bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiphysics Modeling of a Brittle‐Ductile Lithosphere: 2. Semi‐brittle, Semi‐ductile Deformation and Damage Rheology
Authors: Jacquey Antoine B. , Cacace Mauro
Published: December 2019

The brittle‐ductile transition is a domain of finite extent characterized by high differential stress where both brittle and ductile deformation are likely to occur. Understanding its depth location, extent, and stability through time is of relevance for diverse applications including subduction dynamics, mantle‐surface interactions, and, more recently, proper targeting of high‐enthalpy unconventional geothermal resources, where local thermal conditions may activate ductile creep at shallower depths than expected. In this contribution, we describe a thermodynamically consistent physical framework and its numerical implementation, therefore extending the formulation of the companion paper Jacquey and Cacace (2020, https://doi.org/10.1029/2019JB018474) to model thermo‐hydro‐mechanical coupled processes responsible for the occurrence of transitional semi‐brittle, semi‐ductile behavior in porous rocks. We make use of a damage rheology to account for the macroscopic effects of microstructural processes leading to brittle‐like material weakening and of a rate‐dependent plastic model to account for ductile material behavior. Our formulation additionally considers the role of porosity and its evolution during loading in controlling the volumetric mechanical response of a stressed rock. By means of dedicated applications, we discuss how our damage poro‐visco‐elasto‐viscoplastic rheology can effectively reconcile the style of localized deformation under different confining pressure conditions as well as the bulk macroscopic material response as recorded by laboratory experiments under full triaxial conditions.
The Generation of Nonlinear Internal Waves in the South China Sea: A Three‐Dimensional, Nonhydrostatic Numerical Study
Authors: Lai Zhigang , Jin Guangzhen , Huang Yongmao , Chen Haiyun , Shang Xiaodong , Xiong Xuejun
Published: December 2019

The generation of nonlinear internal waves (NLIWs) by stratified tidal flow over an isolated topography has been a subject of research for many years. However, the enhanced complexity of the dynamics as a consequence of flow over two topographical features has been less studied and understood. Here, we report results of the generation of type‐A and type‐B NLIWs in the South China Sea that originate from a double‐ridge system. Based on a realistic three‐dimensional nonhydrostatic simulation, it is found that type‐A NLIWs are generated at the western ridge through the mechanism of internal tide release, while the generation of type‐B NLIWs occurs at the eastern ridge as a consequence of internal wave interaction. Associated with the ridge height, separation distance, and modulated tidal forcing, the generation of type‐B NLIWs is strongly modified by the resonant process between the two ridges. As a result, type‐A and type‐B NLIWs appear in the observations with alternating large and small amplitudes. In addition, with a detailed knowledge of the generation, it is also found that the different arrival time of these waves could be due to their different generation times. Finally, the reflection/transmission of type‐B NLIWs at the subcritical western ridge is suggested as a key feature of resonance. However, it is governed by hydraulically controlled flow instead of the ratio of the local topographic slope to the internal wave beam angle.
Interannual Variability of the Natal Pulse
Authors: Yamagami Yoko , Tozuka Tomoki , Qiu Bo
Published: December 2019

Satellite altimetry data and high‐resolution model output are used to investigate the mechanism of interannual variations of the solitary meander in the Agulhas Current, called the Natal Pulse. It is shown that most of the Natal Pulses are triggered by anticyclonic eddies originating from the Southeast Madagascar Current (SEMC) and anticyclonic eddies of the Mozambique Channel are the secondary source. In addition to the barotropic conversion suggested by previous studies, the advection of eddy kinetic energy (EKE) plays a statistically significant role in the growth of the Natal Pulse. The number of anticyclonic eddies arriving at the Natal Bight largely explains the interannual variations in the Natal Pulse. The barotropic conversion from the SEMC, whose interannual variations are likely related to the remote wind forcing, is the main EKE source and corresponds well with the interannual variations of anticyclonic eddies generated off the southern coast of Madagascar. It is also shown that the interannual variations of the Natal Pulse are linked to large‐scale wind variability in the southern Indian Ocean.
Alkalinity in Tidal Tributaries of the Chesapeake Bay
Authors: Najjar Raymond G. , Herrmann Maria , Cintrón Del Valle Sebastián M. , Friedman Jaclyn R. , Friedrichs Marjorie A.M. , Harris Lora A. , Shadwick Elizabeth H. , Stets Edward G. , Woodland Ryan J.
Published: December 2019

Despite the important role of alkalinity in estuarine carbon cycling, the seasonal and decadal variability of alkalinity, particularly within multiple tidal tributaries of the same estuary, is poorly understood. Here we analyze more than 25,000 alkalinity measurements, mostly from the 1980s and 1990s, in the major tidal tributaries of the Chesapeake Bay, a large, coastal‐plain estuary of eastern North America. The long‐term means of alkalinity in tidal‐fresh waters vary by a factor of 6 among seven tidal tributaries, reflecting the alkalinity of nontidal rivers draining to these estuaries. At 25 stations, mostly in the Potomac River Estuary, we find significant long‐term increasing trends that exceed the trends in the nontidal rivers upstream of those stations. Box model calculations in the Potomac River Estuary indicate that the main cause of the estuarine trends is a declining alkalinity sink. The magnitude of this sink is consistent with a simple model of calcification by the invasive bivalve Corbicula fluminea. More generally, in tidal tributaries fed by high‐alkalinity nontidal rivers, alkalinity is consumed, with sinks ranging from 8% to 27% of the upstream input. In contrast, tidal tributaries that are fed by low‐alkalinity nontidal rivers have sources of alkalinity amounting to 34% to 171% of the upstream input. For a single estuarine system, the Chesapeake Bay has diverse alkalinity dynamics and can thus serve as a laboratory for studying the numerous processes influencing alkalinity among the world's estuaries.
First 10 Months of TGF Observations by ASIM
Authors: Østgaard N. , Neubert T. , Reglero V. , Ullaland K. , Yang S. , Genov G. , Marisaldi M. , Mezentsev A. , Kochkin P. , Lehtinen N. , Sarria D. , Qureshi B. H. , Solberg A. , Maiorana C. , Albrechtsen K. , Budtz‐Jørgensen C. , Kuvvetli I. , Christiansen F. , Chanrion O. , Heumesser M. , Navarro‐Gonzalez J. , Connell P. , Eyles C. , Christian H. , Al‐nussirat S.
Published: December 2019

The Atmosphere‐Space Interactions Monitor (ASIM) was launched to the International Space Station on 2 April 2018. The ASIM payload consists of two main instruments, the Modular X‐ray and Gamma‐ray Sensor (MXGS) for imaging and spectral analysis of Terrestrial Gamma‐ray Flashes (TGFs) and the Modular Multi‐spectral Imaging Array for detection, imaging, and spectral analysis of Transient Luminous Events and lightning. ASIM is the first space mission designed for simultaneous observations of Transient Luminous Events, TGFs, and optical lightning. During the first 10 months of operation (2 June 2018 to 1 April 2019) the MXGS has observed 217 TGFs. In this paper we report several unprecedented measurements and new scientific results obtained by ASIM during this period: (1) simultaneous TGF observations by Fermi Gamma‐ray Burst Monitor and ASIM MXGS revealing the very good detection capability of ASIM MXGS and showing substructures in the TGF, (2) TGFs and Elves produced during the same lightning flash and even simultaneously have been observed, (3) first imaging of TGFs giving a unique source location, (4) strong statistical support for TGFs being produced during the upward propagation of a leader just before a large current pulse heats up the channel and emits a strong optical pulse, and (5) the t50 duration of TGFs observed from space is shorter than previously reported.
Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice
Authors: Dieterich Andrew , Srivastava Prachi , Sharif Aitesam , Stech Karina , Floeder Joseph , Yohn Samantha E. , Samuels Benjamin A.
Published: December 2019

Behavioral approaches utilizing rodents to study mood disorders have focused primarily on negative valence behaviors associated with potential threat (anxiety-related behaviors). However, for disorders such as depression, positive valence behaviors that assess reward processing may be more translationally valid and predictive of antidepressant treatment outcome. Chronic corticosterone (CORT) administration is a well-validated pharmacological stressor that increases avoidance in negative valence behaviors associated with anxiety1–4. However, whether chronic stress paradigms such as CORT administration also lead to deficits in positive valence behaviors remains unclear. We treated male C57BL/6J mice with chronic CORT and assessed both negative and positive valence behaviors. We found that CORT induced avoidance in the open field and NSF. Interestingly, CORT also impaired instrumental acquisition, reduced sensitivity to a devalued outcome, reduced breakpoint in progressive ratio, and impaired performance in probabilistic reversal learning. Taken together, these results demonstrate that chronic CORT administration at the same dosage both induces avoidance in negative valence behaviors associated with anxiety and impairs positive valence behaviors associated with reward processing. These data suggest that CORT administration is a useful experimental system for preclinical approaches to studying stress-induced mood disorders.
Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification
Authors: Hwang Charles , Marini Simone , Huber Amanda K. , Stepien David M. , Sorkin Michael , Loder Shawn , Pagani Chase A. , Li John , Visser Noelle D. , Vasquez Kaetlin , Garada Mohamed A. , Li Shuli , Xu Jiajia , Hsu Ching-Yun , Yu Paul B. , James Aaron W. , Mishina Yuji , Agarwal Shailesh , Li Jun , Levi Benjamin
Published: December 2019

Heterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone. Based on these clinical observations, we set out to examine the role of vascular signaling in HO. Vascular endothelial growth factor A (VEGFA) has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis. Our findings, using a validated mouse model of HO, demonstrate that HO lesions are highly vascular, and that VEGFA is critical to ectopic bone formation, despite lacking a contribution of endothelial cells within the developing anlagen.
Metabolic rewiring and redox alterations in malignant pleural mesothelioma
Authors: Urso Loredana , Cavallari Ilaria , Sharova Evgeniya , Ciccarese Francesco , Pasello Giulia , Ciminale Vincenzo
Published: December 2019

Malignant pleural mesothelioma (MPM) is a rare malignancy of mesothelial cells with increasing incidence, and in many cases, dismal prognosis due to its aggressiveness and lack of effective therapies. Environmental and occupational exposure to asbestos is considered the main aetiological factor for MPM. Inhaled asbestos fibres accumulate in the lungs and induce the generation of reactive oxygen species (ROS) due to the presence of iron associated with the fibrous silicates and to the activation of macrophages and inflammation. Chronic inflammation and a ROS-enriched microenvironment can foster the malignant transformation of mesothelial cells. In addition, MPM cells have a highly glycolytic metabolic profile and are positive in18F-FDG PET analysis. Loss-of-function mutations of BRCA-associated protein 1 (BAP1) are a major contributor to the metabolic rewiring of MPM cells. A subset of MPM tumours show loss of the methyladenosine phosphorylase (MTAP) locus, resulting in profound alterations in polyamine metabolism, ATP and methionine salvage pathways, as well as changes in epigenetic control of gene expression. This review provides an overview of the perturbations in metabolism and ROS homoeostasis of MPM cells and the role of these alterations in malignant transformation and tumour progression.
All-trans retinoic acid enhances, and a pan-RAR antagonist counteracts, the stem cell promoting activity of EVI1 in acute myeloid leukemia
Authors: Nguyen Chi Huu , Bauer Katharina , Hackl Hubert , Schlerka Angela , Koller Elisabeth , Hladik Anastasiya , Stoiber Dagmar , Zuber Johannes , Staber Philipp B. , Hoelbl-Kovacic Andrea , Purton Louise E. , Grebien Florian , Wieser Rotraud
Published: December 2019

Ecotropic virus integration site 1 (EVI1), whose overexpression characterizes a particularly aggressive subtype of acute myeloid leukemia (AML), enhanced anti-leukemic activities of all-trans retinoic acid (atRA) in cell lines and patient samples. However, the drivers of leukemia formation, therapy resistance, and relapse are leukemic stem cells (LSCs), whose properties were hardly reflected in these experimental setups. The present study was designed to address the effects of, and interactions between, EVI1 and retinoids in AML LSCs. We report that Evi1 reduced the maturation of leukemic cells and promoted the abundance, quiescence, and activity of LSCs in an MLL-AF9-driven mouse model of AML. atRA further augmented these effects in an Evi1 dependent manner. EVI1 also strongly enhanced atRA regulated gene transcription in LSC enriched cells. One of their jointly regulated targets, Notch4, was an important mediator of their effects on leukemic stemness. In vitro exposure of leukemic cells to a pan-RAR antagonist caused effects opposite to those of atRA. In vivo antagonist treatment delayed leukemogenesis and reduced LSC abundance, quiescence, and activity in Evi1high AML. Key results were confirmed in human myeloid cell lines retaining some stem cell characteristics as well as in primary human AML samples. In summary, our study is the first to report the importance of EVI1 for key properties of AML LSCs. Furthermore, it shows that atRA enhances, and a pan-RAR antagonist counteracts, the effects of EVI1 on AML stemness, thus raising the possibility of using RAR antagonists in the therapy of EVI1high AML.
Circ_0001955 facilitates hepatocellular carcinoma (HCC) tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11
Authors: Yao Zhicheng , Xu Ruiyun , Yuan Lin , Xu Mingxing , Zhuang Haiyun , Li Yanjie , Zhang Yi , Lin Nan
Published: December 2019

Circular RNAs (circRNAs) have been increasingly demonstrated to function as novel promising therapeutic RNA molecules for diverse human diseases, including cancer. Although the important role of circRNAs has been well documented in HCC, the complex mechanisms of circRNAs in HCC need to be elucidated. Here, a novel circRNA circ_0001955 was identified from three GSE datasets (GSE7852, GSE94508, and GSE97322) as a differentially expressed circRNA between HCC and normal samples. We revealed that circ_0001955, TRAF6 and MAPK11 levels were increased, while miR-516a-5p levels were decreased in HCC tumor tissues compared to adjacent normal tissues. Knockdown of circ_0001955 repressed HCC tumor growth in vitro and in vivo, while overexpression of circ_0001955 exhibited the opposite effect. Circ_0001955 was identified as a sponge for miR-145-5p and miR-516a-5p, and TRAF6 and MAPK11 were demonstrated to be two target genes of miR-516a-5p. In conclusion, circ_0001955 facilitated HCC tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11 expression.
A cysteine near the C-terminus of UCH-L1 is dispensable for catalytic activity but is required to promote AKT phosphorylation, eIF4F assembly, and malignant B-cell survival
Authors: Hussain Sajjad , Bedekovics Tibor , Ali Asma , Zaid Omar , May Danielle G. , Roux Kyle J. , Galardy Paul J.
Published: December 2019

The enzyme UCH-L1 is a neuro-endocrine and germinal center B-cell marker that contributes to the development and aggressive behavior of mature B-cell malignancies. While mutations in this enzyme have been associated with Parkinson’s disease, relatively little is known about the molecular features associated with the biochemical activities of UCH-L1. Here we use a survival-based complementation assay and site-directed mutagenesis and identify a novel role for the C-terminus of UCH-L1 in supporting cell survival. The C220 residue is required for UCH-L1 to promote the assembly of mTOR complex 2 and phosphorylation of the pro-survival kinase AKT. While this residue was previously described as a potential farnesylation site, destruction of the putative CAAX motif by adding a C-terminal epitope tag did not interfere with cell survival, indicating an alternate mechanism. We used proximity-based proteomics comparing the proteomes of wild-type and C220S UCH-L1 and identified a selective loss of association with RNA-binding proteins including components of the translation initiation machinery. As a consequence, the C220S mutant did not promote the assembly of the eIF4F complex. These data identify a novel role for the C-terminus of UCH-L1 in supporting pro-survival and metabolic activities in malignant B-cells. This finding may lead to the development of therapeutics with selective activity towards malignancy that potentially avoid neuronal toxicities.
Bioinspired design of flexible armor based on chiton scales
Authors: Connors Matthew , Yang Ting , Hosny Ahmed , Deng Zhifei , Yazdandoost Fatemeh , Massaadi Hajar , Eernisse Douglas , Mirzaeifar Reza , Dean Mason N. , Weaver James C. , Ortiz Christine , Li Ling
Published: December 2019

Man-made armors often rely on rigid structures for mechanical protection, which typically results in a trade-off with flexibility and maneuverability. Chitons, a group of marine mollusks, evolved scaled armors that address similar challenges. Many chiton species possess hundreds of small, mineralized scales arrayed on the soft girdle that surrounds their overlapping shell plates. Ensuring both flexibility for locomotion and protection of the underlying soft body, the scaled girdle is an excellent model for multifunctional armor design. Here we conduct a systematic study of the material composition, nanomechanical properties, three-dimensional geometry, and interspecific structural diversity of chiton girdle scales. Moreover, inspired by the tessellated organization of chiton scales, we fabricate a synthetic flexible scaled armor analogue using parametric computational modeling and multi-material 3D printing. This approach allows us to conduct a quantitative evaluation of our chiton-inspired armor to assess its orientation-dependent flexibility and protection capabilities.
New insects feeding on dinosaur feathers in mid-Cretaceous amber
Authors: Gao Taiping , Yin Xiangchu , Shih Chungkun , Rasnitsyn Alexandr P. , Xu Xing , Chen Sha , Wang Chen , Ren Dong
Published: December 2019

Due to a lack of Mesozoic fossil records, the origins and early evolution of feather-feeding behaviors by insects are obscure. Here, we report ten nymph specimens of a new lineage of insect, Mesophthirus engeli gen et. sp. nov. within Mesophthiridae fam. nov. from the mid-Cretaceous (ca. 100 Mya) Myanmar (Burmese) amber. This new insect clade shows a series of ectoparasitic morphological characters such as tiny wingless body, head with strong chewing mouthparts, robust and short antennae having long setae, legs with only one single tarsal claw associated with two additional long setae, etc. Most significantly, these insects are preserved with partially damaged dinosaur feathers, the damage of which was probably made by these insects’ integument-feeding behaviors. This finding demonstrates that feather-feeding behaviors of insects originated at least in mid-Cretaceous, accompanying the radiation of feathered dinosaurs including early birds.
Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn’s disease
Authors: Ziegler Jörn F. , Böttcher Chotima , Letizia Marilena , Yerinde Cansu , Wu Hao , Freise Inka , Rodriguez-Sillke Yasmina , Stoyanova Ani K. , Kreis Martin E. , Asbach Patrick , Kunkel Desiree , Priller Josef , Anagnostopoulos Ioannis , Kühl Anja A. , Miehle Konstanze , Stumvoll Michael , Tran Florian , Fredrich Broder , Forster Michael , Franke Andre , Bojarski Christian , Glauben Rainer , Löscher Britt-Sabina , Siegmund Britta , Weidinger Carl
Published: December 2019

Leptin has been shown to modulate intestinal inflammation in mice. However, clinical evidence regarding its immune-stimulatory potential in human Crohn’s disease remains sparse. We here describe a patient with the unique combination of acquired generalized lipodystrophy and Crohn’s disease (AGLCD) featuring a lack of adipose tissue, leptin deficiency and intestinal inflammation. Using mass and flow cytometry, immunohistochemistry and functional metabolic analyses, the AGLCD patient was compared to healthy individuals and Crohn’s disease patients regarding immune cell composition, function and metabolism and the effects of recombinant N-methionylleptin (rLeptin) were evaluated. We provide evidence that rLeptin exerts diverse pro-inflammatory effects on immune cell differentiation and function, including the metabolic reprogramming of immune cells and the induction of TNFα, ultimately aggravating Crohn’s disease in the AGLCD patient, which can be reversed by anti-TNFα therapy. Our results indicate that leptin is required for human immune homeostasis and contributes to autoimmunity in a TNFα-dependent manner.
Active generation and magnetic actuation of microrobotic swarms in bio-fluids
Authors: Yu Jiangfan , Jin Dongdong , Chan Kai-Fung , Wang Qianqian , Yuan Ke , Zhang Li
Published: December 2019

In nature, various types of animals will form self-organised large-scale structures. Through designing wireless actuation methods, microrobots can emulate natural swarm behaviours, which have drawn extensive attention due to their great potential in biomedical applications. However, as the prerequisite for their in-vivo applications, whether microrobotic swarms can take effect in bio-fluids with complex components has yet to be fully investigated. In this work, we first categorise magnetic active swarms into three types, and individually investigate the generation and navigation behaviours of two types of the swarms in bio-fluids. The influences of viscosities, ionic strengths and mesh-like structures are studied. A strategy is then proposed to select the optimised swarms in different fluidic environments based on their physical properties, and the results are further validated in various bio-fluids. Moreover, we also realise the swarm generation and navigation in bovine eyeballs, which also validates the proposed prediction in the ex-vivo environment.
Androgen receptor gene expression in primary breast cancer
Authors: Vidula Neelima , Yau Christina , Wolf Denise , Rugo Hope S.
Published: December 2019

We studied androgen receptor (AR) gene expression in primary breast cancer (BC) to determine associations with clinical characteristics and outcomes in the I-SPY 1 study. AR was evaluated in I-SPY 1 (n = 149) using expression microarrays. Associations of AR with clinical and tumor features were determined using the Wilcoxon rank sum test (two-level factors) or the Kruskal–Wallis test (multi-level factors). We identified an optimal AR cut-point to maximize recurrence-free survival (RFS) differences between AR biomarker stratified groups, and assessed the association between the AR stratified groups and RFS using the Cox proportional hazard model. Pearson correlations between AR and selected genes were determined in I-SPY 1, METABRIC (n = 1992), and TCGA (n = 817). AR was lower in triple negative BC vs. hormone receptor positive (HR+)/HER2− and HER2+ disease (p < 0.00001), and lower in basal-like BC (p < 0.00001). AR was higher in grade I/II vs. III tumors (p < 0.00001), in patients >age 50 (p = 0.05), and in node negative disease (p = 0.006). Higher AR was associated with better RFS (p = 0.0007), which remained significant after receptor subtype adjustment (p = 0.01). AR correlated with expression of luminal, HER2, and steroid hormone genes. AR expression was related to clinicopathologic features, intrinsic subtype, and correlated with improved outcome.
FDA oversight of NSIGHT genomic research: the need for an integrated systems approach to regulation
Authors: Milko Laura V. , Chen Flavia , Chan Kee , Brower Amy M. , Agrawal Pankaj B. , Beggs Alan H. , Berg Jonathan S. , Brenner Steven E. , Holm Ingrid A. , Koenig Barbara A. , Parad Richard B. , Powell Cynthia M. , Kingsmore Stephen F.
Published: December 2019

The National Institutes of Health (NIH) funded the Newborn Sequencing In Genomic medicine and public HealTh (NSIGHT) Consortium to investigate the implications, challenges, and opportunities associated with the possible use of genomic sequence information in the newborn period. Following announcement of the NSIGHT awardees in 2013, the Food and Drug Administration (FDA) contacted investigators and requested that pre-submissions to investigational device exemptions (IDE) be submitted for the use of genomic sequencing under Title 21 of the Code of Federal Regulations (21 CFR) part 812. IDE regulation permits clinical investigation of medical devices that have not been approved by the FDA. To our knowledge, this marked the first time the FDA determined that NIH-funded clinical genomic research projects are subject to IDE regulation. Here, we review the history of and rationale behind FDA oversight of clinical research and the NSIGHT Consortium’s experiences in navigating the IDE process. Overall, NSIGHT investigators found that FDA’s application of existing IDE regulations and medical device definitions aligned imprecisely with the aims of publicly funded exploratory clinical research protocols. IDE risk assessments by the FDA were similar to, but distinct from, protocol risk assessments conducted by local Institutional Review Boards (IRBs), and had the potential to reflect novel oversight of emerging genomic technologies. However, the pre-IDE and IDE process delayed the start of NSIGHT research studies by an average of 10 months, and significantly limited the scope of investigation in two of the four NIH approved projects. Based on the experience of the NSIGHT Consortium, we conclude that policies and practices governing the development and use of novel genomic technologies in clinical research urgently need clarification in order to mitigate potentially conflicting or redundant oversight by IRBs, NIH, FDA, and state authorities.
Coat-and-print patterning of silver nanowires for flexible and transparent electronics
Authors: Li Weiwei , Meredov Azat , Shamim Atif
Published: December 2019

Silver nanowires (Ag NWs) possess excellent optoelectronic properties, which have led to many technology-focused applications of transparent and flexible electronics. Many of these applications require patterning of Ag NWs into desired shapes, for which mask-based and printing-based techniques have been developed and widely used. However, there are still several limitations associated to these techniques. These limitations, such as complicated patterning procedures, limited patterning area, and compromised optical transparency, hamper the efficient fabrication of high-performance Ag NW patterns. Here, we propose a coat-and-print approach for effectively patterning Ag NWs. We printed a polymer-based ink on the spin-coated Ag NW films. The ink acts as a protective layer to help remove excess Ag NWs from the substrate and then dissolves itself into an organic solvent. In this way, we can take advantage of both coating-based techniques (lead to Ag NWs with high transparency) and printing-based techniques (efficiently pattern diverse shapes). The resultant Ag NW patterns exhibit comparable conductivity (sheet resistance: 7.1 to 30 Ohm/sq) and transparency (transmittance: 84 to 95% at λ = 550 nm) to those made by conventional coating methods. In addition, the patterned Ag NWs exhibit robust mechanical stability and reliability, surviving extensive bending and peeling tests. Due to higher conductivity, efficient patterning ability and inherent transparency, this material system and application method is highly suitable for transparent and flexible electronics. As a proof of concept, this research demonstrates a wide-band antenna, operating in the mm-wave range that includes the 5G communication band. The proposed antenna exhibits a wide bandwidth of 26 GHz (from 17.9 GHz to 44 GHz), robust return loss under 1000 cyclic bending (bending radius of 3.5 mm), and decent transparency over the entire visible wavelength (86.8% transmittance at λ = 550 nm). This work’s promising results indicate that this method can be adapted for roll-to-roll manufacturing to efficiently produce patterned and optically transparent devices.
SMN complex member Gemin3 self-interacts and has a functional relationship with ALS-linked proteins TDP-43, FUS and Sod1
Authors: Cacciottolo Rebecca , Ciantar Joanna , Lanfranco Maia , Borg Rebecca M. , Vassallo Neville , Bordonné Rémy , Cauchi Ruben J.
Published: December 2019

The predominant motor neuron disease in infants and adults is spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), respectively. SMA is caused by insufficient levels of the Survival Motor Neuron (SMN) protein, which operates as part of the multiprotein SMN complex that includes the DEAD-box RNA helicase Gemin3/DDX20/DP103. C9orf72, SOD1, TDP-43 and FUS are ranked as the four major genes causing familial ALS. Accumulating evidence has revealed a surprising molecular overlap between SMA and ALS. Here, we ask the question of whether Drosophila can also be exploited to study shared pathogenic pathways. Focusing on motor behaviour, muscle mass and survival, we show that disruption of either TBPH/TDP-43 or Caz/FUS enhance defects associated with Gemin3 loss-of-function. Gemin3-associated neuromuscular junction overgrowth was however suppressed. Sod1 depletion had a modifying effect in late adulthood. We also show that Gemin3 self-interacts and Gem3ΔN, a helicase domain deletion mutant, retains the ability to interact with its wild-type counterpart. Importantly, mutant:wild-type dimers are favoured more than wild-type:wild-type dimers. In addition to reinforcing the link between SMA and ALS, further exploration of mechanistic overlaps is now possible in a genetically tractable model organism. Notably, Gemin3 can be elevated to a candidate for modifying motor neuron degeneration.
Monocrystalline Silicon Carbide Disk Resonators on Phononic Crystals with Ultra-Low Dissipation Bulk Acoustic Wave Modes
Authors: Hamelin Benoit , Yang Jeremy , Daruwalla Anosh , Wen Haoran , Ayazi Farrokh
Published: December 2019

Micromechanical resonators with ultra-low energy dissipation are essential for a wide range of applications, such as navigation in GPS-denied environments. Routinely implemented in silicon (Si), their energy dissipation often reaches the quantum limits of Si, which can be surpassed by using materials with lower intrinsic loss. This paper explores dissipation limits in 4H monocrystalline silicon carbide-on-insulator (4H-SiCOI) mechanical resonators fabricated at wafer-level, and reports on ultra-high quality-factors (Q) in gyroscopic-mode disk resonators. The SiC disk resonators are anchored upon an acoustically-engineered Si substrate containing a phononic crystal which suppresses anchor loss and promises QANCHOR near 1 Billion by design. Operating deep in the adiabatic regime, the bulk acoustic wave (BAW) modes of solid SiC disks are mostly free of bulk thermoelastic damping. Capacitively-transduced SiC BAW disk resonators consistently display gyroscopic m = 3 modes with Q-factors above 2 Million (M) at 6.29 MHz, limited by surface TED due to microscale roughness along the disk sidewalls. The surface TED limit is revealed by optical measurements on a SiC disk, with nanoscale smooth sidewalls, exhibiting Q = 18 M at 5.3 MHz, corresponding to f · Q = 9 · 1013 Hz, a 5-fold improvement over the Akhiezer limit of Si. Our results pave the path for integrated SiC resonators and resonant gyroscopes with Q-factors beyond the reach of Si.
New endoscopic procedure for bladder wall closure: results from the porcine model
Authors: Oliveira Carlos , Barros Alexandre A. , Reis Rui L. , Correia-Pinto Jorge , Lima Estêvão
Published: December 2019

Upper urinary tract urothelial carcinomas are usually managed by radical nephroureterectomy (RNU), often followed by intravesical chemotherapy to minimize recurrence. Open surgery is the gold standard procedure for RNU, but it associates with high morbidity, and it has been increasingly replaced by minimally invasive strategies, such as laparoscopy and endoscopy. Although effective, endoscopic ureteral excision leaves the bladder unsutured, increasing the risk of tumor spillage, and precluding the immediate administration of intravesical chemotherapy. Here we describe a new method to close the bladder wall after ureteral excision, using barbed sutures via the endoscopic access. Our results in 8 female pigs demonstrate that this method is effective to close the bladder wall. The procedure was completed in a median time of 24 min, and no adverse events were registered in the follow-up or at the three-week necropsy. This technique improves a previous approach described by our group because the device is more flexible and allows to tie the knots inside the bladder. Barbed sutures have been used in the clinical practice for other types of surgeries, and therefore this method can further be adapted to human patients with no safety concerns. Its use may allow to administer intravesical chemotherapy, which reduces tumor recurrence and improves patient outcomes.
Ion transporter gene expression is linked to the thermal sensitivity of calcification in the reef coral Stylophora pistillata
Authors: Bernardet C. , Tambutté E. , Techer N. , Tambutté S. , Venn A. A.
Published: December 2019

Coral calcification underpins biodiverse reef ecosystems, but the physiology underlying the thermal sensitivity of corals to changing seawater temperatures remains unclear. Furthermore, light is also a key factor in modulating calcification rates, but a mechanistic understanding of how light interacts with temperature to affect coral calcification is lacking. Here, we characterized the thermal performance curve (TPC) of calcification of the wide-spread, model coral species Stylophora pistillata, and used gene expression analysis to investigate the role of ion transport mechanisms in thermally-driven declines in day and nighttime calcification. Focusing on genes linked to transport of dissolved inorganic carbon (DIC), calcium and H+, our study reveals a high degree of coherence between physiological responses (e.g. calcification and respiration) with distinct gene expression patterns to the different temperatures in day and night conditions. At low temperatures, calcification and gene expression linked to DIC transport processes were downregulated, but showed little response to light. By contrast, at elevated temperature, light had a positive effect on calcification and stimulated a more functionally diverse gene expression response of ion transporters. Overall, our findings highlight the role of mechanisms linked to DIC, calcium and H+ transport in the thermal sensitivity of coral calcification and how this sensitivity is influenced by light.
Laundry wastewater treatment using a combination of sand filter, bio-char and teff straw media
Authors: Yaseen Zaher Mundher , Zigale Tibebu Tsegaye , Tiyasha  , D. Ravi Kumar , Salih Sinan Q. , Awasthi Suyash , Tung Tran Minh , Al-Ansari Nadhir , Bhagat Suraj Kumar
Published: December 2019

Numerous researchers have expressed concern over the emerging water scarcity issues around the globe. Economic water scarcity is severe in the developing countries; thus, the use of inexpensive wastewater treatment strategies can help minimize this issue. An abundant amount of laundry wastewater (LWW) is generated daily and various wastewater treatment researches have been performed to achieve suitable techniques. This study addressed this issue by considering the economic perspective of the treatment technique through the selection of easily available materials. The proposed technique is a combination of locally available absorbent materials such as sand, biochar, and teff straw in a media. Biochar was prepared from eucalyptus wood, teff straw was derived from teff stem, and sand was obtained from indigenous crushed stones. In this study, the range of laundry wastewater flow rate was calculated as 6.23–17.58 m3/day; also studied were the efficiency of the media in terms of the removal percentage of contamination and the flux rate. The performances of biochar and teff straw were assessed based on the operation parameters and the percentage removal efficiency at different flux rates; the assessment showed 0.4 L/min flux rate to exhibit the maximum removal efficiency. Chemical oxygen demand, biological oxygen demand, and total alkalinity removal rate varied from 79% to ≥83%; total solids and total suspended solids showed 92% to ≥99% removal efficiency, while dissolved oxygen, total dissolved solids, pH, and electrical conductivity showed 22% to ≥62% removal efficiency. The optimum range of pH was evaluated between 5.8–7.1. The statistical analysis for finding the correlated matrix of laundry wastewater parameters showed the following correlations: COD (r = −0.84), TS (r = −0.83), and BOD (r = −0.81), while DO exhibited highest negative correlation. This study demonstrated the prospective of LWW treatment using inexpensive materials. The proposed treatment process involved low-cost materials and exhibited efficiency in the removal of contaminants; its operation is simple and can be reproduced in different scenarios.
The effect of intraoperative imaging on surgical navigation for laparoscopic liver resection surgery
Authors: Teatini Andrea , Pelanis Egidijus , Aghayan Davit L. , Kumar Rahul Prasanna , Palomar Rafael , Fretland Åsmund Avdem , Edwin Bjørn , Elle Ole Jakob
Published: December 2019

Conventional surgical navigation systems rely on preoperative imaging to provide guidance. In laparoscopic liver surgery, insufflation of the abdomen (pneumoperitoneum) can cause deformations on the liver, introducing inaccuracies in the correspondence between the preoperative images and the intraoperative reality. This study evaluates the improvements provided by intraoperative imaging for laparoscopic liver surgical navigation, when displayed as augmented reality (AR). Significant differences were found in terms of accuracy of the AR, in favor of intraoperative imaging. In addition, results showed an effect of user-induced error: image-to-patient registration based on annotations performed by clinicians caused 33% more inaccuracy as compared to image-to-patient registration algorithms that do not depend on user annotations. Hence, to achieve accurate surgical navigation for laparoscopic liver surgery, intraoperative imaging is recommendable to compensate for deformation. Moreover, user annotation errors may lead to inaccuracies in registration processes.
Scaling of species distribution explains the vast potential marine prokaryote diversity
Authors: Eguíluz Victor M. , Salazar Guillem , Fernández-Gracia Juan , Pearman John K. , Gasol Josep M. , Acinas Silvia G. , Sunagawa Shinichi , Irigoien Xabier , Duarte Carlos M.
Published: December 2019

Global ocean expeditions have provided minimum estimates of ocean’s prokaryote diversity, supported by apparent asymptotes in the number of prokaryotes with sampling effort, of about 40,000 species, representing <1% of the species cataloged in the Earth Microbiome Project, despite being the largest habitat in the biosphere. Here we demonstrate that the abundance of prokaryote OTUs follows a scaling that can be represented by a power-law distribution, and as a consequence, we demonstrate, mathematically and through simulations, that the asymptote of rarefaction curves is an apparent one, which is only reached with sample sizes approaching the entire ecosystem. We experimentally confirm these findings using exhaustive repeated sampling of a prokaryote community in the Red Sea and the exploration of global assessments of prokaryote diversity in the ocean. Our findings indicate that, far from having achieved a thorough sampling of prokaryote species abundance in the ocean, global expeditions provide just a start for this quest as the richness in the global ocean is much larger than estimated.
Nano-encapsulated Escherichia coli Divisome Anchor ZipA, and in Complex with FtsZ
Authors: Lee Sarah C. , Collins Richard , Lin Yu-pin , Jamshad Mohammed , Broughton Claire , Harris Sarah A. , Hanson Benjamin S , Tognoloni Cecilia , Parslow Rosemary A. , Terry Ann E. , Rodger Alison , Smith Corinne J. , Edler Karen J. , Ford Robert , Roper David I. , Dafforn Timothy R.
Published: December 2019

The E. coli membrane protein ZipA, binds to the tubulin homologue FtsZ, in the early stage of cell division. We isolated ZipA in a Styrene Maleic Acid lipid particle (SMALP) preserving its position and integrity with native E. coli membrane lipids. Direct binding of ZipA to FtsZ is demonstrated, including FtsZ fibre bundles decorated with ZipA. Using Cryo-Electron Microscopy, small-angle X-ray and neutron scattering, we determine the encapsulated-ZipA structure in isolation, and in complex with FtsZ to a resolution of 1.6 nm. Three regions can be identified from the structure which correspond to, SMALP encapsulated membrane and ZipA transmembrane helix, a separate short compact tether, and ZipA globular head which binds FtsZ. The complex extends 12 nm from the membrane in a compact structure, supported by mesoscale modelling techniques, measuring the movement and stiffness of the regions within ZipA provides molecular scale analysis and visualisation of the early divisome.
A multi-genotype therapeutic human papillomavirus vaccine elicits potent T cell responses to conserved regions of early proteins
Authors: Hancock Gemma , Blight Joshua , Lopez-Camacho Cesar , Kopycinski Jakub , Pocock Mamatha , Byrne Wendy , Price Michael J. , Kemlo Phillip , Evans Ranoromanana Ionitiana , Bloss Angela , Saunders Kathryn , Kirton Richard , Andersson Monique , Hellner Karin , Reyes-Sandoval Arturo , Dorrell Lucy
Published: December 2019

Despite an efficacious prophylactic human papillomavirus (HPV) vaccine there is still a considerable global burden of HPV-related disease. Therapeutic vaccines that could prevent cancers in at-risk women are urgently needed. Most candidate therapeutic vaccines have focused on two high-risk (hr) HPV genotypes, 16 and 18, and two viral targets, E6 and E7, which may limit global coverage and efficacy. We designed the synthetic gene ‘5GHPV3′ by selecting conserved regions from each of the six early proteins and generating consensus sequences to represent five hrHPV genotypes. 5GHPV3 was delivered by plasmid DNA, chimpanzee adenovirus (ChAdOx1) and modified vaccinia Ankara (MVA) vectors in prime-boost regimens to mice. ChAdOx1-5GHPV3 / MVA-5GHPV3 induced higher magnitude and more durable HPV-specific T cell responses than other regimens. Vaccine-induced T cells were polyfunctional and persisted at high frequencies for at least six weeks. Importantly, HPV-specific effector CD8 + T cells were detected in the cervix following systemic administration of ChAdOx1-5GHPV3 / MVA-5GHPV3 and increased in frequency over time, indicating continued trafficking of T cells to the cervix. Finally, T cells specific for 5GHPV3 encoded antigens were detected by IFN-γ Elispot in women with current or past hrHPV infections, confirming the presence of epitopes relevant to natural immune control.
Nanoparticle Contrast-enhanced T1-Mapping Enables Estimation of Placental Fractional Blood Volume in a Pregnant Mouse Model
Authors: Badachhape Andrew A. , Devkota Laxman , Stupin Igor V. , Sarkar Poonam , Srivastava Mayank , Tanifum Eric A. , Fox Karin A. , Yallampalli Chandrasekhar , Annapragada Ananth V. , Ghaghada Ketan B.
Published: December 2019

Non-invasive methods for estimating placental fractional blood volume (FBV) are of great interest for characterization of vascular perfusion in placentae during pregnancy to identify placental insufficiency that may be indicative of local ischemia or fetal growth restriction (FGR). Nanoparticle contrast-enhanced magnetic resonance imaging (CE-MRI) may enable direct placental FBV estimation and may provide a reliable, 3D alternative to assess maternal-side placental perfusion. In this pre-clinical study, we investigated if placental FBV at 14, 16, and 18 days of gestation could be estimated through contrast-enhanced MRI using a long circulating blood-pool liposomal gadolinium contrast agent that does not penetrate the placental barrier. Placental FBV estimates of 0.47 ± 0.06 (E14.5), 0.50 ± 0.04 (E16.5), and 0.52 ± 0.04 (E18.5) were found through fitting pre-contrast and post-contrast T1 values in placental tissue using a variable flip angle method. MRI-derived placental FBV was validated against nanoparticle contrast-enhanced computed tomography (CE-CT) derived placental FBV, where signal is directly proportional to the concentration of iodine contrast agent. The results demonstrate successful estimation of the placental FBV, with values statistically indistinguishable from the CT derived values.
Utility of diffusion tensor imaging for guiding the treatment of lumbar disc herniation by percutaneous transforaminal endoscopic discectomy
Authors: Li Jiaqi , Cui Hao , Liu Zhipeng , Sun Yapeng , Zhang Fei , Sun Yingcai , Zhang Wei
Published: December 2019

The purpose of this study was to evaluate the utility of diffusion tensor imaging (DTI) for guiding the treatment of lumbar disc herniation (LDH) by percutaneous transforaminal endoscopic discectomy (PTED). We collected the clinical data of a total of 19 patients: 10 with unilateral S1 nerve root injury, 6 with unilateral L5 nerve root injury, and 3 with unilateral L5 and S1 nerve root injury. All patients underwent DTI before surgery, 3 days post-surgery, 30 days post-surgery, and 90 days post-surgery. The comparison of the fractional anisotropy (FA) values of compressed lateral nerve roots before surgery and 3, 30, and 90 days post-surgery demonstrated the recovery of nerve roots to be a dynamic process. A significant difference was found in the FA values between compressed lateral nerve roots preoperatively and normal lateral nerve roots before surgery, 3 days post-surgery and 30 days post-surgery (p < 0.05). There was no significant difference in FA values between compressed lateral nerve roots and normal ones 90 days post-surgery (p > 0.05). DTI can be used for the accurate diagnosis of LDH, as well as for postoperative evaluation and prognosis, and it is thus useful for the selection of surgical timing.