bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of implant‐delivered insulin on bone formation in osteoporotic rats
Authors: Malekzadeh Behnosh Ö. , Erlandsson Malin C. , Tengvall Pentti , Palmquist Anders , Ransjo Maria , Bokarewa Maria I. , Westerlund Anna
Published: April 2018

Osteoporosis is a major cause of age‐related fractures. Healing complications in osteoporotic patients are often associated with increased mortality and morbidity. Stimulation of the implant‐adjacent bone could be beneficial in terms of the surgical outcome. Over the past decade, numerous investigations have implicated insulin in normal bone growth, and recent studies have described the advantages of administering insulin locally to increase bone formation. Therefore, we hypothesized that insulin‐coated titanium implants would increase bone formation in osteoporotic animals. The aim of this study was to evaluate the effects of insulin delivered from an implant surface on bone‐related gene expression and bone formation in osteoporotic rats. Characterizations of the surfaces of insulin‐coated and control implants were performed using ellipsometry and interferometry. Forty ovariectomized and four healthy Sprague Dawley rats were used and implants were inserted in the tibias. The systemic effect of insulin was assessed by measuring the blood glucose levels and total body weight. The animals were sacrificed either 1 day or 3 weeks postimplantation. Implant‐adherent cells were analyzed by quantitative real‐time PCR, and the bone adjacent to the implants was examined by microcomputed tomography and histomorphometry. The insulin‐coated implants had no systemic effects. The insulin‐coated samples demonstrated significantly lower expression of the gene for interleukin 1β (p = 0.019) at 1 day, and significantly exhibited more periosteal callus (p = 0.029) at 3 weeks. Locally delivered insulin has potential for promoting bone formation and it exerts potentially anti‐inflammatory effects in osteoporotic rats. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2472–2480, 2018.
The natural mathematics of behavior analysis
Authors: Li Don , Hautus Michael J. , Elliffe Douglas
Published: April 2018

Models that generate event records have very general scope regarding the dimensions of the target behavior that we measure. From a set of predicted event records, we can generate predictions for any dependent variable that we could compute from the event records of our subjects. In this sense, models that generate event records permit us a freely multivariate analysis. To explore this proposition, we conducted a multivariate examination of Catania's Operant Reserve on single VI schedules in transition using a Markov Chain Monte Carlo scheme for Approximate Bayesian Computation. Although we found systematic deviations between our implementation of Catania's Operant Reserve and our observed data (e.g., mismatches in the shape of the interresponse time distributions), the general approach that we have demonstrated represents an avenue for modelling behavior that transcends the typical constraints of algebraic models.
Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD)
Authors: Khoury Paneez , Akuthota Praveen , Ackerman Steven J , Arron Joseph R , Bochner Bruce S , Collins Margaret H , Kahn Jean-Emmanuel , Fulkerson Patricia C , Gleich Gerald J , Gopal-Srivastava Rashmi , Jacobsen Elizabeth A , Leiferman Kristen M , Francesca Levi-Schaffer , Mathur Sameer K , Minnicozzi Michael , Prussin Calman , Rothenberg Marc E , Roufosse Florence , Sable Kathleen , Simon Dagmar , Simon Hans-Uwe , Spencer Lisa A , Steinfeld Jonathan , Wardlaw Andrew J , Wechsler Michael E , Weller Peter F , Klion Amy D
Published: April 2018

Eosinophil-associated diseases (EADs) are rare, heterogeneous disorders characterized by the presence of eosinophils in tissues and/or peripheral blood resulting in immunopathology. The heterogeneity of tissue involvement, lack of sufficient animal models, technical challenges in working with eosinophils, and lack of standardized histopathologic approaches have hampered progress in basic research. Additionally, clinical trials and drug development for rare EADs are limited by the lack of primary and surrogate endpoints, biomarkers, and validated patient-reported outcomes. Researchers with expertise in eosinophil biology and eosinophil-related diseases reviewed the state of current eosinophil research, resources, progress, and unmet needs in the field since the 2012 meeting of the NIH Taskforce on the Research of Eosinophil-Associated Diseases (TREAD). RE-TREAD focused on gaps in basic science, translational, and clinical research on eosinophils and eosinophil-related pathogenesis. Improved recapitulation of human eosinophil biology and pathogenesis in murine models was felt to be of importance. Characterization of eosinophil phenotypes, the role of eosinophil subsets in tissues, identification of biomarkers of eosinophil activation and tissue load, and a better understanding of the role of eosinophils in human disease were prioritized. Finally, an unmet need for tools for use in clinical trials was emphasized. Histopathologic scoring, patient- and clinician-reported outcomes, and appropriate coding were deemed of paramount importance for research collaborations, drug development, and approval by regulatory agencies. Further exploration of the eosinophil genome, epigenome, and proteome was also encouraged. Although progress has been made since 2012, unmet needs in eosinophil research remain a priority.

Review on eosinophil biology and eosinophil-related disorders (2012–2017) with a focus on continued unmet needs in eosinophil-associated diseases.
Aqueous chlorination of sulfamethazine and sulfamethoxypyridazine: Kinetics and transformation products identification
Authors: Nassar Rania , Rifai Ahmad , Trivella Aurélien , Mazellier Patrick , Mokh Samia , Al‐Iskandarani Mohamad
Published: April 2018

Sulfonamides (SNs) are synthetic antimicrobial agents. These substances are continually introduced into the environment, and they may spread and maintain bacterial resistance in the different compartments. The chlorination of 2 SNs, namely, sulfamethazine (SMT) and sulfamethoxypyridazine (SMP), was investigated to study their reactivity with chlorine at typical concentrations for water treatment conditions. Experiments conducted in purified water show an acceleration of SMT and SMP degradation of a factor 1.5 by comparison to drinking water matrix. This difference is due to pH variation and competitive reactions between SNs and mineral and organic compounds, with chlorine in drinking water. In the presence of an excess of chlorine (6.7 μmol·L−1) in ultrapure water at pH 7.2, second‐order degradation rate constants were equal to 4.5 × 102M−1·s−1 and 5.2 × 102M−1·s−1 for SMT and SMP, respectively. The structures of transformation products were investigated by liquid chromatography tandem mass spectrometry analyses with equimolar concentrations between chlorine and SNs. SO2 elimination, cyclization, and electrophilic substitutions were the main pathways of by‐products formation. Moreover, the toxicity of the proposed structures was predicted by using toxicity estimation software tool program. The results indicated that most by‐products may present developmental toxicity.
Projected shift of Köppen–Geiger zones in the central Europe: A first insight into the implications for ecosystems and the society
Authors: Skalák Petr , Farda Aleš , Zahradníček Pavel , Trnka Miroslav , Hlásny Tomáš , Štěpánek Petr
Published: April 2018

We examined a future change of Köppen–Geiger climate classification zones in central Europe in the 21st century using the high‐resolution (10 km) bias‐corrected simulations of two regional climate models following the IPCC SRES A1B emission scenario. Temperate oceanic climate (Cfb) will remain the dominant climate type in central Europe but it will extent into higher altitudes and replace boreal or colder climate types that will practically vanish by the end of the 21st century. There is a risk of large‐scale expansion of humid subtropical (Cfa) climate in lower altitudes where 20–50% of population lives nowadays. In the end of the century the majority of arable land and permanent crops areas will be in the Cfa zone. A growing occurrence of Cfa‐like or Mediterranean climate‐like (Csa) years will reach up to 50% at some locations where 1.4 million people live today. Almost all agriculturally important areas and two thirds of the current population will be exposed to the occurrence of Cfa‐ and Csa‐like years at least once in 10 years which may result into a lower production of rain‐fed crops as it was the case of of Cfa‐ and Csa‐like years of 2000, 2012 and 2015.
How the two nodes of the tropical Atlantic sea surface temperature dipole relate the climate of the surrounding regions during austral autumn
Authors: Kayano Mary Toshie , Andreoli Rita Valéria , Garcia Sâmia Regina , de Souza Rodrigo Augusto Ferreira
Published: April 2018

The relations of both nodes of the tropical Atlantic (TA) cross‐equatorial sea surface temperature (SST) gradient (GRAD) mode to the climate of northeast Brazil (NEB) during the 1901–2012 period are examined separately. The GRAD mode consists of a SST anomalous pattern anti‐symmetric about the equator with centres in the region of the northeasterly and southwesterly trade winds. The positive GRAD (PGRAD) (negative GRAD [NGRAD]) modes defined by their northern or southern nodes are considered separately, as well as, if they are preceded or not by an El Niño (EN) (a La Niña, LN). The PGRAD mode defined by the northern (southern) node and preceded by an EN is indicated by PGRAD_TNA_EN (PGRAD_TSA_EN), and that not preceded by an EN is indicated by PGRAD_TNA (PGRAD_TSA). The corresponding NGRAD modes are indicated by NGRAD_TNA_LN, NGRAD_TSA_LN, NGRAD_TNA and NGRAD_TSA. Our analysis is limited to the NEB rainy season (March–May), when the GRAD mode is more pronounced and the NEB rainfall is more closely related to the TA SST variations. In general, the South Atlantic subtropical high is crucial in defining the cross‐equatorial flow, responsible for the anomalous meridional positioning of the Atlantic inter‐tropical convergence zone. When a positive (negative) dipole‐like SST anomaly pattern is established in the TA, the negative (positive) rainfall anomalies occupy most of NEB. This is the case of the PGRAD_TSA_EN, PGRAD_TNA, NGRAD_TSA_LN and NGRAD_TNA_LN. Most of the GRAD modes defined by TNA are also related to the El Niño‐Southern Oscillation (ENSO), in such a way that an EN (a LN) precedes a PGRAD (NGRAD) event, and most of the GRAD modes defined by TSA do not depend on the ENSO. Also, the PGRAD events are well distributed during both Atlantic multidecadal oscillation phases and the NGRAD events occur preferably during its cold phase.
Season‐dependent warming characteristics observed at 12 stations in South Korea over the recent 100 years
Authors: Choi Woosuk , Ho Chang‐Hoi , Kim Maeng‐Ki , Kim Jinwon , Yoo Hee‐Dong , Jhun Jong‐Ghap , Jeong Jee‐Hoon
Published: April 2018

A number of studies on the surface warming in the Korean Peninsula reported that there has been a notable increasing trend of surface air temperatures over the past several decades. Here, by analysing long‐term surface air temperature data at 12 stations in South Korea that have records longer than 60 years, the authors show that the warming of spring and autumn temperatures is characterized by quasi‐linear increases with time whereas the warming in winter and summer is characterized by one or two abrupt jumps. Change‐point analysis of the seasonal‐mean temperature time series shows that abrupt jumps in winter temperatures occurred in the late 1940s and late 1980s, while the jump in summer temperatures occurred in 1994 at most stations. The shape of the frequency distribution of the daily‐mean temperature anomalies at all stations shifts to the warmer side after the jumps for both winter and summer. This shift in turn results in the decrease of cold extremes in winter and the increase of warm extremes in summer at all stations. Our results indicate that recent temperature records in South Korea are characterized by the two different types of warming according to seasons.
Carotid Artery Stiffness Assessment by Ultrafast Ultrasound Imaging: Feasibility and Potential Influencing Factors
Authors: Pan Fu‐shun , Yu Liang , Luo Jia , Wu Ri‐dong , Xu Ming , Liang Jin‐yu , Zheng Yan‐ling , Xie Xiao‐yan
Published: April 2018

Objectives

To evaluate the feasibility of the ultrafast ultrasound pulsed wave velocity (PWV) for carotid stiffness assessment and potential influencing factors.

Methods

Ultrafast PWV measurements of 442 carotid arteries in 162 consecutive patients (patient group) and 66 healthy volunteers (control group) were performed. High‐ and very high‐frequency transducers were used in 110 carotid segments. The ultrafast PWVs at the beginning and end of systole were automatically measured. The correlations between the intima‐media thickness (IMT) and ultrafast PWV and the equipment and carotid factors influencing the utility of ultrafast PWV were analyzed.

Results

Each ultrafast PWV acquisition was completed within 1 minute. The intraobserver variability showed mean differences ± SD of 0.12 ± 1.28 m/s for the PWV before systole and 0.06 ± 1.30 m/s for the PWV at the end of systole. Ultrafast PWV measurements were more likely obtained with the very high‐ frequency transducer when the IMT was less than 1.5 mm (P < .05). A generalized linear mixed‐effects model analysis showed that the very high‐frequency transducer had a greater ability to obtain a valid carotid ultrafast PWV measurement with an IMT of less than 1.5 mm (P < .05). The IMT was positively correlated with the PWV before systole and at the end of systole (r = 0.207–0.771; all P < .05) in the control group, patient group, and carotid subgroup with an IMT of less than 1.5 mm. A multiple regression analysis showed that the IMT and plaque were important independent factors in predicting failure of the ultrafast PWV (P < .001).

Conclusions

The ultrafast PWV is an effective and user‐friendly method for evaluating carotid stiffness. The IMT and transducer type are factors influencing the ability to obtain an ultrafast PWV measurement.
Quantitative mapping of soil salinity using the DUALEM‐21S instrument and EM inversion software
Authors: Koganti Triven , Narjary Bhaskar , Zare Ehsan , Pathan Aslam Latif , Huang Jingyi , Triantafilis John
Published: April 2018

To generate baseline data for the purpose of monitoring the efficacy of remediation of a degraded landscape, we demonstrate a method for 3‐dimensional mapping of electrical conductivity of saturated soil paste extract (ECe) across a study field in central Haryana, India. This is achieved by establishing a linear relationship between calculated true electrical conductivity (σ) and laboratory measured ECe at various depths (0–0.3, 0.3–0.6, 0.6–0.9, and 0.9–1.2 m). We estimate σ by inverting DUALEM‐21S apparent electrical conductivity (ECa) data using a quasi‐3‐dimensional inversion algorithm (EM4Soil‐V302). The best linear relationship (ECe = −11.814 + 0.043 × σ) was achieved using full solution (FS), S1 inversion algorithm, and a damping factor (λ) of 0.6 that had a large coefficient of determination (R2 = 0.84). A cross‐validation technique was used to validate the model, and given the high accuracy (RMSE = 8.31 dS m−1), small bias (mean error = −0.0628 dS m−1), large R2 = 0.82, and Lin's concordance (0.93), between measured and predicted ECe, we were well able to predict the ECe distribution at all the four depths. However, the predictions made in the topsoil (0–0.3 m) at a few locations were poor due to limited data availability in areas where ECa changed rapidly. In this regard, improvements in prediction can be achieved by collection of ECa in more closely spaced transects, particularly in areas where ECa varies over short spatial scales. Also, equivalent results can be achieved using smaller combinations of ECa data (i.e., DAULEM‐1S, DUALEM‐2S), although with some loss in precision, bias, and concordance.
Cabells’ Journal Whitelist and Blacklist: Intelligent data for informed journal evaluations
Authors: Bisaccio Michael
Published: April 2018

Key points

Cabells’ Whitelist of ca. 11,000 quality journals has recently been joined by a Blacklist of over 8,300 journals that fail basic quality criteria.

Cabells’ Journal Blacklist is the only searchable database of deceptive and fraudulent journals with comprehensive reports detailing violations.

Key components for establishing the Blacklist were objectivity and transparency with respect to the evaluation process and selection criteria, and unbiased evaluations.

The Blacklist evaluation criteria were tested to ensure accurate judgement and are continually evolving to maintain suitability.

Over 800 journals are added to the Blacklist each month.
Nano‐scaled and aggregated films to protect carbon steel from corrosion in hydrochloric acid
Authors: Ma Lan , He Yi , Luo Pingya , Zhang Liyun , Zhou Yanqiu , Zhang Lei
Published: April 2018

An efficient corrosion inhibitor named BTA‐IM is reported in this contribution. The inhibition performance of BTA‐IM for carbon steel in 1 M HCl is investigated and the possible inhibition mechanism is proposed. According to weight‐loss experiments, the inhibition efficiency of BTA‐IM can reach to 98%. Secondly, the morphology investigation illustrates that the nano‐scaled, dendrimer‐like, and multi‐layer films cover the metal surface regularly and compactly through self‐assembly. Thirdly, the thickness of the films on surface of metal is gradually increased with the increasing dosage of inhibitor, and the aggregated films are obtained. Possibly, the aggregated films are born of absorption films and the increased concentration of BTA‐IM, giving rise to the regular and compact films.
Ordering Polymer‐Grafted Nanoparticles at Oil–Air Interfaces under Magnetic Fields
Authors: Liu Siqi , Wang Haoyu , Akcora Pinar
Published: April 2018

Polymer‐grafted magnetic nanoparticles at oil–air interfaces are examined to reveal the role of chain length and anisotropy on particle packing order in thin films. It is found that particles grafted with intermediate chain lengths and sparse grafting densities exhibit enhanced packing order with increasing magnetic field strength. Voronoi tessellation results present an increase in the cell area distribution of these samples, suggesting that chain conformations are affected. For the longest graft length, particles become more disordered under magnetic fields. It is proposed that fluctuations in the bridged chains rearrange particles into less ordered packing with field application and the mechanism of packing order differs for varying graft chain lengths. Grafting anisotropy is found to determine the spatial nanoparticle organization in assembled monolayers.
Targeting HSP60 by subcutaneous injections of jetPEI/HSP60‐shRNA destabilizes cytoplasmic survivin and inhibits hepatocellular carcinoma growth
Authors: Huang Ya‐Hui , Lin Kwang‐Huei , Yu Jau‐Song , Wu Ting‐Jung , Lee Wei‐Chen , Chao Chuck C.‐K. , Pan Tai‐Long , Yeh Chau‐Ting
Published: April 2018

Heat shock protein 60 (HSP60) overexpresses in various types of cancer, but its expression levels and functions in hepatocellular carcinoma (HCC) are still in dispute. We aim to clarify this issue and examine whether HSP60 could be a therapeutic target for HCC. We found drastically enhanced cell apoptosis and suppressed cell proliferation in two HCC cell lines with HSP60‐silencing, and also indicated survivin was involved in this regulatory process in vitro and in vivo. However, HSP60‐silencing in normal human hepatocytes only resulted in a minimal reduction of cell proliferation but without effects on cell apoptosis. We also showed HSP60 interacted with cytosolic but not mitochondrial survivin by immunoprecipitation assay. A rigorous method was used to standardize quantification from immunoblot assay to obtain more precise expression levels of HSP60 and survivin. The expression of HSP60 and survivin positively correlated in both cancerous and non‐cancerous liver tissues (P < 0.001) after analyzing 145 surgically removed HCC tissues. A total of 56.6% of HCC patients overexpressed HSP60 in cancerous tissues, and 40.0% under‐expressed HSP60. Higher expression of HSP60 and survivin in non‐cancerous tissues both correlated with shorter overall survival (P = 0.029 and P < 0.001, respectively). Finally, we evaluated the therapeutic potential of HSP60 using extraneous delivery of jetPEI/shHSP60 complexes. The treatment results showed significant reduction of tumor weight by 44.3% (P < 0.05), accompanied by under‐expression of survivin. These studies suggested that HSP60 not only served as a prognostic marker but also served as a novel therapeutic target for HCC.
Dual role of Par‐4 in abrogation of EMT and switching on Mesenchymal to Epithelial Transition (MET) in metastatic pancreatic cancer cells
Authors: Katoch Archana , Suklabaidya Sujit , Chakraborty Souneek , Nayak Debasis , Rasool Reyaz U. , Sharma Deepak , Mukherjee Debaraj , Faheem Mir M. , Kumar Anmol , Sharma Parduman R. , Senapati Shantibhusan , Kumar Lekha D. , Goswami Anindya
Published: April 2018

Epithelial‐mesenchymal transition (EMT) is a critical event that occurs during the invasion and metastatic spread of cancer cells. Here, we conceive a dual mechanism of Par‐4‐mediated inhibition of EMT and induction of MET in metastatic pancreatic cancer cells. First, we demonstrate that 1,1′‐β‐D‐glucopyranosyl‐3,3′‐bis(5‐bromoindolyl)‐octyl methane (NGD16), an N‐glycosylated derivative of medicinally important phytochemical 3,3′‐diindolylmethane (DIM) abrogates EMT by inducing pro‐apoptotic protein Par‐4. Induction of Par‐4 (by NGD16 or ectopic overexpression) strongly impedes invasion with inhibition of major mesenchymal markers viz. Vimentin and Twist‐1 epithelial marker‐ E‐cadherin. Further, NGD16 triggers MET phenotypes in pancreatic cancer cells by augmenting ALK2/Smad4 signaling in a Par‐4‐dependent manner. Conversely, siRNA‐mediated silencing of endogenous Par‐4 unveil reversal of MET with diminished E‐cadherin expression and invasive phenotypes. Additionally, we demonstrate that intact Smad4 is essential for Par‐4‐mediated maintenance of E‐cadherin level in MET induced cells. Notably, we imply that Par‐4 induction regulates E‐cadherin levels in the pancreatic cancer cells via modulating Twist‐1 promoter activity. Finally, in vivo studies with syngenic mouse metastatic pancreatic cancer model reveal that NGD16 strongly suppresses metastatic burden, ascites formation, and prolongs the overall survival of animals effectively.
Do brain structural abnormalities differentiate separate forms of urgency urinary incontinence?
Authors: Clarkson Becky D. , Griffiths Derek , Resnick Neil M.
Published: April 2018

Aims

Urgency urinary incontinence (UUI) is a major problem for seniors. The underlying mechanisms of disease and therapy are unknown. We sought structural brain abnormalities that might underlie the functional differences previously observed by functional Magnetic Resonance Imaging in UUI patients versus controls, or among UUI responders versus non‐responders to therapy—and thereby reveal potential disease mechanisms and therapeutic targets.

Methods

Secondary study of a trial of biofeedback‐assisted pelvic floor muscle training (BFB) in 60 women (>60 yrs) with UUI, plus 11 age‐matched continent controls. Brain structural abnormalities were investigated using: (1) white‐matter hyperintensities (WMH); (2) diffusion tensor imaging (DTI) to reveal white‐matter pathways with impaired integrity; and (3) voxel‐based morphometry (VBM) to show regions of atrophy or hypertrophy.

Results

WMH burden was greater in UUI patients than controls (globally and in superior longitudinal fasciculus and cingulum), suggesting a possible causal connection. WMH burden was unexpectedly greater in responders than non‐responders to BFB, and appeared to increase in non‐responders but not in responders. DTI revealed even worse integrity of the cingulum than was apparent by WMH. VBM showed parahippocampal atrophy in UUI.

Conclusions

Many women with UUI have white‐matter damage that interferes with pathways critical to bladder control; they can be taught by techniques like BFB to exert stronger control over the bladder. For others, in whom abnormalities of key brain areas are less marked, UUI's cause may reside elsewhere, and therapy targeting these brain centers may be less effective than therapy targeting the bladder or other brain centers.
Dual‐frequency irradiation CEST‐MRI of endogenous bulk mobile proteins
Authors: Goerke Steffen , Breitling Johannes , Zaiss Moritz , Windschuh Johannes , Kunz Patrick , Schuenke Patrick , Paech Daniel , Longo Dario L. , Klika Karel D. , Ladd Mark E. , Bachert Peter
Published: April 2018

A novel MRI contrast is proposed which enables the selective detection of endogenous bulk mobile proteins in vivo. Such a non‐invasive imaging technique may be of particular interest for many diseases associated with pathological alterations of protein expression, such as cancer and neurodegenerative disorders. Specificity to mobile proteins was achieved by the selective measurement of intramolecular spin diffusion and the removal of semi‐solid macromolecular signal components by a correction procedure. For this purpose, the approach of chemical exchange saturation transfer (CEST) was extended to a radiofrequency (RF) irradiation scheme at two different frequency offsets (dualCEST). Using protein model solutions, it was demonstrated that the dualCEST technique allows the calculation of an image contrast which is exclusively sensitive to changes in concentration, molecular size and the folding state of mobile proteins. With respect to application in humans, dualCEST overcomes the selectivity limitations at relatively low magnetic field strengths, and thus enables examinations on clinical MR scanners. The feasibility of dualCEST examinations in humans was verified by a proof‐of‐principle examination of a brain tumor patient at 3 T. With its specificity for the mobile fraction of the proteome, its comparable sensitivity to conventional water proton MRI and its applicability to clinical MR scanners, this technique represents a further step towards the non‐invasive imaging of proteomic changes in humans.
The oxen of Oxon Hill Manor: Pathological analyses and cattle husbandry in eighteenth‐century Maryland
Authors: Carlson Dietmeier Jenna Kay
Published: April 2018

The methodologies for identifying and analyzing draught cattle from the archaeological record have been developed and refined over the past 20 years. In assessing the pathological manifestations present on complete Bos taurus metapodials and phalanges from the 18‐century Chesapeake plantation known as Oxon Hill Manor, this research reveals the applicability of the pathological index to studies of traction animals and animal husbandry in historical North American faunal assemblages. This research also utilizes the newly established modified pathological index as a means of assessing incomplete metapodials for possible pathological signatures of traction. As Oxon Hill Manor was home to an elite planting family, the site provides the opportunity to explore the changing roles of draught oxen with the shift from tobacco to diversified agriculture in the last half of the 18th century. Combined with evidence from the documentary record of Oxon Hill Manor, this research demonstrates that analyses of cattle pathologies can be used not only to evaluate the presence of draught oxen in the zooarchaeological record but also to illuminate nuances in husbandry practices pertaining to all cattle at the site.
Electrical conductivity and dielectric properties of nanofibrillated cellulose thin films from bagasse
Authors: Abdel‐karim Amal M. , Salama A. H. , Hassan Mohammad L.
Published: April 2018

Nanocelluloses are potential candidates for applications in flexible electronic due to their unique physical and mechanical properties. However, electrical properties of these materials have not investigated thoroughly to study their electrical properties. In the current work, electrical properties of nanocellulose films prepared from bagasse pulp were studied and compared with those of bagasse pulp fibers. Two kinds of nanocelluloses were used in the current study: microfibrillated cellulose (MFC) and TEMPO‐oxidized nanofibrillated cellulose (NFC). The crystallinity, grain size, and morphology of the different nanocelluloses were studied using X‐ray diffraction and transmission electron microscopy techniques. The dc‐, ac‐ electrical conductivity, dielectric constant ɛ′, and dielectric loss ɛ″ of non‐plasticized and glycerol‐plasticized nanocellulose films were studied in the temperature range from 298 to 373 K and in the frequency range from 0.1 KHz to 5 MHz. The results showed that the dc‐ electrical conductivity verifies Arrhenius equation and the activation energies varied in the range of 0.9 to 0.42 eV. Ac‐electrical conductivity increased with frequency and fitted with power law equation, which ensures that the conduction goes through hopping mechanism. The dielectric constant decreased with increasing frequency and increased with increasing temperature, probably due to the free movement of dipole molecular chains within the cellulose fiber. Glycerol‐plasticized NFC (NFC‐G) film had the highest dielectric constant and ac‐electrical conductivity values of 79 800 and 2.80× 10−3ohm−1 cm−1, respectively. The high values of dielectric constant and conductivity of the prepared films support their use in electronic components.
Using disruptive insertional mutagenesis to identify the in situ structure‐function landscape of the Shigella translocator protein IpaB
Authors: Barta Michael L. , Tachiyama Shoichi , Muthuramalingam Meenakumari , Arizmendi Olivia , Villanueva Cecilia E. , Ramyar Kasra X. , Geisbrecht Brian V. , Lovell Scott , Battaile Kevin P. , Picking Wendy L. , Picking William D.
Published: April 2018

Bacterial type III secretion systems (T3SS) are used to inject proteins into mammalian cells to subvert cellular functions. The Shigella T3SS apparatus (T3SA) is comprised of a basal body, cytoplasmic sorting platform and exposed needle with needle “tip complex” (TC). TC maturation occurs when the translocator protein IpaB is recruited to the needle tip where both IpaD and IpaB control secretion induction. IpaB insertion into the host membrane is the first step of translocon pore formation and secretion induction. We employed disruptive insertional mutagenesis, using bacteriophage T4 lysozyme (T4L), within predicted IpaB loops to show how topological features affect TC functions (secretion control, translocon formation and effector secretion). Insertions within the N‐terminal half of IpaB were most likely to result in a loss of steady‐state secretion control, however, all but the two that were not recognized by the T3SA retained nearly wild‐type hemolysis (translocon formation) and invasiveness levels (effector secretion). In contrast, all but one insertion in the C‐terminal half of IpaB maintained secretion control but were impaired for hemolysis and invasion. These nature of the data suggest the latter mutants are defective in a post‐secretion event, most likely due to impaired interactions with the second translocator protein IpaC. Intriguingly, only two insertion mutants displayed readily detectable T4L on the bacterial surface. The data create a picture in which the makeup and structure of a functional T3SA TC is highly amenable to physical perturbation, indicating that the tertiary structure of IpaB within the TC is more plastic than previously realized.
Disruption of the E. coli LptC dimerization interface and characterization of lipopolysaccharide and LptA binding to monomeric LptC
Authors: Schultz Kathryn M. , Fischer Matthew A. , Noey Elizabeth L. , Klug Candice S.
Published: April 2018

Lipopolysaccharide (LPS) is an essential element of nearly all Gram‐negative bacterial outer membranes and serves to protect the cell from adverse environmental stresses. Seven members of the lipopolysaccharide transport (Lpt) protein family function together to transport LPS from the inner membrane (IM) to the outer leaflet of the outer membrane of bacteria such as Escherichia coli. Each of these proteins has a solved crystal structure, including LptC, which is a largely periplasmic protein that is associated with the IM LptB2FG complex and anchored to the membrane by an N‐terminal helix. LptC directly binds LPS and is hypothesized to be involved in the transfer of LPS to another periplasmic protein, LptA. Purified and in solution, LptC forms a dimer. Here, point mutations designed to disrupt formation of the dimer are characterized using site‐directed spin labeling double electron electron resonance (DEER) spectroscopy, light scattering, circular dichroism, and computational modeling. The computational studies reveal the molecular interactions that drive dimerization of LptC and elucidate how the disruptive mutations change this interaction, while the DEER and light scattering studies identify which mutants disrupt the dimer. And, using electron paramagnetic resonance spectroscopy and comparing the results to the previous quantitative characterization of the interactions between dimeric LptC and LPS and LptA, the functional consequences of monomeric LptC were also determined. These results indicate that disruption of the dimer does not affect LPS or LptA binding and that monomeric LptC binds LPS and LptA at levels similar to dimeric LptC.
A comprehensive review of phytochemical profile, bioactives for pharmaceuticals, and pharmacological attributes of Azadirachta indica
Authors: Saleem Sumaira , Muhammad Gulzar , Hussain Muhammad Ajaz , Bukhari Syed Nasir Abbas
Published: April 2018

Azadirachta indica L. is a multipurpose medicinal tree of family Meliaceae. It occurs in tropical and semitropical regions of the world. Different parts of this miraculous tree are used to treat pyrexia, headache, ulcer, respiratory disorders, cancer, diabetes, leprosy, malaria, dengue, chicken pox, and dermal complications. The tree is popular for its pharmacological attributes such as hypolipidemic, antifertility, microbicidal, antidiabetic, anti‐inflammatory, hepatoprotective, antipyretic, hypoglycemic, insecticidal, nematicidal, antiulcer, antioxidant, neuroprotective, cardioprotective, and antileishmaniasis properties. A. indica is also rich in various phytochemicals for pharmaceuticals such as alkaloids, steroids, flavonoids, terpenoids, fatty acids, and carbohydrates. The fungicidal potential of the tree is due to the presence of azadirachtin and nimbin. Herein, we have compiled a comprehensive review of phytochemical profile, pharmacological attributes, and therapeutic prospective of this multipurpose tree.
Quercetin improves postpartum hypogalactia in milk‐deficient mice via stimulating prolactin production in pituitary gland
Authors: Lin Man , Wang Na , Yao Bei , Zhong Yao , Lin Yan , You Tianhui
Published: April 2018

Postpartum dysgalactia is a common clinical problem for lactating women. Seeking out the safe and efficient phytoestrogens will be a promising strategy for postpartum dysgalactia therapy. In this study, the postpartum mice within four groups, including control group, the model group, and the treatment groups intragastrically administrated with normal saline, bromocriptine, bromocriptine plus 17α‐ethinyl estradiol, and bromocriptine plus quercetin, respectively, were used. The results showed that quercetin, a kind of natural phytoestrogen, could efficiently promote lactation yield and mammary gland development in the agalactosis mice produced by bromocriptine administration. Mechanically, quercetin, such as 17α‐ethinyl estradiol, significantly stimulated prolactin (PRL) production and deposition in the mammary gland in the agalactosis mice determined by western blotting, quantitative polymerase chain reaction, and enzyme‐linked immunosorbent assay, respectively. Furthermore, quercetin could increase the expression of β‐casein, stearoyl‐CoA desaturase, fatty acid synthase, and α‐lactalbumin in the breast tissues that are responsible for the production of fatty acid, lactose, and galactose in the milk at the transcriptional level determined by quantitative polymerase chain reaction. Specifically, quercetin promoted primary mammary epithelial cell proliferation and stimulated prolactin receptor (PRLR) expression probably via AKT activation in vitro. In conclusion, this study indicates that estrogen‐like quercetin promotes mammary gland development and lactation yield in milk‐deficient mice, probably via stimulating PRL expression and release from the pituitary gland, as well as induces PRLR expression in primary mammary epithelial cells.
Astragalus polysaccharides exerts anti‐infective activity by inducing human cathelicidin antimicrobial peptide LL‐37 in respiratory epithelial cells
Authors: Zhao Lin , Tan Shuai , Zhang Hai , Liu Peng , Tan Yu‐Zhu , Li Jia‐Chuan , Jia Da , Shen Xiao‐Fei
Published: April 2018

Astragalus polysaccharides (APS), one of the major active components in Astragalus membranaceus, is an effective immunomodulator used in the treatment of immunological diseases in China. However, the anti‐infective action and mechanism of APS is not fully known. In the present study, we found that APS induced the expression of human cathelicidin antimicrobial peptide LL‐37, a key host anti‐infective molecule, in both mRNA and protein levels in respiratory epithelial cells HBE16 and A549. Furthermore, the lysate and supernatant from APS‐treated HBE16 cells both exhibited an obvious antibacterial action, which was partially neutralizated by LL‐37 monoclonal antibody. In addition, APS also significantly elevated the phosphorylation of p38 MAPK and JNK and caused the degradation of IκBα. Specific inhibitors of p38 MAPK, JNK, or NF‐κB obviously abolished APS‐induced LL‐37 synthesis and antibacterial activity, respectively. Taken together, our results confirmed the enhancement of APS on LL‐37 induction and antibacterial action in respiratory epithelial cells, which may be attributed to activation of p38 MAPK/JNK and NF‐κB pathways. Furthermore, these results also supported the clinical application of APS in the treatment of infectious diseases.
Phytotherapeutics in cancer invasion and metastasis
Authors: Salehi Bahare , Zucca Paolo , Sharifi‐Rad Mehdi , Pezzani Raffaele , Rajabi Sadegh , Setzer William N. , Varoni Elena Maria , Iriti Marcello , Kobarfard Farzad , Sharifi‐Rad Javad
Published: April 2018

Cancer is a multifactorial disease, and therefore, a multitarget approach is needed to face the complex cancer biology, based on the combined use of different natural and synthetic anticancer agents able to target synergistically multiple signaling pathways involved in carcinogenesis, including angiogenesis and metastasis. In this view, the plant kingdom represents an unlimited source of phytotherapeutics with promising perspectives in the field of anticancer drug discovery. This narrative review aims to provide an updated overview on the bioactive phytochemicals exhibiting a promising potential as adjuvants in conventional anticancer therapies, with emphasis on antiangiogenic and antimetastatic activities.
Acute hematological and mood perception effects of bitter orange extract (p‐synephrine) consumed alone and in combination with caffeine: A placebo‐controlled, double‐blind study
Authors: Bush Jill A. , Ratamess Nicholas A. , Stohs Sidney J. , Ellis Nicole L. , Vought Ira T. , O'Grady Elizabeth A. , Kuper Jeremy D. , Kang Jie , Faigenbaum Avery D.
Published: April 2018

The purpose of this study was to examine acute hematological and mood perception responses to supplementation with p‐synephrine alone and in combination with caffeine during quiet sitting. Sixteen subjects visited the laboratory on 6 occasions and were given (in randomized double‐blind manner) 103‐mg p‐synephrine (S), 233‐mg caffeine + 104‐mg p‐synephrine, 240‐mg caffeine, 337‐mg caffeine + 46‐mg p‐synephrine, 325‐mg caffeine, or a placebo (PL). The subjects sat quietly for 3 hr while completing mood state questionnaires every 30 min. Venous blood samples were collected at baseline (pre) and 3 hr (post) to determine immune, lipid, and chemistry panels. Compared with PL, no significant supplement differences were observed during the S trial with the exception of differential time effects seen in hematocrit (decrease in PL, no change in S), triglycerides and very low‐density lipoproteins (no changes in PL, significant decreases in S), and iron (no change in PL, significant elevation in S). Supplements containing caffeine showed increased feelings of attention, excitement, energy, and vigor. These data indicate that consumption of 103‐mg p‐synephrine does not negatively impact acute blood parameters, does not augment the effects of caffeine, or produce stimulant‐like perceptual mood effects.
Baicalin is a substrate of OATP2B1 and OATP1B3
Authors: Kalapos‐Kovács Bernadett , Juhász Viktória , Temesszentandrási‐Ambrus Csilla , Magda Balázs , Szabó Pál T. , Antal István , Klebovich Imre , Krajcsi Péter
Published: April 2018

The use and significance of baicalin, the main bioactive component found in Radix Scutellaria, have been on the rise due to its interesting pharmacological properties. Baicalin, a low passive permeability compound, is directly absorbed from the upper intestine and its hepatic elimination is dominant. However, interaction but no transport studies have implicated organic anion‐transporting polypeptides in its cellular uptake. By using mammalian cells stably expressing the uptake transporters of interest, we are showing that baicalin is a potent substrate of Organic anion‐transporting polypeptide 2B1 (OATP2B1) and less potent substrate of OATP1B3. OATP2B1 and OATP1B3 transport baicalin and may play a role in the hepatic uptake of baicalin formed in the intestine.
Switching linear parameter‐varying control with improved local performance and optimized switching surfaces
Authors: Zhao Pan , Nagamune Ryozo
Published: April 2018

This paper presents a novel approach to designing switching linear parameter‐varying (SLPV) controllers with improved local performance and an algorithm for optimizing switching surfaces to further improve the performance of the SLPV controllers. The design approach utilizes the weighted average of the local L2‐gain bounds (representing the local performance) as the cost function to be minimized, whereas the maximum of the local L2‐gain bounds (representing the worst‐case performance over all subsets) is bounded with a tuning parameter. The tuning parameter is useful for taking the trade‐off between the local performance and the worst‐case performance. An algorithm based on the particle swarm optimization is introduced to optimize the switching surfaces of an SLPV controller. The efficacy of the proposed SLPV controller design approach and switching surface optimization algorithm is demonstrated on both a numerical example and a physical example of air‐fuel ratio control of an automotive engine.
Adaptive synchronization control of networked robot systems without velocity measurements
Authors: Zhang Bin , Jia Yingmin , Du Junping
Published: April 2018

This paper addresses the adaptive synchronization control problem of networked robot systems characterized by the Lagrangian function, where exact dynamic models are unknown and velocity measurements are unavailable. A class of distributed observers, comprised of multiple dynamic variables and static variables, are established based on no a priori restriction on the boundness of the observer states. The observer is compatible for different control schemes with or without structure uncertainties. Using the estimated states given by the observer, adaptive distributed control input is developed, and then, closed‐loop dynamic models for filtered vectors are established. It is proven that our proposed control scheme permits global exact state estimation and global asymptotic synchronization while compensating for structure uncertainties. Simulations are provided to demonstrate the effectiveness of the results.
Effects of air temperature and discharge on Upper Mississippi River summer water temperatures
Authors: Gray B.R. , Robertson D.M. , Rogala J.T.
Published: April 2018

Recent interest in the potential effects of climate change has prompted studies of air temperature and precipitation associations with water temperatures in rivers and streams. We examined associations between summer surface water temperatures and both air temperature and discharge for 5 reaches of the Upper Mississippi River during 1994–2011. Water–air temperature associations at a given reach approximated 1:1 when estimated under an assumption of reach independence but declined to approximately 1:2 when water temperatures were permitted to covary among reaches and were also adjusted for upstream air temperatures. Estimated water temperature–discharge associations were weak. An apparently novel feature of this study is that of addressing changes in associations between water and air temperatures when both are correlated among reaches.
Response‐adaptive treatment allocation for survival trials with clustered right‐censored data
Authors: Su Pei‐Fang , Cheung Siu Hung
Published: April 2018

A comparison of 2 treatments with survival outcomes in a clinical study may require treatment randomization on clusters of multiple units with correlated responses. For example, for patients with otitis media in both ears, a specific treatment is normally given to a single patient, and hence, the 2 ears constitute a cluster. Statistical procedures are available for comparison of treatment efficacies. The conventional approach for treatment allocation is the adoption of a balanced design, in which half of the patients are assigned to each treatment arm. However, considering the increasing acceptability of responsive‐adaptive designs in recent years because of their desirable features, we have developed a response‐adaptive treatment allocation scheme for survival trials with clustered data. The proposed treatment allocation scheme is superior to the balanced design in that it allows more patients to receive the better treatment. At the same time, the test power for comparing treatment efficacies using our treatment allocation scheme remains highly competitive. The advantage of the proposed randomization procedure is supported by a simulation study and the redesign of a clinical study.