bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocytosis triggers V-ATPase-SYK–mediated priming of cGAS activation and innate immune response
Authors: Yang Yu-Lin , Cao Li-Bo , He Wen-Rui , Zhong Li , Guo Yi , Yang Qing , Shu Hong-Bing , Hu Ming-Ming
Published: October 2022

The current view of nucleic acid–mediated innate immunity is that binding of intracellular sensors to nucleic acids is sufficient for their activation. Here, we report that endocytosis of virus or foreign DNA initiates a priming signal for the DNA sensor cyclic GMP-AMP synthase (cGAS)–mediated innate immune response. Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H
+
pump (V-ATPase), where SYK is activated and then phosphorylates human cGAS
Y214/215
(mouse cGas
Y200/201
) to prime its activation. Upon binding to DNA, the primed cGAS initiates robust cGAMP production and mediator of IRF3 activation/stimulator of interferon genes-dependent innate immune response. Consistently, blocking the V-ATPase-SYK axis impairs DNA virus- and transfected DNA-induced cGAMP production and expression of antiviral genes. Our findings reveal that V-ATPase-SYK–mediated tyrosine phosphorylation of cGAS following endocytosis of virus or other cargos serves as a priming signal for cGAS activation and innate immune response.
Geometrically programmed self-limited assembly of tubules using DNA origami colloids
Authors: Hayakawa Daichi , Videbaek Thomas E. , Hall Douglas M. , Fang Huang , Sigl Christian , Feigl Elija , Dietz Hendrik , Fraden Seth , Hagan Michael F. , Grason Gregory M. , Rogers W. Benjamin
Published: October 2022

Self-assembly is one of the most promising strategies for making functional materials at the nanoscale, yet new design principles for making self-limiting architectures, rather than spatially unlimited periodic lattice structures, are needed. To address this challenge, we explore the tradeoffs between addressable assembly and self-closing assembly of a specific class of self-limiting structures: cylindrical tubules. We make triangular subunits using DNA origami that have specific, valence-limited interactions and designed binding angles, and we study their assembly into tubules that have a self-limited width that is much larger than the size of an individual subunit. In the simplest case, the tubules are assembled from a single component by geometrically programming the dihedral angles between neighboring subunits. We show that the tubules can reach many micrometers in length and that their average width can be prescribed through the dihedral angles. We find that there is a distribution in the width and the chirality of the tubules, which we rationalize by developing a model that considers the finite bending rigidity of the assembled structure as well as the mechanism of self-closure. Finally, we demonstrate that the distributions of tubules can be further sculpted by increasing the number of subunit species, thereby increasing the assembly complexity, and demonstrate that using two subunit species successfully reduces the number of available end states by half. These results help to shed light on the roles of assembly complexity and geometry in self-limited assembly and could be extended to other self-limiting architectures, such as shells, toroids, or triply periodic frameworks.
Differential interactions of resting, activated, and desensitized states of the α7 nicotinic acetylcholine receptor with lipidic modulators
Authors: Zhuang Yuxuan , Noviello Colleen M. , Hibbs Ryan E. , Howard Rebecca J. , Lindahl Erik
Published: October 2022

The α7 nicotinic acetylcholine receptor is a pentameric ligand-gated ion channel that modulates neuronal excitability, largely by allowing Ca2+permeation. Agonist binding promotes transition from a resting state to an activated state, and then rapidly to a desensitized state. Recently, cryogenic electron microscopy (cryo-EM) structures of the human α7 receptor in nanodiscs were reported in multiple conformations. These were selectively stabilized by inhibitory, activating, or potentiating compounds. However, the functional annotation of these structures and their differential interactions with unresolved lipids and ligands remain incomplete. Here, we characterized their ion permeation, membrane interactions, and ligand binding using computational electrophysiology, free-energy calculations, and coarse-grained molecular dynamics. In contrast to nonconductive structures in apparent resting and desensitized states, the structure determined in the presence of the potentiator PNU-120596 was consistent with an activated state permeable to Ca2+. Transition to this state was associated with compression and rearrangement of the membrane, particularly in the vicinity of the peripheral MX helix. An intersubunit transmembrane site was implicated in selective binding of either PNU-120596 in the activated state or cholesterol in the desensitized state. This substantiates functional assignment of all three lipid-embedded α7-receptor structures with ion-permeation simulations. It also proposes testable models of their state-dependent interactions with lipophilic ligands, including a mechanism for allosteric modulation at the transmembrane subunit interface.
Transmembrane proteins tetraspanin 4 and CD9 sense membrane curvature
Authors: Dharan Raviv , Goren Shahar , Cheppali Sudheer Kumar , Shendrik Petr , Brand Guy , Vaknin Alisa , Yu Li , Kozlov Michael M. , Sorkin Raya
Published: October 2022

Multiple membrane-shaping and remodeling processes are associated with tetraspanin proteins by yet unknown mechanisms. Tetraspanins constitute a family of proteins with four transmembrane domains present in every cell type. Prominent examples are tetraspanin4 and CD9, which are required for the fundamental cellular processes of migrasome formation and fertilization, respectively. These proteins are enriched in curved membrane structures, such as cellular retraction fibers and oocyte microvilli. The factors driving this enrichment are, however, unknown. Here, we revealed that tetraspanin4 and CD9 are curvature sensors with a preference for positive membrane curvature. To this end, we used a biomimetic system emulating membranes of cell retraction fibers and oocyte microvilli by membrane tubes pulled out of giant plasma membrane vesicles with controllable membrane tension and curvature. We developed a simple thermodynamic model for the partitioning of curvature sensors between flat and tubular membranes, which allowed us to estimate the individual intrinsic curvatures of the two proteins. Overall, our findings illuminate the process of migrasome formation and oocyte microvilli shaping and provide insight into the role of tetraspanin proteins in membrane remodeling processes.
14-3-3τ drives estrogen receptor loss via ERα36 induction and GATA3 inhibition in breast cancer
Authors: Garan Lidija A. Wilhelms , Xiao Yang , Lin Weei-Chin
Published: October 2022

About one-fourth of recurrent estrogen receptor–positive (ER+) breast cancers lose ER expression, leading to endocrine therapy failure. However, the mechanisms underlying ER loss remain to be fully explored. We now show that 14-3-3τ, up-regulated in ∼60% of breast cancer, drives the conversion of ER+ to ER– and epithelial-to-mesenchymal transition (EMT). We identify ERα36, an isoform of ERα66, as a downstream effector of 14-3-3τ. Overexpression of 14-3-3τ induces ERα36 in xenografts and tumor spheroids. The regulation is further supported by a positive correlation between ERα36 and 14-3-3τ expression in human breast cancers. ERα36 can antagonize ERα66 and inhibit ERα66 expression. Isoform-specific depletion of ERα36 blocks the ER conversion and EMT induced by 14-3-3τ overexpression in tumor spheroids, thus establishing ERα36 as a key mediator in 14-3-3τ-driven ER loss and EMT. ERα36 promoter is repressed by GATA3, which can be phosphorylated by AKT at consensus binding sites for 14-3-3. Upon AKT activation, 14-3-3τ binds phosphorylated GATA3 and facilitates the degradation of GATA3 causing GATA3 to lose transcriptional control over its target genes ERα66 and ERα36. We also demonstrate a role for the collaboration between 14-3-3τ and AKT in ERα36 induction and endocrine therapy resistance by three-dimensional spheroid and tamoxifen treatment models in MCF7 and T47D ER+ breast cancer cells. Thus, the 14-3-3τ-ERα36 regulation provides a previously unrecognized mechanism for ER loss and endocrine therapy failure.
The origin of carbonate mud and implications for global climate
Authors: Geyman Emily C. , Wu Ziman , Nadeau Matthew D. , Edmonsond Stacey , Turner Andrew , Purkis Sam J. , Howes Bolton , Dyer Blake , Ahm Anne-Sofie C. , Yao Nan , Deutsch Curtis A. , Higgins John A. , Stolper Daniel A. , Maloof Adam C.
Published: October 2022

Carbonate mud represents one of the most important geochemical archives for reconstructing ancient climatic, environmental, and evolutionary change from the rock record. Mud also represents a major sink in the global carbon cycle. Yet, there remains no consensus about how and where carbonate mud is formed. Here, we present stable isotope and trace-element data from carbonate constituents in the Bahamas, including ooids, corals, foraminifera, and algae. We use geochemical fingerprinting to demonstrate that carbonate mud cannot be sourced from the abrasion and mixture of any combination of these macroscopic grains. Instead, an inverse Bayesian mixing model requires the presence of an additional aragonite source. We posit that this source represents a direct seawater precipitate. We use geological and geochemical data to show that “whitings” are unlikely to be the dominant source of this precipitate and, instead, present a model for mud precipitation on the bank margins that can explain the geographical distribution, clumped-isotope thermometry, and stable isotope signature of carbonate mud. Next, we address the enigma of why mud and ooids are so abundant in the Bahamas, yet so rare in the rest of the world: Mediterranean outflow feeds the Bahamas with the most alkaline waters in the modern ocean (>99.7th-percentile). Such high alkalinity appears to be a prerequisite for the nonskeletal carbonate factory because, when Mediterranean outflow was reduced in the Miocene, Bahamian carbonate export ceased for 3-million-years. Finally, we show how shutting off and turning on the shallow carbonate factory can send ripples through the global climate system.
Wettability-based ultrasensitive detection of amphiphiles through directed concentration at disordered regions in self-assembled monolayers
Authors: Yao Yuxing , Bennett Robert K. A. , Xu Yang , Rather Adil M. , Li Shucong , Cheung Tung Chun , Bhanji Alisha , Kreder Michael J. , Daniel Dan , Adera Solomon , Aizenberg Joanna , Wang Xiaoguang
Published: October 2022

Various forms of ecological monitoring and disease diagnosis rely upon the detection of amphiphiles, including lipids, lipopolysaccharides, and lipoproteins, at ultralow concentrations in small droplets. Although assays based on droplets’ wettability provide promising options in some cases, their reliance on the measurements of surface and bulk properties of whole droplets (e.g., contact angles, surface tensions) makes it difficult to monitor trace amounts of these amphiphiles within small-volume samples. Here, we report a design principle in which self-assembled monolayer–functionalized microstructured surfaces coated with silicone oil create locally disordered regions within a droplet’s contact lines to effectively concentrate amphiphiles within the areas that dominate the droplet static friction. Remarkably, such surfaces enable the ultrasensitive, naked-eye detection of amphiphiles through changes in the droplets’ sliding angles, even when the concentration is four to five orders of magnitude below their critical micelle concentration. We develop a thermodynamic model to explain the partitioning of amphiphiles at the contact line by their cooperative association within the disordered, loosely packed regions of the self-assembled monolayer. Based on this local analyte concentrating effect, we showcase laboratory-on-a-chip surfaces with positionally dependent pinning forces capable of both detecting industrially and biologically relevant amphiphiles (e.g., bacterial endotoxins), as well as sorting aqueous droplets into discrete groups based on their amphiphile concentrations. Furthermore, we demonstrate that the sliding behavior of amphiphile-laden aqueous droplets provides insight into the amphiphile’s effective length, thereby allowing these surfaces to discriminate between analytes with highly disparate molecular sizes.
14-Carbon demonstrates that some illegal ivory is being taken from government stockpiles
Authors: Cerling Thure E. , Brown John E. , Hoareau Yves , Kahumbu Paula , Odhacha Tobias , Southon John R. , Wasser Samuel K.
Published: October 2022

The 14-carbon in animal tissues records the time that the tissues are formed; since the 1960s, using the “bomb curve” for
14
C, the age of animal death can be determined accurately. Using animal tissue samples of known collection and formation dates for calibration, we determine the age of ivory samples from four ivory seizures made by law enforcement agencies between 2017 and 2019. The
14
C measurements from these seizures show that most ivory in the illegal wildlife trade is from animals from recent poaching activities. However, one seizure has a large fraction of ivory that is more than 30 y old, consistent with markings on the tusks indicating they were derived from a government stockpile.
Dynamic processing of hunger and thirst by common mesolimbic neural ensembles
Authors: Tan Bowen , Nöbauer Tobias , Browne Caleb J. , Nestler Eric J. , Vaziri Alipasha , Friedman Jeffrey M.
Published: October 2022

The nucleus accumbens (NAc) is a canonical reward center that regulates feeding and drinking but it is not known whether these behaviors are mediated by same or different neurons. We employed two-photon calcium imaging in awake, behaving mice and found that during the appetitive phase, both hunger and thirst are sensed by a nearly identical population of individual D1 and D2 neurons in the NAc that respond monophasically to food cues in fasted animals and water cues in dehydrated animals. During the consummatory phase, we identified three distinct neuronal clusters that are temporally correlated with action initiation, consumption, and cessation shared by feeding and drinking. These dynamic clusters also show a nearly complete overlap of individual D1 neurons and extensive overlap among D2 neurons. Modulating D1 and D2 neural activities revealed analogous effects on feeding versus drinking behaviors. In aggregate, these data show that a highly overlapping set of D1 and D2 neurons in NAc detect food and water reward and elicit concordant responses to hunger and thirst. These studies establish a general role of this mesolimbic pathway in mediating instinctive behaviors by controlling motivation-associated variables rather than conferring behavioral specificity.
Recent changes in spoken British English in verbal and nominal constructions
Authors: Schneider Gerold
Published: October 2022

Starting from a data-driven approach, the current paper compares the BNC1994 spoken to the BNC2014. We first narrow down possible research questions due to differences in the compilation and transcription of the two BNC generations. Then we investigate three robustly detectable changes at the level of lexis and morphosyntax: (1) gender and class differences, (2) the increase of be- and get-passive constructions and -ing forms from the verbal domain, and (3) the increase of noun compounds from the nominal domain. We also focus on the social context in which linguistic changes are embedded: which noun compounds particularly increase; which words are overused by which gender or social class? Technology seems to be a driver in the further advance of the construction of noun compounds, and strong swearing seems to have decreased between 1994 and 2014.
High-Performance Indium-Gallium-Zinc-Oxide Thin-Film Transistors with Stacked Al2O3/HfO2 Dielectrics
Authors: Li Yue , Zhu Li , Chen Chunsheng , Zhu Ying , Wan Changjin , Wan Qing
Published: October 2022

High-performance amorphous indium-gallium-zinc-oxide thin-film transistors (a-IGZO TFTs) gated by Al2O3/HfO2 stacked dielectric films are investigated. The optimized TFTs with Al2O3 (2.0 nm)/HfO2 (13 nm) stacked gate dielectrics demonstrate the best performance, including low total trap density N
t, low subthreshold swing voltage, large switching ratio I
ON/OFF, high mobility μ
FE, and low operating voltage, equal to 1.35 × 1012 cm−2, 88 mV/dec, 5.24 × 108, 14.2 cm2/V⋅s, and 2.0 V, respectively. Furthermore, a low-voltage-operated resistor-loaded inverter has been fabricated based on such an a-IGZO TFT, showing ideal full swing characteristics and high gain of ∼27 at 3.0 V. These results indicate a-IGZO TFTs gated by optimized Al2O3/HfO2 stacked dielectrics are of great interests for low-power, high performance, and large-area display and emerging electronics.
Constraining GUP models using limits on SME coefficients
Authors: Gomes André Herkenhoff
Published: October 2022

Generalized uncertainty principles (GUP) and, independently, Lorentz symmetry violations are two common features in many candidate theories of quantum gravity. Despite that, the overlap between both has received limited attention so far. In this brief paper, we carry out further investigations on this topic. At the nonrelativistic level and in the realm of commutative spacetime coordinates, a large class of both isotropic and anisotropic GUP models is shown to produce signals experimentally indistinguishable from those predicted by the standard model extension (SME), the common framework for studying Lorentz-violating phenomena beyond the standard model. This identification is used to constrain GUP models using current limits on SME coefficients. In particular, bounds on isotropic GUP models are improved by a factor of 107 compared to current spectroscopic bounds and anisotropic models are constrained for the first time.
Modeling heavy-ion fusion cross section data via a novel artificial intelligence approach
Authors: Dell’Aquila Daniele , Gnoffo Brunilde , Lombardo Ivano , Porto Francesco , Russo Marco
Published: October 2022

We perform a comprehensive analysis of complete fusion cross section data with the aim to derive, in a completely data-driven way, a model suitable to predict the integrated cross section of the fusion between light-to-medium mass nuclei at above barrier energies. To this end, we adopted a novel artificial intelligence approach, based on a hybridization of genetic programming and artificial neural networks, capable to derive an analytical model for the description of experimental data. The approach enables to perform a global search for computationally simple models over several variables and a considerable body of nuclear data. The derived phenomenological formula can serve to reproduce the trend of fusion cross section for a large variety of light to intermediate mass collision systems in an energy domain ranging approximately from the Coulomb barrier to the onset of multi-fragmentation phenomena.
Navier–Stokes equations: regularity criteria in terms of the derivatives of several fundamental quantities along the streamlines—the case of a bounded domain
Authors: Guo Zhengguang , Kučera Petr , Skalak Zdenek
Published: October 2022

In this paper we deal with the conditional regularity of the weak solutions of the Navier–Stokes equations on a bounded domain endowed with Navier boundary conditions, Navier-type boundary conditions or Dirichlet boundary conditions. We prove the regularity criteria which are based on the directional derivatives of several fundamental quantities along the streamlines, namely the velocity magnitude, the kinetic energy, the pressure, the velocity field and the Bernoulli pressure. In striking contrast to the known criteria in which the mentioned quantities were differentiated along a fixed vector, our criteria are mostly optimal for the whole range of parameters and have a clear physical meaning.
A traveling wave bifurcation analysis of turbulent pipe flow
Authors: Engel Maximilian , Kuehn Christian , de Rijk Björn
Published: October 2022

Using various techniques from dynamical systems theory, we rigorously study an experimentally validated model by [Barkley et al 2015 Nature
526 550–3], which describes the rise of turbulent pipe flow via a PDE system of reduced complexity. The fast evolution of turbulence is governed by reaction-diffusion dynamics coupled to the centerline velocity, which evolves with advection of Burgers’ type and a slow relaminarization term. Applying to this model a spatial dynamics ansatz and geometric singular perturbation theory, we prove the existence of a heteroclinic loop between a turbulent and a laminar steady state and establish a cascade of bifurcations of various traveling waves mediating the transition to turbulence. The most complicated behaviour can be found in an intermediate Reynolds number regime, where the traveling waves exhibit arbitrarily long periodic-like dynamics indicating the onset of chaos. Our analysis provides a systematic mathematical approach to identifying the transition to spatio–temporal turbulent structures that may also be applicable to other models arising in fluid dynamics.
Poincaré series for surfaces with boundary
Authors: Chaubet Yann
Published: October 2022

We provide a meromorphic continuation for Poincaré series counting orthogeodesics of a negatively curved surface with totally geodesic boundary, as well as for Poincaré series counting geodesic arcs linking two points. For the latter series, we show that the value at zero coincides with the inverse of the Euler characteristic of the surface.
Existence and uniqueness of equilibrium states for systems with specification at a fixed scale: an improved Climenhaga–Thompson criterion*
Authors: Pacifico Maria Jose , Yang Fan , Yang Jiagang
Published: October 2022

We consider the uniqueness of equilibrium states for dynamical systems that satisfy certain weak, non-uniform versions of specification, expansivity, and the Bowen property at a fixed scale. Following Climenhaga–Thompson’s approach which was originally due to Bowen and Franco, we prove that equilibrium states are unique even when the weak specification assumption only holds on a small collection of orbit segments. This improvement will be crucial in a subsequent work, where we will prove that (open and densely) every Lorenz attractor supports a unique measure of maximal entropy.
Circularly polarized scalar induced gravitational waves from the Chern-Simons modified gravity
Authors: Zhang Fengge , Feng Jia-Xi , Gao Xian
Published: October 2022

We investigate the scalar induced gravitational waves (SIGWs) in the Chern-Simons (CS) modified gravity during the radiation dominated era. The SIGWs are circularly polarized, which provide us a tool to test the possible parity violation in the early universe. We derive the semianalytic expressions to evaluate the fractional energy density of the SIGWs, ΩGW, which receives contributions from the general relativity (GR) and the correction due to the parity-violating term, respectively. We find that the degree of the circular polarization of the SIGWs can be as large as of order unity, although the contribution to ΩGW from the CS term is at most of the same order as that from the GR.
An Improved Radio Pointing Model for SHARC II of the Caltech Submillimeter Observatory Telescope
Authors: Chen Weirui , Wang Zheng , Zhou Xiaojun
Published: October 2022

In this research, we develop a new method of upgrading the radio pointing model of an important instrument of the Caltech Submillimeter Observatory (CSO) telescope, i.e., the Submillimeter High Angular Resolution Camera II (SHARC II), by making three types of structural reconstruction of its existing model. First, the axial displacement of the secondary reflector of the telescope is introduced to the radio pointing model for SHARC II. Second, the multi-layer perceptron is applied for better describing higher-order terms in the radio pointing model, which are hard to be mathematically formulated. Third, a receding horizon modeling method is proposed to replace the time-dependent term in the existing model, for better reducing the negative impact of the time drift on the model’s accuracy. Results of numerical experiments and statistical significance analysis based on the real pointing data of SHARC II show that the reconstructed radio pointing model can improve the accuracy of estimating the pointing error, and the proposed method of upgrading the radio pointing model is effective. Considering that the CSO telescope will be moved from the old site at Maunakea, Hawaii to the new site at the Chajnantor Plateau in Chile, the proposed methods of upgrading the radio pointing model are expected to be employed for pointing correction after the telescope is refurbished at the new site.
Maximum mass of anisotropic charged strange quark stars in a higher dimensional approach (D ≥ 4)
Authors: Saha A. , Goswamiy K.B. , Dasz B. , Chattopadhyayx P.K.
Published: October 2022

In this article, a new class of solutions of Einstein-Maxwell field equations of relativistic strange quark stars obtained in dimensions

, is shown. We assume that the geometry of space-time is pseudo-spheroid, embedded in Euclidean space of

dimensions. The MIT bag model equation of state

is employed to study the relevant properties of strange quark stars. For the causal and non-negative nature of the square of the radial sound velocity

, we observe that some restrictions exist on the reduced radius

, where R is a parameter related to the curvature of the space-time, and b is the radius of the star. The spheroidal parameter λ used here defines the metric potential of the

component, which is pseudo-spheroidal in nature. We note that the pressure anisotropy and charge have some effects on λ. The maximum mass for a given surface density (

) or bag constant

assumes a maximum value in dimension

and decreases for other values of D. The generalized Buchdahl limit for a higher dimensional charged star is also obeyed in this model. We observe that in this model, we can predict the mass of a strange quark star using a suitable value of the electric charge (Q) and bag constant (B). Energy and stability conditions are also satisfied in this model. Stability is also studied considering the dependence of the Lagrangian perturbation of radial pressure (

) on the frequency of normal modes of oscillations. The tidal Love number and tidal de-formability are also evaluated.
Torsion Fields Generated by the Quantum Effects of Macro-bodies
Authors: Chen Da-Ming
Published: October 2022

We generalize Einstein’s General Relativity (GR) by assuming that all matter (including macro-objects) has quantum effects. An appropriate theory to fulfill this task is Gauge Theory Gravity (GTG) developed by the Cambridge group. GTG is a “spin-torsion” theory, according to which, gravitational effects are described by a pair of gauge fields defined over a flat Minkowski background spacetime. The matter content is completely described by the Dirac spinor field, and the quantum effects of matter are identified as the spin tensor derived from the spinor field. The existence of the spin of matter results in the torsion field defined over spacetime. Torsion field plays the role of Bohmian quantum potential which turns out to be a kind of repulsive force as opposed to the gravitational potential which is attractive. The equivalence principle remains and essential in this theory so that GR is relegated to a locally approximate theory wherein the quantum effects (torsion) are negligible. As a toy model, we assume that the macro matter content can be described by the covariant Dirac equation and apply this theory to the simplest radially symmetric and static gravitational systems. Consequently, by virtue of the cosmological principle, we are led to a static universe model in which the Hubble redshifts arise from the torsion fields.
Optimal data generation for machine learned interatomic potentials
Authors: Allen Connor , Bartók Albert P
Published: October 2022

Machine learning interatomic potentials (MLIPs) are routinely used atomic simulations, but generating databases of atomic configurations used in fitting these models is a laborious process, requiring significant computational and human effort. A computationally efficient method is presented to generate databases of atomic configurations that contain optimal information on the small-displacement regime of the potential energy surface of bulk crystalline matter. Utilising non-diagonal supercell (Lloyd-Williams and Monserrat 2015 Phys. Rev. B 92 184301), an automatic process is suggested for ab initio data generation. MLIPs were fitted for Al, W, Mg and Si, which very closely reproduce the ab initio phonon and elastic properties. The protocol can be easily adapted to other materials and can be inserted in the workflow of any flavour of MLIP generation.
Autologous Platelet-Rich Plasma in Clitoral Reconstructive Surgery After Female Genital Mutilation/Cutting: A Pilot Case Study
Authors: Tognazzo Enrico , Berndt Sarah , Abdulcadir Jasmine
Published: October 2022

Background

Postoperative healing after clitoral reconstruction (CR) for female genital mutilation/cutting can be long and painful due to prolonged clitoral re-epithelialization time (up to 3 months). Autologous platelet-rich plasma (A-PRP) might reduce postoperative clitoral epithelialization time and pain.

Objectives

The authors assessed postoperative clitoral re-epithelialization time and pain after intraoperative clitoral administration of A-PRP.

Methods

Five consecutive women underwent CR (Foldès technique) followed by the administration of A-PRP Regen Lab SA (Le Mont-sur-Lausanne, Switzerland) plasma and glue, injected inside and applied above the re-exposed clitoris, respectively. We recorded surgical complications, postoperative clitoral pain (visual analogue scale), painkiller intake, time to complete re-epithelialization, and the experienced subjective changes in sexual response and perception of their own body image referred by women.

Results

Sexual distress/dysfunction as well as the desire to be physically and symbolically “repaired” were the reasons behind women's requests for surgery. None of the women suffered from chronic vulvar or non-vulvar pain. All women achieved complete clitoral epithelialization by day 80, 3 women between day 54 and 70, and only 1 woman was still taking 1 g of paracetamol twice a day at 2 months postoperative. She had stopped it before the 3-month control. There were no short- or long-term complications. All women described easier access and stimulation of their clitoris as well as improved sexual arousal, lubrication, and pleasure and claimed to be satisfied with their restored body image.

Conclusions

A-PRP could expedite postoperative clitoral epithelialization and reduce postoperative pain after CR after female genital mutilation/cutting.

Level of Evidence: 4
CEDA: integrating gene expression data with CRISPR-pooled screen data identifies essential genes with higher expression
Authors: Zhao Yue , Yu Lianbo , Wu Xue , Li Haoran , Coombes Kevin R , Au Kin Fai , Cheng Lijun , Li Lang
Published: October 2022

Motivation

Clustered regularly interspaced short palindromic repeats (CRISPR)-based genetic perturbation screen is a powerful tool to probe gene function. However, experimental noises, especially for the lowly expressed genes, need to be accounted for to maintain proper control of false positive rate.

Methods

We develop a statistical method, named CRISPR screen with Expression Data Analysis (CEDA), to integrate gene expression profiles and CRISPR screen data for identifying essential genes. CEDA stratifies genes based on expression level and adopts a three-component mixture model for the log-fold change of single-guide RNAs (sgRNAs). Empirical Bayesian prior and expectation–maximization algorithm are used for parameter estimation and false discovery rate inference.

Results

Taking advantage of gene expression data, CEDA identifies essential genes with higher expression. Compared to existing methods, CEDA shows comparable reliability but higher sensitivity in detecting essential genes with moderate sgRNA fold change. Therefore, using the same CRISPR data, CEDA generates an additional hit gene list.

Supplementary information

Supplementary data are available at Bioinformatics online.
Complementary contribution of the medial and lateral human parietal cortex to grasping: a repetitive TMS study
Authors: Breveglieri Rossella , Borgomaneri Sara , Filippini Matteo , Tessari Alessia , Galletti Claudio , Davare Marco , Fattori Patrizia
Published: October 2022

The dexterous control of our grasping actions relies on the cooperative activation of many brain areas. In the parietal lobe, 2 grasp-related areas collaborate to orchestrate an accurate grasping action: dorsolateral area AIP and dorsomedial area V6A. Single-cell recordings in monkeys and fMRI studies in humans have suggested that both these areas specify grip aperture and wrist orientation, but encode these grasping parameters differently, depending on the context. To elucidate the causal role of phAIP and hV6A, we stimulated these areas, while participants were performing grasping actions (unperturbed grasping). rTMS over phAIP impaired the wrist orientation process, whereas stimulation over hV6A impaired grip aperture encoding. In a small percentage of trials, an unexpected reprogramming of grip aperture or wrist orientation was required (perturbed grasping). In these cases, rTMS over hV6A or over phAIP impaired reprogramming of both grip aperture and wrist orientation. These results represent the first direct demonstration of a different encoding of grasping parameters by 2 grasp-related parietal areas.
Clinical Features of Patients Hospitalized for All Routes of Anthrax, 1880–2018: A Systematic Review
Authors: Hendricks Katherine , Person Marissa K , Bradley John S , Mongkolrattanothai Thitipong , Hupert Nathaniel , Eichacker Peter , Friedlander Arthur M , Bower William A
Published: October 2022

Background

Anthrax is a toxin-mediated zoonotic disease caused by Bacillus anthracis, with a worldwide distribution recognized for millennia. Bacillus anthracis is considered a potential biowarfare agent.

Methods

We completed a systematic review for clinical and demographic characteristics of adults and children hospitalized with anthrax (cutaneous, inhalation, ingestion, injection [from contaminated heroin], primary meningitis) abstracted from published case reports, case series, and line lists in English from 1880 through 2018, assessing treatment impact by type and severity of disease. We analyzed geographic distribution, route of infection, exposure to anthrax, and incubation period.

Results

Data on 764 adults and 167 children were reviewed. Most cases reported for 1880 through 1915 were from Europe; those for 1916 through 1950 were from North America; and from 1951 on, cases were from Asia. Cutaneous was the most common form of anthrax for all populations. Since 1960, adult anthrax mortality has ranged from 31% for cutaneous to 90% for primary meningitis. Median incubation periods ranged from 1 day (interquartile range [IQR], 0–4) for injection to 7 days (IQR, 4–9) for inhalation anthrax. Most patients with inhalation anthrax developed pleural effusions and more than half with ingestion anthrax developed ascites. Treatment and critical care advances have improved survival for those with systemic symptoms, from approximately 30% in those untreated to approximately 70% in those receiving antimicrobials or antiserum/antitoxin.

Conclusions

This review provides an improved evidence base for both clinical care of individual anthrax patients and public health planning for wide-area aerosol releases of B. anthracis spores.
Evaluation of Amoxicillin and Amoxicillin-Clavulanate (Augmentin) for Antimicrobial Postexposure Prophylaxis Following Bacillus anthracis Inhalational Exposure in Cynomolgus Macaques
Authors: Slay Raymond M , Hatch Graham J , Hewitt Judith A
Published: October 2022

Amoxicillin is a broad-spectrum antibiotic used to treat a variety of gram-positive and gram-negative infections, such as infections of the ear, nose, and throat, genitourinary tract, skin, and lower respiratory tract; gonorrhea; and Helicobacter pylori. The prophylactic benefit of both amoxicillin and Augmentin (amoxicillin-clavulanate for use against β-lactamase–expressing bacteria) was evaluated for inhalation anthrax in cynomolgus macaques in 2 studies. A pilot study on amoxicillin-clavulanate that used a portion of the study animals demonstrated empirically that dosing twice a day was efficacious. In a subsequent study on both amoxicillin and amoxicillin-clavulanate that used the remaining study animals, the animals were treated orally every 12 hours on days 1–28 postchallenge and followed for an additional 60 days (total of 88 days from day of aerosol challenge to when the animals were culled). The animals from each treatment arm of the 2 studies were completely protected. All untreated animals succumbed to the infection. The degree of protection observed in this study suggests that both amoxicillin and amoxicillin-clavulanate, administered prophylactically over a period of 28 days after a lethal exposure to Bacillus anthracis spores, is sufficient for full protection.
Postexposure Prophylaxis and Treatment of Bacillus anthracis Infections: A Systematic Review and Meta-analyses of Animal Models, 1947–2019
Authors: Kennedy Jordan L , Bulitta Jürgen B , Chatham-Stephens Kevin , Person Marissa K , Cook Rachel , Mongkolrattanothai Thitipong , Shin Eunjeong , Yu Patricia , Negron Maria E , Bower William A , Hendricks Katherine
Published: October 2022

Background

Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies.

Methods

We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans.

Results

We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx.

Conclusions

These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.
Aiming too high or scoring too low? Heterogeneous immigrant–native gaps in upper secondary enrollment and outcomes beyond the transition in France
Authors: Ferrara Alessandro
Published: October 2022

The children of immigrants usually make more ambitious enrolment choices than native students with comparable socioeconomic status and academic achievement. Less is known about how ethnic choice effects vary by socioeconomic status and previous achievement simultaneously, and whether they only hold true for some immigrant–native comparisons. Moreover, few studies investigate outcomes after the educational transition, so the consequences of ambitious choices remain unclear. I investigate immigrant–native gaps in the decision to enroll in academic upper secondary education and in outcomes after the transition for two cohorts of French students. I find that ethnic choice effects are positive only for students with an intermediate or working class background, and are largest for those with lower to middle achievement from the working class. Migrant disadvantages in outcomes after the transition were reduced between cohorts. In the latest cohort, immigrant-origin and native students enrolled in academic upper secondary were equally likely to complete the track and enroll in tertiary education. However, immigrant-origin students were still disadvantaged in terms of graduation track, grades, and timing. Using counterfactual reweighting strategies, I show that similar and substantial portions of these disadvantages were explained by the ambitious academic choices and lower prior performance of immigrant-origin students. However, while their ambitious choices also increase enrolment rates and hence overall attainment for immigrant-origin students, their lower prior performance reduces both. I suggest that policies should reduce immigrant disadvantages in early achievement to allow high-aspiring, yet often disadvantaged, immigrant-origin students to succeed in ambitious educational paths.
The seismic dispersion and attenuation characteristics of organic shales
Authors: Li Hui , Huang Qi , Zhao Luanxiao , Wang Yirong , Cai Zhenjia , Qin Xuan , Gao Jinghuai , Han Dehua
Published: October 2022

To improve our understanding of wave dispersion and adsorption signature of organic shales, we select a set of vertical shale samples cored from different formations and conduct the forced-oscillation measurements in seismic frequencies of 2–800 Hz at the oven-dried conditions. The results demonstrated that both Young's modulus and Poisson's ratio of immature Barnett and Eagle Ford shales and mature Mancos shale remain roughly constant and the extensional attenuations are also insignificant at the entire frequency band. However, the mature Jungar shale exhibits strong dispersions with the magnitude of 23.4 per cent for Young's modulus at the confining pressure of 3.4 MPa. The dispersion and magnitude of Jungar shale overall exhibit a decreasing trend with increasing pressure, but still maintain strong attenuation at the confining pressure of 20.8 MPa. It is found that the single parameter of TOC, thermal maturity and clay content are not the controlling factors of wave dispersion and adsorption signatures. Instead, the geochemical index ${\rm{TOC}} \times {S_1}/({S_1}{\rm{ + }}{S_2})$ is positively correlated with dispersion and attenuation magnitude, suggesting that organic richness and maturity level jointly control the wave adsorption characteristics. Geochemical analysis and phenomenological modelling imply that such kinds of energy dissipation in organic shales are possibly caused by the viscous friction at interfaces between inorganic grains and the surface of liquefied or bitumen-filled organic matter. Besides, a modified standard linear solid model containing multiple sets of a characteristic frequency is proposed and well captures the continuous dispersion signatures considering that the Jungar shale contains various maturity-induced viscous organic matter.
Use of Straighteners and Other Hair Products and Incident Uterine Cancer
Authors: Chang Che-Jung , O’Brien Katie M , Keil Alexander P , Gaston Symielle A , Jackson Chandra L , Sandler Dale P , White Alexandra J
Published: October 2022

Background

Hair products may contain hazardous chemicals with endocrine-disrupting and carcinogenic properties. Previous studies have found hair product use to be associated with a higher risk of hormone-sensitive cancers including breast and ovarian cancer; however, to our knowledge, no previous study has investigated the relationship with uterine cancer.

Methods

We examined associations between hair product use and incident uterine cancer among 33 947 Sister Study participants aged 35-74 years who had a uterus at enrollment (2003-2009). In baseline questionnaires, participants in this large, racially and ethnically diverse prospective cohort self-reported their use of hair products in the prior 12 months, including hair dyes; straighteners, relaxers, or pressing products; and permanents or body waves. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations between hair product use and uterine cancer using Cox proportional hazard models. All statistical tests were 2-sided.

Results

Over an average of 10.9 years of follow-up, 378 uterine cancer cases were identified. Ever vs never use of straightening products in the previous 12 months was associated with higher incident uterine cancer rates (HR = 1.80, 95% CI = 1.12 to 2.88). The association was stronger when comparing frequent use (>4 times in the past 12 months) vs never use (HR = 2.55, 95% CI = 1.46 to 4.45; Ptrend = .002). Use of other hair products, including dyes and permanents or body waves, was not associated with incident uterine cancer.

Conclusion

These findings are the first epidemiologic evidence of association between use of straightening products and uterine cancer. More research is warranted to replicate our findings in other settings and to identify specific chemicals driving this observed association.
The Enhancing Oncology Model: Leveraging improvement science to increase health equity in value-based care
Authors: Patel Tej A , Jain Bhav , Parikh Ravi B
Published: October 2022

The Oncology Care Model (OCM), launched in 2016 by the Centers for Medicare and Medicaid Services, was the first demonstration of value-based payment in oncology. Although the OCM delivered mixed results in terms of quality of care and total episode costs, the model had no statistically significant impact on remediating racial, ethnic, and socioeconomic disparities among beneficiaries. These deficits have been prominent in other aspects of US healthcare, and as a result, the Institute for Healthcare Improvement has advocated for stakeholders to leverage improvement science, an applied science that focuses on implementing rapid cycles for change, to identify and overcome barriers to health equity. With the announcement of the new Enhancing Oncology Model, a continuation of the OCM’s efforts in introducing value to cancer care for episodes surrounding chemotherapy administration, both policymakers and providers must apply tenets of improvement science and make eliminating disparities in alternative payment models a forefront objective. In this commentary, we discuss previous inequities in alternative payment models, the role that improvement science plays in addressing health-care disparities, and steps that stakeholders can take to maximize equitable outcomes in the Enhancing Oncology Model.