting flame with the split-based extended quadrature method of moments
Authors: Ferraro Federica , Gierth Sandro , Salenbauch Steffen , Han Wang , Hasse Christian
Published: June 2022

The Method of Moments (MOM) has largely been applied to investigate sooting laminar and turbulent flames. However, the classical MOM is not able to characterize a continuous particle size distribution (PSD). Without access to information on the PSD, it is difficult to accurately take into account particle oxidation, which is crucial for shrinking and eliminating soot particles. Recently, the Split-based Extended Quadrature Method of Moments (S-EQMOM) has been proposed as a numerically robust alternative to overcome this issue [Salenbauch et al., “A numerically robust method of moments with number density function reconstruction and its application to soot formation, growth, and oxidation,” J. Aerosol Sci. 128, 34–49 (2019)]. The main advantage is that a continuous particle number density function can be reconstructed by superimposing kernel density functions (KDFs). Moreover, the S-EQMOM primary nodes are determined individually for each KDF, improving the moment realizability. In this work, the S-EQMOM is combined with a large eddy simulation/presumed-probability density function flamelet/progress variable approach for predicting soot formation in the Delft Adelaide Flame III. The target flame features low/high sooting propensity/intermittency and comprehensive flow/scalar/soot data are available for model validation. Simulation results are compared with the experimental data for both the gas phase and the particulate phase. Good quantitative agreement has been obtained especially in terms of the soot volume fraction. The reconstructed PSD reveals predominantly unimodal/bimodal distributions in the first/downstream portion of this flame with particle diameters smaller than 100 nm. By investigating the instantaneous and statistical sooting behavior at the flame tip, it has been found that the experimentally observed soot intermittency is linked to mixture fraction fluctuations around its stoichiometric value that exhibits a bimodal probability density function.
Burden of trichomoniasis among older adults in the United States: a systematic review
Authors: Lindrose Alyssa R. , Htet Kyaw Zin , O’Connell Samantha , Marsh James , Kissinger Patricia J.
Published: June 2022

Despite being one of the most common sexually transmitted infections (STIs) in the United States, the epidemiology of trichomoniasis remains understudied. One population that has been historically overlooked regarding STIs is that of older adults, despite many individuals remaining sexually active well into their older years. We investigated the reported prevalence and incidence of trichomoniasis in adults aged ≥45 years in the United States using a systematic literature review. Twelve articles were included in the review, all assessing prevalence of trichomoniasis in this age group. Notably, no included articles assessed trichomoniasis incidence. Data collected encompassed several decades, from 1993 to 2016. Estimates of infection prevalence varied widely and ranged from 0.2% to 21.4% in included populations, with the highest prevalence typically seen among individuals seeking diagnostic testing for STIs. Several studies found increased risk for trichomoniasis in older patients compared to younger age groups. This is the first review to examine the risk of trichomoniasis in older adults, and the surprisingly high prevalence suggests that older adults may merit increased screening for trichomoniasis and sexual health education.
Measuring thermodynamic preferences to form non-native conformations in nucleic acids using ultraviolet melting
Authors: Rangadurai Atul , Shi Honglue , Xu Yu , Liu Bei , Abou Assi Hala , Boom John D. , Zhou Huiqing , Kimsey Isaac J. , Al-Hashimi Hashim M.
Published: June 2022

Thermodynamic preferences to form non-native conformations are crucial for understanding how nucleic acids fold and function. However, they are difficult to measure experimentally because this requires accurately determining the population of minor low-abundance (<10%) conformations in a sea of other conformations. Here, we show that melting experiments enable facile measurements of thermodynamic preferences to adopt nonnative conformations in DNA and RNA. The key to this “delta-melt” approach is to use chemical modifications to render specific minor non-native conformations the major state. The validity and robustness of delta-melt is established for four different non-native conformations under various physiological conditions and sequence contexts through independent measurements of thermodynamic preferences using NMR. Delta-melt is faster relative to NMR, simple, and cost-effective and enables thermodynamic preferences to be measured for exceptionally low-populated conformations. Using delta-melt, we obtained rare insights into conformational cooperativity, obtaining evidence for significant cooperativity (1.0 to 2.5 kcal/mol) when simultaneously forming two adjacent Hoogsteen base pairs. We also measured the thermodynamic preferences to form G-C+and A-T Hoogsteen and A-T base open states for nearly all 16 trinucleotide sequence contexts and found distinct sequence-specific variations on the order of 2 to 3 kcal/mol. This rich landscape of sequence-specific non-native minor conformations in the DNA double helix may help shape the sequence specificity of DNA biochemistry. Thus, melting experiments can now be used to access thermodynamic information regarding regions of the free energy landscape of biomolecules beyond the native folded and unfolded conformations.
Antiochus’ and Cicero’s different theories of memory in the Lucullus
Authors: Hösle Vittorio
Published: June 2022

The essay deals with an important epistemological debate in the Lucullus: Can there be remembrance of false beliefs, as Cicero argues against his interlocutor, who defends Antiochus’ position? It is shown that Antiochus, like Aristoteles, considers ‘remember’ to be a double achievement verb: Remembrance occurs only if a correct past perception is faithfully transmitted to the present. Cicero, on the other hand, insists that faithful transmission can also occur with false beliefs. The distinction seems to be analogous to that between valid and sound inference in contemporary Stoic logic. Finally, I discuss differences between ancient and modern forms of skepticism, address the issue of why misremembering plays no role in the Lucullus, and find an answer in Cicero’s doctrine of the orator.
„Virtus cerebri – organum animae“
Authors: Jeck Udo Reinhold
Published: June 2022

The first part of this essay analyses the beginning of the philosophy of the brain in early Greece by looking at
the Pythagorean theories of the brain. The knowledge of this innovative achievement of the Pythagorean school was never completely
lost; it also got through to the Middle Ages.

The second part focuses on the effect of Pythagorean thinking on Albert the Great. Albert systematically studied
all available sources on Pythagoreanism and in doing so acquired extensive knowledge of this philosophical movement. In the
process, he also thought through the psychology of the Pythagoreans and came across their brain theory, which he carefully
analysed, commented on, and criticised.

Albert interpreted the brain-theoretical theses of the Pythagoreans that came to his knowledge from the viewpoint
of a speculative construct of Pythagorean psychology, but in essence his accounts, as the third part of this article proves, match
the historically secured facts from ancient sources: Albert knew that the Pythagoreans had not only thought out the relationship
between mind and brain, but had also considered the question, which is so intensely debated today, whether animals think.

The fourth and final part concludes the investigation by reconstructing the basic lines of Albert’s own brain
theory: Albert developed a philosophy of the mind which, although allowing a mediated relationship of the intellect with the
brain, rather emphasised the separation of the mind from the somatic sphere. From his point of view, the brain has no decisive
function in the thought process. Because the Pythagoreans had thought differently, Albert only took critical note of their
views.
love and beloved metaphors in Jordanian Arabic and English songs
Authors: Zibin Aseel , Altakhaineh Abdel Rahman Mitib , Hamdan Hady Jihad
Published: June 2022

This study examinesloveandbelovedmetaphors from the cross-cultural perspective of Jordanian Arabic (JA) and English. The conceptual models suggested by Lakoff and Johnson (1980,1999) andKövecses (2014)and force dynamics proposed byTalmy (1988)are adopted as the theoretical frameworks for this study. The data was collected from contemporary songs by Jordanian and English-speaking artists. Unlike previous comparative studies onloveandbelovedmetaphors, this study demonstrates that source domains found in JA songs such aspain/suffering, sadness, weakness, wound, stupid endeavour, crueltyanddeadly forcealso exist in English songs to conceptualiselove.It is argued that while the use of these source domains in JA is expected as they form part of the prototypical cognitive model ofloveor thelovematrix in JA, they could be viewed as nonprototypical in English. The analysis also revealed certain JA culture-specific source domains used to conceptualisethe object of love [beloved], i.e.arabian oryxandbasil. We argued that despite the existence of similar conceptual metaphors in the two languages, geographical, historical and ideological factors may have an effect on the prevailing conceptual frames in a certain speech community creating some differences in the metaphorical conceptualisations ofloveandbeloved.
Fbxo7 promotes Cdk6 activity to inhibit PFKP and glycolysis in T cells
Authors: Harris Rebecca , Yang Ming , Schmidt Christina , Royet Chloe , Singh Sarbjit , Natarajan Amarnath , Morris May , Frezza Christian , Laman Heike
Published: June 2022

Fbxo7 is associated with cancer and Parkinson’s disease. Although Fbxo7 recruits substrates for SCF-type ubiquitin ligases, it also promotes Cdk6 activation in a ligase-independent fashion. We discovered PFKP, the gatekeeper of glycolysis, in a screen for Fbxo7 substrates. PFKP is an essential Cdk6 substrate in some T-ALL cells. We investigated the molecular relationship between Fbxo7, Cdk6, and PFKP, and the effect of Fbxo7 on T cell metabolism, viability, and activation. Fbxo7 promotes Cdk6-independent ubiquitination and Cdk6-dependent phosphorylation of PFKP. Importantly, Fbxo7-deficient cells have reduced Cdk6 activity, and hematopoietic and lymphocytic cells show high expression and significant dependency on Fbxo7. CD4+ T cells with reduced Fbxo7 show increased glycolysis, despite lower cell viability and activation levels. Metabolomic studies of activated CD4+ T cells confirm increased glycolytic flux in Fbxo7-deficient cells, alongside altered nucleotide biosynthesis and arginine metabolism. We show Fbxo7 expression is glucose-responsive at the mRNA and protein level and propose Fbxo7 inhibits PFKP and glycolysis via its activation of Cdk6.
Cryo-EM Data Statistics and Theoretical Analysis of KaiC Hexamer
Authors: Han Xu , Wu Zhaolong , Yang Tian , Ouyang Qi
Published: June 2022

Cryo-electron microscopy (cryo-EM) provides a powerful tool to resolve the structure of biological macromolecules in natural state. One advantage of cryo-EM technology is that different conformation states of a protein complex structure can be simultaneously built, and the distribution of different states can be measured. This provides a tool to push cryo-EM technology beyond just to resolve protein structures, but to obtain the thermodynamic properties of protein machines. Here, we used a deep manifold learning framework to get the conformational landscape of KaiC proteins, and further obtained the thermodynamic properties of this central oscillator component in the circadian clock by means of statistical physics.
Partially Diffusive Helium-Silica Compound under High Pressure
Authors: Liu Cong , Wang Junjie , Deng Xin , Wang Xiaomeng , Pickard Chris J. , Helled Ravit , Wu Zhongqing , Wang Hui-Tian , Xing Dingyu , Sun Jian
Published: June 2022

Helium is the second most abundant element in the universe, and together with silica, they are important components of giant planets. Exploring the reactivity and state of helium and silica under high pressure is crucial for understanding of the evolution and internal structure of giant planets. Here, using first-principles calculations and crystal structure predictions, we identify four stable phases of a helium-silica compound with seven/eight-coordinated silicon atoms at pressure of 600–4000 GPa, corresponding to the interior condition of the outer planets in the solar system. The density of HeSiO2 agrees with current structure models of the planets. This helium-silica compound exhibits a superionic-like helium diffusive state under the high-pressure and high-temperature conditions along the isentropes of Saturn, a metallic fluid state in Jupiter, and a solid state in the deep interiors of Uranus and Neptune. These results show that helium may affect the erosion of the rocky core in giant planets and may help to form a diluted core region, which not only highlight the reactivity of helium under high pressure but also provide evidence helpful for building more sophisticated interior models of giant planets.
An adaptive parametric level-set method for lung health monitoring with smartphone-based electrical impedance tomography
Authors: Wu Y , Chen B , Liu K , Zhou T , Gao G , Yao J
Published: June 2022

In this paper, an adaptive parametric level-set method is presented for lung health monitoring with smartphone-based electrical impedance tomography (EIT). Firstly, assuming that the conductivity distribution to be reconstructed is piecewise constant, the shape of lung-like targets is represented by a PLS function using a Gaussian radial basis function. Secondly, the unknown parameters (e.g. centers, widths, and weights) are computed adaptively without a prior information about targets. Thirdly, rectified Adam is proposed to adaptively adjust the learning rate during the iterative process. The proposed method is evaluated quantitatively by simulated lung imaging, water tank tests, and human breathing data. In addition, the robustness of the proposed method is performed by considering different gradient descent methods and different number of RBF centers. The reconstruction results show that the proposed method not only overcomes some problems associated with the traditional level-set method (e.g. reinitialization and use of signed distance function), but also avoids empirical parameter selections in the PLS method, resulting in faster imaging speed and better imaging quality with an average image correlation coefficient greater than 0.90. It is found that the one-second rate of the proposed method is closer to the true value with an average error of no more than 2% when the forced vital capacity tests are repeatedly performed on five volunteers with healthy lungs. The proposed method is promising in providing the reliable assessment of lung health monitoring with smartphone-based EIT.
Phonon assisted electron emission from quasi-freestanding bilayer epitaxial graphene microstructures
Authors: Lewis Daniel , Jordan Brendan , Pedowitz Michael , Pennachio Daniel J , Hajzus Jenifer R , Myers-Ward Rachael , Daniels Kevin M
Published: June 2022

Electron emission from quasi-freestanding bilayer epitaxial graphene (QFEG) on a silicon carbide substrate is reported, demonstrating emission currents as high as 8.5 μA, at ∼200 °C, under 0.3 Torr vacuum. Given the significantly low turn-on temperature of these QFEG devices, ∼150°C, the electron emission is explained by phonon-assisted electron emission, where the acoustic and optical phonons of QFEG causes carrier acceleration and emission. Devices of differing dimensions and shapes are fabricated via a simple and scalable fabrication procedure and tested. Variations in device morphology increase the density of dangling bonds, which can act as electron emission sites. Devices exhibit emission enhancement at increased temperatures, attributed to greater phonon densities. Devices exhibit emission under various test conditions, and a superior design and operating methodology are identified.
Current density limitation during disruptions due to plasma-sheaths
Authors: Adamek J. , Artola F.J. , Loarte A. , Matveeva E. , Cavalier J. , Pitts R.A. , Roccella R. , Lehnen M. , Havlicek J. , Hron M. , Panek R. , Team the COMPASS
Published: June 2022

The presented experimental study realized in the COMPASS tokamak demonstrates, for the first time, that the current density that flows from the plasma into the vacuum vessel during disruptions is limited by the ion particle flux. Such a limitation shows that, at least in COMPASS, the sheath that forms between the plasma and the first wall dominates the halo current flow. This observation is achieved by measuring simultaneously the ion saturation current with negatively biased Langmuir probes and the halo current with grounded probes to the vacuum vessel. These comparative measurements, which were never performed during disruptions in other machines, directly confirm that the halo current density remains below the ion particle flux in COMPASS. The study also shows, using Mirnov coils measurement, that the total electric current entering the wall grows with the plasma current while the current density obtained by Langmuir probes remains unaffected. This, together with the current density limitation, leads to a novel finding that the halo current width increases with the pre-disruptive plasma current, which limits the local forces. The new findings reported here could also provide potential constraints on the modeling of disruption-induced loads on future reactor scale tokamaks and motivation for further experiments on existing devices.
Electrochemical performance of Palmyra palm shell activated carbon prepared by carbonization followed by microwave reflux treatment
Authors: Punon Mavin , Jarernboon Wirat , Laokul Paveena
Published: June 2022

High-performance supercapacitor electrodes were prepared using activated carbon from Palmyra palm shells. The raw biomass was carbonized at 800 °C under argon atmosphere, followed by a microwave refluxing process with a mixture of HNO3/H2SO4 as catalytic solution. The activated carbons with and without reflux treatment were characterized by XRD, Raman, SEM, BET-BJH, FT-IR and XPS techniques. The electrochemical properties of the as-prepared materials were studied in a potential range from −1 to 0 V in a 6 M KOH solution. The results showed that the highest specific capacitance, 182 F g−1 at a current density of 1 A g−1, was obtained in a sample with microwave-assisted reflux. This value is 1.5 times higher than that of an identical sample without reflux modification. Microwave reflux produces materials with a high specific surface area and promotes the formation of active functional groups on the surfaces of the carbon materials.
Cost-Effectiveness of Masked Hypertension Screening and Treatment in US Adults With Suspected Masked Hypertension: A Simulation Study
Authors: Green Matthew B , Shimbo Daichi , Schwartz Joseph E , Bress Adam P , King Jordan B , Muntner Paul , Sheppard James P , McManus Richard J , Kohli-Lynch Ciaran N , Zhang Yiyi , Shea Steven , Moran Andrew E , Bellows Brandon K
Published: June 2022

BACKGROUND

Recent US blood pressure (BP) guidelines recommend using ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) to screen adults for masked hypertension. However, limited evidence exists of the expected long-term effects of screening for and treating masked hypertension.

METHODS

We estimated the lifetime health and economic outcomes of screening for and treating masked hypertension using the Cardiovascular Disease (CVD) Policy Model, a validated microsimulation model. We simulated a cohort of 100,000 US adults aged ≥20 years with suspected masked hypertension (i.e., office BP 120–129/<80 mm Hg, not taking antihypertensive medications, without CVD history). We compared usual care only (i.e., no screening), usual care plus ABPM, and usual care plus HBPM. We projected total direct healthcare costs (2021 USD), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Future costs and QALYs were discounted 3% annually. Secondary outcomes included CVD events and serious adverse events.

RESULTS

Relative to usual care, adding masked hypertension screening and treatment with ABPM and HBPM was projected to prevent 14.3 and 20.5 CVD events per 100,000 person-years, increase the proportion experiencing any treatment-related serious adverse events by 2.7 and 5.1 percentage points, and increase mean total costs by $1,076 and $1,046, respectively. Compared with usual care, adding ABPM was estimated to cost $85,164/QALY gained. HBPM resulted in lower QALYs than usual care due to increased treatment-related adverse events and pill-taking disutility.

CONCLUSIONS

The results from our simulation study suggest screening with ABPM and treating masked hypertension is cost-effective in US adults with suspected masked hypertension.
A Dynamic Anatomic Study of Parasacral Perforators: Mapping, Perforasome, and Applications for Buttock Enhancement
Authors: Claro Gilles , Lupon Elise , Dargai Farouk , Bekara Farid , Mokrane Fatima Zohra , Chaput Benoit
Published: June 2022

Background

Due to the lack of knowledge about parasacral artery perforators, flaps from this region cannot be used with complete confidence in their security and effectiveness. Knowledge of the clusters and perforasome of these perforators could help in the design of more reliable flaps and extend the range of applications.

Objectives

This study aimed to identify the location, number, and density of perforators, and to subsequently analyze the perfusion flow and linking vessel distribution.

Methods

Five fresh cadavers were harvested and dissected. For the mapping, after injecting lateral sacral arteries with colored latex, perforators with a diameter of >0.5 cm were examined in 5 sacral regions. All data were collected on the suprafascial plane, with an orthonormal coordinate system placed on iliac crests and median lines. For perforasome analysis, 5 perforators and 3 three sacral flaps were injected with radiopaque dye. A dynamic (4-dimensional) computed tomographic angiography completed the analysis.

Results

A mean [standard deviation] of 8.4 [1.36] perforators per corpse, with a mean diameter of 0.72 [0.14] mm, were identified. There was a higher density of parasacral perforators close to the median line and 7.6 cm above the iliac crests. This pattern was not a random distribution (P < 0.05). The perfusion area was preferentially in the superior gluteal region. Perfusion flow was permitted by the dominant direct-linking vessels towards adjacent lumbar perforators, oriented diagonally upward and outward to the midline.

Conclusions

Parasacral perforator flaps appear to be a useful procedure in reconstruction and in aesthetic surgery, especially in gluteal augmentation. Their reliability depends on sound anatomic knowledge, with accurate preoperative perforator mapping.
Establishment and Molecular Modeling Study of Cyclodextrin-Based Synergistic Enantioseparation Systems with Three New Amino Acid Chiral Ionic Liquids as Additives in Capillary Electrophoresis
Authors: Liu Jie , Zhang Jian , Zhu Dongyang , Zhu Xinqi , Du Yingxiang , Ma Xiaofei , Feng Zijie , Sun Xiaodong , Xu Hui
Published: June 2022

Chiral ionic liquids (CILs) have attracted more and more attention due to their superior performance as chiral additives in capillary electrophoresis. In this work, based on the cyclodextrin (CD) derivatives and three new amino acid CILs (trifluoroacetate-L-Hydroxyproline, nitric acid-L-Hydroxyproline and trifluoroacetate-L-threonine), the new synergistic systems were established for chiral drug separation. In contrast to the traditional single glucosyl-β-CD (Glu-β-CD) separation system, the CIL/Glu-β-CD synergistic systems achieved improved resolution of three model drug racemates. Some experimental variables, such as CIL concentration, Glu-β-CD concentration, buffer pH, applied voltage, and the type and proportion of organic modifier, were optimized in the trifluoroacetate-L-Hydroxyproline/Glu-β-CD synergistic system. In addition, the recognition process in the synergistic system was studied through the molecular modeling method.
Prognostic impact of carcinoembryonic antigen in 1822 surgically treated esophageal squamous cell carcinoma: multi-institutional study of the Japan Esophageal Society
Authors: Suzuki Takashi , Yajima Satoshi , Okamura Akihiko , Yoshida Naoya , Taniyama Yusuke , Murakami Kentaro , Ohkura Yu , Nakajima Yasuaki , Yagi Koichi , Fukuda Takashi , Ogawa Ryo , Hoshino Isamu , Kunisaki Chikara , Narumiya Kosuke , Tsubosa Yasuhiro , Yamada Kazuhiko , Shimada Hideaki ,   Japan Esophageal Society Promotion Research: p53 Antibody Multicenter Research Group
Published: June 2022

Background

Previous studies have evaluated the clinicopathological significance of carcinoembryonic antigen (CEA) of esophageal cancer in relatively small numbers of patients. Therefore, this study aimed to clarify the prognostic significance of CEA in 1822 patients with esophageal squamous cell carcinoma (SCC).

Methods

Based on the Japanese Esophageal Society nationwide multi-institutional retrospective study, a total of 1,748 surgically treated ESCC from 15 hospitals were enrolled to evaluate prognostic impact of preoperative CEA values. Among them, 605 patients were categorized to up-front surgery group, and 1,217 patients were categorized to neoadjuvant therapy group. The CEA threshold for positivity was 3.7 ng/ml. The clinicopathological and prognostic impact of CEA was evaluated by univariate and multivariate analysis in each treatment modality groups.

Results

In total, the CEA positive rate was 25.8% (470/1822). CEA-positive status was significantly associated with distant metastasis (P = 0.004) but not associated with other factors. CEA-positive status was associated with poor overall survival (P < 0.001) in univariate analysis as well as multivariate analysis (P = 0.003).

Conclusions

CEA was an independent prognostic determinant of overall survival in esophageal SCC. Based on the subgroup analysis, regardless of the treatment modality, patients with high pretreatment CEA showed poor overall survival.
Extracellular ST6GAL1 regulates monocyte–macrophage development and survival
Authors: Rusiniak Michael E , Punch Patrick R , Hait Nitai C , Maiti Aparna , Burns Robert T , Chapla Digantkumar , Moremen Kelley W , Zhao Peng , Wells Lance , Hoffmeister Karin , Lau Joseph T Y
Published: June 2022

Interaction of immune cells with the systemic environment is necessary for the coordinated development and execution of immune responses. Monocyte-macrophage lineage cells reside at the junction of innate and adaptive immunity. Previously we reported that the sialyltransferase ST6GAL1 in the extracellular milieu modulates B cell development and IgG production, granulocyte production, and attenuates acute airway inflammation to bacterial challenge in mouse models. Here, we report that extracellular ST6GAL1 also elicits profound responses in monocyte-macrophage lineage cells. We show that recombinant ST6GAL1 adheres to subsets of thioglycolate-elicited inflammatory cells in the mouse peritoneum and to cultured human monocyte THP-1 cells. Exposure of the inflammatory cells to recombinant ST6GAL1 elicited wholesale changes in the gene expression profile of primary mouse myeloid cells; most notable was the striking up-regulation of monocyte-macrophage and monocyte-derived dendritic cell development pathway signature genes and transcription factors PU.1, NFκB and their target genes, driving increased monocyte-macrophage population and survival ex vivo. In the cultured human monocyte cells, the essential cell surface receptor of the monocyte-macrophage lineage, the M-CSF receptor (M-CSF-R, Csfr1) was a target of extracellular ST6GAL1 catalytic activity. Extracellular ST6GAL1 activated the M-CSF-R and initiated intracellular signaling events, namely, the nuclear translocation of NFκB subunit p65, and phosphorylation of ERK 1/2 and AKT. The findings implicate extracellular ST6GAL1 in monocyte development by a mechanism initiated at the cell surface and support an emerging paradigm of an extracellular glycan-modifying enzyme as a central regulator coordinating immune hematopoietic cell development and function.
The critical role of the TB5 domain of fibrillin-1 in endochondral ossification
Authors: Delhon Laure , Mougin Zakaria , Jonquet Jérémie , Bibimbou Angélique , Dubail Johanne , Bou-Chaaya Cynthia , Goudin Nicolas , Le Goff Wilfried , Boileau Catherine , Cormier-Daire Valérie , Le Goff Carine
Published: June 2022

Mutations in the fibrillin-1 (FBN1) gene are responsible for the autosomal dominant form of geleophysic dysplasia (GD), which is characterized by short stature and extremities, thick skin and cardiovascular disease. All known FBN1 mutations in patients with GD are localized within the region encoding the transforming growth factor-β binding protein-like 5 (TB5) domain of this protein. Herein, we generated a knock-in mouse model, Fbn1Y1698C by introducing the p.Tyr1696Cys mutation from a patient with GD into the TB5 domain of murine Fbn1 to elucidate the specific role of this domain in endochondral ossification. We found that both Fbn1Y1698C/+ and Fbn1Y1698C/Y1698C mice exhibited a reduced stature reminiscent of the human GD phenotype. The Fbn1 point mutation introduced in these mice affected the growth plate formation owing to abnormal chondrocyte differentiation such that mutant chondrocytes failed to establish a dense microfibrillar network composed of FBN1. This original Fbn1 mutant mouse model offers new insight into the pathogenic events underlying GD. Our findings suggest that the etiology of GD involves the dysregulation of the extracellular matrix composed of an abnormal FBN1 microfibril network impacting the differentiation of the chondrocytes.
Revisiting nuclear hedging: ballistic missiles and the Iranian example
Authors: Hiim Henrik Stålhane
Published: June 2022

Technological shifts have made nascent nuclear arsenals more vulnerable. This article examines how this affects nuclear hedgers—that is, states deliberately seeking nuclear latency or the capability to develop the bomb. It argues that growing vulnerabilities provide hedgers with increasing incentives to acquire sophisticated ballistic missiles. Possession of missiles is crucial to limit the ‘window of vulnerability’ between a nuclear breakout decision and the attainment of a nuclear arsenal with deterrence value. The article illustrates this tendency through a case-study of the Iranian missile and rocket programs. It finds that missile acquisition has indeed been an integral part of Iran's hedging strategy, and that several of the systems it has acquired indicate an interest in nuclear weapons delivery. Furthermore, Iran's sophisticated missile arsenal significantly shortens its path to a credible nuclear deterrent. The article contributes to the proliferation literature, which has overlooked that the development of missiles is an increasingly important element of contemporary nuclear hedging. Its findings show that missiles increasingly need to be considered in scholarly assessments of states' nuclear latency and hedging, and in discussions about how difficult it is to acquire nuclear weapons. Moreover, the findings indicate that practitioners working to prevent proliferation should prioritize tracking missile programs.
Impact of the Early COVID-19 Pandemic on Burn Care: A Multi-National Study
Authors: Vasudevan Ananya , Bailey Hannah M , Sager Alan , Kazis Lewis E
Published: June 2022

This qualitative study documents and analyzes COVID-19’s impacts on burn care in twelve nations. Burn care saw valuable improvements in surgical techniques, skin grafting, and other acute treatments during the decades before the COVID-19 pandemic which increased severely burned patients’ survival rates and quality of life. Detailed interviews, conducted in the 12 nations reveal that the COVID-19 pandemic greatly affected the delivery of acute and rehabilitation services for burn patients. Resources have been suctioned away from non-COVID healthcare and burn care has not been spared. Acute, post-acute rehabilitation, and mental health services have all suffered. Weak preparation has deeply burdened health care services in most nations, resulting in lower access to care. Access problems have accelerated innovations like telehealth in many nations. The spread of misinformation through social and traditional media has contributed to the varied responses to COVID-19. This compounded problems in health care delivery. Burn care providers delivered services for survivors during extremely difficult circumstances by continuing to furnish acute and long-term services for patients with complex disease. Emphasis on future pandemic preparedness will be vital because they undermine all aspects of burn care and patient outcomes. As the COVID-19 pandemic continues to unfold around the world, it will be important to continue to monitor and analyze the adaptability of nations, health care systems, and burn care providers.
Impact of adherence to criteria on oncological outcomes of radical prostatectomy in patients opting for active surveillance: data from the PRIAS-JAPAN study
Authors: Tohi Yoichiro , Kato Takuma , Miyakawa Jimpei , Matsumoto Ryuji , Sasaki Hiroshi , Mitsuzuka Koji , Inokuchi Junichi , Matsumura Masafumi , Yokomizo Akira , Kinoshita Hidefumi , Hara Isao , Kawamura Norihiko , Hashimoto Kohei , Inoue Masaharu , Teishima Jun , Kanno Hidenori , Fukuhara Hiroshi , Maruyama Satoru , Sakamoto Shinichi , Saito Toshihiro , Kakehi Yoshiyuki , Sugimoto Mikio
Published: June 2022

Objectives

This study aimed to evaluate whether oncological outcomes of radical prostatectomy differ depending on adherence to the criteria in patients who opt for active surveillance.

Materials and methods

We retrospectively reviewed the data of 1035 patients enrolled in a prospective cohort of the PRIAS-JAPAN study. After applying the exclusion criteria, 136 of 162 patients were analyzed. Triggers for radical prostatectomy due to pathological reclassification on repeat biopsy were defined as on-criteria. Off-criteria triggers were defined as those other than on-criteria triggers. Unfavorable pathology on radical prostatectomy was defined as pathological ≥T3, ≥GS 4 + 3 and pathological N positivity. We compared the pathological findings on radical prostatectomy and prostate-specific antigen recurrence-free survival between the two groups. The off-criteria group included 35 patients (25.7%), half of whom received radical prostatectomy within 35 months.

Results

There were significant differences in median prostate-specific antigen before radical prostatectomy between the on-criteria and off-criteria groups (6.1 vs. 8.3 ng/ml, P = 0.007). The percentage of unfavorable pathologies on radical prostatectomy was lower in the off-criteria group than that in the on-criteria group (40.6 vs. 31.4%); however, the differences were not statistically significant (P = 0.421). No significant difference in prostate-specific antigen recurrence-free survival was observed between the groups during the postoperative follow-up period (median: 36 months) (log-rank P = 0.828).

Conclusions

Half of the off-criteria patients underwent radical prostatectomy within 3 years of beginning active surveillance, and their pathological findings were not worse than those of the on-criteria patients.
Performing the Self through Orientalizing the Kurds in Isabella Bird’s Journeys in Persia and Kurdistan
Authors: Ghaderi Farah , Heidari Himan
Published: June 2022

This article fleshes out the various ways Isabella Bird performs the self in her travel account, Journeys in Persia and Kurdistan (1891), mainly in her engagement with the Kurdish people. Deploying Judith Butler’s theory of performativity of gender, we argue that travel writing is empowering for Bird because it offers her a viable platform to perform a variety of selves through which she can voice her complicated and nuanced socio-political views and promote her image. Moreover, we contend that Bird’s representation of the Kurds and their region is informed by Orientalist ideology of the time as well as her own complex subject position. The fluidity of Bird’s identity, which is represented through performing a rich diversity of masculine and feminine selves in her account, exposes the constructed nature of gender. Bird not only undermines the prescribed gender boundaries of her time, but also demands the right for herself, as a woman writer, to be both caring and daring by playing the roles of a brave traveller, intellectual explorer, devoted Hakim, shrewd political analyst, religious commentator, and receptive ethnographer in Journeys.
New insights into the role of melatonin in photosynthesis
Authors: Yang Sijia , Zhao Yuqing , Qin Xiaolong , Ding Chunbang , Chen Yanger , Tang Zizhong , Huang Yan , Reiter Russel J , Yuan Shu , Yuan Ming
Published: June 2022

There are numerous studies on enhancing plant resistance to stress using melatonin, but few studies about its effect on photosynthesis. Herein, we summarized the role of melatonin in photosynthesis. Melatonin regulates chlorophyll synthesis and degradation through the transcription of related genes and hormone signals. It protects photosynthetic proteins and maintains the photosynthetic process through improving the transcription of photosystem genes, activating the antioxidant system, and promoting the xanthophyll cycle. Melatonin potentially regulates plant stomatal movement through CAND2/PMTR1. Finally, it controls the photosynthetic carbon cycle by regulating the metabolism of sugar, the gluconeogenesis pathway, and the degradation and transport of transient starch.
miR156 regulates somatic embryogenesis by modulating starch accumulation in citrus
Authors: Feng Meng-Qi , Lu Meng-Di , Long Jian-Mei , Yin Zhao-Ping , Jiang Nan , Wang Peng-Bo , Liu Yue , Guo Wen-Wu , Wu Xiao-Meng
Published: June 2022

Somatic embryogenesis (SE) is a major regeneration approach for in vitro cultured tissues of plants, including citrus. However, SE capability is difficult to maintain, and recalcitrance to SE has become a major obstacle to plant biotechnology. We previously reported that miR156-SPL modules regulate SE in citrus callus. However, the downstream regulatory pathway of the miR156-SPL module in SE remains unclear. In this study, we found that transcription factors CsAGL15 and CsFUS3 bind to the CsMIR156A promoter and activate its expression. Suppression of csi-miR156a function leads to up-regulation of four target genes, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (CsSPL) genes, and reduction of SE efficiency. In the short tandem target mimic (STTM)-miR156a overexpression callus (MIM156), the number of amyloplasts and starch content were significantly reduced, and genes involved in starch synthesis and transport were down-regulated. csi-miR172d was down-regulated, whereas the target genes, CsTOE1.1 and CsTOE1.2, which inhibit the expression of starch biosynthesis genes, were up-regulated. In our working model, CsAGL15 and CsFUS3 activate csi-miR156a, which represses CsSPLs and further regulates csi-miR172d and CsTOEs, thus altering starch accumulation in callus cells and regulating SE in citrus. This study elucidates the pathway of miR156-SPLs and miR172-TOEs-mediated regulation of SE, and provides new insights into enhancing SE capability in citrus.
Two homeologous MATE transporter genes,NtMATE21andNtMATE22, are involved in the modulation of plant growth and flavonol transport inNicotiana tabacum
Authors: Gani Umar , Nautiyal Abhishek Kumar , Kundan Maridul , Rout Biswaranjan , Pandey Ashutosh , Misra Prashant
Published: June 2022

The multidrug and toxic compound extrusion (MATE) protein family has been implicated in the transport of a diverse range of molecules, including specialized metabolites. In tobacco (Nicotiana tabacum), only a limited number of MATE transporters have been functionally characterized, and no MATE transporter has been studied in the context of flavonoid transport in this plant species so far. In the present study, we characterize two homeologous tobacco MATE genes, NtMATE21 and NtMATE22, and demonstrate their role in flavonol transport and in plant growth and development. The expression of these two genes was reported to be up-regulated in trichomes as compared with the trichome-free leaf. The transcript levels of NtMATE21 and NtMATE22 were found to be higher in flavonol overproducing tobacco transgenic lines as compared with wild type tobacco. The two transporters were demonstrated to be localized to the plasma membrane. Genetic manipulation of NtMATE21 and NtMATE22 led to altered growth phenotypes and modulated flavonol contents in N. tabacum. The β-glucuronidase and green fluorescent protein fusion transgenic lines of promoter regions suggested that NtMATE21 and NtMATE22 are exclusively expressed in the trichome heads in the leaf tissue and petals. Moreover, in a transient transactivation assay, NtMYB12, a flavonol-specific MYB transcription factor, was found to transactivate the expression of NtMATE21 and NtMATE22 genes. Together, our results strongly suggest the involvement of NtMATE21 and NtMATE22 in flavonol transport as well as in the regulation of plant growth and development.
On the energy dependence of the QPO phenomenon in the black hole system MAXI J1535-571
Authors: Garg Akash , Misra Ranjeev , Sen Somasri
Published: June 2022

Previous analysis of AstroSat observations of the black hole system MAXI J1535-571 have revealed the presence of a strong Quasi-Periodic Oscillation (QPO) whose frequency is correlated with the high energy spectral index. Here, we fit the spectra as emitted from a truncated disc with an inner hot corona, study the QPO frequency dependence on other spectral parameters and model the energy-dependent r.m.s and time-lag of the QPO to identify the physical spectral parameters whose variation are responsible for the QPO. The QPO frequency is found to also correlate with the scattering fraction (i.e. the fraction of the soft photons Comptonized) and its dependence on the accretion rate and inner disc radii is consistent with it being the dynamical frequency. The time-lag between the hard and soft photons is negative for QPO frequency >2.2 Hz and is positive for lesser values, making this the second black hole system to show this behaviour after GRS 1915+105. Modelling the energy-dependent time-lag and r.m.s requires correlated variation of the accretion rate, inner disc radii, and the coronal heating rate, with the latter having a time-lag compared to the other two for QPO frequencies less than <2.2 Hz and which changes sign (i.e. the coronal heating variation precedes the accretion rate one) for higher values. The implications of the results are discussed.
Constraining baryonic feedback and cosmology with weak-lensing, X-ray, and kinematic Sunyaev–Zeldovich observations
Authors: Schneider Aurel , Giri Sambit K , Amodeo Stefania , Refregier Alexandre
Published: June 2022

Modern weak-lensing observations are becoming increasingly sensitive to baryonic feedback processes which are still poorly understood. So far, this challenge has been faced either by imposing scale-cuts in the data or by modelling baryonic effects with simple, one-parameter models. In this paper, we rely on a more general, seven-parameter prescription of baryonic feedback effects, which is primarily motivated by observations and has been shown to agree with a plethora of hydrodynamical simulations. By combining weak-lensing data from the Kilo-Degree Survey (KiDS-1000) with observations of gas around galaxy clusters, we are able to constrain baryonic parameters and learn more about feedback and cosmology. In particular, we use cluster gas fractions from X-ray data and gas profiles from kinematic Sunyaev–Zeldovich (kSZ) observations to provide evidence for baryonic feedback that is stronger than predicted by most hydrodynamical simulations. In terms of the matter power spectrum, we report a beyond-per cent effect at wave-modes above k ∼ 0.1–0.45 $h\, {\rm Mpc}^{-1}$ and a maximum suppression of 12–33 per cent at k ∼ 7 $h\, {\rm Mpc}^{-1}$ (68 per cent confidence level). Regarding the combined parameter Σ8 = σ8(Ωm/0.3)0.58, we find the known tension with the Planck satellite data to be reduced from 3.8σ to 2.9σ once baryonic effects are fully included in the analysis pipeline. The tension is further decreased to 2.6σ when the weak-lensing data are combined with X-ray and kSZ observations. We conclude that, while baryonic feedback effects become more important in modern weak-lensing surveys, they are unlikely to act as the main culprit for the observed Σ8-tension.
CRISPR-Cas12a targeting of ssDNA plays no detectable role in immunity
Authors: Marino Nicole D , Pinilla-Redondo Rafael , Bondy-Denomy Joseph
Published: June 2022

CRISPR-Cas12a (Cpf1) is a bacterial RNA-guided nuclease that cuts double-stranded DNA (dsDNA) at sites specified by a CRISPR RNA (crRNA) guide. Additional activities have been ascribed to this enzyme in vitro: site-specific (cis) single-stranded DNA (ssDNA) cleavage and indiscriminate (trans) degradation of ssDNA, RNA, and dsDNA after activation by a complementary target. The ability of Cas12a to cleave nucleic acids indiscriminately has been harnessed for many applications, including diagnostics, but it remains unknown if it contributes to bacterial immunity. Here, we provide evidence that cleavage of ssDNA in cis or in trans by Cas12a is insufficient to impact immunity. Using LbCas12a expressed in either Pseudomonas aeruginosa or Escherichia coli, we observed that cleavage of dsDNA targets did not elicit cell death or dormancy, suggesting insignificant levels of collateral damage against host RNA or DNA. Canonical immunity against invasive dsDNA also had no impact on the replicative fitness of co-infecting dsDNA phage, ssDNA phage or plasmid in trans. Lastly, crRNAs complementary to invasive ssDNA did not provide protection, suggesting that ssDNA cleavage does not occur in vivo or is insignificant. Overall, these results suggest that CRISPR-Cas12a immunity predominantly occurs via canonical targeting of dsDNA, and that the other activities do not significantly impact infection outcomes.