bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interdependent Infrastructure as Linked Social, Ecological, and Technological Systems (SETSs) to Address Lock‐in and Enhance Resilience
Authors: Markolf Samuel A. , Chester Mikhail V. , Eisenberg Daniel A. , Iwaniec David M. , Davidson Cliff I. , Zimmerman Rae , Miller Thaddeus R. , Ruddell Benjamin L. , Chang Heejun 
Published: November 2018

AbstractTraditional infrastructure adaptation to extreme weather events (and now climate change) has typically been techno‐centric and heavily grounded in robustness—the capacity to prevent or minimize disruptions via a risk‐based approach that emphasizes control, armoring, and strengthening (e.g., raising the height of levees). However, climate and nonclimate challenges facing infrastructure are not purely technological. Ecological and social systems also warrant consideration to manage issues of overconfidence, inflexibility, interdependence, and resource utilization—among others. As a result, techno‐centric adaptation strategies can result in unwanted tradeoffs, unintended consequences, and underaddressed vulnerabilities. Techno‐centric strategies that lock‐in today's infrastructure systems to vulnerable future design, management, and regulatory practices may be particularly problematic by exacerbating these ecological and social issues rather than ameliorating them. Given these challenges, we develop a conceptual model and infrastructure adaptation case studies to argue the following: (1) infrastructure systems are not simply technological and should be understood as complex and interconnected social, ecological, and technological systems (SETSs); (2) infrastructure challenges, like lock‐in, stem from SETS interactions that are often overlooked and underappreciated; (3) framing infrastructure with a SETS lens can help identify and prevent maladaptive issues like lock‐in; and (4) a SETS lens can also highlight effective infrastructure adaptation strategies that may not traditionally be considered. Ultimately, we find that treating infrastructure as SETS shows promise for increasing the adaptive capacity of infrastructure systems by highlighting how lock‐in and vulnerabilities evolve and how multidisciplinary strategies can be deployed to address these challenges by broadening the options for adaptation.
Probabilistic Surface Heat Flow Estimates Assimilating Paleoclimate History: New Implications for the Thermochemical Structure of Ireland
Authors: Mather Ben , Farrell Thomas , Fullea Javier 
Published: November 2018

AbstractRegions where surface temperature has increased since past glaciation events, such as Ireland, underestimate the heat output of the Earth unless paleoclimate corrections are applied. We apply probabilistic techniques to quantify the uncertainty of 22 paleoclimate‐corrected heat flow estimates in Ireland, which assimilate multiple surface temperature histories associated with 130 ka of glacial oscillation in the British Isles. Heat flow values increase by ∼15 mW/m2 after a paleoclimate correction and provide new insights into the thermochemical structure of the lithosphere. The heat flow regime is broadly delineated by the Iapetus Suture Zone that separates Laurentian to the north and Avalonian terranes to the south (mean surface heat flow of 73 ± 14 and 65 ± 14 mW/m2, respectively). The degree to which heat‐producing elements are partitioned into the uppermost crust is described by the differentiation index of a heat flow province. From Bayesian inversion, we determine that radiogenic elements are substantially more differentiated in the uppermost crust of Laurentia (DI=2.8 ± 1.4) than Avalonia (DI=1.5 ± 1.3), despite a moderately enriched lower crust (0.8 ± 0.3 μW/m3). This is facilitated by a thin yet highly radiogenic layer in the uppermost crust of Laurentia (3.9 ± 1.8 μW/m3). Extrapolating these results across the British Isles and Newfoundland suggests that heat‐producing elements have been more successfully reworked into the upper crust to the north of the Iapetus Suture Zone during continental accretion between Laurentia and Avalonia.
Spectrum of Liver Disease in Hepatitis B Virus (HBV) Patients Co-infected with Human Immunodeficiency Virus (HIV): Results of the HBV-HIV Cohort Study
Authors: Sterling Richard K. , Wahed Abdus S. , King Wendy C. , Kleiner David E. , Khalili Mandana , Sulkowski Mark , Chung Raymond T. , Jain Mamta K. , Lisker-Melman Mauricio , Wong David K. , Ghany Marc G. ,   the HIV-HBV Cohort Study of the Hepatitis B Research Network
Published: November 2018

BACKGROUND:
Because most HBV/HIV co-infected patients on combination antiretroviral therapy (cART) have suppressed HBV DNA and normal liver enzymes, the histologic spectrum of liver disease in HBV/HIV coinfection is poorly defined. To address this gap in knowledge, we conducted a prospective study to comprehensively characterize liver disease severity assessed by liver biopsy in a well-defined cohort of HBV/HIV patients in North America receiving cART.

METHODS:
Adult HIV/HBsAg positive patients on stable cART were recruited. Demographic, clinical, serological, and virological data were collected. Liver histology was assessed by a central pathology committee. The association of demographic, clinical, serologic, and virologic characteristics with liver histology was assessed using logistic regression.

RESULTS:
In this cross-sectional analysis, the mean age of the cohort (N = 139) was 49 years; 92% were male, 51% were non-Hispanic black, 7% had at-risk alcohol use with a median duration of infections of 14 years. The median ALT was 28 IU/L and CD4 count was 568 cells/mm3. Almost all (99%) were on cART. Three-fourths (75%) had undetectable HIV RNA (<20 copies/mL). HBeAg was positive in 62%, HBV DNA was below the limit of quantification (<20 IU/mL) in 57% and <1000 IU/ mL in 80%; 7% had incomplete viral suppression (HBV DNA ≥1000 IU/mL and HIV RNA <20 copies/mL). Liver histology (available in n = 114) showed significant periportal, lobular, and portal inflammation (scores ≥2) in 14%, 31%, and 22% respectively. Over a third (37%) had significant fibrosis (Ishak stage ≥2); 24% had advanced fibrosis (Ishak stage ≥3). Higher ALT (adjusted OR 1.19 per 10 IU/L; 95% CI [1.01, 1.41]; p = 0.03) and lower platelet count (adjusted OR 0.81 per 20,000 mm3; 95% CI [0.67–0.97]; p = 0.02) but not HBV DNA were independently associated with advanced fibrosis.

CONCLUSIONS:
In this cohort of patients with HBV/HIV coinfection receiving long-term cART with viral suppression, we observed significant fibrosis in more than one-third of patients.
Mettl3-mediated m6A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis
Authors: Wu Yunshu , Xie Liang , Wang Mengyuan , Xiong Qiuchan , Guo Yuchen , Liang Yu , Li Jing , Sheng Rui , Deng Peng , Wang Yuan , Zheng Rixin , Jiang Yizhou , Ye Ling , Chen Qianming , Zhou Xuedong , Lin Shuibin , Yuan Quan 
Published: November 2018

AbstractN6-methyladenosine (m6A) is the most abundant epigenetic modification in eukaryotic mRNAs and is essential for multiple RNA processing events during mammalian development and disease control. Here we show that conditional knockout of the m6A methyltransferase Mettl3 in bone marrow mesenchymal stem cells (MSCs) induces pathological features of osteoporosis in mice. Mettl3 loss-of-function results in impaired bone formation, incompetent osteogenic differentiation potential and increased marrow adiposity. Moreover, Mettl3 overexpression in MSCs protects the mice from estrogen deficiency-induced osteoporosis. Mechanistically, we identify PTH (parathyroid hormone)/Pth1r (parathyroid hormone receptor-1) signaling axis as an important downstream pathway for m6A regulation in MSCs. Knockout of Mettl3 reduces the translation efficiency of MSCs lineage allocator Pth1r, and disrupts the PTH-induced osteogenic and adipogenic responses in vivo. Our results demonstrate the pathological outcomes of m6A mis-regulation in MSCs and unveil novel epitranscriptomic mechanism in skeletal health and diseases.
Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer
Authors: Ishaque Naveed , Abba Mohammed L. , Hauser Christine , Patil Nitin , Paramasivam Nagarajan , Huebschmann Daniel , Leupold Jörg Hendrik , Balasubramanian Gnana Prakash , Kleinheinz Kortine , Toprak Umut H. , Hutter Barbara , Benner Axel , Shavinskaya Anna , Zhou Chan , Gu Zuguang , Kerssemakers Jules , Marx Alexander , Moniuszko Marcin , Kozlowski Miroslaw , Reszec Joanna , Niklinski Jacek , Eils Jürgen , Schlesner Matthias , Eils Roland , Brors Benedikt , Allgayer Heike 
Published: November 2018

AbstractIncomplete understanding of the metastatic process hinders personalized therapy. Here we report the most comprehensive whole-genome study of colorectal metastases vs. matched primary tumors. 65% of somatic mutations originate from a common progenitor, with 15% being tumor- and 19% metastasis-specific, implicating a higher mutation rate in metastases. Tumor- and metastasis-specific mutations harbor elevated levels of BRCAness. We confirm multistage progression with new components ARHGEF7/ARHGEF33. Recurrently mutated non-coding elements include ncRNAs RP11-594N15.3, AC010091, SNHG14, 3’ UTRs of FOXP2, DACH2, TRPM3, XKR4, ANO5, CBL, CBLB, the latter four potentially dual protagonists in metastasis and efferocytosis-/PD-L1 mediated immunosuppression. Actionable metastasis-specific lesions include FAT1, FGF1, BRCA2, KDR, and AKT2-, AKT3-, and PDGFRA-3’ UTRs. Metastasis specific mutations are enriched in PI3K-Akt signaling, cell adhesion, ECM and hepatic stellate activation genes, suggesting genetic programs for site-specific colonization. Our results put forward hypotheses on tumor and metastasis evolution, and evidence for metastasis-specific events relevant for personalized therapy.
Scalable high performance radio frequency electronics based on large domain bilayer MoS2
Authors: Gao Qingguo , Zhang Zhenfeng , Xu Xiaole , Song Jian , Li Xuefei , Wu Yanqing 
Published: November 2018

AbstractAtomically-thin layered molybdenum disulfide (MoS2) has attracted tremendous research attention for their potential applications in high performance DC and radio frequency electronics, especially for flexible electronics. Bilayer MoS2 is expected to have higher electron mobility and higher density of states with higher performance compared with single layer MoS2. Here, we systematically investigate the synthesis of high quality bilayer MoS2 by chemical vapor deposition on molten glass with increasing domain sizes up to 200 μm. High performance transistors with optimized high-κ dielectrics deliver ON-current of 427 μA μm−1 at 300 K and a record high ON-current of 1.52 mA μm−1 at 4.3 K. Moreover, radio frequency transistors are demonstrated with an extrinsic high cut-off frequency of 7.2 GHz and record high extrinsic maximum frequency of oscillation of 23 GHz, together with gigahertz MoS2 mixers on flexible polyimide substrate, showing the great potential for future high performance DC and high-frequency electronics.
Myths and reality of HPbI3 in halide perovskite solar cells
Authors: Ke Weijun , Spanopoulos Ioannis , Stoumpos Constantinos C. , Kanatzidis Mercouri G. 
Published: November 2018

AbstractAll-inorganic perovskites have a special place in halide perovskite family because of their potential for better stability. However, the representative cesium lead iodide (CsPbI3) is metastable and spontaneously converts to the non-perovskite structure at room temperature. Here, we demonstrate that what appears to be all-inorganic CsPbI3 stabilized in its perovskite form using the purported intermediate known as hydrogen lead iodide (HPbI3) is, in fact, the hybrid perovskite cesium dimethylammonium lead iodide (Cs1−xDMAxPbI3, x = 0.2 to 0.5). Thus, many of the reported all-inorganic perovskites are actually still hybrid organic-inorganic perovskites, as strongly evidenced by a wide battery of experimental techniques presented here. Solar cells based on the representative composition Cs0.7DMA0.3PbI3 can achieve an average power conversion efficiency of 9.27 ± 1.28% (max 12.62%). These results provide an alternative angle to look at previous results pertaining all-inorganic CsPbI3 while the DMA cation is now revealed as an alternative A site cation.
Microfluidic active loading of single cells enables analysis of complex clinical specimens
Authors: Calistri Nicholas L. , Kimmerling Robert J. , Malinowski Seth W. , Touat Mehdi , Stevens Mark M. , Olcum Selim , Ligon Keith L. , Manalis Scott R. 
Published: November 2018

AbstractA fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, an automated, optically-triggered fluidic system that improves measurement throughput and robustness by controlling entry of individual cells into a measurement channel. We apply active loading to samples over a range of concentrations (1–1000 particles μL−1), demonstrate that measurement time can be decreased by up to 20-fold, and show theoretically that performance of some types of existing single-cell microfluidic devices can be improved by implementing active loading. Finally, we demonstrate how active loading improves clinical feasibility for acute, single-cell drug sensitivity measurements by deploying it to a preclinical setting where we assess patient samples from normal brain, primary and metastatic brain cancers containing a complex, difficult-to-measure mixture of confounding biological debris.
Colorectal cancer liver metastatic growth depends on PAD4-driven citrullination of the extracellular matrix
Authors: Yuzhalin A. E. , Gordon-Weeks A. N. , Tognoli M. L. , Jones K. , Markelc B. , Konietzny R. , Fischer R. , Muth A. , O’Neill E. , Thompson P. R. , Venables P. J. , Kessler B. M. , Lim S. Y. , Muschel R. J. 
Published: November 2018

AbstractCitrullination of proteins, a post-translational conversion of arginine residues to citrulline, is recognized in rheumatoid arthritis, but largely undocumented in cancer. Here we show that citrullination of the extracellular matrix by cancer cell derived peptidylarginine deiminase 4 (PAD4) is essential for the growth of liver metastases from colorectal cancer (CRC). Using proteomics, we demonstrate that liver metastases exhibit higher levels of citrullination and PAD4 than unaffected liver, primary CRC or adjacent colonic mucosa. Functional significance for citrullination in metastatic growth is evident in murine models where inhibition of citrullination substantially reduces liver metastatic burden. Additionally, citrullination of a key matrix component collagen type I promotes greater adhesion and decreased migration of CRC cells along with increased expression of characteristic epithelial markers, suggesting a role for citrullination in promoting mesenchymal-to-epithelial transition and liver metastasis. Overall, our study reveals the potential for PAD4-dependant citrullination to drive the progression of CRC liver metastasis.
Superhydrophobic and Compressible Silica-polyHIPE Covalently Bonded Porous Networks via Emulsion Templating for Oil Spill Cleanup and Recovery
Authors: Mahadik D. B. , Lee Kyu-Yeon , Ghorpade R. V. , Park Hyung-Ho 
Published: November 2018

AbstractWe synthesize porous polyHIPE networks with silanol functionalities in the polyHIPE backbone. These silanol functionalities are used for covalent bonding with silica aerogels embedded in the polyHIPE. Covalent bonding between silica and polyHIPE networks are confirmed using Fourier-transform infrared spectroscopy and scanning electron microscopy. Silica aerogels covalently bonded with polyHIPE network show macroporous and mesoporous morphologies and possess excellent properties like high bendability, high elasticity, superhydrophobicity (~160°), low density (~0.128 g/cm3), and low thermal conductivity (~0.045 W/m·K). Oil absorption from water/oil mixtures and recovery of the absorbed oil (by squeezing) from flexible silica-polyHIPE networks is studied. The silica-polyHIPE is shown to absorb crude oil ~16-times its own weight and can be reused multiple times after recovery. Hence, such materials are very important for oil spill cleanup applications from aqueous systems.
TRPV2 is required for mechanical nociception and the stretch-evoked response of primary sensory neurons
Authors: Katanosaka Kimiaki , Takatsu Satomi , Mizumura Kazue , Naruse Keiji , Katanosaka Yuki 
Published: November 2018

AbstractMechanotransduction plays important roles in many sensory processes, including touch, pain, hearing, and proprioception. However, the molecular mechanisms of mechanical nociception have remained unclear. Here, we showed that elimination of transient receptor potential vanilloid 2 (TRPV2) in mice resulted in the deficit of mechanical nociception due to the lack of mechanosensitivity in a subclass of adult primary sensory neurons (PSNs). The PSN-specific TRPV2-deficient mice showed behavioural impairment of mechanical nociception in tail-pressure and von Frey hair tests, without defects in axonal growth and neuronal composition. Conversely, the mice displayed normal behaviour to noxious heat and non-noxious tactile stimuli. Furthermore, based on the stretch-evoked Ca2+ response of cultured PSNs, we characterised two types of stretch-activated neurons in normal mice; fast-decay high-threshold and slow-decay low-threshold mechanosensitive. The cultured neurons from TRPV2-deficient mice lacked stretch-evoked Ca2+ responses by fast-decay neurons normally activated by high-threshold mechanical stimulation. These results demonstrated that TRPV2 has a critical role in mechanical nociception in the adult somatosensory system.
Gene expression profile of muscle adaptation to high-intensity intermittent exercise training in young men
Authors: Miyamoto-Mikami Eri , Tsuji Katsunori , Horii Naoki , Hasegawa Natsuki , Fujie Shumpei , Homma Toshiyuki , Uchida Masataka , Hamaoka Takafumi , Kanehisa Hiroaki , Tabata Izumi , Iemitsu Motoyuki 
Published: November 2018

AbstractHigh-intensity intermittent exercise training (HIIT) has been proposed as an effective approach for improving both, the aerobic and anaerobic exercise capacity. However, the detailed molecular response of the skeletal muscle to HIIT remains unknown. We examined the effects of the HIIT on the global gene expression in the human skeletal muscle. Eleven young healthy men participated in the study and completed a 6-week HIIT program involving exhaustive 6–7 sets of 20-s cycling periods with 10-s rests. In addition to determining the maximal oxygen uptake ($${\dot{{\rm{V}}}{\rm{O}}}_{2{\rm{\max }}}$$V˙O2max), maximal accumulated oxygen deficit, and thigh muscle cross-sectional area (CSA), muscle biopsy samples were obtained from the vastus lateralis before and after the training to analyse the skeletal muscle transcriptome. The HIIT program significantly increased the$${\dot{{\rm{V}}}{\rm{O}}}_{2{\rm{\max }}}$$V˙O2max, maximal accumulated oxygen deficit, and thigh muscle CSA. The expression of 79 genes was significantly elevated (fold-change >1.2), and that of 73 genes was significantly reduced (fold-change <0.8) after HIIT. Gene ontology analysis of the up-regulated genes revealed that the significantly enriched categories were “glucose metabolism”, “extracellular matrix”, “angiogenesis”, and “mitochondrial membrane”. By providing information about a set of genes in the human skeletal muscle that responds to the HIIT, the study provided insight into the mechanism of skeletal muscle adaptation to HIIT.
Activation of α7 Nicotinic Acetylcholine Receptor Ameliorates Zymosan-Induced Acute Kidney Injury in BALB/c Mice
Authors: Ibrahim Sherehan M. , Al-Shorbagy Muhammad Y. , Abdallah Dalaal M. , El-Abhar Hanan S. 
Published: November 2018

AbstractZymosan, a natural compound, provokes acute peritonitis and multiple organ dysfunction that affects the kidney, beside other organs via exaggerated inflammatory response. The aim of the present study is to test the role of cholinergic anti-inflammatory pathway (CAP) in alleviating acute kidney injury (AKI) induced by zymosan in BALB/c mice, using galantamine, a cholinesterase inhibitor, known to act via α7 nicotinic acetylcholine receptor (α7 nAChR) to stimulate CAP. Galantamine verified its anti-inflammatory effect by elevating acetylcholine (ACh) level, while abating the interleukin-6/ janus kinase 2 (Y1007/1008)/ signal transducer and activator of transcription 3 (Y705) (IL-6/ pY(1007/1008)-JAK2/ pY705-STAT3) inflammatory axis, with a consequent inhibition in suppressor of cytokine signaling 3 (SOCS3). This effect entails also the nuclear factor-kappa B (p65)/ high mobility group box protein-1/ (NF-κB (p65)/ HMGB-1) signaling pathway. Furthermore, the reno-curattive effect of galantamine was associated by a reduction in plasma creatinine (Cr), cystatin (Cys)-C, IL-18, and renal neutrophil gelatinase-associated lipocalin (NGAL), as well as an improved histopathological structure. Blocking the α7 nAChR by methyllycaconitine abolished the beneficial effect of galantamine to document the involvement of this receptor and the CAP in the amelioration of AKI induced by zymosan.
The kinetic characteristics of human and trypanosomatid phosphofructokinases for the reverse reaction
Authors: Fernandes Peter M. , Kinkead James , McNae Iain W. , Bringaud Frédéric , Michels Paul A.M. , Walkinshaw Malcolm D. 
Published: November 2018

Abstract
Eukaryotic ATP-dependent phosphofructokinases (PFKs) are often considered unidirectional enzymes catalysing the transfer of a phospho moiety from ATP to fructose 6-phosphate to produce ADP and fructose 1,6-bisphosphate. The reverse reaction is not generally considered to occur under normal conditions and has never been demonstrated for any eukaryotic ATP-dependent PFKs, though it does occur in inorganic pyrophosphate-dependent PFKs and has been experimentally shown for bacterial ATP-dependent PFKs. The evidence is provided via two orthogonal assays that all three human PFK isoforms can catalyse the reverse reaction in vitro, allowing determination of kinetic properties. Additionally, the reverse reaction was shown possible for PFKs from three clinically important trypanosomatids; these enzymes are contained within glycosomes in vivo. This compartmentalisation may facilitate reversal, given the potential for trypanosomatids to have an altered ATP/ADP ratio in glycosomes compared with the cytosol. The kinetic properties of each trypanosomatid PFK were determined, including the response to natural and artificial modulators of enzyme activity. The possible physiological relevance of the reverse reaction in trypanosomatid and human PFKs is discussed.