bluuebunny/crossref_metadata_2025_split huggingface dataset:
Representative Elementary Volumes, Hysteresis, and Heterogeneity in Multiphase Flow From the Pore to Continuum Scale
Authors: Jackson S. J. , Lin Q. , Krevor S. 
Published: March 2020

AbstractRepresentative elementary volumes (REVs) and heterogeneity are key concepts in continuum multiphase flow, yet their manifestation from the pore‐scale and associated impacts with the flow regime are not well understood. We use a multi‐scale experimental and modeling approach to elucidate the role of REVs, hysteresis, and heterogeneity in multiphase flow in two distinct water‐wetting Bentheimer sandstones. Experimental observations during steady‐state drainage and imbibition resolve the pore space at 6
m across a field of view up to 12
65 mm with simultaneous measurements of differential pressure during fluid flow. The REV for porosity and capillary pressure is
2 mm
for both samples, with 5% relative uncertainty. In contrast, due to macroscopic capillary pressure heterogeneities, the REV for saturation varies between 3.4 and 157.5 mm
, dependent on the fractional flow. Accurate knowledge of this REV uncertainty is critical in assessing continuum scale model validity and predictiveness. We validate the Land trapping model directly by predicting observed non‐wetting fluid connectivity at multiple imbibition states to within the REV uncertainty for homogeneous media. With this, observed hysteresis in the measured relative permeability is entirely removed when considering the connected saturation, validating conceptual hysteresis models based on connected pathway flow. REV scale heterogeneities in capillary pressure are shown to impact flow and trapping characteristics; when built into 3D continuum scale numerical models with hysteresis we are able to predict the variations in trapping and relative permeability observed between the two samples with different heterogeneity structures. The experimental data set herein provides an excellent benchmark for future development of continuum scale modeling frameworks.
Spatial and Temporal Patterns in Baseflow Recession in the Continental United States
Authors: Tashie Arik , Pavelsky Tamlin , Emanuel Ryan E. 
Published: March 2020

AbstractBaseflow is often treated according to a unique storage‐discharge relationship. However, recent innovations in baseflow recession analysis have allowed novel findings regarding the variability of both the stability of baseflow and its nonlinearity (i.e., the concavity of the hydrograph), as well as the regional clustering of these characteristics. We investigate spatial and temporal patterns in the character of baseflow recession for over 1,000 watersheds in the continental United States. We discover seasonal patterns in both the stability and nonlinearity of baseflow which vary systematically across large regions. Further, we relate these baseflow characteristics to their potential physical drivers, including estimates of evapotranspiration, watershed storage, the distribution of watershed storage, and precipitation. While coincident watershed storage is the best predictor of baseflow stability in many regions (particularly the Appalachian Mountains), evapotranspiration from 2 to 3 months previous is the best predictor of baseflow stability in other regions (particularly the Pacific Northwest). We also discuss the novel finding that baseflow nonlinearity has increased significantly in most watersheds across the United States since 1980.
Hippocampal TNF-death receptors, caspase cell death cascades, and IL-8 in alcohol use disorder
Authors: Liu Wen , Vetreno Ryan P. , Crews Fulton T. 
Published: March 2020

AbstractThe relationship between increased neuroimmune gene expression and hippocampal degeneration in alcohol use disorder (AUD) and other mental diseases is poorly understood. We report here that tumor necrosis factor receptor superfamily death receptor 3 (TNFRSF25, DR3) and Fas receptors (Fas) that initiate caspase cell death cascades are increased in AUD hippocampus and following a rat adolescent binge drinking model. Death receptors are known inducers of apoptosis and cell death that recruit death domain (DD) proteins FADD and TRADD and caspases to form death-inducing signaling complexes (DISC). In postmortem human AUD hippocampus, mRNA and IHC protein are increased for the entire death receptor cascade. In AUD hippocampus, ligand–death receptor pairs, i.e., TL1A-DR3 and FasL–Fas, were increased, as well as FADD and TRADD, and active caspase-8, -7, -9, and caspase-3. Further, pNFκB p65, a key neuroimmune transcription factor, and IL-8, a chemokine, were significantly increased. Interestingly, across AUD patients, increases in DR3 and Fas correlated with TRADD, and TRADD with active caspase+IR and IL-8+IR, consistent with coordinated activation of neuronal DISC mediated death cascades and neuroimmune gene induction in AUD. These findings support a role for DR3 and Fas neuroimmune signaling in AUD hippocampal neurodegeneration.
miR-27a is a master regulator of metabolic reprogramming and chemoresistance in colorectal cancer
Authors: Barisciano Giovannina , Colangelo Tommaso , Rosato Valeria , Muccillo Livio , Taddei Maria Letizia , Ippolito Luigi , Chiarugi Paola , Galgani Mario , Bruzzaniti Sara , Matarese Giuseppe , Fassan Matteo , Agostini Marco , Bergamo Francesca , Pucciarelli Salvatore , Carbone Annalucia , Mazzoccoli Gianluigi , Colantuoni Vittorio , Bianchi Fabrizio , Sabatino Lina 
Published: March 2020

AbstractBackgroundMetabolic reprogramming towards aerobic glycolysis in cancer supports unrestricted cell proliferation, survival and chemoresistance. The molecular bases of these processes are still undefined. Recent reports suggest crucial roles for microRNAs. Here, we provide new evidence of the implication of miR-27a in modulating colorectal cancer (CRC) metabolism and chemoresistance.MethodsA survey of miR-27a expression profile in TCGA-COAD dataset revealed that miR-27a-overexpressing CRCs are enriched in gene signatures of mitochondrial dysfunction, deregulated oxidative phosphorylation, mTOR activation and reduced chemosensitivity. The same pathways were analysed in cell lines in which we modified miR-27a levels. The response to chemotherapy was investigated in an independent cohort and cell lines.ResultsmiR-27a upregulation in vitro associated with impaired oxidative phosphorylation, overall mitochondrial activities and slight influence on glycolysis. miR-27a hampered AMPK, enhanced mTOR signalling and acted in concert with oncogenes and tumour cell metabolic regulators to force an aerobic glycolytic metabolism supporting biomass production, unrestricted growth and chemoresistance. This latter association was confirmed in our cohort of patients and cell lines.ConclusionsWe disclose an unprecedented role for miR-27a as a master regulator of cancer metabolism reprogramming that impinges on CRC response to chemotherapy, underscoring its theragnostic properties.
53BP1 loss rescues embryonic lethality but not genomic instability of BRCA1 total knockout mice
Authors: Chen Jiyuan , Li Peng , Song Licun , Bai Long , Huen Michael S. Y. , Liu Yidan , Lu Lin-Yu 
Published: March 2020

AbstractBRCA1 is critical for DNA double-strand break (DSB) repair by homologous recombination (HR). BRCA1 deficient mice are embryonic lethal. Previous studies have shown that 53BP1 knockout (KO) rescues embryonic lethality of BRCA1 hypomorphic mutant mice by restoring HR. Here, we show that 53BP1 KO can partially rescue embryonic lethality of BRCA1 total KO mice, but HR is not restored in BRCA1-53BP1 double knockout (DKO) mice. As a result, BRCA1-53BP1 DKO cells are extremely sensitive to PARP inhibitors (PARPi). In addition to HR deficiency, BRCA1-53BP1 DKO cells have elevated microhomology-mediated end joining (MMEJ) activity and G2/M cell cycle checkpoint defects, causing severe genomic instability in these cells. Interestingly, BRCA1-53BP1 DKO mice rapidly develop thymic lymphoma that is 100% penetrant, which is not observed in any BRCA1 mutant mice rescued by 53BP1 KO. Taken together, our study reveals that 53BP1 KO can partially rescue embryonic lethality caused by complete BRCA1 loss without rescuing HR-related defects. This finding suggests that loss of 53BP1 can support the development of cancers with silenced BRCA1 expression without causing PARPi resistance.
Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sjögren’s syndrome
Authors: Hu Lei , Xu Junji , Wu Tingting , Fan Zhipeng , Sun Lingyun , Liu Yi , Li Yan , Zhang Chunmei , Wang Jingsong , Ding Yaozhong , Wang Songlin 
Published: March 2020

AbstractMesenchymal stem cell (MSCs) transplantation has been used to treat Sjögren’s syndrome (SS) based on the immunoregulatory properties of MSCs. However, the effectiveness need improving and its underlying intrinsic mechanisms remain largely unknown. Here, we show that Id3 is upregulated in bone marrow-derived MSCs (BMMSCs) isolated from NOD/ShiLtJ mice, a widely used SS model, compared with ICR mice as control, suggesting that it functions in SS development and therapy. Transplantation of Id3-deficient BMMSCs rescues salivary gland function more effective than wild-type BMMSCs in NOD/ShiLtJ mice. Mechanistically, we show that ID3 negatively regulated BMP4 expression by preventing binding of basic helix–loop–helix protein E2A to the promoter of the Bmp4 gene. BMP4 in turn promoted PGE2 production in MSCs, and exhibited enhanced suppressive activities of T-cell proliferation and Th1 differentiation. Importantly, BMMSCs from SS patients showed significantly lower BMP4 and PGE2 expression than those from healthy individuals. Taken together, our findings revealed the targeting Id3 may be therapeutically useful for improving MSC immunoregulation and effectiveness of MSCs therapy for SS.
Identification of region-specific astrocyte subtypes at single cell resolution
Authors: Batiuk Mykhailo Y. , Martirosyan Araks , Wahis Jérôme , de Vin Filip , Marneffe Catherine , Kusserow Carola , Koeppen Jordan , Viana João Filipe , Oliveira João Filipe , Voet Thierry , Ponting Chris P. , Belgard T. Grant , Holt Matthew G. 
Published: March 2020

AbstractAstrocytes, a major cell type found throughout the central nervous system, have general roles in the modulation of synapse formation and synaptic transmission, blood–brain barrier formation, and regulation of blood flow, as well as metabolic support of other brain resident cells. Crucially, emerging evidence shows specific adaptations and astrocyte-encoded functions in regions, such as the spinal cord and cerebellum. To investigate the true extent of astrocyte molecular diversity across forebrain regions, we used single-cell RNA sequencing. Our analysis identifies five transcriptomically distinct astrocyte subtypes in adult mouse cortex and hippocampus. Validation of our data in situ reveals distinct spatial positioning of defined subtypes, reflecting the distribution of morphologically and physiologically distinct astrocyte populations. Our findings are evidence for specialized astrocyte subtypes between and within brain regions. The data are available through an online database (https://holt-sc.glialab.org/), providing a resource on which to base explorations of local astrocyte diversity and function in the brain.
Determining the adsorption energies of small molecules with the intrinsic properties of adsorbates and substrates
Authors: Gao Wang , Chen Yun , Li Bo , Liu Shan-Ping , Liu Xin , Jiang Qing 
Published: March 2020

AbstractAdsorption is essential for many processes on surfaces; therefore, an accurate prediction of adsorption properties is demanded from both fundamental and technological points of view. Particularly, identifying the intrinsic determinants of adsorption energy has been a long-term goal in surface science. Herein, we propose a predictive model for quantitative determination of the adsorption energies of small molecules on metallic materials and oxides, by using a linear combination of the valence and electronegativity of surface atoms and the coordination of active sites, with the corresponding prefactors determined by the valence of adsorbates. This model quantifies the effect of the intrinsic properties of adsorbates and substrates on adsorbate–substrate bonding, derives naturally the well-known adsorption-energy scaling relations, and accounts for the efficiency and limitation of engineering the adsorption energy and reaction energy. All involved parameters are predictable and thus allow the rapid rational design of materials with optimal adsorption properties.
A methylated lysine is a switch point for conformational communication in the chaperone Hsp90
Authors: Rehn Alexandra , Lawatscheck Jannis , Jokisch Marie-Lena , Mader Sophie L. , Luo Qi , Tippel Franziska , Blank Birgit , Richter Klaus , Lang Kathrin , Kaila Ville R. I. , Buchner Johannes 
Published: March 2020

AbstractMethylation of a conserved lysine in C-terminal domain of the molecular chaperone Hsp90 was shown previously to affect its in vivo function. However, the underlying mechanism remained elusive. Through a combined experimental and computational approach, this study shows that this site is very sensitive to sidechain modifications and crucial for Hsp90 activity in vitro and in vivo. Our results demonstrate that this particular lysine serves as a switch point for the regulation of Hsp90 functions by influencing its conformational cycle, ATPase activity, co-chaperone regulation, and client activation of yeast and human Hsp90. Incorporation of the methylated lysine via genetic code expansion specifically shows that upon modification, the conformational cycle of Hsp90 is altered. Molecular dynamics simulations including the methylated lysine suggest specific conformational changes that are propagated through Hsp90. Thus, methylation of the C-terminal lysine allows a precise allosteric tuning of Hsp90 activity via long distances.
Structural basis of RNA polymerase I pre-initiation complex formation and promoter melting
Authors: Pilsl Michael , Engel Christoph 
Published: March 2020

AbstractTranscription of the ribosomal RNA precursor by RNA polymerase (Pol) I is a prerequisite for the biosynthesis of ribosomes in eukaryotes. Compared to Pols II and III, the mechanisms underlying promoter recognition, initiation complex formation and DNA melting by Pol I substantially diverge. Here, we report the high-resolution cryo-EM reconstruction of a Pol I early initiation intermediate assembled on a double-stranded promoter scaffold that prevents the establishment of downstream DNA contacts. Our analyses demonstrate how efficient promoter-backbone interaction is achieved by combined re-arrangements of flexible regions in the ‘core factor’ subunits Rrn7 and Rrn11. Furthermore, structure-function analysis illustrates how destabilization of the melted DNA region correlates with contraction of the polymerase cleft upon transcription activation, thereby combining promoter recruitment with DNA-melting. This suggests that molecular mechanisms and structural features of Pol I initiation have co-evolved to support the efficient melting, initial transcription and promoter clearance required for high-level rRNA synthesis.
Molecularly tunable thin-film nanocomposite membranes with enhanced molecular sieving for organic solvent forward osmosis
Authors: Li Bofan , Japip Susilo , Chung Tai-Shung 
Published: March 2020

AbstractThin-film nanocomposites (TFN) functionalized with tunable molecular-sieving nanomaterials have been employed to tailor membranes, with an enhanced permeability and selectivity. Herein, water-soluble hollow cup-like macrocyclic molecules, sulfothiacalix[4]arene (STCAss) and sulfocalix[4]arene (SCA), are ionically bonded into the polyamide network to engineer the molecular-sieving properties of TFN membranes for organic solvent forward osmosis (OSFO). Introducing both STCAss and SCA into the polyamide network not only increases the free volume, but also reduces the thickness of the TFN layers. Combining with their molecularly tunable size of the lower cavities, both STCAss and SCA enable the TFN membranes to size exclusively reject the draw solutes, but only STCAss-functionalized membrane has an ethanol flux doubling the pristine one under the FO and PRO modes in OSFO processes; leading the functionalized polyamide network with remarkable improvements in OSFO performance. This study may provide insights to molecularly functionalize TFN membranes using multifunctional nano-fillers for sustainable separations.
A FinFET with one atomic layer channel
Authors: Chen Mao-Lin , Sun Xingdan , Liu Hang , Wang Hanwen , Zhu Qianbing , Wang Shasha , Du Haifeng , Dong Baojuan , Zhang Jing , Sun Yun , Qiu Song , Alava Thomas , Liu Song , Sun Dong-Ming , Han Zheng 
Published: March 2020

AbstractSince its invention in the 1960s, one of the most significant evolutions of metal-oxide-semiconductor field effect transistors (MOS-FETs) would be the three dimensionalized version that makes the semiconducting channel vertically wrapped by conformal gate electrodes, also recognized as FinFET. During the past decades, the width of fin (W$${}_{{\rm{fin}}}$$fin) in FinFETs has shrunk from about 150 nm to a few nanometers. However, W$${}_{{\rm{fin}}}$$fin seems to have been levelling off in recent years, owing to the limitation of lithography precision. Here, we show that by adapting a template-growth method, different types of mono-layered two-dimensional crystals are isolated in a vertical manner. Based on this, FinFETs with one atomic layer fin are obtained, with on/off ratios reaching $$\sim\!\! 10^{7}$$~107. Our findings push the FinFET to the sub 1 nm fin-width limit, and may shed light on the next generation nanoelectronics for higher integration and lower power consumption.
Pseudo-Occlusion of the Internal Carotid Artery in Acute Ischemic Stroke: Clinical Outcome after Mechanical Thrombectomy
Authors: Jung Woo Sang , Lee Jin Soo , Solander Sten , Choi Jin Wook 
Published: March 2020

AbstractPseudo-occlusion (PO) of the cervical internal carotid artery (cICA) can be caused by distal ICA occlusion. We explored the clinical impact of PO after mechanical thrombectomy (MT). Patients who underwent MT to treat distal ICA occlusions between July 2012 and March 2018 were reviewed. A cICA-PO was defined as when single phase computed tomography angiography (CTA) revealed a gradual decline in contrast above the level of the carotid bulb. We investigated the relationship between a cICA-PO and outcome; we also explored the association between successful recanalization and outcome. Among 71 patients, 40 (56.3%) exhibited cICA-PO and more likely to experience poor outcomes (80.0% vs. 25.8%, P < 0.001), hemorrhagic transformation (32.5% vs. 9.6%, P = 0.01), and a lower rate of successful recanalization (65.0% vs. 90.3%, P = 0.014) than the non-PO group. In binary logistic regression, a cICA-PO was independently associated with a poor outcome (odds ratio, 4.278; 95% CI, 1.080–33.006; P = 0.045). In the cICA-PO group, all patients who failed recanalization (n = 15) experienced poor outcomes, as did 69.2% of patients in whom recanalization was successful (P = 0.018). cICA-POs are common and have worse outcomes than non-PO patients. Patients with cICA-POs are more likely to exhibit poor outcomes after MT, particularly when recanalization fails.
Quantitative 3D imaging parameters improve prediction of hip osteoarthritis outcome
Authors: Turmezei T. D. , Treece G. M. , Gee A. H. , Sigurdsson S. , Jonsson H. , Aspelund T. , Gudnason V. , Poole K. E. S. 
Published: March 2020

AbstractOsteoarthritis is an increasingly important health problem for which the main treatment remains joint replacement. Therapy developments have been hampered by a lack of biomarkers that can reliably predict disease, while 2D radiographs interpreted by human observers are still the gold standard for clinical trial imaging assessment. We propose a 3D approach using computed tomography—a fast, readily available clinical technique—that can be applied in the assessment of osteoarthritis using a new quantitative 3D analysis technique called joint space mapping (JSM). We demonstrate the application of JSM at the hip in 263 healthy older adults from the AGES-Reykjavík cohort, examining relationships between 3D joint space width, 3D joint shape, and future joint replacement. Using JSM, statistical shape modelling, and statistical parametric mapping, we show an 18% improvement in prediction of joint replacement using 3D metrics combined with radiographic Kellgren & Lawrence grade (AUC 0.86) over the existing 2D FDA-approved gold standard of minimum 2D joint space width (AUC 0.73). We also show that assessment of joint asymmetry can reveal significant differences between individuals destined for joint replacement versus controls at regions of the joint that are not captured by radiographs. This technique is immediately implementable with standard imaging technologies.
RORγt may Influence the Microenvironment of Thyroid Cancer Predicting Favorable Prognosis
Authors: Cunha Lucas Leite , Morari Elaine Cristina , Nonogaki Suely , Bufalo Natassia Elena , da Assumpção Ligia Vera Montalli , Soares Fernando Augusto , Vassallo José , Ward Laura Sterian 
Published: March 2020

AbstractWe aimed to investigate the role of RORγt (Retinoic acid-related orphan receptor gamma) in the tumor microenvironment of differentiated thyroid carcinoma. We retrospectively analyzed 56 patients (48 papillary and 8 follicular thyroid carcinomas). Immunohistochemical expression of RORγt was compared to other immune markers previously investigated by our group, clinical and pathological information. All patients presented cytoplasmic expression of RORγt in thyroid tumor cells. Seven (12.5%) patients presented no nuclear expression of RORγt. Positivity was few (up to 10%) in 14 patients; 10 to 50% in 5 patients (8.9%); and more than 50% in 30 patients (53.6%). Nuclear RORγt positivity was associated with absence of distant metastasis at diagnosis (p = 0.013) and the need of less cumulative doses of radioactive iodine (p = 0.039). Patients whose tumors were positive for nuclear RORγt presented higher 10-years relapse-free survival rate than those patients who were negative for RORγt (p = 0.023). We classified the patients according to the clustering of immunological immunohistochemical markers. We were able to distinguish a subset (A) of 38 patients who presented high expression of nuclear RORγt and tended to be scarce in proinflammatory immune markers. Other 16 patients integrated a second subset (B) whose tumor microenvironment accumulated proinflammatory markers and presented low expression of nuclear nuclear RORγt. Distant metastasis at diagnosis were more frequent among patients from cluster B than from cluster A (p = 0.008). Our results reinforce that the expression of RORγt together with other immune markers might help predict the prognosis of patients with thyroid cancer and help individualize clinical management.