bluuebunny/crossref_metadata_2025 huggingface dataset:
High-yield parallel fabrication of quantum-dot monolayer single-electron devices displaying Coulomb staircase, contacted by graphene
Authors: Fruhman Joel M. , Astier Hippolyte P.A.G. , Ehrler Bruno , Böhm Marcus L. , Eyre Lissa F. L. , Kidambi Piran R. , Sassi Ugo , De Fazio Domenico , Griffiths Jonathan P. , Robson Alexander J. , Robinson Benjamin J. , Hofmann Stephan , Ferrari Andrea C. , Ford Christopher J. B.
Published: July 2021

It is challenging for conventional top-down lithography to fabricate reproducible devices very close to atomic dimensions, whereas identical molecules and very similar nanoparticles can be made bottom-up in large quantities, and can be self-assembled on surfaces. The challenge is to fabricate electrical contacts to many such small objects at the same time, so that nanocrystals and molecules can be incorporated into conventional integrated circuits. Here, we report a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene. This produces single-electron effects, in the form of a Coulomb staircase, with a yield of 87 ± 13% in device areas ranging from < 800 nm2 to 16 μm2, containing up to 650,000 nanoparticles. Our technique offers scalable assembly of ultra-high densities of functional particles or molecules that could be used in electronic integrated circuits, as memories, switches, sensors or thermoelectric generators.
Oil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2
Authors: Juang Duane S. , Juang Terry D. , Dudley Dawn M. , Newman Christina M. , Accola Molly A. , Rehrauer William M. , Friedrich Thomas C. , O’Connor David H. , Beebe David J.
Published: July 2021

The COVID-19 pandemic exposed difficulties in scaling current quantitative PCR (qPCR)-based diagnostic methodologies for large-scale infectious disease testing. Bottlenecks include lengthy multi-step processes for nucleic acid extraction followed by qPCR readouts, which require costly instrumentation and infrastructure, as well as reagent and plastic consumable shortages stemming from supply chain constraints. Here we report an Oil Immersed Lossless Total Analysis System (OIL-TAS), which integrates RNA extraction and detection onto a single device that is simple, rapid, cost effective, and requires minimal supplies and infrastructure to perform. We validated the performance of OIL-TAS using contrived SARS-CoV-2 viral particle samples and clinical nasopharyngeal swab samples. OIL-TAS showed a 93% positive predictive agreement (n = 57) and 100% negative predictive agreement (n = 10) with clinical SARS-CoV-2 qPCR assays in testing clinical samples, highlighting its potential to be a faster, cheaper, and easier-to-deploy alternative for infectious disease testing.
Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity
Authors: Bui Linh T. , Winters Nichelle I. , Chung Mei-I , Joseph Chitra , Gutierrez Austin J. , Habermann Arun C. , Adams Taylor S. , Schupp Jonas C. , Poli Sergio , Peter Lance M. , Taylor Chase J. , Blackburn Jessica B. , Richmond Bradley W. , Nicholson Andrew G. , Rassl Doris , Wallace William A. , Rosas Ivan O. , Jenkins R. Gisli , Kaminski Naftali , Kropski Jonathan A. , Banovich Nicholas E. ,   Human Cell Atlas Lung Biological Network, Misharin Alexander V. , Tsankov Alexander M. , Spira Avrum , Barbry Pascal , Brazma Alvis , Samakovlis Christos , Shepherd Douglas P. , Rawlins Emma L. , Theis Fabian J. , Griffonnet Jennifer , Lee Haeock , Schiller Herbert B. , Hofman Paul , Powell Joseph E. , Schultze Joachim L. , Whitsett Jeffrey , Choi Jiyeon , Lundeberg Joakim , Kaminski Naftali , Kropski Jonathan A. , Banovich Nicholas E. , Ordovas-Montanes Jose , Rajagopal Jayaraj , Meyer Kerstin B. , Krasnow Mark A. , Saeb‐Parsy Kourosh , Zhang Kun , Lafyatis Robert , Leroy Sylvie , Haniffa Muzlifah , Nawijn Martijn C. , Nikolić Marko Z. , van den Berge Maarten , Kuhnemund Malte , Marquette Charles-Hugo , Von Papen Michael , Eickelberg Oliver , Rosenblatt-Rosen Orit , Reyfman Paul A. , Pe’er Dana , Horvath Peter , Tata Purushothama Rao , Regev Aviv , Rojas Mauricio , Seibold Max A. , Shalek Alex K. , Spence Jason R. , Teichmann Sarah A. , Quake Stephen , Duong Thu Elizabeth , Biancalani Tommaso , Desai Tushar , Sun Xin , Zaragosi Laure Emmanuelle
Published: July 2021

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection.
Coordination of biradial-to-radial symmetry and tissue polarity by HD-ZIP II proteins
Authors: Carabelli Monica , Turchi Luana , Morelli Giorgio , Østergaard Lars , Ruberti Ida , Moubayidin Laila
Published: July 2021

Symmetry establishment is a critical process in the development of multicellular organs and requires careful coordination of polarity axes while cells actively divide within tissues. Formation of the apical style in the Arabidopsis gynoecium involves a bilateral-to-radial symmetry transition, a stepwise process underpinned by the dynamic distribution of the plant morphogen auxin. Here we show that SPATULA (SPT) and the HECATE (HEC) bHLH proteins mediate the final step in the style radialisation process and synergistically control the expression of adaxial-identity genes, HOMEOBOX ARABIDOPSIS THALIANA 3 (HAT3) and ARABIDOPSIS THALIANA HOMEOBOX 4 (ATHB4). HAT3/ATHB4 module drives radialisation of the apical style by promoting basal-to-apical auxin flow and via a negative feedback mechanism that finetune auxin distribution through repression of SPT expression and cytokinin sensitivity. Thus, this work reveals the molecular basis of axes-coordination and hormonal cross-talk during the sequential steps of symmetry transition in the Arabidopsis style.
A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes
Authors: Thomas Christopher , Wetherall Benjamin , Levasseur Mark D. , Harris Rebecca J. , Kerridge Scott T. , Higgins Jonathan M. G. , Davies Owen R. , Madgwick Suzanne
Published: July 2021

Successful cell division relies on the timely removal of key cell cycle proteins such as securin. Securin inhibits separase, which cleaves the cohesin rings holding chromosomes together. Securin must be depleted before anaphase to ensure chromosome segregation occurs with anaphase. Here we find that in meiosis I, mouse oocytes contain an excess of securin over separase. We reveal a mechanism that promotes excess securin destruction in prometaphase I. Importantly, this mechanism relies on two phenylalanine residues within the separase-interacting segment (SIS) of securin that are only exposed when securin is not bound to separase. We suggest that these residues facilitate the removal of non-separase-bound securin ahead of metaphase, as inhibiting this period of destruction by mutating both residues causes the majority of oocytes to arrest in meiosis I. We further propose that cellular securin levels exceed the amount an oocyte is capable of removing in metaphase alone, such that the prometaphase destruction mechanism identified here is essential for correct meiotic progression in mouse oocytes.
Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer
Authors: Huang Yanjuan , Guan Zilin , Dai Xiuling , Shen Yifeng , Wei Qin , Ren Lingling , Jiang Jingwen , Xiao Zhanghong , Jiang Yali , Liu Di , Huang Zeqian , Xu Xiaoyu , Luo Yong , Zhao Chunshun
Published: July 2021

Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors. Oxa(IV)@ZnPc@M exhibits an anti-tumor M1 phenotype polarization and can efficiently home to primary and bone metastatic tumors. Additionally, therapeutics inside Oxa(IV)@ZnPc@M undergo NIR triggered release, which can kill primary tumors via combined chemo-photodynamic therapy and induce immunogenic cell death simultaneously. Oxa(IV)@ZnPc@M combined with anti-PD-L1 can eliminate primary and bone metastatic tumors, activate tumor-specific antitumor immune response, and improve overall survival with limited systemic toxicity. Therefore, this all-in-one macrophage provides a treatment platform for effective therapy of primary and bone metastatic tumors.
Lineage-specific protection and immune imprinting shape the age distributions of influenza B cases
Authors: Vieira Marcos C. , Donato Celeste M. , Arevalo Philip , Rimmelzwaan Guus F. , Wood Timothy , Lopez Liza , Huang Q. Sue , Dhanasekaran Vijaykrishna , Koelle Katia , Cobey Sarah
Published: July 2021

How a history of influenza virus infections contributes to protection is not fully understood, but such protection might explain the contrasting age distributions of cases of the two lineages of influenza B, B/Victoria and B/Yamagata. Fitting a statistical model to those distributions using surveillance data from New Zealand, we found they could be explained by historical changes in lineage frequencies combined with cross-protection between strains of the same lineage. We found additional protection against B/Yamagata in people for whom it was their first influenza B infection, similar to the immune imprinting observed in influenza A. While the data were not informative about B/Victoria imprinting, B/Yamagata imprinting could explain the fewer B/Yamagata than B/Victoria cases in cohorts born in the 1990s and the bimodal age distribution of B/Yamagata cases. Longitudinal studies can test if these forms of protection inferred from historical data extend to more recent strains and other populations.
Three-dimensional atomic mapping of ligands on palladium nanoparticles by atom probe tomography
Authors: Jang Kyuseon , Kim Se-Ho , Jun Hosun , Jung Chanwon , Yu Jiwon , Lee Sangheon , Choi Pyuck-Pa
Published: July 2021

Capping ligands are crucial to synthesizing colloidal nanoparticles with functional properties. However, the synergistic effect between different ligands and their distribution on crystallographic surfaces of nanoparticles during colloidal synthesis is still unclear despite powerful spectroscopic techniques, due to a lack of direct imaging techniques. In this study, atom probe tomography is adopted to investigate the three-dimensional atomic-scale distribution of two of the most common types of these ligands, cetrimonium (C19H42N) and halide (Br and Cl) ions, on Pd nanoparticles. The results, validated using density functional theory, demonstrate that the Br anions adsorbed on the nanoparticle surfaces promote the adsorption of the cetrimonium cations through electrostatic interactions, stabilizing the Pd {111} facets. In contrast, the Cl anions are not strongly adsorbed onto the Pd surfaces. The high density of adsorbed cetrimonium cations for Br anion additions results in the formation of multiple-twinned nanoparticles with superior oxidation resistance.
The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling
Authors: Moon Eui Jung , Mello Stephano S. , Li Caiyun G. , Chi Jen-Tsan , Thakkar Kaushik , Kirkland Jacob G. , Lagory Edward L. , Lee Ik Jae , Diep Anh N. , Miao Yu , Rafat Marjan , Vilalta Marta , Castellini Laura , Krieg Adam J. , Graves Edward E. , Attardi Laura D. , Giaccia Amato J.
Published: July 2021

Hypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.
Intracellular lipid droplet accumulation occurs early following viral infection and is required for an efficient interferon response
Authors: Monson E. A. , Crosse K. M. , Duan M. , Chen W. , O’Shea R. D. , Wakim L. M. , Carr J. M. , Whelan D. R. , Helbig K. J.
Published: July 2021

Lipid droplets (LDs) are increasingly recognized as critical organelles in signalling events, transient protein sequestration and inter-organelle interactions. However, the role LDs play in antiviral innate immune pathways remains unknown. Here we demonstrate that induction of LDs occurs as early as 2 h post-viral infection, is transient and returns to basal levels by 72 h. This phenomenon occurs following viral infections, both in vitro and in vivo. Virally driven in vitro LD induction is type-I interferon (IFN) independent, and dependent on Epidermal Growth Factor Receptor (EGFR) engagement, offering an alternate mechanism of LD induction in comparison to our traditional understanding of their biogenesis. Additionally, LD induction corresponds with enhanced cellular type-I and -III IFN production in infected cells, with enhanced LD accumulation decreasing viral replication of both Herpes Simplex virus 1 (HSV-1) and Zika virus (ZIKV). Here, we demonstrate, that LDs play vital roles in facilitating the magnitude of the early antiviral immune response specifically through the enhanced modulation of IFN following viral infection, and control of viral replication. By identifying LDs as a critical signalling organelle, this data represents a paradigm shift in our understanding of the molecular mechanisms which coordinate an effective antiviral response.
Ultrafast olivine-ringwoodite transformation during shock compression
Authors: Okuchi Takuo , Seto Yusuke , Tomioka Naotaka , Matsuoka Takeshi , Albertazzi Bruno , Hartley Nicholas J. , Inubushi Yuichi , Katagiri Kento , Kodama Ryosuke , Pikuz Tatiana A. , Purevjav Narangoo , Miyanishi Kohei , Sato Tomoko , Sekine Toshimori , Sueda Keiichi , Tanaka Kazuo A. , Tange Yoshinori , Togashi Tadashi , Umeda Yuhei , Yabuuchi Toshinori , Yabashi Makina , Ozaki Norimasa
Published: July 2021

Meteorites from interplanetary space often include high-pressure polymorphs of their constituent minerals, which provide records of past hypervelocity collisions. These collisions were expected to occur between kilometre-sized asteroids, generating transient high-pressure states lasting for several seconds to facilitate mineral transformations across the relevant phase boundaries. However, their mechanisms in such a short timescale were never experimentally evaluated and remained speculative. Here, we show a nanosecond transformation mechanism yielding ringwoodite, which is the most typical high-pressure mineral in meteorites. An olivine crystal was shock-compressed by a focused high-power laser pulse, and the transformation was time-resolved by femtosecond diffractometry using an X-ray free electron laser. Our results show the formation of ringwoodite through a faster, diffusionless process, suggesting that ringwoodite can form from collisions between much smaller bodies, such as metre to submetre-sized asteroids, at common relative velocities. Even nominally unshocked meteorites could therefore contain signatures of high-pressure states from past collisions.
Autonomous reinforcement learning agent for chemical vapor deposition synthesis of quantum materials
Authors: Rajak Pankaj , Krishnamoorthy Aravind , Mishra Ankit , Kalia Rajiv , Nakano Aiichiro , Vashishta Priya
Published: July 2021

Predictive materials synthesis is the primary bottleneck in realizing functional and quantum materials. Strategies for synthesis of promising materials are currently identified by time-consuming trial and error and there are no known predictive schemes to design synthesis parameters for materials. We use offline reinforcement learning (RL) to predict optimal synthesis schedules, i.e., a time-sequence of reaction conditions like temperatures and concentrations, for the synthesis of semiconducting monolayer MoS2 using chemical vapor deposition. The RL agent, trained on 10,000 computational synthesis simulations, learned threshold temperatures and chemical potentials for onset of chemical reactions and predicted previously unknown synthesis schedules that produce well-sulfidized crystalline, phase-pure MoS2. The model can be extended to multi-task objectives such as predicting profiles for synthesis of complex structures including multi-phase heterostructures and can predict long-time behavior of reacting systems, far beyond the domain of molecular dynamics simulations, making these predictions directly relevant to experimental synthesis.
Predicting thermoelectric properties from chemical formula with explicitly identifying dopant effects
Authors: Na Gyoung S. , Jang Seunghun , Chang Hyunju
Published: July 2021

Dopants play an important role in synthesizing materials to improve target materials properties or stabilize the materials. In particular, the dopants are essential to improve thermoelectic performances of the materials. However, existing machine learning methods cannot accurately predict the materials properties of doped materials due to severely nonlinear relations with their materials properties. Here, we propose a unified architecture of neural networks, called DopNet, to accurately predict the materials properties of the doped materials. DopNet identifies the effects of the dopants by explicitly and independently embedding the host materials and the dopants. In our evaluations, DopNet outperformed existing machine learning methods in predicting experimentally measured thermoelectric properties, and the error of DopNet in predicting a figure of merit (ZT) was 0.06 in mean absolute error. In particular, DopNet was significantly effective in an extrapolation problem that predicts ZTs of unknown materials, which is a key task to discover novel thermoelectric materials.
A molecular roadmap towards organic donor-acceptor complexes with high-performance thermoelectric response
Authors: Shi Wen , Deng Tianqi , Wong Zicong Marvin , Wu Gang , Yang Shuo-Wang
Published: July 2021

As a unique class of molecular electronic materials, organic donor–acceptor complexes now exhibit tantalizing prospect for heat–electricity interconversion. Over the past decades, in design of these materials for thermoelectric applications, consistent efforts have been made to synthesize a wide variety of structures and to characterize their properties. However, hitherto, one of the paramount conundrums, namely lack of systematic molecular design principles, has not been addressed yet. Here, based on ab initio calculations, and by comprehensively examining the underlying correlation among thermoelectric power factors, non-intuitive transport processes, and fundamental chemical structures for 13 prototypical organic donor–acceptor complexes, we establish a unified roadmap for rational development of these materials with increased thermoelectric response. We corroborate that the energy levels of frontier molecular orbitals in the isolated donor and acceptor molecules control the charge transfer, electronic property, charge transport, and thermoelectric performance in the solid-state complexes. Our results demonstrate that tailoring a suitable energy-level difference between donor’s highest occupied molecular orbital and acceptor’s lowest unoccupied molecular orbital holds the key to achieving an outstanding power factor. Moreover, we reveal that the charge-transfer-caused Coulomb scattering governs the charge and thermoelectric transport in organic donor–acceptor complexes.
Riemann zeros from Floquet engineering a trapped-ion qubit
Authors: He Ran , Ai Ming-Zhong , Cui Jin-Ming , Huang Yun-Feng , Han Yong-Jian , Li Chuan-Feng , Guo Guang-Can , Sierra G. , Creffield C. E.
Published: July 2021

The non-trivial zeros of the Riemann zeta function are central objects in number theory. In particular, they enable one to reproduce the prime numbers. They have also attracted the attention of physicists working in random matrix theory and quantum chaos for decades. Here we present an experimental observation of the lowest non-trivial Riemann zeros by using a trapped-ion qubit in a Paul trap, periodically driven with microwave fields. The waveform of the driving is engineered such that the dynamics of the ion is frozen when the driving parameters coincide with a zero of the real component of the zeta function. Scanning over the driving amplitude thus enables the locations of the Riemann zeros to be measured experimentally to a high degree of accuracy, providing a physical embodiment of these fascinating mathematical objects in the quantum realm.
Immunologic mechanisms of seasonal influenza vaccination administered by microneedle patch from a randomized phase I trial
Authors: Rouphael Nadine G. , Lai Lilin , Tandon Sonia , McCullough Michele Paine , Kong Yunchuan , Kabbani Sarah , Natrajan Muktha S. , Xu Yongxian , Zhu Yerun , Wang Dongli , O’Shea Jesse , Sherman Amy , Yu Tianwei , Henry Sebastien , McAllister Devin , Stadlbauer Daniel , Khurana Surender , Golding Hana , Krammer Florian , Mulligan Mark J. , Prausnitz Mark R.
Published: July 2021

In a phase 1 randomized, single-center clinical trial, inactivated influenza virus vaccine delivered through dissolvable microneedle patches (MNPs) was found to be safe and immunogenic. Here, we compare the humoral and cellular immunologic responses in a subset of participants receiving influenza vaccination by MNP to the intramuscular (IM) route of administration. We collected serum, plasma, and peripheral blood mononuclear cells in 22 participants up to 180 days post-vaccination. Hemagglutination inhibition (HAI) titers and antibody avidity were similar after MNP and IM vaccination, even though MNP vaccination used a lower antigen dose. MNPs generated higher neuraminidase inhibition (NAI) titers for all three influenza virus vaccine strains tested and triggered a larger percentage of circulating T follicular helper cells (CD4 + CXCR5 + CXCR3 + ICOS + PD-1+) compared to the IM route. Our study indicates that inactivated influenza virus vaccination by MNP produces humoral and cellular immune response that are similar or greater than IM vaccination.
Tetramethylguanidine-functionalized melamine as a multifunctional organocatalyst for the expeditious synthesis of 1,2,4-triazoloquinazolinones
Authors: Keshavarz Mahnoush , Dekamin Mohammad G. , Mamaghani Manouchehr , Nikpassand Mohammad
Published: July 2021

Novel nano-ordered 1,1,3,3-tetramethylguanidine-functionalized melamine (Melamine@TMG) organocatalyst was prepared and adequately identified by various techniques including FTIR, EDX, XRD and SEM spectroscopic or microscopic methods as well as TGA and DTG analytical methods. The Melamine@TMG, as an effective multifunctional organocatalyst, was found to promote smoothly the three-component synthesis of 1,2,4-triazoloquinazolinone derivatives using cyclic dimedone, 3-amino-1,2,4-triazole and different benzaldehyde derivatives in EtOH at 40 °C. This practical method afforded the desired products in high to excellent yields (86–99%) and short reaction times (10–25 min). The main advantages of this new method are the use of heterogeneous multifunctional nanocatalyst, simple work-up procedure with no need for chromatographic purification, highly selective conversion of substrates and recyclability of the catalyst, which could be used in five consecutive runs with only a small decrease in its activity.
Clubroot resistance derived from the European Brassica napus cv. ‘Tosca’ is not effective against virulent Plasmodiophora brassicae isolates from Alberta, Canada
Authors: Fredua-Agyeman Rudolph , Hwang Sheau-Fang , Zhang Hui , Falak Igor , Huang Xiuqiang , Strelkov Stephen E.
Published: July 2021

In this study, clubroot resistance in the resynthesized European winter Brassica napus cv. ‘Tosca’ was introgressed into a Canadian spring canola line ‘11SR0099’, which was then crossed with the clubroot susceptible spring line ‘12DH0001’ to produce F1 seeds. The F1 plants were used to develop a doubled haploid (DH) mapping population. The parents and the DH lines were screened against ‘old’ pathotypes 2F, 3H, 5I, 6M and 8N of the clubroot pathogen, Plasmodiophora brassicae, as well as against the ‘new’ pathotypes 5X, 5L, 2B, 3A, 3D, 5G, 8E, 5C, 8J, 5K, 3O and 8P. Genotyping was conducted using a Brassica 15K SNP array. The clubroot screening showed that ‘Tosca, ‘11SR0099’ and the resistant DH lines were resistant to three (2F, 3H and 5I) of the five ‘old’ pathotypes and four (2B, 3O, 8E and 8P) of the 12 ‘new’ pathotypes, while being moderately resistant to the ‘old’ pathotype 8N and the ‘new’ pathotypes 3D and 5G. ‘Tosca’ was susceptible to isolates representing pathotype 3A (the most common among the ‘new’ pathotypes) as well as pathotypes 6M, 5X, 5L, 5K and 8J. Linkage analysis and QTL mapping identified a ca. 0.88–0.95 Mb genomic region on the A03 chromosome of ‘Tosca’ as conferring resistance to pathotypes 2F, 3H, 5I, 2B, 3D, 5G, 8E, 3O and 8P. The identified QTL genomic region housed the CRk, Crr3 and CRd gene(s). However, the susceptibility of ‘Tosca’ to most of the common virulent pathotypes makes it unattractive as a sole CR donor in the breeding of commercial canola varieties in western Canada.
Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray
Authors: Higashi Yuya , Matsumoto Kotaro , Saitoh Hiroyuki , Shiro Ayumi , Ma Yue , Laird Mathilde , Chinnathambi Shanmugavel , Birault Albane , Doan Tan Le Hoang , Yasuda Ryo , Tajima Toshiki , Kawachi Tetsuya , Tamanoi Fuyuhiko
Published: July 2021

X-ray irradiation of high Z elements causes photoelectric effects that include the release of Auger electrons that can induce localized DNA breaks. We have previously established a tumor spheroid-based assay that used gadolinium containing mesoporous silica nanoparticles and synchrotron-generated monochromatic X-rays. In this work, we focused on iodine and synthesized iodine-containing porous organosilica (IPO) nanoparticles. IPO were loaded onto tumor spheroids and the spheroids were irradiated with 33.2 keV monochromatic X-ray. After incubation in CO2 incubator, destruction of tumor spheroids was observed which was accompanied by apoptosis induction, as determined by the TUNEL assay. By employing the γH2AX assay, we detected double strand DNA cleavages immediately after the irradiation. These results suggest that IPO first generate double strand DNA breaks upon X-ray irradiation followed by apoptosis induction of cancer cells. Use of three different monochromatic X-rays having energy levels of 33.0, 33.2 and 33.4 keV as well as X-rays with 0.1 keV energy intervals showed that the optimum effect of all three events (spheroid destruction, apoptosis induction and generation of double strand DNA breaks) occurred with a 33.2 keV monochromatic X-ray. These results uncover the preferential effect of K-edge energy X-ray for tumor spheroid destruction mediated by iodine containing nanoparticles.
Quantitative observation of monochromatic X-rays emitted from implosion hotspot in high spatial resolution in inertial confinement fusion
Authors: Ren Kuan , Wu Junfeng , Dong Jianjun , Li Yaran , Huang Tianxuan , Zhao Hang , Liu Yaoyuan , Cao Zhurong , Zhang Jiyan , Mu Baozhong , Yan Ji , Jiang Wei , Pu Yudong , Li Yulong , Peng Xiaoshi , Xu Tao , Yang Jiamin , Lan Ke , Ding Yongkun , Jiang Shaoen , Wang Feng
Published: July 2021

In inertial confinement fusion, quantitative and high-spatial resolution ($$< 10\,\upmu $$

<
10

μ

m) measurements of the X-rays self-emitted by the hotspot are critical for studying the physical processes of the implosion stagnation stage. Herein, the 8 ± 0.39-keV monochromatic X-ray distribution from the entire hotspot is quantitatively observed in 5-$$\upmu $$
μ
m spatial resolution using a Kirkpatrick–Baez microscope, with impacts from the responses of the diagnosis system removed, for the first time, in implosion experiments at the 100 kJ laser facility in China. Two-dimensional calculations along with 2.5% P2 drive asymmetry and 0.3 ablator self-emission are congruent with the experimental results, especially for the photon number distribution, hotspot profile, and neutron yield. Theoretical calculations enabled a better understanding of the experimental results. Furthermore, the origins of the 17.81% contour profile of the deuterium-deuterium hotspot and the accurate Gaussian source approximation of the core emission area in the implosion capsule are clarified in detail. This work is significant for quantitatively exploring the physical conditions of the hotspot and updating the theoretical model of capsule implosion.
Unveiling the third dimension in morphometry with automated quantitative volumetric computations
Authors: Frank Lawrence R. , Rowe Timothy B. , Boyer Doug M. , Witmer Lawrence M. , Galinsky Vitaly L.
Published: July 2021

As computed tomography and related technologies have become mainstream tools across a broad range of scientific applications, each new generation of instrumentation produces larger volumes of more-complex 3D data. Lagging behind are step-wise improvements in computational methods to rapidly analyze these new large, complex datasets. Here we describe novel computational methods to capture and quantify volumetric information, and to efficiently characterize and compare shape volumes. It is based on innovative theoretical and computational reformulation of volumetric computing. It consists of two theoretical constructs and their numerical implementation: the spherical wave decomposition (SWD), that provides fast, accurate automated characterization of shapes embedded within complex 3D datasets; and symplectomorphic registration with phase space regularization by entropy spectrum pathways (SYMREG), that is a non-linear volumetric registration method that allows homologous structures to be correctly warped to each other or a common template for comparison. Together, these constitute the Shape Analysis for Phenomics from Imaging Data (SAPID) method. We demonstrate its ability to automatically provide rapid quantitative segmentation and characterization of single unique datasets, and both inter-and intra-specific comparative analyses. We go beyond pairwise comparisons and analyze collections of samples from 3D data repositories, highlighting the magnified potential our method has when applied to data collections. We discuss the potential of SAPID in the broader context of generating normative morphologies required for meaningfully quantifying and comparing variations in complex 3D anatomical structures and systems.
Intrauterine﻿ growth restriction weakens anticontractile influence of NO in coronary arteries of adult rats
Authors: Selivanova Ekaterina K. , Shvetsova Anastasia A. , Shilova Lyubov D. , Tarasova Olga S. , Gaynullina Dina K.
Published: July 2021

Intrauterine growth restriction (IUGR) is one of the most common pathologies of pregnancy. The cardiovascular consequences of IUGR do not disappear in adulthood and can manifest themselves in pathological alterations of vasomotor control. The hypothesis was tested that IUGR weakens anticontractile influence of NO and augments procontractile influence of Rho-kinase in arteries of adult offspring. To model IUGR in the rat, dams were 50% food restricted starting from the gestational day 11 till delivery. Mesenteric and coronary arteries of male offspring were studied at the age of 3 months using wire myography, qPCR, and Western blotting. Contractile responses of mesenteric arteries to α1-adrenoceptor agonist methoxamine as well as influences of NO and Rho-kinase did not differ between control and IUGR rats. However, coronary arteries of IUGR rats demonstrated elevated contraction to thromboxane A2 receptor agonist U46619 due to weakened anticontractile influence of NO and enhanced role of Rho-kinase in the endothelium. This was accompanied by reduced abundance of SODI protein and elevated content of RhoA protein in coronary arteries of IUGR rats. IUGR considerably changes the regulation of coronary vascular tone in adulthood and, therefore, can serve as a risk factor for the development of cardiac disorders.
Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer
Authors: Shaath Hibah , Toor Salman M. , Nada Mohamed Abu , Elkord Eyad , Alajez Nehad M.
Published: July 2021

Colorectal cancer (CRC) remains a global disease burden and a leading cause of cancer related deaths worldwide. The identification of aberrantly expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), and the resulting molecular interactions and signaling networks is essential for better understanding of CRC, identification of novel diagnostic biomarkers and potential development of therapeutic interventions. Herein, we performed microRNA (miRNA) sequencing on fifteen CRC and their non-tumor adjacent tissues and whole transcriptome RNA-Seq on six paired samples from the same cohort and identified alterations in miRNA, mRNA, and lncRNA expression. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in CRC, including ERBB2, RABL6, FOXM1, and NFKB networks, while functional annotation highlighted activation of cell proliferation and migration as the hallmark of CRC. IPA in combination with in silico prediction algorithms and experimentally validated databases gave insight into the complex associations and interactions between downregulated miRNAs and upregulated mRNAs in CRC and vice versa. Additionally, potential interaction between differentially expressed lncRNAs such as H19, SNHG5, and GATA2-AS1 with multiple miRNAs has been revealed. Taken together, our data provides thorough analysis of dysregulated protein-coding and non-coding RNAs in CRC highlighting numerous associations and regulatory networks thus providing better understanding of CRC.
Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice
Authors: Sousa Marciana V. , Amaral Andressa G. , Freitas Jessica A. , Murata Gilson M. , Watanabe Elieser H. , Balbo Bruno E. , Tavares Marcelo D. , Hortegal Renato A. , Rocon Camila , Souza Leandro E. , Irigoyen Maria C. , Salemi Vera M. , Onuchic Luiz F.
Published: July 2021

Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13–18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals. Smoking increased serum urea nitrogen in cystic and noncystic mice and independently enhanced tubular cell proliferation and apoptosis. Smoking also increased renal fibrosis, however this effect was much higher in cystic than in noncystic animals. Pkd1 deficiency and smoking showed independent and additive effects on reducing renal levels of glutathione. Systolic function and several cardiac structural parameters were also negatively affected by smoking and the Pkd1-deficient status, following independent and additive patterns. Smoking did not increase, however, cardiac apoptosis or fibrosis in cystic and noncystic mice. Notably, smoking promoted a much higher reduction in body weight in Pkd1-deficient than in noncystic animals. Our findings show that smoking aggravated the renal and cardiac phenotypes of Pkd1-deficient cystic mice, suggesting that similar effects may occur in human ADPKD.
Maximal modularity and the optimal size of parliaments
Authors: Gamberi Luca , Förster Yanik-Pascal , Tzanis Evan , Annibale Alessia , Vivo Pierpaolo
Published: July 2021

An important question in representative democracies is how to determine the optimal parliament size of a given country. According to an old conjecture, known as the cubic root law, there is a fairly universal power-law relation, with an exponent equal to 1/3, between the size of an elected parliament and the country’s population. Empirical data in modern European countries support such universality but are consistent with a larger exponent. In this work, we analyse this intriguing regularity using tools from complex networks theory. We model the population of a democratic country as a random network, drawn from a growth model, where each node is assigned a constituency membership sampled from an available set of size D. We calculate analytically the modularity of the population and find that its functional relation with the number of constituencies is strongly non-monotonic, exhibiting a maximum that depends on the population size. The criterion of maximal modularity allows us to predict that the number of representatives should scale as a power-law in the size of the population, a finding that is qualitatively confirmed by the empirical analysis of real-world data.
Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds
Authors: Nagano Hisato , Suematsu Yoshitaka , Takuma Megumi , Aoki Shimpo , Satoh Ayano , Takayama Eiji , Kinoshita Manabu , Morimoto Yuji , Takeoka Shinji , Fujie Toshinori , Kiyosawa Tomoharu
Published: July 2021

The short survival time of transplanted adipose-derived mesenchymal stem cells (ASCs) is a problem for skin wound healing. Transplantation after the formation of cellular spheroids has been investigated as a promising method for prolonging cellular survival. However, there have been technical restrictions for transplantation of spheroids in clinical practice. Here, we show an effective method for transplantation of ASC spheroids onto skin wounds in order to efficiently cure refractory ulcers. To assist anchoring of spheroids onto skin wounds, we used a 120-nm-thick free-standing film (nanosheet) that has a highly adhesive property. Bioluminescence imaging showed that ASC spheroids carried by the nanosheet survived for 14 days, which is about two-times longer than that previously reported. Wounds treated with a nanosheet carrying ASC spheroids were 4-times smaller than untreated wounds on day 14. This method for transplantation of spheroids could be applied to cell therapy for various refractory skin wounds.
A system biology approach based on metabolic biomarkers and protein–protein interactions for identifying pathways underlying schizophrenia and bipolar disorder
Authors: Altaf-Ul-Amin Md. , Hirose Kazuhisa , Nani João V. , Porta Lucas C. , Tasic Ljubica , Hossain Shaikh Farhad , Huang Ming , Ono Naoaki , Hayashi Mirian A. F. , Kanaya Shigehiko
Published: July 2021

Mental disorders (MDs), including schizophrenia (SCZ) and bipolar disorder (BD), have attracted special attention from scientists due to their high prevalence and significantly debilitating clinical features. The diagnosis of MDs is still essentially based on clinical interviews, and intensive efforts to introduce biochemical based diagnostic methods have faced several difficulties for implementation in clinics, due to the complexity and still limited knowledge in MDs. In this context, aiming for improving the knowledge in etiology and pathophysiology, many authors have reported several alterations in metabolites in MDs and other brain diseases. After potentially fishing all metabolite biomarkers reported up to now for SCZ and BD, we investigated here the proteins related to these metabolites in order to construct a protein–protein interaction (PPI) network associated with these diseases. We determined the statistically significant clusters in this PPI network and, based on these clusters, we identified 28 significant pathways for SCZ and BDs that essentially compose three groups representing three major systems, namely stress response, energy and neuron systems. By characterizing new pathways with potential to innovate the diagnosis and treatment of psychiatric diseases, the present data may also contribute to the proposal of new intervention for the treatment of still unmet aspects in MDs.
Differences in heart rate variability and body composition in breast cancer survivors and women without cancer
Authors: Escutia-Reyes Daniel , de Jesús Garduño-García José , Emilio-López-Chávez Gerardo , Gómez-Villanueva Ángel , Pliego-Carrillo Adriana Cristina , Soto-Piña Alexandra Estela , Reyes-Lagos José Javier
Published: July 2021

The aim of this study was to explore cardiac autonomic changes assessed by linear and nonlinear indexes of heart rate variability (HRV) and body composition modifications in breast cancer survivors and cancer-free control women. Women who were breast cancer survivors (BCS, n = 27) and without cancer with similar characteristics (Control, n = 31) were recruited for this study. We calculated some relevant linear and nonlinear parameters of 5 min of RR interval time series such as mean RR interval (RRave), the corrected Poincaré index (cSD1/SD2), the sample entropy (SampEn), the long-term fractal scaling exponent (α2) and 2UV from symbolic dynamics. Additionally, we indirectly assessed body composition measures such as body weight, fat mass, visceral fat rating (VFR), normalized VRF (nVFR), muscle mass, metabolic age, and total body water. We found that diverse HRV indexes and only one body composition measure showed statistical differences (p < 0.05) between the BCS and Control groups. RRave: 729 (648–802) vs. 795 (713–852) ms; cSD2/SD1: 3.4 (2.7–5.0) vs. 2.9 (2.3–3.5); SampEn: 1.5 (1.3–1.8) vs. 1.7 (1.5–1.8); α2: 0.6 (0.3–0.6) vs. 0.5 (0.4–0.5); 2UV: 7.1 (4.3–11.5) vs. 10.8 (6.4–15.7) and nVFR 0.12 (0.11–0.13) vs. 0.10 (0.08–0.12) points/kg, respectively. The nVFR was strongly significantly correlated with several indexes of HRV only in the BCS group.Our findings suggest that BCS exhibit lower parasympathetic cardiac activity and changes in HRV patterns compared to Controls. A concomitant increase of visceral fat, among other factors, may contribute to cardiac autonomic disturbances and changes in HRV patterns in BCS.
Reinforcement learning control of a biomechanical model of the upper extremity
Authors: Fischer Florian , Bachinski Miroslav , Klar Markus , Fleig Arthur , Müller Jörg
Published: July 2021

Among the infinite number of possible movements that can be produced, humans are commonly assumed to choose those that optimize criteria such as minimizing movement time, subject to certain movement constraints like signal-dependent and constant motor noise. While so far these assumptions have only been evaluated for simplified point-mass or planar models, we address the question of whether they can predict reaching movements in a full skeletal model of the human upper extremity. We learn a control policy using a motor babbling approach as implemented in reinforcement learning, using aimed movements of the tip of the right index finger towards randomly placed 3D targets of varying size. We use a state-of-the-art biomechanical model, which includes seven actuated degrees of freedom. To deal with the curse of dimensionality, we use a simplified second-order muscle model, acting at each degree of freedom instead of individual muscles. The results confirm that the assumptions of signal-dependent and constant motor noise, together with the objective of movement time minimization, are sufficient for a state-of-the-art skeletal model of the human upper extremity to reproduce complex phenomena of human movement, in particular Fitts’ Law and the$$\frac{2}{3}$$23Power Law. This result supports the notion that control of the complex human biomechanical system can plausibly be determined by a set of simple assumptions and can easily be learned.
A proposal for a new morphological classification of the popliteus muscle tendon with potential clinical and biomechanical significance
Authors: Olewnik Łukasz , LaPrade Robert F. , Paulsen Friedrich , Gonera Bartosz , Kurtys Konrad , Podgórski Michał , Aragonés Paloma , Sanudo J. Ramón , Polguj Michał
Published: July 2021

The purpose of this study was to characterize the morphological variations in the proximal attachments and create an accurate classification of the PPM for use in planning surgical procedures in this area, for evaluating radiological imaging and rehabilitation. One hundred and thirty-four lower limbs of body donors (52 woman and 82 man) fixed in 10% formalin solution were examined. The popliteus muscle was present in all 134 limbs. Four main types were identified with subtypes. The most common type was Type I (34.3%), characterized by a single tendon in the popliteus sulcus. Type II (30.6%) characterized by a main tendon in the popliteus sulcus and accessory bands. This type was divided into five subtypes (A–E) based on presence of specific accessory bands. Type III (15.3%) was characterized by two tendons in the popliteal sulcus. Type IV (19.4%) was characterized by two tendons in the popliteus sulcus and additional bands. This type was also divided into five subtypes (A–E) based on presence of specific accessory bands. The popliteofibular ligament was present in 90.3% of cases. A new classification based on a proximal attachment is proposed. The popliteus tendon is characterized by a very high morphological variability, which can affect posterolateral knee stability and the natural rotation of the tibia. Such a classification system may be useful for clinicians performing medical procedures within the knee joint, including orthopedic surgeons.