bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive Transport Modeling of Swelling Processes in Clay‐sulfate Rocks
Authors: Schweizer Daniel , Prommer Henning , Blum Philipp , Siade Adam J. , Butscher Christoph 
Published: August 2018

AbstractSwelling of clay‐sulfate rocks often causes large problems in geotechnical applications such as tunneling. The primary mechanism inducing the increase in rock volume is the chemical transformation of anhydrite to gypsum, which is triggered by the ingress of groundwater. In the present study, a novel conceptual and numerical modeling approach is developed that emphasizes the effect of groundwater flow in conjunction with the associated availability of water and changing geochemical conditions on the chemical transformation of anhydrite to gypsum. A reactive transport model was developed and hydraulic, reactive, and solute transport as well as mechanical model parameters were estimated through an inversion process, constrained by geodetic ground heave measurements from a study site in Staufen, Germany. The conceptual model of the swelling process was implemented numerically through a dual‐domain modeling approach, whereby the mobile domain accounts for solute transport along discontinuities, and the immobile reactive domain represents the matrix. A mass transfer process accounts for diffusive and/or capillary water transport into the matrix, where the rate‐limited transformation of anhydrite to gypsum takes place. The model calculates heave at the land surface depending on water inflow, the transformation of anhydrite into gypsum and the local stress conditions exerted by overburden pressure. The results show that the proposed reactive transport modeling approach is suitable to quantify the observed swelling‐induced heave at the study site with a plausible parameterization. The study also highlights that diffusion is a decisive factor for the effective rate of anhydrite dissolution and, therefore, the overall chemical transformation process.
Release of c-FLIP brake selectively sensitizes human cancer cells to TLR3-mediated apoptosis
Authors: Alkurdi Lugain , Virard François , Vanbervliet Béatrice , Weber Kathrin , Toscano Florent , Bonnin Marc , Le Stang Nolwenn , Lantuejoul Sylvie , Micheau Olivier , Renno Toufic , Lebecque Serge , Estornes Yann 
Published: August 2018

AbstractToll-like receptor 3 (TLR3) mediates innate immune responses by sensing viral dsRNA, but also induces apoptosis selectively in cancer cells. Our analysis by immunohistochemistry revealed that TLR3 is frequently overexpressed in 130 non-small cell lung cancer (NSCLC) patients’ samples compared with normal bronchial epithelium (P < 0.0001, Mann–Whitney test), supporting the therapeutic potential of TLR3 ligand for this type of cancer. However, a proportion of TLR3-expressing cancer cell lines, including NSCLC, remain resistant to TLR3-mediated apoptosis, and the underlying mechanism of resistance remains unclear. We here investigated the molecular basis conferring resistance to non-transformed vs. transformed cells against TLR3-mediated cell death. In non-transformed epithelial cells cellular FLICE-like inhibitory protein (c-FLIP) and cellular Inhibitor of APoptosis (cIAPs) ubiquitin ligases exerted an efficient double brake on apoptosis signaling. In contrast, releasing only one of these two brakes was sufficient to overcome the resistance of 8/8 cancer cell lines tested. Remarkably, the release of the c-FLIP, but not cIAPs, brake only results in the sensitization of all human cancer cells to TLR3-mediated apoptosis. Taking advantage of the difference between transformed and non-transformed cells, we developed a rational strategy by combining the chemotherapeutic agent paclitaxel, which decreases c-FLIP expression, with TLR3 ligand. This combination was highly synergistic for triggering apoptosis in cancer cells but not in non-transformed cells. In vivo, the combination of paclitaxel with dsRNA delayed tumor growth and prolonged survival in a mouse xenograft lung tumor model. In conclusion, combining the release of the c-FLIP brake with TLR3 ligand synergizes to selectively kill cancer cells, and could represent an efficient and safe therapy against TLR3-expressing cancers such as NSCLC.
CXCL1 derived from tumor-associated macrophages promotes breast cancer metastasis via activating NF-κB/SOX4 signaling
Authors: Wang Neng , Liu Weiping , Zheng Yifeng , Wang Shengqi , Yang Bowen , Li Min , Song Juxian , Zhang Fengxue , Zhang Xiaotong , Wang Qi , Wang Zhiyu 
Published: August 2018

AbstractTumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and multiple TAM-secreted cytokines have been identified associating with poor clinical outcomes. However, the therapeutic targets existing in the loop between TAMs and cancer cells are still required for further investigation. Here in, cytokine array validated that C-X-C motif chemokine ligand 1 (CXCL1) is the most abundant chemokine secreted by TAMs, and CXCL1 can promote breast cancer migration and invasion ability, as well as epithelial–mesenchymal transition in both mouse and human breast cancer cells. QPCR screening further validated SOX4 as the highest responsive gene following CXCL1 administration. Mechanistic study revealed that CXCL1 binds to SOX4 promoter and activates its transcription via NF-κB pathway. In vivo breast cancer xenografts demonstrated that CXCL1 silencing in TAMs results in a significant reduction in breast cancer growth and metastatic burden. Bioinformatic analysis and clinical investigation finally suggested that high CXCL1 expression is significantly correlated with breast cancer lymph node metastasis, poor overall survival and basal-like subtype. Taken together, our results indicated that TAMs/CXCL1 promotes breast cancer metastasis via NF-κB/SOX4 activation, and CXCL1-based therapy might become a novel strategy for breast cancer metastasis prevention.
Novel AF1q/MLLT11 favorably affects imatinib resistance and cell survival in chronic myeloid leukemia
Authors: Li Wei , Ji Min , Lu Fei , Pang Yihua , Dong Xin , Zhang Jingru , Li Peng , Ye Jingjing , Zang Shaolei , Ma Daoxin , Ji Chunyan 
Published: August 2018

AbstractTyrosine kinase inhibitor treatment of chronic myeloid leukemia (CML) has demonstrated beneficial effects. However, resistance to tyrosine kinase inhibitors and disease relapse are still a challenge for CML therapy. In this study, we analyzed bone marrow samples from 149 CML patients and 15 control donors, and investigated the affect of AF1q on CML cell survival and engraftment in vitro and in vivo. We found that AF1q/MLLT11 expression was significantly upregulated in CML patients, especially in CD34+ CML cells. Elevated AF1q expression was associated with disease progression. Knockdown of AF1q enhanced imatinib sensitivity, induced apoptosis, and suppressed growth in CML cells. Moreover, AF1q deficiency sensitized CD34+ CML cells to imatinib. In contrast, upregulation of AF1q promoted cell survival, protected CML cells from imatinib-induced apoptosis, and increased engraftment of CML cells in vivo. We further identified a positive correlation between AF1q and CD44 expression in chronic phase CML patients and CD34+ CML cells. Importantly, AF1q contributes to imatinib-resistance in CML by regulating the expression of CD44. These findings reveal a novel BCR-ABL-independent pathway, AF1q/CD44, involves imatinib resistance in CML, thus representing a potential therapeutic target for imatinib-resistant CML patients.
PI3Ka-Akt1-mediated Prdm4 induction in adipose tissue increases energy expenditure, inhibits weight gain, and improves insulin resistance in diet-induced obese mice
Authors: Song No-Joon , Chang Seo-Hyuk , Kim Suji , Panic Vanja , Jang Byung-Hyun , Yun Ui Jeong , Choi Jin Hee , Li Zhen , Park Ki-Moon , Yoon Jung-Hoon , Kim Sunghwan , Yoo Jae Hyuk , Ling Jing , Thomas Kirk , Villanueva Claudio J. , Li Dean Y. , Ahn Jee-Yin , Ku Jin-Mo , Park Kye Won 
Published: August 2018

AbstractStimulation of white adipose tissue (WAT) browning is considered as a potential approach to treat obesity and metabolic diseases. Our previous studies have shown that phytochemical butein can stimulate WAT browning through induction of Prdm4 in adipocytes. Here, we investigated the effects of butein on diet-induced obesity and its underlying molecular mechanism. Treatment with butein prevented weight gains and improved metabolic profiles in diet-induced obese mice. Butein treatment groups also displayed higher body temperature, increased energy expenditure, and enhanced expression of thermogenic genes in adipose tissue. Butein also suppressed body weight gains and improved glucose and insulin tolerance in mice housed at thermoneutrality (30 °C). These effects were associated with adipose-selective induction of Prdm4, suggesting the role of Prdm4 in butein-mediated anti-obese effects. To directly assess the in vivo role of Prdm4, we generated aP2-Prdm4 transgenic mouse lines overexpressing Prdm4 in adipose tissues. Adipose-specific transgenic expression of Prdm4 recapitulated the butein’s actions in stimulating energy expenditure, cold tolerance, and thermogenic gene expression, resulting in prevention of obesity and improvement of metabolism. Mechanistically, direct inhibition of PI3Kα activity followed by selective suppression of its downstream Akt1 mirrored butein’s effect on Ucp1 expression and oxygen consumption. In addition, effects of butein were completely abolished in Akt1 KO mouse embryonic fibroblasts. Together, these studies demonstrate the role of butein in obesity and metabolic diseases, further highlighting that adipose PI3Kα–Akt1–Prdm4 axis is a regulator of energy expenditure.
Correlators in simultaneous measurement of non-commuting qubit observables
Authors: Atalaya Juan , Hacohen-Gourgy Shay , Martin Leigh S. , Siddiqi Irfan , Korotkov Alexander N. 
Published: August 2018

AbstractOne of the hallmarks of quantum mechanics is the impossibility of simultaneous measurement of non-commuting observables with projective measurements. This, however, can be circumvented by using continuous quantum measurements. Here we investigate the temporal correlations of the output signals of detectors continuously and simultaneously measuring the qubit observables σz and σz cosφ + σx sinφ, for various angles φ. Using the quantum Bayesian formalism, we obtain analytical expressions for the correlators, which we find to be in good agreement with those obtained from experimentally measured output signals. The agreement is particularly good for cross-correlators, even at times shorter than the cavity modes decay time. We further discuss how the correlators can be applied for parameter estimation, and use them to infer a small residual qubit Hamiltonian arising from calibration inaccuracy in the experimental data. Our work opens up new possibilities to perform quantum metrology based on temporal correlations of measured data.
FR58P1a; a new uncoupler of OXPHOS that inhibits migration in triple-negative breast cancer cells via Sirt1/AMPK/β1-integrin pathway
Authors: Urra Félix A. , Muñoz Felipe , Córdova-Delgado Miguel , Ramírez María Paz , Peña-Ahumada Bárbara , Rios Melany , Cruz Pablo , Ahumada-Castro Ulises , Bustos Galdo , Silva-Pavez Eduardo , Pulgar Rodrigo , Morales Danna , Varela Diego , Millas-Vargas Juan Pablo , Retamal Evelyn , Ramírez-Rodríguez Oney , Pessoa-Mahana Hernán , Pavani Mario , Ferreira Jorge , Cárdenas César , Araya-Maturana Ramiro 
Published: August 2018

AbstractHighly malignant triple-negative breast cancer (TNBC) cells rely mostly on glycolysis to maintain cellular homeostasis; however, mitochondria are still required for migration and metastasis. Taking advantage of the metabolic flexibility of TNBC MDA-MB-231 cells to generate subpopulations with glycolytic or oxidative phenotypes, we screened phenolic compounds containing an ortho-carbonyl group with mitochondrial activity and identified a bromoalkyl-ester of hydroquinone named FR58P1a, as a mitochondrial metabolism-affecting compound that uncouples OXPHOS through a protonophoric mechanism. In contrast to well-known protonophore uncoupler FCCP, FR58P1a does not depolarize the plasma membrane and its effect on the mitochondrial membrane potential and bioenergetics is moderate suggesting a mild uncoupling of OXPHOS. FR58P1a activates AMPK in a Sirt1-dependent fashion. Although the activation of Sirt1/AMPK axis by FR58P1a has a cyto-protective role, selectively inhibits fibronectin-dependent adhesion and migration in TNBC cells but not in non-tumoral MCF10A cells by decreasing β1-integrin at the cell surface. Prolonged exposure to FR58P1a triggers a metabolic reprograming in TNBC cells characterized by down-regulation of OXPHOS-related genes that promote cell survival but comprise their ability to migrate. Taken together, our results show that TNBC cell migration is susceptible to mitochondrial alterations induced by small molecules as FR58P1a, which may have therapeutic implications.
Perinatal Outcome in Women with a Vietnamese Migration Background – Retrospective Comparative Data Analysis of 3000 Deliveries
Authors: Boxall Nicole , David Matthias , Schalinski Elisabeth , Breckenkamp Jürgen , Razum Oliver , Hellmeyer Lars 
Published: August 2018

Abstract
Introduction Perinatal data of women with a Vietnamese migration background have not been systematically studied in Germany to date. Numerous details of important maternal and child outcomes were compared and analysed. The studyʼs primary parameters were the frequency of and indication for c-section.
Methodology The perinatal data from a Berlin hospital were analysed retrospectively. The women (Vietnamese migration background vs. autochthonous) were grouped using name analysis. Datasets of 3002 women giving birth, including 999 women with a Vietnamese migration background, were included. The associations between primary or secondary cesarean delivery and different child outcomes depending on the migration background (exposure) were studied using logistical regression analysis.
Results Women with a Vietnamese migration background have a lower c-section rate of 8.0% for primary and 12.6% for secondary c-section than women without a migration background (11.1% primary and 16.4% secondary c-section respectively). Regression analysis shows that the odds that women with a Vietnamese migration background will have a primary (OR 0.75; p = 0.0884) or secondary c-section (OR 0.82; p = 0.1137) are not significantly lower. A Vietnamese migration background was associated with higher odds for an episiotomy but not for a grade 3 – 4 perineal tear. A Vietnamese migration background does not have a significant influence on poor 5-min Apgar scores ≤ 7 and low umbilical cord arterial pH values ≤ 7.10. Newborns of mothers with a Vietnamese migration background have higher odds of a relatively higher birth weight (> 3110 g).
Summary There was no evidence that women with a Vietnamese migration background are delivered more often by caesarean section. There were also no differences as regards important child outcome data from women in the comparator group. Overall, the results do not provide any evidence for poorer quality of care of women with a Vietnamese migration background in Berlin despite the cultural and communication barriers in the reality of care provision.
MECHANISMS INVOLVED IN 5-HT STIMULATION OF PROSTACYCLIN PRODUCTION BY BOVINE AORTIC SMOOTH MUSCLE CELLS
Authors: Demolle D , Cragoe E J , Boeynaems J M 
Published: August 2018

Serotonin (5-HT) stimulates prostacyclin (PGI2) production by bovine aortic smooth muscle cells in culture via 5-HT2 receptors (1). These cells express a synthetic phenotype (2), whereas the majority of the smooth muscle cells in the media from adult arteries are in a contractile state. We have now shown that 5-HT (1-10 μM) also stimulates PGI2 production by a preparation of contractile smooth muscle cells : explants from bovine aortic media cultured for short periods. This effect is independent from 5-HT2 receptors : it is only partially inhibited (±30%) by ketan-serin (a selective and potent 5-HT2 antagonist) and is perfectly mimicked by a 5-HT1 agonist, 5-carboxamidotryptamine. 5-HT2 receptors seem to be linked to a phospholipase C (3), with subsequent accumulation of inositol tr isphosphate , Ins(1,4,5)P3, and diacylglycerol, an activator of protein kinase C. We have observed a stimulatory effect of phorbol 12-myristate, 13-acetate (a selective activator of kinase C) on PGI2 production by the bovine aortic smooth muscle cells (synthetic state), whereas it was totally ineffective on media explants preparation (contractile state). Furthermore, in the smooth muscle cells in culture, the 5-HT effect can be inhibited by (ethyl-isopropyl)amiloride, a potent and selective inhibitor of the Na+/H+ antiporter. In conclusion it appears that the regulation mechanisms of PGI2 production in arterial smooth muscle cells are strongly dependent an the phenotypic state of these cells. The control of PGI2 release via 5-HT2 receptors seems to involve a cytoplasmic alkalinization, via the activation of protein kinase C. The mechanism of 5-HT action in the media explants remains to be elucidated.(1) Coughlin, S.R. et al.: Proc . Natl. Acad. Sci. USA 78(11), 7134-7138, 1981.(2) Chamley-Campbell, J.H. and Campbell, G.K.: Atherosclerosis 40, 347-357, 1981.(3) Roth, B.L. et al.: J. Pharm. Exp. Ther. 238(2), 480-485, 1986.
ULTRASTRUCTURAL INVESTIGATIONS ON THE MECHANISM OF “SHEAR-INDUCED PLATELET ACTIVATION”
Authors: Wurzinger L J , Opitz R , Schmid-Schönbein H 
Published: August 2018

High shear forces are suspected to play a triggering role in the initiation of arterial thrombosis, by activating platelets and the coagulation system. In an earlier study a shear stress of 170 N/m2 acting for only 7 milliseconds (ms) on platelet rich plasma (PRP) was found to induce a significant increase in platelet factor 3 availability (Thromb. Haemost. 54: 381-386; 1985). To clarify the question whether platelets can be activated directly by mechanical forces in analogy to smooth muscle cells, electron micrographs of platelets subjected to laminar shear stress were analysed with morphometric methods. The level of activation of platelet suspensions was quantified by assessing 1) the elongation of platelet profiles giving a measure for the “flatness” of the discoid resting platelets, and 2) the centralization of granules.Exposure to a shear stress of 170 N/m2 for 113 ms leaves ca. 15 % of the platelets irreversibly damaged, featuring degenerative ballooning, with break-down of internal structure and cell membrane defects. The remaining 85 % appear typically activated with rounded shape, extension of pseudopods and centralization of granules. Addition of “ADP-scavengers” to the suspension medium totally changes the appearance of sheared platelets: still a comparable proportion of them has undergone irreversible degenerative changes, but the “surviving” population lacks ultrastructural signs of platelet activation. This is reflected in values of the morphometric parameters which are close to the level of unsheared control samples.It is therefore concluded that “shear-induced platelet activation” cannot be ascribed to a direct stimulating effect of shear forces, but rather to secondary biochemical activation by adenine nucleotides leaking from a small percentage of shear destroyed platelets. The latter process, however, requires a well stirred though undiluted environment, as it is provided in vortices and eddies.
THROMBOPHILIA:ITS CAUSES AND A ROUGH ESTIMATE OF ITS PREVALENCE
Authors: Briët E , Engesser L , Brommer E J P , Broekmans A W , Bertina R M 
Published: August 2018

Idiopathic venous thrombosis and embolism have gained widespread interest since the discovery that, deficiencies of antithrombin III, protein C, and protein S are associated with familial venous thrombophilia. The purpose of our study was to obtain an estimate of the prevalence of this syndrome and to establish the etiology in as many cases as possible.We collaborated with specialists from 37 Dutch hospitals, covering about 10% of the Dutch population. A history as well as blood samples were obtained from 113 unrelated cases with familial thrombophilia and from 90 isolated cases. Assuming that each proband in a family with thrombophilia has an average of four affected relatives, a rough estimate of the prevalence of familial thrombophilia in The Netherlands is 40 cases per 100.000. The prevalence of non-familial thrombophilia is probably lower.In 35 out of the 113 familial cases we established a diagnosis of hereditary antithrombin III deficiency (n=5), protein C deficiency (type I: n=9; type II: n=4), protein S deficiency (n=15) and dysfibrinogenemia (n=2). In 36 cases we found no abnormality at all and in the remaining 42 cases abnormalities were found in one or more of the following: heparin cofactor II, factor V, factor VII, factor VIII, von Willebrand factor, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor, alpha 2 antiplasmin and histidine rich glycoprotein. In most of these cases, however, the hereditary nature of the abnormalities could not be demonstrated and the causal relationships remain to be established.In the 90 isolated cases, we diagnosed hereditary deficiencies of anti thrombin III, protein C and protein S each in one case and a lupus anticoagulant in two cases. In 54 cases no abnormality was found and in the remaining 31 cases various abnormalities were found in one or more of the proteins mentioned above.We conclude that the syndrome of thrombophilia is not rare but its true prevalence needs to be established by more rigorous means. An etiological diagnosis can be made with confidence in only one third of the familial cases and in less than 10 percent of the isolated cases.
EARLY RESULTS OF A RANDOMIZED, DOUBLE-BLIND DOSE-RANGING STUDY OF I.V. STREPTOKINASE FOR ACUTE MYOCARDIAL INFARCTION
Authors: Six A J , Louwerenburg J W , Braams R , Mosterd W L , Bredero A C , Kerkkamp H J , Brommer E J P , van Hemel N M 
Published: August 2018

101 patients suffering from acute myocardial infarction during less than 4 hours were immediately treated with intravenous (i.v.) streptokinase (SK), infused in 1 hour. No concomitant medications like steroids, salicylates or anti-arrhythmic drugs were routinely given.Patients were blindly allocated to one of four dosages of SK (see below). Coronary angiography was performed within 3 hours after SK infusion in 90% of all patients . The infarct-related vessel was open in 59% of 91 patients. The results in the four dosage groups were as follows:Haematomas at the puncture site were common complications in all groups. No strokes occurred, nor life-threatening bleeding complications. Blood transfusion was needed in only one parient, who had an important bleeding and formation of a large haematoma at the puncture site.It is concluded that there is a trend to better results of higher doses of i.v. SK in patients suffering from acute myocardial infarction without an evident rise of the rate of complications. The efficacy and safety of recently developed fibrinolytic drugs and streptokinase should be compared at optimal dosages.