bluuebunny/crossref_metadata_2025 huggingface dataset:
How many proteins can be identified in a 2DE gel spot within an analysis of a complex human cancer tissue proteome?
Authors: Zhan Xianquan , Yang Haiyan , Peng Fang , Li Jianglin , Mu Yun , Long Ying , Cheng Tingting , Huang Yuda , Li Zhao , Lu Miaolong , Li Na , Li Maoyu , Liu Jianping , Jungblut Peter R.
Published: December 2017

Two‐dimensional gel electrophoresis (2DE) in proteomics is traditionally assumed to contain only one or two proteins in each 2DE spot. However, 2DE resolution is being complemented by the rapid development of high sensitivity mass spectrometers. Here we compared MALDI‐MS, LC‐Q‐TOF MS and LC‐Orbitrap Velos MS for the identification of proteins within one spot. With LC‐Orbitrap Velos MS each Coomassie Blue‐stained 2DE spot contained an average of at least 42 and 63 proteins/spot in an analysis of a human glioblastoma proteome and a human pituitary adenoma proteome, respectively, if a single gel spot was analyzed. If a pool of three matched gel spots was analyzed this number further increased up to an average of 230 and 118 proteins/spot for glioblastoma and pituitary adenoma proteome, respectively. Multiple proteins per spot confirm the necessity of isotopic labeling in large‐scale quantification of different protein species in a proteome. Furthermore, a protein abundance analysis revealed that most of the identified proteins in each analyzed 2DE spot were low‐abundance proteins. Many proteins were present in several of the analyzed spots showing the ability of 2DE‐MS to separate at the protein species level. Therefore, 2DE coupled with high‐sensitivity LC‐MS has a clearly higher sensitivity as expected until now to detect, identify and quantify low abundance proteins in a complex human proteome with an estimated resolution of about 500 000 protein species. This clearly exceeds the resolution power of bottom‐up LC‐MS investigations.
A functional SNP in the 3′‐UTR of TAP2 gene interacts with microRNA hsa‐miR‐1270 to suppress the gene expression
Authors: Knox Bridgett , Wang Yong , Rogers Lora J. , Xuan Jiekun , Yu Dianke , Guan Huaijin , Chen Jiwei , Shi Tieliu , Ning Baitang , Kadlubar Susan A.
Published: December 2017

The transporter associated with antigen processing 2 (TAP2) is involved in the development of multidrug resistance and the etiology of immunological diseases. In this study, we investigated whether the expression of TAP2 can be perturbed by single nucleotide polymorphisms (SNPs) located in 3′‐untranslated region (3′‐UTR) of the gene via interactions with microRNAs. Using a series of in silico assays, we selected the candidate microRNAs (miRNAs) with the potential to interact with functional SNPs of TAP2. The SNP rs241456—located in the 3′‐UTR of TAP2—resides in a potential binding site for hsa‐miR‐1270 and hsa‐miR‐620. HEK 293 cells, from a human kidney cell line, were used to characterize the extent of binding of miRNAs to each polymorphic allele of the SNP by a luciferase reporter gene assay. RNA electrophoretic mobility shift assays were used to evaluate the interaction between the miRNAs and each allele sequence of the SNP. We found that hsa‐miR‐1270 inhibited luciferase activity by binding to the T allele of the SNP in an allele‐specific manner. A negative correlation was also found between the expression of hsa‐miR‐1270 and the T allele of the SNP in kidney tissues. Our findings support the hypothesis that hsa‐miR‐1270 suppresses the production of TAP2 by binding to this SNP in the 3′‐UTR of this gene. Environ. Mol. Mutagen. 59:134–143, 2018. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
A Ceramic‐Based Separator for High‐Temperature Supercapacitors
Authors: Qin Bin , Han Yu , Ren Yuxin , Sui Dong , Zhou Ying , Zhang Miao , Sun Zhenhe , Ma Yanfeng , Chen Yongsheng
Published: December 2017

Currently, supercapacitors have the shortcoming of limited operation temperature mainly owing to the low thermal stability of separators, which seriously hinder their application at high temperatures. In this work, a simple and universal method for the fabrication of high‐temperature standing ceramic‐based separators is reported. It was demonstrated that such a separator can withstand over 350 °C without any shrinkage. Supercapacitors fabricated by using such separators can be operated at as high as 120 °C efficiently and even after 9000 cycles at 2.5 V operation voltage, their capacitance still retained approximately 88 % of their initial performance. To the best of our knowledge, this is the first report of a separator with such high thermal stability.
Robotic photosieving from low‐cost multirotor sUAS: a proof‐of‐concept
Authors: Carbonneau P.E. , Bizzi S. , Marchetti G.
Published: December 2017

Measurement of riverbed material grain sizes is now a routine part of fieldwork in fluvial geomorphology and lotic ecology. In the last decade, several authors have proposed remote sensing approaches of grain size measurements based on terrestrial and aerial imagery. Given the current rise of small unmanned aerial system (sUAS) applications in geomorphology, there is now increasing interest in the application of these remotely sensed grain size mapping methods to sUAS imagery. However, success in this area has been limited owing to two fundamental problems: lack of constraint of image scale for sUAS imagery and blurring effects in sUAS images and resulting orthomosaics. In this work, we solve the former by showing that SfM‐photogrammetry can be used in a direct georeferencing (DG) workflow (i.e. with no ground validation) in order to predict image scale within margins of 3%. We then propose a novel approach of robotic photosieving of dry exposed riverbed grains that relies on near‐ground images acquired from a low‐cost sUAS and which does not require the presence of ground control points or visible scale objects. We demonstrate that this absence of scale objects does not affect photosieving outputs thus resulting in a low‐cost and efficient sampling method for surficial grains. Copyright © 2017 John Wiley & Sons, Ltd.
Spectral‐efficient resource allocation for mixed services in OFDMA‐based 5G heterogeneous networks
Authors: Le Nam‐Tran , Jayalath Dhammika , Coetzee Jacob
Published: December 2017

One of the principal thrusts of proposed fifth‐generation networks is the provisioning of mixed services or heterogeneous quality of service, which includes delay‐sensitive and delay‐tolerant services. Guaranteeing the fairness in data rate among end users in such a complex network brings many challenges. In this paper, we consider heterogeneous quality of service and fairness in the problem of spectrally efficient resource allocation in orthogonal frequency‐division multiple access (OFDMA)‐based fifth‐generation heterogeneous networks with femtocells. We aim to maximize the total capacity of all femtocells while satisfying the following: fairness constraint for delay‐tolerant users, minimum throughput for delay‐sensitive users, cross‐tier interference threshold of femtocell heterogeneous networks, and exclusive property of OFDMA subchannels. The formulated problem is combinatorial and nonconvex due to the integer constraint of OFDMA subchannels and the nonaffine equality constraint of the fairness. To make the problem more tractable, we propose to maximize the overall throughput over instantaneous data rate instead of power and subchannel. By doing this, the fairness equality becomes affine on instantaneous data rate. The feasible domain of the problem is redefined with the constraints of subchannels readily included. The transformed problem takes the standard convex form, which is much simpler and is easily solved using the Lagrangian dual method. The proposed algorithm has a low complexity and provides a higher spectral efficiency compared with existing algorithms.
Late Neoproterozoic–Early Palaeozoic stratigraphic succession, Western Himalaya, North Pakistan: Detrital zircon provenance and tectonic implications
Authors: Qasim Muhammad , Ding Lin , Khan Muhammad Asif , Umar Muhammad , Jadoon Ishtiaq A.K. , Haneef Muhammad , Baral Upendra , Cai Fulong , Shah Azeem , Yao Wei
Published: December 2017

This paper presents the first ever detrital zircon U–Pb–Hf isotopic study for the Late Neoproterozoic–Early Palaeozoic stratigraphic succession exposed in the Hazara Basin, Western Himalaya, North Pakistan. This time span represents the break‐up of the supercontinent Rodinia and final assembly of Gondwana. The detrital record of the Late Neoproterozoic succession indicates well‐mixed detritus shed from within the Indian Craton, especially the Central Indian provenance (including the Delhi Fold Belt, Aravalli Orogen, and Bundlekhand Craton). The εHf(t) values are mostly negative, and Hf TDMC ages are clustered at 2.0–2.4 Ga, which indicates the derivation from an ancient reworked crustal source. In addition, the presence of a few positive εHf(t) values in the Late Neoproterozoic sequence indicates addition of the juvenile crust that corresponds to the period of the Rodinia break‐up. However, dissimilarities with detrital signatures from the Australian continent may indicate break‐up of the Rodinia supercontinent and detachment of Australia from India prior to ~754 Ma, which is the depositional age of the Hazara Formation. In addition, the angular unconformity at the base of the Abbottabad Formation represents the compressional tectonics that might be associated with the Pan‐African (Indo‐Antarctic Craton collision with the East African Orogen during 800–700 Ma) orogeny. The presence of the metamorphism and deformation in the rocks below the unconformity supports such an event prior to deposition of the Early Palaeozoic Abbottabad Formation. Similarly, the appearance of the Pan‐African detritus in the Early Palaeozoic Abbottabad Formation could be due to closure of the ocean basin between Eastern and Western Gondwana along the Mozambique Suture. This provenance change may indicate the final assembly of supercontinent Gondwana.
Changing brain connectivity dynamics: From early childhood to adulthood
Authors: Faghiri Ashkan , Stephen Julia M. , Wang Yu‐Ping , Wilson Tony W. , Calhoun Vince D.
Published: December 2017

Brain maturation through adolescence has been the topic of recent studies. Previous works have evaluated changes in morphometry and also changes in functional connectivity. However, most resting‐state fMRI studies have focused on static connectivity. Here we examine the relationship between age/maturity and the dynamics of brain functional connectivity. Utilizing a resting fMRI dataset comprised 421 subjects ages 3–22 from the PING study, we first performed group ICA to extract independent components and their time courses. Next, dynamic functional network connectivity (dFNC) was calculated via a sliding window followed by clusteringofconnectivity patterns into 5 states. Finally, we evaluated the relationship between age and the amount of time each participant spent in each state as well as the transitions among different states. Results showed that older participants tend to spend more time in states which reflect overall stronger connectivity patterns throughout the brain. In addition, the relationship between age and state transition is symmetric. This can mean individuals change functional connectivity through time within a specific set of states. On the whole, results indicated that dynamic functional connectivity is an important factor to consider when examining brain development across childhood.
Fronto‐parietal coding of goal‐directed actions performed by artificial agents
Authors: Kupferberg Aleksandra , Iacoboni Marco , Flanagin Virginia , Huber Markus , Kasparbauer Anna , Baumgartner Thomas , Hasler Gregor , Schmidt Florian , Borst Christoph , Glasauer Stefan
Published: December 2017

With advances in technology, artificial agents such as humanoid robots will soon become a part of our daily lives. For safe and intuitive collaboration, it is important to understand the goals behind their motor actions. In humans, this process is mediated by changes in activity in fronto‐parietal brain areas. The extent to which these areas are activated when observing artificial agents indicates the naturalness and easiness of interaction. Previous studies indicated that fronto‐parietal activity does not depend on whether the agent is human or artificial. However, it is unknown whether this activity is modulated by observing grasping (self‐related action) and pointing actions (other‐related action) performed by an artificial agent depending on the action goal. Therefore, we designed an experiment in which subjects observed human and artificial agents perform pointing and grasping actions aimed at two different object categories suggesting different goals. We found a signal increase in the bilateral inferior parietal lobule and the premotor cortex when tool versus food items were pointed to or grasped by both agents, probably reflecting the association of hand actions with the functional use of tools. Our results show that goal attribution engages the fronto‐parietal network not only for observing a human but also a robotic agent for both self‐related and social actions. The debriefing after the experiment has shown that actions of human‐like artificial agents can be perceived as being goal‐directed. Therefore, humans will be able to interact with service robots intuitively in various domains such as education, healthcare, public service, and entertainment.
Differential patterns of dynamic functional connectivity variability of striato–cortical circuitry in children with benign epilepsy with centrotemporal spikes
Authors: Li Rong , Liao Wei , Yu Yangyang , Chen Heng , Guo Xiaonan , Tang Ye‐Lei , Chen Huafu
Published: December 2017

Benign epilepsy with centrotemporal spikes (BECTS) is characterized by abnormal (static) functional interactions among cortical and subcortical regions, regardless of the active or chronic epileptic state. However, human brain connectivity is dynamic and associated with ongoing rhythmic activity. The dynamic functional connectivity (dFC) of the distinct striato–cortical circuitry associated with or without interictal epileptiform discharges (IEDs) are poorly understood in BECTS. Herein, we captured the pattern of dFC using sliding window correlation of putamen subregions in the BECTS (without IEDs, n = 23; with IEDs, n = 20) and sex‐ and age‐matched healthy controls (HCs, n = 28) during rest. Furthermore, we quantified dFC variability using their standard deviation. Compared with HCs and patients without IEDs, patients with IEDs exhibited excessive variability in the dorsal striatal‐sensorimotor circuitry related to typical seizure semiology. By contrast, excessive stability (decreased dFC variability) was found in the ventral striatal–cognitive circuitry (p < .05, GRF corrected). In addition, correlation analysis revealed that the excessive variability in the dorsal striatal‐sensorimotor circuitry was related to highly frequent IEDs (p < .05, uncorrected). Our finding of excessive variability in the dorsal striatal‐sensorimotor circuitry could be an indication of increased sensitivity to regional fluctuations in the epileptogenic zone, while excessive stability in the ventral striatal–cognitive circuitry could represent compensatory mechanisms that prevent or postpone cognitive impairments in BECTS. Overall, the differentiated dynamics of the striato–cortical circuitry extend our understanding of interactions among epileptic activity, striato–cortical functional architecture, and neurocognitive processes in BECTS.
Automated quality assessment of structural magnetic resonance images in children: Comparison with visual inspection and surface‐based reconstruction
Authors: White Tonya , Jansen Philip R. , Muetzel Ryan L. , Sudre Gustavo , El Marroun Hanan , Tiemeier Henning , Qiu Anqi , Shaw Philip , Michael Andrew M. , Verhulst Frank C.
Published: December 2017

Motion‐related artifacts are one of the major challenges associated with pediatric neuroimaging. Recent studies have shown a relationship between visual quality ratings of T1 images and cortical reconstruction measures. Automated algorithms offer more precision in quantifying movement‐related artifacts compared to visual inspection. Thus, the goal of this study was to test three different automated quality assessment algorithms for structural MRI scans. The three algorithms included a Fourier‐, integral‐, and a gradient‐based approach which were run on raw T1‐weighted imaging data collected from four different scanners. The four cohorts included a total of 6,662 MRI scans from two waves of the Generation R Study, the NIH NHGRI Study, and the GUSTO Study. Using receiver operating characteristics with visually inspected quality ratings of the T1 images, the area under the curve (AUC) for the gradient algorithm, which performed better than either the integral or Fourier approaches, was 0.95, 0.88, and 0.82 for the Generation R, NHGRI, and GUSTO studies, respectively. For scans of poor initial quality, repeating the scan often resulted in a better quality second image. Finally, we found that even minor differences in automated quality measurements were associated with FreeSurfer derived measures of cortical thickness and surface area, even in scans that were rated as good quality. Our findings suggest that the inclusion of automated quality assessment measures can augment visual inspection and may find use as a covariate in analyses or to identify thresholds to exclude poor quality data.
Growing incidence of thyroid carcinoma in recent years: Factors underlying overdiagnosis
Authors: Sanabria Alvaro , Kowalski Luiz P. , Shah Jatin P. , Nixon Iain J. , Angelos Peter , Williams Michelle D. , Rinaldo Alessandra , Ferlito Alfio
Published: December 2017

There is an increasing incidence of well‐differentiated thyroid cancer worldwide. Much of the increase is secondary to increased detection of small, low‐risk tumors, with questionable clinical significance. This review addresses the factors that contribute to the increasing incidence and considers environmental, and patient‐based and clinician‐led influences. Articles addressing the causes of the increased incidence were critically reviewed. A complex interplay of environmental, medical, and social pressures has resulted in increased awareness of the thyroid disease risk, increased screening of thyroid cancers, and increased diagnosis of thyroid cancers. Although there is evidence to suggest that the true disease incidence may be changing slightly, most of the increase is related to factors that promote early diagnosis of low‐risk lesions, which is resulting in a significant phenomenon of overdiagnosis. An improved understanding of these pressures at a global level will enable healthcare policymakers to react appropriately to this challenge in the future.
Pharyngeal perforation after anterior cervical spine surgery treated by transoral endoscopic surgery
Authors: Rama‐López Julio , Tomás‐Fernandez Meritxell , García‐Garza César , Martínez‐Madrigal Milton
Published: December 2017

Background

Anterior cervical fixation has been used since 1967 for multiple pathologies like traumatism, compressive myelopathy, or spinal infections.

Methods

We report the case of a patient who had undergone cervical spine surgery 10 years previously and presented to our clinic with a pharyngeal fistula due to surgical screw displacement that was treated by transoral endoscopic surgery.

Results

The immediate postoperative period occurred without incidence and complete odynophagia resolution. The patient was discharged home the fourth day after surgery. Follow‐up after 1 year showed no evidence of spinal fixation hardware mobilization.

Conclusion

We consider the transoral endoscopic approach a feasible low comorbidity technique to treat anterior cervical plate mobilization with pharyngeal and pharyngoesophageal perforations.
The short‐term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct‐acting antivirals: An ERCHIVES study
Authors: Li Darrick K. , Ren Yanjie , Fierer Daniel S. , Rutledge Stephanie , Shaikh Obaid S. , Lo Re Vincent , Simon Tracey , Abou‐Samra Abdul‐Badi , Chung Raymond T. , Butt Adeel A.
Published: December 2017

Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct‐acting antivirals (DAAs). However, making definitive conclusions has been challenging because of the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon (IFN)‐based regimens. We performed a retrospective, population‐based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, risk of HCC was not higher in the DAA group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval, 0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC‐free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1,000 person‐years; P = 0.78 and log‐rank P = 0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1,000 person‐years) compared to those treated with either IFN or DAAs (P = 0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log‐rank, P = 0.0004). Conclusion: DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (Hepatology 2018;67:2244‐2253).
Retaining professionally employed new mothers: The importance of maternal confidence and workplace support to their intent to stay
Authors: Ladge Jamie J. , Humberd Beth K. , Eddleston Kimberly A.
Published: December 2017

In this multimethod study, we explore why some new mothers may “opt out” of the workforce while others stay after the birth of their first child. Findings from a qualitative study of 40 professionally employed new mothers revealed the importance of maternal confidence, managerial support, and work hours to their experience of work–family conflict (WFC) and subsequent intent to stay with their organization. We tested these relationships in a follow‐up survey‐based study of 802 professionally employed first‐time mothers and found that the relationship between maternal confidence and intent to stay is mediated by WFC, suggesting that WFC acts as an important cross‐domain mechanism that links confidence in a nonwork role to women's intent to stay with their organization. We also found that for women who work full‐time, those who lack maternal confidence experience significantly greater WFC than those with strong maternal confidence. While we did not find support for managerial support as a moderator in the quantitative study, our analysis revealed that it directly affects WFC and intent to stay. To increase professionally employed new mothers’ intent to stay with their organization, our study therefore emphasizes the importance of nurturing maternal confidence and encouraging managers to display support for working parents.
Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake
Authors: Kaji Kosuke , Nishimura Norihisa , Seki Kenichiro , Sato Shinya , Saikawa Soichiro , Nakanishi Keisuke , Furukawa Masanori , Kawaratani Hideto , Kitade Mitsuteru , Moriya Kei , Namisaki Tadashi , Yoshiji Hitoshi
Published: December 2017

Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2‐Is to attenuate cancer growth of SGLT2‐expressing cancer cells, little is known about the effects of SGLT2‐Is on hepatocellular carcinoma (HCC). Here, we investigate the anti‐cancer properties of a SGLT2‐I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells. Canagliflozin exerted antiproliferative effects on SGLT2‐expressing Huh7 and HepG2 cells in a dose‐dependent manner by inhibiting glycolytic metabolism including glucose uptake, lactate and intracellular ATP production. This agent also induced G2/M arrest and apoptosis with inhibited phosphorylation of ERK, p38 and AKT and cleavage of caspase3. Xenograft tumor growth assay showed that oral administration of canagliflozin (10 mg/kg/day) significantly reduced subcutaneous tumor burdens in a glycemic status‐independent manner, and attenuated intratumor vascularization in Huh7‐ and HepG2‐derived xenograft tumors in BALB/c nude mice. In vitro, canagliflozin suppressed the increased human umbilical vein endothelial cell (HUVEC) proliferation and tubular formation which were observed in Huh7 or HepG2 co‐cultures. By contrast, canagliflozin had no effect on tumor growth and intratumor angiogenesis in SGLT2‐null HLE‐derived xenograft models. These results indicate that SGLT2‐I therapy is a potential new strategy for the treatment of HCC.
Trends in incidence, mortality and survival of penile squamous cell carcinoma in Norway 1956–2015
Authors: Hansen Bo T. , Orumaa Madleen , Lie A. Kathrine , Brennhovd Bjørn , Nygård Mari
Published: December 2017

We examine trends in incidence, mortality and survival of penile squamous cell carcinoma (SCC) in Norway over 60 years. Data on all cases of penile cancer diagnosed in Norway during 1956–2015 were obtained from the Cancer Registry of Norway. Trends in age‐standardized rates of penile SCC incidence, mortality and 5‐year relative survival were assessed by the annual percentage change statistic and joinpoint regression. A total of 1,596 penile cancer cases were diagnosed during 1956–2015, among which 1,474 (92.4%) were SCC. During 2011–2015, the age‐standardized incidence and mortality of penile SCC were 0.91 (95% confidence interval (CI): 0.78; 1.05) and 0.50 (0.42; 0.60) per 100,000, respectively, and the 5‐year relative survival was 61.6% (41.9; 76.4). The incidence of SCC increased during 1956–2015, with an average annual percentage change (AAPC) of 0.80% (0.46; 1.15). The increase was strongest among men diagnosed at a relatively early age (age<=64 years; AAPC: 1.47% (0.90; 2.05)). Mortality also increased over the study period (AAPC: 0.47% (0.10; 0.85)), whereas 5‐year relative survival did not change (AAPC: 0.08% (−0.19; 0.36)). We conclude that the incidence of penile SCC has increased at a moderate and constant rate during 1956–2015, and that the most consistent increase occurred among younger men. Mortality also increased during the study period. However, survival did not change, thus changes in diagnostics and treatment had little impact on survival from penile SCC. Since a substantial proportion of penile SCC is caused by human papillomavirus (HPV), the incidence increase may in part be attributed to increased exposure to HPV in the population.
Traveling‐wave Phenomena in a Model of Autocrine Signaling Coupled with Dynamics of the MAPK Cascade
Authors: Přibyl Michal , Schreiber Igor
Published: December 2017

Recently we have revealed a minimal reaction subnetwork in the MAPK (mitogen‐activated protein kinase) cascade that is responsible for the emergence of bistable and oscillatory behavior. Here we examine a possible mechanism that provides for the propagation of increased MAPK activity in cell populations by interconnecting the intracellular MAPK subnetwork with the ligand‐receptor signaling machinery. Such approach allows for significant reduction of the dimensionality of the parameter space on one hand and the conservation of dynamical complexity of the system on the other hand. The coupled model predicts coexistence of one, two or three different stable steady states, or the coexistence of a stable steady state and periodic solution. We found two robust and physiologically relevant characteristics of the proposed model: (i) There is a very large region of coexistence of at least one stable steady state with non‐zero MAPK activity and one steady state with zero MAPK activity in the parameter space. (ii) Spontaneous traveling front waves always switching originally inactive cells into ligand releasing cells emerge in adjacent cell populations, e. g. in healthy and injured tissues. Moreover, the formation of composite traveling front waves and spatial oscillatory patterns of MAPK activity are predicted and discussed.
Terpenes Show Nanomolar Affinity and Selective Binding with Cucurbit[8]uril
Authors: Romero Miguel A. , González‐Delgado José A. , Mendoza Johan , Arteaga Jesús F. , Basílio Nuno , Pischel Uwe
Published: December 2017

Eucalyptol, fenchyl alcohol, and geranylamine were tested for the binding to cucurbit[8]uril. Nanomolar affinities were found, giving rise to a highly selective binding of the terpenes by cucurbit[8]uril when compared to the smaller cucurbit[7]uril. This was rationalized with a better size fit with the larger macrocycle. These notions were supported by the calculation of the packing coefficient and NMR measurements of the free and complexed terpenes. The binding process is mainly enthalpically driven, which is associated with the release of high‐energy water.
Impact of Climate Change on Basin Hydrological Characteristics and Thermal Structure of Reservoirs
Authors: Dalilsafaee Sepehr , Niksokhan Mohammad Hossein , Moshtaghi Bahman
Published: December 2017

In this study, a hydrodynamic model of water quality (CE‐QUAL‐W2) coupled with a hydrological model (SWAT) with emission scenarios predicted by general circulation models in the future were applied to examine the impact of climate change on the thermal structure of a reservoir. According to the results, the mean annual air temperature will increase from 1.47 to 1.80°C (B1) and from 2.00 to 2.11°C (A2). The average of the monthly precipitation total will also increase from 2.95 to 3.17 mm (A2) and from 5.32 to 9.67 mm (B1) in the future. The results of the hydrological model indicate river flow reduction (A2 scenario), no variation (ECHAM5‐OM B1) and increase (HadCM3 B1) in the future. Also, the occurrence time of maximum and minimum monthly discharges are projected to change. To determine the importance of upstream watershed hydrology on thermal structure modelling, the simulation was carried out twice, once with and then without the SWAT model. By comparing the results, it was concluded that by applying the coupled model, the climate change impact on upstream hydrology characteristics and temperature effect both in the surface and bottom layers, altered duration of the stratification cycle and its onset and termination, could be simulated successfully. Copyright © 2017 John Wiley & Sons, Ltd.
Language and Identity Construction: The Case of a Refugee Digital Bricoleur
Authors: Karam Fares J.
Published: December 2017

The United States is the biggest resettlement country of refugees referred by the United Nations High Commissioner for Refugees; however, educational resettlement efforts have been unsuccessful in responding to the needs of refugee students, and educational research has thus far presented a deficit‐oriented narrative that ignores the skills and agency of these students. This study challenges such deficit‐oriented presentations by examining how Zein, an adolescent refugee English learner, uses language to construct his identity and position himself as a digital bricoleur (someone creatively using different materials to produce new artifacts). We learn from Zein that classroom tasks with multimodal dimensions can provide spaces for refugee students to negotiate their engagement with classroom tasks to better align them to their interests and identities, make connections between their school‐based and out‐of‐school literacy practices, and practice their agency to produce counternarratives that challenge deficit perspectives of refugee students.
Bacterial nanocellulose‐IKVAV hydrogel matrix modulates melanoma tumor cell adhesion and proliferation and induces vasculogenic mimicry in vitro
Authors: Reis Emily M. dos , Berti Fernanda V. , Colla Guilherme , Porto Luismar M.
Published: December 2017

Vasculogenic mimicry process has generated great interest over the past decade. So far, however, there have been only a few matrices available that allow us to study that process in vitro. Here, we have developed an innovative hydrogel platform with defined composition that mimics the structural architecture and biological functions of the extracellular matrix for vasculogenic mimicry of human melanoma cells (SK‐MEL‐28). We chemically immobilized IKVAV peptide on bacterial nanocellulose (BNC) fibers. BNC‐IKVAV hydrogel was found to improve the adhesion and proliferation of SK‐MEL‐28 cells on the top and bottom surfaces. Particularly, the bottom surface of BNC‐IKVAV induced SK‐MEL‐28 cells to organize themselves as well‐established networks related to the vasculogenic mimicry process. Finally, our results showed that not only BNC‐IKVAV but also BNC hydrogels can potentially be used as a three‐dimensional platform that allows the screening of antitumor drugs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2741–2749, 2018.
Cardiac tissue regeneration: A preliminary study on carbon‐based nanotubes gelatin scaffold
Authors: Cabiati Manuela , Vozzi Federico , Gemma Federica , Montemurro Francesca , De Maria Carmelo , Vozzi Giovanni , Domenici Claudio , Del Ry Silvia
Published: December 2017

The aim of this study was set‐up and test of gelatin and carbon nanotubes scaffolds. Gelatin‐based (5%) genipin cross‐linked (0.2%) scaffolds embedding single‐walled carbon nanotubes (SWCNTs, 0.3, 0.5, 0.7, 0.9, and 1.3% w/w) were prepared and mechanically/electrically characterized. For biological evaluation, H9c2 cell line was cultured for 10 days. Cytotoxicity, cell growth and differentiation, immunohistochemistry, and real‐time PCR analysis were performed. Myoblast and cardiac differentiation were obtained by serum reduction to 1% (C1%) and stimulation with 50 nM all trans‐retinoic acid (CRA), respectively. Immunohistochemistry showed elongated myotubes in C1% while round and multinucleated cells in CRA with also a significantly increased expression of natriuretic peptides (NP) and ET‐1 receptors in parallel with a decreased ET‐1. On scaffolds, cell viability was similar for Gel–SWCNT0.3%/0.9%; NP and ET systems expression decreased in both concentrations with respect to control and CX‐43, mainly due to a lacking of complete differentiation in cardiac phenotype during that time. Although further analyses on novel biomaterials are necessary, these results represent a useful starting point to develop new biomaterial‐based scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2750–2762, 2018.
Osteoprotection Through the Deletion of the Transcription Factor Rorβ in Mice
Authors: Farr Joshua N , Weivoda Megan M , Nicks Kristy M , Fraser Daniel G , Negley Brittany A , Onken Jennifer L , Thicke Brianne S , Ruan Ming , Liu Hong , Forrest Douglas , Hawse John R , Khosla Sundeep , Monroe David G
Published: December 2017

There is a clinical need to identify new molecular targets for the treatment of osteoporosis, particularly those that simultaneously inhibit bone resorption while stimulating bone formation. We have previously shown in overexpression studies that retinoic acid receptor-related orphan receptor β (Rorβ) suppresses in vitro osteoblast differentiation. In addition, the expression of Rorβ is markedly increased in bone marrow–derived mesenchymal stromal cells with aging in both mice and humans. Here we establish a critical role for Rorβ in regulating bone metabolism using a combination of in vitro and in vivo studies. We used Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing to demonstrate that loss of Rorβ in osteoblasts enhances Wnt signaling, specifically through increased recruitment of β-catenin to T-cell factor/lymphoid enhancer factor (Tcf/Lef) DNA binding sites in the promoters of the Wnt target genes Tcf7 and Opg. This resulted in increased osteogenic gene expression and suppressed osteoclast formation through increased osteoprotegerin (OPG) secretion in Rorβ-deficient cells. Consistent with our in vitro data, genetic deletion of Rorβ in both female and male mice resulted in preserved bone mass and microarchitecture with advancing age due to increased bone formation with a concomitant decrease in resorption. The improved skeletal phenotype in the Rorβ–/– mice was also associated with increased bone protein levels of TCF7 and OPG. These data demonstrate that loss of Rorβ has beneficial skeletal effects by increasing bone formation and decreasing bone resorption, at least in part through β-catenin–dependent activation of the Wnt pathway. Thus, inhibition of Rorβ represents a novel approach to potentially prevent or reverse osteoporosis. © 2017 American Society for Bone and Mineral Research.
Inactivation of mTORC1 Signaling in Osterix-Expressing Cells Impairs B-cell Differentiation
Authors: Wang Yongkui , Xiao Min , Tao Chen , Chen Jing , Wang Zhenyu , Yang Jun , Chen Zhenguo , Zou Zhipeng , Liu Anling , Cai Daozhang , Jiang Yu , Ding Changhai , Li Mangmang , Bai Xiaochun
Published: December 2017

Osteoblasts provide a microenvironmental niche for B-cell commitment and maturation in the bone marrow (BM). Any abnormity of osteoblasts function may result in the defect of B lymphopoiesis. Signaling from mechanistic target of rapamycin complex 1 (mTORC1) has been implicated in regulating the expansion and differentiation of osteoblasts. Thus, we raise a hypothesis that mTORC1 signaling in osteoblasts plays a vital role in B-cell development. Inactivation of mTORC1 in osterix-expressing cells (mainly osteoblast lineage) through Osx-Cre-directed deletion of Raptor (an mTORC1-specific component) resulted in a reduction in the total B-cell population in the BM, which was due to a block in early B-cell development from the pro-B to pre-B cell stage. Further mechanistic studies revealed that this defect was the result of reduction of interleukin-7 (IL-7) expression in osterix-expressing immature osteoblasts, which caused the abnormality of IL-7/Stat5 signaling in early B lymphocytes, leading to an increased apoptosis of pre-B plus immature B cells. In vitro and in vivo studies demonstrated that the addition of exogenous IL-7 partially restored B lymphopoiesis in the BM of Raptor mutant mice. Furthermore, total BM cells cultured in conditioned media from Raptor null immature osteoblasts or media with anti-IL-7 neutralizing antibody failed to differentiate into pre-B and immature B cells, indicating that inactivation of mTORC1 in immature osteoblast cannot fully support normal B-cell development. Taken together, these findings demonstrate a novel role for mTORC1 in the regulation of bone marrow environments that support B-cell differentiation via regulating IL-7 expression. © 2017 American Society for Bone and Mineral Research.
The effect of postnatal manganese exposure on the NMDA receptor signaling pathway in rat hippocampus
Authors: Wang Lei , Fu HuanHuan , Liu Bin , Liu XiaoYan , Chen WeiWei , Yu XiaoDan
Published: December 2017

Overexposure to manganese (Mn) is associated with neurological disorders in children. Evidence indicated that N‐methyl‐d‐aspartate (NMDA) receptor signaling pathway was critical for neurobehavioral function. However, whether NMDA receptor signaling pathway contributes to Mn‐induced neurotoxicity remains unknown. In this study, newborn Sprague–Dawley rats were randomly assigned to four groups exposed to 0, 10, 20, and 30 mg/kg of Mn2+ by intraperitoneal injection (n = 10/group: five males and five females). After 3 weeks of Mn exposure, messenger RNA (mRNA) and protein expression of NMDA receptor subunits (NR1, NR2A, and NR2B), cAMP‐response element binding protein (CREB), and brain‐derived neurotrophic factor (BDNF) in hippocampus were measured by real‐time quantitative RT‐PCR and Western blot. In Mn‐exposed rats, decreased mRNA and protein expression of NR1, NR2A, and NR2B, CREB, and BDNF was observed. The results imply that downregulated NMDA receptor signaling pathway may be of vital importance in the neuropathological process of Mn‐induced neurotoxicity.
Selection of antioxidants against ovarian oxidative stress in mouse model
Authors: Li Bojiang , Weng Qiannan , Liu Zequn , Shen Ming , Zhang Jiaqing , Wu Wangjun , Liu Honglin
Published: December 2017

Oxidative stress (OS) plays an important role in the process of ovarian granulosa cell apoptosis and follicular atresia. The aim of this study was to select antioxidant against OS in ovary tissue. Firstly, we chose the six antioxidants and analyzed the reactive oxygen species (ROS) level in the ovary tissue. The results showed that proanthocyanidins, gallic acid, curcumin, and carotene decrease the ROS level compared with control group. We further demonstrated that both proanthocyanidins and gallic acid increase the antioxidant enzymes activity. Moreover, change in the ROS level was not observed in proanthocyanidins and gallic acid group of brain, liver, spleen, and kidney tissues. Finally, we found that proanthocyanidins and gallic acid inhibit pro‐apoptotic genes expression in granulosa cells. Taken together, proanthocyanidins and gallic acid may be the most acceptable and optimal antioxidants specifically against ovarian OS and also may be involved in the inhibition of granulosa cells apoptosis in mouse ovary.
27Al NMR MAS Spectral Studies Inferring the Initiation of Geopolymerization Reaction on Together Mechanochemical Grinding of Raw Materials
Authors: Bhardwaj Pooja , Gupta Rainy , Mishra Deepti , Mudgal Manish , Amritphale Sudhir Sitaram
Published: December 2017

Chemical shifts and intensities of the 27Al NMR signals provide structural information about the environment of Al nuclei in presence of an external magnetic field. This paper analyzes the structural information of the aluminum nuclei present in the precursor material after mechanochemical co‐grinding of the raw materials, namely fly ash, NaOH, and amorphous tricalcium phosphate [Ca3(PO4)2], with the help of 27Al MAS NMR spectral studies. The results indicate transformation of the sixfold coordination Al ions with oxygen AlQ6 present in aluminosilicate material fly ash to fourfold AlQ4 and fivefold AlQ5 in the precursor material. The variation in chemical shift is between δ 64 and 65 ppm. This indicates that, in addition to direct bonding to the oxygen atom, the Al tetrahedron is also bonded to Si as [AlQ4(4Si)]. Thus, the mechanochemical co‐grinding of the raw materials initiates a solid‐state chemical reaction among them. The addition of water alone to this precursor material results in the formation of the geopolymeric material unlike the conventional geopolymeric system which requires the addition of a highly alkaline aqueous solution to fly ash. This study helps in the determination of the reaction mechanism during the mechanochemical transformation of raw materials into the geopolymeric product by a novel process.
Group divisible covering designs with block size four
Authors: Wei Hengjia , Ge Gennian , Colbourn Charles J.
Published: December 2017

Group divisible covering designs (GDCDs) were introduced by Heinrich and Yin as a natural generalization of both covering designs and group divisible designs. They have applications in software testing and universal data compression. The minimum number of blocks in a k‐GDCD of type is a covering number denoted by . When , the values of have been determined completely for all possible pairs . When , Francetić et al. constructed many families of optimal GDCDs, but the determination remained far from complete. In this paper, two specific 4‐IGDDs are constructed, thereby completing the existence problem for 4‐IGDDs of type . Then, additional families of optimal 4‐GDCDs are constructed. Consequently the cases for whose status remains undetermined arise when and , when and , and in several small families for which one of g and u is fixed.
Synergistic actions of vitamin D and metformin on skeletal muscles and insulin resistance of type 2 diabetic rats
Authors: Amin Shaimaa N. , Hussein Usama K. , Yassa Hanan D. , Hassan Sherif S. , Rashed Laila A.
Published: December 2017

Diabetes Mellitus is a chronic generalized disorder due to insulin insufficiency or resistance. Skeletal muscles represent one of the most important target organs that is affected by insulin signaling. The aim of the current work was to investigate the effect of metformin versus vitamin D (and also simultaneous administration) therapy in type 2 diabetic (T2D) rats on the state of the muscle and insulin sensitivity. Thirty six male rats constituted the animal model and have been divided into five groups: control, Diabetic, Diabetic + Metformin, Diabetic + Vitamin D, Diabetic + Metformin + Vitamin D. Blood samples were taken for biochemical measurements of serum calcium, interleukin‐6 (IL‐6), Triglycerides (TG), glucose, insulin, and calculation of HOMA‐IR, and then rats were sacrificed, dissected for removal of gastrocnemius muscle that is used for both biochemical, histopathological and electron microscopy examination. Oral administration of vitamin D alone or in combination with metformin improved insulin sensitivity in skeletal muscles, and sustained the metabolic complications along with muscle atrophy and inflammation in T2D rats. We demonstrated super‐beneficial action on insulin resistance of additional vitamin D therapy in T2DM rats that were insufficiently controlled by metformin alone.
Dickkopf homolog 3 (DKK3): A candidate for detection and treatment of cancers?
Authors: Hamzehzadeh Leila , Caraglia Michele , Atkin Stephen L. , Sahebkar Amirhossein
Published: December 2017

Wnt signaling is an evolutionary highly conserved pathway that is modulated by several inhibitors and activators, and plays a key role in numerous physiological processes. One of the extracellular Wnt inhibitors is the DKK (Dickkopf Homolog) family which has four members (Dkk1‐4) and a unique Dkk3‐related gene, Dkkl1 (soggy). DKK3 is a divergent member of the DKK protein family. Evidence suggests that DKK3 may serve as a potential therapeutic target in several types of human cancers. We review here the biological role of DKK3 as a tumor suppressor gene (TSG) or oncogene, and its correlation with various miRNAs. In addition, we discuss the role of polymorphisms and promoter methylation of the DKK3 gene, and of its expression in regulating cancer cell proliferation. Finally, we propose that DKK3 may be considered as both a biomarker and a therapeutic target in different cancers.