bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late Quaternary Fault Slip Rate Within the Qilian Orogen, Insight Into the Deformation Kinematics for the NE Tibetan Plateau
Authors: Hu Xiaofei , Cao Xilin , Li Tao , Mao Junwei , Zhang Jian , He Xin , Zhang Ya'nan , Pan Baotian 
Published: April 2021

AbstractVarious kinematic models have been proposed to explain the growth process of wide compressive orogens, and the deformation rate within the entire range of the orogen (rather than that of the leading‐edge fault) provides valuable information for model evaluation. Within the Qilian Orogen, between the central and northern Qilian Shan mountain in China, we studied the deformation of a series of Quaternary fluvial terraces across the North Tuolai Shan Fault (NTF), including optically stimulated luminescence dating of terrace ages. The results show that the six levels of terraces (T6 to T1) were formed at 58.4 ± 4.4 ka, 53 ± 5 ka, 46 ± 5 ka, 38 ± 5 ka, 23.2 ± 1.8 ka, and 4.8 ± 0.4 ka, respectively. Field investigations revealed that these terrace surfaces are faulted and folded by the NTF. Based on the deformation and ages of the terraces across the fault, the vertical slip rate is estimated as 1.5 ± 0.1 mm/yr, and the shortening rate is 0.9 ± 0.1 mm/yr, with a fault dip of 58°–60°. This deformation rate is similar to rates determined along the leading‐edge fault in the northern Qilian Shan and along the fault in the southern Qilian Shan. The widely distributed shortening across the ∼300‐km‐wide Qilian Orogen supports the kinematics of distributed upper crustal shortening across the Qilian Orogen, with a ductile lower crust, rather than a large, gradually propagating crustal‐scale deformation wedge.
Altered network and rescue of human neurons derived from individuals with early-onset genetic epilepsy
Authors: Negraes Priscilla D. , Trujillo Cleber A. , Yu Nam-Kyung , Wu Wei , Yao Hang , Liang Nicholas , Lautz Jonathan D. , Kwok Ellius , McClatchy Daniel , Diedrich Jolene , de Bartolome Salvador Martinez , Truong Justin , Szeto Ryan , Tran Timothy , Herai Roberto H. , Smith Stephen E. P. , Haddad Gabriel G. , Yates John R. , Muotri Alysson R. 
Published: April 2021

AbstractEarly-onset epileptic encephalopathies are severe disorders often associated with specific genetic mutations. In this context, the CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by early-onset seizures, intellectual delay, and motor dysfunction. Although crucial for proper brain development, the precise targets of CDKL5 and its relation to patients’ symptoms are still unknown. Here, induced pluripotent stem cells derived from individuals deficient in CDKL5 protein were used to generate neural cells. Proteomic and phosphoproteomic approaches revealed disruption of several pathways, including microtubule-based processes and cytoskeleton organization. While CDD-derived neural progenitor cells have proliferation defects, neurons showed morphological alterations and compromised glutamatergic synaptogenesis. Moreover, the electrical activity of CDD cortical neurons revealed hyperexcitability during development, leading to an overly synchronized network. Many parameters of this hyperactive network were rescued by lead compounds selected from a human high-throughput drug screening platform. Our results enlighten cellular, molecular, and neural network mechanisms of genetic epilepsy that could ultimately promote novel therapeutic opportunities for patients.
Synergistic action of phage phiIPLA-RODI and lytic protein CHAPSH3b: a combination strategy to target Staphylococcus aureus biofilms
Authors: Duarte Ana Catarina , Fernández Lucía , De Maesschalck Vincent , Gutiérrez Diana , Campelo Ana Belén , Briers Yves , Lavigne Rob , Rodríguez Ana , García Pilar 
Published: April 2021

AbstractStaphylococcus aureus is considered a priority pathogen due to its increasing acquisition of antibiotic resistance determinants. Additionally, this microbe has the ability to form recalcitrant biofilms on different biotic and inert surfaces. In this context, bacteriophages and their derived lytic proteins may be a forward-looking strategy to help combat staphylococcal biofilms. However, these antimicrobials exhibit individual limitations that may be overcome by combining them with other compounds. This work investigates the combination of a phage-derived lytic protein, CHAPSH3b, and the virulent bacteriophage phiIPLA-RODI. The obtained results show the synergy between both antimicrobials for the treatment of 24-h-old S. aureus biofilms, with greater reductions in viable cell counts observed when phage and lysin are applied together compared to the individual treatments. Time-kill curves and confocal microscopy revealed that the fast antibacterial action of CHAPSH3b reduces the population up to 7 hours after initial exposure, which is subsequently followed by phage predation, limiting regrowth of the bacterial population. Moreover, at least 90% of bacteriophage insensitive mutants are susceptible to the lytic protein. Therefore, CHAPSH3b might help curtail the development of phage resistance during treatment. The combination of the lysin and phiIPLA-RODI also showed promising results in an ex vivo pig skin model of wound infection. Overall, the results of this study demonstrate that the combination of phage-derived lytic proteins and bacteriophages can be a viable strategy to develop improved antibiofilm products.
Path-encoded high-dimensional quantum communication over a 2-km multicore fiber
Authors: Da Lio Beatrice , Cozzolino Daniele , Biagi Nicola , Ding Yunhong , Rottwitt Karsten , Zavatta Alessandro , Bacco Davide , Oxenløwe Leif K. 
Published: April 2021

AbstractQuantum key distribution (QKD) protocols based on high-dimensional quantum states have shown the route to increase the key rate generation while benefiting of enhanced error tolerance, thus overcoming the limitations of two-dimensional QKD protocols. Nonetheless, the reliable transmission through fiber links of high-dimensional quantum states remains an open challenge that must be addressed to boost their application. Here, we demonstrate the reliable transmission over a 2-km-long multicore fiber of path-encoded high-dimensional quantum states. Leveraging on a phase-locked loop system, a stable interferometric detection is guaranteed, allowing for low error rates and the generation of 6.3 Mbit/s of a secret key rate.
Vaccine-induced, but not natural immunity, against the Streptococcal inhibitor of complement protects against invasive disease
Authors: Tan Lionel K. K. , Reglinski Mark , Teo Daryl , Reza Nada , Lamb Lucy E. M. , Nageshwaran Vaitehi , Turner Claire E. , Wikstrom Mats , Frick Inga-Maria , Bjorck Lars , Sriskandan Shiranee 
Published: April 2021

AbstractHighly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full-length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole-blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We, therefore, propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full-length SIC permits the development of protective antibodies against all SIC domains.
Thermal and mechanical characterization of high performance polymer fabrics for applications in wearable devices
Authors: Candadai Aaditya A. , Nadler Emily J. , Burke Jack S. , Weibel Justin A. , Marconnet Amy M. 
Published: April 2021

AbstractWith advances in flexible and wearable device technology, thermal regulation will become increasingly important. Fabrics and substrates used for such applications will be required to effectively spread any heat generated in the devices to ensure user comfort and safety, while also preventing overheating of the electronic components. Commercial fabrics consisting of ultra-high molecular weight polyethylene (UHMW-PE) fibers are currently used in personal body armor and sports gear owing to their high strength, durability, and abrasion resistance. In addition to superior mechanical properties, UHMW-PE fibers exhibit very high axial thermal conductivity due to a high degree of polymer chain orientation. However, these materials have not been widely explored for thermal management applications in flexible and wearable devices. Assessment of their suitability for such applications requires characterization of the thermal and mechanical properties of UHMW-PE in the fabric form that will ultimately be used to construct heat spreading materials. Here, we use advanced techniques to characterize the thermal and mechanical properties of UHMW-PE fabrics, as well as other conventional flexible materials and fabrics. An infrared microscopy-based approach measures the effective in-plane thermal conductivity, while an ASTM-based bend testing method quantifies the bending stiffness. We also characterize the effective thermal behavior of fabrics when subjected to creasing and thermal annealing to assess their reliability for relevant practical engineering applications. Fabrics consisting of UHMW-PE fibers have significantly higher thermal conductivities than the benchmark conventional materials while possessing good mechanical flexibility, thereby showcasing great potential as substrates for flexible and wearable heat spreading application.
Anandamide alters the membrane properties, halts the cell division and prevents drug efflux in multidrug resistant Staphylococcus aureus
Authors: Banerjee Shreya , Sionov Ronit Vogt , Feldman Mark , Smoum Reem , Mechoulam Raphael , Steinberg Doron 
Published: April 2021

AbstractAntibiotic resistance is a serious public health problem throughout the world. Overcoming methicillin and multidrug-resistant Staphylococcus aureus (MRSA/MDRSA) infections has become a challenge and there is an urgent need for new therapeutic approaches. We have previously demonstrated that the endocannabinoid Anandamide (AEA) can sensitize MRSA to antibiotics. Here we have studied the mechanism of action using a MDRSA clinical isolate that are sensitized by AEA to methicillin and norfloxacin. We found that AEA treatment halts the growth of both antibiotic-sensitive and antibiotic-resistant S. aureus. The AEA-treated bacteria become elongated and the membranes become ruffled with many protrusions. AEA treatment also leads to an increase in the percentage of bacteria having a complete septum, suggesting that the cell division is halted at this stage. The latter is supported by cell cycle analysis that shows an accumulation of bacteria in the G2/M phase after AEA treatment. We further observed that AEA causes a dose-dependent membrane depolarization that is partly relieved upon time. Nile red staining of the bacterial membranes indicates that AEA alters the membrane structures. Importantly, 4′-6-diamidino-2-phenylindole (DAPI) accumulation assay and ethidium bromide efflux (EtBr) assay unveiled that AEA leads to a dose-dependent drug accumulation by inhibiting drug efflux. In conclusion, our study demonstrates that AEA interferes with cell division, alters the membrane properties of MDRSA, and leads to increased intracellular drug retention, which can contribute to the sensitization of MDRSA to antibiotics.
New lineages of photobionts in Bolivian lichens expand our knowledge on habitat preferences and distribution of Asterochloris algae
Authors: Kosecka Magdalena , Guzow-Krzemińska Beata , Černajová Ivana , Škaloud Pavel , Jabłońska Agnieszka , Kukwa Martin 
Published: April 2021

AbstractWe studied the biodiversity of Asterochloris photobionts found in Bolivian lichens to better understand their global spatial distribution and adaptation strategies in the context of a worldwide phylogeny of the genus. Based on nuclear ITS rDNA, the chloroplast rbcL gene and the actin type I gene we reconstructed a phylogenetic tree that recovered nine new Asterochloris lineages, while 32 Bolivian photobiont samples were assigned to 12 previously recognized Asterochloris lineages. We also show that some previously discovered Asterochloris photobiont species and lineages may occur in a broader spectrum of climatic conditions, and mycobiont species and photobionts may show different preferences along an altitude gradient. To reveal general patterns of of mycobiont specificity towards the photobiont in Asterochloris, we tested the influence of climate, altitude, geographical distance and effects of symbiotic partner (mycobiont) at the species level of three genera of lichen forming fungi: Stereocaulon, Cladonia and Lepraria. Further, we compared the specificity of mycobionts towards Asterochloris photobionts in cosmopolitan, Neotropical, and Pantropical lichen forming fungi. Interestingly, cosmopolitan species showed the lowest specificity to their photobionts, but also the lowest haplotype diversity. Neotropical and Paleotropical mycobionts, however, were more specific.
Deep learning can accelerate and quantify simulated localized correlated spectroscopy
Authors: Iqbal Zohaib , Nguyen Dan , Thomas Michael Albert , Jiang Steve 
Published: April 2021

AbstractNuclear magnetic resonance spectroscopy (MRS) allows for the determination of atomic structures and concentrations of different chemicals in a biochemical sample of interest. MRS is used in vivo clinically to aid in the diagnosis of several pathologies that affect metabolic pathways in the body. Typically, this experiment produces a one dimensional (1D) 1H spectrum containing several peaks that are well associated with biochemicals, or metabolites. However, since many of these peaks overlap, distinguishing chemicals with similar atomic structures becomes much more challenging. One technique capable of overcoming this issue is the localized correlated spectroscopy (L-COSY) experiment, which acquires a second spectral dimension and spreads overlapping signal across this second dimension. Unfortunately, the acquisition of a two dimensional (2D) spectroscopy experiment is extremely time consuming. Furthermore, quantitation of a 2D spectrum is more complex. Recently, artificial intelligence has emerged in the field of medicine as a powerful force capable of diagnosing disease, aiding in treatment, and even predicting treatment outcome. In this study, we utilize deep learning to: (1) accelerate the L-COSY experiment and (2) quantify L-COSY spectra. All training and testing samples were produced using simulated metabolite spectra for chemicals found in the human body. We demonstrate that our deep learning model greatly outperforms compressed sensing based reconstruction of L-COSY spectra at higher acceleration factors. Specifically, at four-fold acceleration, our method has less than 5% normalized mean squared error, whereas compressed sensing yields 20% normalized mean squared error. We also show that at low SNR (25% noise compared to maximum signal), our deep learning model has less than 8% normalized mean squared error for quantitation of L-COSY spectra. These pilot simulation results appear promising and may help improve the efficiency and accuracy of L-COSY experiments in the future.
Racial disparities in COVID-19 outcomes exist despite comparable Elixhauser comorbidity indices between Blacks, Hispanics, Native Americans, and Whites
Authors: Qeadan Fares , VanSant-Webb Elizabeth , Tingey Benjamin , Rogers Tiana N. , Brooks Ellen , Mensah Nana A. , Winkfield Karen M. , Saeed Ali I. , English Kevin , Rogers Charles R. 
Published: April 2021

AbstractFactors contributing to racial inequities in outcomes from coronavirus disease 2019 (COVID-19) remain poorly understood. We compared by race the risk of 4 COVID-19 health outcomes––maximum length of hospital stay (LOS), invasive ventilation, hospitalization exceeding 24 h, and death––stratified by Elixhauser comorbidity index (ECI) ranking. Outcomes and ECI scores were constructed from retrospective data obtained from the Cerner COVID-19 De-Identified Data cohort. We hypothesized that racial disparities in COVID-19 outcomes would exist despite comparable ECI scores among non-Hispanic (NH) Blacks, Hispanics, American Indians/Alaska Natives (AI/ANs), and NH Whites. Compared with NH Whites, NH Blacks had longer hospital LOS, higher rates of ventilator dependence, and a higher mortality rate; AI/ANs, higher odds of hospitalization for ECI = 0 but lower for ECI ≥ 5, longer LOS for ECI = 0, a higher risk of death across all ECI categories except ECI ≥ 5, and higher odds of ventilator dependence; Hispanics, a lower risk of death across all ECI categories except ECI = 0, lower odds of hospitalization, shorter LOS for ECI ≥ 5, and higher odds of ventilator dependence for ECI = 0 but lower for ECI = 1–4. Our findings contest arguments that higher comorbidity levels explain elevated COVID-19 death rates among NH Blacks and AI/ANs compared with Hispanics and NH Whites.
ExoSTING, an extracellular vesicle loaded with STING agonists, promotes tumor immune surveillance
Authors: Jang Su Chul , Economides Kyriakos D. , Moniz Raymond J. , Sia Chang Ling , Lewis Nuruddeen , McCoy Christine , Zi Tong , Zhang Kelvin , Harrison Rane A. , Lim Joanne , Dey Joyoti , Grenley Marc , Kirwin Katherine , Ross Nikki L. , Bourdeau Raymond , Villiger-Oberbek Agata , Estes Scott , Xu Ke , Sanchez-Salazar Jorge , Dooley Kevin , Dahlberg William K. , Williams Douglas E. , Sathyanarayanan Sriram 
Published: April 2021

AbstractCyclic dinucleotide (CDN) agonists of the STimulator of InterferoN Genes (STING) pathway have shown immune activation and tumor clearance in pre-clinical models. However, CDNs administered intratumorally also promote STING activation leading to direct cytotoxicity of many cell types in the tumor microenvironment (TME), systemic inflammation due to rapid tumor extravasation of the CDN, and immune ablation in the TME. These result in a failure to establish immunological memory. ExoSTING, an engineered extracellular vesicle (EV) exogenously loaded with CDN, enhances the potency of CDN and preferentially activates antigen presenting cells in the TME. Following intratumoral injection, exoSTING was retained within the tumor, enhanced local Th1 responses and recruitment of CD8+ T cells, and generated systemic anti-tumor immunity to the tumor. ExoSTING at therapeutically active doses did not induce systemic inflammatory cytokines, resulting in an enhanced therapeutic window. ExoSTING is a novel, differentiated therapeutic candidate that leverages the natural biology of EVs to enhance the activity of CDNs.
Increased expression of peptides from non-coding genes in cancer proteomics datasets suggests potential tumor neoantigens
Authors: Xiang Rong , Ma Leyao , Yang Mingyu , Zheng Zetian , Chen Xiaofang , Jia Fujian , Xie Fanfan , Zhou Yiming , Li Fuqiang , Wu Kui , Zhu Yafeng 
Published: April 2021

AbstractNeoantigen-based immunotherapy has yielded promising results in clinical trials. However, it is limited to tumor-specific mutations, and is often tailored to individual patients. Identifying suitable tumor-specific antigens is still a major challenge. Previous proteogenomics studies have identified peptides encoded by predicted non-coding sequences in human genome. To investigate whether tumors express specific peptides encoded by non-coding genes, we analyzed published proteomics data from five cancer types including 933 tumor samples and 275 matched normal samples and compared these to data from 31 different healthy human tissues. Our results reveal that many predicted non-coding genes such as DGCR9 and RHOXF1P3 encode peptides that are overexpressed in tumors compared to normal controls. Furthermore, from the non-coding genes-encoded peptides specifically detected in cancers, we predict a large number of “dark antigens” (neoantigens from non-coding genomic regions), which may provide an alternative source of neoantigens beyond standard tumor specific mutations.
Frequency microcomb stabilization via dual-microwave control
Authors: Vinod Abhinav Kumar , Huang Shu-Wei , Yang Jinghui , Yu Mingbin , Kwong Dim-Lee , Wong Chee Wei 
Published: April 2021

AbstractOptical frequency comb technology has been the cornerstone for scientific breakthroughs in precision metrology. In particular, the unique phase-coherent link between microwave and optical frequencies solves the long-standing puzzle of precision optical frequency synthesis. While the current bulk mode-locked laser frequency comb has had great success in extending the scientific frontier, its use in real-world applications beyond the laboratory setting remains an unsolved challenge due to the relatively large size, weight and power consumption. Recently microresonator-based frequency combs have emerged as a candidate solution with chip-scale implementation and scalability. The wider-system precision control and stabilization approaches for frequency microcombs, however, requires external nonlinear processes and multiple peripherals which constrain their application space. Here we demonstrate an internal phase-stabilized frequency microcomb that does not require nonlinear second-third harmonic generation nor optical external frequency references. We demonstrate that the optical frequency can be stabilized by control of two internally accessible parameters: an intrinsic comb offset ξ and the comb spacing frep. Both parameters are phase-locked to microwave references, with phase noise residuals of 55 and 20 mrad respectively, and the resulting comb-to-comb optical frequency uncertainty is 80 mHz or less. Out-of-loop measurements confirm good coherence and stability across the comb, with measured optical frequency instability of 2 × 10−11 at 20-second gate time. Our measurements are supported by analytical theory including the cavity-induced modulation instability. We further describe an application of our technique in the generation of low noise microwaves and demonstrate noise suppression of the repetition rate below the microwave stabilization limit achieved.
Acoustic Willis meta-atom beyond the bounds of passivity and reciprocity
Authors: Cho Choonlae , Wen Xinhua , Park Namkyoo , Li Jensen 
Published: April 2021

AbstractWillis metamaterial enables exotic manipulations of acoustic waves with a precise combination of bulk modulus, mass density, and Willis parameters. While the realization of unrestricted and completely decoupled constitutive parameters would extend the horizon of future applications, the restriction of passivity and reciprocity dictate a hard bound in the values of achievable polarizabilities and correlations between them. Here, we break the bound of passivity and reciprocity by instituting a basis and independent kernel for each constitutive polarization in a virtualized metamaterial platform, active metamaterials realizing artificial polarization with the digital convolution. We demonstrate decoupled control of all four constitutive parameters in a nonreciprocal regime, at the same time achieving values of polarizabilities beyond the passivity limit. Broadband, flat-response nonreciprocal Willis coupling is also demonstrated with analytically designed causal frequency dispersion. Our approach will be useful for nonreciprocal wave manipulation and communication for broadband operation.
Understanding the hierarchical behavior of Bi2WO6 with enhanced photocatalytic nitrogen fixation activity
Authors: Bao Liang , Yuan Yong-jun , Zhang Huaiwei , Zhang Xuefeng , Xu Gang 
Published: April 2021

The hierarchical Bi2WO6 nanostructures exhibit an excellent photocatalytic nitrogen fixation rate due to chemisorption on the hierarchical structures and enhanced surface oxygen vacancies (OVs).