bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catchment zoning to enhance co‐benefits and minimize trade‐offs between ecosystem services and freshwater biodiversity conservation
Authors: Hermoso Virgilio , Cattarino Lorenzo , Linke Simon , Kennard Mark J. 
Published: March 2018

AbstractIntegrating ecosystem services (ESs) in landscape planning can help to identify conservation opportunities by finding co‐benefits between biodiversity conservation and the maintenance of regulating and cultural ecosystem services. The adequate integration of ESs needs careful consideration of potential trade‐offs, however, especially between provisioning services and biodiversity conservation (e.g. the potentially negative consequences of agricultural water extraction within areas important for the maintenance of biodiversity). These trade‐offs have been overlooked in systematic spatial planning to date, especially in freshwater systems.marxan with zoneswas used to identify priority areas for the conservation of freshwater biodiversity (139 species of freshwater fish, turtles, and waterbirds) and the provision of freshwater ESs in the Daly River, northern Australia. Four different surrogates for ESs were mapped, including those potentially incompatible with conservation goals (i.e. groundwater provision for agriculture and recreational fisheries) and those that are more compatible with conservation (i.e. flood regulation by riparian forests; provision of perennial water). The spatial allocation of multiple management zones was prioritized: (i) three conservation zones, aiming to represent freshwater biodiversity and compatible ESs to enhance co‐benefits; and (ii) two production zones, where access to provisioning ESs could be granted. The representation of ESs obtained when using the multi‐zoning approach was compared with that achieved with a single management zone approach. The comparison was performed across different representation targets.Different results were found with low and high targets for ESs. With low targets (<25% of all ESs), the multi‐zoning approach achieved up to 53% more co‐benefits than the single‐zone approach. With high targets (>25% of all ESs), the trade‐offs avoided were more evident, with up to 56% less representation of incompatible ESs within conservation zones.Multi‐zone planning could help decision makers respond better to the increasingly complex catchment management context, caused by an increasing demand for provisioning services and a diminishing availability of resources, as well as manage and plan for challenges in other realms facing similar problems.
Distributed Strain Sensing in der Geotechnik
Authors: Kindler Arne , Großwig Stephan 
Published: March 2018

AbstractMit dem vorliegenden Beitrag soll eine Empfehlung für den Einsatz der ortsverteilten faseroptischen Dehnungsmessung (Distributed Strain Sensing) in der Geotechnik gegeben werden. Hintergrund hierfür ist der vermehrte Einsatz dieses Messverfahrens im Spezialtiefbau. Das Feld der ortsverteilten faseroptischen Sensortechnik ist ein weitgefächertes Gebiet. So gibt es Messverfahren für dynamische (Zeitauflösung im kHz‐Bereich) und nicht dynamische Messungen (Zeitauflösung im MHz‐Bereich bis stationär). Das in diesem Beitrag behandelte Messgebiet bezieht sich ausschließlich auf nicht dynamische Dehnungsmessungen mittels Distributed Sensing. Der Beitrag umfasst eine Kurzdarstellung/Gegenüberstellung zwischen Einzelpunktmessung und ortsverteilter Messung, dem „Distributed Sensing“. Darüber hinaus wird kurz das bisherige Einsatzgebiet für das Distributed Strain Sensing dargestellt und mit ausgeführten Beispielen unterlegt. Die Autoren versuchen trotz einer Vielzahl eigener Arbeiten die Referenznachweise weit zu fassen. Im Weiteren werden die wesentlichen erforderlichen faseroptischen Kabelkonstruktionen aufgezeigt und konstruktive Hinweise zur Montage gegeben. Abschließend werden Hinweise zum Mindestumfang eines Messberichts sowie zur Auswertung von „Distributed Strain Sensing“‐Messungen gegeben.Es ist angedacht, in einem weiteren Beitrag Hinweise zur Ausschreibung der „Distributed Strain Sensing“‐Messungen in der Geotechnik zu geben, um dem ausschreibenden Ingenieur ein Arbeitsmittel an die Hand zu geben, damit der Planer im Ergebnis seiner Vergabe das gewünschte Messverfahren erhält.
Enantioseparation of (RS)‐fexofenadine and enhanced detection as the diastereomeric amide and anhydride derivatives using liquid chromatography‐mass spectrometry
Authors: Malik Poonam , Bhushan Ravi 
Published: March 2018

AbstractEnantioselective analysis of (RS)‐fexofenadine was carried out by achiral HPLC via a derivatization approach using N‐hydroxy‐benzotriazolyl‐(S)‐naproxen ester (synthesized for this purpose) and three chirally pure amines as chiral derivatizing reagents. There occurred formation of amide and anhydride types of diastereomeric derivatives. These were separated and isolated by HPLC (analytical and preparative). The structures and configurations were verified via recording full‐scan product ion mass spectra using LC‐MS, 1HNMR spectra, Chem3D Pro 12.0 software and the software Gaussian 09 Rev.A.02 program and hybrid density functional B3LYP with 6‐31G basis set supplemented with polarimetry. Experimental conditions for synthesis and separations were optimized and the elution order was established. Analytical separation was performed on a C18 analytical column with different ratios of MeCN–TEAP buffer and MeOH–TEAP buffer (v/v) adjusted to pH 7.5 as mobile phase at a flow rate of 0.7 mL min‐1. Detection was performed via UV absorbance at 225 nm. The method was validated in accordance with International Conference on Harmonization guidelines. The detection limits were 6.25 and 7.87 ng mL‐1 for first and second eluting diastereomeric derivatives, respectively.
Trps1 is associated with the multidrug resistance of lung cancer cell by regulating MGMT gene expression
Authors: Liu Hongxiang , Liao Yi , Tang Meng , Wu Tao , Tan Deli , Zhang Shixin , Wang Haidong 
Published: March 2018

AbstractMultidrug resistance (MDR) often leads to chemotherapy failure of lung cancer and has been linking to the cellular expression of several DNA transcription‐ and repair‐related genes such as Trps1 and MGMT. However, their roles in the formation of MDR are largely unknown. In this study, overexpression/knockdown, luciferase assay and ChIP assay were performed to study the relationship between Trps1 and MGMT, as well as their roles in MDR formation. Our results demonstrated that Trps1 and MGMT expression both increased in drug‐resistant lung cancer cell line (H446/CDDP). Silencing of Trps1 resulted in downregulation of MGMT expression and decrease in the multidrug sensitivity of H446/CDDP cells, while Trps1 overexpression exhibited the opposite effects in H446 cells. Ectopic expression of MGMT had no effect on Trps1 expression, but enhanced the IC50 values of H446 cells or rescued the IC50 values of Trps1‐silenced H446/CDDP cells in treatment of multidrug. Our data further showed that, mechanistically, Trps1 acted as a transcription activator that directly induced MGMT transcription by binding to the MGMT promoter. Taken together, we consider that upregulation of Trps1 induces MGMT transcription contributing to the formation of MDR in lung cancer cells. Our findings proved potential targets for reversing MDR in clinical chemotherapy of lung cancer.
The importance of greater speed in drug development for advanced malignancies
Authors: Stewart David J. , Stewart Andrew A. , Wheatley‐Price Paul , Batist Gerald , Kantarjian Hagop M. , Schiller Joan , Clemons Mark , Bradford John‐Peter , Gillespie Laurel , Kurzrock Razelle 
Published: March 2018

AbstractIt takes on average 6–12 years to develop new anticancer drugs from discovery to approval. Effective new agents prolong survival. To demonstrate the importance of rapid drug approval, we calculated life‐years potentially saved if selected agents were approved more rapidly. As illustrative examples, we used 27 trials documenting improvements in survival. We multiplied improvement in median survival by numbers of patients dying annually and multiplied this by number of years from drug discovery until approval. For every year by which time to drug approval could have been shortened, there would have been a median number of life‐years potentially saved of 79,920 worldwide per drug. Median number of life‐years lost between time of drug discovery and approval was 1,020,900 per example. If we were able to use available opportunities to decrease the time required to take a drug from discovery to approval to 5 years, the median number of life‐years saved per example would have been 523,890 worldwide. Various publications have identified opportunities to speed drug development without sacrificing patient safety. While many investigational drugs prove to be ineffective, some significantly prolong survival and/or reduce suffering. These illustrative examples suggest that a substantial number of life‐years could potentially be saved by increasing the efficiency of development of new drugs for advanced malignancies.
MRI‐guided interventional natural killer cell delivery for liver tumor treatment
Authors: Su Zhanliang , Wang Xifu , Zheng Linfeng , Lyu Tianchu , Figini Matteo , Wang Bin , Procissi Daniel , Shangguan Junjie , Sun Chong , Pan Liang , Qin Lei , Zhang Bin , Velichko Yury , Salem Riad , Yaghmai Vahid , Larson Andrew C. , Zhang Zhuoli 
Published: March 2018

AbstractWhile natural killer (NK) cell‐based adoptive transfer immunotherapy (ATI) provides only modest clinical success in cancer patients. This study was hypothesized that MRI‐guided transcatheter intra‐hepatic arterial (IHA) infusion permits local delivery to liver tumors to improve outcomes during NK‐based ATI in a rat model of hepatocellular carcinoma (HCC). Mouse NK cells were labeled with clinically applicable iron nanocomplexes. Twenty rat HCC models were assigned to three groups: transcatheter IHA saline infusion as the control group, transcatheter IHA NK infusion group, and intravenous (IV) NK infusion group. MRI studies were performed at baseline and at 24 h, 48 h, and 8 days postinfusion. There was a significant difference in tumor R2* values between baseline and 24 h following the selective transcatheter IHA NK delivery to the tumors (P = 0.039) when compared to IV NK infusion (P = 0.803). At 8 days postinfusion, there were significant differences in tumor volumes between the control, IV, and IHA NK infusion groups (control vs. IV, P = 0.196; control vs. IHA, P < 0.001; and IV vs. IHA, P = 0.001). Moreover, there was a strong correlation between tumor R2* value change (∆R2*) at 24 h postinfusion and tumor volume change (∆volume) at 8 days in IHA group (R2 = 0.704, P < 0.001). Clinically applicable labeled NK cells with 12‐h labeling time can be tracked by MRI. Transcatheter IHA infusion improves NK cell homing efficacy and immunotherapeutic efficiency. The change in tumor R2* value 24 h postinfusion is an important early biomarker for prediction of longitudinal response.
Tumor‐derived extracellular vesicles activate primary monocytes
Authors: Gärtner Kathrin , Battke Christina , Dünzkofer Judith , Hüls Corinna , von Neubeck Bettina , Kellner Mar‐ kus , Fiestas Elena , Fackler Susanne , Lang Stephan , Zeidler Reinhard 
Published: March 2018

AbstractTumor cells educate immune effector cells in their vicinity by releasing factors that manipulate their phenotype and function. In fact, the thus generated immunosuppressive tumor microenvironment constitutes an integral part and a hallmark of solid tumors and contributes significantly to tumor development and immune escape. It has long been thought that soluble factors like prostaglandin E2 and TGF‐β are the main mediators of these effects. But tumor cells also constantly release large number of extracellular vesicles (EVs), which are important conveyors of immune responses. We show here that tumor‐derived EVs interact with primary monocytes and induce an activated phenotype, which is also observed in tumor‐associated macrophages. Thus, both tumor‐derived EVs and soluble factors together collaborate to form the immunosuppressive milieu of the tumor environment.
RFX1 participates in doxorubicin‐induced hepatitis B virus reactivation
Authors: Wang Jie , Jia Junqiao , Chen Ran , Ding Shanlong , Xu Qiang , Zhang Ting , Chen Xiangmei , Liu Shuang , Lu Fengmin 
Published: March 2018

AbstractCytotoxic chemotherapy drugs, including doxorubicin, can directly promote hepatitis B virus (HBV) replication, but the mechanism has not been fully clarified. This study investigated the potential mechanism underlying the cytotoxic chemotherapy‐mediated direct promotion of HBV replication. We found that HBV replication and regulatory factor X box 1 gene (RFX1) expression were simultaneously promoted by doxorubicin treatment. The amount of RFX1 bound to the HBV enhancer I was significantly increased under doxorubicin treatment. Furthermore, the activity of doxorubicin in promoting HBV replication was significantly attenuated when the expression of endogenous RFX1 was knocked down, and the EP element of HBV enhancer I, an element that mediated the binding of RFX1 and HBV enhancer I, was mutated. In addition, two different sequences of the conserved EP element were found among HBV genotypes A‐D, and doxorubicin could promote the replication of HBV harboring either of the conserved EP elements. Here, a novel pathway in which doxorubicin promoted HBV replication via RFX1 was identified, and it might participate in doxorubicin‐induced HBV reactivation. These findings would be helpful in preventing HBV reactivation during anticancer chemotherapy.
A duration model analysis of consumer preferences and determinants of video game consumption
Authors: Kaimann Daniel , Stroh‐Maraun Nadja , Cox Joe 
Published: March 2018

AbstractDespite the enormous revenues generated by the video game industry in recent years, relatively little research has been undertaken into consumer preferences and the determinants of video game consumption. This study addresses this deficiency through the analysis of data from a popular online video game that includes historic behavioural information for 1,408 consumers participating in 728,811 unique rounds of gameplay. We analyse these data with the goal of estimating determinants of the aggregate amount of time that a consumer spends playing the game. Through the estimation of duration models, we show that less experienced consumers are less likely to continue playing the game at any given point, possibly due to having achieved mastery and becoming bored. However, we also find that consumers tend to play the game for longer periods when using a wider range of character roles and vehicles, implying that a consumer's interest can be maintained through exposure to greater variety. Our results represent the first such evidence on in‐game consumer preferences, which has important implications for video game consumption through optimisation of gameplay experiences to satisfy these preferences.
Reaction Mechanism of Prephenate Dehydrogenase from the Alternative Tyrosine Biosynthesis Pathway in Plants
Authors: Holland Cynthia K. , Jez Joseph M. 
Published: March 2018

AbstractUnlike metazoans, plants, bacteria, and fungi retain the enzymatic machinery necessary to synthesize the three aromatic amino acids l‐phenylalanine, l‐tyrosine, and l‐tryptophan de novo. In legumes, such as soybean, alfalfa, and common bean, prephenate dehydrogenase (PDH) catalyzes the tyrosine‐insensitive biosynthesis of 4‐hydroxyphenylpyruvate, a precursor to tyrosine. The three‐dimensional structure of soybean PDH1 was recently solved in complex with the NADP+ cofactor. This structure allowed for the identification of both the cofactor‐ and ligand‐binding sites. Here, we present steady‐state kinetic analysis of twenty site‐directed active‐site mutants of soybean (Glycine max) PDH compared to wild‐type. Molecular docking of the substrate, prephenate, into the active site of the enzyme revealed its potential interactions with the active site residues and made a case for the importance of each residue in substrate recognition and/or catalysis, most likely through transition state stabilization. Overall, these results suggested that the active site of the enzyme is highly sensitive to any changes, as even subtle alterations substantially reduced the catalytic efficiency of the enzyme.
Characterization of the Actinonin Biosynthetic Gene Cluster
Authors: Wolf Felix , Leipoldt Franziska , Kulik Andreas , Wibberg Daniel , Kalinowski Jörn , Kaysser Leonard 
Published: March 2018

AbstractThe hydroxamate moiety of the natural product actinonin mediates inhibition of metalloproteinases because of its chelating properties towards divalent cations in the active site of those enzymes. Owing to its antimicrobial activity, actinonin has served as a lead compound for the development of new antibiotic drug candidates. Recently, we identified a putative gene cluster for the biosynthesis of actinonin. Here, we confirm and characterize this cluster by heterologous pathway expression and gene‐deletion experiments. We assigned the biosynthetic gene cluster to actinonin production and determine the cluster boundaries. Furthermore, we establish that ActI, an AurF‐like oxygenase, is responsible for the N‐hydroxylation reaction that forms the hydroxamate warhead. Our findings provide the basis for more detailed investigations of actinonin biosynthesis.
Impact of HAS‐BLED score to predict trans femoral transcatheter aortic valve replacement outcomes
Authors: Honda Yohsuke , Yamawaki Masahiro , Araki Motoharu , Tada Norio , Naganuma Toru , Yamanaka Futoshi , Watanabe Yusuke , Yamamoto Masanori , Shirai Shinichi , Hayashida Kentaro ,   on behalf of the OCEAN‐TAVI investigators
Published: March 2018

AbstractBackgroundPredictors of bleeding and mortality after trans femoral transcatheter aortic valve replacement (TF‐TAVR) has not been thoroughly investigated.ObjectiveThe aim of this study was to assess whether Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly (HAS‐BLED) score has predictive value for bleeding and mortality in patients after TAVR.MethodsBetween October 2013 and April 2016, 969 patients underwent TF‐TAVI were prospectively included in the OCEAN‐TAVI registry from Japan. The primary outcomes were severe bleeding (including life‐threatening and major bleeding defined in The Valve Academic Research Consortium‐2 criteria) and mortality within 1 year after TAVR.ResultsElderly (84 ± 5 years) and high surgical risk patients (The Society of Thoracic Surgery Risk Score 6.7 [4.6–9.3]) were enrolled. Severe bleeding and mortality had occurred in 177 patients (18.2%) and 66 patients (6.8%), respectively. On multivariate analysis, HAS‐BLED score was associated with severe bleeding (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.41–2.00; p < 0.001) and mortality (HR, 2.04, 95% CI, 1.56–2.69, P < 0.001). A HAS‐BLED score threshold of 4 points (area under the curve 0.71 for severe bleeding, 0.72 for mortality) predicted a higher rate of severe bleeding (25.3% vs. 14.4%, P < 0.001) and mortality (16.2% vs. 4.0%, P < 0.001).ConclusionsHAS‐BLED score could predict the risk of severe bleeding and mortality in patients who underwent TF‐TAVR independent of the presence of atrial fibrillation.
An algorithmic approach for the management of ostial right coronary artery chronic total occlusions
Authors: Avran Alexandre , Boukhris Marouane , Drogoul Laurent , Brilakis Emanouil S 
Published: March 2018

AbstractTreatment of ostial chronic total occlusions (CTOs) of the right coronary artery (RCA) can be challenging. We present an algorithmic approach to the management of such lesions that incorporates all contemporary equipment and techniques. If the RCA ostium can be engaged with a guide catheter then antegrade crossing attempts should be performed. If the antegrade guidewire enters the subintimal space, re‐entry into the distal true lumen is performed provided that the antegrade guide catheter provides enough support. If re‐entry cannot be achieved, the antegrade wire is left in place to facilitate retrograde recanalization attempts (usually performed using the reverse controlled antegrade and retrograde tracking and dissection—reverse CART—technique). If the RCA ostium cannot be engaged with a guide catheter (for example in flush ostial occlusions) or if the guide catheter does not provide sufficient support, a primary retrograde approach is required, aiming for retrograde guidewire puncture into the aorta, followed by snaring and externalization. Retrograde guidewire puncture can be challenging, requiring use of stiff, highly penetrating guidewires or occasionally use of the Carlino technique. The aforementioned algorithm can facilitate crossing of ostial RCA CTOs.
The first transapical transcatheter aortic valve‐in‐valve implantation using the J‐valve system into a failed biophysio aortic prosthesis in a patient with high risk of coronary obstruction
Authors: Ye Jian , Lee Arthur J. , Blanke Philipp , Webb John 
Published: March 2018

AbstractWe report the first successful valve‐in‐valve (ViV) implantation into a failed Edwards Biophysio surgical prosthesis (Edwards Lifesciences, Irvine, CA) and also the first use of the J‐Valve system (Jie Cheng Medical Technologies, Suzhou, China) in a ViV configuration. A 77‐year old male had symptomatic severe aortic stenosis secondary to failure of a 25 mm Biophysio bioprosthetic valve implanted 11 years previously, along with concomitant coronary artery bypass grafting. Transthoracic echocardiography (TTE) revealed calcified leaflets, a mean aortic gradient of 50 mm Hg, and an estimated valve area of 0.9 cm2 with no aortic insufficiency. The patient had low coronary ostial height with the right coronary artery arising only 8.5 mm from the valve annulus and the left main coronary artery arising only 9.4 mm from the valve annulus. Risk of coronary ostial obstruction was especially concerning in context of both the patient's extremely low coronary ostial height and the unique structure of the Biophysio valve. Under general anesthesia, transapical transcatheter aortic ViV implantation with a 25 mm J‐Valve was performed in a hybrid operating room. The J‐Valve prosthesis was deployed in the 25 mm Biophysio surgical valve without difficulty or complications. There were no intraoperative or postoperative complications. The patient was discharged home after 3 days. TTE at 1 year showed a mean aortic valve gradient of 14 mm Hg, and no aortic insufficiency. This case demonstrated that J‐Valve implantation may be a new option for patients at high risk for coronary obstruction.