bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1b Trial of Ficlatuzumab, a Humanized Hepatocyte Growth Factor Inhibitory Monoclonal Antibody, in Combination With Gefitinib in Asian Patients With NSCLC
Authors: Tan Eng‐Huat , Lim Wan‐Teck , Ahn Myung‐Ju , Ng Quan‐Sing , Ahn Jin Seok , Shao‐Weng Tan Daniel , Sun Jong‐Mu , Han May , Payumo Francis C. , McKee Krista , Yin Wei , Credi Marc , Agarwal Shefali , Jac Jaroslaw , Park Keunchil 
Published: January 2018

AbstractHepatocyte growth factor (HGF)/c‐Met pathway dysregulation is a mechanism for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Ficlatuzumab (AV‐299; SCH 900105), a humanized IgG1κ HGF inhibitory monoclonal antibody, prevents HGF/c‐Met pathway ligand–mediated activation. This phase 1b study assessed the safety/tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus gefitinib in Asian patients with previously treated advanced non–small cell lung cancer (NSCLC). Patients received intravenous ficlatuzumab either 10 mg/kg (cohort 1; n = 3) or 20 mg/kg (cohort 2; n = 12) every 2 weeks plus oral gefitinib 250 mg daily. Patients tolerated the drug combination well. Four treatment‐related grade 3/4 adverse events were reported in 3 patients (cohort 2). Pharmacokinetic profiles for ficlatuzumab and gefitinib were consistent with prior single‐agent trials. Partial responses were achieved in 5 patients (4 confirmed), all in cohort 2; objective response rate (ORR) was 33% (duration, 1.9–6.4 months). Responding patients had no prior EGFR TKI treatment, 2 without an EGFR mutation. Four additional patients had disease stabilization (cohort 2; duration, 2.7–9.1 months; 42% ORR). The recommended phase 2 dose for ficlatuzumab plus gefitinib 250 mg/day was 20 mg/kg every 2 weeks. This drug combination has shown preliminary dose‐related antitumor activity in advanced NSCLC.
Sensitive and rapid determination of pyrethroids in human blood by gas chromatography–tandem mass spectrometry with ultrasound‐assisted dispersive liquid‐liquid microextraction
Authors: Gao Xue , Guo Hao , Wang Junwei , Zhao Qingbiao 
Published: January 2018

AbstractIn this study, a sensitive and fast procedure of ultrasonic‐assisted dispersive liquid‐liquid microextraction (UADLLME) coupled with gas chromatography–tandem mass spectrometry (GC–MS/MS) for the determination of major pyrethroid pesticides (permethrin, tetramethrin, bifenthrin, fenvalerate, flucythrinate, fluvalinate, fenpropathrin, deltamethrin, and cyhalothrin) in blood samples was developed. Response surface methodology (RSM) combined with Box‐Behnken design (BBD) and ANOVA function was used to optimize key factors affecting the extraction efficiency of UADLLME procedure. Target compounds were analyzed by GC‐MS/MS. Under the optimal conditions, good linearity (R2>0.99) was achieved for all the analytes in the concentration range of 0.5 to 100 μg L‐1. The recoveries for spiked samples at 3 concentration levels were between 70.2 and 91.8%, with relative standard deviations (RSD) lower than 10%. Very low limits of detection (LODs) and limits of quantification (LOQs) ranging from 0.01 to 0.1 μg L‐1 and from 0.03 to 0.3 μg L‐1 were achieved. This method was successfully applied to the determination of low concentration of pyrethroids in blood samples from real forensic cases. High sensitivity, fast determination, simplicity in operation, small sample volume, and low usage of organic solvents are the advantages of this method. This methodology is of important value for sensitive and quick determination of residue pesticides and metabolites, study of residue pesticides behavior in human body, as well as application in real forensic cases.
The chemistry and pharmacology of synthetic cannabinoid SDB‐006 and its regioisomeric fluorinated and methoxylated analogs
Authors: Banister Samuel D. , Olson Alexander , Winchester Matthew , Stuart Jordyn , Edington Amelia R. , Kevin Richard C. , Longworth Mitchell , Herrera Marco , Connor Mark , McGregor Iain S. , Gerona Roy R. , Kassiou Michael 
Published: January 2018

AbstractSynthetic cannabinoids are the largest and most structurally diverse class of new psychoactive substances, with manufacturers often using isomerism to evade detection and circumvent legal restriction. The regioisomeric methoxy‐ and fluorine‐substituted analogs of SDB‐006 (N‐benzyl‐1‐pentyl‐1H‐indole‐3‐carboxamide) were synthesized and could not be differentiated by gas chromatography–mass spectrometry (GC–MS), but were distinguishable by liquid chromatography–quadrupole time‐of‐flight–MS (LC–QTOF–MS). In a fluorescence‐based plate reader membrane potential assay, SDB‐006 acted as a potent agonist at human cannabinoid receptors (CB1 EC50 = 19 nM). All methoxy‐ and fluorine‐substituted analogs showed reduced potency compared to SDB‐006, although the 2‐fluorinated analog (EC50 = 166 nM) was comparable to known synthetic cannabinoid RCS‐4 (EC50 = 146 nM). Using biotelemetry in rats, SDB‐006 and RCS‐4 evoked comparable reduction in body temperature (~0.7°C at a dose of 10 mg/kg), suggesting lower potency than the recent synthetic cannabinoid AB‐CHMINACA (>2°C, 3 mg/kg).
Dispersal and population state of an endangered island lizard following a conservation translocation
Authors: Angeli Nicole F. , Lundgren Ian F. , Pollock Clayton G. , Hillis‐Starr Zandy M. , Fitzgerald Lee A. 
Published: January 2018

AbstractPopulation size is widely used as a unit of ecological analysis, yet to estimate population size requires accounting for observed and latent heterogeneity influencing dispersion of individuals across landscapes. In newly established populations, such as when animals are translocated for conservation, dispersal and availability of resources influence patterns of abundance. We developed a process to estimate population size using N‐mixture models and spatial models for newly established and dispersing populations. We used our approach to estimate the population size of critically endangered St. Croix ground lizards (Ameiva polops) five years after translocation of 57 individuals to Buck Island, an offshore island of St. Croix, United States Virgin Islands. Estimates of population size incorporated abiotic variables, dispersal limits, and operative environmental temperature available to the lizards to account for low species detection. Operative environmental temperature and distance from the translocation site were always important in fitting the N‐mixture model indicating effects of dispersal and species biology on estimates of population size. We found that the population is increasing its range across the island by 5–10% every six months. We spatially interpolated site‐specific abundance from the N‐mixture model to the entire island, and we estimated 1,473 (95% CI, 940–1,802) St. Croix ground lizards on Buck Island in 2013 corresponding to survey results. This represents a 26‐fold increase since the translocation. We predicted the future dispersal of the lizards to all habitats on Buck Island, with the potential for the population to increase by another five times in the future. Incorporating biologically relevant covariates as explicit parameters in population models can improve predictions of population size and the future spread of species introduced to new localities.
Nitrogen addition and ecosystem functioning: Both species abundances and traits alter community structure and function
Authors: Tatarko Anna R. , Knops Johannes M. H. 
Published: January 2018

AbstractIncreased nutrient inputs can cause shifts in plant community composition and plant functional traits, both of which affect ecosystem function. We studied community‐ and species‐level leaf functional trait changes in a full factorial nitrogen (N), phosphorus (P), and potassium (K) fertilization experiment in a semi‐arid grassland. Nitrogen was the only nutrient addition to significantly affect leaf functional traits, and N addition increased community‐weighted specific leaf area (SLA) by 19%, leaf chlorophyll content by 34%, height by 26%, and leaf dry matter content (LDMC) decreased by 11% while leaf thickness and toughness did not change significantly. At the species level, most species contributed to the community‐weighted trait and increased in SLA, chlorophyll, height, and LDMC with N addition. These intraspecific changes in functional traits account for 51–71% of the community‐level changes in SLA, chlorophyll, plant height, and LDMC. The remaining change is due to species abundance changes; the two most abundant species (Bouteloua gracilis and Carex filifolia) decreased in abundance with N addition while subdominant species increased in abundance. We also found annual variation in SLA, chlorophyll, plant height, and LDMC to be as important in influencing traits as N addition, likely due to differences in precipitation. Aboveground net primary productivity (ANPP) did not change significantly with N addition. However, N addition caused a 34% increase in leaf area index (LAI) and a 67% increase in canopy chlorophyll density. We demonstrate that nitrogen‐induced changes in both functional traits and species abundances magnify ANPP changes in LAI and canopy chlorophyll density. Therefore, ANPP underestimates N addition‐induced ecosystem‐level changes in the canopy vegetation.
Sea Salts Flavored with Mediterranean Herbs and Fruits Prevent Cholesterol and Phospholipid Membrane Oxidation and Cell Free Radical Generation
Authors: Rosa Antonella , Putzu Danilo , Atzeri Angela , Cesare Marincola Flaminia , Sarais Giorgia 
Published: January 2018

The authors evaluated and compared, with respect to normal salt, the antioxidant activity of commercial sea salts flavored with Mediterranean herbs and fruits in chemical models of lipid peroxidation and in cell cultures. Salts flavored with myrtle, rosemary, and a mixture of herbs/plants preserves liposomes from Cu2+‐induced oxidation. Methanol extracts obtained from all flavored sea salts significantly reduces the reactive oxygen species generation in Caco‐2 cells, while extracts obtained from myrtle, rosemary, and mixed herbs/plants salts prevents cholesterol oxidative degradation (140 °C). 1H NMR spectroscopy led to the identification of carbohydrates, organic acids, and amino acids in salt extracts. The phenol content of flavored salts is estimated by the Folin–Ciocalteu procedure and HPLC–DAD analyses. The results of this work assess the potential antioxidant role and health benefits of the use of flavored sea salts in foods instead of normal salt.Practical Applications: This preliminary study evidences that the addition of sea salts flavored with Mediterranean herbs and fruits to food products could represents a strategy to preserve salt‐induced lipid oxidation and a source of antioxidants with potential health benefits.Four sea salts flavored with Mediterranean herbs/plants and fruits inhibit cholesterol/liposomes oxidation and reduce cell ROS generation.
Understanding land use and cover change impacts on run‐off and sediment load at flood events on the Loess Plateau, China
Authors: Zhang Xiaoping , Lin Pengfei , Chen Hao , Yan Rui , Zhang Jianjun , Yu Yipeng , Liu Erjia , Yang Yahui , Zhao Wenhui , Lv Du , Lei Siyue , Liu Baoyuan , Yang Xihua , Li Zhiguang 
Published: January 2018

AbstractThe Loess Plateau has been experiencing large‐scale land use and cover changes (LUCCs) over the past 50 years. It is well known about the significant decreasing trend of annual streamflow and sediment load in the catchments in this area. However, how surface run‐off and sediment load behaved in response to LUCC at flood events remained a research question. We investigated 371 flood events from 1963 to 2011 in a typical medium‐sized catchment within the Plateau in order to understand how LUCC affected the surface run‐off generation and sediment load and their behaviours based on the analysis of return periods. The results showed that the mean annual surface run‐off and sediment load from flood events accounted for 49.6% and 91.8% of their mean annual totals. The reduction of surface run‐off and associated sediment yield in floods explained about 85.0% and 89.2% of declines in the total annual streamflow and sediment load, respectively. The occurrences of flood events and peak sediment concentrations greater than 500 kg/m3showed a significantly downward trend, yet the counterclockwise loop events still dominated the flood event processes in the catchment. The results suggest that LUCC over the past 50 years resulted in significant changes in the water balance components and associated soil erosion and sediment transportation in the catchment. This was achieved mainly by reducing surface run‐off and sediment yield during floods with return period of less than 5 years. Run‐off–sediment load behaviour during the extreme events with greater than 10‐year return periods has not changed. Outcomes from this study are useful in understanding the eco‐hydrological processes and assisting the sustainable catchment management and land use planning on the Loess Plateau, and the methodologies are general and applicable to similar areas worldwide.
Multiple biological defects caused by calycosin‐7‐O‐β‐d‐glucoside in the nematode Caenorhabditis elegans are associated with the activation of oxidative damage
Authors: Zhang Jianqin , Xue Xiaoli , Yang Yang , Ma Wen , Han Yan , Qin Xuemei 
Published: January 2018

AbstractCalycosin‐7‐O‐β‐d‐glucoside (CG) is an important active isoflavone compound in Radix Astragali that has many bioactivities. However, the toxicological effects and related toxicological mechanism of CG have been rarely documented. The purpose of the present study was to evaluate the toxicity effects of CG on the model organism Caenorhabditis elegans. Some characteristics of the nematode, including lifespan, movement behavior and reproductive capacity, were used to detect the toxic effects of CG on C. elegans. The results showed that CG could shorten the lifespan of C. elegans by up to 25.3% and severely damage the movement of N2 larvae compared with the control group. Moreover, CG could prolong the generation times and reduce the brood sizes. Furthermore, CG promoted the formation of reactive oxygen species (ROS), which caused oxidative stress, increased the mRNA expression of sod‐1, sod‐2, sod‐3, sod‐5, ctl‐1, ctl‐2 and ctl‐3, and induced the antioxidant enzymes activities of superoxide dismutase and catalase to scavenge free radicals. However, antioxidant treatment experiments showed that Trolox could reduce the level of ROS caused by CG to the normal state of the control. These results suggested that the generation and elimination of ROS could not restore normal homeostasis in C. elegans treated by CG. These findings indicated that the activation of oxidative damage is one of the most important toxic mechanisms of CG in C. elegans.
Morphological specializations of the epidermis of an angler catfish Chaca chaca (Siluriformes, Chacidae) in relation to its ecological niche: A scanning electron microscopic investigation
Authors: Mistri Arup , Kumari Usha , Mittal Swati , Mittal Ajay Kumar 
Published: January 2018

AbstractThe present work was undertaken with the aim to deduce morphological adaptations in skin of an angler catfish Chaca chaca by means of scanning electron microscopy. The fish is nocturnal, bottom dwelling, sluggish, ambush predator, lives in sand, mud, or soft substrates often buried and camouflaged for protection and to feed. The surface of the epidermis is covered with polygonal epithelial cells, each having surface relief of microridges forming intricate patterns. In between epithelial cells irregularly distributed mucous cell openings, randomly distributed epidermal specialized structures, taste buds, and neuromasts are discernible. The epidermal specialized structures are keratinized. These are either irregularly the rounded elevated plaque like or the cone shaped structures. The superficial keratinized cells could frequently be discernible exfoliated at the surface. At intervals, characteristic epidermal projections could be observed. Surface of these projections at intervals is differentiated into short stumpy protuberances, each bearing a taste bud at its summit. Further, near the basal portion of these epidermal projections, conical, or rounded plaque like epidermal specialized structures are also discernible. The surface sculpture of the skin of Chaca chaca is associated with the structural and functional significance and physiological adaptations of the epidermis with respect to its ecological niche.
Tandem mass spectroscopy as a tool for investigation of complexes of PNP‐lariat ether derivative with metal ions
Authors: Gutowska Natalia , Seliger Piotr , Andrijewski Grzegorz , Adamus Grażyna , Kwiecień Iwona 
Published: January 2018

AbstractThe novel PNP‐lariat ether L with cyclotriphosphazene ring incorporated in the macrocyclic structure was synthesized and checked by the electrospray mass spectrometry (ESI‐MS) method for the ability to bind different types of ions Ag+, Ca2+, Cd2+, Cu2+, and Pb2+. Furthermore, the stability constants of the abovementioned ion complexes with the investigated ligand have been determined by direct and competitive potentiometric methods. To evaluate the stability of various complex types and to confirm the way of metal cation binding, the tandem mass spectra of the investigated ligand and its complexes were taken. As a result, we obtained quite a good relationship between the number and main types of complex species observed in ESI‐MS experiments and the forms of complexes for which the stabilization constants were determined by potentiometric methods. Moreover, we also concluded that in case of big discrepancies of stability constants, ESI‐MS experiments could provide information about the most stable form of the complexes, but they fail when the differences between the strength of the coordination binding are slightly different.
Seasonal prediction skill of Indian summer monsoon rainfall in NMME models and monsoon mission CFSv2
Authors: Pillai Prasanth A. , Rao Suryachandra A. , Ramu Dandi A. , Pradhan Maheswar , George Gibies 
Published: January 2018

ABSTRACTThe present study compares the Indian summer monsoon rainfall (ISMR) prediction skill of monsoon mission climate forecast system version 2 (CFSv2‐T382) with that of the seasonal prediction models participating in US National Multi‐Model Ensemble (NMME) project. In general, the present‐day models simulate cooler than observed sea surface temperature (SST) in majority of the Tropics and extratropics. The model rainfall has strong dry bias over major continental regions and wet bias over tropical oceans. Meanwhile, prediction of the boundary forcing such as SST is essential for driving the atmospheric response through teleconnections. It is noted that even though the prediction skill for SST boundary forcings like El Niño‐Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD) is not at the best in CFSv2‐T382 compared to a few of the NMME models, it shows better skill for ISMR hindcasts initialized at 3‐month lead time (February IC). This may be attributed to the better teleconnection pattern of ENSO and IOD in CFSv2‐T382, which has minimum biases in equatorial Indo‐Pacific region. It also has a better ISMR–SST teleconnections in the Tropics with a pattern correlation of around 0.6. In many of the NMME models, the better prediction skill of the inter‐annual variability of SST indices is not transformed into the improvement of ISMR skill through teleconnections. It is therefore concluded that having good prediction skill for major SST boundary forcings is not sufficient, but capturing the appropriate teleconnections of these SST boundary forcings in the model is critical for the better prediction of ISMR. The study points out that the present‐day seasonal prediction systems need to be improved in their simulation of tropical SST–monsoon teleconnections, which can improve the seasonal prediction skill of Indian summer monsoon further. One area where the immediate focus is required is the Indian Ocean SST and ISMR teleconnection.
Sources of moisture for different intensities of summer rainfall over the Chinese Loess Plateau during 1979–2009
Authors: Hu Qin , Jiang Dabang , Lang Xianmei 
Published: January 2018

ABSTRACTIn this study, moisture sources for different intensities of summer (June–July–August) rainfall over the Chinese Loess Plateau (CLP) were investigated by performing a transient simulation for the period 1979–2009 using the Lagrangian particle dispersion model FLEXPART. The results showed that continental areas surrounding the CLP, namely northwestern China–eastern central Asia and central eastern China, were major moisture source regions for summer rainfall over the CLP and that oceanic moisture originated from the East China Sea, the South China Sea, the Bay of Bengal, and the Arabian Sea played a secondary role. The moisture contribution of northwestern China–eastern central Asia to the CLP significantly decreased with increasing intensity of rainfall, whereas the contribution of central eastern China to the CLP slightly increased. Moreover, the moisture contribution of oceanic source regions to the CLP increased with the increased rainfall intensity. The East China Sea and the Bay of Bengal were the two most substantial oceanic moisture source regions for the 0–5th percentile (0–P5th) to 50th–75th percentile (P50th–P75th) rainfall classes, whereas the South China Sea and the Bay of Bengal were the two most substantial oceanic moisture source regions for the 75th–95th percentile (P75th–P95th) and the 95th–100th percentile (P95th–P100th) rainfall classes.