bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harnessing nanomedicine for enhanced immunotherapy for breast cancer brain metastases
Authors: Carney Christine P. , Pandey Nikhil , Kapur Anshika , Woodworth Graeme F. , Winkles Jeffrey A. , Kim Anthony J. 
Published: October 2021

AbstractBrain metastases (BMs) are the most common type of brain tumor, and the incidence among breast cancer (BC) patients has been steadily increasing over the past two decades. Indeed, ~ 30% of all patients with metastatic BC will develop BMs, and due to few effective treatments, many will succumb to the disease within a year. Historically, patients with BMs have been largely excluded from clinical trials investigating systemic therapies including immunotherapies (ITs) due to limited brain penetration of systemically administered drugs combined with previous assumptions that BMs are poorly immunogenic. It is now understood that the central nervous system (CNS) is an immunologically distinct site and there is increasing evidence that enhancing immune responses to BCBMs will improve patient outcomes and the efficacy of current treatment regimens. Progress in IT for BCBMs, however, has been slow due to several intrinsic limitations to drug delivery within the brain, substantial safety concerns, and few known targets for BCBM IT. Emerging studies demonstrate that nanomedicine may be a powerful approach to overcome such limitations, and has the potential to greatly improve IT strategies for BMs specifically. This review summarizes the evidence for IT as an effective strategy for BCBM treatment and focuses on the nanotherapeutic strategies currently being explored for BCBMs including targeting the blood–brain/tumor barrier (BBB/BTB), tumor cells, and tumor-supporting immune cells for concentrated drug release within BCBMs, as well as use of nanoparticles (NPs) for delivering immunomodulatory agents, for inducing immunogenic cell death, or for potentiating anti-tumor T cell responses.Graphical abstract
A novel lightweight authentication and privacy-preserving protocol for vehicular ad hoc networks
Authors: Theodore Shaji K. A. , Gandhi K. Rajiv , Palanisamy V. 
Published: October 2021

AbstractVehicular ad hoc network (VANET) is commonly employed in intelligent transportation system (ITS) that allows the exchange of traffic data among vehicles and nearby environment to accomplish effective driving experience. Privacy and security are the challenging issues that exist in the safety needs of the VANET. Any particular leakage of the vehicle details such as route data might result in serious impacts, and therefore, authentication and privacy-preserving protocols are needed to enhance safety in VANET. With this motivation, this paper presents a new lightweight authentication and privacy-preserving protocol using improved timed efficient stream loss-tolerant authentication with cuckoo filter (ITESLA-CF) for VANETs. The proposed model encompasses different stages of operations such as initialization, registration, mutual authentication, broadcast and verification, and vehicle revocation phases. In addition, the ITESLA-CF technique has effective broadcast authentication as TESLA with minimal memory requirement. Besides, the ITESLA-CF technique includes a cuckoo filter to save the authentic information of vehicles that exist in the RSU’s range. The proposed model has lightweight mutual authentication among the parties and it offers robust anonymity to accomplish privacy and resists ordinary attacks. To ensure the better performance of the ITESLA-CF technique, an extensive set of simulations take place and the results are assessed in terms of different measures. The resultant experimental values pointed out the supremacy of the ITESLA-CF technique over the recent state of art methods.
Strong Stability Preserving IMEX Methods for Partitioned Systems of Differential Equations
Authors: Izzo Giuseppe , Jackiewicz Zdzisław 
Published: October 2021

AbstractWe investigate strong stability preserving (SSP) implicit-explicit (IMEX) methods for partitioned systems of differential equations with stiff and nonstiff subsystems. Conditions for order p and stage order $$q=p$$

q
=
p

are derived, and characterization of SSP IMEX methods is provided following the recent work by Spijker. Stability properties of these methods with respect to the decoupled linear system with a complex parameter, and a coupled linear system with real parameters are also investigated. Examples of methods up to the order $$p=4$$

p
=
4

and stage order $$q=p$$

q
=
p

are provided. Numerical examples on six partitioned test systems confirm that the derived methods achieve the expected order of convergence for large range of stepsizes of integration, and they are also suitable for preserving the accuracy in the stiff limit or preserving the positivity of the numerical solution for large stepsizes.
The wandering subspace property and Shimorin’s condition of shift operator on the weighted Bergman spaces
Authors: Wu Changhui , Wang Zhijie , Yu Tao 
Published: October 2021

AbstractIn the present paper, we first study the wandering subspace property of the shift operator on the $$I_{a}$$

I
a

type zero based invariant subspaces of the weighted Bergman spaces $$L_{a}^{2}(dA_{n})(n=0,2)$$

L

a

2

(
d

A
n

)

(
n
=
0
,
2
)

via the spectrum of some Toeplitz operators on the Hardy space $$H^{2}$$

H
2

. Second, we give examples to show that Shimorin’s condition for the shift operator fails on the $$I_{a}$$

I
a

type zero based invariant subspaces of the weighted Bergman spaces $$L_{a}^{2}(dA_{\alpha })(\alpha >0)$$

L

a

2

(
d

A
α

)

(
α
>
0
)

.
Porous silicon pillar structures/photosynthetic reaction centre protein hybrid for bioelectronic applications
Authors: Hajdu Kata , Balderas-Valadez R. Fabiola , Carlino Alessandro , Agarwal Vivechana , Nagy László 
Published: October 2021

AbstractPhotosynthetic biomaterials have attracted considerable attention at different levels of the biological organisation, from molecules to the biosphere, due to a variety of artificial application possibilities. During photosynthesis, the first steps of the conversion of light energy into chemical energy take place in a pigment–protein complex, called reaction centre (RC). In our experiments photosynthetic reaction centre protein, purified from Rhodobacter sphaeroides R-26 purple bacteria, was bound to porous silicon pillars (PSiP) after the electropolymerisation of aniline onto the surface. This new type of biohybrid material showed remarkable photoactivity in terms of measured photocurrent under light excitation in an electrochemical cell. The photocurrent was found to increase considerably after the addition of ubiquinone (UQ-0), an e−-acceptor mediator of the RC. The photoactivity of the complex was found to decrease by the addition of terbutryn, the chemical which inhibits the e−-transport on the acceptor side of the RC. In addition to the generation of sizeable light-induced photocurrents, using the PSiP/RC photoactive hybrid nanocomposite material, the system was found to be sensitive towards RC inhibitors and herbicides. This highly ordered patterned 3D structure opens new solution for designing low-power (bio-)optoelectronic, biophotonic and biosensing devices.
Graphical abstract
Microseismicity Appears to Outline Highly Coupled Regions on the Central Chile Megathrust
Authors: Sippl C. , Moreno M. , Benavente R. 
Published: October 2021

AbstractWe compiled a novel microseismicity catalog for the Central Chile megathrust (29°–35°S), comprising 8,750 earthquakes between April 2014 and December 2018. These events describe a pattern of three trenchward open half‐ellipses, consisting of a continuous, coast‐parallel seismicity band at 30–45 km depth, and narrow elongated seismicity clusters that protrude to the shallow megathrust and separate largely aseismic regions along strike. To test whether these shapes could outline highly coupled regions (“asperities”) on the megathrust, we invert GPS displacement data for interplate locking. The best‐fit locking model does not show good correspondence to seismicity, possibly due to lacking resolution. When we prescribe high locking inside the half‐ellipses, however, we obtain models with similar data fits that are preferred according to the Bayesian Information Criterion (BIC). We thus propose that seismicity on the Central Chile megathrust may outline three adjacent highly coupled regions, two of them located between the rupture areas of the 2010 Maule and the 2015 Illapel earthquakes, a segment of the Chilean margin that may be in a late interseismic stage of the seismic cycle.
Formation of Ejecta and Dust Pond Deposits on Asteroid Vesta
Authors: Parekh R. , Otto K. A. , Matz K. D. , Jaumann R. , Krohn K. , Roatsch T. , Kersten E. , Elgner S. , Russell C. T. , Raymond C. A. 
Published: November 2021

AbstractDust and melt ponds have been studied on planetary bodies including Eros, Itokawa, and the Moon. However, depending on the nature of the regolith material properties and the location of the planetary body, the formation mechanism of the ponded features varies. On Eros and Itokawa, ponded features are formed from dry regolith materials whereas on the Moon similar features are thought to be produced by ejecta melt. On the surface of Vesta, we have identified type 1, ejecta ponds, and type 2, dust ponds. On Vesta type 1 pond are located in the vicinity of ejecta melt of large impact craters. The material is uniformly distributed across the crater floor producing smooth pond surfaces which have a constant slope and shallow depth. The hosting crater of melt‐like ponds has a low raised rim and is located on relatively low elevated regions. Whereas, the type 2 ponds on Vesta reveal an undulating surface that is frequently displaced from the crater center or extends toward the crater wall with an abruptly changing slope. We suggested that for the production of the type 2 ponds, localized seismic diffusion and volatile‐induced fluidization may be responsible for Vesta. Due to Vesta's large size (in comparison to Eros and Itokawa), the surface may have experienced local‐scale rare high‐amplitude seismic diffusion which was sufficient to drift fine material. Similarly, short‐lived volatile activities were capable to transfer dusty material on to the surface. Segregation and smoothing of transferred material lack further surface activities, hindering the formation of smooth morphology.
Evaluating Flat‐Crater Floor Fill Compositions and Morphologies: Insight Into Formation Processes
Authors: Pan C. , Edwards C. S. , Rogers A. D. 
Published: October 2021

AbstractNumerous impact craters on Mars have been deeply filled, raising questions about the potential processes that contributed to infilling. Previously proposed processes include ponding of impact melt, aeolian sedimentation, lacustrine sedimentation, or volcanic infilling. Better constraints on the infilling processes of flat floor craters are needed to assess the relative roles of impact, volcanic and sedimentary resurfacing processes throughout Mars history. In this study, we investigate the compositional, thermophysical, and morphological properties of floor materials within a subset of 119 high thermal inertia craters. For each crater, the degree of etching and crater retention of the floor morphologies, as well as the floor mineralogy were characterized. We find evidence for crater infilling by effusive volcanism and by sedimentation (e.g., pyroclastic, volcaniclastic, and/or epiclastic), with weak, clastic rocks being most common. A majority of studied craters also show evidence for olivine enrichments. There is no clear trend between the olivine enrichment and floor morphologies, indicating that olivine is likely associated with both effusive and explosive volcanism. Our observations support the hypothesis that pyroclastic activity may have been widespread on early Mars.
The Release of Energy During Protein Synthesis at Ultramafic‐Hosted Submarine Hydrothermal Ecosystems
Authors: Dick Jeffrey M. , Shock Everett L. 
Published: October 2021

AbstractThere are fundamental geochemical reasons why environments surrounding submarine hydrothermal systems are primary productivity hotspots compared with the majority of the seafloor, or with conditions deep in seafloor sediments. As reduced hydrothermal fluids mix with oxidized seawater, elements in incompatible oxidation states are brought together. The resulting rich supplies of disequilibria can be dissipated by primary productivity over wide ranges of temperature and pressure. Synthesis of many amino acids is an energy‐releasing process as fluids from submarine ultramafic‐hosted hydrothermal systems mix with seawater, raising questions about the overall energetics of protein synthesis. Here we show that protein synthesis is also an energy‐releasing process in seawater‐hydrothermal fluid mixtures in ultramafic‐hosted systems, and consider some implications for microbial metabolism, biogeochemical cycles, hydrothermal ecosystem dynamics, and the emergence of life at submarine hydrothermal systems.
Predicting CMEs Using ELEvoHI With STEREO‐HI Beacon Data
Authors: Bauer Maike , Amerstorfer Tanja , Hinterreiter Jürgen , Weiss Andreas J. , Davies Jackie A. , Möstl Christian , Amerstorfer Ute V. , Reiss Martin A. , Harrison Richard A. 
Published: October 2021

AbstractBeing able to accurately predict the arrival of coronal mass ejections (CMEs) at Earth has been a long‐standing problem in space weather research and operations. In this study, we use the ELlipse Evolution model based on Heliospheric Imager (ELEvoHI) to predict the arrival time and speed of 10 CME events that were observed by HI on the STEREO‐A spacecraft between 2010 and 2020. Additionally, we introduce a Python tool for downloading and preparing STEREO‐HI data, as well as tracking CMEs. In contrast to most previous studies, we use not only science data, which have a relatively high spatial and temporal resolution, but also lower‐quality beacon data, which are—in contrast to science data—provided in real‐time by the STEREO‐A spacecraft. We do not use data from the STEREO‐B spacecraft. We get a mean absolute error of 8.81 ± 3.18 hr/59 ± 31 km s−1 for arrival time/speed predictions using science data and 11.36 ± 8.69 hr/106 ± 61 km s−1 for beacon data. We find that using science data generally leads to more accurate predictions, but using beacon data with the ELEvoHI model is certainly a viable choice in the absence of higher resolution real‐time data. We propose that these differences could be minimized if not eliminated altogether if higher quality real‐time data were available, either by enhancing the quality of the already available data or coming from a new mission carrying a HI instrument on‐board.
Optical coherent dot-product chip for sophisticated deep learning regression
Authors: Xu Shaofu , Wang Jing , Shu Haowen , Zhang Zhike , Yi Sicheng , Bai Bowen , Wang Xingjun , Liu Jianguo , Zou Weiwen 
Published: November 2021

AbstractOptical implementations of neural networks (ONNs) herald the next-generation high-speed and energy-efficient deep learning computing by harnessing the technical advantages of large bandwidth and high parallelism of optics. However, due to the problems of the incomplete numerical domain, limited hardware scale, or inadequate numerical accuracy, the majority of existing ONNs were studied for basic classification tasks. Given that regression is a fundamental form of deep learning and accounts for a large part of current artificial intelligence applications, it is necessary to master deep learning regression for further development and deployment of ONNs. Here, we demonstrate a silicon-based optical coherent dot-product chip (OCDC) capable of completing deep learning regression tasks. The OCDC adopts optical fields to carry out operations in the complete real-value domain instead of in only the positive domain. Via reusing, a single chip conducts matrix multiplications and convolutions in neural networks of any complexity. Also, hardware deviations are compensated via in-situ backpropagation control provided the simplicity of chip architecture. Therefore, the OCDC meets the requirements for sophisticated regression tasks and we successfully demonstrate a representative neural network, the AUTOMAP (a cutting-edge neural network model for image reconstruction). The quality of reconstructed images by the OCDC and a 32-bit digital computer is comparable. To the best of our knowledge, there is no precedent of performing such state-of-the-art regression tasks on ONN chips. It is anticipated that the OCDC can promote the novel accomplishment of ONNs in modern AI applications including autonomous driving, natural language processing, and scientific study.
Activation of cannabinoid receptor 2 alleviates glucocorticoid-induced osteonecrosis of femoral head with osteogenesis and maintenance of blood supply
Authors: Sun Houyi , Zhang Weicheng , Yang Ning , Xue Yi , Wang Tianhao , Wang Hongzhi , Zheng Kai , Wang Yijun , Zhu Feng , Yang Huilin , Xu Wei , Xu Yaozeng , Geng Dechun 
Published: October 2021

AbstractIn glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH), downregulated osteogenic ability and damaged blood supply are two key pathogenic mechanisms. Studies suggested that cannabinoid receptor 2 (CB2) is expressed in bone tissue and it plays a positive role in osteogenesis. However, whether CB2 could enhance bone formation and blood supply in GC-induced ONFH remains unknown. In this study, we focused on the effect of CB2 in GC-induced ONFH and possible mechanisms in vitro and in vivo. By using GC-induced ONFH rat model, rat-bone mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) to address the interaction of CB2 in vitro and in vivo, we evaluate the osteogenic and angiogenic effect variation and possible mechanisms. Micro-CT, histological staining, angiography, calcein labeling, Alizarin red staining (ARS), alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) staining, TUNEL staining, migration assay, scratch assay, and tube formation were applied in this study. Our results showed that selective activation of CB2 alleviates GC-induced ONFH. The activation of CB2 strengthened the osteogenic activity of BMSCs under the influence of GCs by promotion of GSK-3β/β-catenin signaling pathway. Furthermore, CB2 promoted HUVECs migration and tube-forming capacities. Our findings indicated that CB2 may serve as a rational new treatment strategy against GC-induced ONFH by osteogenesis activation and maintenance of blood supply.
Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway
Authors: Tian Wen , Yang Xianglin , Yang He , Lv Meiwen , Sun Xinran , Zhou Baosen 
Published: October 2021

AbstractGlobally, lung cancer remains one of the most prevalent malignant cancers. However, molecular mechanisms and functions involved in its pathogenesis have not been clearly elucidated. This study aimed to evaluate the specific regulatory mechanisms of exosomal miR-338-3p/CHL1/MAPK signaling pathway axis in non-small-cell lung cancer. Western blotting and qRT-PCR (reverse transcription-polymerase chain reaction) were used to determine the expression levels of CHL1 and exosomal miR-338-3p in NSCLC (non-small-cell lung cancer). The CHL1 gene was upregulated and downregulated to evaluate its functions in NSCLC progression. In vitro MTS and apoptotic assays were used to investigate the functions of CHL1 and exosomal miR-338-3p in NSCLC progression. The high-throughput sequencing was used to explore differently expressed exosomal miRNAs. The biological relationships between MAPK signaling pathway and CHL1 and exosomal miR-338-3p in NSCLC were predicted through bioinformatics analyses and verified by western blotting. Elevated CHL1 levels were observed in NSCLC tissues and cells. Upregulated CHL1 expression enhanced NSCLC cells’ progression by promoting tumor cells proliferation while suppressing their apoptosis. Conversely, the downregulation of the CHL1 gene inhibited NSCLC cells’ growth and promoted tumor cells’ apoptotic rate. Additionally, CHL1 activated the MAPK signaling pathway. Besides, we confirmed that miR-338-3p directly sponged with CHL1 to mediate tumor cells progression. Moreover, exosomal miR-338-3p serum levels in NSCLC patients were found to be low. BEAS-2B cells can transfer exosomal miR-338-3p to A549 cells and SK-MES-1 cells. In addition, elevated exosomal miR-338-3p levels significantly inhibited tumor cells proliferation and promoted their apoptosis by suppressing activation of the MAPK signaling pathway. Exosomal miR-338-3p suppresses tumor cells' metastasis by downregulating the expression of CHL1 through MAPK signaling pathway inactivation.
Lipophagy deficiency exacerbates ectopic lipid accumulation and tubular cells injury in diabetic nephropathy
Authors: Han Yachun , Xiong Shan , Zhao Hao , Yang Shikun , Yang Ming , Zhu Xuejing , Jiang Na , Xiong Xiaofen , Gao Peng , Wei Ling , Xiao Ying , Sun Lin 
Published: October 2021

AbstractAutophagy-mediated lipotoxicity plays a critical role in the progression of diabetic nephropathy (DN), but the precise mechanism is not fully understood. Whether lipophagy, a selective type of autophagy participates in renal ectopic lipid deposition (ELD) and lipotoxicity in the kidney of DN is unknown. Here, decreased lipophagy, increased ELD and lipotoxcity were observed in tubular cells of patients with DN, which were accompanied with reduced expression of AdipoR1 and p-AMPK. Similar results were found in db/db mice, these changes were reversed by AdipoRon, an adiponectin receptor activator that promotes autophagy. Additionally, a significantly decreased level of lipophagy was observed in HK-2 cells, a human proximal tubular cell line treated with high glucose, which was consistent with increased lipid deposition, apoptosis and fibrosis, while were partially alleviated by AdipoRon. However, these effects were abolished by pretreatment with ULK1 inhibitor SBI-0206965, autophagy inhibitor chloroquine and enhanced by AMPK activator AICAR. These data suggested by the first time that autophagy-mediated lipophagy deficiency plays a critical role in the ELD and lipid-related renal injury of DN.
Gasdermin D mediates host cell death but not interleukin-1β secretion in Mycobacterium tuberculosis-infected macrophages
Authors: Theobald Sebastian J. , Gräb Jessica , Fritsch Melanie , Suárez Isabelle , Eisfeld Hannah S. , Winter Sandra , Koch Maximilian , Hölscher Christoph , Pasparakis Manolis , Kashkar Hamid , Rybniker Jan 
Published: October 2021

AbstractNecrotic cell death represents a major pathogenic mechanism of Mycobacterium tuberculosis (Mtb) infection. It is increasingly evident that Mtb induces several types of regulated necrosis but how these are interconnected and linked to the release of pro-inflammatory cytokines remains unknown. Exploiting a clinical cohort of tuberculosis patients, we show here that the number and size of necrotic lesions correlates with IL-1β plasma levels as a strong indicator of inflammasome activation. Our mechanistic studies reveal that Mtb triggers mitochondrial permeability transition (mPT) and subsequently extensive macrophage necrosis, which requires activation of the NLRP3 inflammasome. NLRP3-driven mitochondrial damage is dependent on proteolytic activation of the pore-forming effector protein gasdermin D (GSDMD), which links two distinct cell death machineries. Intriguingly, GSDMD, but not the membranolytic mycobacterial ESX-1 secretion system, is dispensable for IL-1β secretion from Mtb-infected macrophages. Thus, our study dissects a novel mechanism of pathogen-induced regulated necrosis by identifying mitochondria as central regulatory hubs capable of delineating cytokine secretion and lytic cell death.