bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative margin design and optimized isocenter to minimize the normal tissue in target volumes for single-isocenter multi-target stereotactic radiosurgery
Authors: Yock Adam D , Grees Beshoi , Luo Guozhen
Published: September 2023

Objective. Treating multiple brain metastases in a single plan is a popular radiosurgery technique. However, targets positioned off-isocenter are subject to rotational uncertainties. This work introduces two new planning target volumes (PTVs) that address this increased uncertainty. The volume of normal tissue included in these PTVs when paired with optimized isocenters are evaluated and compared with conventional methods. Approach. Sets of 1000 random multi-target radiosurgery patients were simulated, each patient with a random number of spherical targets (2–10). Each target had a random volume (0.1–15 cc) and was randomly positioned between 5 and 50 mm or 100 mm from isocenter. Two new PTVs (‘LensPTV’ and ‘SwipePTV’) and conventional isotropic PTVs were created using isocenters derived from the center-of-centroids, the center-of-mass, or optimized per PTV type. The total volume of normal tissue in the PTVs for each patient was calculated and compared using 1 mm translations and 0.5°, 1.0°, and 2.0° rotations. Main results. Using the new PTVs and/or using optimized isocenters decreased the total volume of normal tissue in the PTVs per patient. The SwipePTV, in particular, provided the greatest decrease. Compared to the SwipePTV, the LensPTV and the conventional isotropic PTV included an extra 0.68 and 0.73 cc of normal tissue per patient (median), respectively, when using 50 mm max distance to isocenter and 1° max rotation angle. Under these conditions, 25% of patients had extra volume of normal tissue ≥ 0.96 and 1.04 cc. When using 100 mm max distance to isocenter and 2° max rotation angle, 25% of patients had extra volume of normal tissue ≥ 4.35 and 5.75 cc. Significance. PTVs like those presented here, especially when paired with optimized isocenters, can decrease the total volume of included normal tissue and reduce the risk of toxicity without compromising target coverage.
Experimental study on effect of temperature and moisture on piezoresistive effect of carbon nanotube concrete
Authors: Qin Yu , Tang Yujie , Ruan Pengzhen , Wang Ting , Wang Weina
Published: September 2023

Carbon nanotube (CNT) reinforced cement based composite materials can be used as self-sensing sensors for intelligent monitoring of concrete structures. In practical engineering, concrete structures are affected and restricted by various environmental factors. Therefore, this paper conducted experimental research on the influencing factors of the piezoresistive effect of CNT concrete. The main influencing factors selected include CNT concentration (0 wt.%–0.5 wt.%), moisture content (immersion time of 0 min–120 min), and temperature (20 °C–60 °C). The experimental results show that the specimen with a CNT concentration of 0.5 wt.% has a higher stress sensitivity (SES), and the change in resistivity shows good stability and repeatability under cyclic stress. The resistivity decreases with prolongation of immersion time, and the SES increases first and then decreases, reaching a peak at 30 min of immersion. When the temperature increases from 20 °C to 60 °C, the resistivity decreases. The influence of temperature on dry and wet specimens is different. In the moisture state, the fraction change in resistivity and SES always decreased. In the dry state, as the temperature increases, the SES first increases and then decreases, with the maximum value occurring at 30 °C.
Current limiting and recovery characteristics of an AC fast recovery superconducting fault current-limiting breaker
Authors: Zhang Qi , Song Meng , Li Li , Xiang Bin , Tang Zhengquan , Li Hongxu , Yuan Zhongbin , Du Huixin , Geng Yingsan , Liu Zhiyuan , Wang Jianhua
Published: September 2023

With the continuous development of the power grid, the high short-circuit fault current threatens the reliability of the power system. When the short-circuit current is greater than the interrupting capacity of the circuit breaker, the fault current will not be interrupted. Resistive-type superconducting fault current limiter (R-SFCL) has little loss in normal conditions. When a short-circuit fault occurs, R-SFCL can respond within a few milliseconds and limit the fault current. But the recovery time of R-SFCL is too long to satisfy the reclosing demand in the power grid. In this paper, an AC fast recovery superconducting fault current-limiting breaker (FR-SFCB) is proposed. With the operation of a fast switch connected with the superconducting coil, one of the parallel superconducting branches is disconnected, which could provide higher current limiting resistance and decrease the fault current need to be interrupted in fault conditions. Because of the shorter current flowing time, the heat generation and temperature of the advanced disconnected branch are less which can reduce the recovery time significantly. An experimental model is established based on thyristors and superconducting tapes. The effects of prospective current (I
p) and the types of superconducting tapes on the current limiting resistance and recovery time of FR-SFCB are investigated. Experimental results show that with the disconnection of the flowing branch, the current limiting resistance of the proposed FR-SFCB increases to more than 3 times of the normal R-SFCL. At the same time, when the FR-SFCB resistance after current limiting is lower than the room temperature resistance, the recovery time of the flowing branch decreases by at least 50%. With access to fast switches, the proposed FR-SFCB can suppress the short-circuit fault current effectively and improve the stability of the power system.
Engineered asymmetric diffractions of diagonal-line odd-symmetric phase gratings
Authors: Hua Shuo , Zhang Xiao-Jun , Chen Yao-Tong , Liu Yi-Mou , Wu Jin-Hui
Published: September 2023

A two-dimensional multi-element phase grating has been designed in terms of the offset refractive index to exhibit the spatially odd symmetry (antisymmetry) along one transparent diagonal line with an even number of rectangular elements while leaving other elements in a unit cell opaque. This grating can be engineered to attain a few intriguing phenomena of asymmetric diffraction, including the elimination of equally spaced oblique diffraction lines, the elimination of alternately crossed oblique diffraction lines, and the selection of equally spaced oblique diffraction lines. These phenomena of engineered asymmetric diffraction are well explained via destructive interference between transmitted field amplitudes from paired, dual-paired, and successive elements along the transparent diagonal line.
Reconfigurable skyrmion logic gates with auto-annihilating skyrmion function
Authors: Xu Min , Chen Yuliang , Chen Wenlong , Hu Changjing , Zhang Zhiyu , Jiang Guiqian , Zhang Jinyu
Published: September 2023

Skyrmions are a spin texture with topological protection properties, which can be considered as an excellent candidate for the next generation of high-speed, nonvolatile, and low-power consumption spin devices due to their unique dynamic characteristics. In this work, we propose reconfigurable skyrmion-based logic gates with auto-annihilating skyrmion function, and six logical operations can be implemented in our model relying on the competition among the spin transfer torque (STT), skyrmion Hall effect (SkHE), skyrmion-edge repulsion, skyrmion-skyrmion topological repulsion, and voltage-controlled magnetic anisotropy (VCMA) effect. The influence of temperature on the logical operation processes indicates that the temperature range for achieving all types of logic operations and automatic annihilation function is 0–96 K. The function of automatically clearing skyrmions after the completion of logic operations can free up space for storing unnecessary skyrmions, and save energy consumption for applying additional current to eliminate them. Our results can be beneficial for the design and development of magnetic skyrmion logic gates.
Darboux transformation, infinite conservation laws, and exact solutions for the nonlocal Hirota equation with variable coefficients
Authors: Liu 刘 Jinzhou 锦洲 , Yan 闫 Xinying 鑫颖 , Jin 金 Meng 梦 , Xin 辛 Xiangpeng 祥鹏
Published: September 2023

This article presents the construction of a nonlocal Hirota equation with variable coefficients and its Darboux transformation. Using zero-seed solutions, 1-soliton and 2-soliton solutions of the equation are constructed through the Darboux transformation, along with the expression for N-soliton solutions. Influence of coefficients that are taken as a function of time instead of a constant, i.e., coefficient function δ(t), on the solutions is investigated by choosing the coefficient function δ(t), and the dynamics of the solutions are analyzed. This article utilizes the Lax pair to construct infinite conservation laws and extends it to nonlocal equations. The study of infinite conservation laws for nonlocal equations holds significant implications for the integrability of nonlocal equations.
Analysis of functional connectivity using machine learning and deep learning in different data modalities from individuals with schizophrenia
Authors: Alves Caroline L , Toutain Thaise G L de O. , Porto Joel Augusto Moura , Aguiar Patrícia Maria de Carvalho , de Sena Eduardo Pondé , Rodrigues Francisco A , Pineda Aruane M , Thielemann Christiane
Published: September 2023

Objective. Schizophrenia (SCZ) is a severe mental disorder associated with persistent or recurrent psychosis, hallucinations, delusions, and thought disorders that affect approximately 26 million people worldwide, according to the World Health Organization. Several studies encompass machine learning (ML) and deep learning algorithms to automate the diagnosis of this mental disorder. Others study SCZ brain networks to get new insights into the dynamics of information processing in individuals suffering from the condition. In this paper, we offer a rigorous approach with ML and deep learning techniques for evaluating connectivity matrices and measures of complex networks to establish an automated diagnosis and comprehend the topology and dynamics of brain networks in SCZ individuals. Approach. For this purpose, we employed an functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) dataset. In addition, we combined EEG measures, i.e. Hjorth mobility and complexity, with complex network measurements to be analyzed in our model for the first time in the literature. Main results. When comparing the SCZ group to the control group, we found a high positive correlation between the left superior parietal lobe and the left motor cortex and a positive correlation between the left dorsal posterior cingulate cortex and the left primary motor. Regarding complex network measures, the diameter, which corresponds to the longest shortest path length in a network, may be regarded as a biomarker because it is the most crucial measure in different data modalities. Furthermore, the SCZ brain networks exhibit less segregation and a lower distribution of information. As a result, EEG measures outperformed complex networks in capturing the brain alterations associated with SCZ. Significance. Our model achieved an area under receiver operating characteristic curve (AUC) of 100% and an accuracy of 98.5% for the fMRI, an AUC of 95%, and an accuracy of 95.4% for the EEG data set. These are excellent classification results. Furthermore, we investigated the impact of specific brain connections and network measures on these results, which helped us better describe changes in the diseased brain.
Isothermal annealing of radiation defects in silicon bulk material of diodes from 8” silicon wafers
Authors: Kieseler Jan , Dias de Almeida Pedro Gonçalo , Kałuzińska Oliwia Agnieszka , Mühlnikel Marie Christin , Diehl Leena , Sicking Eva , Zehetner Philipp
Published: September 2023

The high luminosity upgrade of the LHC will provide unique physics opportunities, such as
the observation of rare processes and precision measurements. However, the accompanying harsh
radiation environment will also pose unprecedented challenged to the detector performance and
hardware. In this paper, we study the radiation induced damage and its macroscopic isothermal
annealing behaviour of the bulk material from new 8” silicon wafers using diode test
structures. The sensor properties are determined through measurements of the diode capacitance and
leakage current for three thicknesses, two material types, and neutron fluences from 6.5·
1014 to 1 · 1016 neq/cm2.
A optomechanical design for Fabry-Perot Interferometer
Authors: Mahavarkar Prasanna
Published: September 2023

Fabry-Perot Interferometer are particularly useful for high-resolution spectroscopy and
other applications including astronomy and intra-cavity laser-line narrowing. Fabry-Perot etalon
with diameters 1 mm square to 100 mm circular are commercially available and using a conglomerate
of optomechanical components and lenses form a Fabry-Perot Interferometer (FPI) system. The etalon
when illuminated with a known wavelength laser beam through fore-optics transmits the interference
pattern onto a detector through back-optics and thus the image formed on the detector is a
concentric circular interference fringe pattern. A sharp pattern with a maximum number of fringes
is achieved by introducing a correct combination of the fore and back optomechanical system.
Commercially available interferometer inclusive of the optics and the etalon are expensive and
beyond the purchasing capacity of budget-conscious users. An alternative to these ready-made
interferometer is to manufacture an indigenous optomechanical system and integrate it with the
commercially available etalon that delivers a low cost, less weight, and a fairly simple FPI. This
report discusses in detail one such system designed and developed in our institute laboratory. The
important parameter finesse is calculated and its accuracy is found to be 85%. The developed
system with further modifications, like the insertion of the field-of-view module, may serve as an
alternative for the large size-based integrating sphere systems that are deployed in the field
for observations.
Identifying opportunity hot spots for reducing the risk of wildfire-caused carbon loss in western US conifer forests
Authors: Peeler Jamie L , McCauley Lisa , Metlen Kerry L , Woolley Travis , Davis Kimberley T , Robles Marcos D , Haugo Ryan D , Riley Karin L , Higuera Philip E , Fargione Joseph E , Addington Robert N , Bassett Steven , Blankenship Kori , Case Michael J , Chapman Teresa B , Smith Edward , Swaty Randy , Welch Nathan
Published: September 2023

The escalating climate and wildfire crises have generated worldwide interest in using proactive forest management (e.g. forest thinning, prescribed fire, cultural burning) to mitigate the risk of wildfire-caused carbon loss in forests. To estimate the risk of wildfire-caused carbon loss in western United States (US) conifer forests, we used a generalizable framework to evaluate interactions among wildfire hazard and carbon exposure and vulnerability. By evaluating where high social adaptive capacity for proactive forest management overlaps with carbon most vulnerable to wildfire-caused carbon loss, we identified opportunity hot spots for reducing the risk of wildfire-caused carbon loss. We found that relative to their total forest area, California, New Mexico, and Arizona contained the greatest proportion of carbon highly vulnerable to wildfire-caused loss. We also observed widespread opportunities in the western US for using proactive forest management to reduce the risk of wildfire-caused carbon loss, with many areas containing opportunities for simultaneously mitigating the greatest risk from wildfire to carbon and human communities. Finally, we highlighted collaborative and equitable processes that provide pathways to achieving timely climate- and wildfire-mitigation goals at opportunity hot spots.
The PMIP4 simulated dryland aridity changes during the Last Interglacial
Authors: Liu Shanshan , Zhou Xuecheng
Published: September 2023

The dryland is one of the most important land ecosystems on the planet, and its changes are closely bound up with one-third of the world’s population. Investigating dryland climate change during the Last Interglacial (LIG; ∼127 ka ago) can advance our knowledge of dryland climate behaviors in an orbitally-induced warmer-than-present scenario. Based on the multiple model outputs from the Paleoclimate Modelling Intercomparison Project Phase 4, we suggest that the dryland areas during the LIG are 37% wetter than that during the preindustrial period as measured by the aridity index (AI), and 37% of the preindustrial drylands correspondingly convert to wetter subtypes. Spatially, there are hemispheric differences with drylands wetting and contracting in the Northern Hemisphere but desiccating and expanding in the Southern Hemisphere. Further diagnosis indicates that the altered precipitation is the dominant contributor to more than 72% of the AI changes, and the precipitation change is mainly attributed to the orbitally-induced redistribution of incoming insolation and heat. The secondary factor is the relative humidity change, exaggerating the AI changes in the same direction as the precipitation does. The simulation agrees reasonably with reconstructions for most regions, except Australia and southern Africa. The simulated changes in dryland aridity and the mechanism differ from that in future warming scenarios, so we claim that the LIG as a potential analogue for a warmer future does not fully hold for the dryland climate.
Quantum information criteria for model selection in quantum state estimation
Authors: Yano Hiroshi , Yamamoto Naoki
Published: September 2023

Quantum state estimation (or state tomography) is an indispensable task in quantum information processing. Because full state tomography that determines all elements of the density matrix is computationally demanding, one usually takes the strategy of assuming a certain model of quantum states and identifying the model parameters. However, it is difficult to make a valid assumption given little prior knowledge on a quantum state of interest, and thus we need a reasonable model selection method for quantum state estimation. Actually, in the classical statistical estimation theory, several types of information criteria have been established and widely used in practice for appropriately choosing a classical statistical model. In this study, we propose quantum information criteria for evaluating the quality of the estimated quantum state in terms of the quantum relative entropy, which is a natural quantum analogue of the classical information criterion defined in terms of Kullback–Leibler divergence. In particular, we derive two quantum information criteria depending on the type of an estimator for the quantum relative entropy; one uses the log-likelihood and the other uses the classical shadow. The general role of information criteria is to predict the performance of an estimated model for unseen data, although it is a function of only sampled data; this generalization capability of the proposed quantum information criteria is evaluated in numerical simulations.
First-passage functionals for Ornstein–Uhlenbeck process with stochastic resetting
Authors: Dubey Ashutosh , Pal Arnab
Published: September 2023

We study the statistical properties of first-passage Brownian functionals (FPBFs) of an Ornstein–Uhlenbeck process in the presence of stochastic resetting. We consider a one dimensional set-up where the diffusing particle sets off from x
0 and resets to

x

R

at a certain rate r. The particle diffuses in a harmonic potential (with strength k) which is centered around the origin. The center also serves as an absorbing boundary for the particle and we denote the first passage time (FPT) of the particle to the center as

t

f

. In this set-up, we investigate the following functionals: (i) local time

T

l
o
c

=

∫
0

t

f

d

τ
 
δ
(
x
−

x

R

)

i.e. the time a particle spends around

x

R

until the first passage, (ii) occupation or residence time

T

r
e
s

=

∫
0

t

f

d

τ
 
θ
(
x
−

x

R

)

i.e. the time a particle typically spends above

x

R

until the first passage and (iii) the FPT

t

f

to the origin. We employ the Feynman–Kac formalism for renewal process to derive the analytical expression for the first moment of all the three FPBFs mentioned above. In particular, we find that resetting can either prolong or shorten the mean residence and FPT depending on the system parameters. The transition between these two behaviors or phases can be characterized precisely in terms of optimal resetting rates, which interestingly undergo a continuous transition as we vary the trap stiffness k. We characterize this transition and identify the critical-parameter and -coefficient for both the cases. We also showcase other interesting interplay between the resetting rate and potential strength on the statistics of these observables. Our analytical results are in excellent agreement with the numerical simulations.
Electrical resistance-based monitoring of CFRP thickness during vacuum assisted resin infusion
Authors: Jeong Woo Nam , Um Moon-Kwang , Kim Wie-Dae , Roh Hyung Doh
Published: September 2023

During vacuum-assisted resin infusion (VARI), the thickness of the fabric manufactured into carbon fiber (CF)-reinforced plastic was monitored using electrical resistance, which was correlated with the mechanical and electrical status of the CF with respect to resin infiltration. Furthermore, the electrical network within CF varied in terms of its volume and number of electrical contacts. These phenomena were monitored by installing a Cu tape on the mold. Thus, an in-situ qualitative monitoring system for composite manufacturing was developed utilizing the electrical resistance variations in the fabric. The proposed thickness-monitoring system for VARI can potentially minimize the cost, time, and labor in composite industries.
Probing NV and SiV charge state dynamics using high-voltage nanosecond pulse and photoluminescence spectral analysis
Authors: Pambukhchyan Artur , Weng Sizhe , Aravind Indu , Cronin Stephen B , Takahashi Susumu
Published: September 2023

Nitrogen-vacancy (NV) and silicon-vacancy (SiV) color defects in diamond are promising systems for applications in quantum technology. The NV and SiV centers have multiple charge states, and their charge states have different electronic, optical and spin properties. For the NV centers, most investigations for quantum sensing applications are targeted on the negatively charged NV (NV−), and it is important for the NV centers to be in the NV− state. However, it is known that the NV centers are converted to the neutrally charged state (NV0) under laser excitation. An energetically favorable charge state for the NV and SiV centers depends on their local environments. It is essential to understand and control the charge state dynamics for their quantum applications. In this work, we discuss the charge state dynamics of NV and SiV centers under high-voltage nanosecond pulse discharges. The NV and SiV centers coexist in the diamond crystal. The high-voltage pulses enable manipulating the charge states efficiently. These voltage-induced changes in charge states are probed by their photoluminescence spectral analysis. The analysis result from the present experiment shows that the high-voltage nanosecond pulses cause shifts of the chemical potential and can convert the charge states of NV and SiV centers with the transition rates of ∼MHz. This result also indicates that the major population of the SiV centers in the sample is the doubly negatively charged state (SiV2−), which is often overlooked because of its non-fluorescent and non-magnetic nature. This demonstration paves a path for a method of rapid manipulation of the NV and SiV charge states in the future.
Sufficient condition for compactness of the \overline{∂}-Neumann operator using the Levi core
Authors: Treuer John
Published: September 2023

On a smooth, bounded pseudoconvex domain

Ω
\Omega

in

C

n

\mathbb {C}^n

, to verify that Catlin’s Property (

P
P

) holds for

b
Ω

b\Omega

, it suffices to check that it holds on the set of D’Angelo infinite type boundary points. In this note, we consider the support of the Levi core,

S

C

(

N

)

S_{\mathfrak {C}(\mathcal {N})}

, a subset of the infinite type points, and show that Property (

P
P

) holds for

b
Ω

b\Omega

if and only if it holds for

S

C

(

N

)

S_{\mathfrak {C}(\mathcal {N})}

. Consequently, if Property (

P
P

) holds on

S

C

(

N

)

S_{\mathfrak {C}(\mathcal {N})}

, then the

∂
¯

\overline {\partial }

-Neumann operator

N
1

N_1

is compact on

Ω
\Omega

.
Compact semisimple 2-categories
Authors: Décoppet Thibault
Published: September 2023

Working over an arbitrary field, we define compact semisimple 2-categories, and show that every compact semisimple 2-category is equivalent to the 2-category of separable module 1-categories over a finite semisimple tensor 1-category. Then, we prove that, over an algebraically closed field or a real closed field, compact semisimple 2-categories are finite. Finally, we explain how a number of key results in the theory of finite semisimple 2-categories over an algebraically closed field of characteristic zero can be generalized to compact semisimple 2-categories.
Caveola mechanotransduction reinforces the cortical cytoskeleton to promote epithelial resilience
Authors: Brooks John W. , Tillu Vikas , Eckert Julia , Verma Suzie , Collins Brett M. , Parton Robert G. , Yap Alpha S.
Published: September 2023

As physical barriers, epithelia must preserve their integrity when challenged by mechanical stresses. Cell–cell junctions linked to the cortical cytoskeleton play key roles in this process, often with mechanotransduction mechanisms that reinforce tissues. Caveolae are mechanosensitive organelles that buffer tension via disassembly. Loss of caveolae, through caveolin-1 or cavin1 depletion, causes activation of PtdIns(4, 5)P2 signaling, recruitment of FMNL2 formin, and enhanced-cortical actin assembly. How this equates to physiological responses in epithelial cells containing endogenous caveolae is unknown. Here we examined the effect of mechanically inducing acute disassembly of caveolae in epithelia. We show that perturbation of caveolae, through direct mechanical stress, reinforces the actin cortex at adherens junctions. Increasing interactions with membrane lipids by introducing multiple phosphatidylserine-binding undecad cavin1 (UC1) repeat domains into cavin1 rendered caveolae more stable to mechanical stimuli. This molecular stabilization blocked cortical reinforcement in response to mechanical stress. Cortical reinforcement elicited by the mechanically induced disassembly of caveolae increased epithelial resilience against tensile stresses. These findings identify the actin cortex as a target of caveola mechanotransduction that contributes to epithelial integrity.
The Arf-GAP Age2 localizes to the late-Golgi via a conserved amphipathic helix
Authors: Manzer Kaitlyn M. , Fromme J. Christopher
Published: September 2023

Arf GTPases are central regulators of the Golgi complex, which serves as the nexus of membrane-trafficking pathways in eukaryotic cells. Arf proteins recruit dozens of effectors to modify membranes, sort cargos, and create and tether transport vesicles, and are therefore essential for orchestrating Golgi trafficking. The regulation of Arf activity is controlled by the action of Arf-GEFs which activate via nucleotide exchange, and Arf-GAPs which inactivate via nucleotide hydrolysis. The localization dynamics of Arf GTPases and their Arf-GAPs during Golgi maturation have not been reported. Here we use the budding yeast model to examine the temporal localization of the Golgi Arf-GAPs. We also determine the mechanisms used by the Arf-GAP Age2 to localize to the Golgi. We find that the catalytic activity of Age2 and a conserved sequence in the unstructured C-terminal domain of Age2 are both required for Golgi localization. This sequence is predicted to form an amphipathic helix and mediates direct binding of Age2 to membranes in vitro. We also report the development of a probe for sensing active Arf1 in living cells and use this probe to characterize the temporal dynamics of Arf1 during Golgi maturation.
Letter to the editor: testing the effectiveness of MyPROSLE in classifying patients with lupus nephritis
Authors: Leventhal Emily L , Daamen Andrea R , Lipsky Peter E
Published: September 2023

Because of the clinical heterogeneity among patients with systemic lupus erythematosus (SLE), developing molecular profiles that predict clinical features can be useful in creating a personalized approach to treatment. Toro-Domínguez et al. created a web tool to aid in therapeutic decision making for clinicians that predicts clinical features associated with SLE from blood transcriptomic data. Specifically, they present a machine learning model that predicts the presence of proliferative nephritis from blood transcriptomics. Here, we report use of the tool in independent datasets and found that it did not perform sufficiently well to consider replacement of the standard kidney biopsy as a diagnostic procedure.
3D based generative PROTAC linker design with reinforcement learning
Authors: Li Baiqing , Ran Ting , Chen Hongming
Published: September 2023

Proteolysis targeting chimera (PROTAC), has emerged as an effective modality to selectively degrade disease-related proteins by harnessing the ubiquitin-proteasome system. Due to PROTACs’ hetero-bifunctional characteristics, in which a linker joins a warhead binding to a protein of interest (POI), conferring specificity and a E3-ligand binding to an E3 ubiquitin ligase, this could trigger the ubiquitination and transportation of POI to the proteasome, followed by degradation. The rational PROTAC linker design is challenging due to its relatively large molecular weight and the complexity of maintaining the binding mode of warhead and E3-ligand in the binding pockets of counterpart. Conventional linker generation method can only generate linkers in either 1D SMILES or 2D graph, without taking into account the information of ternary structures. Here we propose a novel 3D linker generative model PROTAC-INVENT which can not only generate SMILES of PROTAC but also its 3D putative binding conformation coupled with the target protein and the E3 ligase. The model is trained jointly with the RL approach to bias the generation of PROTAC structures toward pre-defined 2D and 3D based properties. Examples were provided to demonstrate the utility of the model for generating reasonable 3D conformation of PROTACs. On the other hand, our results show that the associated workflow for 3D PROTAC conformation generation can also be used as an efficient docking protocol for PROTACs.
Melatonin-pretreated human umbilical cord mesenchymal stem cells improved endometrium regeneration and fertility recovery through macrophage immunomodulation in rats with intrauterine adhesions
Authors: Qin Weili , Wang Jiawei , Hu Qianwen , Qin Rongyan , Ma Nana , Zheng Fengque , Tian Wencai , Jiang Jinghang , Li Ting , Jin Yufu , Liao Ming , Qin Aiping
Published: September 2023

Intrauterine adhesions (IUA) are a common gynecological problem. Stem cell therapy has been widely used in the treatment of IUA. However, due to the complex and harsh microenvironment of the uterine cavity, the effectiveness of such therapy is greatly inhibited. This study aimed to investigate whether melatonin pretreatment enhances the efficacy of human umbilical cord mesenchymal stem cells (HucMSCs) in IUA treatment in rats. First, we explored the effect of melatonin on the biological activity of HucMSCs in vitro through a macrophage co-culture system, Cell Counting Kit 8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (EdU), flow cytometry, immunofluorescence staining, and qRT-PCR. Subsequently, we established the IUA rat model and tracked the distribution of HucMSCs in this model. In addition, we observed the number of M1 and M2 macrophages through immunofluorescence staining and detected the levels of inflammatory cytokines. Four weeks after cell transplantation, HE, Masson, and immunohistochemical staining were performed. In vitro experiments showed that melatonin pretreatment of HucMSCs promoted proliferation, reduced apoptosis, up-regulated the stemness gene, and regulated macrophage polarization. In vivo, melatonin pretreatment caused more HucMSCs to remain in the uterine cavity. Melatonin-pretreated HucMSCs recruited more macrophages, regulated macrophage polarization, and reduced inflammation. Melatonin-pretreated HucMSCs relieved fibrosis, increased endometrium thickness, and up-regulated CD34, vimentin, proliferating cell nuclear antigen (PCNA), and alpha small muscle antigen (α-SMA) expression. Fertility tests showed that melatonin-pretreated HucMSCs increased the number of embryos. In summary, pretreatment with melatonin was beneficial for HucMSC treatment because it enhanced the cell’s ability to recruit macrophages and regulate macrophage polarization, which led to the regeneration of the endometrium and improved pregnancy outcomes.
Distal hereditary motor neuropathy caused by coenzyme Q deficiency due toCOQ7variants
Authors: Desbats Maria Andrea , Salviati Leonardo
Published: September 2023

This scientific commentary refers to ‘Biallelic variants in COQ7 cause distal hereditary motor neuropathy with upper motor neuron signs’ by Rebelo et al. (https://doi.org/10.1093/brain/awad158).
What (wo)men want? Evidence from a factorial survey on preferred work hours in couples after childbirth
Authors: Begall Katia
Published: September 2023

The division of labour remains persistently gendered, in particular among couples with children. Previous research shows that women’s lower economic resources are an important factor driving these inequalities, but because gender and (relative) earnings are highly correlated in male–female couples, their relative importance is difficult to disentangle with observational data. Using a factorial survey conducted among approximately 700 employed men and women of childbearing age in Sweden, the United Kingdom, and the Netherlands, the contribution of relative earnings and gender in explaining work-care divisions in couples with children is disentangled. The results show that men and women do not differ in their preferences for their own work hours after childbirth, but both prefer the father to work more hours than the mother. Moreover, the combination of own and partners’ preferred hours shows that men and women in all three countries prefer a modified male-breadwinner model after childbirth in scenarios where the male partner earns more or partners have equal earnings. Preferences for egalitarian divisions of labour appear to be slightly stronger in men compared to women and respondents with more egalitarian views on care tasks show less gender-specialization.
Single-cell transcriptomics supports presence of cryptic species and reveals low levels of population genetic diversity in two testate amoebae morphospecies with large population sizes
Authors: Weiner Agnes K M , Sehein Taylor , Cote-L’Heureux Auden , Sleith Robin S , Greco Mattia , Malekshahi Clara , Ryan-Embry Chase , Ostriker Naomi , Katz Laura A
Published: September 2023

The enormous population sizes and wide biogeographical distribution of many microbial eukaryotes set the expectation of high levels of intraspecific genetic variation. However, studies investigating protist populations remain scarce, mostly due to limited ‘omics data. Instead, most genetics studies of microeukaryotes have thus far relied on single loci, which can be misleading and do not easily allow for detection of recombination, a hallmark of sexual reproduction. Here, we analyze >40 genes from 72 single-cell transcriptomes from two morphospecies—Hyalosphenia papilio and Hyalosphenia elegans—of testate amoebae (Arcellinida, Amoebozoa) to assess genetic diversity in samples collected over four years from New England bogs. We confirm the existence of cryptic species based on our multilocus dataset, which provides evidence of recombination within and high levels of divergence between the cryptic species. At the same time, total levels of genetic diversity within cryptic species are low, suggesting that these abundant organisms have small effective population sizes, perhaps due to extinction and repopulation events coupled with efficient modes of dispersal. This study is one of the first to investigate population genetics in uncultivable heterotrophic protists using transcriptomics data and contributes towards understanding cryptic species of nonmodel microeukaryotes.
The fitness landscape of a community of Darwin’s finches
Authors: Beausoleil Marc-Olivier , Carrión Paola Lorena , Podos Jeffrey , Camacho Carlos , Rabadán-González Julio , Richard Roxanne , Lalla Kristen , Raeymaekers Joost A M , Knutie Sarah A , De León Luis F , Chaves Jaime A , Clayton Dale H , Koop Jennifer A H , Sharpe Diana M T , Gotanda Kiyoko M , Huber Sarah K , Barrett Rowan D H , Hendry Andrew P
Published: September 2023

Divergent natural selection should lead to adaptive radiation—that is, the rapid evolution of phenotypic and ecological diversity originating from a single clade. The drivers of adaptive radiation have often been conceptualized through the concept of “adaptive landscapes,” yet formal empirical estimates of adaptive landscapes for natural adaptive radiations have proven elusive. Here, we use a 17-year dataset of Darwin’s ground finches (Geospiza spp.) at an intensively studied site on Santa Cruz (Galápagos) to estimate individual apparent lifespan in relation to beak traits. We use these estimates to model a multi-species fitness landscape, which we also convert to a formal adaptive landscape. We then assess the correspondence between estimated fitness peaks and observed phenotypes for each of five phenotypic modes (G. fuliginosa, G. fortis [small and large morphotypes], G. magnirostris, and G. scandens). The fitness and adaptive landscapes show 5 and 4 peaks, respectively, and, as expected, the adaptive landscape was smoother than the fitness landscape. Each of the five phenotypic modes appeared reasonably close to the corresponding fitness peak, yet interesting deviations were also documented and examined. By estimating adaptive landscapes in an ongoing adaptive radiation, our study demonstrates their utility as a quantitative tool for exploring and predicting adaptive radiation.
AcbHLH144 transcription factor negatively regulates phenolic biosynthesis to modulate pineapple internal browning
Authors: Li Qian , Wang Guang , Zhang Ling , Zhu Shijiang
Published: September 2023

Internal browning (IB), a major physiological disorder of pineapples, usually happens in postharvest processes, but the underlying mechanism remains elusive. The bHLH transcription factors are involved in regulating various biological processes, but whether they could regulate tissue browning in fruit during storage remains unknown. Here we showed that the phenolic biosynthesis pathway was activated in pineapples showing IB following 9 days of storage. AcbHLH144 expression was the highest of the 180 transcription factors identified, downregulated in pineapple with IB, and negatively correlated with the major phenolic biosynthetic genes. AcbHLH144 was shown to be localized in the nucleus and its transient overexpression in pineapples and overexpression in Arabidopsis decreased phenolic biosynthesis. The yeast one-hybrid assay and electrophoretic mobility shift assay showed that AcbHLH144 directly bound to the Ac4CL5 promoter and the dual-luciferase reporter assay showed that it inactivated Ac4CL5 transcription. These results strongly suggest AcbHLH144 as a repressor for phenolic biosynthesis. Abscisic acid (ABA) alleviated IB, reduced phenolic accumulation, and downregulated phenolic biosynthetic genes, including Ac4CL5. Transcriptomic analysis showed that AcbHLH144 was the most upregulated of all 39 bHLHs in response to ABA. ABA enhanced AcbHLH144 expression, reduced phenolic contents, and downregulated phenolic biosynthetic genes in pineapples transiently overexpressing AcbHLH144. Moreover, ABA enhanced enzyme activity of GUS driven by the AcbHLH144 promoter. These results showed that AcbHLH144 as a repressor for phenolic biosynthesis could be activated by ABA. Collectively, the work demonstrated that AcbHLH144 negatively regulated phenolic biosynthesis via inactivating Ac4CL5 transcription to modulate pineapple IB. The findings provide novel insight into the role of AcbHLH144 in modulating pineapple IB during postharvest processes.
Management of Perianal Fistulizing Crohn’s Disease
Authors: Singh Arshdeep , Midha Vandana , Kochhar Gursimran Singh , Shen Bo , Sood Ajit
Published: September 2023

Perianal fistulizing Crohn’s disease (CD) represents a severe phenotype of CD that is associated with significant morbidity and reduction in quality of life. Perianal fistulizing CD is caused by a complex interplay of genetic predisposition, immune dysregulation, gut dysbiosis, and various unknown physiological and mechanical factors. A multidisciplinary approach is hence required for optimal management . A detailed anatomical description and classification of perianal fistula, including comprehensive clinical, endoscopic, and radiological diagnostic workup, is an important prerequisite to treatment. For simple perianal fistulas, use of antibiotics and immunomodulators, with or without fistulotomy, are appropriate measures. The medical management of complex perianal fistula, on the other hand, requires adequate control of infection before initiation of therapy with immunomodulators. In active complex perianal fistula, anti-tumor necrosis factors remain the most accepted therapy, with concomitant use of antibiotics or immunomodulators enhancing the efficacy. For patients refractory to anti-tumor necrosis factors, treatment with anti-integrins, anti-interleukins, and small molecules is being evaluated. Mesenchymal stem cells, hyperbaric oxygen therapy, and exclusive enteral nutrition have also been investigated as adjunct therapies. Despite the expansion of the medical armamentarium, a large proportion of the patients require surgical interventions. In this review, we provide an up-to-date overview of the pathophysiology, clinical presentation, diagnosis, and medical management of perianal fistulizing CD. A brief overview of the surgical management of perianal fistulizing CD is also provided.
Solar reflection and effect of roof surfaces material characteristics in heat island mitigation: toward green building and urban sustainability in Ha’il, Saudi Arabia
Authors: Boujelbene Mohamed , Boukholda Ismail , Guesmi Tawfik , Amara Mouldi Ben , Khalilpoor Nima
Published: September 2023

Several materials have the ability to absorb, accumulate and transmit solar radiation to their surrounding environment. The thermal island effect and micro-climate of urban areas are subject to notable influence from the composition of materials within the city’s crust. The present investigation was carried out with the aim of assessing the impact of roofing and pavement materials’ properties on solar reflection and their potential to mitigate urban heat islands (UHIs). A study of an experimental nature was carried out on a total of 20 conventional materials that are commonly used in the construction of roofs, sidewalks, streets and rooftops in Ha’il, Saudi Arabia. The objective of the research was to investigate the impact of different urban surface materials on the rise of ambient air temperature in their vicinity. The present investigation aimed to assess the thermal performance of the specimens, with the purpose of ascertaining the impact of the thermophysical and radiative characteristics of the substances. The findings of the experiments indicate that the Solar Reflectance and temperature of the surrounding environment are primarily influenced by the color and substance of surface materials. Conversely, the texture’s condition has a comparatively minor effect. Both effective factors play an equally significant role in the overall mechanism of increasing the ambient air temperature. The results suggest that a significant proportion of the samples exhibit a maximum surface temperature exceeding 59.4°C, while concurrently displaying a Solar Reflectance Index and albedo <49%. Meanwhile, the implementation of green roofs composed of various types of vegetation, including grass, can effectively alleviate the UHI phenomenon.
Human Shields and the Gulf War
Authors: de la Paz Alexander
Published: September 2023

From late August to early December 1990, Iraq held hundreds of Western and Japanese civilians at strategic sites as “human shields” against the Gulf War coalition. While there is a consensus that these foreign nationals would have influenced the coalition’s offensive had they not been released before the onset of hostilities, their impact remains poorly understood. This note draws on newly available archival records, among other sources, to throw new light on this old question. The record shows that leaders were reconciled with the prospect of hostage casualties and the expected political fallout. Military necessity and limited intelligence about the hostages’ whereabouts precluded avoiding every shielded target. At the same time, public opinion was divided on the hostage problem, especially in the United States. In response, leaders planned to take special precautionary measures and mount a rescue operation in Kuwait City. These measures, overall, appeared to exceed those employed for other targets, and exposed coalition forces to additional risks. US decision-makers may also have been motivated by the belief that proceeding undeterred could discourage others from resorting to the same stratagem in the future. The findings advance research on the Gulf War and the problem of human shields in war.
Response to glecaprevir/pibrentasvir in HIV/HCV-coinfected patients in clinical practice
Authors: Gonzalez-Serna Alejandro , Corma-Gomez Anaïs , Tellez Francisco , Corona-Mata Diana , Rios-Villegas María Jose , Merino Dolores , Galera Carlos , Collado-Romacho Antonio Ramon , De Los Santos Ignacio , Cucurull Josep , Santos Marta , García-Martín Sofía , Rivero Antonio , Real Luis Miguel , Macias Juan
Published: September 2023

Objectives

HIV infection has been associated with lower rates of sustained viral response (SVR) with direct-acting antivirals (DAAs). There are few data on glecaprevir/pibrentasvir (G/P) in HIV/HCV coinfection outside clinical trials.

Methods

The HEPAVIR-DAA cohort, which recruits HIV/HCV-coinfected patients (NCT02057003) and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are two concurrent ongoing multicentre cohorts of patients receiving anti-HCV treatment. Patients starting G/P included in those cohorts were analysed. Overall SVR (ITT), discontinuations due to adverse effects, and dropouts were evaluated and compared between both cohorts.

Results

Of the 644 patients who started G/P with evaluable SVR, 132 were HIV/HCV coinfected. Overall SVR rates were 487/512 (95.1%) in HCV-monoinfected patients versus 126/132 (95.5%) in HIV/HCV-coinfected patients (P = 1.000). One patient (0.8%) relapsed, and another (0.8%) discontinued treatment due to side effects. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected versus HCV-monoinfected patients. The main reason for not reaching SVR among HIV/HCV-coinfected patients was premature dropout linked to active drug use.

Conclusions

G/P in HIV/HCV coinfection was highly effective and tolerable in clinical practice. SVR to 8 or 12 weeks of treatment with G/P was similar in HIV/HCV-coinfected compared with HCV-monoinfected patients but active drug use is still a barrier to reach HCV microelimination.